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Sample records for cell rearrangements guided

  1. Dynamic 3D cell rearrangements guided by a fibronectin matrix underlie somitogenesis.

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    Gabriel G Martins

    Full Text Available Somites are transient segments formed in a rostro-caudal progression during vertebrate development. In chick embryos, segmentation of a new pair of somites occurs every 90 minutes and involves a mesenchyme-to-epithelium transition of cells from the presomitic mesoderm. Little is known about the cellular rearrangements involved, and, although it is known that the fibronectin extracellular matrix is required, its actual role remains elusive. Using 3D and 4D imaging of somite formation we discovered that somitogenesis consists of a complex choreography of individual cell movements. Epithelialization starts medially with the formation of a transient epithelium of cuboidal cells, followed by cell elongation and reorganization into a pseudostratified epithelium of spindle-shaped epitheloid cells. Mesenchymal cells are then recruited to this medial epithelium through accretion, a phenomenon that spreads to all sides, except the lateral side of the forming somite, which epithelializes by cell elongation and intercalation. Surprisingly, an important contribution to the somite epithelium also comes from the continuous egression of mesenchymal cells from the core into the epithelium via its apical side. Inhibition of fibronectin matrix assembly first slows down the rate, and then halts somite formation, without affecting pseudopodial activity or cell body movements. Rather, cell elongation, centripetal alignment, N-cadherin polarization and egression are impaired, showing that the fibronectin matrix plays a role in polarizing and guiding the exploratory behavior of somitic cells. To our knowledge, this is the first 4D in vivo recording of a full mesenchyme-to-epithelium transition. This approach brought new insights into this event and highlighted the importance of the extracellular matrix as a guiding cue during morphogenesis.

  2. ERG gene rearrangements are common in prostatic small cell carcinomas

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    Lotan, Tamara L.; Gupta, Nilesh S; Wang, Wenle; Toubaji, Antoun; Haffner, Michael C; Chaux, Alcides; Hicks, Jessica L.; Meeker, Alan K.; Bieberich, Charles J.; De Marzo, Angelo M.; Epstein, Jonathan I; Netto, George J.

    2011-01-01

    Small cell carcinoma of the prostate is a rare subtype with an aggressive clinical course. Despite the frequent occurrence of ERG gene rearrangements in acinar carcinoma, the incidence of these rearrangements in prostatic small cell carcinoma is unclear. In addition, molecular markers to distinguish prostatic small cell carcinomas from lung and bladder small cell carcinomas may be clinically useful. We examined the occurrence of ERG gene rearrangements by fluorescence in situ hybridization in...

  3. Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion

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    Shibukawa, Yukinao; Yamazaki, Natsuko; Kumasawa, Keiichi; Daimon, Etsuko; Tajiri, Michiko; Okada, Yuka; Ikawa, Masahito; Wada, Yoshinao

    2010-01-01

    Cell–cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted Be...

  4. Calponin 3 regulates actin cytoskeleton rearrangement in trophoblastic cell fusion.

    Science.gov (United States)

    Shibukawa, Yukinao; Yamazaki, Natsuko; Kumasawa, Keiichi; Daimon, Etsuko; Tajiri, Michiko; Okada, Yuka; Ikawa, Masahito; Wada, Yoshinao

    2010-11-15

    Cell-cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted BeWo cell fusion. CNN3 at the cytoplasmic face of cytoskeleton was dislocated from F-actin with forskolin treatment and diffused into the cytoplasm in a phosphorylation-dependent manner. Phosphorylation sites were located at Ser293/296 in the C-terminal region, and deletion of this region or site-specific disruption of Ser293/296 suppressed syncytium formation. These CNN3 mutants were colocalized with F-actin and remained there after forskolin treatment, suggesting that dissociation of CNN3 from F-actin is modulated by the phosphorylation status of the C-terminal region unique to CNN3 in the CNN family proteins. The mutant missing these phosphorylation sites displayed a dominant negative effect on cell fusion, while replacement of Ser293/296 with aspartic acid enhanced syncytium formation. These results indicated that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent. PMID:20861310

  5. Genome rearrangement affects RNA virus adaptability on prostate cancer cells

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    Pesko, Kendra; Voigt, Emily A.; Swick, Adam; Morley, Valerie J.; Timm, Collin; Yin, John; Paul E. Turner

    2015-01-01

    Gene order is often highly conserved within taxonomic groups, such that organisms with rearranged genomes tend to be less fit than wild type gene orders, and suggesting natural selection favors genome architectures that maximize fitness. But it is unclear whether rearranged genomes hinder adaptability: capacity to evolutionarily improve in a new environment. Negative-sense non-segmented RNA viruses (order Mononegavirales) have specific genome architecture: 3′ UTR – core protein genes – envelo...

  6. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

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    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P.; Islas-Morris-Hernandez, A.; Borget, I.; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. Results ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24–55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7–11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. Conclusion We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged

  7. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

    OpenAIRE

    Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P; Islas-Morris-Hernandez, A.; Borget, I; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

    2015-01-01

    Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluoresce...

  8. Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells.

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    Mai Nanya

    Full Text Available Etoposide, a topoisomerase 2 (TOP2 inhibitor, is associated with the development of KMT2A (MLL-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. Etoposide-induced Kmt2a breakage was detected in fetal liver hematopoietic stem cells using a newly developed chromatin immunoprecipitation (ChIP assay. Assessment of etoposide-induced chromosomal translocation by next-generation RNA sequencing (RNA-seq identified several chimeric fusion messenger RNAs that were generated by etoposide treatment. However, Kmt2a (Mll-rearranged fusion mRNA was detected in Atm-knockout mice, which are defective in the DNA damage response, but not in wild-type mice. The present findings suggest that in utero exposure to TOP2 inhibitors induces Kmt2a rearrangement when the DNA damage response is defective.

  9. Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis

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    Rygiel, Karolina A.; Tuppen, Helen A.; Grady, John P.; Vincent, Amy; Blakely, Emma L.; Reeve, Amy K.; Taylor, Robert W.; Picard, Martin; Miller, James; Turnbull, Doug M.

    2016-01-01

    Mitochondrial DNA (mtDNA) rearrangements are an important cause of mitochondrial disease and age related mitochondrial dysfunction in tissues including brain and skeletal muscle. It is known that different mtDNA deletions accumulate in single cells, but the detailed nature of these rearrangements is still unknown. To evaluate this we used a complementary set of sensitive assays to explore the mtDNA rearrangements in individual cells from patients with sporadic inclusion body myositis, a late-onset inflammatory myopathy with prominent mitochondrial changes. We identified large-scale mtDNA deletions in individual muscle fibres with 20% of cytochrome c oxidase-deficient myofibres accumulating two or more mtDNA deletions. The majority of deletions removed only the major arc but ∼10% of all deletions extended into the minor arc removing the origin of light strand replication (OL) and a variable number of genes. Some mtDNA molecules contained two deletion sites. Additionally, we found evidence of mitochondrial genome duplications allowing replication and clonal expansion of these complex rearranged molecules. The extended spectrum of mtDNA rearrangements in single cells provides insight into the process of clonal expansion which is fundamental to our understanding of the role of mtDNA mutations in ageing and disease. PMID:27131788

  10. Mosaic (MSC) cucumbers regenerated from independent cell cultures possess different mitochondrial rearrangements.

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    Bartoszewski, Grzegorz; Malepszy, Stefan; Havey, Michael J

    2004-02-01

    Passage of the highly inbred cucumber ( Cucumis sativus L.) line B through cell culture produces progenies with paternally transmitted, mosaic (MSC) phenotypes. Because the mitochondrial genome of cucumber shows paternal transmission, we evaluated for structural polymorphisms by hybridizing cosmids spanning the entire mitochondrial genome of Arabidopsis thaliana L. to DNA-gel blots of four independently generated MSC and four wild-type cucumbers. Polymorphisms were identified by cosmids carrying rrn18, nad5-exon2, rpl5, and the previously described JLV5 deletion. Polymorphisms revealed by rrn18 and nad5-exon2 were due to one rearrangement bringing together these two coding regions. The polymorphism revealed by rpl5 was unique to MSC16 and was due to rearrangement(s) placing the rpl5 region next to the forward junction of the JLV5 deletion. The rearrangement near rpl5 existed as a sublimon in wild-type inbred B, but was not detected in the cultivar Calypso. Although RNA-gel blots revealed reduced transcription of rpl5 in MSC16 relative to wild-type cucumber, Western analyses revealed no differences for the RPL5 protein and the genetic basis of the MSC16 phenotype remains enigmatic. We evaluated 17 MSC and wild-type lines regenerated from independent cell-culture experiments for these structural polymorphisms and identified eight different patterns, indicating that the passage of cucumber through cell culture may be a unique mechanism to induce or select for novel rearrangements affecting mitochondrial gene expression. PMID:14586555

  11. A case report of CIC-rearranged undifferentiated small round cell sarcoma in the cerebrum.

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    Ito, Mayumi; Ishikawa, Misawo; Kitajima, Masateru; Narita, Jun; Hattori, Shinya; Endo, Otone; Goto, Keisuke

    2016-10-01

    CIC-rearranged undifferentiated small round cell sarcoma (CIC-rearranged USRCS) is a recently established type of Ewing-like small round cell sarcomas, characterized by CIC gene rearrangement, most commonly CIC-DUX4 fusion. This report presents the second case of CIC-rearranged USRCS arising primarily in the cerebrum. A 64-year-old otherwise healthy woman presented with a 1 × 1 cm sized hemorrhagic subcortical tumor in the left temporo-parietal lobe. The tumor repeatedly recurred, and the patient underwent three surgeries, chemotherapy with doxorubicin and ifosfamide, and radiotherapy, as well as gamma knife surgery. Systemic examination revealed no other extracranial masses. Imprint cytology revealed small to moderate-sized round-to-ovoid tumor cells with mild pleomorphism and variations in size and shape. The nuclei contained finely granular chromatin, and some had easily-recognizable nucleoli. The tumor exhibited a mainly cytoplasmic pattern of CD99 immunostaining, rather than a diffuse membranous pattern. The tumor also exhibited diffuse positivity for calretinin and p16, as well as partial positivity for WT1 (nuclear and cytoplasmic staining pattern) and D2-40. FISH assessment showed CIC split signals. In conclusion, CIC-rearranged USRCSs can occur primarily in the cerebrum. It would be impossible to diagnose them through cytology alone, but cytology would be useful to rule out other small round cell brain tumors including gliomas, lymphomas, carcinomas, and germinoma. Immunohistochemical analysis including tests for CD99, calretinin, and WT1 would help to suggest CIC-rearranged USRCSs and distinguish them from Ewing sarcomas. Additionally, immunohistochemistry for p16 might be useful in the diagnosis. Diagn. Cytopathol. 2016;44:828-832. © 2016 Wiley Periodicals, Inc. PMID:27324529

  12. Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia.

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    Jonsson, O G; Kitchens, R. L.; Baer, R J; Buchanan, G. R.; Smith, R G

    1991-01-01

    Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemi...

  13. Antibody repertoire development in fetal and neonatal piglets. XXII. Lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine

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    PCR was used to detect VDJ and VJ rearrangement, expression of RAG-1, TdT and VpreB and the presence of signal joint circles (SJC) in an effort to identify sites of B cell lymphogenesis in tissue lysates and sorted leukocytes of fetal and newborn piglets. VDJ, VlambdaJlambda but not VkappaJkappa re...

  14. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

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    Tsuta, K; Kohno, T.; Yoshida, A.; Shimada, Y.; Asamura, H.; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcriptio...

  15. Activation of lipid peroxidation as a mechanism of plant cell rearrangements under microgravity

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    Baranenko, V. V.

    Activation of the lipid peroxidation (LP) is a universal process perturbating cell membranes under different unfavourable conditions. It is suggested that the LP can be one of the important mechanisms of plant cell rearrangements under altered gravity as well. The purpose of this investigation is to study the LP intensity in pea leaves and chloroplasts under 7- and 14-day clinorotation. The intensification of the LP under both terms of clinorotation particularly under more prolonged, is detected. The adaptive increase in the unsaturated fatty acid content under 7-day clinorotation and their minor decrease under 14-day clinorotation are revealed. The lowering of electron transport rate in both photosystems, particularly in PSI, is established. The results confirm that the LPmay be one of the mechanisms of plant cell rearrangements under microgravity.

  16. Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells

    International Nuclear Information System (INIS)

    Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state

  17. Deletional rearrangement in the human T-cell receptor α-chain locus

    International Nuclear Information System (INIS)

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed α and β. In the course of characterizing human T-cell tumors with an immature (CD4-, CD8-) surface phenotype, the authors detected a 2-kilobase α-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early α) located between the α-chain variable- and joining-region genes had been spliced to the α constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the α gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature α gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the γδ heterodimeric receptor and is deleted from mature (αβ-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (γδ-expressing) T cells and mature (αβ-expressing) T cells

  18. Fusion of short telomeres in human cells is characterized by extensive deletion and microhomology, and can result in complex rearrangements

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    Letsolo, Boitelo T.; Rowson, Jan; Baird, Duncan M.

    2009-01-01

    Telomere fusion is an important mutational event that has the potential to lead to large-scale genomic rearrangements of the types frequently observed in cancer. We have developed single-molecule approaches to detect, isolate and characterize the DNA sequence of telomere fusion events in human cells. Using these assays, we have detected complex fusion events that include fusion with interstitial loci adjacent to fragile sites, intra-molecular rearrangements, and fusion events involving the te...

  19. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

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    Ryohei Katayama; Takuya Sakashita; Noriko Yanagitani; Hironori Ninomiya; Atsushi Horiike; Luc Friboulet; Gainor, Justin F.; Noriko Motoi; Akito Dobashi; Seiji Sakata; Yuichi Tambo; Satoru Kitazono; Shigeo Sato; Sumie Koike; John Iafrate, A.

    2015-01-01

    The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emerge...

  20. Circulating lymphoma cells in patients with B & T non-Hodgkin's lymphoma detected by immunoglobulin and T-cell receptor gene rearrangement.

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    Brada, M.; Mizutani, S; Molgaard, H.; Sloane, J P; Treleaven, J.; Horwich, A.; Peckham, M J

    1987-01-01

    We studied peripheral blood mononuclear cells from 50 patients with active B- and T-cell non-Hodgkin's lymphoma by DNA hybridisation. Nineteen patients (38%) had circulating clones of cells detected by immunoglobulin gene rearrangement (17 patients) or T-cell receptor gene rearrangement (2 patients) with JH and J beta 2 probes. Lymphoma tissue and peripheral blood were studied simultaneously in 22 patients, 9 of which had a circulating clone of cells in peripheral blood. In 7 patients the gen...

  1. Quantitative insights into actin rearrangements and bacterial target site selection fromSalmonella Typhimurium infection of micropatterned cells

    OpenAIRE

    Vonaesch, Pascale; Cardini, Steven; Sellin, Mikael E.; Goud, Bruno; Hardt, Wolf-Dietrich; Schauer, Kristine

    2013-01-01

    Reorganization of the host cell actin cytoskeleton is crucial during pathogen invasion. We established micropatterned cells as a standardized infection model for cell invasion to quantitatively study actin rearrangements triggered by Salmonella Typhimurium (S. Tm). Micropatterns of extracellular matrix proteins force cells to adopt a reproducible shape avoiding strong cell-to-cell variations, a major limitation in classical cell culture conditions. S. Tm induced F-actin-rich ruffles and invad...

  2. Rearrangement of S-100 immunoreactive Langerhans' cells in human psoriatic skin treated with peptide T.

    Science.gov (United States)

    Wang, L; Hilliges, M; Talme, T; Marcusson, J A; Wetterberg, L; Johansson, O

    1995-01-01

    Dendritic cells marked by protein S-100 (S-100) antiserum in the suprabasal layers of the epidermis have previously been identified to be Langerhans' cells. In this study, S-100 immunoreactive cells have been investigated in psoriatic lesioned skin during and after peptide T treatment. Peptide T is an octapeptide with affinity for the CD4 receptor. Nine patients were intravenously infused with peptide T, 2 mg in 500 ml saline per day for 28 days. Sections from involved skin before, every week during, and after the treatment were processed by indirect immunofluorescence using S-100 antiserum. Before the treatment the epidermal Langerhans' cells were numerically decreased or even completely gone in the involved skin of psoriasis as compared to skin from normal healthy controls, while the dermal dendritic cells instead were increased and gathered in cell clusters around vascular structures. Four of the nine patients had histopathological improvements after the peptide T treatment, and, in those cases, the dendritic cells in the dermis were reduced in number, and the Langerhans' cells in the epidermis were numerically increased as well as even reversed to normal position and morphology. These changes in the distribution and density of Langerhans' cells represent their rearrangement during the course of psoriasis and/or the remission after peptide T treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7727353

  3. Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor.

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    Luria, S; Gross, G; Horowitz, M; Givol, D

    1987-11-01

    We cloned and compared the sequence of a rearranged human T cell receptor (TCR) V alpha J alpha gene and its germline counterparts. The only difference in the coding region sequence was confined to the joining region where three nucleotides, TTG, unaccountable by either V alpha or J alpha sequence, were present. By nuclease S1 mapping we identified the mRNA start of the alpha chain 70 nucleotides upstream from the initiator ATG. A 600 bp fragment containing the sequences upstream to the ATG drives the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene. This promoter activity is T cell specific since it can be demonstrated in human T cells but not in B cells or HeLa cells. A 1.1 kb BamHI- HindIII fragment located 5' to the first exon of the C alpha gene was found to enhance transcription from either the heterologous SV40 promoter or the homologous TCR alpha chain promoter. This enhancement activity was independent of the location of the fragment with respect to CAT and was specific to lymphoid cells (either T or B cells) but cannot be demonstrated in HeLa cells. PMID:3501368

  4. TPR-MET oncogenic rearrangement: detection by polymerase chain reaction amplification of the transcript and expression in human tumor cell lines.

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    Soman, N R; Wogan, G N; Rhim, J S

    1990-01-01

    Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No information has been available about the possible occurrence of this rearrangement in human tumors. To facilitate rapid screening of human cell lines and tumor samples for this specific gene rearrangement, we developed a sensitive detection method based ...

  5. Is ALK-gene rearrangement overlooked in primary gastrointestinal T-cell lymphomas? About two cases.

    Science.gov (United States)

    Mneimneh, Wadad S; Vyas, Shikhar Gautam; Cheng, Liang; Cummings, Oscar W; Czader, Magdalena

    2015-12-01

    A 41-year-old male patient with a history of ankylosing spondylitis and Crohn disease, treated with immunomodulators and disease-modifying drugs, was diagnosed with a primary intestinal T-cell lymphoma that followed a 7.5-year-course. This transmural proliferation lacked cytological characteristics of anaplastic large cell lymphoma (ALCL), and was CD8-positive, and CD30- and anaplastic lymphoma kinase (ALK)-negative by immunohistochemistry (IHC). However, ALK-gene rearrangement (ALK-gr) was detected by fluorescence in situ hybridization (FISH) in both initial and persistent disease. The possibility of indolent T-cell lymphoproliferative disease of the gastrointestinal tract with atypical features (transmural involvement) related to ALK-gr was suggested. A previous case of aggressive 'enteropathy-associated ALCL' in the context of celiac disease was recently reported, which also lacked anaplastic morphology, and where CD30 and ALK expression was incidentally demonstrated by IHC, and ALK-gr subsequently confirmed by FISH. These two recent cases represent two distinct rare entities pertaining to the group of primary intestinal T-cell lymphomas, and they both show unexpected ALK-gr. This suggests that ALK-gr has been overlooked in the group of primary intestinal T-cell lymphomas. Performing IHC and FISH tests for ALK-gr in primary gastrointestinal T-cell lymphomas might be of importance, particularly with the advancement of targeted therapy that could impact treatment and prognosis. PMID:26531107

  6. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

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    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets. PMID:26089205

  7. Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

    International Nuclear Information System (INIS)

    We reclassified a large series of non-Hogkin's lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs

  8. Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

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    Lee, Seung Sook; Cho, Kyung Ja; Lee, Sun Joo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-12-01

    We reclassified a large series of non-Hogkin`s lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs.

  9. Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. Black-Right-Pointing-Pointer Rac1 is activated in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous

  10. Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

    International Nuclear Information System (INIS)

    Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

  11. Discrete Element Modeling Results of Proppant Rearrangement in the Cooke Conductivity Cell

    Energy Technology Data Exchange (ETDEWEB)

    Earl Mattson; Hai Huang; Michael Conway; Lisa O' Connell

    2014-02-01

    The study of propped fracture conductivity began in earnest with the development of the Cooke cell which later became part of the initial API standard. Subsequent developments included a patented multicell design to conduct 4 tests in a press at the same time. Other modifications have been used by various investigators. Recent studies by the Stim-Lab proppant consortium have indicated that the flow field across a Cooke proppant conductivity testing cell may not be uniform as initially believed which resulted is significantly different conductivity results. Post test analysis of low temperature metal alloy injections at the termination of proppant testing prior to the release of the applied stress suggest that higher flow is to be expected along the sides and top of the proppant pack than compared to the middle of the pack. To evaluate these experimental findings, a physics-based two-dimensional (2-D) discrete element model (DEM) was developed and applied to simulate proppant rearrangement during stress loading in the Cooke conductivity cell and the resulting porosity field. Analysis of these simulations are critical to understanding the impact of modification to the testing cell as well as understanding key proppant conductivity issues such as how these effects are manifested in proppant concentration testing results. The 2-D DEM model was constructed to represent a realistic cross section of the Cooke cell with a distribution of four material properties, three that represented the Cooke cell (steel, sandstone,square rings), and one representing the proppant. In principle, Cooke cell materials can be approximated as assemblies of independent discrete elements (particles) of various sizes and material properties that interact via cohesive interactions, repulsive forces, and frictional forces. The macroscopic behavior can then be modeled as the collective behavior of many interacting discrete elements. This DEM model is particularly suitable for modeling proppant

  12. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    Science.gov (United States)

    Katayama, Ryohei; Sakashita, Takuya; Yanagitani, Noriko; Ninomiya, Hironori; Horiike, Atsushi; Friboulet, Luc; Gainor, Justin F.; Motoi, Noriko; Dobashi, Akito; Sakata, Seiji; Tambo, Yuichi; Kitazono, Satoru; Sato, Shigeo; Koike, Sumie; John Iafrate, A.; Mino-Kenudson, Mari; Ishikawa, Yuichi; Shaw, Alice T.; Engelman, Jeffrey A.; Takeuchi, Kengo; Nishio, Makoto; Fujita, Naoya

    2015-01-01

    The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression. PMID:26870817

  13. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ryohei Katayama

    2016-01-01

    Full Text Available The anaplastic lymphoma kinase (ALK fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC. Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1 overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.

  14. Lack of structural rearrangement in c-kit and stem cell factor genes in Hong Kong Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia

    OpenAIRE

    Chui, CH; Leung, PHM; Lau, FY; Wan, TSK; Cheng, G.; Chan, LC

    1998-01-01

    Stem cell factor is a haemopoietic growth factor that interacts with the c-kit--encoded transmembrane tyrosine kinase receptor during signal transduction in haemopoietic progenitor stem cells. We have screened 127 Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia for structural rearrangements in the stem cell factor and c-kit genes using Southern blot analysis. No structural rearrangements were detected in any of the bone marrow samples that were tested. It seems that...

  15. Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements

    OpenAIRE

    Homminga, Irene; Vuerhard, Maartje J.; Langerak, Anton W; Buijs-Gladdines, Jessica; Pieters, Rob; Meijerink, Jules P. P.

    2012-01-01

    Translocation of the LYL1 oncogene are rare in T-cell acute lymphoblastic leukemia, whereas the homologous TAL1 gene is rearranged in approximately 20% of patients. Previous gene-expression studies have identified an immature T-cell acute lymphoblastic leukemia subgroup with high LYL1 expression in the absence of chromosomal aberrations. Molecular characterization of a t(7;19)(q34;p13) in a pediatric T-cell acute lymphoblastic leukemia patient led to the identification of a translocation betw...

  16. Consistency of VDJ Rearrangement and Substitution Parameters Enables Accurate B Cell Receptor Sequence Annotation.

    Directory of Open Access Journals (Sweden)

    Duncan K Ralph

    2016-01-01

    Full Text Available VDJ rearrangement and somatic hypermutation work together to produce antibody-coding B cell receptor (BCR sequences for a remarkable diversity of antigens. It is now possible to sequence these BCRs in high throughput; analysis of these sequences is bringing new insight into how antibodies develop, in particular for broadly-neutralizing antibodies against HIV and influenza. A fundamental step in such sequence analysis is to annotate each base as coming from a specific one of the V, D, or J genes, or from an N-addition (a.k.a. non-templated insertion. Previous work has used simple parametric distributions to model transitions from state to state in a hidden Markov model (HMM of VDJ recombination, and assumed that mutations occur via the same process across sites. However, codon frame and other effects have been observed to violate these parametric assumptions for such coding sequences, suggesting that a non-parametric approach to modeling the recombination process could be useful. In our paper, we find that indeed large modern data sets suggest a model using parameter-rich per-allele categorical distributions for HMM transition probabilities and per-allele-per-position mutation probabilities, and that using such a model for inference leads to significantly improved results. We present an accurate and efficient BCR sequence annotation software package using a novel HMM "factorization" strategy. This package, called partis (https://github.com/psathyrella/partis/, is built on a new general-purpose HMM compiler that can perform efficient inference given a simple text description of an HMM.

  17. TPR-MET oncogenic rearrangement: Detection by polymerase chain reaction amplification of the transcript and expression in human tumor cells lines

    International Nuclear Information System (INIS)

    Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No information has been available about the possible occurrence of this rearrangement in human tumors. To facilitate rapid screening of human cell lines and tumor samples for this specific gene rearrangement; the authors developed a sensitive detection method based on polymerase chain reaction (PCR) amplification of TPR-MET mRNA. cDNA was generated from cellular transcripts by using one of the PCR primers, which was then used as a template for PCR amplification of a 205-base-pair region carrying the breakpoint. An end-labeled internal probe was hybridized in solution to an aliquot of the PCR product for detecting amplification. Cells could be directly screened by the assay without prior isolation of RNA. A 205-base-pair DNA fragment characteristic of the TRP-MET rearrangement was detected in cell lines previously known to contain this altered sequence. The rearrangement was also detected at very low levels in the parental (nontransformed) cell line, HOS TE-85. A preliminary survey of cell lines derived from a variety of human tumors indicates that TPR-MET rearrangement occurred and was expressed at very low frequencies by cells from 7 of 14 tumors of nonhematopoietic origin

  18. Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.

    Science.gov (United States)

    Valera, Alexandra; Epistolio, Samantha; Colomo, Lluis; Riva, Alice; Balagué, Olga; Dlouhy, Ivan; Tzankov, Alexandar; Bühler, Marco; Haralambieva, Eugenia; Campo, Elias; Soldini, Davide; Mazzucchelli, Luca; Martin, Vittoria

    2016-08-01

    MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression. PMID:27125356

  19. Emp is a component of the nuclear matrix of mammalian cells and undergoes dynamic rearrangements during cell division

    International Nuclear Information System (INIS)

    Emp, originally detected in erythroblastic islands, is expressed in numerous cell types and tissues suggesting a functionality not limited to hematopoiesis. To study the function of Emp in non-hematopoietic cells, an epitope-tagged recombinant human Emp was expressed in HEK cells. Preliminary studies revealed that Emp partitioned into both the nuclear and Triton X-100-insoluble cytoskeletal fractions in approximately a 4:1 ratio. In this study, we report investigations of Emp in the nucleus. Sequential extractions of interphase nuclei showed that recombinant Emp was present predominantly in the nuclear matrix. Immunofluorescence microscopy showed that Emp was present in typical nuclear speckles enriched with the spliceosome assembly factor SC35 and partially co-localized with actin staining. Coimmunoprecipitation and GST-pull-down assays confirmed the apparent close association of Emp with nuclear actin. During mitosis, Emp was detected at the mitotic spindle/spindle poles, as well as in the contractile ring during cytokinesis. These results suggest that Emp undergoes dynamic rearrangements within the nuclear architecture that are correlated with cell division

  20. Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells

    NARCIS (Netherlands)

    Pohjoismaki, J.L.; Goffart, S.; Spelbrink, J.N.

    2011-01-01

    Pathological mitochondrial DNA (mtDNA) rearrangements have been proposed to result from repair of double-strand breaks caused by blockage of mitochondrial DNA (mtDNA) replication. As mtDNA deletions are seen only in post-mitotic tissues, it has been suggested that they are selected out in actively d

  1. Application of the inter-line PCR for the analyse of genomic rearrangements in radiation-transformed mammalian cell lines

    International Nuclear Information System (INIS)

    Repetitive DNA sequences of the LINE-family (long interspersed elements) that are widely distributed among the mammalian genome can be activated or altered by the exposure to ionizing radiation [1]. By the integration at new sites in the genome alterations in the expression of genes that are involved in cell transformation and/or carcinogenesis may occur [2, 3]. A new technique -the inter-LINE PCR - has been developed in order to detect and analyse such genomic rearrangements in radiation-transformed cell lines. From the sites of transformation- or tumour-specific changes in the genome it might be possible to develop new tumour markers for diagnostic purpose. (orig.)

  2. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer

    Science.gov (United States)

    Nilsson, R. Jonas A.; Karachaliou, Niki; Berenguer, Jordi; Gimenez-Capitan, Ana; Schellen, Pepijn; Teixido, Cristina; Tannous, Jihane; Kuiper, Justine L.; Drees, Esther; Grabowska, Magda; van Keulen, Marte; Heideman, Danielle A.M.; Thunnissen, Erik; Dingemans, Anne-Marie C.; Viteri, Santiago; Tannous, Bakhos A.; Drozdowskyj, Ana; Rosell, Rafael; Smit, Egbert F.; Wurdinger, Thomas

    2016-01-01

    Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone. PMID:26544515

  3. Pediatric B-Cell Lymphoma With Lymphoblastic Morphology, TdT Expression, MYC Rearrangement, and Features Overlapping With Burkitt Lymphoma.

    Science.gov (United States)

    Meznarich, Jessica; Miles, Rodney; Paxton, Christian N; Afify, Zeinab

    2016-05-01

    Burkitt lymphoma (BL) and B-lymphoblastic lymphoma are subtypes of pediatric non-Hodgkin lymphoma with different presenting features, treatment, and outcomes. This case report documents a 5-year-old female who presented with B-cell lymphoma with lymphoblastic morphology, terminal deoxynucleotidyl transferase expression, MYC rearrangement, and features overlapping with BL. Genomic microarray analysis identified a gain on the long arm of chromosome 1 without other definitive changes. She was treated according to a BL protocol and remains in remission 16-months after initial diagnosis. PMID:26785246

  4. Clinicopathologic characteristics andtherapeutic responses ofChinese patients withnon-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement

    Institute of Scientific and Technical Information of China (English)

    ShaFu; HaiYunWang; FangWang; MaYanHuang; LingDeng; XiaoZhang; ZuLuYe; JianYong Shao

    2015-01-01

    Introduction:The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6%of lung adenocarcinoma cases and deifnes a molecular subgroup of tumors characterized by clinical sensitivity toALK inhibitors such as crizotinib. This study aimed to identify the relationship betweenALK rearrangement and the clinico‑pathologic characteristics of non‑small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy toALK rearrangement in NSCLC patients. Methods:A total of 487 lung cancer patients who underwent testing forALK rearrangement in our department were included in this study.ALK rearrangement was examined by using lfuorescence insitu hybridization (FISH) assay. Results:Among the 487 patients, 44 (9.0%) were diagnosed withALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non‑smokers and of a young age (≤58years old), the frequency ofALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non‑adenocarcinoma tumor type (P=0.006), poorly differentiated tumors (P=0.001), advanced‑stage tumors (P<0.001), smoking history (P=0.008), and wild‑type epidermal growth factor receptor (EGFR) (P=0.008). Moreover, patients with poorly differentiated and advanced‑stage tumors had a shorter time to cancer progression compared with those with well differentiated (P=0.023) and early‑stage tumors (P=0.001), respectively. Conclusions:ALK‑rearranged NSCLC tends to occur in younger individuals who are either non‑smokers or light smokers with adenocarcinoma. Patients withALK rearrangement might beneift fromALK inhibitor therapy.

  5. Detection of clonal B cells in microdissected reactive lymphoproliferations: possible diagnostic pitfalls in PCR analysis of immunoglobulin heavy chain gene rearrangement

    DEFF Research Database (Denmark)

    Zhou, X.G.; Sandvej, K.; Gregersen, Niels;

    1999-01-01

    Aims-To evaluate the specificity of standard and fluorescence based (GENESCAN) polymerase chain reaction (PCR) immunoglobulin heavy chain (IgH) gene rearrangement analysis in complete and microdissected paraffin wax embedded sections from lymphoid proliferations. Methods-PCR IgH gene rearrangement...... analysis of whole sections and microdissected fragments (n = 62) from paraffin wax embedded reactive lymph nodes (n = 6) and tonsils (n = 3). Amplificant analysis used both standard methods and automated high resolution fluorescence based quantification and size determination using GENESCAN software...... rearrangement analysis is a sensitive and specific method for demonstrating B cell clonality in whole paraffin wax embedded sections. However, oligoclonal and monoclonal rearrangement patterns are regularly encountered in small tissue fragments from otherwise unremarkable reactive lymphoproliferations, possibly...

  6. The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements

    Science.gov (United States)

    Yang, Hua; Huang, Sai; Zhu, Cheng-Ying; Gao, Li; Zhu, Hai-Yan; Lv, Na; Jing, Yu; Yu, Li

    2016-01-01

    Background Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. Material/Methods This retrospective study took place from April 2008 to November 2011 in the People’s Liberation Army General Hospital. A total 433 AML patients were screened by multiple nested reverse transcription polymerase chain reaction (RT-PCR) to determine the incidence of the 11 MLL gene rearrangements. There were 68 cases of MLL gene rearrangements, for a positive rate of 15.7%. A total of 24 patients underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and 34 patients received at least 4 cycles of chemotherapy. Ten patients were lost to follow-up. Results The median follow-up was 29 months. The complete remission (CR) rate was 85.4%. The overall survival (OS) was 57.4±5.9 months for the Allo-HSCT group and 21.0±2.1 months for the chemotherapy group. The Allo-HSCT group had superior survival compared with the chemotherapy group (5-year OS: 59±17% vs. 13±8%, P0.05). Multivariate analysis showed that transplantation, platelets >50×109/L at onset, and CR are associated with a better OS in MLL rearranged AML patients. Patients with thrombocytopenia and extramedullary involvement were prone to relapse. Conclusions Our results suggest that Allo-HSCT is superior to chemotherapy alone for treating MLL rearranged AML patients. Patients treated with Allo-HSCT have a better prognosis and a longer survival. CR is an independent prognostic factor for OS, and extramedullary involvement is an independent prognostic factor for DFS. MLL rearranged AML patients with thrombocytopenia at onset <50×109 had very bad OS and DFS. PMID:27373985

  7. A Systemic Review of Resistance Mechanisms and Ongoing Clinical Trials in ALK-rearranged Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    VictorCohen

    2014-07-01

    Full Text Available The identification of oncogenic driver driver mutations in non-small cell lung cancer has led to a paradigm shift and the development of specific molecular treatments. Tumors harboring a rearranged EML4-ALK fusion oncogene are highly sensitive to therapy with ALK-targeted inhibitors. Crizotinib is the first approved treatment for advanced lung tumors containing this genetic abnormality. In this mini review, we discuss the existing data on crizotinib as well as ongoing trials involving this medication. A brief overview of the known resistance mechanisms to criztotinib will also be presented followed by a summary of the ongoing trials involving next-generation ALK inhibitors or other targeted therapies in patients with ALK+ NSCLC.

  8. ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice?

    Science.gov (United States)

    Girard, Nicolas; Audigier-Valette, Clarisse; Cortot, Alexis B; Mennecier, Bertrand; Debieuvre, Didier; Planchard, David; Zalcman, Gérard; Moro-Sibilot, Denis; Cadranel, Jacques; Barlési, Fabrice

    2015-02-01

    Crizotinib (XALKORI™, Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer. Optimizing the management of frequent crizotinib-related adverse events is crucial to ensure its continuous administration and reproduce the response and survival rates reported in clinical trials. Here, we propose some practical measures, which are mostly derived from the recommendations given to the investigators of the PROFILE 1001, 1005, 1007 and 1014 trials and are based on experience and scientific findings regarding the management of these disorders. While visual disturbances or bradycardia are frequent but benign, the severity of the cardiac and hepatic adverse events requires special attention potential to QT interval prolongations and to the monitoring of electrolyte levels and liver function, taking into account potential drug-drug interactions. PMID:25413260

  9. Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer.

    Science.gov (United States)

    Doshi, Shivang; Ray, David; Stein, Karen; Zhang, Jie; Koduru, Prasad; Fogt, Franz; Wellman, Axel; Wat, Ricky; Mathews, Charles

    2016-01-01

    Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies-IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe) than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe). The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies. PMID:26838801

  10. Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shivang Doshi

    2016-01-01

    Full Text Available Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH and immunohistochemistry (IHC. However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies—IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe. The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies.

  11. T cell factor-1 controls the lifetime of CD4+ CD8+ thymocytes in vivo and distal T cell receptor α-chain rearrangement required for NKT cell development.

    Directory of Open Access Journals (Sweden)

    Archna Sharma

    Full Text Available Natural killer T (NKT cells are a component of innate and adaptive immune systems implicated in immune, autoimmune responses and in the control of obesity and cancer. NKT cells develop from common CD4+ CD8+ double positive (DP thymocyte precursors after the rearrangement and expression of T cell receptor (TCR Vα14-Jα18 gene. Temporal regulation and late appearance of Vα14-Jα18 rearrangement in immature DP thymocytes has been demonstrated. However, the precise control of lifetime of DP thymocytes in vivo that enables distal rearrangements remains incompletely defined. Here we demonstrate that T cell factor (TCF-1, encoded by the Tcf7 gene, is critical for the extended lifetime of DP thymocytes. TCF-1-deficient DP thymocytes fail to undergo TCR Vα14-Jα18 rearrangement and produce significantly fewer NKT cells. Ectopic expression of Bcl-xL permits Vα14-Jα18 rearrangement and rescues NKT cell development. We report that TCF-1 regulates expression of RORγt, which regulates DP thymocyte survival by controlling expression of Bcl-xL. We posit that TCF-1 along with its cofactors controls the lifetime of DP thymocytes in vivo.

  12. DNA between variable and joining gene segments of immunoglobulin kappa light chain is frequently retained in cells that rearrange the kappa locus.

    OpenAIRE

    Van Ness, B G; Coleclough, C; Perry, R P; Weigert, M

    1982-01-01

    A systematic analysis of the fate of the DNA between kappa chain variable (V kappa) and joining (J kappa) genes in cells that have rearranged kappa loci was carried out. The DNA from a variety of kappa-producing plasmacytomas, lambda-producing hybridomas, and kappa-expressing lymphocytes was digested, fractionated by size, and analyzed with two probes containing sequences 5' of J kappa. In 13 of 28 plasmacytomas examined the rearrangement of V kappa and J kappa appears to be accompanied by lo...

  13. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Okuma Y

    2015-06-01

    Full Text Available Yusuke Okuma,1,2 Yuichiro Tanaka,3 Tina Kamei,1 Yukio Hosomi,1 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 2Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, 3Department of Ophthalmology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, Japan Abstract: Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient’s remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash. Keywords: lung cancer, ALK rearrangement, alectinib, choroidal metastasis, molecular targeted

  14. Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression

    International Nuclear Information System (INIS)

    Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus. After injection into athymic nude mice by four different routes, primary tumors and secondary lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and mRNA expression of both genes for comparison with the originally injected transformed cells and untransformed 3T3 cells. For all tumors (primary or secondary), the v-Ki-ras gene was amplified and v-Ki-ras mRNA expression was highly elevated above that observed in the original transformed cell population. In two of five lung metastases from the i.v. and footpad injection routes, rearranged Ki-ras DNA sequences were observed. Micrometastases from the s.c. route of injection did not display these alterations. Injection of footpad lung tumor cells with rearrangements into a second group of animals led to multiple lung metastases with even further rearrangements correlating with more effective lung colonization/growth ability. However, reinjection of an i.v. lung tumor with rearranged Ki-ras led to no further rearrangements in the lung microfoci tumors isolated > 40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this amplification with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors

  15. A Dual Role for Melatonin in Medaka Ovulation: Ensuring Prostaglandin Synthesis and Actin Cytoskeleton Rearrangement in Follicular Cells.

    Science.gov (United States)

    Ogiwara, Katsueki; Takahashi, Takayuki

    2016-03-01

    Understanding the direct effects of melatonin on vertebrate ovulation remains a challenge. The present study provides the first characterization of the role of melatonin in ovulation using the teleost medaka. The melatonin receptor antagonist luzindole inhibited in vitro follicle ovulation. In the preovulatory follicles, arylalkylamineN-acetyltransferase 1a and hydroxyindole-O-methyltransferase 2, the enzymes responsible for melatonin synthesis, were expressed in the granulosa cells throughout the 24 h spawning cycle. The granulosa cells of the follicle also expressed the melatonin receptor 1a-a. An in vitro characterization study using medaka OLHNI-2 cells revealed that melatonin and luzindole act as an agonist and an antagonist, respectively, of the melatonin receptor. The intracellular cAMP levels in these cells were reduced after melatonin treatment. The expression of cytosolic phospholipase A2 group 4a (Pla2g4a), the enzyme producing arachidonic acid (cyclooxygenase-2 substrate), was inhibited in the granulosa cells in luzindole-treated follicles. Follicular prostaglandin E2levels and in vitro follicle ovulation were suppressed in follicles isolated at 12 h prior to ovulation and incubated with the Pla2g4a inhibitor AACOCF3. The G-actin:F-actin ratios in follicular cells increased with approaching ovulation, but this increase was suppressed after luzindole treatment. The phosphorylation of moesin, an ezrin-radixin-moesin protein, was inhibited in the follicular cells in luzindole-treated follicles. These results indicate a dual role for melatonin in medaka ovulation: melatonin ensures prostaglandin E2synthesis throughout the spawning cycle and induces actin cytoskeleton rearrangement in the follicular cells at ovulation. PMID:26864196

  16. T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

    OpenAIRE

    Griesinger, F; Greenberg, J M; Kersey, J H

    1989-01-01

    We have studied recombinatorial events of the T cell receptor delta and gamma chain genes in hematopoietic malignancies and related these to normal stages of lymphoid differentiation. T cell receptor delta gene recombinatorial events were found in 91% of acute T cell lymphoblastic leukemia, 68% of non-T, non-B lymphoid precursor acute lymphoblastic leukemia (ALL) and 80% of mixed lineage acute leukemias. Mature B-lineage leukemias and acute nonlymphocytic leukemias retained the T-cell recepto...

  17. Regulation of immunoglobulin gene rearrangement and expression.

    Science.gov (United States)

    Taussig, M J; Sims, M J; Krawinkel, U

    1989-05-01

    The molecular genetic events leading to Ig expression and their control formed the topic of a recent EMBO workshop. This report by Michael Taussig, Martin Sims and Ulrich Krawinkel discusses contributions dealing with genes expressed in early pre-B cells, the mechanism of rearrangement, aberrant rearrangements seen in B cells of SCID mice, the feedback control of rearrangement as studied in transgenic mice, the control of Ig expression at the transcriptional and post-transcriptional levels, and class switching. PMID:2787158

  18. The Transcriptional Consequences of Somatic Amplifications, Deletions, and Rearrangements in a Human Lung Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Lucy F Stead

    2012-11-01

    Full Text Available Lung cancer causes more deaths, worldwide, than any other cancer. Several histologic subtypes exist. Currently, there is a dearth of targeted therapies for treating one of the main subtypes: squamous cell carcinoma (SCC. As for many cancers, lung SCC karyotypes are often highly anomalous owing to large somatic structural variants, some of which are seen repeatedly in lung SCC, indicating a potential causal association for genes therein. We chose to characterize a lung SCC genome to unprecedented detail and integrate our findings with the concurrently characterized transcriptome. We aimed to ascertain how somatic structural changes affected gene expression within the cell in ways that could confer a pathogenic phenotype. We sequenced the genomes of a lung SCC cell line (LUDLU-1 and its matched lymphocyte cell line (AGLCL to more than 50x coverage. We also sequenced the transcriptomes of LUDLU-1 and a normal bronchial epithelium cell line (LIMM-NBE1, resulting in more than 600 million aligned reads per sample, including both coding and non-coding RNA (ncRNA, in a strand-directional manner. We also captured small RNA (<30 bp. We discovered significant, but weak, correlations between copy number and expression for protein-coding genes, antisense transcripts, long intergenic ncRNA, and microRNA (miRNA. We found that miRNA undergo the largest change in overall expression pattern between the normal bronchial epithelium and the tumor cell line. We found evidence of transcription across the novel genomic sequence created from six somatic structural variants. For each part of our integrated analysis, we highlight candidate genes that have undergone the largest expression changes.

  19. Antibody repertoire development in fetal and neonatal piglets. XXII. lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine

    Czech Academy of Sciences Publication Activity Database

    Sun, X.; Wertz, N.; Lager, K.; Šinkora, Marek; Štěpánová, Kateřina; Tobin, G.; Butler, J. E.

    2012-01-01

    Roč. 137, č. 2 (2012), s. 149-159. ISSN 0019-2805 R&D Projects: GA ČR GAP502/10/0038; GA MŠk ME09089 Institutional support: RVO:61388971 Keywords : B-cell lymphogenesis * fetal * RAG-1 Subject RIV: EC - Immunology Impact factor: 3.705, year: 2012

  20. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.

    Science.gov (United States)

    Okuma, Yusuke; Tanaka, Yuichiro; Kamei, Tina; Hosomi, Yukio; Okamura, Tatsuru

    2015-01-01

    Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash. PMID:26082648

  1. Genome-Wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells

    OpenAIRE

    Chiarle, Roberto; Zhang, Yu; Frock, Richard L.; Lewis, Susanna M.; Molinie, Benoit; Ho, Yu-Jui; Myers, Darienne R; Choi, Vivian W.; Compagno, Mara; Malkin, Daniel J.; Neuberg, Donna; Monti, Stefano; Giallourakis, Cosmas C.; Gostissa, Monica; Alt, Frederick W.

    2011-01-01

    While chromosomal translocations are common pathogenetic events in cancer, mechanisms that promote them are poorly understood. To elucidate translocation mechanisms in mammalian cells, we developed high throughput, genome-wide translocation sequencing (HTGTS). We employed HTGTS to identify tens of thousands of independent translocation junctions involving fixed I-SceI meganuclease-generated DNA double strand breaks (DSBs) within the c-myc oncogene or IgH locus of B lymphocytes induced for Act...

  2. Retinoids and glucocorticoids have opposite effects on actin cytoskeleton rearrangement in hippocampal HT22 cells.

    Science.gov (United States)

    Hélène, Roumes; Julie, Brossaud; Aloïs, Lemelletier; Marie-Pierre, Moisan; Véronique, Pallet; Anabelle, Redonnet; Jean-Benoît, Corcuff

    2016-02-01

    A chronic excess of glucocorticoids elicits deleterious effects in the hippocampus. Conversely, retinoic acid plays a major role in aging brain plasticity. As synaptic plasticity depends on mechanisms related to cell morphology, we investigated the involvement of retinoic acid and glucocorticoids in the remodelling of the HT22 neurons actin cytoskeleton. Cells exhibited a significantly more elongated shape with retinoic acid and a rounder shape with dexamethasone; retinoic acid reversed the effects of dexamethasone. Actin expression and abundance were unchanged by retinoic acid or dexamethasone but F-actin organization was dramatically modified. Indeed, retinoic acid and dexamethasone increased (70 ± 7% and 176 ± 5%) cortical actin while retinoic acid suppressed the effect of dexamethasone (90 ± 6%). Retinoic acid decreased (-22 ± 9%) and dexamethasone increased (134 ± 16%) actin stress fibres. Retinoic acid also suppressed the effect of dexamethasone (-21 ± 7%). Spectrin is a key protein in the actin network remodelling. Its abundance was decreased by retinoic acid and increased by dexamethasone (-21 ± 11% and 52 ± 10%). However, retinoic acid did not modify the effect of dexamethasone (48 ± 7%). Calpain activity on spectrin was increased by retinoic acid and decreased by dexamethasone (26 ± 14% and -57 ± 5%); retinoic acid mildly but significantly modified the effect of dexamethasone (-44 ± 7%). The calpain inhibitor calpeptin suppressed the effects of retinoic acid and dexamethasone on cell shape and actin stress fibres remodelling but did not modify the effects on cortical actin. Retinoic acid and dexamethasone have a dramatic but mainly opposite effect on actin cytoskeleton remodelling. These effects originate, at least partly, from calpain activity. PMID:26748244

  3. 1p/19q codeletion and RET rearrangements in small-cell lung cancer

    OpenAIRE

    Lu H; Xu H; Xie F; Qin J; Han N; Fan Y; Mao W

    2016-01-01

    Hongyang Lu,1,2 Haimiao Xu,3 Fajun Xie,2 Jing Qin,2 Na Han,2 Yun Fan,1,2 Weimin Mao1 1Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), 2Department of Thoracic Medical Oncology, 3Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: The prognosis of small-cell lung cancer (SCLC) is poor despite reports suggesting modest improvement in survival. To date, c...

  4. Setd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement.

    Science.gov (United States)

    Tusi, Betsabeh Khoramian; Deng, Changwang; Salz, Tal; Zeumer, Leilani; Li, Yangqiu; So, Chi Wai Eric; Morel, Laurence M; Qiu, Yi; Huang, Suming

    2015-04-01

    SETD1A is a member of trithorax-related histone methyltransferases that methylate lysine 4 at histone H3 (H3K4). We showed previously that Setd1a is required for mesoderm specification and hematopoietic lineage differentiation in vitro. However, it remains unknown whether or not Setd1a controls specific hematopoietic lineage commitment and differentiation during animal development. Here, we reported that homozygous Setd1a knockout (KO) mice are embryonic lethal. Loss of the Setd1a gene in the hematopoietic compartment resulted in a blockage of the progenitor B-cell-to-precursor B-cell development in bone marrow (BM) and B-cell maturation in spleen. The Setd1a-cKO (conditional knockout) mice exhibited an enlarged spleen with disrupted spleen architecture and leukocytopenia. Mechanistically, Setd1a deficiency in BM reduced the levels of H3K4me3 at critical B-cell gene loci, including Pax5 and Rag1/2, which are critical for the IgH (Ig heavy-chain) locus contractions and rearrangement. Subsequently, the differential long-range looped interactions of the enhancer Eμ with proximal 5' DH region and 3' regulatory regions as well as with Pax5-activated intergenic repeat elements and 5' distal VH genes were compromised by the Setd1a-cKO. Together, our findings revealed a critical role of Setd1a and its mediated epigenetic modifications in regulating the IgH rearrangement and B-cell development. PMID:25550471

  5. MLL-rearranged acute lymphoblastic leukaemia stem cell interactions with bone marrow stroma promote survival and therapeutic resistance that can be overcome with CXCR4 antagonism

    OpenAIRE

    Sison, Edward Allan R; Rau, Rachel E.; McIntyre, Emily; LI Li; Small, Donald; Brown, Patrick

    2013-01-01

    Infants with MLL-rearranged (MLL-R) acute lymphoblastic leukaemia (ALL) have a dismal prognosis. While most patients achieve remission, approximately half of patients recur with a short latency to relapse. This suggests that chemotherapy-resistant leukaemia stem cells (LSCs) survive and can recapitulate the leukaemia. We hypothesized that interactions between LSCs and the bone marrow microenvironment mediate survival and chemotherapy resistance in MLL-R ALL. Using primary samples of infant ML...

  6. Construction of a multicolor GeneScan analytical system to detect clonal rearrangements of immunoglobulin and T cell receptor genes in canine lymphoid tumors.

    Science.gov (United States)

    Goto-Koshino, Yuko; Mochizuki, Hiroyuki; Sato, Masahiko; Nakashima, Ko; Hiyoshi, Saaya; Fujiwara-Igarashi, Aki; Maeda, Shingo; Nakamura, Kenji; Uchida, Kazuyuki; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

    2015-05-15

    Polymerase chain reaction (PCR) amplification to detect immunoglobulin heavy chain (IgH) and T cell receptor γ-chain (TCRγ) gene rearrangements has recently become widely used as part of the diagnostic strategy for lymphoid tumors in dogs. In this study, we constructed a multicolor GeneScan analytical system to improve the sensitivity and resolution of the clonality analysis of antigen receptor gene rearrangements in dogs. We used 7 reactions per sample, with 2 PCR conditions, to amplify IgH/TCRγ and control genes. By using multicolor-labeled primers, these 7 PCR products could be combined into 3 tubes before capillary electrophoresis. Clonal rearrangement of the IgH/TCRγ genes was detected in 93.3% of dogs with multicentric lymphoma and 84.6% of dogs with gastrointestinal lymphoma. Detection sensitivity of the clonally expanded cells in the background of normal peripheral blood mononuclear cells was 1-10%. The multicolor GeneScan analytical system developed here may prove to be helpful for the diagnosis of lymphoid tumors in dogs. PMID:25840823

  7. Local calcium elevation and cell elongation initiate guided motility in electrically stimulated osteoblast-like cells.

    Directory of Open Access Journals (Sweden)

    Nurdan Ozkucur

    rearrangements underlying EF-guided migration of osteoblast-like cell types and reveal a requirement for calcium in these reactions. We show for the first time here that dcEFs trigger different patterns of intracellular calcium elevation and positional shifting in osteogenic cell types that migrate in opposite directions.

  8. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells.

    Directory of Open Access Journals (Sweden)

    Cong Haolong

    Full Text Available Enterovirus 71 (EV71 is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human.

  9. The structure, rearrangement, and ontogenic expression of DB and JB gene segments of the Mexican axolotl T-cell antigen receptor beta chain (TCRB).

    Science.gov (United States)

    Kerfourn, F; Charlemagne, J; Fellah, J S

    1996-01-01

    We sequenced a total of 189 independent rearrangements in which the VB7.1 element is associated with CB1 (99 clones) or CB2 (90 clones) isotypes of the T-cell receptor (TCR) beta chain in the Mexican axolotl. Three stages of development were analyzed: 2.5 months, 10 months, and 25 months. Three JB1 segments were associated with the VB-CB1 rearrangements and six JB2 segments with VB-CB2. As in other vertebrates, some amino acid positions were conserved in all Jbetas (e. g., Phe-108, Gly-109, Gly-111, Thr-112, and Val-116). Two 11 nucleotides DB-like sequences, differed by one (A or T) central residue and could be productively read in the three putative reading frames. Most of the DB1 and JB1 segments were in the VB-CB1 clones, and most of the DB2 and JB2 segments were in the VB-CB2 clones, suggesting that the TCRB locus is organized into independent DB-JB-CB clusters that used the same collection of VB segments. About 40% of the beta-chain VDJ junctions in 2.5-month-old larvae had N nucleotides, compared with about 73% in 10 - 25-month old animals. The beta-chain VDJ junctions had about 30% of defective rearrangements at all stages of development, which could be due to the slow rate of cell division in the axolotl lymphoid organs, and the large genome in this urodele. Many of the axolotl CDRbeta3 sequences deduced for in frame VDJ rearrangements are the same in animals of different origins. Such redundancy could be a statistical effect due to the small number of thymocytes in the developing axolotl, rather than to some bias due to junctional preferences. PMID:8753858

  10. Chronic morphine treatment attenuates cell growth of human BT474 breast cancer cells by rearrangement of the ErbB signalling network.

    Directory of Open Access Journals (Sweden)

    Inka Regine Weingaertner

    Full Text Available There is increasing evidence that opioid analgesics may interfere with tumour growth. It is currently thought that these effects are mediated by transactivation of receptor tyrosine kinase (RTK-controlled ERK1/2 and Akt signalling. The growth of many breast cancer cells is dependent on hyperactive ErbB receptor networks and one of the most successful approaches in antineoplastic therapy during the last decade was the development of ErbB-targeted therapies. However, the response rates of single therapies are often poor and resistance mechanisms evolve rapidly. To date there is no information about the ability of opioid analgesics to interfere with the growth of ErbB-driven cancers.Here we demonstrate that ErbB2 overexpressing BT474 human breast cancer cells carry fully functional endogenous µ-opioid receptors. Most interestingly, the acute opioid effects on basal and Heregulin-stimulated ERK1/2 and Akt phosphorylation changed considerably during chronic Morphine treatment. Investigation of the underlying mechanism by the use of protein kinase inhibitors and co-immunoprecipitation studies revealed that chronic Morphine treatment results in rearrangement of the ErbB signalling network leading to dissociation of ERK1/2 from Akt signalling and a switch from ErbB1/ErbB3 to ErbB1/ErbB2-dependent cell growth. In chronically Morphine-treated cells Heregulin-stimulated ERK1/2 signalling is redirected via a newly established PI3K- and metalloproteinase-dependent feedback loop. Together, these alterations result in apoptosis of BT474 cells. A similar switch in Heregulin-stimulated ERK1/2 signalling from an ErbB2-independent to an ErbB2-, PI3K- and metalloproteinase-dependent mechanism was also observed in κ-opioid receptor expressing SKBR3 human mammary adenocarcinoma cells.The present data demonstrate that the ErbB receptor network of human breast cancer cells represents a target for chronic Morphine treatment. Rearrangement of ErbB signalling by chronic

  11. Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy.

    Science.gov (United States)

    Gardner, Rebecca; Wu, David; Cherian, Sindhu; Fang, Min; Hanafi, Laïla-Aïcha; Finney, Olivia; Smithers, Hannah; Jensen, Michael C; Riddell, Stanley R; Maloney, David G; Turtle, Cameron J

    2016-05-19

    Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treating patients with relapsed and refractory CD19(+) B-cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells. All patients achieved complete remission (CR) in the bone marrow by flow cytometry after CD19 CAR-T-cell therapy; however, within 1 month of CAR-T-cell infusion, 2 of the patients developed acute myeloid leukemia (AML) that was clonally related to their B-ALL, a novel mechanism of CD19-negative immune escape. These reports have implications for the management of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T-cell therapy. PMID:26907630

  12. The involvement of a LINE-1 element in a DNA rearrangement upstream of the mdr1a gene in a taxol multidrug-resistant murine cell line.

    Science.gov (United States)

    Cohen, D; Higman, S M; Hsu, S I; Horwitz, S B

    1992-10-01

    Two closely related but functionally distinct P-glycoprotein isoforms are encoded by the murine multidrug-resistance genes mdr1a and mdr1b. In a series of independently selected multidrug-resistant (MDR) J774.2 cell lines, mdr gene amplification and/or overexpression and overproduction of either the mdr1a or mdr1b products, or both gene products, correlates with the MDR phenotype. To investigate the possibility that mutations in the promoter regions of the mdr1a or mdr1b genes could influence their differential expression, mdr promoter-specific probes were used to detect and map potential structural alterations. An unusual structural rearrangement was found in the 5'-region of the amplified mdr1a allele in J7.T1, a cell line selected with taxol. To characterize this rearrangement, the regulatory regions of the mdr1a and mdr1b genes were analyzed. Whereas no gross structural alterations were detected by Southern blot hybridization using the mdr1b promoter probe, a novel amplified EcoRI fragment was detected by the mdr1a promoter probe. To determine the precise nature of this mutation, an mdr1a 5'-genomic clone was isolated from J7.T1 cells. Sequence analysis revealed an unusual DNA rearrangement consisting of the mdr1b gene, from its fourth intron toward its 3'-end, upstream of an intact mdr1a promoter on the amplified allele. We propose that this event occurred by an unequal sister chromatid exchange that was mediated by LINE-1 repetitive elements. PMID:1356977

  13. Degradations and Rearrangement Reactions

    Science.gov (United States)

    Zhang, Jianbo

    This section deals with recent reports concerning degradation and rearrangement reactions of free sugars as well as some glycosides. The transformations are classified in chemical and enzymatic ways. In addition, the Maillard reaction will be discussed as an example of degradation and rearrangement transformation and its application in current research in the fields of chemistry and biology.

  14. Comparative investigations of T cell receptor gamma gene rearrangements in frozen and formalin-fixed paraffin wax-embedded tissues by capillary electrophoresis

    DEFF Research Database (Denmark)

    Christensen, M; Funder, A D; Bendix, K;

    2006-01-01

    AIM: To compare clonal T cell receptor gamma (TCRgamma) gene rearrangements in frozen and formalin-fixed paraffin wax-embedded (FFPE) tissue, using capillary electrophoresis for use in diagnostics, as T cell lymphomas may be difficult to diagnose by conventional methods. METHODS: The DNA for PCR...... was extracted from frozen and FFPE tissue, cell lines and blood. PCR primers Vgamma1-8, Vgamma9, Vgamma10 or Vgamma11 (5' end labelled) combined with a mixture of JgammaP1/JgammaP/JgammaP2/Jgamma2 (unlabelled) were used. Monoclonal cases were sequenced and clonality, reproducibility, sensitivity and...... specificity analyses were carried out. RESULTS: In all cases the molecular test was found to be in agreement with the histological diagnosis. Discrepancies were found between frozen and FFPE tissue in 18 of 56 (32%) tests. The method was highly reproducible. The sensitivity was found to be 0.5% for cell lines...

  15. B-Cell Chronic Lymphocytic Leukemia with 11q22.3 Rearrangement in Patient with Chronic Myeloid Leukemia Treated with Imatinib.

    Science.gov (United States)

    Lewandowski, Krzysztof; Gniot, Michał; Lewandowska, Maria; Wache, Anna; Ratajczak, Błażej; Czyż, Anna; Jarmuż-Szymczak, Małgorzata; Komarnicki, Mieczysław

    2016-01-01

    The coexistence of two diseases chronic myeloid leukemia (CML) and B-cell chronic lymphocytic leukemia (B-CLL) is a rare phenomenon. Both neoplastic disorders have several common epidemiological denominators (they occur more often in men over 50 years of age) but different origin and long term prognosis. In this paper we described the clinical and pathological findings in patient with CML in major molecular response who developed B-CLL with 11q22.3 rearrangement and Coombs positive hemolytic anemia during the imatinib treatment. Due to the presence of the symptoms of autoimmune hemolytic anemia and optimal CML response to the imatinib treatment, the decision about combined therapy with prednisone and imatinib was made. During the follow-up, the normalization of complete blood count and resolution of peripheral lymphadenopathy were noted. The hematologic response of B-CLL was diagnosed. The repeated FISH analysis of cultured peripheral blood lymphocytes showed 2% of cells carrying 11q22.3 rearrangement. At the same time, molecular monitoring confirmed the deep molecular response of CML. The effectiveness of such combination in the described case raises the question about the best therapeutic option in such situation, especially in patients with good imatinib tolerance and optimal response. PMID:27034682

  16. [ALK-rearranged non-small cell lung cancer: how to optimize treatment with crizotinib in routine practice?].

    Science.gov (United States)

    Audigier-Valette, Clarisse; Girard, Nicolas; Cortot, Alexis B; Mennecier, Bertrand; Debieuvre, Didier; Planchard, David; Zalcman, Gérard; Moro-Sibilot, Denis; Cadranel, Jacques; Barlesi, Fabrice

    2014-09-01

    Crizotinib (XALKORI(™), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer. This work from an expert group, based on the review of the data from the Profile studies, aims to provide practical elements in order to optimize the tolerability of crizotinib. Specific major or frequent side effects of crizotinib are discussed: visual disturbances, cardiac effects, elevated transaminases, and hypogonadism. In the routine practice, patients should be advised about visual disturbances, especially with regard to driving in low brightness. Digestive disorders related to crizotinib are exceptionally persistent or severe. Dietary measures and symptomatic treatments usually control these disorders. It is recommended to perform an electrocardiogram before introduction of crizotinib, to identify prolonged QT interval. Torsades de pointes may produce dizziness or syncope. Hypogonadism should be considered in case of fatigue, decreased libido, and even depression, taking into account that these symptoms may be related to cancer; testosterone serum level should be measured to identify patients that may be eligible to receive a supplementation. Monitoring of liver function tests, including transaminases and bilirubin, is necessary. To conclude, these practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with crizotinib. PMID:25299566

  17. Sister chromatid exchanges, hyperdiploidy and chromosomal rearrangements studied in cells from melanoma-prone individuals belonging to families with the dysplastic nevus syndrome.

    Science.gov (United States)

    Jaspers, N G; Roza-de Jongh, E J; Donselaar, I G; Van Velzen-Tillemans, J T; van Hemel, J O; Rümke, P; van der Kamp, A W

    1987-01-01

    Cytogenetic investigations were performed on 25 individuals belonging to six melanoma-prone families with multiple melanocytic lesions (the dysplastic nevus syndrome, DNS). Patients having DNS with or without a history of melanoma were compared with clinically normal relatives and unrelated normal controls. The results indicate normal frequencies of hyperdiploidy and spontaneous sister chromatid exchanges in the fibroblasts of all individuals studied. Karyotypic analyses were carried out on the members of one family. The patients with DNS had a normal constitutional karyotype. In lymphocytes or fibroblasts from five patients, however, increased frequencies of cells with random chromosomal rearrangements were observed. These abnormalities, mainly translocations and inversions, were not found in two of the patients' spouses and in six clinically normal relatives. In the fibroblast cultures considerable clonal selection of cytogenetically abnormal cells occurred. PMID:3791172

  18. Rearrangements of Cycloalkenyl Aryl Ethers

    Directory of Open Access Journals (Sweden)

    Mercedesz Törincsi

    2016-04-01

    Full Text Available Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the case of cycloocthylphenyl ether the consecutive Claisen and Cope rearrangements were followed by an alkyl migration. The mechanism of this novel rearrangement reaction is also discussed.

  19. Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Thys, Ryan G., E-mail: rthys@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Lehman, Christine E., E-mail: clehman@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Pierce, Levi C.T., E-mail: Levipierce@gmail.com [Human Longevity, Inc., San Diego, California 92121 (United States); Wang, Yuh-Hwa, E-mail: yw4b@virginia.edu [Department of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908-0733 (United States)

    2015-09-15

    Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

  20. Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

  1. Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Guo L

    2015-10-01

    Full Text Available Liting Guo,1,* Haijun Zhang,1,* Weiwei Shao,2 Baoan Chen1 1Department of Hematology and Oncology (Key Department of Jiangsu Medicine, The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, 2Department of Pathology, the First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Crizotinib, the first clinically designed and synthesized as a tyrosine kinase inhibitor targeting mesenchymal–epithelial transition factor, indicating marked anticancer activity in patients with advanced, anaplastic lymphoma kinase-positive non-small-cell lung cancer, was approved by the US Food and Drug Administration in 2011. In this review, we focus on the efficacy of crizotinib compared with chemotherapy in advanced anaplastic lymphoma kinase-positive lung cancer and present the role of crizotinib as a personalized alternative in previously treated patients with non-small-cell lung cancer. Keywords: crizotinib, anaplastic lymphoma kinase rearrangement, non-small-cell lung cancer 

  2. The COP9 signalosome mediates transcriptional and metabolic response to hormones, oxidative stress protection and cell wall rearrangement during fungal development.

    Science.gov (United States)

    Nahlik, Krystyna; Dumkow, Marc; Bayram, Ozgür; Helmstaedt, Kerstin; Busch, Silke; Valerius, Oliver; Gerke, Jennifer; Hoppert, Michael; Schwier, Elke; Opitz, Lennart; Westermann, Mieke; Grond, Stephanie; Feussner, Kirstin; Goebel, Cornelia; Kaever, Alexander; Meinicke, Peter; Feussner, Ivo; Braus, Gerhard H

    2010-11-01

    The COP9 signalosome complex (CSN) is a crucial regulator of ubiquitin ligases. Defects in CSN result in embryonic impairment and death in higher eukaryotes, whereas the filamentous fungus Aspergillus nidulans survives without CSN, but is unable to complete sexual development. We investigated overall impact of CSN activity on A. nidulans cells by combined transcriptome, proteome and metabolome analysis. Absence of csn5/csnE affects transcription of at least 15% of genes during development, including numerous oxidoreductases. csnE deletion leads to changes in the fungal proteome indicating impaired redox regulation and hypersensitivity to oxidative stress. CSN promotes the formation of asexual spores by regulating developmental hormones produced by PpoA and PpoC dioxygenases. We identify more than 100 metabolites, including orsellinic acid derivatives, accumulating preferentially in the csnE mutant. We also show that CSN is required to activate glucanases and other cell wall recycling enzymes during development. These findings suggest a dual role for CSN during development: it is required early for protection against oxidative stress and hormone regulation and is later essential for control of the secondary metabolism and cell wall rearrangement. PMID:21062371

  3. Interferon α Inhibits a Src-mediated Pathway Necessary for Shigella-induced Cytoskeletal Rearrangements in Epithelial Cells

    OpenAIRE

    Duménil, G.; Olivo, J.C.; S. Pellegrini; Fellous, M.; Sansonetti, P J; Nhieu, G. Tran Van

    1998-01-01

    Shigella flexneri, the causative agent of bacillary dysentery, has the ability to enter nonphagocytic cells. The interferon (IFN) family of cytokines was found to inhibit Shigella invasion of cultured epithelial cells. We show here that IFN-α inhibits a Src-dependent signaling cascade triggered by Shigella that leads to the reorganization of the host cell cytoskeleton. Immunofluorescence studies showed that IFN-α inhibits Shigella-induced actin polymerization required for bacterial entry into...

  4. NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements

    DEFF Research Database (Denmark)

    Weischelfeldt, Joachim Lütken; Damgaard, Inge; Bryder, David;

    2008-01-01

    been addressed in detail. Here we use mouse genetics to demonstrate that hematopoietic-specific deletion of Upf2, a core NMD factor, led to the rapid, complete, and lasting cell-autonomous extinction of all hematopoietic stem and progenitor populations. In contrast, more differentiated cells were only...

  5. Rearrangements in ground and excited states

    CERN Document Server

    de Mayo, Paul

    2013-01-01

    Rearrangements in Ground and Excited States, Volume 2 covers essays on the theoretical approach of rearrangements; the rearrangements involving boron; and the molecular rearrangements of organosilicon compounds. The book also includes essays on the polytopal rearrangement at phosphorus; the rearrangement in coordination complexes; and the reversible thermal intramolecular rearrangements of metal carbonyls. Chemists and people involved in the study of rearrangements will find the book invaluable.

  6. Rearrangements in ground and excited states

    CERN Document Server

    de Mayo, Paul

    2013-01-01

    Rearrangements in Ground and Excited States, Volume 3 presents essays on the chemical generation of excited states; the cis-trans isomerization of olefins; and the photochemical rearrangements in trienes. The book also includes essays on the zimmerman rearrangements; the photochemical rearrangements of enones; the photochemical rearrangements of conjugated cyclic dienones; and the rearrangements of the benzene ring. Essays on the photo rearrangements via biradicals of simple carbonyl compounds; the photochemical rearrangements involving three-membered rings or five-membered ring heterocycles;

  7. The chemokine (C-C motif) ligand protein synthesis inhibitor bindarit prevents cytoskeletal rearrangement and contraction of human mesangial cells.

    Science.gov (United States)

    Paccosi, Sara; Giachi, Matelda; Di Gennaro, Paola; Guglielmotti, Angelo; Parenti, Astrid

    2016-09-01

    Intraglomerular mesangial cells (MCs) maintain structural and functional integrity of renal glomerular microcirculation and homeostasis of mesangial matrix. Following different types of injury, MCs change their phenotype upregulating the expression of α-smooth muscle actin (α-SMA), changing contractile abilities and increasing the production of matrix proteins, chemokines and cytokines. CCL2 is a chemokine known to be involved in the pathogenesis of renal diseases. Its glomerular upregulation correlates with the extent of renal damage. Bindarit is an indazolic derivative endowed with anti-inflammatory activity when tested in experimental diseases. It selectively inhibits the synthesis of inflammatory C-C chemokines including CCL2, CCL7 and CCL8. This work aims to analyse bindarit effects on ET1-, AngII- and TGFβ-induced mesangial cell dysfunction. Bindarit significantly reduced AngII-, ET1- and TGFβ-induced α-SMA upregulation. In a collagen contraction assay, bindarit reduced AngII-, ET1- and TGFβ-induced HRMC contraction. Within 3-6h stimulation, vinculin organization and phosphorylation was significantly impaired by bindarit in AngII-, ET1- and TGFβ-stimulated cells without any effect on F-actin distribution. Conversely, p38 phosphorylation was not significantly inhibited by bindarit. Our data strengthen the importance of CCL2 on ET-1, AngII- and TGFβ-induced mesangial cell dysfunction, adding new insights into the cellular mechanisms responsible of bindarit protective effects in human MC dysfunction. PMID:27309675

  8. Rapid and dramatic response to alectinib in an anaplastic lymphoma kinase rearranged non-small-cell lung cancer patient who is critically ill.

    Science.gov (United States)

    Yoshida, Tatsuya; Hida, Toyoaki; Yatabe, Yasushi

    2016-07-01

    Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown promising clinical activity in the treatment of non-small-cell lung cancer (NSCLC) that harbors ALK rearrangement. The next-generation ALK-TKI, alectinib, has been reported to have potent efficacy in ALK-positive NSCLC patients including on mutations that confer resistance to crizotinib, which was the first ALK-TKI approved for ALK-positive NSCLC. The efficacy and safety of ALK-TKIs, including crizotinib and alectinib, as the first-line treatment in critically ill patients is unclear. We report one ALK-positive NSCLC patient with poor performance status (PS) and disseminated intravascular coagulation because of respiratory failure and multiple metastases, and experienced the rapid and dramatic response to alectinib without adverse events that can lead to discontinuation and dose reduction of the drug. After a couple of months of treatment with alectinib, radiological review indicated a complete response. The present case is the first reported case of rapid and marked response to alectinib in ALK-positive NSCLC patients who had poor PS and severe organ dysfunction, such as disseminated intravascular coagulation. Further investigation of the safety and efficacy of ALK-TKI for ALK-positive NSCLC patients who are critically ill is warranted. PMID:26938871

  9. Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia

    Directory of Open Access Journals (Sweden)

    M.M. Sales

    2005-05-01

    Full Text Available We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia.

  10. Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia.

    Science.gov (United States)

    Sales, M M; Bezerra, C N A; Hiraki, Y; Melo, N B; Rebouças, N A

    2005-05-01

    We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta) in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I)-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V) segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia. PMID:15917950

  11. Standard guide for general design considerations for hot cell equipment

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 Intent: 1.1.1 The intent of this guide is to provide general design and operating considerations for the safe and dependable operation of remotely operated hot cell equipment. Hot cell equipment is hardware used to handle, process, or analyze nuclear or radioactive material in a shielded room. The equipment is placed behind radiation shield walls and cannot be directly accessed by the operators or by maintenance personnel because of the radiation exposure hazards. Therefore, the equipment is operated remotely, either with or without the aid of viewing. 1.1.2 This guide may apply to equipment in other radioactive remotely operated facilities such as suited entry repair areas, canyons or caves, but does not apply to equipment used in commercial power reactors. 1.1.3 This guide does not apply to equipment used in gloveboxes. 1.2 Applicability: 1.2.1 This guide is intended for persons who are tasked with the planning, design, procurement, fabrication, installation, or testing of equipment used in rem...

  12. Down-regulation of estrogen receptor-alpha and rearranged during transfection tyrosine kinase is associated with withaferin a-induced apoptosis in MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Samadi Abbas K

    2011-10-01

    Full Text Available Abstract Background Withaferin A (WA, a naturally occurring withanolide, induces apoptosis in both estrogen-responsive MCF-7 and estrogen-independent MDA-MB-231 breast cancer cell lines with higher sensitivity in MCF-7 cells, but the underlying mechanisms are not well defined. The purpose of this study was to determine the anti-cancer effects of WA in MCF-7 breast cancer cells and explore alterations in estrogen receptor alpha (ERα and its associated molecules in vitro as novel mechanisms of WA action. Methods The effects of WA on MCF-7 viability and proliferation were evaluated by 3-(4, 5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS assay and trypan blue exclusion assays. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC/propidium iodide (PI flow cytometry and Western blot analysis of poly (ADP-ribose polymerase (PARP cleavage. Cell cycle effects were analyzed by PI flow cytometry. Western blotting was also conducted to examine alterations in the expression of ERα and pathways that are associated with ERα function. Results WA resulted in growth inhibition and decreased viability in MCF-7 cells with an IC50 of 576 nM for 72 h. It also caused a dose- and time-dependent apoptosis and G2/M cell cycle arrest. WA-induced apoptosis was associated with down-regulation of ERα, REarranged during Transfection (RET tyrosine kinase, and heat shock factor-1 (HSF1, as well as up-regulation of phosphorylated p38 mitogen-activated protein kinase (phospho-p38 MAPK, p53 and p21 protein expression. Co-treatment with protein synthesis inhibitor cycloheximide or proteasome inhibitor MG132 revealed that depletion of ERα by WA is post-translational, due to proteasome-dependent ERα degradation. Conclusions Taken together, down-regulation of ERα, RET, HSF1 and up-regulation of phospho-p38 MAPK, p53, p21 are involved in the pro-apoptotic and growth-inhibitory effects of WA in MCF-7 breast cancer cells in

  13. PAX8 is transcribed aberrantly in cervical tumors and derived cell lines due to complex gene rearrangements.

    Science.gov (United States)

    López-Urrutia, Eduardo; Pedroza-Torres, Abraham; Fernández-Retana, Jorge; De Leon, David Cantu; Morales-González, Fermín; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; García-Mendez, Jorge; García-Castillo, Verónica; Bautista-Isidro, Osvaldo; Pérez-Plasencia, Carlos

    2016-07-01

    The transcription factor PAX8, a member of the paired box-containing gene family with an important role in embryogenesis of the kidney, thyroid gland and nervous system, has been described as a biomarker in tumors of the thyroid, parathyroid, kidney and thymus. The PAX8 gene gives rise to four isoforms, through alternative mRNA splicing, but the splicing pattern in tumors is not yet established. Cervical cancer has a positive expression of PAX8; however, there is no available data determining which PAX8 isoform or isoforms are present in cervical cancer tissues as well as in cervical carcinoma-derived cell lines. Instead of a differential pattern of splicing isoforms, we found numerous previously unreported PAX8 aberrant transcripts ranging from 378 to 542 bases and present in both cervical carcinoma-derived cell lines and tumor samples. This is the first report of PAX8 aberrant transcript production in cervical cancer. Reported PAX8 isoforms possess differential transactivation properties; therefore, besides being a helpful marker for detection of cancer, PAX8 isoforms can plausibly exert differential regulation properties during carcinogenesis. PMID:27175788

  14. Super-resolution imaging of C-type lectin spatial rearrangement within the dendritic cell plasma membrane at fungal microbe contact sites

    Directory of Open Access Journals (Sweden)

    Michelle S Itano

    2014-08-01

    Full Text Available Dendritic cells express DC-SIGN and CD206, C-type lectins (CTLs that bind a variety of pathogens and may facilitate pathogen uptake for subsequent antigen presentation. Both proteins form punctate membrane nanodomains (~80 nm on naïve cells. We analyzed the spatiotemporal distribution of CTLs following host-fungal particle contact using confocal microscopy and three distinct methods of cluster identification and measurement of receptor clusters in super-resolution datasets: DBSCAN, Pair Correlation and a custom implementation of the Getis spatial statistic. Quantitative analysis of confocal and super-resolution images demonstrated that CTL nanodomains become concentrated in the contact site relative to non-contact membrane after the first hour of exposure and established that this recruitment is sustained out to four hours. DC-SIGN nanodomains in fungal contact sites exhibit a 70% area increase and a 38% decrease in interdomain separation. Contact site CD206 nanodomains possess 90% greater area and 42% lower interdomain separation relative to non-contact regions. Contact site CTL clusters appear as disk-shaped domains of approximately 150-175 nm in diameter. The increase in length scale of CTL nanostructure in contact sites suggests that the smaller nanodomains on resting membranes may merge during fungal nanodomain structure, or that they become packed closely enough to achieve sub-resolution inter-domain edge separations of < 30 nm. This study provides evidence of local receptor spatial rearrangements on the nanoscale that occur in the plasma membrane upon pathogen binding and may direct important signaling interactions required to recognize and respond to the presence of a relatively large pathogen.

  15. Super-resolution imaging of C-type lectin spatial rearrangement within the dendritic cell plasma membrane at fungal microbe contact sites

    Science.gov (United States)

    Itano, Michelle; Graus, Matthew; Pehlke, Carolyn; Wester, Michael; Liu, Ping; Lidke, Keith; Thompson, Nancy; Jacobson, Ken; Neumann, Aaron

    2014-08-01

    Dendritic cells express DC-SIGN and CD206, C-type lectins (CTLs) that bind a variety of pathogens and may facilitate pathogen uptake for subsequent antigen presentation. Both proteins form punctate membrane nanodomains (~80 nm) on naïve cells. We analyzed the spatiotemporal distribution of CTLs following host-fungal particle contact using confocal microscopy and three distinct methods of cluster identification and measurement of receptor clusters in super-resolution datasets: DBSCAN, Pair Correlation and a custom implementation of the Getis spatial statistic. Quantitative analysis of confocal and super-resolution images demonstrated that CTL nanodomains become concentrated in the contact site relative to non-contact membrane after the first hour of exposure and established that this recruitment is sustained out to four hours. DC-SIGN nanodomains in fungal contact sites exhibit a 70% area increase and a 38% decrease in interdomain separation. Contact site CD206 nanodomains possess 90% greater area and 42% lower interdomain separation relative to non-contact regions. Contact site CTL clusters appear as disk-shaped domains of approximately 150-175 nm in diameter. The increase in length scale of CTL nanostructure in contact sites suggests that the smaller nanodomains on resting membranes may merge during fungal nanodomain structure, or that they become packed closely enough to achieve sub-resolution inter-domain edge separations of < 30 nm. This study provides evidence of local receptor spatial rearrangements on the nanoscale that occur in the plasma membrane upon pathogen binding and may direct important signaling interactions required to recognize and respond to the presence of a relatively large pathogen.

  16. The Evolving Context of Driver Mutations: ROS1 Rearrangement in Metastatic Non-Small Cell Lung Cancer.

    Science.gov (United States)

    DeCaire, Ximena; Streu, Erin

    2016-09-01

    A previously healthy, 30-year-old Filipino woman presented to an emergency department with complaints of shortness of breath and mild cough. She denied constitutional symptoms, such as night sweats, fevers, loss of appetite, or weight loss. Additional investigation revealed bilateral pleural and pericardial effusions with no obvious lung lesions or masses. The pericardial fluid was drained and preliminary cytology revealed atypical carcinoma cells. Her past medical history included an embryonic pregnancy and a benign breast cyst that was biopsied in the Philippines. She had immigrated to Canada two years earlier, was working full-time, and was living with her sister. She was planning on returning to the Philippines to wed and had a strong support system in Canada. She had never smoked cigarettes or consumed alcohol and had no family history of cancer. The patient was exposed to secondhand smoke as a child.
. PMID:27541546

  17. A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements.

    Science.gov (United States)

    Jarosova, Marie; Kriegova, Eva; Schneiderova, Petra; Fillerova, Regina; Prochazka, Vit; Mikesova, Michaela; Flodr, Patrik; Indrak, Karel; Papajik, Tomas

    2016-04-01

    BCL6 rearrangements (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. In DLBCL, the translocations occur predominantly in the "major breakpoint region" encompassing the first noncoding exon and a part of the first intron of BCL6; few cases with "alternative breakpoint cluster" located 245-285 kb 5' BCL6 were also described. The regulatory sequences of known Ig and non-Ig partners replace the 5' untranslated region of the BCL6 in the same transcriptional orientation. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 translocations were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 translocations, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator. Hereby we provide comprehensive information about known non-Ig translocation partners and clinical consequences of BCL6 rearrangements in DLBCL. Moreover, we describe a novel reciprocal translocation t(3;10) in refractory patient with DLBCL with the breaking points at 5' untranslated region of BCL6 and 5' untranslated region of the RASGEF1A gene on chromosome 10q11.21 loci; this rearrangement was associated with low BCL6 and RASGEF1A gene expressions. Our patient harbouring dual chromosomal rearrangement involving BCL2 and BCL6 genes relapsed three-times and died soon; thus, further supporting the notion that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. There is evidence of prognostic value of BCL6 rearrangements also in rituximab era. PMID:26319027

  18. Evolution of B-cell malignancy; Pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene

    International Nuclear Information System (INIS)

    The authors have analyzed the molecular genetics of the breakpoints involved in the t(8;14) and t(14;18) translocations of an acute pre-B-cell leukemia from a patient with a history of follicular lymphoma. In this patient's leukemic cells, the breakpoint of the t(14;18) translocation occurred in the major breakpoint-cluster region of the BCL2 gene and became linked to the JH4 joining-region gene segment of the immunoglobulin heavy-chain locus on the 14q+ chromosome as previously observed in follicular lymphoma. An N region and heptamer and nonamer signal sequences indicated that this translocation occurred as a mistake in VH-DH-JH joining (where VH and DH are the variable and diversity segments). In the t(8;14) translocation, the breakpoint was located immediately 5' of the first exon of the MYC protooncogene, which was juxtaposed with the Cγ2 constant gene segment of the second 14q+ chromosome. The finding of repeated sequences typical of switch regions suggested that this translocation occurred during heavy-chain isotype switching, resulting in progression to pre-B-cell leukemia with both the 5(8;14) and the t(14;18) translocations. The terminal deoxynucleotidyltransferase-positive phenotype of the patient's leukemic cells further suggests that the pre-B-cell leukemia was derived from a pre-B cell carrying a t(14;18) translocation in the original follicular lymphoma. The polymerase chain reaction method was then used to identify cancer cells in the bone marrow of the patient

  19. Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy

    International Nuclear Information System (INIS)

    Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy

  20. Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles

    DEFF Research Database (Denmark)

    Lima, K; Abrahamsen, Gitte Meldgaard; Foelling, I;

    2010-01-01

    -expression of CD3, CD45RA and CCR9 (r=0.84) as well as with the CD4+ and CD8+ T cell subtypes. RTE-related T cell counts also paralleled age-related TREC reductions. CD45RA+ T cells correlated well with absolute counts of CD4+ (r=0.87) and CD8+ (r=0.75) RTE-related T cells. Apart from CD45RA- T cells, all T......Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry for...... direct subtyping of recent thymic emigrant (RTE)-related T cells in 43 patients (aged 1-54 years; median 9 years) from all over Norway and in age-matched healthy controls. Thymic volumes were estimated by ultrasound in patients. TREC levels correlated well with RTE-related T cells defined by co...

  1. GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Disease): A guide for patients and families after stem cell transplant The immune system is the body's tool ... and attacking them. When you receive a donor's stem cells (the “graft”), the stem cells recreate the donor's ...

  2. Claisen thermally rearranged (CTR) polymers

    Science.gov (United States)

    Tena, Alberto; Rangou, Sofia; Shishatskiy, Sergey; Filiz, Volkan; Abetz, Volker

    2016-01-01

    Thermally rearranged (TR) polymers, which are considered the next-generation of membrane materials because of their excellent transport properties and high thermal and chemical stability, are proven to have significant drawbacks because of the high temperature required for the rearrangement and low degree of conversion during this process. We demonstrate that using a [3,3]-sigmatropic rearrangement, the temperature required for the rearrangement of a solid glassy polymer was reduced by 200°C. Conversions of functionalized polyimide to polybenzoxazole of more than 97% were achieved. These highly mechanically stable polymers were almost five times more permeable and had more than two times higher degrees of conversion than the reference polymer treated under the same conditions. Properties of these second-generation TR polymers provide the possibility of preparing efficient polymer membranes in a form of, for example, thin-film composite membranes for various gas and liquid membrane separation applications.

  3. Targeted genomic rearrangements using CRISPR/Cas technology

    OpenAIRE

    Choi, Peter S.; Meyerson, Matthew

    2014-01-01

    Genomic rearrangements are frequently observed in cancer cells but have been difficult to generate in a highly specific manner for functional analysis. Here we report the application of CRISPR/Cas technology to successfully generate several types of chromosomal rearrangements implicated as driver events in lung cancer, including the CD74-ROS1 translocation event and the EML4-ALK and KIF5B-RET inversion events. Our results demonstrate that Cas9-induced DNA breaks promote efficient rearrangemen...

  4. Characterization of the T-cell receptor gamma chain gene rearrangements as an adjunct tool in the diagnosis of T-cell lymphomas in the gastrointestinal tract of cats.

    Science.gov (United States)

    Gress, Verena; Wolfesberger, Birgitt; Fuchs-Baumgartinger, Andrea; Nedorost, Nora; Saalmüller, Armin; Schwendenwein, Ilse; Rütgen, Barbara C; Hammer, Sabine E

    2016-08-01

    Feline alimentary lymphoma is the most common hematopoietic neoplasia in cats. It affects mainly the small intestines and is most frequently of T-cell origin. Evaluation of a fine needle aspirate is often the first step in the diagnostic work-up. Differentiation between a resident mature lymphocyte population as encountered in inflammatory bowel disease and small cell lymphoma cannot be achieved by cytology alone. Even full thickness biopsies evaluated by histopathology can be inconclusive. These cases warrant the application of complementary tools like PCR-based T-cell receptor (TCR) clonality testing for confirmation. The aim of this study was to optimize the DNA extraction protocol for formalin fixed and paraffin embedded tissues (FFPE) and to establish a heteroduplex analysis to enhance resolution of the PCR fragments of the T-cell receptor gamma (TCRG) V-J gene. The new protocols resulted in improved quantity and quality of the extracted DNA. Heteroduplex analysis of the samples improved the resolution of the electrophoresis results so that rules for interpretation of the different patterns could be established. Application of this improved setup detected clonal rearrangements in at least one TCRG primer reaction in 31 of 36 of our feline intestinal lymphoma samples after DNA quality testing. PMID:27474005

  5. Immune cell profiling to guide therapeutic decisions in rheumatic diseases.

    Science.gov (United States)

    Ermann, Joerg; Rao, Deepak A; Teslovich, Nikola C; Brenner, Michael B; Raychaudhuri, Soumya

    2015-09-01

    Biomarkers are needed to guide treatment decisions for patients with rheumatic diseases. Although the phenotypic and functional analysis of immune cells is an appealing strategy for understanding immune-mediated disease processes, immune cell profiling currently has no role in clinical rheumatology. New technologies, including mass cytometry, gene expression profiling by RNA sequencing (RNA-seq) and multiplexed functional assays, enable the analysis of immune cell function with unprecedented detail and promise not only a deeper understanding of pathogenesis, but also the discovery of novel biomarkers. The large and complex data sets generated by these technologies--big data--require specialized approaches for analysis and visualization of results. Standardization of assays and definition of the range of normal values are additional challenges when translating these novel approaches into clinical practice. In this Review, we discuss technological advances in the high-dimensional analysis of immune cells and consider how these developments might support the discovery of predictive biomarkers to benefit the practice of rheumatology and improve patient care. PMID:26034835

  6. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

    DEFF Research Database (Denmark)

    Mann, Georg; Attarbaschi, Andishe; Schrappe, Martin;

    2010-01-01

    To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL(+)), we compared the outcome of MLL(+) patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376...... such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only...

  7. Gene activation by induced DNA rearrangements

    International Nuclear Information System (INIS)

    A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

  8. THE RELATIONSHIP BETWEEN NON-HODGKIN'S LYMPHOMA AND THE GENE REARRANGEMENT

    Institute of Scientific and Technical Information of China (English)

    Guo Sutang; Liu Yongchang; Sun Junning

    1998-01-01

    Objective:To investigate the pattern of clonal rearrangement of immunoglobulin heavy chain gene (IGH) and T-cell receptor γ gene (TCRγ) of NonHodgkin's lymphoma (NHL). Methods: Bone marrow smears of 211 patients of NHL were detected by PCR, the rearranged IGH and TCRγ gene was amplified using oligonucleotide primers. Results: The clonal rearrangement of IGH gene was detectable in 51.2%(108/211); the clonal rearrangement of TCRγ gene was detectable in 21.3% (45/211); both IGH and TCRγwas detectable in 5.7% (12/211);no clonal rearrangement in 21.8% (46/211). And compared clonal gene rearrangement with pathological type and primary site of tumor. Ten patients of NHL were investigated serially. 5/10 patients still had clonal gene rearrangement at clinical complete remission. Conclusion: It demonstrated that this assay may be useful in monitoring the minimal residual disease (MRD) and in evaluating effectiveness of therapy.

  9. Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

  10. Guiding pancreatic beta cells to target electrodes in a whole-cell biosensor for diabetes.

    Science.gov (United States)

    Pedraza, Eileen; Karajić, Aleksandar; Raoux, Matthieu; Perrier, Romain; Pirog, Antoine; Lebreton, Fanny; Arbault, Stéphane; Gaitan, Julien; Renaud, Sylvie; Kuhn, Alexander; Lang, Jochen

    2015-10-01

    We are developing a cell-based bioelectronic glucose sensor that exploits the multi-parametric sensing ability of pancreatic islet cells for the treatment of diabetes. These cells sense changes in the concentration of glucose and physiological hormones and immediately react by generating electrical signals. In our sensor, signals from multiple cells are recorded as field potentials by a micro-electrode array (MEA). Thus, cell response to various factors can be assessed rapidly and with high throughput. However, signal quality and consequently overall sensor performance rely critically on close cell-electrode proximity. Therefore, we present here a non-invasive method of further exploiting the electrical properties of these cells to guide them towards multiple micro-electrodes via electrophoresis. Parameters were optimized by measuring the cell's zeta potential and modeling the electric field distribution. Clonal and primary mouse or human β-cells migrated directly to target electrodes during the application of a 1 V potential between MEA electrodes for 3 minutes. The morphology, insulin secretion, and electrophysiological characteristics were not altered compared to controls. Thus, cell manipulation on standard MEAs was achieved without introducing any external components and while maintaining the performance of the biosensor. Since the analysis of the cells' electrical activity was performed in real time via on-chip recording and processing, this work demonstrates that our biosensor is operational from the first step of electrically guiding cells to the final step of automatic recognition. Our favorable results with pancreatic islets, which are highly sensitive and fragile cells, are encouraging for the extension of this technique to other cell types and microarray devices. PMID:26282013

  11. Will the requirement by the US FDA to simultaneously co-develop companion diagnostics (CDx delay the approval of receptor tyrosine kinase (RTK inhibitors for RTK-rearranged (ROS1-, RET-, AXL-, PDGFR-a-, NTRK1- non-small cell lung cancer globally?

    Directory of Open Access Journals (Sweden)

    Sai-HongIgnatiusOu

    2014-04-01

    Full Text Available The discovery of anaplastic lymphoma kinase (ALK rearrangement in non-small cell lung cancer (NSCLC in 2007 and the approval of crizotinib for the treatment of advanced ALK-rearranged NSCLC in 2011 represents a landmark in the development of targeted oncology therapy. The approval of crizotinib was accompanied simultaneously by the approval of approval of the Vysis (Abbott Molecular break-apart fluorescence in situ hybridization test as the companion diagnostic (CDx test to detect ALK rearrangement. Pfizer, the manufacturer of crizotinib, sponsored the screening of thousands of patients and the standardization of the ALK FISH test as part of the approval process for crizotinib, a first in class ALK inhibitor. Many pharmaceutical companies are now using the FDA-approved ALK FISH assay to enroll patients onto trials for their own respective ALK inhibitors. In essence they are “piggybacking” on the FDA-approved ALK FISH assay without having to pay for the development of a CDx, nor screening for ALK-rearranged NSCLC patients in the protocols because screening for ALK rearrangement is now the standard of care in NSCLC after the approval of crizotinib. Since 2007, rearrangement in more RTKs such as ROS1, RET, AXL, PDGFR-α, and NTRK1 have been discovered in NSCLC but the incidence of each subtype of RTK-rearranged NSCLC is quite rare. Crizotinib has now demonstrated significant clinical activity in ROS1-rearranged NSCLC patients. Whether crizotinib will gain official FDA approval for use in ROS1-rearranged NSCLC, on the other hand, remains unclear as there is no test for ROS1 rearrangement currently being developed to support US FDA approval as a CDx. This may be due in part to the fact that the full cost associated with the development of a pre-market approved (PMA-approved CDx must be borne by the company seeking the first drug approval in a new indication. Given the low incidence of ROS1 rearrangement in NSCLC, and the availability of

  12. Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient.

    Directory of Open Access Journals (Sweden)

    Manami Miyai

    Full Text Available Comprehensive immunological evaluation is crucial for monitoring patients undergoing antigen-specific cancer immunotherapy. The identification and quantification of T cell responses is most important for the further development of such therapies. Using well-characterized clinical samples from a high responder patient (TK-f01 in an NY-ESO-1f peptide vaccine study, we performed high-throughput T cell receptor β-chain (TCRB gene next generation sequencing (NGS to monitor the frequency of NY-ESO-1-specific CD8+ T cells. We compared these results with those of conventional immunological assays, such as IFN-γ capture, tetramer binding and limiting dilution clonality assays. We sequenced human TCRB complementarity-determining region 3 (CDR3 rearrangements of two NY-ESO-1f-specific CD8+ T cell clones, 6-8L and 2F6, as well as PBMCs over the course of peptide vaccination. Clone 6-8L possessed the TCRB CDR3 gene TCRBV11-03*01 and BJ02-01*01 with amino acid sequence CASSLRGNEQFF, whereas 2F6 possessed TCRBV05-08*01 and BJ02-04*01 (CASSLVGTNIQYF. Using these two sequences as models, we evaluated the frequency of NY-ESO-1-specific CD8+ T cells in PBMCs ex vivo. The 6-8L CDR3 sequence was the second most frequent in PBMC and was present at high frequency (0.7133% even prior to vaccination, and sustained over the course of vaccination. Despite a marked expansion of NY-ESO-1-specific CD8+ T cells detected from the first through 6th vaccination by tetramer staining and IFN-γ capture assays, as evaluated by CDR3 sequencing the frequency did not increase with increasing rounds of peptide vaccination. By clonal analysis using 12 day in vitro stimulation, the frequency of B*52:01-restricted NY-ESO-1f peptide-specific CD8+ T cells in PBMCs was estimated as only 0.0023%, far below the 0.7133% by NGS sequencing. Thus, assays requiring in vitro stimulation might be underestimating the frequency of clones with lower proliferation potential. High-throughput TCRB

  13. Secondary Heavy Chain Rearrangement

    OpenAIRE

    Sekiguchi, Debora R.; Eisenberg, Robert A.; Weigert, Martin

    2003-01-01

    The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti–double-stranded (ds...

  14. Clonal rearrangements in human irradiated fibroblasts

    International Nuclear Information System (INIS)

    The cytogenetic dose response following in vivo localized irradiation is difficult to establish because of the occurrence of clones defined by chromosome alterations, with various proliferative rates. The biological meaning of these clones is not well understood. Two sets of experiments were performed to follow their behavior. R-banded karyotypes were established on human fibroblasts irradiated either before or after initiation of the cultures. Clones were observed in cultures developed after irradiation of biopsies, whereas irradiated cultures exhibited karyotypes with multiple non-clonal rearrangements. This difference suggests that most radiation-induced chromosome anomalies do not confer a selective advantage on the carrier cells in vitro. The appearance of clonal anomalies following biopsy irradiation would rather be a consequence of a strong selection at the time of the growth of the cells out of the explants, which would give rise to the progeny of a limited number of progenitor cells

  15. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged Non-Small Cell Lung Cancer with brain metastases

    Science.gov (United States)

    Subbiah, Vivek; Berry, Jenny; Roxas, Michael; Guha-Thakurta, Nandita; Subbiah, Ishwaria Mohan; Ali, Siraj M.; McMahon, Caitlin; Miller, Vincent; Cascone, Tina; Pai, Shobha; Tang, Zhenya; Heymach, John V.

    2016-01-01

    In-frame fusion KIF5B (the-kinesin-family-5B-gene)-RET transcripts have been characterized in 1–2% of non-small cell lung cancers and are known oncogenic drivers. The RET tyrosine kinase inhibitor, vandetanib, suppresses fusion-induced, anchorage-independent growth activity. In vitro studies have shown that vandetanib is a high-affinity substrate of breast cancer resistance protein (Bcrp1/Abcg2) but is not transported by P-glycoprotein (P-gp), limiting its blood-brain barrier penetration. A co-administration strategy to enhance the brain accumulation of vandetanib by modulating P-gp/Abcb1- and Bcrp1/Abcg2-mediated efflux with mTOR inhibitors, specifically everolimus, was shown to increase the blood-brain barrier penetration. We report the first bench to bed-side evidence that RET inhibitor combined with an mTOR inhibitor is active against brain-metastatic RET-rearranged lung cancer and the first evidence of blood-brain barrier penetration. A 74 year old female with progressive adenocarcinoma of the lung (wild-type EGFR and no ALK rearrangement) presented for therapy options. A deletion of 5’RET was revealed by FISH assay, indicating RET-gene rearrangement. Because of progressive disease in the brain, she was enrolled in a clinical trial with vandetanib and everolimus (NCT01582191). Comprehensive genomic profiling revealed fusion of KIF5B (the-kinesin-family-5B-gene) and RET, in addition to AKT2 gene amplification. After 2 cycles of therapy a repeat MRI brain showed a decrease in the intracranial disease burden and PET /CT showed systemic response as well. Interestingly, AKT2 amplification seen is a critical component of the PI3K/mTOR pathway, alterations of which has been associated with both de novo and acquired resistance to targeted therapy. The addition of everolimus may have both overcome the AKT2 amplification to produce a response in addition to its direct effects on the RET gene. Our case report forms the first evidence of blood

  16. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases.

    Science.gov (United States)

    Subbiah, Vivek; Berry, Jenny; Roxas, Michael; Guha-Thakurta, Nandita; Subbiah, Ishwaria Mohan; Ali, Siraj M; McMahon, Caitlin; Miller, Vincent; Cascone, Tina; Pai, Shobha; Tang, Zhenya; Heymach, John V

    2015-07-01

    In-frame fusion KIF5B (the-kinesin-family-5B-gene)-RET transcripts have been characterized in 1-2% of non-small cell lung cancers and are known oncogenic drivers. The RET tyrosine kinase inhibitor, vandetanib, suppresses fusion-induced, anchorage-independent growth activity. In vitro studies have shown that vandetanib is a high-affinity substrate of breast cancer resistance protein (Bcrp1/Abcg2) but is not transported by P-glycoprotein (P-gp), limiting its blood-brain barrier penetration. A co-administration strategy to enhance the brain accumulation of vandetanib by modulating P-gp/Abcb1- and Bcrp1/Abcg2-mediated efflux with mTOR inhibitors, specifically everolimus, was shown to increase the blood-brain barrier penetration. We report the first bench-to-bedside evidence that RET inhibitor combined with an mTOR inhibitor is active against brain-metastatic RET-rearranged lung cancer and the first evidence of blood-brain barrier penetration. A 74-year-old female with progressive adenocarcinoma of the lung (wild-type EGFR and no ALK rearrangement) presented for therapy options. A deletion of 5'RET was revealed by FISH assay, indicating RET-gene rearrangement. Because of progressive disease in the brain, she was enrolled in a clinical trial with vandetanib and everolimus (NCT01582191). Comprehensive genomic profiling revealed fusion of KIF5B (the-kinesin-family-5B-gene) and RET, in addition to AKT2 gene amplification. After two cycles of therapy a repeat MRI brain showed a decrease in the intracranial disease burden and PET/CT showed systemic response as well. Interestingly, AKT2 amplification seen is a critical component of the PI3K/mTOR pathway, alterations of which has been associated with both de novo and acquired resistance to targeted therapy. The addition of everolimus may have both overcome the AKT2 amplification to produce a response in addition to its direct effects on the RET gene. Our case report forms the first evidence of blood-brain barrier penetration by

  17. Controlled neuronal cell patterning and guided neurite growth on micropatterned nanofiber platforms

    International Nuclear Information System (INIS)

    Patterning neuronal cells and guiding neurite growth are important for applications such as prosthetics, cell based biosensors, and tissue engineering. In this paper, a microdevice is presented that provides neuronal cell patterning and guided neurite growth on a collagen coated gelatin/PCL nanofiber mat. The pattern consisted of a grid of polystyrene microwells/nodes to confine the cell bodies and orthogonal grooves to guide neurite growth from each node. Vacuum assisted cell seeding was used to localize cell bodies in the microwells and physically separate the cells during seeding. The electrospun nanofiber mats under the polystyrene microstructures were coated with collagen to enhance the cellular attachment and enhance differentiation. We evaluated the performance of our device using adhesion, viability, and differentiation assays of neuron-like PC12 cells compared to controls for vacuum seeding, spatial isolation and guidance, and collagen coating of the fibers. The device provided PC12 cell patterning with increased adhesion, differentiation, and guided neurite outgrowth compared to controls, demonstrating its potential for in vitro neuronal cell patterning studies. (paper)

  18. Detection of clonal immunoglobulin gene rearrangements in the peripheral blood progenitor cells of patients with multiple myeloma: the potential role of purging with CD34 positive selection

    OpenAIRE

    Owen, R. G.; Haynes, A P; Evans, P A; R. J. Johnson; Rawstron, A. C.; McQuaker, G; Smith, G.M; Galvin, M. C.; Barnard, D L; Russell, N H; Child, J. A.; Morgan, G J

    1996-01-01

    Aims—To determine the extent of clonal cell contamination of peripheral blood progenitor cell (PBPC) collections in patients with multiple myeloma (MM) and to assess the purging efficacy of CD34 positive selection.

  19. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  20. 3D Image-Guided Automatic Pipette Positioning for Single Cell Experiments in vivo

    OpenAIRE

    Brian Long; Lu Li; Ulf Knoblich; Hongkui Zeng; Hanchuan Peng

    2015-01-01

    We report a method to facilitate single cell, image-guided experiments including in vivo electrophysiology and electroporation. Our method combines 3D image data acquisition, visualization and on-line image analysis with precise control of physical probes such as electrophysiology microelectrodes in brain tissue in vivo. Adaptive pipette positioning provides a platform for future advances in automated, single cell in vivo experiments.

  1. A reference guide to microbial cell surface hydrophobicity based on contact angles

    NARCIS (Netherlands)

    van der Mei, HC; Busscher, HJ; Bos, R.R.M.

    1998-01-01

    Acid-base interactions form the origin of the hydrophobicity of microbial cell-surfaces and can be quantitated from contact angle measurements on microbial lawns with water, formamide, methyleneiodide and/or alpha-bromonaphthalene. This review provides a reference guide to microbial cell surface hyd

  2. Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma.

    Science.gov (United States)

    Hung, Yin P; Fletcher, Christopher D M; Hornick, Jason L

    2016-04-01

    Ewing sarcoma shows considerable histologic overlap with other round cell tumors. NKX2-2, a homeodomain transcription factor involved in neuroendocrine/glial differentiation and a downstream target of EWSR1-FLI1, has been reported as an immunohistochemical marker for Ewing sarcoma. We assessed the specificity of NKX2-2 for Ewing sarcoma compared with other round cell malignant neoplasms and other soft tissue tumors with EWSR1 translocations. We evaluated whole-tissue sections from 270 cases: 40 Ewing sarcomas (4 with atypical/large cell features), 20 CIC-DUX4 sarcomas, 5 BCOR-CCNB3 sarcomas, 9 unclassified round cell sarcomas, 10 poorly differentiated synovial sarcomas, 10 lymphoblastic lymphomas, 10 alveolar rhabdomyosarcomas, 10 embryonal rhabdomyosarcomas, 10 Merkel cell carcinomas, 10 small cell carcinomas, 20 melanomas, 5 NUT midline carcinomas, 10 Wilms tumors, 10 neuroblastomas, 10 olfactory neuroblastomas, 12 mesenchymal chondrosarcomas, 10 angiomatoid fibrous histiocytomas, 10 clear cell sarcomas, 5 gastrointestinal clear cell sarcoma-like tumors, 5 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas, 10 soft tissue and cutaneous myoepitheliomas, and 19 myoepithelial carcinomas. NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells. NKX2-2 was positive in 37/40 (93%) Ewing sarcomas, including all atypical Ewing sarcomas and cases with known EWSR1-FLI1 or EWSR1-ERG fusion; 85% of Ewing sarcomas showed diffuse (>50%) staining. NKX2-2 was positive in 9 (75%) mesenchymal chondrosarcomas, 8 (80%) olfactory neuroblastomas, 1 CIC-DUX4 sarcoma, 1 poorly differentiated synovial sarcoma, 1 neuroblastoma, 2 unclassified round cell sarcomas, and 3 small cell carcinomas; all other EWSR1-associated tumors were negative for NKX2-2, apart from 1 desmoplastic small round cell tumor, 1 myoepithelioma, and 1 myoepithelial carcinoma. In summary, NKX2-2 is a sensitive but imperfectly specific marker for

  3. Single-walled carbon nanotube exposure induces membrane rearrangement and suppression of receptor-mediated signalling pathways in model mast cells

    Science.gov (United States)

    Umemoto, Eric Y.; Speck, Mark; Shimoda, Lori M.N.; Kahue, Kara; Sung, Carl; Stokes, Alexander J.; Turner, Helen

    2014-01-01

    Carbon nanotubes (CNT) are environmental challenges to the respiratory and gastrointestinal mucosa, and to the dermal immune system. Mast cells (MC) are pro-inflammatory immunocytes that reside at these interfaces with the environment. Mast cells are sources of pro-inflammatory mediators (histamine, serotonin, matrix-active proteases, eicosanoids, prostanoids, cytokines and chemokines), which are released in a calcium-dependent manner following immunological challenge or physico-chemical stimulation. Since C-60 fullerenes, which share geometry with CNT, are suppressive of mast cell-driven inflammatory responses, we explored the effects of unmodified SWCNT aggregates on mast cell signaling pathways, phenotype and pro-inflammatory function. We noted SWCNT suppression of antigen-induced signalling pathways and pro-inflammatory degranulation responses. Mast cells recognize unmodified SWCNT by remodeling the plasma membrane, disaggregating the cortical actin cytoskeleton and relocalizing clathrin. Clathrin was also identified as a component of an affinity-purified ‘interactome’ isolated from MC using an SWCNT affinity matrix for mast cell lysates. Together these data are consistent with the ability of SWCNT to suppress mast cell pro-inflammatory function via a novel recognition mechanism. PMID:24910985

  4. Time to Relax: Mechanical Stress Release Guides Stem Cell Responses.

    Science.gov (United States)

    Sommerfeld, Sven D; Elisseeff, Jennifer H

    2016-02-01

    Stem cells integrate spatiotemporal cues, including the mechanical properties of their microenvironment, into their fate decisions. Chaudhuri et al. (2015) show that the ability of the extracellular matrix to dissipate cell-induced forces, referred to as stress-relaxation, is a key mechanical signal influencing stem cell fate and function. PMID:26849301

  5. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

    Science.gov (United States)

    Stumpel, Dominique J P M; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2015-09-01

    MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. MLL-rearranged infant ALL responds remarkably well to nucleoside analogue drugs in vitro, such as cytarabine and cladribine, and to the demethylating agents decitabine and zebularine as measured by cytotoxicity assays. These observations led to the inclusion of cytarabine into the treatment regimens currently used for infants with ALL. However, survival chances for infants with MLL-rearranged ALL do still not exceed 30-40%. Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Therefore we used both cell line models as well as primary patient cells. Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ∼25 nM. Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Demethylation of the FHIT promoter region was accompanied by subtle re-expression of this gene both at the mRNA and protein level. We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. PMID:26188848

  6. Lack of feedback inhibition of V kappa gene rearrangement by productively rearranged alleles.

    Science.gov (United States)

    Harada, K; Yamagishi, H

    1991-02-01

    Circular DNAs excised by immunoglobulin kappa chain gene rearrangements were cloned and characterized. 16 of 17 clones examined were double recombination products containing a V kappa-J kappa rearrangement (coding joint) as well as the reciprocal element (signal joint) of another V kappa-J kappa rearrangement. These products suggested multiple recombination, primary inversion, and secondary excision. In primary events, 5 of 16 translational reading frames were in-phase. Thus, V kappa gene rearrangement may not be inhibited by the presence of a productively rearranged allele. An unusually large trinucleotide (P) insertion forming a palindrome of 12 nucleotides was also observed in one of the coding joints. PMID:1988542

  7. A practical guide to hydrogels for cell culture.

    Science.gov (United States)

    Caliari, Steven R; Burdick, Jason A

    2016-04-28

    There is growing appreciation of the role that the extracellular environment plays in regulating cell behavior. Mechanical, structural, and compositional cues, either alone or in concert, can drastically alter cell function. Biomaterials, and particularly hydrogels, have been developed and implemented to present defined subsets of these cues for investigating countless cellular processes as a means of understanding morphogenesis, aging, and disease. Although most scientists concede that standard cell culture materials (tissue culture plastic and glass) do a poor job of recapitulating native cellular milieus, there is currently a knowledge barrier for many researchers in regard to the application of hydrogels for cell culture. Here, we introduce hydrogels to those who may be unfamiliar with procedures to culture and study cells with these systems, with a particular focus on commercially available hydrogels. PMID:27123816

  8. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  9. Aptamer-guided gene targeting in yeast and human cells

    OpenAIRE

    Ruff, Patrick; Koh, Kyung Duk; Keskin, Havva; Pai, Rekha B.; Storici, Francesca

    2014-01-01

    Gene targeting is a genetic technique to modify an endogenous DNA sequence in its genomic location via homologous recombination (HR) and is useful both for functional analysis and gene therapy applications. HR is inefficient in most organisms and cell types, including mammalian cells, often limiting the effectiveness of gene targeting. Therefore, increasing HR efficiency remains a major challenge to DNA editing. Here, we present a new concept for gene correction based on the development of DN...

  10. Procuring Stationary Fuel Cells For CHP: A Guide for Federal Facility Decision Makers

    Energy Technology Data Exchange (ETDEWEB)

    Stinton, David P [ORNL; McGervey, Joseph [SRA International, Inc.; Curran, Scott [ORNL

    2011-11-01

    Federal agency leaders are expressing growing interest in using innovative fuel cell combined heat and power (CHP) technology at their sites, motivated by both executive branch sustainability targets and a desire to lead by example in the transition to a clean energy economy. Fuel cell CHP can deliver reliable electricity and heat with 70% to 85% efficiency. Implementing this technology can be a high efficiency, clean energy solution for agencies striving to meet ambitious sustainability requirements with limited budgets. Fuel cell CHP systems can use natural gas or renewable fuels, such as biogas. Procuring Stationary Fuel Cells for CHP: A Guide for Federal Facility Decision Makers presents an overview of the process for planning and implementing a fuel cell CHP project in a concise, step-by-step format. This guide is designed to help agency leaders turn their interest in fuel cell technology into successful installations. This guide concentrates on larger (100 kW and greater) fuel cell CHP systems and does not consider other fuel cell applications such as cars, forklifts, backup power supplies or small generators (<100 kW). Because fuel cell technologies are rapidly evolving and have high up front costs, their deployment poses unique challenges. The electrical and thermal output of the CHP system must be integrated with the building s energy systems. Innovative financing mechanisms allow agencies to make a make versus buy decision to maximize savings. This guide outlines methods that federal agencies may use to procure fuel cell CHP systems with little or no capital investment. Each agency and division, however, has its own set of procurement procedures. This guide was written as a starting point, and it defers to the reader s set of rules if differences exist. The fuel cell industry is maturing, and project developers are gaining experience in working with federal agencies. Technology improvements, cost reductions, and experienced project developers are making

  11. An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response.

    Science.gov (United States)

    Ohlschläger, Peter; Pes, Michaela; Osen, Wolfram; Dürst, Matthias; Schneider, Achim; Gissmann, Lutz; Kaufmann, Andreas M

    2006-04-01

    A new and very promising approach in vaccine development is the application of naked DNA. In comparison to conventional vaccines it offers several advantages, especially if there is a need for the development of low cost vaccines. Infection with high-risk human papillomaviruses (hr-HPVs) is the major risk factor for the development of cervical cancer (cc), the third most common cancer in women worldwide. The HPV E7 oncogene is constitutively expressed in HPV-infected cells and represents an excellent target for immune therapy of HPV-related disease. Therefore, we chose the HPV-16 E7 as model antigen in the development of a therapeutic DNA vaccine candidate. For safety reasons the use of a transforming gene like the HPV-16 E7 for DNA vaccination is not feasible in humans. In consequence we have generated an artificial ("shuffled") HPV-16 E7-gene (HPV-16 E7SH), containing all putative cytotoxic T-lymphocyte (CTLs) epitopes and exhibiting high safety features. Here, we show the induction of a strong E7-wildtype (E7WT) directed cellular and humoral immune response including tumor protection and regression after in vivo immunization in the murine system. Moreover, the vaccine candidate demonstrated immunogenicity in humans, demonstrated by priming of antigen-specific T cells in vitro. Importantly, the artificial HPV-gene has completely lost its transforming properties as measured in soft agar transformation assays. These results may be of importance for the development of vaccines based on oncogenes or oncoproteins. PMID:16472545

  12. The sweet spot: how GAGs help chemokines guide migrating cells.

    Science.gov (United States)

    Monneau, Yoan; Arenzana-Seisdedos, Fernando; Lortat-Jacob, Hugues

    2016-06-01

    Glycosaminoglycans are polysaccharides that occur both at the cell surface and within extracellular matrices. Through their ability to bind to a large array of proteins, almost 500 of which have been identified to date, including most chemokines, these molecules regulate key biologic processes at the cell-tissue interface. To do so, glycosaminoglycans can provide scaffolds to ensure that proteins mediating specific functions will be presented at the correct site and time and can also directly contribute to biologic activities or signaling processes. The binding of chemokines to glycosaminoglycans, which, at the biochemical level, has been mostly studied using heparin, has traditionally been thought of as a mechanism for maintaining haptotactic gradients within tissues along which cells can migrate directionally. Many aspects of chemokine-glycosaminoglycan interactions, however, also suggest that the formation of these complexes could serve additional purposes that go well beyond a simple immobilization process. In addition, progress in glycobiology has revealed that glycosaminoglycan structures, in term of length, sulfation, and epimerization pattern, are specific for cell, tissue, and developmental stage. Glycosaminoglycan regulation and glycosaminoglycan diversity, which cannot be replicated using heparin, thus suggests that these molecules may fine-tune the immune response by selectively recruiting specific chemokines to cell surfaces. In this context, the aim of the present text is to review the chemokine-glycosaminoglycan complexes described to date and provide a critical analysis of the tools, molecules, and strategies that can be used to structurally and functionally investigate the formation of these complexes. PMID:26701132

  13. Drug-loaded biodegradable microspheres for image-guided combinatory epigenetic therapy in cells

    OpenAIRE

    Xu, Ronald X.; Xu, Jeff S.; Zuo, Tao; Shen, Rulong; Huang, Tim H.; Michael F. Tweedle

    2011-01-01

    We synthesize drug-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for image-guided combinatory epigenetic therapy in MCF-10A human mammary epithelial cells. LY294002 and Nile Red are encapsulated in microspheres for sustained drug release and fluorescence microscopic imaging. Drug-loaded microspheres target MCF-10A cells through a three-step binding process involving biotinylated antibody, streptavidin, and biotinylated microspheres. LY294002 loaded microspheres and 5-Aza-2-deoxycy...

  14. Chromosome rearrangements and transposable elements.

    Science.gov (United States)

    Lonnig, Wolf-Ekkehard; Saedler, Heinz

    2002-01-01

    There has been limited corroboration to date for McClintock's vision of gene regulation by transposable elements (TEs), although her proposition on the origin of species by TE-induced complex chromosome reorganizations in combination with gene mutations, i.e., the involvement of both factors in relatively sudden formations of species in many plant and animal genera, has been more promising. Moreover, resolution is in sight for several seemingly contradictory phenomena such as the endless reshuffling of chromosome structures and gene sequences versus synteny and the constancy of living fossils (or stasis in general). Recent wide-ranging investigations have confirmed and enlarged the number of earlier cases of TE target site selection (hot spots for TE integration), implying preestablished rather than accidental chromosome rearrangements for nonhomologous recombination of host DNA. The possibility of a partly predetermined generation of biodiversity and new species is discussed. The views of several leading transposon experts on the rather abrupt origin of new species have not been synthesized into the macroevolutionary theory of the punctuated equilibrium school of paleontology inferred from thoroughly consistent features of the fossil record. PMID:12429698

  15. A short guide to technology development in cell biology

    NARCIS (Netherlands)

    B. van Steensel (Bas)

    2015-01-01

    textabstractNew technologies drive progress in many research fields, including cell biology. Much of technological innovation comes from "bottom-up" efforts by individual students and postdocs. However, technology development can be challenging, and a successful outcome depends on many factors. This

  16. Rearrangement of Legal Holidays Opens Hot Debate

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ On November 9, the National Development and Reform Commission conducted a poll regarding the rearrangement of national legal holidays on its official website.After a year of research and study, a framework for the changes has been completed.

  17. Fourier tranform in exponential rearrangement invariant spaces

    OpenAIRE

    Ostrovsky, E.; Sirota, L.

    2004-01-01

    In this article we investigate the Fourier series and transforms for the functions defined on the $ [0, 2 \\pi]^ d $ or $ R^d $ and belonging to the exponential Orlicz and some other rearrangement invariant (r.i.) spaces.

  18. Environmental cues to guide stem cell fate decision for tissue engineering applications.

    Science.gov (United States)

    Alsberg, Eben; von Recum, Horst A; Mahoney, Melissa J

    2006-09-01

    The human body contains a variety of stem cells capable of both repeated self-renewal and production of specialised, differentiated progeny. Critical to the implementation of these cells in tissue engineering strategies is a thorough understanding of which external signals in the stem cell microenvironment provide cues to control their fate decision in terms of proliferation or differentiation into a desired, specific phenotype. These signals must then be incorporated into tissue regeneration approaches for regulated exposure to stem cells. The precise spatial and temporal presentation of factors directing stem cell behaviour is extremely important during embryogenesis, development and natural healing events, and it is possible that this level of control will be vital to the success of many regenerative therapies. This review covers existing tissue engineering approaches to guide the differentiation of three disparate stem cell populations: mesenchymal, neural and endothelial. These progenitor cells will be of central importance in many future connective, neural and vascular tissue regeneration technologies. PMID:16918253

  19. Rearrangement reactions in ionic liquid media

    OpenAIRE

    Sarmīte Katkeviča

    2009-01-01

    ABSTRACT Ph.D. theses „Rearrangement reactions in ionic liquid media” are devoted to the subject that has gained great actuality and large popularity today - ionic liquids. The research about three different by reaction mechanisms organic transformations – Fries, Beckmann and Claisen rearrangement reactions in ionic liquid media is discussed in the thesis. The novelty of the research is connected with the replacement of organic solvents with environmentally friendly material...

  20. Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

    Science.gov (United States)

    Unachukwu, Uchenna John; Warren, Alice; Li, Ze; Mishra, Shawn; Zhou, Jing; Sauane, Moira; Lim, Hyungsik; Vazquez, Maribel; Redenti, Stephen

    2016-03-01

    To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

  1. Investigation of fuel cells using scanning neutron imaging and a focusing neutron guide

    International Nuclear Information System (INIS)

    We present two different methods to increase the size of available neutron beams in order to allow for the investigation of large objects. Application of these methods is demonstrated for radiographic imaging of fuel cells. The first approach is a scanning procedure based on the coordinated translation of detector and sample through the beam. Further advancement was achieved by installing a focusing neutron guide, which offers an expanded neutron beam size after diverging from a focused point source.

  2. The Role of Direct Current Electric Field-Guided Stem Cell Migration in Neural Regeneration.

    Science.gov (United States)

    Yao, Li; Li, Yongchao

    2016-06-01

    Effective directional axonal growth and neural cell migration are crucial in the neural regeneration of the central nervous system (CNS). Endogenous currents have been detected in many developing nervous systems. Experiments have demonstrated that applied direct current (DC) electric fields (EFs) can guide axonal growth in vitro, and attempts have been made to enhance the regrowth of damaged spinal cord axons using DC EFs in in vivo experiments. Recent work has revealed that the migration of stem cells and stem cell-derived neural cells can be guided by DC EFs. These studies have raised the possibility that endogenous and applied DC EFs can be used to direct neural tissue regeneration. Although the mechanism of EF-directed axonal growth and cell migration has not been fully understood, studies have shown that the polarization of cell membrane proteins and the activation of intracellular signaling molecules are involved in the process. The application of EFs is a promising biotechnology for regeneration of the CNS. PMID:27108005

  3. Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo

    Science.gov (United States)

    Choi, Myunghwan; Choi, Jin Woo; Kim, Seonghoon; Nizamoglu, Sedat; Hahn, Sei Kwang; Yun, Seok Hyun

    2013-12-01

    Polymer hydrogels are widely used as cell scaffolds for biomedical applications. Although the biochemical and biophysical properties of hydrogels have been investigated extensively, little attention has been paid to their potential photonic functionalities. Here, we report cell-integrated polyethylene glycol-based hydrogels for in vivo optical-sensing and therapy applications. Hydrogel patches containing cells were implanted in awake, freely moving mice for several days and shown to offer long-term transparency, biocompatibility, cell viability and light-guiding properties (loss of improved glucose homeostasis. Furthermore, real-time optical readout of encapsulated heat-shock-protein-coupled fluorescent reporter cells made it possible to measure the nanotoxicity of cadmium-based bare and shelled quantum dots (CdTe; CdSe/ZnS) in vivo.

  4. BIOMED-2系统引物用于检测T细胞淋巴瘤石蜡样本T细胞受体γ基因重排的研究%Application of BIOMED-2 primers in analysis of T-cell receptor γ gene rearrangements in paraffin-embedded tissue specimens of T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    唐源; 江炜; 李雷; 纪洪; 李韵; 李甘地; 刘卫平

    2009-01-01

    目的 了解BIOMED-2系统T细胞受体(TCR)γ引物组合对T细胞淋巴瘤的常规石蜡包埋组织样本中TCR基因重排的检出情况及其实用性.方法 用酚/氯仿法提取55例各种组织类型的T细胞淋巴瘤石蜡包埋组织样本的DNA并通过扩增看家基因β-globin检测其质量,利用BIOMED-2系统TCR-γ引物组合和TCR-γ基因通用型引物(TVG/TJX)对55例进行TCR基因重排检测,比较二者的检出率并进行统计学分析.结果 BIOMED-2系统TCR-γ引物组合和TCRγ基因通用型引物(TVG/TJX)的TCR基因重排检出率分别为76.4%和60.0%,前者高于后者,二者的差异无统计学意义(P>0.05).结论 BIOMED-2系统TCRγ引物组合适用于本组T细胞淋巴瘤石蜡包埋组织样本的TCR基因重排检测.%Objective To evaluate the practical values of PCR detectable T-cell receptor (TCR) gene rearrangement in paraffin embedded tissue samples in the diagnosis of T-cell malignancies using BIOMED-2 PCR multiplex tubes TCRγ(A + B). Methods Traditional phenol-chloroform method was used to extract DNA from 55 cases of archival paraffin embedded tissues samples of T-cell malignancies and the DNA quality was evaluated by PCR-based amplification of housekeeping gone β-globin. The selected BIOMED-2 PCR multiplex tubes TCRγ(A + B) were used to detect TCR gene rearrangement and comparison with the results of universal TCR primers (TVG/TJX) was performed. Results Positive detection rates by the BIOMED-2 multiplex tubes TCRγ(A + B) and the universal primers (TVG/TJX) were 76.4% and 60.0%, respectively. There were not statistical difference between the methods (P > 0.05). Conclusion BIOMED-2 multiplex tubes TCRγ(A + B) is suitable for detection of clonal rearrangements of TCR genes in current archival paraffin embeded tissue samples of T-cell malignancies.

  5. [Development and synthetic application of epoxysilane rearrangement].

    Science.gov (United States)

    Sasaki, Michiko

    2008-08-01

    O-Silyl cyanohydrins of beta-silyl-alpha,beta-epoxyaldehyde can function as a highly functionalized homoenolate equivalent via a tandem sequence involving base-promoted ring opening, Brook rearrangement, and alkylation at the allylic position. We named this rearrangement epoxysilane rearrangement. Based on results of mechanistic studies involving competitive experiments using diastereomeric cyanohydrins, we propose a reaction pathway involving a silicate intermediate formed by a concerted process via an anti-opening of the epoxide followed by the formation of an O-Si bond. Moreover, results of mechanistic studies on the rearrangement led to a conceptually novel approach to the chirality transfer in which epoxide chirality can be transferred into carbanion. We demonstrate the usefulness of the rearrangement through application to the following reactions: (1) reaction of gamma-p-toluenesulfonyl-alpha,beta-epoxysilane with alkyl halides and aldehydes followed by treatment with n-Bu4NF, which affords alpha,beta-unsaturated aldehydes (2) reaction of gamma-phosphonio-alpha,beta-epoxysilane with aldehydes, which affords dienol silyl ether derivatives (3) reaction of an enoate bearing an eposysilane moiety at the alpha-position with lithium enolate of 2-chloroacetamide, which affords highly functionalized cyclopropane derivatives. PMID:18670182

  6. FLNA genomic rearrangements cause periventricular nodular heterotopia

    Science.gov (United States)

    Clapham, K.R.; Yu, T.W.; Ganesh, V.S.; Barry, B.; Chan, Y.; Mei, D.; Parrini, E.; Funalot, B.; Dupuis, L.; Nezarati, M.M.; du Souich, C.; van Karnebeek, C.

    2012-01-01

    Objective: To identify copy number variant (CNV) causes of periventricular nodular heterotopia (PNH) in patients for whom FLNA sequencing is negative. Methods: Screening of 35 patients from 33 pedigrees on an Affymetrix 6.0 microarray led to the identification of one individual bearing a CNV that disrupted FLNA. FLNA-disrupting CNVs were also isolated in 2 other individuals by multiplex ligation probe amplification. These 3 cases were further characterized by high-resolution oligo array comparative genomic hybridization (CGH), and the precise junctional breakpoints of the rearrangements were identified by PCR amplification and sequencing. Results: We report 3 cases of PNH caused by nonrecurrent genomic rearrangements that disrupt one copy of FLNA. The first individual carried a 113-kb deletion that removes all but the first exon of FLNA. A second patient harbored a complex rearrangement including a deletion of the 3′ end of FLNA accompanied by a partial duplication event. A third patient bore a 39-kb deletion encompassing all of FLNA and the neighboring gene EMD. High-resolution oligo array CGH of the FLNA locus suggests distinct molecular mechanisms for each of these rearrangements, and implicates nearby low copy repeats in their pathogenesis. Conclusions: These results demonstrate that FLNA is prone to pathogenic rearrangements, and highlight the importance of screening for CNVs in individuals with PNH lacking FLNA point mutations. Neurology® 2012;78:269–278 PMID:22238415

  7. Langerhans Cell Histiocytosis Arising from the Mandible as Diagnosed by US-guided Core Biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soo Jin [Center of Thyroid Cancer, National Cancer Center, Goyang (Korea, Republic of); Kim, Eun Kyung [Research Institute of Radiological Science, Yonsei University Heath System, Seoul (Korea, Republic of); Lee, Min Kyung [Eulji University College of Medicine, Eulji University Hospital, Daejeon (Korea, Republic of)

    2010-09-15

    Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of Langerhans cells. Although LCH is not considered a malignant disease, its appearance on radiographs may be similar to that of a malignant tumor. The diagnosis of LCH is usually made by a soft tissue biopsy, or by bone marrow aspiration or curettage. We present a patient with a mandibular mass confirmed to be LCH by US-guided core needle biopsy, and present a strategy for diagnosing localized LCH of the bone based on the usefulness and reliability of the percutaneous biopsy

  8. Langerhans Cell Histiocytosis Arising from the Mandible as Diagnosed by US-guided Core Biopsy

    International Nuclear Information System (INIS)

    Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of Langerhans cells. Although LCH is not considered a malignant disease, its appearance on radiographs may be similar to that of a malignant tumor. The diagnosis of LCH is usually made by a soft tissue biopsy, or by bone marrow aspiration or curettage. We present a patient with a mandibular mass confirmed to be LCH by US-guided core needle biopsy, and present a strategy for diagnosing localized LCH of the bone based on the usefulness and reliability of the percutaneous biopsy

  9. Chromosomal rearrangements and the pathogenesis of differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Stefan K.G. Grebe

    2011-12-01

    Full Text Available The majority of thyroid cancers arise from the follicular cells of the thyroid gland, which yield a wide variety of distinct morphotypes, ranging from relatively indolent lesions to the most malignant forms of cancer known. The remaining primary thyroid cancers arise from C cells within the gland and result primarily from mutations of the RET protooncogene, germ line mutations of which give rise to the various forms of multiple endocrine neoplasia. The most common of the follicular cell-derived cancers are papillary carcinomas, (PTC, followed by follicular carcinomas (FTC and its Hurthle cell variant (HCC and finally anaplastic carcinomas (ATC. The pathogenesis of many thyroid cancers, of both PTC and FTC morphotype, involves chromosomal translocations. Rearrangements of the RET protoconcogene are known to be involved in the pathogenesis of ca. 50% of PTC. A similar proportion of FTC have been associated with a t(2;3(q13;p25 translocation, fusing the thyroid-specific transcription factor PAX8 with the peroxisome proliferator-activated receptor gamma (PPARγ nuclear receptor, a ubiquitously expressed transcription factor. These rearrangements have analogy with translocations in erythropoetic cells, which form the only other known group of human malignancies that are largely the result of chromosomal translocation events. In this review we compare and contrast the oncogenic properties of thyroid and erythroid chromosomal transformations and speculate on mechanisms leading to their formation.

  10. Rearrangement of cluster structure during fission processes

    DEFF Research Database (Denmark)

    Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Andrey V.;

    2004-01-01

    groups of atoms from the parent cluster is largely independent of the isomer form of the parent cluster. The importance of rearrangement of the cluster structure during the fission process is elucidated. This rearrangement may include transition to another isomer state of the parent cluster before actual......Results of molecular dynamics simulations of fission reactions $Na_10^2+ -->Na_7^++ Na_3^+ and Na_18^2+--> 2Na_9^+ are presented. The dependence of the fission barriers on the isomer structure of the parent cluster is analysed. It is demonstrated that the energy necessary for removing homothetic...

  11. Mouse model for ROS1-rearranged lung cancer.

    Directory of Open Access Journals (Sweden)

    Yasuhito Arai

    Full Text Available Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC. However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22-q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer.

  12. Mouse Model for ROS1-Rearranged Lung Cancer

    Science.gov (United States)

    Takahashi, Hiroyuki; Nakamura, Hiromi; Hama, Natsuko; Kohno, Takashi; Tsuta, Koji; Yoshida, Akihiko; Asamura, Hisao; Mutoh, Michihiro; Hosoda, Fumie; Tsuda, Hitoshi; Shibata, Tatsuhiro

    2013-01-01

    Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22–q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer. PMID:23418494

  13. Rearrangement of nucleosome structure during excision repair in xeroderma pigmentosum (group A) human fibroblasts

    International Nuclear Information System (INIS)

    Rearrangements of chromatic structure during excision repair were examined in xeroderma pigmentosum (XP; complementation group A) human fibroblasts treated with the small-molecule alkylating agent methyl methanesulfonate (MMS). We observed normal levels of repair synthesis in these cells during the first 12 h after exposure to MMS, in contrast to the near zero incorporation of repair patches following exposure to u.v. light. Our results indicate that the relative nuclease sensitivity of newly repaired regions in MMS-treated XP (group A) cells is quantitatively similar to that of newly repaired regions in MMS-treated normal human fibroblasts. This enhanced sensitivity is accompanied by a marked under-representation of repair-incorporated nucleotides in isolated nucleosome core DNA. Pulse-chase experiments demonstrated that these regions rapidly undergo rearrangements in chromatin structure, and both the rate and extent of these rearrangements are similar to those observed in normal cells. (author)

  14. Recent Developments in the Reformatsky-Claisen Rearrangement

    Directory of Open Access Journals (Sweden)

    Susumi Hatakeyama

    2012-11-01

    Full Text Available The rearrangement of allyl a-bromoacetates with Zn dust is known as the Reformatsky-Claisen rearrangement. Whereas the Ireland-Claisen rearrangement has been widely used in the synthesis of a diverse range of natural products, the Zn-mediated Reformatsky-Claisen rearrangement has not been utilized so often. In this article, we will provide an overview of recent advances in the Reformatsky-Claisen rearrangement field, including the In-mediated Reformatsky-Claisen rearrangement we have recently developed.

  15. Mouse Model for ROS1-Rearranged Lung Cancer

    OpenAIRE

    Yasuhito Arai; Yasushi Totoki; Hiroyuki Takahashi; Hiromi Nakamura; Natsuko Hama; Takashi Kohno; Koji Tsuta; Akihiko Yoshida; Hisao Asamura; Michihiro Mutoh; Fumie Hosoda; Hitoshi Tsuda; Tatsuhiro Shibata

    2013-01-01

    Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstiti...

  16. Hydrodynamic guiding for addressing subsets of immobilized cells and molecules in microfluidic systems

    Directory of Open Access Journals (Sweden)

    Beyer Michael

    2003-07-01

    Full Text Available Abstract Background The interest in microfluidics and surface patterning is increasing as the use of these technologies in diverse biomedical applications is substantiated. Controlled molecular and cellular surface patterning is a costly and time-consuming process. Methods for keeping multiple separate experimental conditions on a patterned area are, therefore, needed to amplify the amount of biological information that can be retrieved from a patterned surface area. We describe, in three examples of biomedical applications, how this can be achieved in an open microfluidic system, by hydrodynamically guiding sample fluid over biological molecules and living cells immobilized on a surface. Results A microfluidic format of a standard assay for cell-membrane integrity showed a fast and dose-dependent toxicity of saponin on mammalian cells. A model of the interactions of human mononuclear leukocytes and endothelial cells was established. By contrast to static adhesion assays, cell-cell adhesion in this dynamic model depended on cytokine-mediated activation of both endothelial and blood cells. The microfluidic system allowed the use of unprocessed blood as sample material, and a specific and fast immunoassay for measuring the concentration of C-reactive protein in whole blood was demonstrated. Conclusion The use of hydrodynamic guiding made multiple and dynamic experimental conditions on a small surface area possible. The ability to change the direction of flow and produce two-dimensional grids can increase the number of reactions per surface area even further. The described microfluidic system is widely applicable, and can take advantage of surfaces produced by current and future techniques for patterning in the micro- and nanometer scale.

  17. Molecular Insights in MLL Rearranged Acute Leukemia

    NARCIS (Netherlands)

    R.W. Stam (Ronald)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence (~80%) of rearrangements of the MLL gene, resistance to several important chemotherapeutic drugs, and a poor treatment outcome. With overall survival rates for infant ALL not exceeding 50%

  18. Input-output rearrangement of isolated converters

    DEFF Research Database (Denmark)

    Madsen, Mickey Pierre; Kovacevic, Milovan; Mønster, Jakob Døllner;

    2015-01-01

    This paper presents a new way of rearranging the input and output of isolated converters. The new arrangement posses several advantages, as increased voltage range, higher power handling capabilities, reduced voltage stress and improved efficiency, for applications where galvanic isolation is not a...

  19. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

    Science.gov (United States)

    Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

    2014-03-01

    Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

  20. Image-guided precision manipulation of cells and nanoparticles in microfluidics

    Science.gov (United States)

    Cummins, Zachary

    Manipulation of single cells and particles is important to biology and nanotechnology. Our electrokinetic (EK) tweezers manipulate objects in simple microfluidic devices using gentle fluid and electric forces under vision-based feedback control. In this dissertation, I detail a user-friendly implementation of EK tweezers that allows users to select, position, and assemble cells and nanoparticles. This EK system was used to measure attachment forces between living breast cancer cells, trap single quantum dots with 45 nm accuracy, build nanophotonic circuits, and scan optical properties of nanowires. With a novel multi-layer microfluidic device, EK was also used to guide single microspheres along complex 3D trajectories. The schemes, software, and methods developed here can be used in many settings to precisely manipulate most visible objects, assemble objects into useful structures, and improve the function of lab-on-a-chip microfluidic systems.

  1. SIL-TAL1 Rearrangement is Related with Poor Outcome: A Study from a Chinese Institution

    OpenAIRE

    Wang, Di; Zhu, Guangrong; Wang, Na; Zhou, Xiaoxi; Yang, Yunfan; Zhou, Shiqiu; Xiong, Jie; Jing HE; Jiang, Lijun; Li, Chunrui; Xu, Danmei; Huang, Liang; Zhou, Jianfeng

    2013-01-01

    SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL), however its prognostic implication remains controversial. To investigate the clinical characteristics and outcome of this subtype in Chinese population, we systemically reviewed 62 patients with newly diagnosed T-ALL, including 15 patients with SIL-TAL1 rearrangement. We found that SIL-TAL1+ T-ALL was characterized by higher white blood cell count (P = 0.029) at diagnosis, predominant cortical T-ALL immunophenoty...

  2. Maturation of Stem Cell-Derived Beta-cells Guided by the Expression of Urocortin 3

    OpenAIRE

    van der Meulen, Talitha; Huising, Mark O.

    2014-01-01

    Type 1 diabetes (T1D) is a devastating disease precipitated by an autoimmune response directed at the insulin-producing beta-cells of the pancreas for which no cure exists. Stem cell-derived beta-cells show great promise for a cure as they have the potential to supply unlimited numbers of cells that could be derived from a patient's own cells, thus eliminating the need for immunosuppression. Current in vitro protocols for the differentiation of stem cell-derived beta-cells can successfully ge...

  3. Thermometry of Guided Molecular Beams from a Cryogenic Buffer-Gas Cell

    CERN Document Server

    Wu, X; Zeppenfeld, M; Chervenkov, S; Rempe, G

    2016-01-01

    We present a comprehensive characterization of cold molecular beams from a cryogenic buffer-gas cell, providing an insight into the physics of buffer-gas cooling. Cold molecular beams are extracted from a cryogenic cell by electrostatic guiding, which is also used to measure their velocity distribution. Molecules' rotational-state distribution is probed via radio-frequency resonant depletion spectroscopy. With the help of complete trajectory simulations, yielding the guiding efficiency for all of the thermally populated states, we are able to determine both the rotational and the translational temperature of the molecules at the output of the buffer-gas cell. This thermometry method is demonstrated for various regimes of buffer-gas cooling and beam formation as well as for molecular species of different sizes, $\\rm{CH_3F}$ and $\\rm{CF_3CCH}$. Comparison between the rotational and translational temperatures provides evidence of faster rotational thermalization for the $\\rm{CH_3F-He}$ system in the limit of low...

  4. Collisionless Reconnection in the Large Guide Field Regime: Gyrokinetic Versus Particle-in-Cell Simulations

    CERN Document Server

    TenBarge, J M; Karimabadi, H; Howes, G G; Dorland, W

    2013-01-01

    Results of the first validation of large guide field, $B_g / \\delta B_0 \\gg 1$, gyrokinetic simulations of magnetic reconnection at a fusion and solar corona relevant $\\beta_i = 0.01$ and solar wind relevant $\\beta_i = 1$ are presented, where $\\delta B_0$ is the reconnecting field. Particle-in-cell (PIC) simulations scan a wide range of guide magnetic field strength to test for convergence to the gyrokinetic limit. The gyrokinetic simulations display a high degree of morphological symmetry, to which the PIC simulations converge when $\\beta_i B_g / \\delta B_0 \\gtrsim 1$ and $B_g / \\delta B_0 \\gg 1$. In the regime of convergence, the reconnection rate, relative energy conversion, and overall magnitudes are found to match well between the PIC and gyrokinetic simulations, implying that gyrokinetics is capable of making accurate predictions well outside its regime of formal applicability. These results imply that in the large guide field limit many quantities resulting from the nonlinear evolution of reconnection ...

  5. Langerhans` cell histiocytosis of the spine: use of MRI in guiding biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, G.R.; Saifuddin, A. [Department of Diagnostic Imaging, Royal National Orthopaedic Hospital Trust, Brockley Hill (United Kingdom); Pringle, J.A.S. [Department of Morbid Anatomy, Royal National Orthopaedic Hospital Trust, Brockley Hill (United Kingdom); Noordeen, M.H.; Mehta, M.H. [Department of Spinal Deformities, Royal National Orthopaedic Hospital Trust, Brockley Hill (United Kingdom)

    1998-12-01

    The MRI features of two cases of spinal Langerhans` cell histiocytosis with multilevel involvement are presented in which MRI was of help in differentiating active from inactive healing lesions by the demonstration of signal changes in the vertebral body marrow of the active lesion, manifest as low signal intensity on T1-weighted sequences and high signal intensity on T2-weighted sequences. This distinction could not be made by plain radiography or bone scintigraphy. In cases where biopsy is required for diagnosis, MRI is recommended to guide the biopsy towards levels suggestive of active involvement. (orig.) With 7 figs., 13 refs.

  6. Langerhans' cell histiocytosis of the spine: use of MRI in guiding biopsy

    International Nuclear Information System (INIS)

    The MRI features of two cases of spinal Langerhans' cell histiocytosis with multilevel involvement are presented in which MRI was of help in differentiating active from inactive healing lesions by the demonstration of signal changes in the vertebral body marrow of the active lesion, manifest as low signal intensity on T1-weighted sequences and high signal intensity on T2-weighted sequences. This distinction could not be made by plain radiography or bone scintigraphy. In cases where biopsy is required for diagnosis, MRI is recommended to guide the biopsy towards levels suggestive of active involvement. (orig.)

  7. Effect of image-guided hypofractionated stereotactic radiotherapy on peripheral non-small-cell lung cancer

    OpenAIRE

    Ren, Juan; Wang, Shuwen; Yan, Yanli; Xue, Chaofan; Tan, Li; Ma, Xiaowei

    2016-01-01

    Shu-wen Wang,1 Juan Ren,1 Yan-li Yan,2 Chao-fan Xue,2 Li Tan,2 Xiao-wei Ma2 1Department of Radiotherapy, First Affiliated Hospital of Xian Jiaotong University, 2Medical School of Xian Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Abstract: The objective of this study was to compare the effects of image-guided hypofractionated radiotherapy and conventional fractionated radiotherapy on non-small-cell lung cancer (NSCLC). Fifty stage- and age-matched cases...

  8. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  9. Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

    Directory of Open Access Journals (Sweden)

    Ludwig Hieber

    2011-01-01

    Full Text Available Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY. In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22 of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87% indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis.

  10. Cellular reactions of osteoblast-like cells to a novel nanocomposite membrane for guided bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Meng Yao [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthodontics, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Liu Man [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Stomatology Health Care Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518048 (China); Wang Shaoan [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Mo Anchun [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China)], E-mail: moanchun@163.com; Huang, Cui [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Zuo Yi; Li Jidong [Research Center for Nano-biomaterials, Sichuan University, Chengdu 610041 (China)

    2008-11-15

    This study investigated the bioactivity and biocompatibility of hydroxyapatite nanoparticles (n-HA)/Polyamide-66 (PA66) nanocomposite membrane and expanded-polytetrafluoroethylene (e-PTFE) membrane (as control) to MG63 osteoblast-like cells. The attachment and proliferation of the cells on the porous surface of nHA/PA66 membrane and the surface of e-PTFE membrane were evaluated by scanning electron microscope (SEM) observation and the MTT assay. The bioactivity of the cells on the surface of the two membranes was evaluated by testing cell viability and alkaline phosphatase (ALP) activities. The results suggested that the bioresponse of MG63 osteoblast-like cells on the porous surface of nHA/PA66 membrane was better than the bioresponse on the opposite surface of e-PTFE membrane. Because of a better cell attachment manner, there is a potential utilization of the guided bone regeneration (GBR) membrane to substitute nHA/PA66 membrane for e-PTFE membra0008.

  11. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H

    2014-06-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  12. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    International Nuclear Information System (INIS)

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

  13. Molecular screening of pituitary adenomas for gene mutations and rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

    1993-07-01

    Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

  14. Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure.

    Science.gov (United States)

    Tolosa, Ezequiel J; Fernández-Zapico, Martín E; Battiato, Natalia L; Rovasio, Roberto A

    2016-01-01

    Our aim was to understand the involvement of Sonic hedgehog (Shh) morphogen in the oriented distribution of neural crest cells (NCCs) toward the optic vesicle and to look for potential disorders of this guiding mechanism after ethanol exposure. In vitro directional analysis showed the chemotactic response of NCCs up Shh gradients and to notochord co-cultures (Shh source) or to their conditioned medium, a response inhibited by anti-Shh antibody, receptor inhibitor cyclopamine and anti-Smo morpholino (MO). Expression of the Ptch-Smo receptor complex on in vitro NCCs was also shown. In whole embryos, the expression of Shh mRNA and protein was seen in the ocular region, and of Ptch, Smo and Gli/Sufu system on cephalic NCCs. Anti-Smo MO or Ptch-mutated plasmid (Ptch1(Δloop2)) impaired cephalic NCC migration/distribution, with fewer cells invading the optic region and with higher cell density at the homolateral mesencephalic level. Beads embedded with cyclopamine (Smo-blocking) or Shh (ectopic signal) supported the role of Shh as an in vivo guide molecule for cephalic NCCs. Ethanol exposure perturbed in vitro and in vivo NCC migration. Early stage embryos treated with ethanol, in a model reproducing Fetal Alcohol Syndrome, showed later disruptions of craniofacial development associated with abnormal in situ expression of Shh morphogen. The results show the Shh/Ptch/Smo-dependent migration of NCCs toward the optic vesicle, with the support of specific inactivation with genetic and pharmacological tools. They also help to understand mechanisms of accurate distribution of embryonic cells and of their perturbation by a commonly consumed teratogen, and demonstrate, in addition to its other known developmental functions, a new biological activity of cellular guidance for Shh. PMID:26979762

  15. Selective amine labeling of cell surface proteins guided by coiled-coil assembly.

    Science.gov (United States)

    Yano, Yoshiaki; Furukawa, Nami; Ono, Satoshi; Takeda, Yuki; Matsuzaki, Katsumi

    2016-11-01

    Covalent labeling of target proteins in living cells is useful for both fluorescence live-cell imaging and the subsequent biochemical analyses of the proteins. Here, we report an efficient method for the amine labeling of membrane proteins on the cell surface, guided by a noncovalent coiled-coil interaction. A carboxyl sulfosuccinimidyl ester introduced at the C-terminus of the coiled-coil probe reacted with target proteins under mild labeling conditions ([probe] = 150 nM, pH 7.4, 25°C) for 20 min. Various fluorescent moieties with different hydrophobicities are available for covalent labeling with high signal/background labeling ratios. Using this method, oligomeric states of glycophorin A (GpA) were compared in mammalian CHO-K1 cells and sodium dodecyl sulfate (SDS) micelles. In the cell membranes, no significant self-association of GpA was detected, whereas SDS-PAGE suggested partial dimerization of the proteins. Membrane cholesterol was found to be an important factor that suppressed the dimerization of GpA. Thus, the covalent functionality enables direct comparison of the oligomeric state of membrane proteins under various conditions. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 484-490, 2016. PMID:26285787

  16. Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands.

    Science.gov (United States)

    Cortez, Victor S; Cervantes-Barragan, Luisa; Robinette, Michelle L; Bando, Jennifer K; Wang, Yaming; Geiger, Theresa L; Gilfillan, Susan; Fuchs, Anja; Vivier, Eric; Sun, Joe C; Cella, Marina; Colonna, Marco

    2016-05-17

    The signals guiding differentiation of innate lymphoid cells (ILCs) within tissues are not well understood. Salivary gland (SG) ILCs as well as liver and intestinal intraepithelial ILC1 have markers that denote tissue residency and transforming growth factor-β (TGF-β) imprinting. We deleted Tgfbr2 in cells expressing the ILC and NK marker NKp46 and found that SG ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. Expression of the transcription factor Eomes, which promotes NK cell differentiation, was elevated. Conversely, Eomes deletion in NKp46(+) cells enhanced TGF-β-imprinting of SG ILCs. Thus, TGF-β induces SG ILC differentiation by suppressing Eomes. TGF-β acted through a JNK-dependent, Smad4-independent pathway. Transcriptome analysis demonstrated that SG ILCs had characteristic of both NK cells and ILC1. Finally, TGF-β imprinting of SG ILCs was synchronized with SG development, highlighting the impact of tissue microenvironment on ILC development. PMID:27156386

  17. A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Spiess, S;

    1995-01-01

    We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were...... present in spleen, mesenteric lymph nodes, peritoneal cavity, lamina propria and epithelial layer of the small and large intestine of 6- to 10-month-old, male and female tg scid mice. Only low numbers of CD3+ T cells were recovered from inguinal, popliteal, or axillary lymph nodes. We studied CD4+ T cells...... in these tg scid mice. CD4+ T cells were found in the peritoneal cavity, in the mesenteric lymph nodes and in the intraepithelial layer and lamina propria of the gut. All CD4+ T cells were CD44+ (i.e. showed evidence of antigen-driven differentiation) and expressed the tg V beta 8.2 TcR beta...

  18. Cell Geometry Guides the Dynamic Targeting of Apoplastic GPI-Linked Lipid Transfer Protein to Cell Wall Elements and Cell Borders in Arabidopsis thaliana

    Science.gov (United States)

    Wasteneys, Geoffrey

    2013-01-01

    During cellular morphogenesis, changes in cell shape and cell junction topology are fundamental to normal tissue and organ development. Here we show that apoplastic Glycophosphatidylinositol (GPI)-anchored Lipid Transfer Protein (LTPG) is excluded from cell junctions and flat wall regions, and passively accumulates around their borders in the epidermal cells of Arabidopsis thaliana. Beginning with intense accumulation beneath highly curved cell junction borders, this enrichment is gradually lost as cells become more bulbous during their differentiation. In fully mature epidermal cells, YFP-LTPG often shows a fibrous cellulose microfibril-like pattern within the bulging outer faces. Physical contact between a flat glass surface and bulbous cell surface induces rapid and reversible evacuation from contact sites and accumulation to the curved wall regions surrounding the contact borders. Thus, LTPG distribution is dynamic, responding to changes in cell shape and wall curvature during cell growth and differentiation. We hypothesize that this geometry-based mechanism guides wax-carrying LTPG to functional sites, where it may act to “seal” the vulnerable border surrounding cell-cell junctions and assist in cell wall fortification and cuticular wax deposition. PMID:24260561

  19. ROS1-rearranged lung cancer: a clinicopathologic and molecular study of 15 surgical cases.

    Science.gov (United States)

    Yoshida, Akihiko; Kohno, Takashi; Tsuta, Koji; Wakai, Susumu; Arai, Yasuhito; Shimada, Yoko; Asamura, Hisao; Furuta, Koh; Shibata, Tatsuhiro; Tsuda, Hitoshi

    2013-04-01

    Recent discovery of ROS1 gene fusion in a subset of lung cancers has raised clinical interest, because ROS1 fusion-positive cancers are reportedly sensitive to kinase inhibitors. To better understand these tumors, we examined 799 surgically resected non-small cell lung cancers by reverse transcriptase polymerase chain reaction and identified 15 tumors harboring ROS1 fusion transcripts (2.5% of adenocarcinomas). The most frequent fusion partner was CD74 followed by EZR. The affected patients were often younger nonsmoking female individuals, and they had overall survival rates similar to those of the ROS1 fusion-negative cancer patients. All the ROS1 fusion-positive tumors were adenocarcinomas except 1, which was an adenosquamous carcinoma. Histologic examination identified an at least focal presence of either solid growth with signet-ring cells or cribriform architecture with abundant extracellular mucus in 53% of the cases. These 2 patterns are reportedly also characteristic of anaplastic lymphoma kinase (ALK)-rearranged lung cancers, and our data suggest a phenotypic resemblance between the ROS1-rearranged and ALK-rearranged tumors. All tumors except 1 were immunoreactive to thyroid transcription factor-1. Fluorescence in situ hybridization using ROS1 break-apart probes revealed positive rearrangement signals in 23% to 93% of the tumor cells in ROS1 fusion-positive cancers, which were readily distinguished using a 15% cutoff value from 50 ROS1 fusion-negative tumors tested, which showed 0% to 6% rearrangement signals. However, this perfect test performance was achieved only when isolated 3' signals were included along with classic split signals in the definition of rearrangement positivity. Fluorescence in situ hybridization signal patterns were unrelated to 5' fusion partner genes. All ROS1 fusion-positive tumors lacked alteration of EGFR, KRAS, HER2, ALK, and RET genes. PMID:23426121

  20. ERG–TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin

    OpenAIRE

    Williamson, Sean R; Zhang, Shaobo; Yao, Jorge L.; Huang, Jiaoti; Lopez-Beltran, Antonio; Shen, Steven; Osunkoya, Adeboye O.; MacLennan, Gregory T.; Montironi, Rodolfo; Cheng, Liang

    2011-01-01

    Prostatic carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic small cell carcinoma is a rare variant with aggressive behavior. Distinction between small cell carcinoma of the prostate and urinary bladder may be challenging, especially in small biopsy specimens without associated prostatic adenocarcinoma or urothelial carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane pr...

  1. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva; Johansson, Ulla; Persson, Camilla; Sellberg, Gunilla; Tellhed, Lina; Nilbert, Mef; Borg, Ake

    2008-01-01

    deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...

  2. Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements

    Directory of Open Access Journals (Sweden)

    Sebastiaan van Heesch

    2014-12-01

    Full Text Available Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

  3. Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

    OpenAIRE

    Takahashi, Isao; Sekito,Noriko; Takeuchi, Makoto; Osada, Ken; Matsuzaki,Toshiro; Fukuda, Shunichi; Lai,Minyu; Uchida, Kozaburo; Kimura,Ikuro; Miyamoto,Kanji; Kitajima,Koichi; Sanada, Hiroshi

    1988-01-01

    The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocyt...

  4. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

    NARCIS (Netherlands)

    Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

    2014-01-01

    Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional geno

  5. Dose dependent rearrangement of cellular membranes induced by ionizing radiation

    International Nuclear Information System (INIS)

    The radiation-induced effects at dose rate of 0.35 Gy/min (in vivo) and of ultra-low doses (in vitro) on the cell membranes structural state were shown. The modifications of the membrane protein and lipid components and their dynamic state were revealed at experimental irradiation conditions by fluorescent probe analysis. The principal component analysis of the research data indicates the dose-dependent decrease of plasma membrane structural orderliness of the small intestine enterocytes with the increase of the ionizing irradiation acute dose of 0.5, 1.0, 2.0, 3.0 Gy at dose rate of 0.35 Gy/min. The complex response of the biological structure - the erythrocytes plasma membrane, on the ionizing radiation action at ultra-low doses that occurred through macromolecular structural rearrangements was also demonstrated. The features of the structural rearrangement of the cellular membranes depending on the ionizing radiation dose (dose rate) are found out

  6. Mechanisms of chromosomal rearrangement in the human genome

    Directory of Open Access Journals (Sweden)

    Lieber Michael R

    2010-02-01

    Full Text Available Abstract Many human cancers are associated with characteristic chromosomal rearrangements, especially hematopoietic cancers such as leukemias and lymphomas. The first and most critical step in the rearrangement process is the induction of two DNA double-strand breaks (DSB. In all cases, at least one of the two DSBs is generated by a pathologic process, such as (1 randomly-positioned breaks due to ionizing radiation, free radical oxidative damage, or spontaneous hydrolysis; (2 breaks associated with topoisomerase inhibitor treatment; or (3 breaks at direct or inverted repeat sequences, mediated by unidentified strand breakage mechanisms. In lymphoid cells, one of the two requisite DSBs is often physiologic, the result of V(DJ recombination or class switch recombination (CSR at the lymphoid antigen receptor loci. The RAG complex, which causes the DSBs in V(DJ recombination, can cause (4 sequence-specific, pathologic DSBs at sites that fit the consensus of their normal V(DJ recombination signal targets; or (5 structure-specific, pathologic DSBs at regions of single- to double-strand transition. CSR occurs specifically in the B-cell lineage, and requires (6 activation-induced cytidine deaminase (AID action at sites of single-stranded DNA, which may occur pathologically outside of the normal target loci of class switch recombination regions and somatic hypermutation (SHM zones. Recent work proposes a seventh mechanism: the sequential action of AID and the RAG complex at CpG sites provides a coherent model for the pathologic DSBs at some of the most common sites of translocation in human lymphoma – the bcl-2 gene in follicular lymphoma and diffuse large B-cell lymphoma, and the bcl-1 gene in mantle cell lymphoma.

  7. Gyrokinetic and kinetic particle-in-cell simulations of guide-field reconnection

    Science.gov (United States)

    Munoz Sepulveda, Patricio Alejandro; Büchner, Jörg; Kilian, Patrick; Told, Daniel; Jenko, Frank

    2016-07-01

    Fully kinetic Particle-in-Cell (PIC) simulations of (strong) guide-field reconnection can be computationally very demanding, due to the intrinsic stability and accuracy conditions required by this numerical method. One convenient approach to circumvent this issue is using gyrokinetic theory, an approximation of the Vlasov-Maxwell equations for strongly magnetized plasmas that eliminates the fast gyromotion, and thus reduces the computational cost. Although previous works have started to compare the features of reconnection between both approaches, a complete understanding of the differences is far from being complete. This knowledge is essential to discern the limitations of the gyrokinetic simulations of magnetic reconnection when applied to scenarios with moderate guide fields, such as the Solar corona, in contrast to most of the fusion/laboratory plasmas. We extend a previous work by our group, focused in the differences in the macroscopic flows, by analyzing the heating processes and non-thermal features developed by reconnection between both plasma approximations. We relate these processes by identifying some high-frequency cross-streaming instabilities appearing only in the fully kinetic approach. We characterize the effects of these phenonema such as anisotropic electron heating, beam formation and turbulence under different parameter regimes. And finally, we identify the conditions under which these instabilities tends to become negligible in the fully kinetic model, and thus a comparison with gyrokinetic theory becomes more reliable.

  8. Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome

    DEFF Research Database (Denmark)

    Karrman, Kristina; Forestier, Erik; Heyman, Mats; Andersen, Mette K; Autio, Kirsi; Blennow, Elisabeth; Borgström, Georg; Ehrencrona, Hans; Golovleva, Irina; Heim, Sverre; Heinonen, Kristiina; Hovland, Randi; Johannsson, Johann H; Kerndrup, Gitte; Nordgren, Ann; Palmqvist, Lars; Johansson, Bertil

    2009-01-01

    Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (...

  9. IK-guided PP2A suppresses Aurora B activity in the interphase of tumor cells.

    Science.gov (United States)

    Lee, Sunyi; Jeong, Ae Lee; Park, Jeong Su; Han, Sora; Jang, Chang-Young; Kim, Keun Il; Kim, Yonghwan; Park, Jong Hoon; Lim, Jong-Seok; Lee, Myung Sok; Yang, Young

    2016-09-01

    Aurora B activation is triggered at the mitotic entry and required for proper microtubule-kinetochore attachment at mitotic phase. Therefore, Aurora B should be in inactive form in interphase to prevent aberrant cell cycle progression. However, it is unclear how the inactivation of Aurora B is sustained during interphase. In this study, we find that IK depletion-induced mitotic arrest leads to G2 arrest by Aurora B inhibition, indicating that IK depletion enhances Aurora B activation before mitotic entry. IK binds to Aurora B, and colocalizes on the nuclear foci during interphase. Our data further show that IK inhibits Aurora B activation through recruiting PP2A into IK and Aurora B complex. It is thus believed that IK, as a scaffold protein, guides PP2A into Aurora B to suppress its activity in interphase until mitotic entry. PMID:26906715

  10. Far Red/Near-Infrared AIE Dots for Image-Guided Photodynamic Cancer Cell Ablation.

    Science.gov (United States)

    Feng, Guangxue; Wu, Wenbo; Xu, Shidang; Liu, Bin

    2016-08-24

    We report a facile encapsulation approach to realize bright far red/near-infrared (FR/NIR) fluorescence and efficient singlet oxygen ((1)O2) production of organic fluorogens with aggregation-induced emission (AIEgen) and intramolecular charge transfer (ICT) characteristics for image-guided photodynamic cancer cell ablation. The synthesized AIEgen BTPEAQ possesses donor-acceptor-donor structure, which shows bright fluorescence in solid state. Due to the strong ICT effect, BTPEAQ exhibits poor emission with almost no (1)O2 generation in aqueous solution. Encapsulation of BTPEAQ by DSPE-PEG block copolymer yields polymer-shelled dots, which show enhanced brightness with a fluorescence quantum yield of 3.9% and a (1)O2 quantum yield of 38%. Upon encapsulation by silica, the formed SiO2-shelled dots show much improved fluorescence quantum yield of 12.1% but with no obvious (1)O2 generation. This study clearly demonstrates the importance of encapsulation approach for organic fluorophores, which affects not only the brightness but also the (1)O2 production. After conjugating the polymer-shelled AIE dots with cRGD peptide, the obtained BTPEAQ-cRGD dots show excellent photoablation toward MDA-MB-231 cells with integrin overexpression while keeping control cells intact. PMID:27462722

  11. Adiabatic Rearrangement of Hollow PV Towers

    Directory of Open Access Journals (Sweden)

    Eric A Hendricks

    2010-10-01

    Full Text Available Diabatic heating from deep moist convection in the hurricane eyewall produces a towering annular structure of elevated potential vorticity (PV. This structure has been referred to as a hollow PV tower. The sign reversal of the radial gradient of PV satisfies the Charney-Stern necessary condition for combined barotropic-baroclinic instability. For thin enough annular structures, small perturbations grow exponentially, extract energy from the mean flow, and lead to hollow tower breakdown, with significant vortex structural and intensity change. The three-dimensional adiabatic rearrangements of two prototypical hurricane-like hollow PV towers (one thick and one thin are examined in an idealized framework. For both hollow towers, dynamic instability causes air parcels with high PV to be mixed into the eye preferentially at lower levels, where unstable PV wave growth rates are the largest. Little or no mixing is found to occur at upper levels. The mixing at lower and middle levels is most rapid for the breakdown of the thin hollow tower, consistent with previous barotropic results. For both hollow towers, this advective rearrangement of PV affects the tropical cyclone structure and intensity in a number of ways. First, the minimum central pressure and maximum azimuthal mean velocity simultaneously decrease, consistent with previous barotropic results. Secondly, isosurfaces of absolute angular momentum preferentially shift inward at low levels, implying an adiabatic mechanism by which hurricane eyewall tilt can form. Thirdly, a PV bridge, similar to that previously found in full-physics hurricane simulations, develops as a result of mixing at the isentropic levels where unstable PV waves grow most rapidly. Finally, the balanced mass field resulting from the PV rearrangement is warmer in the eye between 900 and 700 hPa. The location of this warming is consistent with observed warm anomalies in the eye, indicating that in certain instances the hurricane

  12. Rearrangement of Barcelona serveis municipals customer services

    OpenAIRE

    Fullana Roger, Cristina

    2015-01-01

    This document presents the report for the Final Degree Thesis. The subject of the project is the Rearrangement of the Customer Services of the public company Barcelona Serveis Municipals (B:SM). The project is classified in the Management area and it details the definition and adaptation process of a new model in the customer services of B:SM. The origin of the project stands on the opening of the new Calàbria facilities. The purpose of the project is to identify the problems in the curren...

  13. Synthetically Useful Base Induced Rearrangements of Aldonolactones

    DEFF Research Database (Denmark)

    Lundt, Inge; Madsen, Robert

    2001-01-01

    Aldonolactones can be activated at the alpha and omega positions by selective bromination or tosylation. The activated aldonolactones can be transformed into epoxyaldonolactones by treatment with base under non-aqueous conditions. Treatment of epoxy- or bromodeoxyaldonolactones with aqueous base...... gives epoxyaldonates in which the epoxide can undergo Payne rearrangement to more stable epoxyaldonates. These can subsequently be opened by the carboxylate group with inversion of the configuration at the attacked carbon. Using this method a number of less available aldonolactones/acids have been...

  14. Tubule-guided cell-to-cell movement of a plant virus requires class XI myosin motors.

    Directory of Open Access Journals (Sweden)

    Khalid Amari

    2011-10-01

    Full Text Available Cell-to-cell movement of plant viruses occurs via plasmodesmata (PD, organelles that evolved to facilitate intercellular communications. Viral movement proteins (MP modify PD to allow passage of the virus particles or nucleoproteins. This passage occurs via several distinct mechanisms one of which is MP-dependent formation of the tubules that traverse PD and provide a conduit for virion translocation. The MP of tubule-forming viruses including Grapevine fanleaf virus (GFLV recruit the plant PD receptors called Plasmodesmata Located Proteins (PDLP to mediate tubule assembly and virus movement. Here we show that PDLP1 is transported to PD through a specific route within the secretory pathway in a myosin-dependent manner. This transport relies primarily on the class XI myosins XI-K and XI-2. Inactivation of these myosins using dominant negative inhibition results in mislocalization of PDLP and MP and suppression of GFLV movement. We also found that the proper targeting of specific markers of the Golgi apparatus, the plasma membrane, PD, lipid raft subdomains within the plasma membrane, and the tonoplast was not affected by myosin XI-K inhibition. However, the normal tonoplast dynamics required myosin XI-K activity. These results reveal a new pathway of the myosin-dependent protein trafficking to PD that is hijacked by GFLV to promote tubule-guided transport of this virus between plant cells.

  15. Contribution of ultrasound-guided fine-needle aspiration cell blocks of metastatic supraclavicular lymph nodes to the diagnosis of lung cancer

    Directory of Open Access Journals (Sweden)

    Hai-Ying Tian

    2015-01-01

    Conclusion: Cell-block samples from US-guided FNA is a promising, relatively noninvasive technique to provide additional information in lung cancer diagnosis. Analysis of cell blocks allows for genetic analysis of the patients with supraclavicular lymph nodes metastasis.

  16. Control of growth factor binding and release in bisphosphonate functionalized hydrogels guides rapid differentiation of precursor cells in vitro.

    Science.gov (United States)

    Kootala, Sujit; Zhang, Yu; Ghalib, Sara; Tolmachev, Vladimir; Hilborn, Jöns; Ossipov, Dmitri A

    2016-02-01

    An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. The high affinity of matrix-anchored BP groups towards BMP-2 permits guided differentiation of entrapped progenitor cells in 3-D cultures. PMID:26610690

  17. Control of growth factor binding and release in bisphosphonate functionalized hydrogels guides rapid diff erentiation of precursor cells in vitro

    OpenAIRE

    Kootala, Sujit; Zhang, Yu; Ghalib, Sara; Tolmachev, Vladmir; Hilborn, Jöns; Ossipov, Dmitri

    2016-01-01

    An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. The high affinity of matrix-anchored BP groups towards BMP-2 permits guided differentiation of entrapped progenitor cells in 3-D cultures.

  18. The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia.

    Science.gov (United States)

    Li, Yan; Hu, Shimin; Wang, Sa A; Li, Shaoying; Huh, Yang O; Tang, Zhenya; Medeiros, L Jeffrey; Tang, Guilin

    2016-05-01

    Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia. We here report a cohort of 20 chronic lymphocytic leukemia patients with 8q24/MYC rearrangement, 3 detected at time of initial diagnosis and 17 acquired after a median interval of 48 months. At the time when 8q24/MYC arrangement was detected, 18 patients had B-symptoms, 17 had lymphadenopathy, and 17 had splenomegaly. Histologically, typical chronic lymphocytic leukemia morphology was seen in six patients, increased prolymphocytes in nine and Richter's transformation in five patients. Eighteen patients had karyotypic information available that showed t(8;v) in a complex karyotype in 12 patients and in a non-complex karyotype in 6 patients. Fluorescence in situ hybridization confirmed MYC rearrangement in 17/17 patients. All patients required therapy after 8q24/MYC rearrangement was detected. At last follow-up, five of six patients with a non-complex karyotype were alive after a median of 74 months (10~143 months) from the detection of 8q24/MYC rearrangement. In contrast, 10 of 12 patients with a complex karyotype died with a median survival of 5.5 months. We conclude that 8q24/MYC rearrangement in chronic lymphocytic leukemia is rare and often acquired during the course of disease. If it is presented in a complex karyotype, it is often associated with Richter's transformation, refractory to therapy and an aggressive clinical course; on the other hand, if it is present in a non-complex karyotype, patients often respond to risk-adapted therapies and achieve remission. PMID:26916070

  19. Exceptional Complex Chromosomal Rearrangements in Three Generations

    Directory of Open Access Journals (Sweden)

    Hannie Kartapradja

    2015-01-01

    Full Text Available We report an exceptional complex chromosomal rearrangement (CCR found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.

  20. Dispersion-Energy-Driven Wagner-Meerwein Rearrangements in Oligosilanes.

    Science.gov (United States)

    Albers, Lena; Rathjen, Saskia; Baumgartner, Judith; Marschner, Christoph; Müller, Thomas

    2016-06-01

    The installation of structural complex oligosilanes from linear starting materials by Lewis acid induced skeletal rearrangement reactions was studied under stable ion conditions. The produced cations were fully characterized by multinuclear NMR spectroscopy at low temperature, and the reaction course was studied by substitution experiments. The results of density functional theory calculations indicate the decisive role of attractive dispersion forces between neighboring trimethylsilyl groups for product formation in these rearrangement reactions. These attractive dispersion interactions control the course of Wagner-Meerwein rearrangements in oligosilanes, in contrast to the classical rearrangement in hydrocarbon systems, which are dominated by electronic substituent effects such as resonance and hyperconjugation. PMID:27195490

  1. Chemokine-guided CD4+ T cell help enhances generation of IL-6RalphahighIL-7Ralpha high prememory CD8+ T cells.

    Science.gov (United States)

    Castellino, Flora; Germain, Ronald N

    2007-01-15

    CD4(+) T cells promote effective CD8(+) T cell-mediated immunity, but the timing and mechanistic details of such help remain controversial. Furthermore, the extent to which innate stimuli act independently of help in enhancing CD8(+) T cell responses is also unresolved. Using a noninfectious vaccine model in immunocompetent mice, we show that even in the presence of innate stimuli, CD4(+) T cell help early after priming is required for generating an optimal pool of functional memory CD8(+) T cells. CD4(+) T cell help increased the size of a previously unreported population of IL-6Ralpha(high)IL-7Ralpha(high) prememory CD8(+) T cells shortly after priming that showed a survival advantage in vivo and contributed to the majority of functional memory CD8(+) T cells after the contraction phase. In accord with our recent demonstration of chemokine-guided recruitment of naive CD8(+) T cells to sites of CD4(+) T cell-dendritic cell interactions, the generation of IL-6Ralpha(high)IL-7Ralpha(high) prememory as well as functional memory CD8(+) T cells depended on the early postvaccination action of the inflammatory chemokines CCL3 and CCL4. Together, these findings support a model of CD8(+) T cell memory cell differentiation involving the delivery of key signals early in the priming process based on chemokine-guided attraction of naive CD8(+) T cells to sites of Ag-driven interactions between TLR-activated dendritic cells and CD4(+) T cells. They also reveal that elevated IL-6Ralpha expression by a subset of CD8(+) T cells represents an early imprint of CD4(+) T cell helper function that actively contributes to the survival of activated CD8(+) T cells. PMID:17202339

  2. Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy

    Science.gov (United States)

    Rahmi, Gabriel; Pidial, Laetitia; Silva, Amanda K. A.; Blondiaux, Eléonore; Meresse, Bertrand; Gazeau, Florence; Autret, Gwennhael; Balvay, Daniel; Cuenod, Charles André; Perretta, Silvana; Tavitian, Bertrand; Wilhelm, Claire; Cellier, Christophe; Clément, Olivier

    2016-01-01

    Cell sheet technology opens new perspectives in tissue regeneration therapy by providing readily implantable, scaffold-free 3D tissue constructs. Many studies have focused on the therapeutic effects of cell sheet implantation while relatively little attention has concerned the fate of the implanted cells in vivo. The aim of the present study was to track longitudinally the cells implanted in the cell sheets in vivo in target tissues. To this end we (i) endowed bone marrow-derived mesenchymal stem cells (BMMSCs) with imaging properties by double labeling with fluorescent and magnetic tracers, (ii) applied BMMSC cell sheets to a digestive fistula model in mice, (iii) tracked the BMMSC fate in vivo by MRI and probe-based confocal laser endomicroscopy (pCLE), and (iv) quantified healing of the fistula. We show that image-guided longitudinal follow-up can document both the fate of the cell sheet-derived BMMSCs and their healing capacity. Moreover, our theranostic approach informs on the mechanism of action, either directly by integration of cell sheet-derived BMMSCs into the host tissue or indirectly through the release of signaling molecules in the host tissue. Multimodal imaging and clinical evaluation converged to attest that cell sheet grafting resulted in minimal clinical inflammation, improved fistula healing, reduced tissue fibrosis and enhanced microvasculature density. At the molecular level, cell sheet transplantation induced an increase in the expression of anti-inflammatory cytokines (TGF-ß2 and IL-10) and host intestinal growth factors involved in tissue repair (EGF and VEGF). Multimodal imaging is useful for tracking cell sheets and for noninvasive follow-up of their regenerative properties. PMID:27022420

  3. Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Juliana Godoy Assumpcao

    2013-01-01

    Full Text Available OBJECTIVE To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. METHODS Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. RESULTS Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%. For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%, then TCRG (61.4%, and TCRD and IgK (47.7%; for T-acute lymphocytic leukemia, TCRG (80.0%, and TCRD and Sil-Tal deletion (20.0% were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7. CONCLUSION Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

  4. Bootstrapping phylogenies inferred from rearrangement data

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2012-08-01

    Full Text Available Abstract Background Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. Results We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Conclusions Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its

  5. Gyrokinetic and kinetic particle-in-cell simulations of guide-field reconnection. I. Macroscopic effects of the electron flows

    International Nuclear Information System (INIS)

    In this work, we compare gyrokinetic (GK) with fully kinetic Particle-in-Cell (PIC) simulations of magnetic reconnection in the limit of strong guide field. In particular, we analyze the limits of applicability of the GK plasma model compared to a fully kinetic description of force free current sheets for finite guide fields (bg). Here, we report the first part of an extended comparison, focusing on the macroscopic effects of the electron flows. For a low beta plasma (βi = 0.01), it is shown that both plasma models develop magnetic reconnection with similar features in the secondary magnetic islands if a sufficiently high guide field (bg ≳ 30) is imposed in the kinetic PIC simulations. Outside of these regions, in the separatrices close to the X points, the convergence between both plasma descriptions is less restrictive (bg ≳ 5). Kinetic PIC simulations using guide fields bg ≲ 30 reveal secondary magnetic islands with a core magnetic field and less energetic flows inside of them in comparison to the GK or kinetic PIC runs with stronger guide fields. We find that these processes are mostly due to an initial shear flow absent in the GK initialization and negligible in the kinetic PIC high guide field regime, in addition to fast outflows on the order of the ion thermal speed that violate the GK ordering. Since secondary magnetic islands appear after the reconnection peak time, a kinetic PIC/GK comparison is more accurate in the linear phase of magnetic reconnection. For a high beta plasma (βi = 1.0) where reconnection rates and fluctuations levels are reduced, similar processes happen in the secondary magnetic islands in the fully kinetic description, but requiring much lower guide fields (bg ≲ 3)

  6. Gyrokinetic and kinetic particle-in-cell simulations of guide-field reconnection. I. Macroscopic effects of the electron flows

    Science.gov (United States)

    Muñoz, P. A.; Told, D.; Kilian, P.; Büchner, J.; Jenko, F.

    2015-08-01

    In this work, we compare gyrokinetic (GK) with fully kinetic Particle-in-Cell (PIC) simulations of magnetic reconnection in the limit of strong guide field. In particular, we analyze the limits of applicability of the GK plasma model compared to a fully kinetic description of force free current sheets for finite guide fields (bg). Here, we report the first part of an extended comparison, focusing on the macroscopic effects of the electron flows. For a low beta plasma (βi = 0.01), it is shown that both plasma models develop magnetic reconnection with similar features in the secondary magnetic islands if a sufficiently high guide field (bg ≳ 30) is imposed in the kinetic PIC simulations. Outside of these regions, in the separatrices close to the X points, the convergence between both plasma descriptions is less restrictive (bg ≳ 5). Kinetic PIC simulations using guide fields bg ≲ 30 reveal secondary magnetic islands with a core magnetic field and less energetic flows inside of them in comparison to the GK or kinetic PIC runs with stronger guide fields. We find that these processes are mostly due to an initial shear flow absent in the GK initialization and negligible in the kinetic PIC high guide field regime, in addition to fast outflows on the order of the ion thermal speed that violate the GK ordering. Since secondary magnetic islands appear after the reconnection peak time, a kinetic PIC/GK comparison is more accurate in the linear phase of magnetic reconnection. For a high beta plasma (βi = 1.0) where reconnection rates and fluctuations levels are reduced, similar processes happen in the secondary magnetic islands in the fully kinetic description, but requiring much lower guide fields (bg ≲ 3).

  7. Chromosomal rearrangement in autotetraploid plants of Arabidopsis thaliana.

    Science.gov (United States)

    Weiss, H; Maluszynska, J

    2000-01-01

    Recent development of cytogenetic techniques has facilitated significant progress in Arabidopsis thaliana karyotype studies. Double-target FISH with rRNA genes provides makers that allow individual chromosome in the genome to be distinguished. Those studies have revealed that the number and position of rDNA loci is ecotype-specific. Arabidopsis is believed to be a true diploid (x = 5) with numerous ecotypes (accessions) and only a very few natural polyploid populations reported. Few studies were undertaken to induce polyploidy in Arabidopsis, however none of those gave the cytogenetic characteristics of polyploid plants. Our analysis of chromosome pairing of colchicine-induced autotetraploid Arabidopsis (Wilna ecotype) revealed preferential bivalent pairing in PMCs (pollen mother cells). In order to attempt to explain this phenomenon, first of all more detailed cytogenetic studies of autopolyploid plants have been undertaken. The localization of 45S and 5S rDNA loci in the diploid and autotetraploid plants revealed that Wilna ecotypes belongs to the group of Arabidopsis accessions with only two 5S rDNA loci present in a genome. Furthermore, the rearrangement of 45S rDNA locus in autopolyploid, when compared to the diploid plants of the same ecotype, was revealed. These results are interesting also in the context of the recently emphasised role of polyploidy in plant evolution and speciation. Arabidopsis, despite having small chromosomes, is a good system to study chromosome behaviour in relation to diploidization of autopolyploids and to evaluate the degree of chromosomal rearrangements during this process. PMID:11433970

  8. Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kyung Park

    2010-07-01

    Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

  9. Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

    Energy Technology Data Exchange (ETDEWEB)

    Do, To Uyen [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Ho, Bay; Shih, Shyh-Jen [Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Vaughan, Andrew, E-mail: Andrew.vaughan@ucdmc.ucdavis.edu [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States)

    2012-12-15

    Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient.

  10. Microenvironmental geometry guides platelet adhesion and spreading: a quantitative analysis at the single cell level.

    Directory of Open Access Journals (Sweden)

    Ashley Kita

    Full Text Available To activate clot formation and maintain hemostasis, platelets adhere and spread onto sites of vascular injury. Although this process is well-characterized biochemically, how the physical and spatial cues in the microenvironment affect platelet adhesion and spreading remain unclear. In this study, we applied deep UV photolithography and protein micro/nanostamping to quantitatively investigate and characterize the spatial guidance of platelet spreading at the single cell level and with nanoscale resolution. Platelets adhered to and spread only onto micropatterned collagen or fibrinogen surfaces and followed the microenvironmental geometry with high fidelity and with single micron precision. Using micropatterned lines of different widths, we determined that platelets are able to conform to micropatterned stripes as thin as 0.6 µm and adopt a maximum aspect ratio of 19 on those protein patterns. Interestingly, platelets were also able to span and spread over non-patterned regions of up to 5 µm, a length consistent with that of maximally extended filopodia. This process appears to be mediated by platelet filopodia that are sensitive to spatial cues. Finally, we observed that microenvironmental geometry directly affects platelet biology, such as the spatial organization and distribution of the platelet actin cytoskeleton. Our data demonstrate that platelet spreading is a finely-tuned and spatially-guided process in which spatial cues directly influence the biological aspects of how clot formation is regulated.

  11. Excision of periocular basal cell carcinoma guided by en face frozen section.

    Science.gov (United States)

    Tullett, Mark; Sagili, Suresh; Barrett, Andrew; Malhotra, Raman

    2013-09-01

    We describe a technique for monitoring excision margins in periocular basal cell carcinoma (BCC) using en face frozen sections and report outcomes. We excised periocular BCC with 3mm margins. An outer 1mm sliver of the perimeter of the specimen was mapped and sent for evaluation by en face frozen section. The central tumour mass was processed using routine paraffin sections. A further 3mm level was excised at the site of any affected margin and the outer 1mm sliver was again evaluated by frozen section. We identified 78 patients from November 2003 to July 2009; 67 had primary tumours and 11 (14%) had recurrent BCC of which 52 (66%) were located on the lower eyelid. Growth patterns were nodular (n=34, 43%), infiltrative (n=25, 32%), micronodular (n=12, 16%), and superficial (n=7, 9%). A third of BCC with a clinically nodular appearance showed additional histological patterns including infiltrative and micronodular growth patterns. Of 30 clinically nodular carcinomas, 29 were excised completely with one level, and one required 2 levels of excision for clearance after evaluation by frozen section. Mean follow-up was 23 months (range 2-60). There was one recurrence (1%). Excision of margins guided by en face frozen section is justified by the low rates of recurrence, and it can easily be taught or imported into hospital practice. Clinically nodular BCC have subclinical extensions that can be missed on bread loaf sectioning, which makes the sampling of margins a standard for periocular BCC. PMID:23219018

  12. Local Rearrangements of Droplets in a Dense Emulsion Under Shear Rearrangements

    Science.gov (United States)

    Venkatesh, Vishwas; Dutta, Sudeep; Del Gado, Emanuela; Blair, Daniel

    Jammed suspensions can flow when subjected to shear deformation. The flow properties are complex, depend on shear rates and can be inhomogeneous through the material. The microscopic origin of such flow properties is still a subject of intense research. In this work, we present a study of jammed emulsions under shear deformation, using a combination of experiments and molecular dynamics simulations. In the steady state regime, we investigate the local rearrangement of jammed emulsion droplets at a wide range of shear rates and shear strains and characterise the local rearrangement of droplets in terms of mean square displacement (MSD), displacement maps and displacement correlation function. At small shear strains and high shear rates, we find localised flow events and super diffusive motion of droplets. But at low shear rates, we observe emerging shear localisation from plastic events in an elastic background and avalanches. The characterisation of local rearrangements is also done in the stress over-shoot regime as well in the regime approaching the steady state stress. We observe a transient shear banding that progressively disappears as the pressure reaches a steady state value.

  13. Catalytic rearrangement of the chloroallyl ethers of p-cresol

    International Nuclear Information System (INIS)

    The rearrangement of a series of p-cresol ethers (β- and γ-chloro-, βγ- and βγ,γ-trichloroallyl), catalyzed by boron trifluoride etherate, was studied. Increase in the number of chlorine atoms in the allyl unit of the ether hinders the rearrangement, and its mechanism changes in the investigated series of ethers from intramolecular [3,3]-sigmatropic (with inversion of the allyl unit) to intermolecular, which corresponds to electrophilic substitution in the aromatic ring (without inversion). The presence of the chlorine atom at the β position of the allyl unit promotes rearrangement by a concerted intramolecular mechanism, while a chlorine atom at the γ position promotes rearrangement by an intermolecular stage mechanism. Two chlorine atoms at the γ position give rise mainly to the intermolecular rearrangement path

  14. Symmetric Rearrangements Around Infinity with Applications to Levy Processes

    CERN Document Server

    Drewitz, Alexander; Sun, Rongfeng

    2011-01-01

    We prove a new rearrangement inequality for multiple integrals, which partly generalizes a result of Friedberg and Luttinger (1976) and can be interpreted as involving symmetric rearrangements of domains around infinity. As applications, we prove two comparison results for general Levy processes and their symmetric rearrangements. The first application concerns the survival probability of a point particle in a Poisson field of moving traps following independent Levy motions. We show that the survival probability can only increase if the point particle does not move, and the traps and the Levy motions are symmetrically rearranged. This essentially generalizes an isoperimetric inequality of Peres and Sousi (2011) for the Wiener sausage. In the second application, we show that the q-capacity of a Borel measurable set for a Levy process can only increase if the set and the Levy process are symmetrically rearranged. This result generalizes an inequality obtained by Watanabe (1983) for symmetric Levy processes.

  15. TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia

    DEFF Research Database (Denmark)

    Willer, Anton; Jakobsen, Janus Schou; Ohlsson, E;

    2015-01-01

    orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). TGIF1/TGIF2 are relatively uncharacterized TALE transcription factors, which, in contrast to the remaining family, have been shown to act as transcriptional repressors. Given the general......-AF9-transformed cells promoted differentiation and cell cycle exit in vitro, and delayed leukemic onset in vivo. Mechanistically, we show that TGIF1 interferes with a MEIS1-dependent transcriptional program by associating with MEIS1-bound regions in a competitive manner and that the MEIS1:TGIF1 ratio...... influence the clinical outcome. Collectively, these findings demonstrate that TALE family members can act both positively and negatively on transcriptional programs responsible for leukemic maintenance and provide novel insights into the regulatory gene expression circuitries in MLL-rearranged AML...

  16. Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): A feasibility study

    OpenAIRE

    Zwaenepoel, Karen; Merkle, Dennis; Cabillic, Florian; Berg, Erica; Belaud-Rotureau, Marc-Antoine; Grazioli, Vittorio; Herelle, Olga; Hummel, Michael; Le Calve, Michele; Lenze, Dido; Mende, Stefanie; Pauwels, Patrick; Quilichini, Benoit; Repetti, Elena

    2015-01-01

    In the past several years we have observed a significant increase in our understanding of molecular mechanisms that drive lung cancer. Specifically in the non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub-group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib, resulting in significant reductions in tumor burden. Phase II and III clinical trials were performed using an ALK break-apart FISH probe kit, making FISH the gold standard for identif...

  17. Fine mapping of V(D)J recombinase mediated rearrangements in human lymphoid malignancies

    OpenAIRE

    Halper-Stromberg, Eitan; Steranka, Jared; Giraldo-Castillo, Nicolas; Fuller, Timothy; Desiderio, Stephen; Burns, Kathleen H.

    2013-01-01

    Background Lymphocytes achieve diversity in antigen recognition in part by rearranging genomic DNA at loci encoding antibodies and cell surface receptors. The process, termed V(D)J recombination, juxtaposes modular coding sequences for antigen binding. Erroneous recombination events causing chromosomal translocations are recognized causes of lymphoid malignancies. Here we show a hybridization based method for sequence enrichment can be used to efficiently and selectively capture genomic DNA a...

  18. TCRgamma gene rearrangement analysis in skin samples and peripheral blood of mycosis fungoides patients:

    OpenAIRE

    Bašanović, Jelena; Cikota, Bojana; Kandolf Sekulović, Lidija; Magić, Zvonko; Medenica, Ljiljana; Pavlović, Miloš; Stojadinović, Olivera; Škiljević, Dušan

    2007-01-01

    Background: Diagnosing mycosis fungoides (MF) can be challenging in the early stage of the disease because histopathological features may simulate a varietyof benign inflammatory skin diseases. Assessment of T-cell clonality was found to be useful in diagnosis and follow-up of patients. Objective: In this study, PCR-based TCRgamma gene rearrangement analysis was performed in skin and peripheral blood samples of patients with MF treated at the two largest referral centers in Serbia, and the re...

  19. Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

    International Nuclear Information System (INIS)

    Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells

  20. T细胞受体γ引物组合检测蕈样肉芽肿基因重排的研究%Application of BIOMED-2 primers in the detection of T cell receptor γ gene rearrangements in patients with mycosis fungoides

    Institute of Scientific and Technical Information of China (English)

    陈柳青; 陈金波; 段逸群; 李东升; 董碧麟; 张红梅; 俞鑫

    2013-01-01

    Objective To estimate the value of BIOMED-2 primers for the detection of T cell receptor γ (TCR-γ) gene rearrangements in different types of specimens from patients with mycosis fungoides (MF).Methods Totally,15 paraffin-embedded tissue specimens,14 fresh tissue specimens and 18 whole blood specimens were obtained from 28 patients with MF,and subjected to DNA extraction.BIOMED-2 multiplex PCR tubes TCRγ (A+B) were used for the analysis of TCRγgene rearrangements.Data were processed by SPSS 13.0 software,and statistical analysis was done by chi-square test and Fisher's exact probability test.Results TCR-γ gene rearrangements were detected in 3 paraffin-embedded tissue specimens,11 fresh tissue specimens and 12 blood specimens,with significant differences in the detection rate between the three samples (x2 =13.047,P < 0.01).The fresh tissue samples showed a significantly higher detection rate than the paraffin-embedded tissue samples (X2 =12.523,P < 0.01).The detection rate of TCRγgene rearrangements was 3/6 in paraffin-embedded tissue samples collected in 2011,significantly higher than that in the other 9 paraffin-embedded tissue samples collected before 2011 (Fisher's exact probability test,P =0.044),but similar to that in 14 fresh tissue specimens (12/14,Fisher's exact probability test,P =0.044).Decreased detection rate of TCRγ gene rearrangements was observed in blood samples compared with fresh tissue specimens,but no statistical difference was observed between the two types of specimens (x2 =2.358,P > 0.05).Conclusions BIOMED-2 multiplex PCR tubes TCRγ(A+B) are suitable for the detection of clonal rearrangements of TCRγgene in different types of specimens,especially in fresh tissue specimens,from patients with MF.%目的 探讨BIOMED-2系统T细胞受体(TCR)γ引物组合在蕈样肉芽肿(MF)患者不同来源标本中TCRγ基因重排检测中的价值.方法 收集28例MF患者15份石蜡组织样本、14份新鲜皮损及18份全血

  1. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    Science.gov (United States)

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. PMID:26296589

  2. 利用Fine-tiling aCGH分析TCR基因重排鉴定T细胞白血病克隆%Analysis of TCR gene rearrangement for identification of T cell leukemia clone by using Fine-tiling aCGH

    Institute of Scientific and Technical Information of China (English)

    郑海涛; 叶铁真; 陈少华; 杨力建; 卢育洪; 李扬秋

    2011-01-01

    AIM: To establish a new method which analyzes T cell receptor (TCR) gene rearrangement for identification of T cells acute lymphoblastic leukemia (T-ALL)clone, it will provide the basis for the study of T-ALL including the chromosome translocation involving TCR loci.METHODS: Total DNA was isolated from peripheral blood mononuclear cells (PBMC) of one case with T-ALL. Using the fine-tiling array comparative genomic hybridization (finetiling aCGH) to analyze the genomic DNA differences of the case and control group, we could find the breakpoints and their position in the chromosomes. According to the preliminary results, we could design the specific primers for the positions of the breakpoints relative to sequence. Furthermore, the ligation-mediated PCR (LM-PCR) and sequence analysis were used to identify the TCR gene rearrangement.And TCR gene expression was detected by RT-PCR. RESULTS: The fine-tiling aCGH results of the T-ALL showed that the TCRα/δ locus of chromosome 14 appeared four breakpoints, corresponding to TCR Vδ1, Vδ2, Jδl and Jδ2.By LM-PCR, sequencing and sequence analysis, TCR gene of the case of T-ALL was involved in Vδ1Dδ2Dδ3Jδl,Vδ2Dδ3Jδ2 rearrangement. RT-PCR results also confirmed the expression of these TCR gene rearrangements. CONCLUSION: The results demonstrated that fine-tiling aCGH and LM-PCR techniques could be used to identify the TCR gene rearrangement as one of the best perfect methods.And it was also a way to find some fusion genes involving in TCR gene.%目的:建立基于分析T细胞受体(TCR)基因重排而确定T细胞-急性淋巴细胞白血病(T-ALL)克隆的新方法,为研究T-ALL中涉及TCR基因位点的染色体易位提供基础.方法:提取1例T-ALL患者外周血单个核细胞(PBMC)的总DNA,利用精细定位的寡核苷酸阵列比较基因组杂交(fine-tiling aCGH)分析样本与对照组基因组DNA的差异,了解不同染色体上可能的断裂点和具体的位点,根据所提供的初步结果,

  3. Chloroplast DNA rearrangements in Campanulaceae: phylogenetic utility of highly rearranged genomes

    Directory of Open Access Journals (Sweden)

    Jansen Robert K

    2004-08-01

    Full Text Available Abstract Background The Campanulaceae (the "hare bell" or "bellflower" family is a derived angiosperm family comprised of about 600 species treated in 35 to 55 genera. Taxonomic treatments vary widely and little phylogenetic work has been done in the family. Gene order in the chloroplast genome usually varies little among vascular plants. However, chloroplast genomes of Campanulaceae represent an exception and phylogenetic analyses solely based on chloroplast rearrangement characters support a reasonably well-resolved tree. Results Chloroplast DNA physical maps were constructed for eighteen representatives of the family. So many gene order changes have occurred among the genomes that characterizing individual mutational events was not always possible. Therefore, we examined different, novel scoring methods to prepare data matrices for cladistic analysis. These approaches yielded largely congruent results but varied in amounts of resolution and homoplasy. The strongly supported nodes were common to all gene order analyses as well as to parallel analyses based on ITS and rbcL sequence data. The results suggest some interesting and unexpected intrafamilial relationships. For example fifteen of the taxa form a derived clade; whereas the remaining three taxa – Platycodon, Codonopsis, and Cyananthus – form the basal clade. This major subdivision of the family corresponds to the distribution of pollen morphology characteristics but is not compatible with previous taxonomic treatments. Conclusions Our use of gene order data in the Campanulaceae provides the most highly resolved phylogeny as yet developed for a plant family using only cpDNA rearrangements. The gene order data showed markedly less homoplasy than sequence data for the same taxa but did not resolve quite as many nodes. The rearrangement characters, though relatively few in number, support robust and meaningful phylogenetic hypotheses and provide new insights into evolutionary

  4. Selenium-Mediated Synthesis of Tetrasubstituted Naphthalenes through Rearrangement

    OpenAIRE

    James Tancock; Thomas Wirth

    2015-01-01

    New β-keto ester substituted stilbene derivatives have been synthesized and cyclized with selenium electrophiles in the presence of Lewis acids. This now allows access to 1,2,3,4-tetrasubstituted naphthalene derivatives as cyclization and rearrangement products.

  5. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    International Nuclear Information System (INIS)

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  6. Development of anaplastic lymphoma kinase (ALK inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer

    Directory of Open Access Journals (Sweden)

    Iwama E

    2014-03-01

    Full Text Available Eiji Iwama,1,2 Isamu Okamoto,3 Taishi Harada,2 Koichi Takayama,2 Yoichi Nakanishi2,3 1Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan Abstract: The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%–5% of non-small-cell lung cancer (NSCLC cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC. Keywords: ALK, rearrangement, NSCLC, ALK inhibitor, targeted therapy, diagnosis

  7. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

    2009-07-07

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  8. Detection of Protein BCL2/JH Rearrangement in Epidermoid Carcinomas of Mouth and Pharynx

    Directory of Open Access Journals (Sweden)

    Montovani, Jair

    2010-09-01

    Full Text Available Introduction: The BCL2 protein found in the internal mothocondrial membrana regulates the apoptosis preventing the programmed cell death. The translocation (14:18, detected in 70 to 85% of the follicular lymphoma, lead the super expression of BCL2 protein, by juxtaposition of BCL2 gene to the JH segment of the immunoglobulins' heavy chain gene. However, the found of the BCL2 expression in head and neck carcinoma are contradictious. Objective: To investigate the presence of the translocation (14:18 of the BCL2 gene in head and neck carcinoma. Method: Sixteen DNA samplers were examinated being 13 of squamous cells carcinoma (SCC and 3 of epidermoid (CE, y means of chain reaction of the polymerase (PCR. Results: The BCL2/JH rearrangement in 2 (15% of the CCE 13 cases and in none of the 3 cases of CE. The average of the frequency of molecules with rearrangement was 46,44x107. Was not observed association between the rearrangement presence and the exhibition to tobacco and alcohol (p=0, 6545. Conclusion: Different from the results found in follicular lymphoma, the presence of the translocation (14; 18 in head and neck carcinomas is not common and, when it occurs, it can be an occasional mutation not associated to exhibition to the tobacco and alcohol.

  9. A versatile reporter system for CRISPR-mediated chromosomal rearrangements

    OpenAIRE

    Li, Yingxiang; Park, Angela I.; Mou, Haiwei; Colpan, Cansu; Bizhanova, Aizhan; Akama-Garren, Elliot; Joshi, Nik; Hendrickson, Eric A; Feldser, David; Yin, Hao; Anderson, Daniel G.; Jacks, Tyler; Weng, Zhiping; Xue, Wen

    2015-01-01

    Although chromosomal deletions and inversions are important in cancer, conventional methods for detecting DNA rearrangements require laborious indirect assays. Here we develop fluorescent reporters to rapidly quantify CRISPR/Cas9-mediated deletions and inversions. We find that inversion depends on the non-homologous end-joining enzyme LIG4. We also engineer deletions and inversions for a 50 kb Pten genomic region in mouse liver. We discover diverse yet sequence-specific indels at the rearrang...

  10. Monotone equimeasurable rearrangements with non-additive probabilities

    OpenAIRE

    Ghossoub, Mario

    2011-01-01

    In the classical theory of monotone equimeasurable rearrangements of functions, “equimeasurability” (i.e. the fact the two functions have the same distribution) is defined relative to a given additive probability measure. These rearrangement tools have been successfully used in many problems in economic theory dealing with uncertainty where the monotonicity of a solution is desired. However, in all of these problems, uncertainty refers to the classical Bayesian understanding of the term, wher...

  11. DNA rearrangements directed by non-coding RNAs in ciliates

    OpenAIRE

    Mochizuki, Kazufumi

    2010-01-01

    Extensive programmed rearrangement of DNA, including DNA elimination, chromosome fragmentation, and DNA descrambling, takes place in the newly developed macronucleus during the sexual reproduction of ciliated protozoa. Recent studies have revealed that two distant classes of ciliates use distinct types of non-coding RNAs to regulate such DNA rearrangement events. DNA elimination in Tetrahymena is regulated by small non-coding RNAs that are produced and utilized in an RNAi-related process. It ...

  12. Mechanisms of chromosomal rearrangement in the human genome

    OpenAIRE

    Lieber Michael R; Tsai Albert G

    2010-01-01

    Abstract Many human cancers are associated with characteristic chromosomal rearrangements, especially hematopoietic cancers such as leukemias and lymphomas. The first and most critical step in the rearrangement process is the induction of two DNA double-strand breaks (DSB). In all cases, at least one of the two DSBs is generated by a pathologic process, such as (1) randomly-positioned breaks due to ionizing radiation, free radical oxidative damage, or spontaneous hydrolysis; (2) breaks associ...

  13. Fuel Cell Power Model Version 2: Startup Guide, System Designs, and Case Studies. Modeling Electricity, Heat, and Hydrogen Generation from Fuel Cell-Based Distributed Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Steward, D.; Penev, M.; Saur, G.; Becker, W.; Zuboy, J.

    2013-06-01

    This guide helps users get started with the U.S. Department of Energy/National Renewable Energy Laboratory Fuel Cell Power (FCPower) Model Version 2, which is a Microsoft Excel workbook that analyzes the technical and economic aspects of high-temperature fuel cell-based distributed energy systems with the aim of providing consistent, transparent, comparable results. This type of energy system would provide onsite-generated heat and electricity to large end users such as hospitals and office complexes. The hydrogen produced could be used for fueling vehicles or stored for later conversion to electricity.

  14. Peripheral blood involvement in non-Hodgkin's lymphoma detected by clonal gene rearrangement as a biological prognostic marker.

    OpenAIRE

    Hiorns, L R; Nicholls, J; Sloane, J P; Horwich, A.; Ashley, S.; Brada, M.

    1994-01-01

    Peripheral blood from 67 patients with non-Hodgkin's lymphoma was examined at initial diagnosis for the presence of circulating lymphoma cells by DNA hybridisation using immunoglobulin and T-cell receptor gene probes. Clonal gene rearrangement was found in 31% (21/67) of patients and correlated with clinical stage, histological grade and bone marrow involvement. Clinical stage and the presence of lymphoma cells in peripheral blood were prognostic factors for progression-free survival in all p...

  15. Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

    International Nuclear Information System (INIS)

    All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

  16. Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci.

    Science.gov (United States)

    Rother, Magdalena B; Palstra, Robert-Jan; Jhunjhunwala, Suchit; van Kester, Kevin A M; van IJcken, Wilfred F J; Hendriks, Rudi W; van Dongen, Jacques J M; Murre, Cornelis; van Zelm, Menno C

    2016-01-01

    Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag(-/-) progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Igh relocated from the nuclear lamina to central domains only at the pro-B cell stage, whereas, Igκ remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci. PMID:26384565

  17. Radiologically guided fine needle lung biopsies in the evaluation of focal pulmonary lesions in allogeneic stem cell transplant recipients.

    Science.gov (United States)

    Jantunen, E; Piilonen, A; Volin, L; Ruutu, P; Parkkali, T; Koukila-Kähkölä, P; Ruutu, T

    2002-02-01

    Lung problems are common in allogeneic stem cell transplant (SCT) recipients. To evaluate the feasibility and diagnostic yield of radiologically guided fine needle lung biopsy (FNLB) in allogeneic SCT recipients with focal pulmonary lesions, a retrospective analysis was carried out. Between 1989 and 1998, radiologists performed a total of 30 FNLBs in 21 allogeneic SCT recipients, guided either by ultrasound (n = 17) or computed tomography (n = 13). The median time from SCT to the first FNLB was 131 days (20-343 days). Prophylactic platelet transfusions were given in 19 procedures (66%). The complications of FNLB included clinically insignificant pneumothorax in four procedures (13%) and self-limiting haemoptysis in one case (3%). The first FNLB was suggestive of invasive pulmonary aspergillosis (IPA) in five patients (24%). Additional clinically useful findings of FNLB included Pseudomonas (two patients) and Nocardia (one patient). The final diagnosis of pulmonary lesions was IPA in 14 patients, immunological lung problems in four patients and other in three patients. Radiologically guided FNLB is feasible in allogeneic SCT recipients and has a low complication rate. The diagnostic yield is high especially for IPA. PMID:11896433

  18. Image-guided tumor ablation for the treatment of recurrent non-small cell lung cancer within the radiation field

    International Nuclear Information System (INIS)

    Purpose: The treatment options for non-small-cell lung cancer (NSCLC) that recurs after irradiation are limited. Image-guided percutaneous thermal ablation is an effective option in treating NSCLC that may provide an alternative to reirradiation. The purpose of this paper is to determine the survival and palliative benefit of image-guided percutaneous thermal ablation in the treatment of NSCLC that recurred within the treatment field of prior external beam radiation therapy. Methods: Twenty patients, median age 70, who had NSCLC recurrences following irradiation were treated with image-guided thermal ablation. Kaplan–Meier analysis was used to assess survival benefit and subjective pain reports were used to investigate pain relief. Results: The median survival time was 13.1 ± SE 1.4 months and the median survival time without local recurrence was 8.5 ± 1.6 months. Eight patients (40%) recurred locally after a median of 3.3 months. Seven out of ten patients (70%) presenting with significant pain had decreased pain at initial post-ablation evaluation. Following the 25 ablations, there were no Grade IV or V, 1 Grade III, 3 Grade II, and 23 Grade I complications. Conclusion: Thermal ablation offers a potential survival benefit compared with other available modalities for the treatment of NSCLC recurring within a previously irradiated field. This promising technique has a good safety profile and may also be useful in providing symptomatic relief.

  19. Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor

    International Nuclear Information System (INIS)

    A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones

  20. Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Panizza, Pedro Sergio Brito; Albuquerque Cavalcanti, Conrado Furtado de [Sírio Libânes Hospital, Radiology and Imaged Guided Intervention Service (Brazil); Yamaguchi, Nise Hitomi [Instituto Avanços em Medicina (Brazil); Leite, Claudia Costa; Cerri, Giovanni Guido; Menezes, Marcos Roberto de, E-mail: marcos.menezes@hc.fm.usp.br [Sírio Libânes Hospital, Radiology and Imaged Guided Intervention Service (Brazil)

    2016-02-15

    A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

  1. Divergence of gene regulation through chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Messing Joachim

    2010-11-01

    Full Text Available Abstract Background The molecular mechanisms that modify genome structures to give birth and death to alleles are still not well understood. To investigate the causative chromosomal rearrangements, we took advantage of the allelic diversity of the duplicated p1 and p2 genes in maize. Both genes encode a transcription factor involved in maysin synthesis, which confers resistance to corn earworm. However, p1 also controls accumulation of reddish pigments in floral tissues and has therefore acquired a new function after gene duplication. p1 alleles vary in their tissue-specific expression, which is indicated in their allele designation: the first suffix refers to red or white pericarp pigmentation and the second to red or white glume pigmentation. Results Comparing chromosomal regions comprising p1-ww[4Co63], P1-rw1077 and P1-rr4B2 alleles with that of the reference genome, P1-wr[B73], enabled us to reconstruct additive events of transposition, chromosome breaks and repairs, and recombination that resulted in phenotypic variation and chimeric regulatory signals. The p1-ww[4Co63] null allele is probably derived from P1-wr[B73] by unequal crossover between large flanking sequences. A transposon insertion in a P1-wr-like allele and NHEJ (non-homologous end-joining could have resulted in the formation of the P1-rw1077 allele. A second NHEJ event, followed by unequal crossover, probably led to the duplication of an enhancer region, creating the P1-rr4B2 allele. Moreover, a rather dynamic picture emerged in the use of polyadenylation signals by different p1 alleles. Interestingly, p1 alleles can be placed on both sides of a large retrotransposon cluster through recombination, while functional p2 alleles have only been found proximal to the cluster. Conclusions Allelic diversity of the p locus exemplifies how gene duplications promote phenotypic variability through composite regulatory signals. Transposition events increase the level of genomic complexity

  2. Characterization of genetic rearrangements in esophageal squamous carcinoma cell lines by a combination of M-FISH and array-CGH: further confirmation of some split genomic regions in primary tumors

    International Nuclear Information System (INIS)

    Chromosomal and genomic aberrations are common features of human cancers. However, chromosomal numerical and structural aberrations, breakpoints and disrupted genes have yet to be identified in esophageal squamous cell carcinoma (ESCC). Using multiplex-fluorescence in situ hybridization (M-FISH) and oligo array-based comparative hybridization (array-CGH), we identified aberrations and breakpoints in six ESCC cell lines. Furthermore, we detected recurrent breakpoints in primary tumors by dual-color FISH. M-FISH and array-CGH results revealed complex numerical and structural aberrations. Frequent gains occurred at 3q26.33-qter, 5p14.1-p11, 7pter-p12.3, 8q24.13-q24.21, 9q31.1-qter, 11p13-p11, 11q11-q13.4, 17q23.3-qter, 18pter-p11, 19 and 20q13.32-qter. Losses were frequent at 18q21.1-qter. Breakpoints that clustered within 1 or 2 Mb were identified, including 9p21.3, 11q13.3-q13.4, 15q25.3 and 3q28. By dual-color FISH, we observed that several recurrent breakpoint regions in cell lines were also present in ESCC tumors. In particular, breakpoints clustered at 11q13.3-q13.4 were identified in 43.3% (58/134) of ESCC tumors. Both 11q13.3-q13.4 splitting and amplification were significantly correlated with lymph node metastasis (LNM) (P = 0.004 and 0.022) and advanced stages (P = 0.004 and 0.039). Multivariate logistic regression analysis revealed that only 11q13.3-q13.4 splitting was an independent predictor for LNM (P = 0.026). The combination of M-FISH and array-CGH helps produce more accurate karyotypes. Our data provide significant, detailed information for appropriate uses of these ESCC cell lines for cytogenetic and molecular biological studies. The aberrations and breakpoints detected in both the cell lines and primary tumors will contribute to identify affected genes involved in the development and progression of ESCC

  3. The B-MYB transcriptional network guides cell cycle progression and fate decisions to sustain self-renewal and the identity of pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Ming Zhan

    Full Text Available Embryonic stem cells (ESCs are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs, and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity.

  4. Collective Classification of Textual Documents by Guided Self-Organization in T-Cell Cross-Regulation Dynamics

    CERN Document Server

    Abi-Haidar, Alaa; 10.1007/s12065-011-0052-5

    2011-01-01

    We present and study an agent-based model of T-Cell cross-regulation in the adaptive immune system, which we apply to binary classification. Our method expands an existing analytical model of T-cell cross-regulation (Carneiro et al. in Immunol Rev 216(1):48-68, 2007) that was used to study the self-organizing dynamics of a single population of T-Cells in interaction with an idealized antigen presenting cell capable of presenting a single antigen. With agent-based modeling we are able to study the self-organizing dynamics of multiple populations of distinct T-cells which interact via antigen presenting cells that present hundreds of distinct antigens. Moreover, we show that such self-organizing dynamics can be guided to produce an effective binary classification of antigens, which is competitive with existing machine learning methods when applied to biomedical text classification. More specifically, here we test our model on a dataset of publicly available full-text biomedical articles provided by the BioCreat...

  5. CT-guided lymphoscintigraphy in patients with squamous cell carcinoma of the head and neck: a feasibility study

    International Nuclear Information System (INIS)

    Accurate knowledge of lymphatic drainage facilitates planning of surgery for patients with squamous cell carcinoma of the head and neck. The aim of this study was to evaluate the feasibility of a new injection technique for lymph node detection in patients with squamous cell carcinoma of the hypopharynx and larynx, in whom simple peritumoural injection is hampered by the tumour localisation. Computed tomography (CT)-guided lymphoscintigraphy was performed in a total of 13 patients with squamous cell carcinoma of the hypopharynx and larynx who could not be injected by simple visual inspection. In a first step, contrast medium-enhanced axial 5-mm-thick CT slices of the neck were obtained. After tumour localisation on these CT images, 1-2 ml contrast medium and, in the event of appropriate distribution, subsequently 50 MBq technetium-99m colloid were injected at one to three peritumoural sites under CT guidance. Peritumoural tracer distribution was controlled by thin-slice CT. Subsequently, planar scintigrams from anterior, right and left lateral views were obtained. In all patients, peritumoural colloid application was feasible, as shown on control CT scans. Post injection, neither severe nor minor complications were noted. The patients complained of only low pain sensations with an average score of 1.8 on a pain scale from 0 to 10. Lymphatic drainage was identified in nine of the 13 patients, with a total of 14 detected lymph nodes. In six patients, ipsilateral sentinel lymph nodes were visualised; bilateral sentinel lymph nodes were identified in one patient and contralateral lymphatic drainage was observed in two patients. CT-guided lymphoscintigraphy is a feasible and minimally invasive diagnostic tool for sentinel lymph node detection in patients with squamous cell carcinoma of the hypopharynx and the larynx. In contrast to endoscopic colloid injection under general anaesthesia, this technique seems to be a well-tolerated method for lymphatic mapping prior to

  6. Simple and Rapid In Vivo Generation of Chromosomal Rearrangements using CRISPR/Cas9 Technology

    Directory of Open Access Journals (Sweden)

    Rafael B. Blasco

    2014-11-01

    Full Text Available Generation of genetically engineered mouse models (GEMMs for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs. Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

  7. A versatile reporter system for CRISPR-mediated chromosomal rearrangements.

    Science.gov (United States)

    Li, Yingxiang; Park, Angela I; Mou, Haiwei; Colpan, Cansu; Bizhanova, Aizhan; Akama-Garren, Elliot; Joshi, Nik; Hendrickson, Eric A; Feldser, David; Yin, Hao; Anderson, Daniel G; Jacks, Tyler; Weng, Zhiping; Xue, Wen

    2015-01-01

    Although chromosomal deletions and inversions are important in cancer, conventional methods for detecting DNA rearrangements require laborious indirect assays. Here we develop fluorescent reporters to rapidly quantify CRISPR/Cas9-mediated deletions and inversions. We find that inversion depends on the non-homologous end-joining enzyme LIG4. We also engineer deletions and inversions for a 50 kb Pten genomic region in mouse liver. We discover diverse yet sequence-specific indels at the rearrangement fusion sites. Moreover, we detect Cas9 cleavage at the fourth nucleotide on the non-complementary strand, leading to staggered instead of blunt DNA breaks. These reporters allow mechanisms of chromosomal rearrangements to be investigated. PMID:26018130

  8. Low-Temperature Cationic Rearrangement in a Bulk Metal Oxide.

    Science.gov (United States)

    Li, Man-Rong; Retuerto, Maria; Stephens, Peter W; Croft, Mark; Sheptyakov, Denis; Pomjakushin, Vladimir; Deng, Zheng; Akamatsu, Hirofumi; Gopalan, Venkatraman; Sánchez-Benítez, Javier; Saouma, Felix O; Jang, Joon I; Walker, David; Greenblatt, Martha

    2016-08-16

    Cationic rearrangement is a compelling strategy for producing desirable physical properties by atomic-scale manipulation. However, activating ionic diffusion typically requires high temperature, and in some cases also high pressure in bulk oxide materials. Herein, we present the cationic rearrangement in bulk Mn2 FeMoO6 at unparalleled low temperatures of 150-300 (o) C. The irreversible ionic motion at ambient pressure, as evidenced by real-time powder synchrotron X-ray and neutron diffraction, and second harmonic generation, leads to a transition from a Ni3 TeO6 -type to an ordered-ilmenite structure, and dramatic changes of the electrical and magnetic properties. This work demonstrates a remarkable cationic rearrangement, with corresponding large changes in the physical properties in a bulk oxide at unprecedented low temperatures. PMID:27203790

  9. 13号染色体重排所致严重少弱畸形精子症患者生精细胞减数分裂分析%Meiotic analysis of spermatogenic cells in severe oligoasthenoteratozoospermia with chromosome 13 rearrangement

    Institute of Scientific and Technical Information of China (English)

    崔英霞; 杨晓玉; 夏欣一; 周洋; 陈颖皓; 胡毓安

    2012-01-01

    Objective: To explore the possible mechanisms of spermatogenic arrest in severe oligoasthenoteratozoospermia induced by supernumerary, ring-neocentric 13ql2. 3 → 13q22 chromosome and reciprocal deletion. Methods: We performed a genomiipwide high-density oaCGH analysis for a case of oligoasthenoteratozoospermia with abnormal chromosome 13 to characterize the breakpoints of the chromosome involved or the gene deletion caused by the rearrangement. We also conducted a fluorescence in situ hybridization analysis on the germ cells using probes of 13ql4/13qter to observe the pairing condition of homologous chromosome 13. Results: We identified by oaCGH analysis a microdeletion of 4 consecutive probes ( A_16_P19757882, A_16_P02744617, A_14_ P108858 and A_16_P02744687 at chrl3ql2.3: 27979261 →28039191) with 59.93 kb between the FLT1 and POMP genes, with no annotated genes in the deleted region. The signals of 13ql4 and 13qter were separated from each other in 90% of all the primary sper-matocytes examined, indicating the unpairing of homologous chromosome 13 or synapse failure. Conclusion: Chromosomal rearrange- merit-induced spermatogenesis failure is caused by the impairing of the homologous chromosomes involved in the first meiotic division of germ cells.%目的:探讨13号染色体长臂相互缺失所致严重少弱畸形精子症患者生精阻滞的可能机制. 方法:对1例13号染色体异常的严重少弱畸形精子症患者血液样本进行全基因组的寡核苷酸微阵列比较基因组杂交分析,以确定受累染色体的断裂点或基因缺失.对患者生殖细胞进行多色荧光原位杂交分析,以观察初级精母细胞13号染色体配对的情况. 结果:寡核苷酸微阵列比较基因组杂交技术显示在13q12.3上有连续4个探针的缺失(A_16_P19757882,A16_P02744617,A_14_ P108858和A_16_P02744687),覆盖59.93 kb,位于基因FLT1和POMP之间,没有注释基因存在.初级精母细胞的减数分裂分析显示同源13

  10. Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.

    Science.gov (United States)

    Kim, Heejin; Min, Kyoung-Ik; Inoue, Keita; Im, Do Jin; Kim, Dong-Pyo; Yoshida, Jun-ichi

    2016-05-01

    In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production. PMID:27151864

  11. Brueckner rearrangement energies in s-shell hypernuclei

    International Nuclear Information System (INIS)

    We consider rearrangement effects in light hypernuclei in the framework of the lowest order Brueckner theory. The energy change of the 4He core of Λ5He when the Λ hyperon is added to 4He is first estimated without much numerical computations. Next, rearrangement contributions in ΔΒΛΛ(ΛΛ6He) are estimated, which are important to deduce the strength of the ΛΛ interaction from the experimental ΔΒΛΛ(ΛΛ6He). (author)

  12. Recurrent DNA inversion rearrangements in the human genome

    DEFF Research Database (Denmark)

    Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia;

    2007-01-01

    Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome. In...... human genomic variation is discussed....... particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located on...

  13. Rearrangement of dypnones to 1,3,5-triarylbenzenes.

    Science.gov (United States)

    Deng, Kai; Huai, Qi-Yong; Shen, Zhi-Lun; Li, Hui-Jing; Liu, Chen; Wu, Yan-Chao

    2015-03-20

    Rearrangement of dypnones to 1,3,5-triarylbenzenes is described. The reaction is proposed to involve an aldol-type self-condensation of dypnones, followed by an intramolecular [2 + 2] cycloaddition and a retro-[2 + 2] cycloaddition. The reaction goes smoothly under obviously milder conditions in comparison to the cyclotrimerization of acetophenones to 1,3,5-triarylbenzenes (10 mol % of TsOH, 80 °C versus 130-148 °C). This unexpected rearrangement would provide new possible considerations in dypnone-involved organic synthesis. PMID:25740008

  14. Ultrafast infrared studies of complex ligand rearrangements in solution

    Energy Technology Data Exchange (ETDEWEB)

    Payne, Christine K.

    2003-05-31

    The complete description of a chemical reaction in solution depends upon an understanding of the reactive molecule as well as its interactions with the surrounding solvent molecules. Using ultrafast infrared spectroscopy it is possible to observe both the solute-solvent interactions and the rearrangement steps which determine the overall course of a chemical reaction. The topics addressed in these studies focus on reaction mechanisms which require the rearrangement of complex ligands and the spectroscopic techniques necessary for the determination of these mechanisms. Ligand rearrangement is studied by considering two different reaction mechanisms for which the rearrangement of a complex ligand constitutes the most important step of the reaction. The first system concerns the rearrangement of a cyclopentadienyl ring as the response of an organometallic complex to a loss of electron density. This mechanism, commonly referred to as ''ring slip'', is frequently cited to explain reaction mechanisms. However, the ring slipped intermediate is too short-lived to be observed using conventional methods. Using a combination of ultrafast infrared spectroscopy and electronic structure calculations it has been shown that the intermediate exists, but does not form an eighteen-electron intermediate as suggested by traditional molecular orbital models. The second example examines the initial steps of alkyne polymerization. Group 6 (Cr, Mo, W) pentacarbonyl species are generated photolytically and used to catalyze the polymerization of unsaturated hydrocarbons through a series of coordination and rearrangement steps. Observing this reaction on the femto- to millisecond timescale indicates that the initial coordination of an alkyne solvent molecule to the metal center results in a stable intermediate that does not rearrange to form the polymer precursor. This suggests that polymerization requires the dissociation of additional carbonyl ligands before

  15. Rearrangement and evolution of mitochondrial genomes in parrots.

    Science.gov (United States)

    Eberhard, Jessica R; Wright, Timothy F

    2016-01-01

    Mitochondrial genome rearrangements that result in control region duplication have been described for a variety of birds, but the mechanisms leading to their appearance and maintenance remain unclear, and their effect on sequence evolution has not been explored. A recent survey of mitochondrial genomes in the Psittaciformes (parrots) found that control region duplications have arisen independently at least six times across the order. We analyzed complete mitochondrial genome sequences from 20 parrot species, including representatives of each lineage with control region duplications, to document the gene order changes and to examine effects of genome rearrangements on patterns of sequence evolution. The gene order previously reported for Amazona parrots was found for four of the six independently derived genome rearrangements, and a previously undescribed gene order was found in Prioniturus luconensis, representing a fifth clade with rearranged genomes; the gene order resulting from the remaining rearrangement event could not be confirmed. In all rearranged genomes, two copies of the control region are present and are very similar at the sequence level, while duplicates of the other genes involved in the rearrangement show signs of degeneration or have been lost altogether. We compared rates of sequence evolution in genomes with and without control region duplications and did not find a consistent acceleration or deceleration associated with the duplications. This could be due to the fact that most of the genome rearrangement events in parrots are ancient, and additionally, to an effect of body size on evolutionary rate that we found for mitochondrial but not nuclear sequences. Base composition analyses found that relative to other birds, parrots have unusually strong compositional asymmetry (AT- and GC-skew) in their coding sequences, especially at fourfold degenerate sites. Furthermore, we found higher AT skew in species with control region duplications. One

  16. Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system.

    Science.gov (United States)

    Morishita, Maki; Muramatsu, Tomoki; Suto, Yumiko; Hirai, Momoki; Konishi, Teruaki; Hayashi, Shin; Shigemizu, Daichi; Tsunoda, Tatsuhiko; Moriyama, Keiji; Inazawa, Johji

    2016-03-01

    Chromothripsis is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event, rather than an accumulation of a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and is thought to be associated with increased malignancy and carcinogenesis. However, the causes and consequences of chromothripsis remain unclear. Therefore, to identify the mechanism underlying the generation of chromothripsis, we investigated whether chromothripsis could be artificially induced by ionizing radiation. We first elicited DNA double-strand breaks in an oral squamous cell carcinoma cell line HOC313-P and its highly metastatic subline HOC313-LM, using Single Particle Irradiation system to Cell (SPICE), a focused vertical microbeam system designed to irradiate a spot within the nuclei of adhesive cells, and then established irradiated monoclonal sublines from them, respectively. SNP array analysis detected a number of chromosomal copy number alterations (CNAs) in these sublines, and one HOC313-LM-derived monoclonal subline irradiated with 200 protons by the microbeam displayed multiple CNAs involved locally in chromosome 7. Multi-color FISH showed a complex translocation of chromosome 7 involving chromosomes 11 and 12. Furthermore, whole genome sequencing analysis revealed multiple de novo complex chromosomal rearrangements localized in chromosomes 2, 5, 7, and 20, resembling chromothripsis. These findings suggested that localized ionizing irradiation within the nucleus may induce chromothripsis-like complex chromosomal alterations via local DNA damage in the nucleus. PMID:26862731

  17. Requirement for CDK6 in MLL-rearranged acute myeloid leukemia.

    Science.gov (United States)

    Placke, Theresa; Faber, Katrin; Nonami, Atsushi; Putwain, Sarah L; Salih, Helmut R; Heidel, Florian H; Krämer, Alwin; Root, David E; Barbie, David A; Krivtsov, Andrei V; Armstrong, Scott A; Hahn, William C; Huntly, Brian J; Sykes, Stephen M; Milsom, Michael D; Scholl, Claudia; Fröhling, Stefan

    2014-07-01

    Chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) trigger aberrant gene expression in hematopoietic progenitors and give rise to an aggressive subtype of acute myeloid leukemia (AML). Insights into MLL fusion-mediated leukemogenesis have not yet translated into better therapies because MLL is difficult to target directly, and the identity of the genes downstream of MLL whose altered transcription mediates leukemic transformation are poorly annotated. We used a functional genetic approach to uncover that AML cells driven by MLL-AF9 are exceptionally reliant on the cell-cycle regulator CDK6, but not its functional homolog CDK4, and that the preferential growth inhibition induced by CDK6 depletion is mediated through enhanced myeloid differentiation. CDK6 essentiality is also evident in AML cells harboring alternate MLL fusions and a mouse model of MLL-AF9-driven leukemia and can be ascribed to transcriptional activation of CDK6 by mutant MLL. Importantly, the context-dependent effects of lowering CDK6 expression are closely phenocopied by a small-molecule CDK6 inhibitor currently in clinical development. These data identify CDK6 as critical effector of MLL fusions in leukemogenesis that might be targeted to overcome the differentiation block associated with MLL-rearranged AML, and underscore that cell-cycle regulators may have distinct, noncanonical, and nonredundant functions in different contexts. PMID:24764564

  18. Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses.

    Science.gov (United States)

    Lian, Jeffrey; Luster, Andrew D

    2015-10-01

    The generation of adaptive immune responses occurs in the lymph node (LN) and requires that lymphocytes locate and interact with cognate antigen-bearing dendritic cells. This process requires the coordinated movement of both innate and adaptive immune cells, and is orchestrated by the chemokine family of chemotactic cytokines. Upon initiation of inflammation, the LN undergoes dramatic changes that include the marked induction of specific chemokines in distinct regions of the reactive LN. These chemokine rich domains establish LN niches that facilitate the differentiation of CD4+ T cells into effector cell subsets and the rapid activation of memory CD8+ T cells. This review will focus on recent advances highlighting the importance of LN chemokines for shaping adaptive immune responses by controlling immune cell migration, positioning, and interactions in the reactive LN. PMID:26067148

  19. Argonaute 2 in cell-secreted microvesicles guides the function of secreted miRNAs in recipient cells.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Lv

    Full Text Available MicroRNAs (miRNAs secreted by cells into microvesicles (MVs form a novel class of signal molecules that mediate intercellular communication. However, several fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism that governs the function or fate of exogenous miRNAs in recipient cells. In the present study, we provide evidence indicating that Argonaute 2 (Ago2 plays a role in stabilizing miRNAs and facilitating the packaging of secreted miRNAs into MVs. More importantly, Ago2 in origin cell-secreted MVs (but not in recipient cells directs the function of secreted miRNAs. First, Ago2 overexpression clearly increased the level of miR-16 in cells transfected with a miR-16 mimic by protecting the miRNAs from degradation in lysosomes. Second, Ago2 overexpression increased the level of miR-16 in cell-secreted MVs, suggesting that Ago2 may facilitate the packaging of secreted miRNAs into MVs. Third, exogenous miR-16 delivered by MVs within the origin cells significantly reduced the Bcl2 protein level in recipient cells, and miR-16 and Bcl2 mRNA were physically associated with exogenous HA-tagged Ago2 (HA-Ago2. Finally, the effect of MV-delivered miR-16 on the production of the Bcl2 protein in recipient cells was not abolished by knocking down Ago2 in the recipient cells.

  20. A cell-regulatory mechanism involving feedback between contraction and tissue formation guides wound healing progression.

    Directory of Open Access Journals (Sweden)

    Clara Valero

    Full Text Available Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.

  1. Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation

    Science.gov (United States)

    Marhavý, Peter; Montesinos, Juan Carlos; Abuzeineh, Anas; Van Damme, Daniel; Vermeer, Joop E.M.; Duclercq, Jerôme; Rakusová, Hana; Nováková, Petra; Friml, Jiři; Geldner, Niko; Benková, Eva

    2016-01-01

    To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved proliferation capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endodermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots. PMID:26883363

  2. A comparison of mathematical models for polarization of single eukaryotic cells in response to guided cues.

    Directory of Open Access Journals (Sweden)

    Alexandra Jilkine

    2011-04-01

    Full Text Available Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons, and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness.

  3. The Petasis-Ferrier rearrangement: developments and applications.

    Science.gov (United States)

    Minbiole, Emily C; Minbiole, Kevin P C

    2016-04-01

    In the mid-1990s, Petasis reexamined a promising but infrequently used rearrangement strategy, the so-called Ferrier-type-II reaction, and provided it with a modern update. Previously, Ferrier had developed a strategy where carbohydrate derivatives would undergo a fragmentation/aldol-type recombination sequence, generating a carbocycle, albeit under the promotion of stoichiometric mercury salts. Petasis' new variant showed the promise to effectively and stereoselectively convert a range of cyclic vinyl acetals to useful tetrahydrofurans and tetrahydropyrans, using less toxic promoters. Since these first reports, the 'Petasis-Ferrier rearrangement' has represented a vibrant area of research and innovation for organic chemists. With numerous applications in complex natural product total synthesis, the utility of the reaction has been resoundingly established. Recent developments have extended the reaction to a broader synthetic context, allowing for in situ generation of rearrangement substrates and more liberal interpretation of what fragmentation/recombination reactions warrant the designation of a Petasis-Ferrier rearrangement. PMID:26732258

  4. Sequence features contributing to chromosomal rearrangements in Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Russell Spencer-Smith

    Full Text Available Through whole genome sequence alignments, breakpoints in chromosomal synteny can be identified and the sequence features associated with these determined. Alignments of the genome sequences of Neisseria gonorrhoeae strain FA1090, N.gonorrhoeae strain NCCP11945, and N. gonorrhoeae strain TCDC-NG08107 reveal chromosomal rearrangements that have occurred. Based on these alignments and dot plot pair-wise comparisons, the overall chromosomal arrangement of strain NCCP11945 and TCDC-NG08107 are very similar, with no large inversions or translocations. The insertion of the Gonococcal Genetic Island in strain NCCP11945 is the most prominent distinguishing feature differentiating these strains. When strain NCCP11945 is compared to strain FA1090, however, 14 breakpoints in chromosomal synteny are identified between these gonococcal strains. The majority of these, 11 of 14, are associated with a prophage, IS elements, or IS-like repeat enclosed elements which appear to have played a role in the rearrangements observed. Additional rearrangements of small regions of the genome are associated with pilin genes. Evidence presented here suggests that the rearrangements of blocks of sequence are mediated by activation of prophage and associated IS elements and reintegration elsewhere in the genome or by homologous recombination between IS-like elements that have generated inversions.

  5. Density Functional Study on the Mechanism of Amadori Rearrangement Reaction

    Institute of Scientific and Technical Information of China (English)

    BAO Xiu-Xiu; CHEN Zu-Qin; XIE Hu-Jun

    2011-01-01

    The reaction mechanism of amadori rearrangement in the initial stage of Maillard reaction has been investigated by means of density functional theory calculations in the gaseous phase and aqueous solution. Cyclic ribose and glycine were taken as the model in the amadori rearrangement. Reaction mechanisms have been proposed, and possibility for the formation of different compounds has been evaluated through calculating the relative energy changes for different steps of the reaction by following the total mass balance. The calculations reveal that the amadori rearrangement initialized via the intramolecular rearrangement, transferring one proton from N(3) to O(4) atom. In the next step, the second proton is also transferred from N(3) to O(4) atom,corresponding to the cleavage of C(4)-O(4) bond and the release of one water molecule. Then another proton is transferred from N(3) to C(5) atom via TS3 with the reaction barrier of 58.3kcal.mol-1 after tunneling the effect correction calculated at the B3LYP/6-31+G(d) level of theory,and this step is rate limiting for the whole catalytic cycle. Ultimately, the product is generated via keto-enolic tautomerization. Present calculation could provide insights into the reaction mechanism of Maillard reaction since experimental evaluation of the role of intermediates in the Maillard reaction is quite complicated.

  6. λ-Rearrangements Characterization of Pringsheim Limit Points

    Directory of Open Access Journals (Sweden)

    Richard F. Patterson

    2007-01-01

    Full Text Available Sufficient conditions are given to assure that a four-dimensional matrix A will have the property that any double sequence x with finite P-limit point has- a λ-rearrangement z such that each finite P-limit point of x is a P-limit point of Az.

  7. Lipschitz Properties in Variable Exponent Problems via Relative Rearrangement

    Institute of Scientific and Technical Information of China (English)

    Jean-Michel RAKOTOSON

    2010-01-01

    The author first studies the Lipschitz properties of the monotone and relative rearrangement mappings in variable exponent Lebesgue spaces completing the result given in[9].This paper is ended by establishing the Lipschitz properties for quasilinear problems with variable exponent when the right-hand side is in some dual spaces of a suitable Sobolev space associated to variable exponent.

  8. Conjugated polyaniline as a result of the benzidine rearrangement

    Czech Academy of Sciences Publication Activity Database

    Sapurina, Irina; Tenkovtsev, A. V.; Stejskal, Jaroslav

    2015-01-01

    Roč. 64, č. 4 (2015), s. 453-465. ISSN 0959-8103 R&D Projects: GA MŠk(CZ) LH14199; GA ČR(CZ) GA13-00270S Institutional support: RVO:61389013 Keywords : anilin e * anilin e oligomers * benzidine rearrangement Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.409, year: 2014

  9. Linear Secret Sharing Schemes and Rearrangements of Access Structures

    Institute of Scientific and Technical Information of China (English)

    Liang-liang Xiao; Mu-lan Liu

    2004-01-01

    In this paper we study linear secret sharing schemes by monotone span programs, according to the relation between realizing access structures by linear secret sharing schemes and computing monotone Boolean functions by monotone span programs. Weconstruct some linear secret sharing schemes. Furthermore, we study the rearrangements of access structures that is very important in practice.

  10. The use of circulating tumor cells in guiding treatment decisions for patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Onstenk, Wendy; de Klaver, Willemijn; de Wit, Ronald; Lolkema, Martijn; Foekens, John; Sleijfer, Stefan

    2016-05-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has drastically changed over the past decade with the advent of several new anti-tumor agents. Oncologists increasingly face dilemmas concerning the best treatment sequence for individual patients since most of the novel compounds have been investigated and subsequently positioned either pre- or post-docetaxel. A currently unmet need exists for biomarkers able to guide treatment decisions and to capture treatment resistance at an early stage thereby allowing for an early change to an alternative strategy. Circulating tumor cells (CTCs) have in this context intensively been investigated over the last years. The CTC count, as determined by the CellSearch System (Janssen Diagnostics LLC, Raritan, NJ), is a strong, independent prognostic factor for overall survival in patients with mCRPC at various time points during treatment and, as an early response marker, outperforms traditional response evaluations using serum prostate specific antigen (PSA) levels, scintigraphy as well as radiography. The focus of research is now shifting toward the predictive value of CTCs and the use of the characterization of CTCs to guide the selection of treatments with the highest chance of success for individual patients. Recently, the presence of the androgen receptor splice variant 7 (AR-V7) has been shown to be a promising predictive factor. In this review, we have explored the clinical value of the enumeration and characterization of CTCs for the treatment of mCRPC and have put the results obtained from recent studies investigating the prognostic and predictive value of CTCs into clinical perspective. PMID:27107266

  11. B cell development and VDJ rearrangement in the fetal pig

    Czech Academy of Sciences Publication Activity Database

    Šinkora, Marek; Šinkorová, J.; Butler, J. E.

    2002-01-01

    Roč. 87, - (2002), s. 341-346. ISSN 0165-2427 R&D Projects: GA ČR GA524/01/0919 Keywords : ontogeny * spectratypic * flow cytometry Subject RIV: EE - Microbiology, Virology Impact factor: 1.659, year: 2002

  12. Programmed genome rearrangements: in lampreys, all cells are not equal.

    Science.gov (United States)

    Sémon, Marie; Schubert, Michael; Laudet, Vincent

    2012-08-21

    How can organisms silence deleterious gene loci? A recent study has shed light on a very brute mechanism in a jawless vertebrate: the irreversible deletion of massive chunks of genomic DNA. PMID:22917513

  13. Nuclear structure in cold rearrangement processes in fission and fusion

    International Nuclear Information System (INIS)

    In fission and fusion of heavy nuclei large numbers of nucleons are rearranged at a scale of excitation energy very small compared to the binding energy of the nuclei. The energies involved are less than 40 MeV at nuclear temperatures below 1.5 MeV. The shapes of the configurations in the rearrangement of a binary system into a monosystem in fusion, or vice versa in fission, change their elongations by as much as 8 fm, the radius of the monosystem. The dynamics of the reactions macroscopically described by a potential energy surface, inertia parameters, dissipation, and a collision energy is strongly modified by the nuclear structure of the participating nuclei. Experiments showing nuclear structure effects in fusion and fission of the heaviest nuclei are reviewed. The reaction kinematics and the multitude of isotopes involved are investigated by detector techniques and by recoil spectrometers. The advancement of the latter allows to find very small reaction branches in the range of 10-5 to 10-10. The experiments reveal nuclear structure effects in all stages of the rearrangement processes. These are discussed pointing to analogies in fusion and fission on the microscopic scale, notwithstanding that both processes macroscopically are irreversible. Heavy clusters, as 132Sn, 208Pb, nuclei with closed shell configurations N=82,126, Z=50,82 survive in large parts of the nuclear rearrangement. They determine the asymmetry in the mass distribution of low energy fission, and they allow to synthesise superheavy elements, until now up to element 112. Experiments on the cold rearrangement in fission and fusion are presented. Here, in the range of excitation energies below 12 MeV the phenomena are observed most convincingly. (orig.)

  14. Nuclear structure in cold rearrangement processes in fission and fusion

    Energy Technology Data Exchange (ETDEWEB)

    Armbruster, P.

    1998-11-01

    In fission and fusion of heavy nuclei large numbers of nucleons are rearranged at a scale of excitation energy very small compared to the binding energy of the nuclei. The energies involved are less than 40 MeV at nuclear temperatures below 1.5 MeV. The shapes of the configurations in the rearrangement of a binary system into a monosystem in fusion, or vice versa in fission, change their elongations by as much as 8 fm, the radius of the monosystem. The dynamics of the reactions macroscopically described by a potential energy surface, inertia parameters, dissipation, and a collision energy is strongly modified by the nuclear structure of the participating nuclei. Experiments showing nuclear structure effects in fusion and fission of the heaviest nuclei are reviewed. The reaction kinematics and the multitude of isotopes involved are investigated by detector techniques and by recoil spectrometers. The advancement of the latter allows to find very small reaction branches in the range of 10{sup -5} to 10{sup -10}. The experiments reveal nuclear structure effects in all stages of the rearrangement processes. These are discussed pointing to analogies in fusion and fission on the microscopic scale, notwithstanding that both processes macroscopically are irreversible. Heavy clusters, as 132Sn, 208Pb, nuclei with closed shell configurations N=82,126, Z=50,82 survive in large parts of the nuclear rearrangement. They determine the asymmetry in the mass distribution of low energy fission, and they allow to synthesise superheavy elements, until now up to element 112. Experiments on the cold rearrangement in fission and fusion are presented. Here, in the range of excitation energies below 12 MeV the phenomena are observed most convincingly. (orig.)

  15. How actin/myosin crosstalks guide the adhesion, locomotion and polarization of cells.

    Science.gov (United States)

    Sackmann, Erich

    2015-11-01

    Cell-tissue-tissue interaction is determined by specific short range forces between cell adhesion molecules (CAMs) and ligands of the tissue, long range repulsion forces mediated by cell surface grafted macromolecules and adhesion-induced elastic stresses in the cell envelope. This interplay of forces triggers the rapid random clustering of tightly coupled linkers. By coupling of actin gel patches to the intracellular domains of the CAMs, these clusters can grow in a secondary process resulting in the formation of functional adhesion microdomains (ADs). The ADs can act as biochemical steering centers by recruiting and activating functional proteins, such as GTPases and associated regulating proteins, through electrostatic-hydrophobic forces with cationic lipid domains that act as attractive centers. First, I summarize physical concepts of cell adhesion revealed by studies of biomimetic systems. Then I describe the role of the adhesion domains as biochemical signaling platforms and force transmission centers promoting cellular protrusions, in terms of a shell string model of cells. Protrusion forces are generated by actin gelation triggered by molecular machines (focal adhesion kinase (FAK), Src-kinases and associated adaptors) which assemble around newly formed integrin clusters. They recruit and activate the GTPases Rac-1 and actin gelation promoters to charged membrane domains via electrostatic-hydrophobic forces. The cell front is pushed forward in a cyclic and stepwise manner and the step-width is determined by the dynamics antagonistic interplay between Rac-1 and RhoA. The global cell polarization in the direction of motion is mediated by the actin-microtubule (MT) crosstalk at adhesion domains. Supramolecular actin-MT assemblies at the front help to promote actin polymerization. At the rear they regulate the dismantling of the ADs through the Ca(++)-mediated activation of the protease calpain and trigger their disruption by RhoA mediated contraction via

  16. Saucy-Marbet Rearrangements of Alkynyl Halides in the Synthesis of Highly Enantiomerically Enriched Allenyl Halides

    OpenAIRE

    Tang, Yu; Shen, Lichun; Dellaria, Becky J.; Richard P. Hsung

    2008-01-01

    A stereospecific Saucy-Marbet rearrangement of alkynyl halides is described here. These rearrangements provide an entry to highly enantiomerically enriched allenyl bromides and chlorides through excellent chirality transfer and the reservation of optical integrity of alkynyl halides.

  17. Ligand flexibility and framework rearrangement in a new family of porous metal-organic frameworks

    DEFF Research Database (Denmark)

    Hawxwell, Samuel M; Espallargas, Guillermo Mínguez; Bradshaw, Darren; Rosseinsky, Matthew J; Prior, Timothy J; Florence, Alastair J; van de Streek, Jacco; Brammer, Lee

    Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs.......Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs....

  18. Claisen, Cope and Related Rearrangements in the Synthesis of Flavour and Fragrance Compounds

    OpenAIRE

    Janusz Nowicki

    2000-01-01

    A review of the use of the Claisen, Cope and related [3,3]-sigmatropic rearrangements, sequential ("tandem") sigmatropic rearrangements and the "ene" reaction in the syntheses of flavour and fragrance compounds is presented.

  19. Primary cutaneous diffuse large B-cell lymphoma, leg type: a study of clinicopathology,immunophenotype and gene rearrangement%原发性皮肤腿型弥漫性大B细胞淋巴瘤七例临床病理学及基因重排研究

    Institute of Scientific and Technical Information of China (English)

    王婷婷; 贾玲; 廖文俊; 陈柳青; 陈喜雪; 熊亚; 郝飞; 朱学骏; 杨希川

    2015-01-01

    Objective To study the clinicopathologic features,immunophenotype and gene rearrangement of primary cutaneous diffuse large B-cell lymphoma,leg type (PCLBCL).Methods Seven cases of PCLBCL were enrolled into the study.Clinicopathologic analysis,immunohistochemical staining and gene rearrangement for IgH and Igκ were undertaken in the study.Results All the seven cases were male,and the median age was 72 years.Patients usually presented with multiple purple tumors,nodules,papules and infiltrative plaques.Two patients had a history of leg injury before onset,and one had mosquito bites.Histologically,the tumor involved the dermis and subcutis with dense and diffuse infiltrative pattern composing of centroblasts and/or immunoblasts.Immunohistochemical staining showed that seven cases (7/7) expressed CD20,six (6/6) expressed bcl-2,four (4/4) expressed MUM-1,four (4/5) expressed CD79a,four (4/5) expressed PAX-5 and four (4/6)expressed bcl-6,respectively.All cases did not express CD3ε,CD45RO,CD1O and CD30.IgH gene rearranged bands were detected in three (3/6)cases and Igκ was detected in one (1/5) case.Six of the seven cases died and the remaining patient,who was 44-year-old,was alive after 22 months of follow-up.Conclusions PCLBCL is rare,predominantly affects elderly male patients.PCLBCL has poor prognosis and high mortality,but younger patients seem to have better prognosis.Some cases had a history of trauma or mosquito bites.The relationship between the history and the onset of PCLBCL needs further evaluation.%目的 探讨原发性皮肤腿型弥漫性大B细胞淋巴瘤(PCLBCL)的临床病理学特点.方法 对7例PCLBCL患者的临床病理资料进行分析,并行免疫组织化学染色及IgH和Igκ基因重排检测.结果 7例均为男性,中位年龄72岁,临床表现为多发的紫红色肿块、结节、丘疹、浸润性斑块.2例有外伤史,1例有蚊虫叮咬史.组织学上肿瘤位于真皮及皮下脂肪层,常见无浸润带.瘤细

  20. Combined X-Ray and fully leaky guided mode studies of the smectic layer and optic tensor configuration in a ferroelectric liquid-crystal cell.

    Science.gov (United States)

    Hodder, B; Sambles, J R; Jenkins, S; Richardson, R M

    2000-10-01

    X-ray scattering together with optical characterization using fully leaky guided modes have been used for the first time to study the same ferroelectric liquid-crystal cell. This enables direct calculation of an accurate cone and chevron description of the liquid-crystal director profile since the layer structure and optic tensor configuration are both well known. PMID:11019296

  1. A protein network-guided screen for cell cycle regulators in Drosophila

    Directory of Open Access Journals (Sweden)

    Kashat Maria A

    2011-05-01

    Full Text Available Abstract Background Large-scale RNAi-based screens are playing a critical role in defining sets of genes that regulate specific cellular processes. Numerous screens have been completed and in some cases more than one screen has examined the same cellular process, enabling a direct comparison of the genes identified in separate screens. Surprisingly, the overlap observed between the results of similar screens is low, suggesting that RNAi screens have relatively high levels of false positives, false negatives, or both. Results We re-examined genes that were identified in two previous RNAi-based cell cycle screens to identify potential false positives and false negatives. We were able to confirm many of the originally observed phenotypes and to reveal many likely false positives. To identify potential false negatives from the previous screens, we used protein interaction networks to select genes for re-screening. We demonstrate cell cycle phenotypes for a significant number of these genes and show that the protein interaction network is an efficient predictor of new cell cycle regulators. Combining our results with the results of the previous screens identified a group of validated, high-confidence cell cycle/cell survival regulators. Examination of the subset of genes from this group that regulate the G1/S cell cycle transition revealed the presence of multiple members of three structurally related protein complexes: the eukaryotic translation initiation factor 3 (eIF3 complex, the COP9 signalosome, and the proteasome lid. Using a combinatorial RNAi approach, we show that while all three of these complexes are required for Cdk2/Cyclin E activity, the eIF3 complex is specifically required for some other step that limits the G1/S cell cycle transition. Conclusions Our results show that false positives and false negatives each play a significant role in the lack of overlap that is observed between similar large-scale RNAi-based screens. Our results

  2. Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives.

    Science.gov (United States)

    Lee, James A; Bubendorf, Lukas; Stahel, Rolf; Peters, Solange

    2013-05-01

    Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8-10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted. PMID:23617353

  3. CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

    International Nuclear Information System (INIS)

    Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 ± 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 ± 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 ± 13.6 min and 43.7 ± 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 ± 8.8 months, local recurrence-free survival was 14.4 ± 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 ± 16.6 ml/min/1.73 m2 before RF ablation vs. 47.2 ± 11.9 ml/min/1.73 m2 after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

  4. Recurrent non-small cell lung cancer: evaluation of CT-guided radiofrequency ablation as salvage therapy

    International Nuclear Information System (INIS)

    Background Radiofrequency ablation (RFA) is a potential application as a salvage tool after failure of surgery, chemotherapy, or radiotherapy of non-small cell lung cancer (NSCLC). Although several studies have evaluated the use of RFA in primary NSCLC, there is little literature on its potential application as a salvage tool. Purpose To evaluate CT-guided RFA employed as a salvage therapy for pulmonary recurrences of NSCLC after prior treatment with chemotherapy, radiation therapy, and/or surgery. Material and Methods A retrospective computer database search yielded 33 patients with biopsy proven primary NSCLC who underwent CT-guided RFA of 39 recurrent tumors following surgery, chemotherapy, and/or radiotherapy. Follow-up imaging was performed with CT and PET-CT. The endpoints of interest were progression-free survival (PFS) and time to local progression (TTLP). PFS and TTLP were compared by lesion size (<3 cm, ≥3 cm). Results The median PFS was 8 months. For patients with a tumor size <3 cm median PFS was 11 months, whereas the median PFS of patients with a tumor size ≥3 cm was 5 months. The difference did not reach statistical significance (P = 0.09). The median TTLP of all tumors was 14 months. TTLP of ablated tumors <3 cm in size was 24 months, compared to 8 months for ablated tumors ≥3 cm in size. The difference did not reach statistical significance (P = 0.07). Conclusion RFA of recurrent NSCLC may be a valuable salvage tool to achieve local tumor control, especially in tumors measuring <3 cm in size

  5. Near-infrared (NIR) fluorescence imaging of head and neck squamous cell carcinoma for fluorescence-guided surgery (Conference Presentation)

    Science.gov (United States)

    Moore, Lindsay; Warram, Jason M.; de Boer, Esther; Carroll, William R.; Morlandt, Anthony; Withrow, Kirk P.; Rosenthal, Eben L.

    2016-03-01

    During fluorescence-guided surgery, a cancer-specific optical probe is injected and visualized using a compatible device intraoperatively to provide visual contrast between diseased and normal tissues to maximize resection of cancer and minimize the resection of precious adjacent normal tissues. Six patients with squamous cell carcinomas of the head and neck region (oral cavity (n=4) or cutaneous (n=2)) were injected with an EGFR-targeting antibody (Cetuximab) conjugated to a near-infrared (NIR) fluorescent dye (IRDye800) 3, 4, or 7 days prior to surgical resection of the cancer. Each patient's tumor was then imaged using a commercially available, open-field NIR fluorescence imaging device each day prior to surgery, intraoperatively, and post-operatively. The mean fluorescence intensity (MFI) of the tumor was calculated for each specimen at each imaging time point. Adjacent normal tissue served as an internal anatomic control for each patient to establish a patient-matched "background" fluorescence. Resected tissues were also imaged using a closed-field NIR imaging device. Tumor to background ratios (TBRs) were calculated for each patient using both devices. Fluorescence histology was correlated with traditional pathology assessment to verify the specificity of antibody-dye conjugate binding. Peak TBRs using the open-field device ranged from 2.2 to 11.3, with an average TBR of 4.9. Peak TBRs were achieved between days 1 and 4. This study demonstrated that a commercially available NIR imaging device suited for intraoperative and clinical use can successfully be used with a fluorescently-labeled dye to delineate between diseased and normal tissue in this single cohort human study, illuminated the potential for its use in fluoresence-guided surgery.

  6. Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome

    Science.gov (United States)

    DNA methylation is an epigenetic mechanism central to the development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited. We used whole genome bisulfite sequencing, and found that differentiation of mouse colonic intestinal stem cell...

  7. Cervical acid phosphatase detection: A guide to abnormal cells in cytology smear screening for cervical cancer

    OpenAIRE

    Deb Prabal; Iyer Venkateswaran; Bhatla Neerja; Markovic O; Verma Kusum

    2008-01-01

    Background: Cervical acid phosphatase-Papanicolaou (CAP-PAP) test has recently been described for detection of acid phosphatase enzyme in abnormal squamous cells, and has been proposed as a biomarker-based technology for the screening of cervical cancer. Materials and Methods: Eighty-one consecutive cervical smears were subjected to routine Papanicolaou (Pap) staining as well as CAP-PAP, which combined cytochemical staining for acid phosphatase with modified Pap stain. Statistical evaluation ...

  8. Chromosome-specific staining to detect genetic rearrangements

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel; Tkachuk, Douglas; Westbrook, Carol

    2013-04-09

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyzes. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  9. Fries Rearrangement of Phenyl Acetate over Solid Acid Catalyst

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A silica-supported zirconium based solid acid (ZS) has been used as catalyst for the Fries rearrangement of phenyl acetate (PA). The catalyst showed a higher PA conversion activity and a much higher selectivity for o-hydroxyacetophenone (o-HAP) than for strongly acidic zeolite catalysts. The supported catalyst was characterized by XRD, IR, XPS, pyridine-TPD and the surface area measurements. The catalytic properties were influenced significantly by pretreatment temperature.

  10. On the rearrangement time of the fission reaction

    OpenAIRE

    Mouze, G.; Ythier, C.

    2010-01-01

    The rearrangement time \\Deltat of the fission reaction can be extracted from the full-width at half maximum (f.w.h.m.) of the isotopic distributions of fission fragments if this width is attributed to an uncertainty \\DeltaN in the neutron-number N of the fragment; then the energy-time uncertainty relation leads to \\Deltat = 0.17 yoctosecond.

  11. First Claisen Rearrangement Reaction in Ionic Liquids with Microwave Heating

    Institute of Scientific and Technical Information of China (English)

    XU Li-Wen; LI Fu-Wei; XIA Chun-Gu

    2003-01-01

    @@ We have demonstrated the first use of the common ionic liquids, [1] bmimBr, bmimBF4 and bmimPF6 as an environmentally benign solvent for the simple Claisen rearrangement under microwave irradiation. In many cases, the re action was carried out in toxic solvents of high boiling point. [2] Here we reported the first example of Claisen rear rangement reaction in green solvents, ionic liquids, under microwave irradiation.

  12. Mauve: Multiple Alignment of Conserved Genomic Sequence With Rearrangements

    OpenAIRE

    Darling, Aaron C.E.; Mau, Bob; Blattner, Frederick R.; Perna, Nicole T.

    2004-01-01

    As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments conserved among all the genomes under considera...

  13. Fries Rearrangement of Phenyl Acetate over Solid Acid Catalyst

    Institute of Scientific and Technical Information of China (English)

    CanXiongGUO; YanLIU; 等

    2002-01-01

    A silica-supported zirconium based solid acid (ZS) has been used as catalyst for the Fries rearrangement of phenyl acetate (PA). The catalyst showed a higher PA conversion activity and a much higher selectivity for o-hydroxyacetophenone (o-HAP) than for strongly acidic zeolite catalysts. The supported catalyst was characterized by XRD,IR,XPS,pyridine-TPD and the surface area measurements. The catalytic properties were influenced significantly by pretreatment temperature.

  14. Recent applications of ring-rearrangement metathesis in organic synthesis

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha

    2015-10-01

    Full Text Available Ring-rearrangement metathesis (RRM involves multiple metathesis processes such as ring-opening metathesis (ROM/ring-closing metathesis (RCM in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008–2014.

  15. Level rearrangement in exotic atoms and quantum dots

    International Nuclear Information System (INIS)

    A presentation and a generalisation are given of the phenomenon of level rearrangement, which occurs when an attractive long-range potential is supplemented by a short-range attractive potential of increasing strength. This problem has been discovered in condensate-matter physics and has also been studied in the physics of exotic atoms. A similar phenomenon occurs in a situation inspired by quantum dots, where a short-range interaction is added to an harmonic confinement. (authors)

  16. RNA-directed epigenetic regulations of DNA rearrangements

    OpenAIRE

    Mochizuki, Kazufumi

    2010-01-01

    Ciliated protozoa undergo extensive DNA rearrangements, including DNA elimination, chromosome breakage and DNA descrambling, when the germline micronucleus produces the new macronucleus during sexual reproduction. It has long been known that many of these events are epigenetically controlled by DNA sequences of the parental macronuclear genome. Recent studies in some model ciliates have revealed that these epigenetic regulations are mediated by non-coding RNAs. DNA elimination in Paramecium a...

  17. Recent applications of ring-rearrangement metathesis in organic synthesis.

    Science.gov (United States)

    Kotha, Sambasivarao; Meshram, Milind; Khedkar, Priti; Banerjee, Shaibal; Deodhar, Deepak

    2015-01-01

    Ring-rearrangement metathesis (RRM) involves multiple metathesis processes such as ring-opening metathesis (ROM)/ring-closing metathesis (RCM) in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008-2014). PMID:26664603

  18. Rearrangement and Convergence in Spaces of Measurable Functions

    Directory of Open Access Journals (Sweden)

    A. Trombetta

    2007-04-01

    Full Text Available We prove that the convergence of a sequence of functions in the space L0 of measurable functions, with respect to the topology of convergence in measure, implies the convergence μ-almost everywhere (μ denotes the Lebesgue measure of the sequence of rearrangements. We obtain nonexpansivity of rearrangement on the space Lâˆ��, and also on Orlicz spaces LN with respect to a finitely additive extended real-valued set function. In the space L∞ and in the space EΦ, of finite elements of an Orlicz space LΦ of a σ-additive set function, we introduce some parameters which estimate the Hausdorff measure of noncompactness. We obtain some relations involving these parameters when passing from a bounded set of L∞, or LΦ, to the set of rearrangements.

  19. Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.

  20. Patterned hydrogel microfibers prepared using multilayered microfluidic devices for guiding network formation of neural cells

    International Nuclear Information System (INIS)

    Multilayered microfluidic devices with a micronozzle array structure have been developed to prepare unique hydrogel microfibers with highly complex cross-sectional morphologies. Hydrogel precursor solutions with different compositions are introduced through vertical micronozzles, united and focused, and continuously gelled to form hydrogel fibers with multiple regions of different physicochemical composition. We prepared alginate hydrogel microfibers with diameters of 60 ∼ 130 μm and 4/8 parallel regions in the periphery. Neuron-like PC12 cells encapsulated in the parallel region, which was made of a soft hydrogel matrix, proliferated and formed linear intercellular networks along the fiber length because of the physical restrictions imposed by the relatively rigid regions. After cultivation for 14 days, one-millimeter-long intercellular networks that structurally mimic complex nerve bundles found in vivo were formed. The proposed fibers should be useful for producing various in vivo linear tissues and should be applicable to regenerative medicine and physiological studies of cells. (papers)

  1. DEFINITION OF A NEW ENTITY OF MALIGNANT EXTRAGONADAL GERM-CELL TUMORS

    NARCIS (Netherlands)

    VANECHTEN, J; DEJONG, B; SINKE, RJ; WEGHUIS, DO; SLEIJFER, DT; OOSTERHUIS, JW

    1995-01-01

    Two malignant extragonadal germ cell tumors are reponed, histologically classified as immature teratomas, having pseudodiploid karyotypes with complex structural rearrangements but lacking isochromosome 12p or other rearrangements involving 12p. The absence of 12p material in structural rearrangemen

  2. Application of polymerase chain reaction to detect rearrangement of immunoglobulin heavy chain genes in lymphoproliferative disease.

    Science.gov (United States)

    Khalil, S H; Siegrist, K; Akhtar, M

    1997-07-01

    As part of our routine work-up in the diagnosis of lymphoproliferative disease, we used a rapid polymerase chain reaction (PCR) assay to amplify the DNA fragments of the framework 3 (FR3) region of the immunoglobulin heavy (IgH) chain genes. The assay does not involve hybridization, nested priming, or sequencing of the amplified PCR product. It was performed on 66 specimens of B-cell lymphoproliferative disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia and follicular lymphoma. Twenty-six specimens of negative controls, including acute myeloid leukemia, chronic myeloid leukemia in myeloid transformation and idiopathic thrombocytopenic purpura, were also analyzed. The assay was performed with 77% sensitivity and 100% specificity. The standard IgH chain gene rearrangement by Southern blot analysis is reserved for the remaining negative cases if clinically indicated. PMID:17353588

  3. Often seen, rarely recognized: mast cell activation disease - a guide to diagnosis and therapeutic options.

    Science.gov (United States)

    Afrin, Lawrence B; H Butterfield, Joseph; Raithel, Martin; J Molderings, Gerhard

    2016-05-01

    Mast cell (MC) disease has long been thought to be just the rare disease of mastocytosis (in various forms, principally cutaneous and systemic), with aberrant MC mediator release at symptomatic levels due to neoplastic MC proliferation. Recent discoveries now show a new view is in order, with mastocytosis capping a metaphorical iceberg now called "MC activation disease" (MCAD, i.e. disease principally manifesting inappropriate MC activation), with the bulk of the iceberg being the recently recognized "MC activation syndrome" (MCAS), featuring inappropriate MC activation to symptomatic levels with little to no inappropriate MC proliferation. Given increasing appreciation of a great menagerie of mutations in MC regulatory elements in mastocytosis and MCAS, the great heterogeneity of MCAD's clinical presentation is unsurprising. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory ± allergic theme. Preliminary epidemiologic investigation suggests MCAD, while often misrecognized, may be substantially prevalent, making it increasingly important that practitioners of all stripes learn how to recognize its more common forms such as MCAS. We review the diagnostically challenging presentation of MCAD (with an emphasis on MCAS) and current thoughts regarding its biology, epidemiology, natural history, diagnostic evaluation, and treatment. Key messages Recent discoveries show a new view of the realm of mast cell disease is in order, with mastocytosis capping a metaphorical iceberg now termed "MC activation disease" (MCAD, i.e. disease principally manifesting inappropriate MC activation) and with the bulk of the iceberg being comprised of the recently recognized "MC activation syndrome" (MCAS), featuring inappropriate MC activation to symptomatic levels with little to no inappropriate MC proliferation. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory

  4. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population.

    Directory of Open Access Journals (Sweden)

    Jianming Ying

    Full Text Available Anaplastic lymphoma kinase (ALK rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.Tissue microarray (TMA was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH, real-time polymerase chain reaction (qRT-PCR, target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.Among the tested cases, 2 (0.44% CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1. One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.

  5. Imperfect conformation of experimental and epidemiological data for frequency of RET/РТС gene rearrangements in papillary thyroid carcinoma for the Chernobyl accident

    Directory of Open Access Journals (Sweden)

    Ushenkova L.N.

    2013-12-01

    Full Text Available In an overview and analytical study of the epidemiological data on the frequency of RET/РТС gene rearrangements in sporadic and radiogenic (patients after radiotherapy, residents of contaminated after the Chernobyl disaster areas, victims after the atomic bombings, etc. carcinomas of the thyroid gland were examined. In general, the observed epidemiological laws were confirmed in radiobiology experiments by irradiation of different cultures of thyroid cells and ex vivo with the exception of Chernobyl cohorts. Induction of RET/РТС gene rearrangements by 131l exposure in children carcinomas of Chernobyl residents in mice did not observe too. It is concluded that the situation with the frequency of RET/РТС rearrangements in thyroid carcinoma in Chernobyl cohorts once again confirms the multifactorial nature of the induction and development of these tumors with a contribution of radiation and non-radiation factors (iodine deficiency and different stresses.

  6. Review of alternative residual contamination guides for the 324 Building B-Cell Cleanout Project. Phase 1

    International Nuclear Information System (INIS)

    This report provides a proposed residual contamination guide (RCG) for the 324 Building B-Cell Cleanout Project, Phase 1, at the Hanford Site. The RCG is expressed as a fraction of the amount of highly dispersible radioactive material that would result in offsite doses equal to the Pacific Northwest Laboratory radiological risk guidelines following the worst credible accident scenario for release of the holdup material. The proposed RCG is 10-1 to 10-2 of the PNL radiological risk guidelines. As part of the development of the RCG, a number of factors were considered. These include the need to provide an appropriate level of flexibility for other activities within the 324 Building that could contribute to the facility's overall radiological risk, uncertainties inherent in safety analyses, and the possible contribution of other 300 Area facilities to overall radiological risk. Because of these factors and the nature of the cleanout project, the RCG is expressed as a range rather than a point value. This report also provides guidance on determining conformance to the RCG, including inspection and measurement techniques, quality assurance requirements, and consideration of uncertainty

  7. Recurrence of renal cell carcinoma diagnosed using contralateral adrenal biopsy with endoscopic ultrasound-guided fine-needle aspiration

    Science.gov (United States)

    TANIMOTO, AZUSA; TAKEUCHI, SHINJI; YAEGASHI, HIROSHI; KOTANI, HIROSHI; KITAI, HIDENORI; NANJO, SHIGEKI; EBI, HIROMICHI; YAMASHITA, KANAME; MOURI, HISATSUGU; OHTSUBO, KOUSHIRO; IKEDA, HIROKO; YANO, SEIJI

    2016-01-01

    A 76-year-old female in whom a renal cell carcinoma (RCC) lesion was resected 19 years previously presented to our hospital with cognitive dysfunction. Magnetic resonance imaging and computed tomography revealed nodules in the brain, lung, adrenal gland and a pelvic osteolytic lesion. To identify the primary cancer site, the present study performed endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the left adrenal lesion. Consequently, the pathological findings of the tissue obtained by EUS-FNA were similar to those of the previous nephrectomy specimen, revealing that the adrenal lesion was the recurrence of RCC. The majority of the metastatic lesions in the patient were reduced in size by the multiple kinase inhibitor, pazopanib. Contralateral adrenal metastasis of RCC is rare and the use of EUS-FNA in the diagnosis of adrenal lesions remains to be elucidated. This is a rare case of adrenal lesion, diagnosed by EUS-FNA. Therefore, EUS-FNA is considered to be a useful diagnostic modality of adrenal metastases from unidentified primary tumor types. PMID:27073657

  8. Epigenetic aspects of lymphocyte antigen receptor gene rearrangement or 'when stochasticity completes randomness'.

    Science.gov (United States)

    Jaeger, Sébastien; Fernandez, Bastien; Ferrier, Pierre

    2013-06-01

    To perform their specific functional role, B and T lymphocytes, cells of the adaptive immune system of jawed vertebrates, need to express one (and, preferably, only one) form of antigen receptor, i.e. the immunoglobulin or T-cell receptor (TCR), respectively. This end goal depends initially on a series of DNA cis-rearrangement events between randomly chosen units from separate clusters of V, D (at some immunoglobulin and TCR loci) and J gene segments, a biomolecular process collectively referred to as V(D)J recombination. V(D)J recombination takes place in immature T and B cells and relies on the so-called RAG nuclease, a site-specific DNA cleavage apparatus that corresponds to the lymphoid-specific moiety of the VDJ recombinase. At the genome level, this recombinase's mission presents substantial biochemical challenges. These relate to the huge distance between (some of) the gene segments that it eventually rearranges and the need to achieve cell-lineage-restricted and developmentally ordered routines with at times, mono-allelic versus bi-allelic discrimination. The entire process must be completed without any recombination errors, instigators of chromosome instability, translocation and, potentially, tumorigenesis. As expected, such a precisely choreographed and yet potentially risky process demands sophisticated controls; epigenetics demonstrates what is possible when calling upon its many facets. In this vignette, we will recall the evidence that almost from the start appeared to link the two topics, V(D)J recombination and epigenetics, before reviewing the latest advances in our knowledge of this joint venture. PMID:23278765

  9. Molecular cytogenetic identification of a rearrangement involving 10q23 in a patient with ALL

    Energy Technology Data Exchange (ETDEWEB)

    Rosemblum-Vos, L.S.; Frantz, C.N.; Punzalan, C.M. [Univ. of Maryland School of Medicine, Baltimore, MD (United States)] [and others

    1994-09-01

    A patient with pre-B cell acute lymphocytic leukemia (ALL) demonstrated a novel complex karyotype, elucidated by fluorescence in situ hybridization (FISH), which involved the region of a rare heritable fragile site at 10q23-q24. An asymptomatic two-year-old white female presented with anemia; her physical examination was normal. WBC was 6,200 with 8% blasts, and 35% atypical lymphocytes. Her bone marrow showed 50% lymphoblasts, expressing CD9, CD10, CD19, CD22, CD24, CD45, and HLA-DR, consistent with B-cell lineage. Cytogenetic examination of a bone marrow biopsy yielded GTG-banded chromosomes of sub-optimal morphology. The karyotype was initially interpreted as mosaic 46,X,-X,+4,-10,+13,der(19)/46,XX with 40% abnormal cells. Subsequent FISH studies revealed the der(19) to be an unbalanced form of the 1;19 translocation frequently found in pre-B cell ALL. Using FISH, we also identified a complex rearrangement in which an X chromosome segment was inserted interstitially into 10q at the q23.3/q24 junction, the location of a rare heritable fragile site. The karyotype has been reinterpreted as 46,X,del(X)(:p11.2{r_arrow}qter), ins(10;X)(q23.3;p11.2p22.3),der(19)t(1;19)(q23p13)/46,XX. To our knowledge, this is only the second reported case involving this breakpoint in ALL-L1, the other being a patient with biphenotypic pre-B/myeloid acute leukemia. Our patient is currently being investigated for this fragile site. The complete elucidation of the chromosomes involved in this complex rearrangement and the possible implications of the chromosome 10 breakpoint would have gone undetected without the application of FISH.

  10. Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided photothermal therapy.

    Science.gov (United States)

    Ren, Xiaoqing; Zheng, Rui; Fang, Xiaoling; Wang, Xiaofei; Zhang, Xiaoyan; Yang, Wuli; Sha, Xianyi

    2016-06-01

    Along with intrinsic magnetic resonance imaging (MRI) advantages, iron oxide nanomaterials capable of photothermal conversion have been reported very recently and have again raised great interest in their designs among biomedical researchers. However, like other inorganic nanomaterials, high macrophage uptake, short blood retention time and unfavorable biodistributions have strongly hampered their applications in vivo. To solve these problems, a rational design of red blood cell (RBC) membrane camouflaged iron oxide magnetic clusters (MNC@RBCs) is presented in this paper. Our data show that by simply introducing an "ultra-stealth" biomimetic coating to iron oxide magnetic nanoclusters (MNCs), MNC@RBCs maintain the imaging and photothermal functionalities inherited from MNCs cores while achieving much lower nonspecific macrophage uptake and dramatically altered fate in vivo. MNC@RBCs with superior prolonged blood retention time, preferred high tumor accumulation and relatively lowered liver biodistribution are demonstrated when injected intravenously in mice, leading to greatly enhanced photothermal therapeutic efficacy by a single treatment without further magnetic force manipulation. Our study illustrates a well prepared integration of MNCs and RBCs, exploiting advantages of both functionalities within a single unit and suggests a promising future for iron-based nanomaterials application in vivo. PMID:27031929

  11. Standard guide for mechanical drive systems for remote operation in hot cell facilities

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2010-01-01

    1.1 Intent: 1.1.1 The intent of this standard is to provide general guidelines for the design, selection, quality assurance, installation, operation, and maintenance of mechanical drive systems used in remote hot cell environments. The term mechanical drive systems used herein, encompasses all individual components used for imparting motion to equipment systems, subsystems, assemblies, and other components. It also includes complete positioning systems and individual units that provide motive power and any position indicators necessary to monitor the motion. 1.2 Applicability: 1.2.1 This standard is intended to be applicable to equipment used under one or more of the following conditions: 1.2.1.1 The materials handled or processed constitute a significant radiation hazard to man or to the environment. 1.2.1.2 The equipment will generally be used over a long-term life cycle (for example, in excess of two years), but equipment intended for use over a shorter life cycle is not excluded. 1.2.1.3 The ...

  12. Rearrangements of microtubule cytoskeleton in stomatal closure of Arabidopsis induced by nitric oxide

    Institute of Scientific and Technical Information of China (English)

    ZHANG YongMei; WU ZhongYi; WANG XueChen; YU Rong

    2008-01-01

    NO (nitric oxide), known as a key signal molecule in plant, plays important roles in regulation of stomatal movement. In this study, microtubule dynamics and its possible mechanism in the NO signal pathway were investigated. The results were as follows: (ⅰ) In vivo stomatal aperture assays revealed that both vinblastine (microtubule-disrupting drug) and SNP (exogenous NO donor) prevented stomatal opening in the light, and vinblastine even could enhance the inhibitory effect of SNP, whereas taxol (a microtubule-stabilizing agent) was able to reduce this effect; (ⅱ) microtubules in the opening Arabi-dopsis guard cells expressing GFP:α-tubulin-6 (AtGFP:α-tubulin-6) were organized in parallel, straight and dense bundles, radiating from the ventral side to the dorsal side, and most of them were localized perpendicularly to the ventral wall; (ⅲ) under the same environmental conditions, treated with SNP for 30 min, the radial arrays of microtubules in guard cells began to break down, twisted partially and be-came oblique or exhibited a random pattern; (ⅳ) furthermore, the involvement of cytosolic Ca2+ in this event was tested. Stomatal aperture assays revealed that BAPTA-AM (a chelator of Ca2+) greatly sup-pressed the effect of NO on stomatal closure; however, it did not show the same function on stomatal closure induced by vinblastine. When BAPTA-AM was added to the SNP-pretreated solution, the SNP-induced disordered microtubulue cytoskeleton in guard cells underwent rearrangement in a time-dependent manner. After 30 min of treatment with BAPTA-AM, the cortical microtubules resumed the original radial distribution, almost the same as the control. All this indicates that NO may promote rearrangement of microtubule cytoskeleton via elevation of [Ca2+]cyt (free Ca2+ concentration in the cy-toplasm), finally leading to stomatal closure.

  13. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance

    DEFF Research Database (Denmark)

    Cruickshank, V Adam; Sroczynska, Patrycja; Sankar, Aditya;

    2015-01-01

    tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the...... selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the...

  14. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18–24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20–30 Gy. The median follow-up was 12 months (range, 1–48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  15. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Greco, Carlo [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Motzer, Robert [Solid Tumor Service, Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Magsanoc, Juan Martin; Pei Xin [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Lovelock, Michael; Mechalakos, Jim [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  16. Confining Bond Rearrangement in the Random Center Vortex Model

    CERN Document Server

    Altarawneh, Derar; Engelhardt, Michael

    2015-01-01

    We present static meson-meson and baryon--anti-baryon potentials in Z(2) and Z(3) random center vortex models for the infrared sector of Yang-Mills theory, i.e., hypercubic lattice models of random vortex world-surfaces. In particular, we calculate Polyakov loop correlators of two static mesons resp. (anti-)baryons in a center vortex background and observe that their expectation values follow the minimal area law and show bond rearrangement behavior. The static meson-meson and baryon--anti-baryon potentials are compared with theoretical predictions and lattice QCD simulations.

  17. Confining bond rearrangement in the random center vortex model

    Science.gov (United States)

    Altarawneh, Derar; Höllwieser, Roman; Engelhardt, Michael

    2016-03-01

    We present static meson-meson and baryon-antibaryon potentials in Z (2 ) and Z (3 ) random center vortex models for the infrared sector of Yang-Mills theory, i.e., hypercubic lattice models of random vortex world surfaces. In particular, we calculate multiple Polyakov loop correlators corresponding to static meson-meson or baryon-antibaryon configurations in a center vortex background and observe that their expectation values follow the minimal area law, displaying bond rearrangement behavior, a characteristic expected for the confining dynamics of the strong interaction. The static meson-meson and baryon-antibaryon potentials are compared with theoretical predictions and lattice QCD simulations.

  18. Acid Rearrangement of Secoiridoids Related to Oleuropein and Secologanin

    DEFF Research Database (Denmark)

    Bianco, Armandodoriano; Jensen, Søren Rosendal; Olesen, Jens;

    2003-01-01

    Acid treatment of an iridoid glycoside results in the cleavage of the acetal bond between the sugar unit and the monoterpenoid aglycon. Iridoids possessing non-conjugated enol ether systems, however, undergo the hydration of the iridoid enol ether functionality in acid medium, as well as the...... hydrolysis of the bond. We examined the acid rearrangement of secoiridoids such as oleuropein (1) and secologanin (2) and their reduction products oleuropeinol (3) and secologaninol (4), to examine whether similar behaviour also occurs in this case....

  19. Mapping Rearrangement for Parallel Concatenated Trellis Coded Modulation

    Directory of Open Access Journals (Sweden)

    Benjillali Mustapha

    2008-01-01

    Full Text Available Abstract Mapping rearrangement (MaRe for the hybrid ARQ (HARQ based on the parallel concatenated trellis coded modulation (PCTCM is analyzed. We demonstrate that the performance of the PCTCM receiver is intrinsically limited by the MaRe design and we propose a new mapping scheme to fit the structure of PCTCM transceivers. Depending on the HARQ scenarios, the proposed scheme offers gains between 0.1 and 2.4 dB when compared with known MaRe schemes.

  20. Autosomal rearrangement in Gryllus assimilis Fabricius, 1775 (Orthoptera, Gryllidae)

    OpenAIRE

    Edison Zefa

    1999-01-01

    Gryllus assimilis L. has a karyotype of 2n = 29 (X0, male) and 30 (XX, female). The above karyotype was encountered along with another in which 2n = 28 (X0, male) and 2n = 29 (XX, female) in a population from the outskirts of Rio Claro city (São Paulo State, Brazil). Of eight specimens studied, five had the heterozygous karyotype involving a translocation and three had the basic karyotype. There were no individuals homozygous for the rearrangement. The heterozygous karyotype was the result of...

  1. Endoscopic ultrasonography-guided trucut biopsy for the preoperative diagnosis of peripancreatic castleman's disease: A case report

    Institute of Scientific and Technical Information of China (English)

    Kyoung Hoon Rhee; Sang Soo Lee; Joo Ryung Huh

    2008-01-01

    Castleman's disease (CD) of the pancreas/peripancreas is extremely rare. The recently introduced, endoscopic ultrasonography (EUS)-guided trucut biopsy (TCB) is a useful diagnostic modality for obtaining tissue samples from peripancreatic lesions. However, its role in diagnosing CD remains unknown. We report a case of localized, peripancreatic, hyaline-vascular CD biopsied using EUS. The pathology results were initially interpreted as an extranodal, marginal-zone B-cell lymphoma. However, polymerase chain reaction (PCR) study for the IgH gene rearrangement revealed a polyclonal pattern. We also reviewed the relevant literature. To our knowledge, this is the first illustrated report on EUS-TCB findings of CD with its pathology results of EUS-TCB mimicked a B-cell lymphoma.

  2. Cytotoxic 1,2-dialkynylimidazole-based aza-enediynes: aza-Bergman rearrangement rates do not predict cytotoxicity.

    Science.gov (United States)

    Laroche, Christophe; Li, Jing; Kerwin, Sean M

    2011-07-28

    A new class of potential antitumor agents inspired by the enediyne antitumor antibiotics has been synthesized: the 1,2-dialkynylimidazoles. The aza-Bergman rearrangement of these 1,2-dialkynylimidazoles has been investigated theoretically at the B3LYP/6-31G(d,p) level and experimentally by measuring the kinetics of rearrangement in 1,4-cyclohexadiene. There is a good correlation between the theoretical and experimental results; subtle substituent effects on the initial aza-Bergman cyclization barrier predicted by theory are confirmed by experiment. Yet, despite the ability of these 1,2-dialkynylimidazoles to undergo Bergman rearrangement to diradical/carbene intermediates under relatively mild conditions, there is no correlation between the rate of Bergman cyclization and cytotoxicity to A459 cells. In addition, cytotoxic 1,2-dialkynylimidazoles do not cause nicking of supercoiled plasmid DNA or cleavage of bovine serum albumin. An alternative mechanism for cytotoxicity involving the unexpected selective thiol addition to the N-ethynyl group of certain 1,2-dialkynylimidazoles is proposed. PMID:21667990

  3. Metastatic renal cell carcinoma from a native kidney of a renal transplant patient diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy

    Directory of Open Access Journals (Sweden)

    Yaseen Alastal

    2015-04-01

    Full Text Available Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy sampling of enlarged lymph nodes is increasingly used to diagnose metastatic tumors, especially of the gastrointestinal tract and the lungs. Herein, we describe the diagnosis of metastatic renal cell carcinoma from a native kidney of a 54 year-old male patient, who had a 5-years history of renal transplant, by EUS-FNA of mediastinal and celiac lymph nodes. Histological and immunohistochemical findings confirmed the origin of metastatic tumor. EUS-FNA with proper cytological evaluation can be useful in the diagnosis of metastatic renal cell carcinoma in renal transplant patients. 

  4. Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1

    OpenAIRE

    Yudan Cao; Yuping Tang; Yanjing Yang; Xiaojing Yan; Zhengjun Li; Lan Gao; Li Zhang; Anwei Ding

    2012-01-01

    The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by 1H, &l...

  5. Gyrokinetic and kinetic particle-in-cell simulations of guide-field reconnection. Part I: macroscopic effects of the electron flows

    CERN Document Server

    Muñoz, P A; Kilian, P; Büchner, J; Jenko, F

    2015-01-01

    In this work, we extend a comparison between gyrokinetic (GK) and fully kinetic Particle-in-Cell (PIC) simulations of magnetic reconnection in the limit of strong guide field started by TenBarge et al. [Phys. Plasmas 21, 020708 (2014)]. By using a different set of kinetic PIC and GK simulation codes (ACRONYM and GENE, respectively), we analyze the limits of applicability of the GK approach when comparing to the force free kinetic simulations in the low guide field (bg) regime. Here we report the first part of a much more extended comparison, focusing on the macroscopic effects of the electron flows. For a low beta plasma (beta_i = 0.01), it is shown that magnetic reconnection only displays similar features between both plasma models for higher kinetic PIC guide fields (bg>30) in the secondary magnetic islands than in the region close to the X points or separatrices (bg>5). Kinetic PIC low guide field runs (53) to be negligible due to the reduced reconnection rate and fluctuation level.

  6. FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Jinks-Robertson, Sue

    2002-02-01

    The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

  7. From Knothe's rearrangement to Brenier's optimal transport map

    CERN Document Server

    Bonnotte, Nicolas

    2012-01-01

    The Brenier optimal map and Knothe-Rosenblatt rearrangement are two instances of a transport map, that is to say a map sending one measure onto another. The main interest of the former is that it solves the Monge-Kantorovich optimal transport problem, while the latter is very easy to compute, being given by an explicit formula. A few years ago, Carlier, Galichon, and Santambrogio showed that the Knothe rearrangement could be seen as the limit of the Brenier map when the quadratic cost degenerates. In this paper, we prove that on the torus (to avoid boundary issues), when all the data are smooth, the evolution is also smooth, and is entirely determined by a PDE for the Kantorovich potential (which determines the map), with a subtle initial condition. The proof requires the use of the Nash-Moser inverse function theorem. This result generalizes the ode discovered by Carlier, Galichon, and Santambrogio when one measure is uniform and the other is discrete, and could pave to way to new numerical methods for optim...

  8. Magnetic field re-arrangement after prominence eruption

    International Nuclear Information System (INIS)

    It has long been known that magnetic reconnection plays a fundamental role in a variety of solar events. Although mainly invoked in flare problems, large-scale loops interconnecting active regions, evolving coronal hole boundaries, the solar magnetic cycle itself, provide different evidence of phenomena which involve magnetic reconnection. A further example might be given by the magnetic field rearrangement which occurs after the eruption of a prominence. Since most often a prominence reforms after its disappearance and may be observed at about the same position it occupied before erupting, the magnetic field has to undergo a temporary disruption to relax back, via reconnection, to a configuration similar to the previous one. The above sequence of events is best observable in the case of two-ribbon (2-R) flares but most probably is associated with all filament eruptions. Even if the explanation of the magnetic field rearrangement after 2-R flares in terms of reconnection is generally accepted, the lack of a three-dimensional model capable of describing the field reconfiguration, has prevented, up to now, a thorough analysis of its topology as traced by Hα/x-ray loops. The purpose of the present work is to present a numerical technique which enables one to predict and visualize the reconnected configuration, at any time t, and therefore allows one to make a significant comparison of observations and model predictions throughout the whole process. 5 refs., 3 figs

  9. Intramolecular photosensitization of the pinene-ocimene rearrangement

    International Nuclear Information System (INIS)

    Bonding of nopol to the para position of acetophenone produces 5,5-dimethyl-2-(2-(p-acetylphenoxy)ethyl)bi-cyclo[3.1.1]hept-2-ene 1, which contains two chromophores: a para-alkoxyacetophenone and an α-pinene, connected by a single methylene group. UV irradiation of I in both benzene and methanol produces none of the intramolecular [2 + 2] cycloaddition that most para-(3-buten-1-oxy)acetophenones undergo. Instead, the pinene unit rearranges to a triene skeleton identical to that of ocimene, a known photoproduct of pinene. At modest conversion the diene portion of the triene is cis but gradually is converted to a 52:48 trans:cis ratio. It is concluded that intramolecular triplet energy transfer from the excited ketone chromophore forms the 1,2-biradical triplet state of the pinene moiety, which then undergoes cyclobutylcarbinyl ring opening to a 1,4-biradical that cleaves to the 1,3,6-triene structure of ocimene. This mechanism is suggested to be responsible for the earlier reported intermolecularly sensitized rearrangement of a-pinene to the ocimene isomers. (author)

  10. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas.

    OpenAIRE

    Sugawa, N; Ekstrand, A J; James, C D; Collins, V P

    1990-01-01

    The epidermal growth factor receptor gene has been found to be amplified and rearranged in human glioblastomas in vivo. Here we present the sequence across a splice junction of aberrant epidermal growth factor receptor transcripts derived from corresponding and uniquely rearranged genes that are coamplified and coexpressed with non-rearranged epidermal growth factor receptor genes in six primary human glioblastomas. Each of these six tumors contains aberrant transcripts derived from identical...

  11. [1,2]-Wittig Rearrangement of THP Acetal Compounds: Facile Synthesis of Aromatic Tertiary Alcohols

    Directory of Open Access Journals (Sweden)

    Feng-Lei Gu

    2011-01-01

    Full Text Available Several sec-aromatic THP acetal compounds have been found to be suitable substrates for the [1,2]-Wittig rearrangement in the absence of an external electrophile, which resulted in the generation of new carbon-carbon bond and the facile synthesis of aromatic tertiary alcohols. More interestingly, an unexpected effect of chlorotrimethylsilane on this [1,2]-Wittig rearrangement of sec-aromatic THP acetal compounds was found, in which two different products involving oxidative procedure were obtained due to the competitive [1,4]-Sigmatropic rearrangement versus [1,2]-Wittig rearrangement

  12. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG

    OpenAIRE

    Rumfelt, Lynn L; Avila, David; Diaz, Marilyn; Bartl, Simona; McKinney, E. Churchill; Flajnik, Martin F.

    2001-01-01

    In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM1gj, from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells (“germline-joined”). Such H chain V genes were discovered over...

  13. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

    International Nuclear Information System (INIS)

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  14. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Lihua [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053 (China); Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Wang, Xiong; Huselstein, Celine [Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS – Université de Lorraine, Biopôle, 54500 Vandoeuvre-lès-Nancy (France); Chen, Yun, E-mail: yunchen@whu.edu.cn [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  15. Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2012-09-01

    Full Text Available The dried roots of Euphorbia kansui (kansui have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by 1H, 13C NMR spectroscopy and ESI-MS as kansuinine A (1, kansuinine B (2, kansuinine C (3, kansuiphorin C (4, 3-O-(2'E,4'Z-decadienoyl-20-O-acetylingenol (5, 3-O-(2'E,4'E-decadienoyl-20-O-acetylingenol (6, 3-O-(2'E,4'Z-decadienoyl-20-deoxyingenol (7, 3-O-benzoyl-20-deoxyingenol (8, 5-O-benzoyl-20-deoxyingenol (9, kansenone (10, epi-kansenone (11, euphol (12. All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids (5–11 exhibited a relatively lower IC50 value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.

  16. Bio-guided isolation of the cytotoxic terpenoids from the roots of Euphorbia kansui against human normal cell lines L-O2 and GES-1.

    Science.gov (United States)

    Zhang, Li; Gao, Lan; Li, Zhengjun; Yan, Xiaojing; Yang, Yanjing; Tang, Yuping; Cao, Yudan; Ding, Anwei

    2012-01-01

    The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by (1)H, (13)C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2'E,4'Edecadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12). All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids (5-11) exhibited a relatively lower IC(50) value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb. PMID:23109850

  17. Charge carrier rearrangement in spinel crystals irradiated at low temperatures

    International Nuclear Information System (INIS)

    The results of an investigation of thermoluminescence (TL) in nominally pure MgAl2O4 spinel single crystals in the temperature range between 80-670 K are presented. For a heating rate of 0.21 K/s, TL spectra exhibit glow peaks in three distinct temperature ranges: 100-160, 270-370 and 470-670 K. The most prominent peaks are at 115, 140, 305, 335, 525, 570 and 605 K. The locations of the temperature maxima, as well as the intensity of the peaks, vary depending on the treatment of the crystals, the type of irradiation and the temperature of irradiation. Measurements of the glow peaks at different emission wavelengths and the use of partial bleaching and isothermal decay techniques for TL, allowed us to propose mechanisms for charge carrier rearrangement at lattice defects and impurity ions, during irradiation and subsequent heating

  18. SYNTHESIS OF ALLYL PHENYL ETHER AND CLAISEN REARRANGEMENT

    Directory of Open Access Journals (Sweden)

    Gagik Torosyan

    2011-12-01

    Full Text Available It has been established the possibility for phenol allylation on natural zeolites and them analogs. Here is demonstrated the synthesis of allyl phenol, which has wide industrial applications. The offered method in comparison with the traditional methods has more advantages – higher selectivity, smaller material and power resources consumption. It has been obtained the mixture of allylating phenols (30% in general with allyl phenyl ether (1 with 80% yields. At 600 K is obtained allylphenyl ether, at 700 K beginning the formation of allyl phenols, which is the result of direct C-allylation of the aromatic ring. It has been investigated the possibility of Claisen rearrangement in the same conditions. All of that are established by gas-liquid chromatography and liquid chromatography data.

  19. Most ultraviolet irradiation induced mutations in the nematode Caenorhabditis elegans are chromosomal rearrangements

    International Nuclear Information System (INIS)

    In this study the utility of 254-nm ultraviolet light (UV) as a magnetic tool in C.elegans is determined. It is demonstrated that irradiation of adult hermaphrodites provides a simple method for the induction of heritable chromosomal rearrangements. A screening protocol was employed that identifies either recessive lethal mutations in the 40 map unit region balanced by the translocation eT1(III;V), or unc-36(III) duplications. Mutations were recovered in 3% of the chromosomes screened after a dose of 120 J/m2. This rate resembles that for 1500 R γ-ray-induced mutations selected in a similar manner. The mutations were classified either as lethals [mapping to Linkage Group (LG)III or LGV] or as putative unc-36 duplications. In contrast to the majority of UV-induced mutations analysed in micro-organisms, a large fraction of the C.elegans UV-induced mutations were found to be not simple intragenic lesions, but deficiencies for more than one adjacent gene or more complex events. Preliminary evidence for this conclusion came from the high frequency of mutations that had a dominant effect causing reduced numbers of adult progeny. Subsequently 6 out of 9 analysed LGV mutations were found to be deficiencies. Other specific rearrangements also identified were: one translocation, sT5(II;III), and two unc-36 duplications, sDp8 and sDp9. It was concluded that UV irradiation can easily be used as an additional tool for the analysis of C.elegans chromosomes, and that C.elegans should prove to be a useful organism in which to study the mechanisms whereby UV acts as a mutagen in cells of complex eukaryotes. (author). 46 refs.; 5 figs.; 4 tabs

  20. Antiproliferative Activity and Induction of Apoptosis in PC-3 Cells by the Chalcone Cardamonin from Campomanesia adamantium (Myrtaceae in a Bioactivity-Guided Study

    Directory of Open Access Journals (Sweden)

    Aislan Cristina Rheder Fagundes Pascoal

    2014-02-01

    Full Text Available The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employed as a medicine for dysentery, stomach problems, diarrhea, cystitis and urethritis. Ethanol extracts of Campomanesia adamantium (Myrtaceae leaves and fruits were evaluated against prostate cancer cells (PC-3. The compound (2E-1-(2,4-dihydroxy-6-methoxyphenyl-3-phenylprop-2-en-1-one, cardamonin was isolated from ethanol extracts of C. adamantium leaves in a bioactivity-guided study and quantified by UPLC-MS/MS. In vitro studies showed that the isolated chalcone cardamonin inhibited prostate cancer cell proliferation and decreased the expression of NFkB1. Moreover, analysis by flow cytometry showed that this compound induced DNA fragmentation, suggesting an effect on apoptosis induction in the PC-3 cell line.

  1. Antiproliferative activity and induction of apoptosis in PC-3 cells by the chalcone cardamonin from Campomanesia adamantium (Myrtaceae) in a bioactivity-guided study.

    Science.gov (United States)

    Pascoal, Aislan Cristina Rheder Fagundes; Ehrenfried, Carlos Augusto; Lopez, Begoña Gimenez-Cassina; de Araujo, Thiago Matos; Pascoal, Vinicius D'ávila Bitencourt; Gilioli, Rovilson; Anhê, Gabriel Forato; Ruiz, Ana Lúcia Tasca Goes; Carvalho, João Ernesto de; Stefanello, Maria Elida Alves; Salvador, Marcos José

    2014-01-01

    The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employed as a medicine for dysentery, stomach problems, diarrhea, cystitis and urethritis. Ethanol extracts of Campomanesia adamantium (Myrtaceae) leaves and fruits were evaluated against prostate cancer cells (PC-3). The compound (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-phenylprop-2-en-1-one, cardamonin) was isolated from ethanol extracts of C. adamantium leaves in a bioactivity-guided study and quantified by UPLC-MS/MS. In vitro studies showed that the isolated chalcone cardamonin inhibited prostate cancer cell proliferation and decreased the expression of NFkB1. Moreover, analysis by flow cytometry showed that this compound induced DNA fragmentation, suggesting an effect on apoptosis induction in the PC-3 cell line. PMID:24514747

  2. Guided labworks

    DEFF Research Database (Denmark)

    Jacobsen, Lærke Bang

    For the last 40 years physics education research has shown poor learning outcomes of guided labs. Still this is found to be a very used teaching method in the upper secodary schools. This study explains the teacher's choice of guided labs throught the concept of redesign as obstacle dislodgement...

  3. Lecture Capture with Real-Time Rearrangement of Visual Elements: Impact on Student Performance

    Science.gov (United States)

    Yu, P.-T.; Wang, B.-Y.; Su, M.-H.

    2015-01-01

    The primary goal of this study is to create and test a lecture-capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the…

  4. Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience

    OpenAIRE

    Karnebeek, van, C.D.; Koevoets, C.; Sluijter, S; Bijlsma, E.K.; Smeets, D.F.C.M.; Redeker, E.J.W.; Hennekam, R C M; Hoovers, J.M.N.

    2002-01-01

    Objective: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre.

  5. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations

    DEFF Research Database (Denmark)

    Rausch, Tobias; Jones, David T W; Zapatka, Marc;

    2012-01-01

    a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a...

  6. Computed Tomography-Guided Core-Needle Biopsy Specimens Demonstrate Epidermal Growth Factor Receptor Mutations in Patients with Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Background: Target therapy with a new class of epidermal growth factor receptor (EGFR) inhibitors shows improved clinical response in EGFR gene-mutated lung cancers. Purpose: To evaluate the use of computed tomography (CT)-guided core-needle biopsy specimens for the assessment of EGFR gene mutation in non-small-cell lung cancer (NSCLC). Material and Methods: Seventeen (nine males, eight females) patients with advanced NSCLC were enrolled in this study. All patients underwent CT-guided core-needle biopsy of the lung tumor prior to treatment with the EGFR inhibitor gefitinib. There were no life-threatening complications of biopsy. The specimens were sent fresh-frozen for EGFR mutation analysis and histopathological study. Results: There were 12 (70.6%) EGFR gene mutants and five (29.4%) nonmutants. The objective response rate to gefitinib therapy was 73.3% (11 of 15 patients), with 91.7% (11 of 12 mutants) for the mutant group and 0% for the nonmutant group. Conclusion: CT-guided core-needle biopsy of advanced NSCLC enables the acquisition of sufficient tissue for EGFR gene mutation analysis

  7. Image-Guided Radiofrequency Ablation for the Treatment of Early Stage Non-small Cell Lung Neoplasm in High-risk Patients

    OpenAIRE

    Pennathur, Arjun; Abbas, Ghulam; Luketich, James D.

    2010-01-01

    Lung cancer is the most common cause of cancer related mortality in the United States. Surgical resection with a lobectomy is the standard treatment for Stage I non-small cell lung cancer (NSCLC). With an aging population however, there are a significant number of patients who have other co-morbidities that preclude surgical resection. Image-guided radiofrequency ablation is a new emerging modality of treatment which may be applicable in this high-risk group of patients. In this article, we r...

  8. CD13 is a novel mediator of monocytic/endothelial cell adhesion

    DEFF Research Database (Denmark)

    Mina-Osorio, Paola; Winnicka, Beata; O'Conor, Catherine;

    2008-01-01

    rearrangement and filopodia formation. Treatment with soluble recombinant (r)CD13 blocks this CD13-dependent adhesion, and CD13 molecules from monocytic and endothelial cells are present in the same immunocomplex, suggesting a direct participation of CD13 in the adhesive interaction. This concept is......During inflammation, cell surface adhesion molecules guide the adhesion and migration of circulating leukocytes across the endothelial cells lining the blood vessels to access the site of injury. The transmembrane molecule CD13 is expressed on monocytes and endothelial cells and has been shown to...... mediate homotypic cell adhesion, which may imply a role for CD13 in inflammatory monocyte trafficking. Here, we show that ligation and clustering of CD13 by mAb or viral ligands potently induce myeloid cell/endothelial adhesion in a signal transduction-dependent manner involving monocytic cytoskeletal...

  9. HBR guides

    CERN Document Server

    Duarte, Nancy; Dillon, Karen

    2015-01-01

    Master your most pressing professional challenges with this seven-volume set that collects the smartest best practices from leading experts all in one place. "HBR Guide to Better Business Writing" and "HBR Guide to Persuasive Presentations" help you perfect your communication skills; "HBR Guide to Managing Up and Across" and "HBR Guide to Office Politics" show you how to build the best professional relationships; "HBR Guide to Finance Basics for Managers" is the one book you'll ever need to teach you about the numbers; "HBR Guide to Project Management" addresses tough questions such as how to manage stakeholder expectations and how to manage uncertainty in a complex project; and "HBR Guide to Getting the Right Work Done" goes beyond basic productivity tips to teach you how to prioritize and focus on your work. This specially priced set of the most popular books in the series makes a perfect gift for aspiring leaders looking for trusted advice. Arm yourself with the advice you need to succeed on the job, from ...

  10. Rhodamine-RCA in vivo labeling guided laser capture microdissection of cancer functional angiogenic vessels in a murine squamous cell carcinoma mouse model

    Directory of Open Access Journals (Sweden)

    Bur Monica

    2006-02-01

    Full Text Available Abstract Background Cancer growth, invasion and metastasis are highly related to tumor-associated neovasculature. The presence and progression of endothelial cells in cancer is chaotic, unorganized, and angiogenic vessels are less functional. Therefore, not all markers appearing on the chaotic endothelial cells are accessible if a drug is given through the vascular route. Identifying endothelial cell markers from functional cancer angiogenic vessels will indicate the accessibility and potential efficacy of vascular targeted therapies. Results In order to quickly and effectively identify endothelial cell markers on the functional and accessible tumor vessels, we developed a novel technique by which tumor angiogenic vessels are labeled in vivo followed by Laser Capture Microdissection of microscopically isolated endothelial cells for genomic screening. Female C3H mice (N = 5 with established SCCVII tumors were treated with Rhodamine-RCA lectin by tail vein injection, and after fluorescence microscopy showed a successful vasculature staining, LCM was then performed on frozen section tissue using the PixCell II instrument with CapSure HS caps under the Rhodamine filter. By this approach, the fluorescent angiogenic endothelial cells were successfully picked up. As a result, the total RNA concentration increased from an average of 33.4 ng/ul +/- 24.3 (mean +/- S.D. to 1913.4 ng/ul +/- 164. Relatively pure RNA was retrieved from both endothelial and epithelial cells as indicated by the 260/280 ratios (range 2.22–2.47. RT-PCR and gene electrophoresis successfully detected CD31 and Beta-Actin molecules with minimal Keratin 19 expression, which served as the negative control. Conclusion Our present study demonstrates that in vivo Rhodamine RCA angiogenic vessel labeling provided a practical approach to effectively guide functional endothelial cell isolation by laser capture microdissection with fluorescent microscopy, resulting in high quality RNA and

  11. Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.

  12. Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

    DEFF Research Database (Denmark)

    Hougs, L; Barington, T; Madsen, HO;

    1993-01-01

    of the B lymphocytes activated in vivo. Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes. After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the......Analysis of rearranged immunoglobulin genes used by B lymphocytes of known specificity is an important tool for the study of diversity and selection of B lymphocytes. Usually hybridoma cell lines are used for such analyses, but they are difficult to obtain from humans and may not be representative...... HibCP-specific B lymphocytes were isolated by antigen-coated immunomagnetic beads. After the purification, at least 98% of the immunoglobulin-secreting recovered cells were HibCP specific. The RNA was isolated and amplified by cDNA synthesis using a kappa constant region primer followed by polymerase...

  13. Ewing Sarcoma With ERG Gene Rearrangements: A Molecular Study Focusing on the Prevalence of FUS-ERG and Common Pitfalls in Detecting EWSR1-ERG Fusions by FISH

    Science.gov (United States)

    Chen, Sonja; Deniz, Kemal; Sung, Yun-Shao; Zhang, Lei; Dry, Sarah; Antonescu, Cristina R.

    2016-01-01

    The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1-ERG being identified in 5–10% of cases, while only a handful of reports document a FUS-ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS-ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS-positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG-rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1-ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3-color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break-apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT-PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG-rearranged SBRCTs. PMID:26690869

  14. Autosomal rearrangement in Gryllus assimilis Fabricius, 1775 (Orthoptera, Gryllidae

    Directory of Open Access Journals (Sweden)

    Edison Zefa

    1999-09-01

    Full Text Available Gryllus assimilis L. has a karyotype of 2n = 29 (X0, male and 30 (XX, female. The above karyotype was encountered along with another in which 2n = 28 (X0, male and 2n = 29 (XX, female in a population from the outskirts of Rio Claro city (São Paulo State, Brazil. Of eight specimens studied, five had the heterozygous karyotype involving a translocation and three had the basic karyotype. There were no individuals homozygous for the rearrangement. The heterozygous karyotype was the result of a chromosomal rearrangement between chromosome pairs 6 and 10, both of which were initially submetacentric. The members of the sixth pair normally have two constrictions in the small arm, with a satellite at the chromosome tip. The chromosome of the tenth pair involved in the translocation was generally submetacentric and probably underwent a pericentric inversion which transported the centromere to a subterminal position before being translocated. In this case, the long arm of the inverted chromosome of the tenth pair was translocated with the satellite of a member of the sixth pair.A espécie Gryllus assimilis L. apresenta 2n = 29, X0 (macho e 2n = 30, XX (fêmea, porém em alguns indivíduos coletados na cidade de Rio Claro, São Paulo, Brasil, foram encontrados dois cariótipos distintos: o cariótipo básico e outro rearranjado, com 2n = 28, X0 e 2n = 29, XX. O rearranjo foi interpretado como sendo autossômico e heterozigoto, caracterizado pela translocação envolvendo dois pares de homólogos submetacêntricos: o par 10, que possivelmente tem um dos elementos com uma inversão pericêntrica, e o par 6, que possui em seu braço curto duas constrições secundárias, diferenciando satélites em suas extremidades.

  15. Medication Guide

    Science.gov (United States)

    ... Size Small Text Medium Text Large Text Contrast Dark on Light Light on Dark Donate Search Menu Donate What is Glaucoma? Care ... Low Vision Resources Medication Guide Resources on the Web » See All Articles Help the Cause Glaucoma affects ...

  16. Micro-cost Analysis of ALK Rearrangement Testing by FISH to Determine Eligibility for Crizotinib Therapy in NSCLC: Implications for Cost Effectiveness of Testing and Treatment

    OpenAIRE

    David Parker; Marc-Antoine Belaud-Rotureau

    2014-01-01

    Break-apart fluorescence in situ hybridization (FISH) is the gold standard test for anaplastic lymphoma kinase (ALK) gene rearrangement. However, this methodology often is assumed to be expensive and potentially cost-prohibitive given the low prevalence of ALK-positive non-small cell lung cancer (NSCLC) cases. To more accurately estimate the cost of ALK testing by FISH, we developed a micro-cost model that accounts for all cost elements of the assay, including laboratory reagents, supplies, c...

  17. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors. PMID:25414829

  18. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors. PMID:25414829

  19. Genomic Rearrangement in Endogenous Long Terminal Repeat Retrotransposons of Rice Lines Introgressed by Wild Rice (Zizania latifolia Griseb.)

    Institute of Scientific and Technical Information of China (English)

    Ye SHEN; Xiu-Yun LIN; Xiao-Hui SHAN; Chun-Jing LIN; Fang-Pu HAN; Jin-Song PANG; Bao LIU

    2005-01-01

    Stochastic introgression of alien DNA may impose a genomic stress to the recipient genome.Herein, we report that apparent de novo genomic rearrangements in 10 of 13 selected endogenous, low-copy, and potentially active long terminal repeat (LTR) retrotransposons occurred in one or more of threerice lines studied that were introgressed by wild rice (Zizania latifolia Griseb.). For nine retrotransposons inwhich both the reverse-transcriptase (RT) region and the LTR region were available, largely concordantrearrangements occurred at both regions in five elements and at the RT region only in the remaining fourelements. A marked proportion of the genomic changes was shared by two or all three introgression linesthat were derived from a single F1 plant. This indicates that most of the genomic changes occurred at earlydevelopmental stages of the F1 somatic cells, which then gave rise to germline cells, and, hence, ensuredinheritance of the changes to later generations. Possible causes and potential implications of the introgres-sion-induced genomic rearrangements in LTR retrotransposons are discussed in the context of plant ge-nome evolution and breeding.

  20. Genomic characterization of large rearrangements of the LDLR gene in Czech patients with familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Fajkus Jiří

    2010-07-01

    Full Text Available Abstract Background Mutations in the LDLR gene are the most frequent cause of Familial hypercholesterolemia, an autosomal dominant disease characterised by elevated concentrations of LDL in blood plasma. In many populations, large genomic rearrangements account for approximately 10% of mutations in the LDLR gene. Methods DNA diagnostics of large genomic rearrangements was based on Multiple Ligation dependent Probe Amplification (MLPA. Subsequent analyses of deletion and duplication breakpoints were performed using long-range PCR, PCR, and DNA sequencing. Results In set of 1441 unrelated FH patients, large genomic rearrangements were found in 37 probands. Eight different types of rearrangements were detected, from them 6 types were novel, not described so far. In all rearrangements, we characterized their exact extent and breakpoint sequences. Conclusions Sequence analysis of deletion and duplication breakpoints indicates that intrachromatid non-allelic homologous recombination (NAHR between Alu elements is involved in 6 events, while a non-homologous end joining (NHEJ is implicated in 2 rearrangements. Our study thus describes for the first time NHEJ as a mechanism involved in genomic rearrangements in the LDLR gene.

  1. In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: A practical guide with case studies

    Directory of Open Access Journals (Sweden)

    Martina eMcDermott

    2014-03-01

    Full Text Available The development of a drug-resistant cell line can take from 3-18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval and optimising the dose of drug for the parent cell line. Clinically-relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between 2-8 fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically-relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299, H460 and temozolomide-resistant melanoma (Malme-3M and HT144 cell lines. Continuous selection produced lapatinib-resistant breast cancer cell line (HCC1954. Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug

  2. Rearrangement of the Extracellular Domain/Extracellular Loop 1 Interface Is Critical for Thyrotropin Receptor Activation.

    Science.gov (United States)

    Schaarschmidt, Joerg; Nagel, Marcus B M; Huth, Sandra; Jaeschke, Holger; Moretti, Rocco; Hintze, Vera; von Bergen, Martin; Kalkhof, Stefan; Meiler, Jens; Paschke, Ralf

    2016-07-01

    The thyroid stimulating hormone receptor (TSHR) is a G protein-coupled receptor (GPCR) with a characteristic large extracellular domain (ECD). TSHR activation is initiated by binding of the hormone ligand TSH to the ECD. How the extracellular binding event triggers the conformational changes in the transmembrane domain (TMD) necessary for intracellular G protein activation is poorly understood. To gain insight in this process, the knowledge on the relative positioning of ECD and TMD and the conformation of the linker region at the interface of ECD and TMD are of particular importance. To generate a structural model for the TSHR we applied an integrated structural biology approach combining computational techniques with experimental data. Chemical cross-linking followed by mass spectrometry yielded 17 unique distance restraints within the ECD of the TSHR, its ligand TSH, and the hormone-receptor complex. These structural restraints generally confirm the expected binding mode of TSH to the ECD as well as the general fold of the domains and were used to guide homology modeling of the ECD. Functional characterization of TSHR mutants confirms the previously suggested close proximity of Ser-281 and Ile-486 within the TSHR. Rigidifying this contact permanently with a disulfide bridge disrupts ligand-induced receptor activation and indicates that rearrangement of the ECD/extracellular loop 1 (ECL1) interface is a critical step in receptor activation. The experimentally verified contact of Ser-281 (ECD) and Ile-486 (TMD) was subsequently utilized in docking homology models of the ECD and the TMD to create a full-length model of a glycoprotein hormone receptor. PMID:27129207

  3. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers.

    Science.gov (United States)

    Yoshida, Akihiko; Tsuta, Koji; Wakai, Susumu; Arai, Yasuhito; Asamura, Hisao; Shibata, Tatsuhiro; Furuta, Koh; Kohno, Takashi; Kushima, Ryoji

    2014-05-01

    The recent discovery and characterization of an oncogenic ROS1 gene fusion in a subset of lung cancers has raised significant clinical interest because small molecule inhibitors may be effective to these tumors. As lung cancers with ROS1 rearrangements comprise only 1-3% of lung adenocarcinomas, patients with such tumors must be identified to gain optimal benefit from molecular therapy. Recently, immunohistochemical analyses using a novel anti-ROS1 rabbit monoclonal antibody (D4D6) have shown promise for accurate identification of ROS1-rearranged cancers. To validate this finding, we compared the immunostaining results of tissue microarrays (TMAs) containing 17 ROS1-rearranged and 253 ROS1-non-rearranged lung carcinomas. All 17 ROS1-rearranged cancers showed ROS1 immunoreactivity mostly in a diffuse and moderate-to-strong manner with an H-score range of 5-300 (median, 260). In contrast, 69% of ROS1-non-rearranged cancers lacked detectable immunoreactivity, whereas the remaining 31% showed reactivity mainly in a weak or focal manner. The H-score for the entire ROS1-non-rearranged group ranged from 0 to 240 (median, 0). The difference in H-score between the two cohorts was statistically significant, and the H-score cutoff (≥150) allowed optimal discrimination (94% sensitivity and 98% specificity). Similar but slightly less-specific performance was achieved using the extent of diffuse (≥75%) staining or ≥2+ staining intensity as cutoffs. CD74-ROS1 and EZR-ROS1 fusions were significantly associated with at least focal globular immunoreactivity and plasma membranous accentuation, respectively, and these patterns were specific to ROS1-rearranged cases. Although full-length ROS1 is expressed in some ROS1-non-rearranged cases, we showed that establishment of an optimal set of interpretative criteria makes ROS1 immunohistochemistry a valuable method to rapidly and accurately screen lung cancer patients for appropriate molecular therapy. PMID:24186139

  4. On the Complexity of Rearrangement Problems under the Breakpoint Distance

    CERN Document Server

    Kovac, Jakub

    2011-01-01

    Tannier et al. introduced a generalization of breakpoint distance for multichromosomal genomes. They showed that the median problem under the breakpoint distance is solvable in polynomial time in the multichromosomal circular and mixed models. This is intriguing, since in all other rearrangement models (DCJ, reversal, unichromosomal or multilinear breakpoint models), the problem is NP-hard. The complexity of the small or even the large phylogeny problem under the breakpoint distance remained an open problem. We improve the algorithm for the median problem and show that it is equivalent to the problem of finding maximum cardinality non-bipartite matching (under linear reduction). On the other hand, we prove that the more general small phylogeny problem is NP-hard. Surprisingly, we show that it is already NP-hard (or even APX-hard) for 4 species (a quartet phylogeny). In other words, while finding an ancestor for 3 species is easy, already finding two ancestors for 4 species is hard. We also show that, in the u...

  5. Structural rearrangement through lanthanide contraction in dinuclear complexes.

    Science.gov (United States)

    Hutchings, Amy-Jayne; Habib, Fatemah; Holmberg, Rebecca J; Korobkov, Ilia; Murugesu, Muralee

    2014-02-17

    A new series of lanthanide complexes was synthesized, and the geometry and preliminary magnetic measurements of the complexes were explored. The specific ligand used (N'-(2-hydroxy-3-methoxybenzylidene)benzhydrazide) (H2hmb) was synthesized using a Schiff-base approach and was employed due to the presence of a coordination pocket that is able to accommodate magnetically selective lanthanide ions. The series can be divided into two groups that are categorized by a drastic structural rearrangement. The first group, Type I, contains six analogous complexes with the formula [M(III)2(Hhmb)3(NCS)3]·2MeOH·py (M = Y 1, Eu 2, Gd 3, Tb 4, Dy 5, Ho 6), while the second group, Type II, contains two dinuclear complexes with formula [M(III)2(Hhmb)2(NCS)4(MeOH)2] (M = Er 7, and Yb 8). Single-crystal X-ray analysis revealed that all M(III) ions in Type I exhibit monocapped distorted square antiprismatic geometries, while those of Type II exhibit distorted dodecahedron geometry. The direct current and alternating current magnetic measurements were carried out on all complexes, with 5, 7, and 8 exhibiting slow relaxation of the magnetization under an applied optimum dc field. Furthermore, complex 8 is the first example of a dinuclear Yb-based single-molecule magnet showing field-dependent multiple relaxation processes. PMID:24499030

  6. Measuring soil layer thickness in land rearrangement with GPR data

    International Nuclear Information System (INIS)

    Accurate measurement of soil layer thickness by GPR (ground penetrating radar) is of great importance for overlay design and quality control/quality assurance for land rearrangement projects. Soil layer detection is complex because of multiple reflections and high attenuation for electromagnetic (EM) waves propagating in the soil media. This paper proposes a novel data processing method based on the reflection and refraction of the EM waves to improve the measurement accuracy. A cross-correlation sequence is introduced to align the traces, and the effects of random noise are reduced by using a forwards and backwards filtering procedure without phase delay. Additionally, the homomorphic deconvolution, namely the power cepstrum, is employed to deconvolve GPR data and, thus, to enhance its interface reflection. The results of the verification test show that the measurement can achieve high accuracy, with an error less than 10%, and the measurement performance is greatly improved by using the new method. Finally, a contour map of the research area is generated automatically for quality detection and quality control guidance. (paper)

  7. Chromosome painting defines genomic rearrangements between red howler monkey subspecies.

    Science.gov (United States)

    Consigliere, S; Stanyon, R; Koehler, U; Agoramoorthy, G; Wienberg, J

    1996-06-01

    We hybridized whole human chromosome-specific DNA libraries to chromosomes of two supposed subspecies of Alouatta seniculus: Alouatta seniculus sara and Alouatta seniculus arctoides. The number of hybridization signals per haploid set is 42 in A. s. sara and 43 in A. s. arctoidea; the two karyotypes differ by at least 16 chromosomal rearrangements, including numerous translocations. An unusual sex chromosome system is shared by both taxa. The sex chromosome system results from a Y translocation with a chromosome homologous to parts of human chromosome 3/15 and can be described as X1X2Y1Y2/X1X1X2X2 (male/female). Both red howlers also have microchromosomes, a highly unusual karyological trait not found in other higher primates. These microchromosomes are not hybridized by any human chromosome paint and therefore are probably composed of repetitive DNA. It is well known that New World monkeys have high karyological variability. It is probable that molecular cytogenetic analyses including chromosome painting will permit an accurate reconstruction of the phylogeny of these monkeys and help establish the ancestral karyotype for higher primates. PMID:8817065

  8. Anisotropic rearrangement of the substrate atoms during Ar bombardment on Pd(0 0 1) surface

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang-Pil [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Kim, Byung-Hyun [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Department of Materials Science and Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Kim, Haeri [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Department of Physics, Ewha Womans University, Seoul 120-750 (Korea, Republic of); Lee, Kwang-Ryeol, E-mail: krlee@kist.re.kr [Computational Science Center, Interdisciplinary Fusion Technology Division, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Chung, Yong-Chae [Department of Materials Science and Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Seo, Jikeun [Department of Ophthalmic Optics, Chodang University, Muan 534-701 (Korea, Republic of); Kim, Jae-Sung [Department of Physics, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2011-11-01

    Using a three-dimensional molecular dynamics (MD) simulation, we investigated the atomic scale rearrangement that occurs on a Pd(0 0 1) surface after energetic bombardment by Ar at room temperature. High energy Ar bombardment provoked the significant rearrangement of Pd atoms in a ballistic manner with a fourfold symmetric lateral distribution aligned along the <1 1 0> direction. The MD simulation of uniform Ar bombardment at normal incidence on a Pd surface reproduced the experimentally observed fourfold symmetric nano-scale surface structure. The present result supports that the ballistic rearrangement of the substrate atoms plays an important role in the ion induced surface structure evolution.

  9. MHC-multimer guided isolation of neoepitopes specific T cells as a potent-personalized cancer treatment strategy.

    Science.gov (United States)

    Bareli, Roni; Cohen, Cyrille J

    2016-07-01

    Analysis of genomic data from patient tumors provides valuable information as to potential T-cell targets such as neoepitopes. We developed an approach to characterize, isolate and utilize neoantigens-specific T cells using MHC/peptide tetramers from fresh tumor digests and peripheral blood. This bears important implications for the implementation of T cell-based immunotherapy. PMID:27622017

  10. CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Martínez-Monge, Rafael; Pagola, María; Vivas, Isabel; López-Picazo, José María

    2008-08-01

    Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of (103)Pd or (125)I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure. After a median follow-up of 13 months (4.6-41.0+ months), no patient has developed local or regional failure. PMID:18243409

  11. Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration

    Science.gov (United States)

    Lopes Pinheiro, Melissa A; Kamermans, Alwin; Garcia-Vallejo, Juan J; van het Hof, Bert; Wierts, Laura; O'Toole, Tom; Boeve, Daniël; Verstege, Marleen; van der Pol, Susanne MA; van Kooyk, Yvette; de Vries, Helga E; Unger, Wendy WJ

    2016-01-01

    Trafficking of myelin-reactive CD4+ T-cells across the brain endothelium, an essential step in the pathogenesis of multiple sclerosis (MS), is suggested to be an antigen-specific process, yet which cells provide this signal is unknown. Here we provide direct evidence that under inflammatory conditions, brain endothelial cells (BECs) stimulate the migration of myelin-reactive CD4+ T-cells by acting as non-professional antigen presenting cells through the processing and presentation of myelin-derived antigens in MHC-II. Inflamed BECs internalized myelin, which was routed to endo-lysosomal compartment for processing in a time-dependent manner. Moreover, myelin/MHC-II complexes on inflamed BECs stimulated the trans-endothelial migration of myelin-reactive Th1 and Th17 2D2 cells, while control antigen loaded BECs did not stimulate T-cell migration. Furthermore, blocking the interaction between myelin/MHC-II complexes and myelin-reactive T-cells prevented T-cell transmigration. These results demonstrate that endothelial cells derived from the brain are capable of enhancing antigen-specific T cell recruitment. DOI: http://dx.doi.org/10.7554/eLife.13149.001 PMID:27336724

  12. Ploidy influences cellular responses to gross chromosomal rearrangements in saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Lemoine Sophie

    2011-06-01

    Full Text Available Abstract Background Gross chromosomal rearrangements (GCRs such as aneuploidy are key factors in genome evolution as well as being common features of human cancer. Their role in tumour initiation and progression has not yet been completely elucidated and the effects of additional chromosomes in cancer cells are still unknown. Most previous studies in which Saccharomyces cerevisiae has been used as a model for cancer cells have been carried out in the haploid context. To obtain new insights on the role of ploidy, the cellular effects of GCRs were compared between the haploid and diploid contexts. Results A total number of 21 haploid and diploid S. cerevisiae strains carrying various types of GCRs (aneuploidies, nonreciprocal translocations, segmental duplications and deletions were studied with a view to determining the effects of ploidy on the cellular responses. Differences in colony and cell morphology as well as in the growth rates were observed between mutant and parental strains. These results suggest that cells are impaired physiologically in both contexts. We also investigated the variation in genomic expression in all the mutants. We observed that gene expression was significantly altered. The data obtained here clearly show that genes involved in energy metabolism, especially in the tricarboxylic acid cycle, are up-regulated in all these mutants. However, the genes involved in the composition of the ribosome or in RNA processing are down-regulated in diploids but up-regulated in haploids. Over-expression of genes involved in the regulation of the proteasome was found to occur only in haploid mutants. Conclusion The present comparisons between the cellular responses of strains carrying GCRs in different ploidy contexts bring to light two main findings. First, GCRs induce a general stress response in all studied mutants, regardless of their ploidy. Secondly, the ploidy context plays a crucial role in maintaining the stoichiometric balance

  13. One-pot oxidation and rearrangement of propargylamines and in situ pyrazole synthesis.

    Science.gov (United States)

    Chen, Jinshan; Properzi, Roberta; Uccello, Daniel P; Young, Jennifer A; Dushin, Russell G; Starr, Jeremy T

    2014-08-15

    Reported here are procedures for a one-pot oxidation and rearrangement of propargylamines to synthesize enaminones, with supporting mechanistic studies. Also reported are the extended one-pot syntheses of pyrazoles, including celecoxib and various heterocyclic compounds. PMID:25069029

  14. Unexpected Stereospecific Rearrangement-Addition Reaction of Trisubstituted Gibberellin Epoxides with Trimethylaluminium

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A novel rearrangement-addition reaction of trisubstituted gibberellin epoxides with trimethylaluminium is reported. The reaction proceeds stereospecifically to give tertiary methyl alcohols. The possible mechanism for the reaction is also discussed.

  15. Low frequency of large genomic rearrangements of BRCA1 and BRCA2 in western Denmark

    DEFF Research Database (Denmark)

    Thomassen, Mads; Gerdes, Anne-Marie; Cruger, Dorthe; Jensen, Peter K A; Kruse, Torben A

    2006-01-01

    Germline mutations in BRCA1 and BRCA2 predispose female carriers to breast and ovarian cancer. The majority of mutations identified are small deletions or insertions or are nonsense mutations. Large genomic rearrangements in BRCA1 are found with varying frequencies in different populations, but...... BRCA2 rearrangements have not been investigated thoroughly. The objective in this study was to determine the frequency of large genomic rearrangements in BRCA1 and BRCA2 in a large group of Danish families with increased risk of breast and ovarian cancer. A total of 617 families previously tested...... negative for mutations involving few bases were screened with multiplex ligation-dependent probe amplification (MLPA). Two deletions in BRCA1 were identified in three families; no large rearrangements were detected in BRCA2. The large deletions constitute 3.8% of the BRCA1 mutations identified, which is...

  16. An efficient algorithm for the contig ordering problem under algebraic rearrangement distance.

    Science.gov (United States)

    Lu, Chin Lung

    2015-11-01

    Assembling a genome from short reads currently obtained by next-generation sequencing techniques often results in a collection of contigs, whose relative position and orientation along the genome being sequenced are unknown. Given two sets of contigs, the contig ordering problem is to order and orient the contigs in each set such that the genome rearrangement distance between the resulting sets of ordered and oriented contigs is minimized. In this article, we utilize the permutation groups in algebra to propose a near-linear time algorithm for solving the contig ordering problem under algebraic rearrangement distance, where the algebraic rearrangement distance between two sets of ordered and oriented contigs is the minimum weight of applicable rearrangement operations required to transform one set into the other. PMID:26247343

  17. Diagnosis of Columnar Cell Lesions and Atypical Ductal Hyperplasia by Ultrasound-Guided Core Biopsy: Findings Associated with Underestimation of Breast Carcinoma.

    Science.gov (United States)

    Ahn, Hye Shin; Jang, Mijung; Kim, Sun Mi; Yun, Bo La; Kim, Sung-Won; Kang, Eun Young; Park, So Yeon

    2016-07-01

    The aim of the study described here was to determine underestimation rates and identify radiologic predictors of underestimation for columnar cell lesions (CCLs) and atypical ductal hyperplasia (ADH) detected by ultrasound-guided core needle biopsy. A total of 103 CCLs and ADH lesions in 100 patients diagnosed by ultrasound-guided core needle biopsy were evaluated. Breast sonographic and mammographic findings were reviewed, and underestimation rates were determined by surgical excision, percutaneous vacuum-assisted excision or 2-y imaging follow-up. All underestimated lesions were ductal carcinoma in situ, and the underestimation rates of flat epithelial atypia (FEA), FEA + ADH and ADH were 5.9% (1/17), 44.4% (4/9) and 27.3% (12/44), respectively. There was no underestimation of CCLs without atypia. The presence of calcifications on ultrasound was significantly associated with underestimation (p = 0.010). Therefore, except for CCLs without atypia, all other lesions may require excision, especially when calcification is present on ultrasound or when FEA + ADH is found. PMID:27067419

  18. Study of percutaneous 125I seeds implantation guided by CT in elderly patients of stage I peripheral non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy, feasibility and safety of CT guided percutaneous 125I seeds implantation in elderly patients of stage I peripheral non-small cell lung cancer (NSCLC). Methods: Clinical data of 16 elderly peripheral stage I NSCLC patients (10 squamous carcinoma and 6 adenocarcinoma; 13 stage IA and 3 stage IB) who received radioactive 125I seeds implantation because of refusal or being unsuited to operation or external radiotherapy were retrospectively analyzed. Prescribed dose was 140 - 160 Gy. Under CT guidance, 125I seeds were implanted percutaneously into tumors for interstitial radiotherapy according to treatment plan system. Results: Mean number of 125I seeds each patient received was 21.1. 12 complete response (CR) and 4 partial response (PR) were achieved. Total response rate (CR + PR) was 100%. 100% patients completed 10 to 56 months of follow-up, 15, 13, 8 and 6 patients completed 1-, 2-, 3-and 4-years' follow-up, respectively. The median local progression free time was 14 months. The 1-, 2-, 3-and 4-year overall survival rate were 60%, 54%, 50% and 33%, respectively (median : 14 months). 7 cases died of non-tumor disease and 5 died of metastasis. No severe complications were observed. Conclusions: CT guided 125I seeds implantation is a safe, reliable and effective radical treatment method for elderly stage I peripheral NSCLC patients, who refuse to or are unsuitable to operation or external radiotherapy. (authors)

  19. Synthesis of Benzofuran Derivatives via Rearrangement and Their Inhibitory Activity on Acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    Ling-Yi Kong

    2010-11-01

    Full Text Available During a synthesis of coumarins to obtain new candidates for treating Alzheimer’s Disease (AD, an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil.

  20. Expedited Synthesis of Benzofuran-2-Carboxylic Acids via Microwave-Assisted Perkin Rearrangement Reaction

    OpenAIRE

    Marriott, Karla-Sue C.; Bartee, Rena; Morrison, Andrew Z.; Stewart, Leonard; Wesby, Julian

    2012-01-01

    3-Halocoumarins are readily converted into benzofuran-2-carboxylic acids via a Perkin (coumarin-benzofuran ring contraction) rearrangement reaction. This rearrangement entails initial base catalyzed ring fission. The resulting phenoxide anion then attacks a vinyl halide to produce the final benzofuran moiety. We explored this reaction under microwave reaction conditions and were able to significantly reduce reaction times as well as obtain very high yields of a series of benzofuran-2-carboxyl...

  1. Computer study of liquid phase sintering - three-dimensional time dependent rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Nikolic, Zoran S [University of Nish, Faculty of Electronic Engineering, Department of Microelectronics, 18000 Nish, PO Box 73 (Serbia); Wakai, Fumihiro, E-mail: zoran.nikolic@elfak.ni.ac.rs [Secure Materials Center, Materials and Structures Laboratory, Tokyo Institute of Technology, R3-23 4259 Nagatsuta, Midori, Yokohama, 226-8503 (Japan)

    2011-03-15

    The rearrangement process during liquid phase sintering has been generally accepted that driven by the capillary forces between solid grains embedded in liquid. This paper outlines a computer-based method for three-dimensional computer simulation of rearrangement during liquid phase sintering. The theoretical models dealing with the fundamental interaction forces that exist between grains attached by liquid bridges will be outlined and the development from these pair-wise interactions to multi-grain models will be described.

  2. Ovarian Hemangiomas Do Not Harbor EWSR1 Rearrangements: Clinicopathologic Characterization of 10 Cases.

    Science.gov (United States)

    Schoolmeester, John Kenneth; Greipp, Patricia T; Keeney, Gary L; Soslow, Robert A

    2015-09-01

    Hemangiomas of the ovary are rare with a majority described as individual reports of unusual clinical presentations or morphologic findings. Both the expected and unexpected pathologic features of these tumors in the ovary are not well detailed. Therefore, we collected the largest series of ovarian hemangiomas to comprehensively define their clinicopathologic associations and examine the significance of hormone receptors in their pathogenesis. In addition, a novel EWSR1-NFATC1 fusion has recently been described in a case of hemangioma of bone. To our knowledge, EWSR1 rearrangement has not been evaluated in hemangiomas of other sites or in a case series. Accordingly, we used fluorescence in situ hybridization to investigate EWSR1 status in a majority of our cases. Clinical presentation was variable and dependent on tumor size. Patient age ranged 48 to 87 yr (median 63 yr). Tumors involved the right (n=6) and left (n=3) ovaries with laterality unknown in 1 case, and size ranged from 0.2 to 5.0 cm (median 1.0 cm). Three of 4 radiologic reports were either equivocal or could not exclude malignancy. Seven cases were of the cavernous type and 3 were mixed cavernous and capillary type. All lesions formed a single discrete, circumscribed mass that displaced the surrounding cortical stroma. The cavernous type showed dilated, thin-walled vessels and vascular thrombi, some of which were associated with dystrophic calcification. In addition to cavernous morphology, the mixed form exhibited features of capillary hemangioma such as lobulated growth of capillary-sized vascular spaces that lacked atypia or multilayering and were linked to a larger feeding vessel. Each tumor expressed CD31, CD34, FLI-1, ERG, but not D240. The hemangioma stromal cells, but not endothelium, expressed estrogen and progesterone receptors in every case. Stromal luteinization was seen in 2 cases. Follow-up ranged 1 to 139 mo and all patients were disease free. All cases were negative for EWSR1

  3. Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

    2009-09-18

    Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human genome; however, appear to have a higher propensity than others to rearrange in any host system. Thus, techniques to detect and accurately characterize such rearrangements need to be developed. We developed a technique termed 'Quantitative DNA Fiber Mapping (QDFM)' that allows accurate tagging of sequence elements of interest with near kilobase accuracy and optimized it for delineation of rearrangements in recombinant DNA clones. This paper demonstrates the power of this microscopic approach by investigating YAC rearrangements. In our examples, high-resolution physical maps for regions within the immunoglobulin lambda variant gene cluster were constructed for three different YAC clones carrying deletions of 95 kb and more. Rearrangements within YACs could be demonstrated unambiguously by pairwise mapping of cosmids along YAC DNA molecules. When coverage by YAC clones was not available, distances between cosmid clones were estimated by hybridization of cosmids onto DNA fibers prepared from human genomic DNA. In addition, the QDFM technology provides essential information about clone stability facilitating closure of the maps of the human genome as well as those of model organisms.

  4. Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements.

    Science.gov (United States)

    Santos, Joana; Mesquita, Diana; Barros-Silva, João D; Jerónimo, Carmen; Henrique, Rui; Morais, António; Paulo, Paula; Teixeira, Manuel R

    2015-01-01

    Gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in several human malignancies, including prostate cancer, and has been implicated in multiple important neoplastic signaling pathways. We recently have shown that GRPR is an ERG and ETV1 target gene in prostate cancer, using a genome-wide scale and exon-level expression microarray platform. Due to its cellular localization, the relevance of its function and the availability of blocking agents, GRPR seems to be a promising candidate as therapeutic target. Our present work shows that effective knockdown of GRPR in LNCaP and VCaP cells attenuates their malignant phenotype by decreasing proliferation, invasion and anchorage-independent growth, while increasing apoptosis. Using an antibody microarray we were able to validate known and identify new targets of GRPR pathway, namely AKT1, PKCε, TYK2 and MST1. Finally, we show that overexpression of these GRPR targets is restricted to prostate carcinomas harboring ERG and/or ETV1 rearrangements, establishing their potential as therapeutic targets for these particular molecular subsets of the disease. PMID:26097883

  5. Variation induced by DNA rearrangement in a transgenic Bt+CpTI cotton strain

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In the development of transgenic Bt + CpTI cotton cultivars, one male and female sterile mutant has been found in a homozygous T4 strain in our laboratory. The mutant plant, as well as its leaves, buds and flowers, is only 1/2-1/3 as large as that of the wild transgenic Bt + CpTI bivalant cotton plants. Cytological observation found that the chromosome number of the mutant is 2n = 52; however, there are 4 - 8 univalents observed in meiosis Ⅰ of pollen mother cells. Laboratory bioassay indicated that the mutant was highly resistant to bollworm as the wild plants. PCR amplification revealed that Bt and CpTI genes in the mutant were still intactly inserted. However, small deletion of flanked area had been observed in the mutant by Southern blotting analysis. So it is proposed that the mutant phenotype might result from either the DNA deletion or T-DNA trans-ferring in plant genome. No such report has been presented that the rearrangement of chromosome structure in a homo-zygous transgenic line occurred. Further analysis is ongoing.

  6. Nuclear dynamics and genetic rearrangement in heterokaryotic colonies of Fusarium oxysporum.

    Science.gov (United States)

    Shahi, Shermineh; Beerens, Bas; Bosch, Martin; Linmans, Jasper; Rep, Martijn

    2016-06-01

    Recent studies have shown horizontal transfer of chromosomes to be a potential key contributor to genome plasticity in asexual fungal pathogens. However, the mechanisms behind horizontal chromosome transfer in eukaryotes are not well understood. Here we investigated the role of conidial anastomosis in heterokaryon formation between incompatible strains of Fusarium oxysporum and determined the importance of heterokaryons for horizontal chromosome transfer. Using live-cell imaging we demonstrate that conidial pairing of incompatible strains under carbon starvation can result in the formation of viable heterokaryotic hyphae in F. oxysporum. Nuclei of the parental lines presumably fuse at some stage as conidia with a single nucleus harboring both marker histones (GFP- and RFP-tagged) are produced. Upon colony formation, this hybrid offspring is subject to progressive and gradual genome rearrangement. The parental genomes appear to become spatially separated and RFP-tagged histones, deriving from one of the strains, Fol4287, are eventually lost. With a PCR-based method we showed that markers for most of the chromosomes of this strain are lost, indicating a lack of Fol4287 chromosomes. This leaves offspring with the genomic background of the other strain (Fo47), but in some cases together with one or two chromosomes from Fol4287, including the chromosome that confers pathogenicity towards tomato. PMID:27013267

  7. Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research.

    Science.gov (United States)

    Engel, Martin; Do-Ha, Dzung; Muñoz, Sonia Sanz; Ooi, Lezanne

    2016-10-01

    Induced pluripotent stem cells and embryonic stem cells have revolutionized cellular neuroscience, providing the opportunity to model neurological diseases and test potential therapeutics in a pre-clinical setting. The power of these models has been widely discussed, but the potential pitfalls of stem cell differentiation in this research are less well described. We have analyzed the literature that describes differentiation of human pluripotent stem cells into three neural cell types that are commonly used to study diseases, including forebrain cholinergic neurons for Alzheimer's disease, midbrain dopaminergic neurons for Parkinson's disease and cortical astrocytes for neurodegenerative and psychiatric disorders. Published protocols for differentiation vary widely in the reported efficiency of target cell generation. Additionally, characterization of the cells by expression profile and functionality differs between studies and is often insufficient, leading to highly variable protocol outcomes. We have synthesized this information into a simple methodology that can be followed when performing or assessing differentiation techniques. Finally we propose three considerations for future research, including the use of physiological O2 conditions, three-dimensional co-culture systems and microfluidics to control feeding cycles and growth factor gradients. Following these guidelines will help researchers to ensure that robust and meaningful data is generated, enabling the full potential of stem cell differentiation for disease modeling and regenerative medicine. PMID:27154043

  8. Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

    OpenAIRE

    Gerlinger, Marco; Quezada, Sergio A; Peggs, Karl S.; Furness, Andrew JS; Fisher, Rosalie; Marafioti, Teresa; Shende, Vishvesh H.; McGranahan, Nicholas; Rowan, Andrew J.; Hazell, Steven; Hamm, David; Robins, Harlan S; Pickering, Lisa; Gore, Martin; Nicol, David L.

    2013-01-01

    The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α- and β-chains (TCRb). Our aim was to assess whether ultra-deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples...

  9. Ultrasonography-guided interstitial brachytherapy using Iridium hairpins for stage I and II squamous cell carcinoma of the mobile tongue

    International Nuclear Information System (INIS)

    Ultrasonography has been introduced in the procedure of implanting Iridium hairpins in interstitial brachytherapy for stage I and II tongue cancer since 2004 to identify the location of the source in and around the tumor. Twenty patients were treated in this manner among 152 patients who were treated between 1994 and 2005. Incidence of both local recurrence and radiation ulcer in each period was examined. Seventeen patients (13%) out of 132 treated until 2003 experienced local recurrence but only 1 patient (5%) among 20 treated after 2004 did so. Especially, all 14 patients with T2 lesion treated after 2004 were controlled. Radiation ulcers occurred in 64 patients (57%) of 132 treated until 2003 and in 9 patients (47%) among 20 treated after 2004. All radiation ulcers except 1 healed within 6 months by conservative care. It was considered that these improvements were obtained by the use of ultrasonography which worked as a useful guide for adjusting the position of the source. (author)

  10. Expert Guide

    DEFF Research Database (Denmark)

    Heiselberg, Per

    that dynamically respond to changes in climate and user demands, the report describes building concepts, design methods and tools that have been tested in theory and practice in buildings around the world. This guide is aimed at designers and consultants and describes the principles of responsive building concepts...

  11. Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound.

    Science.gov (United States)

    Fortin, Pierre-Yves; Lepetit-Coiffé, Matthieu; Genevois, Coralie; Debeissat, Christelle; Quesson, Bruno; Moonen, Chrit T W; Konsman, Jan Pieter; Couillaud, Franck

    2015-09-15

    The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment. PMID:26299614

  12. CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection

    Science.gov (United States)

    Laidlaw, Brian J.; Zhang, Nianzhi; Marshall, Heather D.; Staron, Mathew M.; Guan, Tianxia; Hu, Yinghong; Cauley, Linda S.; Craft, Joe; Kaech, Susan M.

    2014-01-01

    SUMMARY Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4+ T cells are important for the formation of functional lung-resident CD8+ T cells after influenza virus infection. In the absence of CD4+ T cells, CD8+ T cells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8+ T cells to the lung air-ways upon heterosubtypic challenge. CD4+ T cell-derived interferon-γ was necessary for generating lung-resident CD103+ CD8+ Trm CD8 T cells. Furthermore, expression of the transcription factor T-bet was increased in “unhelped” lung Trm cells, and a reduction in T-bet rescued CD103 expression in the absence of CD4+ T cell help. Thus, CD4+ T cell-dependent signals are important to limit expression of T-bet and allow for the development of CD103+ CD8+ Trm cells in the lung airways following respiratory infection. PMID:25308332

  13. Organization of centromeric domains in hepatocyte nuclei: rearrangement associated with de novo activation of the vitellogenin gene family in Xenopus laevis.

    Science.gov (United States)

    Janevski, J; Park, P C; De Boni, U

    1995-04-01

    The existence of a function-dependent, nonrandom organization of chromatin domains within interphase nuclei is supported by evidence which suggests that specific chromatin domains undergo spatial rearrangement under conditions which alter gene expression. Exposure to estrogen of male Xenopus laevis hepatocytes in vitro results in de novo activation of vitellogenin mRNA production and vitellogenin protein synthesis and provides an ideal model to study the association between chromatin organization and changes in gene expression. In a test of the hypothesis that the de novo induction of vitellogenesis in male X. laevis is associated with a spatial rearrangement of specific chromatin domains, centromeric regions were localized by immunofluorescent labeling of associated kinetochore proteins in naive and in estrogen-treated, vitellogenic cells. Analyses by confocal scanning laser microscopy of the three-dimensional spatial distribution of kinetochores in estrogen-treated male hepatocytes showed that a significantly greater proportion of signals was associated with the nuclear periphery than in non-estrogen-treated, naive male cells. In hepatocyte nuclei, quantification of kinetochore signal sizes using image analysis showed that these signals were fewer in number and showed greater variation in size than those of cells in metaphase, with larger signals exhibiting total normalized fluorescence intensities of two, three, four, and five times that associated with kinetochore signals of metaphase cells. These observations are taken to reflect the existence of clustering of kinetochores and, by extension, of centromeres in these cells. In summary, the results show that centromeric domains within interphase nuclei of Xenopus hepatocytes occur as clusters and that these domains undergo spatial rearrangement under conditions which alter the transcriptional state of the cell. PMID:7698222

  14. A Molecular Signature for Purified Definitive Endoderm Guides Differentiation and Isolation of Endoderm from Mouse and Human Embryonic Stem Cells

    OpenAIRE

    Wang, Pei; McKnight, Kristen D.; Wong, David J.; Rodriguez, Ryan T.; Sugiyama, Takuya; Gu, Xueying; Ghodasara, Amar; Qu, Kun; Chang, Howard Y.; Kim, Seung K.

    2012-01-01

    Embryonic definitive endoderm (DE) generates the epithelial compartment of vital organs such as liver, pancreas, and intestine. However, purification of DE in mammals has not been achieved, limiting the molecular “definition” of endoderm, and hindering our understanding of DE development and attempts to produce endoderm from sources such as embryonic stem (ES) cells. Here, we describe purification of mouse DE using fluorescence-activated cell sorting (FACS) and mice harboring a transgene enco...

  15. New, small circular DNA in transfected mammalian cells.

    OpenAIRE

    Wiberg, F C; Sunnerhagen, P; Bjursell, G

    1986-01-01

    Circular DNA isolated by the Hirt procedure from transfected mammalian cells was examined by electron microscopy. Typically, the number of small (1- to 5-kilobase) DNA circles increased about fivefold even though DNA of larger size classes (5 to 15 kilobases) has been transferred. In one case, where extensive rearrangement of the transferred DNA was observed, the rearrangement products were cloned and analyzed. In most cases, however, no rearrangement could be detected, but the amount of smal...

  16. Nanophotothermolysis of multiple scattered cancer cells with carbon nanotubes guided by time-resolved infrared thermal imaging.

    Science.gov (United States)

    Biris, Alexandru S; Boldor, Dorin; Palmer, Jason; Monroe, William T; Mahmood, Meena; Dervishi, Enkeleda; Xu, Yang; Li, Zhongrui; Galanzha, Ekaterina I; Zharov, Vladimir P

    2009-01-01

    Nanophotothermolysis with long laser pulses for treatment of scattered cancer cells and their clusters is introduced with the main focus on real-time monitoring of temperature dynamics inside and around individual cancer cells labeled with carbon nanotubes. This technique utilizes advanced time- and spatially-resolved thermal radiometry imaging for the visualization of laser-induced temperature distribution in multiple-point absorbing targets. The capability of this approach was demonstrated for monitoring of thermal effects under long laser exposure (from millisecond to seconds, wavelength 1,064 nm, maximum power 1 W) of cervical cancer HeLa cells labeled with carbon nanotubes in vitro. The applications are discussed with a focus on the nanophotothermolysis of small tumors, tumor margins, or micrometastases under the guidance of near-IR and microwave radiometry. PMID:19405720

  17. A complex MLL rearrangement identified five years after initial MDS diagnosis results in out-of-frame fusions without progression to acute leukemia.

    Science.gov (United States)

    Meyer, Claus; Kowarz, Eric; Yip, Sze-Fai; Wan, Thomas Shek-Kong; Chan, Tai-Kwong; Dingermann, Theo; Chan, Li-Chong; Marschalek, Rolf

    2011-10-01

    Chromosomal rearrangements of the MLL gene are uncommon in myelodysplastic syndromes (MDSs), and few studies of their molecular structures and oncogenic mechanisms exist. Here, we present a case of de novo MDS with a normal karyotype at initial diagnosis and a mild clinical course. Five years after the initial diagnosis, investigators identified a complex rearrangement of the MLL gene without progression to acute leukemia. The 5' part of the MLL gene is fused out of frame with the LOC100131626 gene, and the 3' part of the MLL gene out of frame with the TCF12 gene. Rapid amplification of complementary DNA 3' ends yielded two main fusion transcripts, which is in concordance with the two described isoforms of the LOC100131626 gene. For both isoform-fusion transcripts, the open reading frame terminates shortly after the breakpoint that is predicted to form two de facto truncated MLL proteins and disrupts the open reading frame of the LOC100131626, TCF12, and UBE4A genes. Neither dimerization nor a transcriptional activation domain, each of which is causally linked to MLL protein-mediated transformation, is present. This and other unusual MLL rearrangements probably represent a subclass of MLL gene abnormalities that have intrinsically no ability or only a weak ability to transform hematopoeitic cells and are identified only in the context of other hematopoetic malignancies. PMID:22137486

  18. Folic Acid-Targeted and Cell Penetrating Peptide-Mediated Theranostic Nanoplatform for High-Efficiency Tri-Modal Imaging-Guided Synergistic Anticancer Phototherapy.

    Science.gov (United States)

    Li, Na; Li, Tingting; Liu, Chen; Ye, Shiyi; Liang, Jiangong; Han, Heyou

    2016-05-01

    A novel nanomaterial with precisely-defined size and shape, biocompatible composition, and excellent stability, which can integrate multi modal targeted imaging and therapy into a single system for visualized therapeutics, has recently attracted significant research interest. Here, we developed a multifunctional nanoplatform based on silica-coated 4-mercaptobenzoic acid-modified gold nanorods (Au NRs) decorated with gold nanoclusters rich in the photosensitizer Ce6 (Au-Ce6 NCs). The nanoparticles also comprised folic acid and cell penetrating peptide molecules anchored on the surface, obtaining the Au@SiO2@Au-cell penetrating peptide nanocomposite. The Au-Ce6 NCs enhanced the photophysical stability, provided numerous bonding sites and offered a large surface-area and interior space to achieve a high drug loading efficiency (up to 55%). The anchored folic acid and cell penetrating peptide synergistically enhanced the efficiency of uptake of nanocomposites by HeLa cells (up to 70.7%) and improved therapeutic efficacy. The nanocomposite also has good water-solubility, excellent biocompatibility, and long-term stability against illumination and exposure to pH 3-12, thus facilitating their bioapplications in cancer theranostics. Here, the nanocomposite was established for high-resolution and noninvasive tri-modal surface-enhanced Raman spectrum/dark-field/fluorescence imaging-guided high-efficiency synergistic photodynamic/photothermal therapy of cancer. Our studies demonstrate that the multifunctional nanocomposite has the potential as a novel and sensitive contrast agent for complementary and synergistic theranostics in the clinic. PMID:27305812

  19. Role of contrast-enhanced ultrasound in evaluating the efficiency of ultrasound guided percutaneous microwave ablation in patients with renal cell carcinoma

    International Nuclear Information System (INIS)

    The aim of the study was to evaluate the efficiency and feasibility of contrast-enhanced ultrasound (CEUS) with Sonovue in assessing of renal cell carcinomas (RCCs) following ultrasound (US)-guided percutaneous microwave ablation (MWA). Seventy-nine patients (60 males and 19 females) with 83 lesions (mean size 3.2±1.6 cm) were treated by US-guided percutaneous MWA. The CEUS results of the third day after the ablation were compared with the synchronous contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) results and biopsy pathological results. The follow-up was performed by CEUS and CT/MRI after 1, 3, 6 months and every 6 months subsequently. The combination of clinical follow-up results and CT/MRI imaging findings was the reference standard of CEUS results for evaluating the therapeutic effect. The identification of residual or recurrence tumour was assessed by two blinded radiologists. On the third day after MWA, CEUS showed 68 of 83 lesions (68/83, 81.9%) successfully ablated and 15 of 83 (18.1%) with residual tumours. Among residual tumours, 13 (86.7%) were confirmed by contrast-enhanced CT/MRI findings and biopsy results. The sensitivity, specificity, accuracy, positive and negative predictive value of CEUS evaluating the short-term MWA effectiveness were 100%, 97.1%, 97.6%, 86.7% and 100%, respectively. During the six years follow-up (median 26 months), the CEUS showed recurrence in 7 patients, and six of them achieved consistent results on CEUS and CT/MRI imaging. The sensitivity, specificity, accuracy, positive and negative predictive value for CEUS evaluating long-term MWA effectiveness were 85.7%, 98.7%, 97.6%, 85.7% and 98.7%, respectively. The post-procedural CEUS demonstrated as an effective and feasible method in evaluating a therapeutic effect of RCCs following MWA

  20. Dose-Guided Radiotherapy: Potential Benefit of Online Dose Recalculation for Stereotactic Lung Irradiation in Patients With Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To determine whether dose-guided radiotherapy (i.e., online recalculation and evaluation of the actual dose distribution) can improve decision making for lung cancer patients treated with stereotactic body radiotherapy. Methods and Materials: For this study 108 cone-beam computed tomography (CBCT) scans of 10 non-small-cell lung cancer patients treated with stereotactic body radiotherapy were analyzed retrospectively. The treatment plans were recalculated on the CBCT scans. The V100% of the internal target volume (ITV) and Dmax of the organs at risk (OARs) were analyzed. Results from the recalculated data were compared with dose estimates for target and OARs by superposition of the originally planned dose distribution on CBCT geometry (i.e., the original dose distribution was assumed to be spatially invariant). Results: Before position correction was applied the V100% of the ITV was 100% in 65% of the cases when an ITV–PTV margin of 5 mm was used and 52% of the cases when a margin of 3 mm was used. After position correction, the difference of Dmax in the OARs with respect to the treatment plan was within 5% in the majority of the cases. When the dose was not recalculated but estimated assuming an invariant dose distribution, clinically relevant errors occurred in both the ITV and the OARs. Conclusion: Dose-guided radiotherapy can be used to determine the actual dose in OARs when the target has moved with respect to the OARs. When the workflow is optimized for speed, it can be used to prevent unnecessary position corrections. Estimating the dose by assuming an invariant dose instead of recalculation of the dose gives clinically relevant errors.

  1. Clinical efficacy of CT-guided 125I radioactive seeds implantation for stage Ⅲ of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical effects of CT-guided 125I radioactive seed implantation in treatment of stage Ⅲ non-small cell lung cancer (NSCLC) and the influential factors of prognosis. Methods: 247 patients of stage Ⅲa/Ⅲb NSCLC underwent CT-guided 125I radioactive seed implantation. The clinical effects and the factors affecting prognosis were analyzed by univariate and multivariate analyses. Results: The 1-, 3-, and 5- year overall survival rates were 82.8%, 23.8%, and 11.5 %, respectively. The median survival time was 24.8 months, and the local control rate was 92.2 %, 63.8%, and 25.7%, respectively. The 5- year overall survival rate was 14.7%, and the median survival time was 29.7 months of the stage Ⅲ, patients. And the 5- year overall survival rate was 11.2%, and the median survival time was 24.0 months at the stage Ⅲb. Univariate analysis showed that age, course of disease, hemoglobin before treatment, clinical stage, maximum diameter of tumor, prescribed dose (PD), post-operational mean dose,post-operational dose covering 100% volume (D100), remedial model were the main prognostic factors; however, multivariate analysis revealed that hemoglobin ≥ 120 g/L before treatment, post-operational dose covering 100% volume (D100) and maximum diameter of tumor were the independent risk factors for predicting the survival. Aerothorax was observed in 37 patients with an incidence rate of 14.9%, and hemothorax was observed in 22 patients with an incidence rate of 9%. Conclusions: 125I radioactive seed implantation therapy is effective in the treatment of stage Ⅲ NSCLC. Hemoglobin level before treatment, post-operational dose covering 100% volume (D100), and maximum diameter of tumor are the main prognostic factors for the NSCLC patients treated with radiotherapy for NSCLC. (authors)

  2. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Horst F Zitzelsberger

    2009-12-01

    Full Text Available Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC, for example, activation of the receptor tyrosine kinase (RTK genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1 by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  3. Aggressive Angiomyxoma with t(12;21) and HMGA2 Rearrangement: Report of a Case and Review of the Literature

    Science.gov (United States)

    Rawlinson, Neil J.; West, William W.; Nelson, Marilu; Bridge, Julia A.

    2008-01-01

    Conventional cytogenetic analysis of an aggressive angiomyxoma of the rectal wall of a 72-year-old female revealed a translocation between the long arms of chromosomes 12 and 21 [46,XX,t(12;21)(q15;q21.1)]. Involvement of the HMGA2 gene locus (12q15) was confirmed by fluorescence in situ hybridization (FISH) using an HMGA2 breakpoint flanking probe set performed on metaphase and interphase cells from an in situ culture of fresh lesional tissue. Karyotypic rearrangements of 12q13-15 are considered recurrent in aggressive angiomyxoma, although reported in only five previous cases. Translocation partner chromosome 21 is novel to the current case. PMID:18295664

  4. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei; Wang, Mei; Weier, Jingly F.; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich G.

    2009-03-09

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  5. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    International Nuclear Information System (INIS)

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations. (authors)

  6. Copy number variation, chromosome rearrangement, and their association with recombination during avian evolution

    Science.gov (United States)

    Völker, Martin; Backström, Niclas; Skinner, Benjamin M.; Langley, Elizabeth J.; Bunzey, Sydney K.; Ellegren, Hans; Griffin, Darren K.

    2010-01-01

    Chromosomal rearrangements and copy number variants (CNVs) play key roles in genome evolution and genetic disease; however, the molecular mechanisms underlying these types of structural genomic variation are not fully understood. The availability of complete genome sequences for two bird species, the chicken and the zebra finch, provides, for the first time, an ideal opportunity to analyze the relationship between structural genomic variation (chromosomal and CNV) and recombination on a genome-wide level. The aims of this study were therefore threefold: (1) to combine bioinformatics, physical mapping to produce comprehensive comparative maps of the genomes of chicken and zebra finch. In so doing, this allowed the identification of evolutionary chromosomal rearrangements distinguishing them. The previously reported interchromosomal conservation of synteny was confirmed, but a larger than expected number of intrachromosomal rearrangements were reported; (2) to hybridize zebra finch genomic DNA to a chicken tiling path microarray and identify CNVs in the zebra finch genome relative to chicken; 32 interspecific CNVs were identified; and (3) to test the hypothesis that there is an association between CNV, chromosomal rearrangements, and recombination by correlating data from (1) and (2) with recombination rate data from a high-resolution genetic linkage map of the zebra finch. We found a highly significant association of both chromosomal rearrangements and CNVs with elevated recombination rates. The results thus provide support for the notion of recombination-based processes playing a major role in avian genome evolution. PMID:20357050

  7. Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

    International Nuclear Information System (INIS)

    During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

  8. Patterns of cellulose microfibril deposition and rearrangement in Nitella: in vivo analysis by a birefringence index. [Nitella axillaris

    Energy Technology Data Exchange (ETDEWEB)

    Richmond, P.A.

    1983-01-01

    The mean alignment of cellulose microfibrils in the wall of a living Nitella internode can be quantified by polarized light microscopy. Microfibrils within the cylindrical wall of a normal internode have a scattered but generally circumferential arrangement. The action of polarized light on such a wall creates a birefringent pattern that relates to microfibrillar organization, including the degree of microfibrillar scatter or mean angular dispersion. This pattern, quantified as a birefringence index (BRI), can be followed during the growth of an individual cell. Changes in the BRI reflect shifts in the patterns of either microfibril deposition, microfibril rearrangements during growth, or both. This diagnostic capability has allowed the dynamics of the following events to be examined in vivo: response of microfibril deposition to addition and removal of antimicrotubule drugs, multinet growth under various conditions of cell expansion, and cellulose synthesis inhibition. This work has shown that cellulose microfibril synthesis is not coupled to cell expansion in Nitella and that the directionality of cell expansion is governed by only an inner portion of the cell wall. 31 references, 7 figures, 1 table.

  9. A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions.

    Directory of Open Access Journals (Sweden)

    Pamela Kanellis

    2007-08-01

    Full Text Available Genome instability is a hallmark of cancer cells. One class of genome aberrations prevalent in tumor cells is termed gross chromosomal rearrangements (GCRs. GCRs comprise chromosome translocations, amplifications, inversions, deletion of whole chromosome arms, and interstitial deletions. Here, we report the results of a genome-wide screen in Saccharomyces cerevisiae aimed at identifying novel suppressors of GCR formation. The most potent novel GCR suppressor identified is BUD16, the gene coding for yeast pyridoxal kinase (Pdxk, a key enzyme in the metabolism of pyridoxal 5' phosphate (PLP, the biologically active form of vitamin B6. We show that Pdxk potently suppresses GCR events by curtailing the appearance of DNA lesions during the cell cycle. We also show that pharmacological inhibition of Pdxk in human cells leads to the production of DSBs and activation of the DNA damage checkpoint. Finally, our evidence suggests that PLP deficiency threatens genome integrity, most likely via its role in dTMP biosynthesis, as Pdxk-deficient cells accumulate uracil in their nuclear DNA and are sensitive to inhibition of ribonucleotide reductase. Since Pdxk links diet to genome stability, our work supports the hypothesis that dietary micronutrients reduce cancer risk by curtailing the accumulation of DNA damage and suggests that micronutrient depletion could be part of a defense mechanism against hyperproliferation.

  10. Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity

    International Nuclear Information System (INIS)

    Nodular ground-glass opacities (nGGO) are a specific type of lung adenocarcinoma. ALK rearrangements and driver mutations such as EGFR and K-ras are frequently found in all types of lung adenocarcinoma. EGFR mutations play a role in the early carcinogenesis of nGGOs, but the role of ALK rearrangement remains unknown. We studied 217 nGGOs resected from 215 lung cancer patients. Pathology, tumor size, tumor disappearance rate, and the EGFR and ALK markers were analyzed. All but one of the resected nGGOs were adenocarcinomas. ALK rearrangements and EGFR mutations were found in 6 (2.8%) and 119 (54.8%) cases. The frequency of ALK rearrangement in nGGO was significantly lower than previously reported in adenocarcinoma. Advanced disease stage (p = 0.018) and larger tumor size (p = 0.037) were more frequent in the ALK rearrangement-positive group than in ALK rearrangement-negative patients. nGGOs with ALK rearrangements were associated with significantly higher pathologic stage and larger maximal and solid diameter in comparison to EGFR-mutated lesions. ALK rearrangement is rare in lung cancer with nGGOs, but is associated with advanced stage and larger tumor size, suggesting its association with aggressive progression of lung adenocarcinoma. ALK rearrangement may not be important in early pathogenesis of nGGO

  11. Comments on the Invariance of Physical Laws Under Particle Re-Arrangement

    CERN Document Server

    Spaans, M

    2007-01-01

    Observationally and experimentally, physical laws express how particles interact. Conversely, physical laws should be invariant under any re-arrangement of those particles, e.g., the laws of gravity do not change if one re-arranges the stars in the sky. To explore the physical meaning of these assertions, arguments are presented that show how the freedom of particle re-arrangement leads to an identical twin associated with any photon. These twins can become spatially separated for astronomically distant objects and are special in that detection of the one causes the disapperance of the other. A tilting detector then leads to brightness variations across an image for twin separations on the order of the detector size.

  12. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

    Directory of Open Access Journals (Sweden)

    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  13. Estimation of kinetics parameters in Beckmann rearrangement of cyclohexanone oxime using genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    WU Jian; LI Zhong; LUO He-an

    2006-01-01

    Beckmann rearrangement mechanism of cyclohexanone oxime, based on the characteristic of self-catalyzed reaction and polymorphism was proposed. According to the suggested mechanism, the basic approach was the rearrangement of OXH+ while the SO3 acts as dehydrating agent and OXSO3 can turn to CPLSO3 ultimately. Considering self-catalyzed reaction between OXSO3 and CPLH+ , kinetic model for Beckmann rearrangement was established. Corresponding parameters were estimated by using float genetic algorithm (GA) and simulation results agree well with the experimental data below -19.3℃. Industrial equipment was simulated and analyzed. Effects of key process parameters such as molar ratio of sulfuric acid to oxime and circulation ratio on the residual oxime are also discussed. The results show that the caprolactam exists as CPLH+ finally in oleum and the minimum molecular ratio of sulfuric acid to oxime can be 0.5 theoretically.

  14. Nanoscopic structural rearrangements of the Cu-filament in conductive-bridge memories

    Science.gov (United States)

    Celano, U.; Giammaria, G.; Goux, L.; Belmonte, A.; Jurczak, M.; Vandervorst, W.

    2016-07-01

    The electrochemical reactions triggering resistive switching in conductive-bridge resistive random access memory (CBRAM) are spatially confined in few tens of nm3. The formation and dissolution of nanoscopic Cu-filaments rely on the displacement of ions in such confined volume, and it is driven by the electric field induced ion migration and nanoscaled redox reactions. The stochastic nature of these fundamental processes leads to a large variability of the device performance. In this work, a combination of two- and three-dimensional scanning probe microscopy (SPM) techniques are used to study the conductive filament (CF) formation, rupture and its nanoscopic structural rearrangements. The high spatial confinement of our approach enables to locally induce RS in a confined area and image it in 3D. A conical shape of the CF is consistently observed, indicating that the ion migration is the rate limiting step in the filament formation when using high quality dielectrics as switching layers. The sub-10 nm electrical contact size of the AFM tip is used to study the filament's dissolution and detect the hopping conduction of Cu during the CF rupture. We consistently observe a tunnel gap formation associated with the tip-induced filament reset. Finally, aiming to match the fundamental understanding with the integrated device operations, we apply scalpel SPM to failed memory cells and directly observe the appearance of filament multiplicity as a major source of failures and variability in CBRAM.The electrochemical reactions triggering resistive switching in conductive-bridge resistive random access memory (CBRAM) are spatially confined in few tens of nm3. The formation and dissolution of nanoscopic Cu-filaments rely on the displacement of ions in such confined volume, and it is driven by the electric field induced ion migration and nanoscaled redox reactions. The stochastic nature of these fundamental processes leads to a large variability of the device performance. In this

  15. Chromosomal Rearrangements as Barriers to Genetic Homogenization between Archaic and Modern Humans.

    Science.gov (United States)

    Rogers, Rebekah L

    2015-12-01

    Chromosomal rearrangements, which shuffle DNA throughout the genome, are an important source of divergence across taxa. Using a paired-end read approach with Illumina sequence data for archaic humans, I identify changes in genome structure that occurred recently in human evolution. Hundreds of rearrangements indicate genomic trafficking between the sex chromosomes and autosomes, raising the possibility of sex-specific changes. Additionally, genes adjacent to genome structure changes in Neanderthals are associated with testis-specific expression, consistent with evolutionary theory that new genes commonly form with expression in the testes. I identify one case of new-gene creation through transposition from the Y chromosome to chromosome 10 that combines the 5'-end of the testis-specific gene Fank1 with previously untranscribed sequence. This new transcript experienced copy number expansion in archaic genomes, indicating rapid genomic change. Among rearrangements identified in Neanderthals, 13% are transposition of selfish genetic elements, whereas 32% appear to be ectopic exchange between repeats. In Denisovan, the pattern is similar but numbers are significantly higher with 18% of rearrangements reflecting transposition and 40% ectopic exchange between distantly related repeats. There is an excess of divergent rearrangements relative to polymorphism in Denisovan, which might result from nonuniform rates of mutation, possibly reflecting a burst of transposable element activity in the lineage that led to Denisovan. Finally, loci containing genome structure changes show diminished rates of introgression from Neanderthals into modern humans, consistent with the hypothesis that rearrangements serve as barriers to gene flow during hybridization. Together, these results suggest that this previously unidentified source of genomic variation has important biological consequences in human evolution. PMID:26399483

  16. Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2010-08-19

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

  17. Application of exterior complex scaling to positron-hydrogencollisions including rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, Philip L.; Stelbovics, Andris T.; Rescigno, Thomas N.; McCurdy, C. William

    2007-12-06

    The first application of an exterior complex scaling method to an atomic scattering problem with distinct rearrangement channels is reported. Calculations are performed for positron-hydrogen collisions in an s-wave model employing an electron-positron potential of V{sub 12} = -(8+(r{sub 1}-r{sub 2}){sup 2}){sup 1/2}, using the time-independent propagating exterior complex scaling (PECS) method. This potential has the correct long-range Coulomb tail of the full problem and the results demonstrate that ECS-based methods can accurately calculate scattering, ionization and positronium formation cross sections in this three-body rearrangement collision.

  18. Experimental observation of local rearrangements in dense quasi-two-dimensional emulsion flow

    Science.gov (United States)

    Chen, Dandan; Desmond, Kenneth W.; Weeks, Eric R.

    2015-06-01

    We experimentally study rearranging regions in slow athermal flow by observing the flow of a concentrated oil-in-water emulsion in a thin chamber with a constricting hopper shape. The gap of the chamber is smaller than the droplet diameters, so that the droplets are compressed into quasi-two-dimensional pancakes. We focus on localized rearrangements known as "T1 events" where four droplets exchange neighbors. Flowing droplets are deformed due to forces from neighboring droplets, and these deformations are decreased by nearby T1 events, with a spatial dependence related to the local structure. We see a tendency of the T1 events to occur in small clusters.

  19. Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

    2007-01-01

    Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid......Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta...

  20. Theory of VVER-1000 fuel rearrangement optimization taking into account both fuel cladding durability and burnup

    International Nuclear Information System (INIS)

    Using the VVER-1000 fuel element (FE) cladding failure estimation method based on creep energy theory (CET-method), it is shown that practically FE cladding rupture life at normal operation conditions can be controlled by an optimal assignment of fuel assembly (FA) rearrangement algorithm. The probabilistic FA rearrangement efficiency criterion based on Monte Carlo Sampling takes into account robust operation conditions and gives results corresponding to the deterministic ones in principle, though the robust efficiency estimation is more conservative. It is proved that CET-method allows us to create an automated complex controlling FE cladding durability in VVER-1000.

  1. Unexpected rearrangements in the synthesis of an unsymmetrical tridentate dianionic N-heterocyclic carbene

    KAUST Repository

    Despagnet-Ayoub, Emmanuelle

    2013-01-01

    Starting from the same ethylenediamine species, three valuable carbene precursors were synthesized under differing conditions: a tridentate dianionic N-heterocyclic carbene bearing an aniline, a phenol and a central dihydroimidazolium salt, its benzimidazolium isomer by intramolecular rearrangement and a dicationic benzimidazolium-benzoxazolium salt by changing the Brønsted acid from HCl to HBF4. A DFT study was performed to understand the rearrangement pathway. The structure of a bis[(NCO)carbene] zirconium complex was determined. © 2013 The Royal Society of Chemistry.

  2. Recurrent chromosomal rearrangements at bands 8q24 and 11q13 in gastric cancer as detected by multicolor spectral karyotyping

    Institute of Scientific and Technical Information of China (English)

    Yasuhide Yamashita; Akio Hagiwara; Hisakazu Yamagishi; Masafumi Taniwaki; Kazuhiro Nishida; Takashi Okuda; Kenichi Nomura; Yosuke Matsumoto; Shoji Mitsufuji; Shigeo Horiike; Hiroyuki Hata; Chohei Sakakura

    2005-01-01

    AIM: To identify chromosomal translocations specific to gastric cancer (GC), spectral karyotyping (SKY) analysis was performed on established cell lines and cancerous ascitic fluids.METHODS: SKY analysis of 10 established cell lines and seven cancerous ascitic fluid samples identified recurrent chromosomal breakpoints and translocations in GC,several of which involved chromosomal loci of oncogenes or tumor suppressor genes.RESULTS: A total of 630 chromosomal breaks were identified. Chromosome no.8 was the most frequently involved in rearrangements (65 breaks), followed by chromosomes no. 11 (53), no. 1 (49), no. 7 (46), no. 13 (37), no. 3 (36), no. 17 (33), and no. 20 (29). Frequent breakpoints were detected in 8q24.1 (30 breaks), 11q13 (29), 13q14 (16), 20q11.2 (14), 7q32 (13), 17q11.2 (13),18q21 (12), 17q23 (9), 18q11.2 (9). SKY analysis identified a total of 242 chromosomal rearrangements including 190 reciprocal and non-reciprocal translocations. The recurrent combinations of chromosomal bands involved in translocations were 8q24.1 and 13q14 (3 cases), 8q24.1 and 11q13 (3), 11q13 and 17q11.2 (2), and 18q11.2 and 20q11.2 (2). Our study validated the ability of SKY to characterize in detail the chromosomal rearrangements in solid tumors and derived cell lines. Moreover,fluorescence in situ hybridization helped to identify the insertions, translocations, and homogeneously staining regions of MYCand CCND1 gene loci.CONCLUSION: The non-random co-localization of certain cytogenetic bands suggests the importance of chromosomal translocations in gastric carcinogenesis, by serving as landmarks for the cloning of GC causing genes.

  3. Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements.

    Directory of Open Access Journals (Sweden)

    Jan Peter Boettcher

    Full Text Available Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp-producing Neisseria gonorrhoeae (P(+GC induces an immediate recruitment of caveolin-1 (Cav1 in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function.

  4. Acidification triggers Andes hantavirus membrane fusion and rearrangement of Gc into a stable post-fusion homotrimer.

    Science.gov (United States)

    Acuña, Rodrigo; Bignon, Eduardo A; Mancini, Roberta; Lozach, Pierre-Yves; Tischler, Nicole D

    2015-11-01

    The hantavirus membrane fusion process is mediated by the Gc envelope glycoprotein from within endosomes. However, little is known about the specific mechanism that triggers Gc fusion activation, and its pre- and post-fusion conformations. We established cell-free in vitro systems to characterize hantavirus fusion activation. Low pH was sufficient to trigger the interaction of virus-like particles with liposomes. This interaction was dependent on a pre-fusion glycoprotein arrangement. Further, low pH induced Gc multimerization changes leading to non-reversible Gc homotrimers. These trimers were resistant to detergent, heat and protease digestion, suggesting characteristics of a stable post-fusion structure. No acid-dependent oligomerization rearrangement was detected for the trypsin-sensitive Gn envelope glycoprotein. Finally, acidification induced fusion of glycoprotein-expressing effector cells with non-susceptible CHO cells. Together, the data provide novel information on the Gc fusion trigger and its non-reversible activation involving lipid interaction, multimerization changes and membrane fusion which ultimately allow hantavirus entry into cells. PMID:26310672

  5. Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Yu Jing

    Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]. The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. METHODS: In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30 years. Overall survival (OS and event-free survival (EFS were analyzed. RESULTS: A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years were enrolled, including those with BCR/ABL transcripts 190 (n = 52, 210 (n = 25, and 230 (n = 2; BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT, and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008, the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012, and also higher than those with TKI salvage administration (P = 0.004. BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each. CONCLUSIONS: The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.

  6. Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review.

    NARCIS (Netherlands)

    Behring, J.; Junker, R.; Walboomers, X.F.; Chessnut, B.; Jansen, J.A.

    2008-01-01

    Collagen barrier membranes are frequently used in both guided tissue regeneration (GTR) and guided bone regeneration (GBR). Collagen used for these devices is available from different species and is often processed to alter the properties of the final product. This is necessary because unprocessed c

  7. Radiation protective nursing intervene of 125I seed implantation in non-small cell lung carcinoma guided by CT

    International Nuclear Information System (INIS)

    Objective: To research radiation protective nursing intervene and important notice of 125I seeds minimally invasive implantation in non-small cell lung carcinoma (NSCLC) by CT. Methods: Under the system of therapy planning system (TPS) and posologic validation, 125I seeds were implanted in 89 cases of NSCLC patients. The consistent radiation protective nursing intervene was used in perioperative period management. The operative successful rate, therapeutic effect and complication rate, therapeutic effect and complication rate was observed. Results: The scientific radiation protective nursing intervene can ensure that the radioactive dose distribution of 125I seed implantation brachytherapy is consistent with the principles of effective and minimally invasive. The operative successful rate was 100%. The local control rate and 1 year survival rate respectively was 97.4% and 92.2%. But the early and later incidence rate of radioactive damaging effect was 14.6% and 1.1% respectively. Leakage of radioactive contamination has not occurred. Conclusion: The consistent TPS and posologic validation 125I seeds implantation integrated scientific radiation protective nursing intervene. It is very important to improve the therapeutic effect of NSCLC and reduce the incidence of complications. (authors)

  8. Complications of image-guided radiofrequency ablation of renal cell carcinoma: causes, imaging features and prevention methods

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo [Sungkyunkwan University School of Medicine, The Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea)

    2009-09-15

    Radiofrequency (RF) ablation is an alternative treatment for renal cell carcinoma (RCC) in patients unable to undergo surgery. Although RF ablation has a low complication rate because of its minimally invasive nature, unintended heat may be conducted by several critical organs during ablation procedures, leading to a variety of complications. Major complications that usually require treatment include bowel injury, ureteral injury, massive bleeding and residual or recurrent tumour. Minor complications that may require only observation include pain, haematoma, haematuria, neuromuscular injury, pneumothorax, infarction and inflammatory tract mass. The most common cause of complications is the tumour's proximity to neighbouring organs. In addition, careless electrode manipulation and the patient's comorbidities may also lead to complications. To avoid many of these complications, the distance between the tumour and neighbouring organs should be widened using methods such as changing the patient's position, using the RF electrode as a lever and hydrodissection. Furthermore, carefully manipulating the RF electrode and assessing the patient's general condition help to prevent complications. In this review, we discuss the complications resulting from RF ablation of RCC with an emphasis on causes, imaging features and prevention methods. (orig.)

  9. Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders;

    2009-01-01

    BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovarian...

  10. Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening

    OpenAIRE

    Lee, Jeeyun; Kim, Hee Cheol; Hong, Jung Yong; Wang, Kai; Kim, Sun Young; Jang, Jiryeon; Kim, Seung Tae; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Lee, Jiyun; Lee, Woo Yong; Park, Yoon Ah; Huh, Jung Wook

    2015-01-01

    Purpose Anaplastic lymphoma kinase (ALK) rearrangement has been detected in colorectal carcinoma (CRC) using advanced molecular diagnostics tests including exon scanning, fluorescence in situ hybridization (FISH), and next generation sequencing (NGS). We investigated if immunohistochemistry (IHC) can be used to detect ALK rearrangement in gastrointestinal malignancies. Experimental designs Tissue microarrays (TMAs) from consecutive gastric carcinoma (GC) and CRC patients who underwent surgica...

  11. Rearrangements during slow compression of a jammed 2D emulsion

    Science.gov (United States)

    Du, Xin; Orellana, Carlos; Hong, Xia; Weeks, Eric

    We experimentally study non-affine motion within an evaporating quasi two-dimensional emulsion system. Our samples are oil-in-water emulsions confined between two close-spaced parallel plates, so that the oil droplets are deformed into pancake shapes. In this system, water slowly evaporates from an open edge of the chamber and, as a consequence, the volume fraction of oil droplets gradually increases. By means of microscopy, we analyzed the motion of droplets and measure the deformation of the droplet's outlines. Based on this information, we calculate the force network and the Voronoi cell when the system approaching jamming state. Using a recently proposed method (J. Rieser et al., arXiv:1509.05496), we calculate the Voronoi cell anisotropy vectors which point from the center of each particle to the corresponding Voronoi cell centroid, and identify void spaces where droplets may be more likely to move toward according to the field of the vectors. These allow us to study the correlations between the force network, the Voronoi vector field, and the non-affine displacements of droplets in our evaporating system.

  12. Chromosomal rearrangements in interspecific hybrids between Nicotiana gossei Domin and N. tabacum L., obtained by crossing with pollen exposed to helium ion beams or gamma-rays

    International Nuclear Information System (INIS)

    It is very difficult to obtain interspecific hybrids between Nicotiana tabacum L. (2n=48) and N. gossei Domin (2n=36), because of strong cross incompatibility. We had already obtained interspecific hybrids between these two species, crossing N. gossei flower with N. tabacum pollen exposed to He ions or gamma-rays. Here, we analyze chromosome constitution of these hybrids by genomic in situ hybridization. In root tip cells of the two hybrids obtained with He ion exposure, most mitotic cells contained 18 chromosomes of N. gossei and 24 chromosomes of N. tabacum. However, in some cells, translocations and insertions between parental genomes were observed. On the other hand, in a hybrid obtained by gamma-ray irradiation, intergenomic rearrangements were not observed, although mitotic cells showed 19 hybridization signals with N. gossei DNA in 41 chromosomes. Such chromosomal changes in structure or constitution may be related to overcoming cross incompatibility between these two species

  13. Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells

    OpenAIRE

    Rong Jian-hui; Li James CB; Chik Stanley CC; Yang Cindy LH; Lee Davy CW; Chan Godfrey CF; Lau Allan SY

    2009-01-01

    Abstract Background Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng's effects remain to be investigated. We hypothesize some biological effects of ginseng are due to its anti-inflammatory effects. Methods Human promonocytic U937 cells were used to investigate the immunomodulatory effects of ginseng following TNF-α treatment. A...

  14. Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

    DEFF Research Database (Denmark)

    Kluth, Martina; Galal, Rami; Krohn, Antje;

    2015-01-01

    Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were...

  15. Isolation of Betulin and Rearrangement to Allobetulin: A Biomimetic Natural Product Synthesis

    Science.gov (United States)

    Green, Brian; Bentley, Michael D.; Chung, Bong Y.; Lynch, Nicholas G.; Jensen, Bruce L.

    2007-01-01

    The triterpenes are a diverse class of widely distributed natural products derived from squalene. Various cyclization and subsequent rearrangement reactions produce many complex structural types. These compounds frequently display a wide divergence of biological properties. For example the pentacyclic triterpene, betulin, is isolated from white…

  16. A proposal for calculating the importance of exchange effects in rearrangement collisions

    International Nuclear Information System (INIS)

    A formalism based on the generator co-ordinate method (GCM) for reactions is derived to test approximations in the most commonly used methods for calculating the rearrangement amplitudes: namely the distorted wave Born approximation (DWBA), the coupled channel Born approximation (CCBA) and the coupled reaction channel (CRC). (author)

  17. Synthesis of cycloheptanoid natural products via tandem 5-exo cyclization/Claisen rearrangement process

    OpenAIRE

    Ovaska, Timo V.

    2010-01-01

    This article describes the development of microwave-assisted oxyanionic 5-exo-dig cyclization-Claisen rearrangement sequence as a convenient “one-pot” route to a variety of seven-membered carbocyclic ring systems. This process was used as the key transformation for the construction of several natural products, including frondosins A, B, and C.

  18. ON THE PECULIARITIES OF THE RING CONTRACTION REACTIONS OF HOMODRIMANES VIA ACID MEDIATED EPOXIDE REARRANGEMENT

    Directory of Open Access Journals (Sweden)

    Veaceslav Kulciţki

    2011-06-01

    Full Text Available A selective rearrangement of a epoxy-homodrimanic substrate is described. Using fluorosulfonic acid at low temperature leads by ring contraction to a perhydrindanic structure. On the contrary, using boron trifluoride-diethyl ether at r.t. selectively brings about angular methyl migration.

  19. Screening for ALK Rearrangements in Lung Cancer: Time for a New Generation of Diagnostics?

    OpenAIRE

    Dagogo-Jack, Ibiayi; Shaw, Alice T.

    2016-01-01

    A study reported in this issue of The Oncologist examined the utility of next-generation sequencing (NGS) in detecting ALK rearrangements. NGS may one day become the standard initial test for molecular genotyping of patients with advanced cancers, and this new generation of ALK diagnostics is a welcome addition to the current screening repertoire.

  20. The rearrangement process in a two-stage broadcast switching network

    DEFF Research Database (Denmark)

    Jacobsen, Søren B.

    1988-01-01

    The rearrangement process in the two-stage broadcast switching network presented by F.K. Hwang and G.W. Richards (ibid., vol.COM-33, no.10, p.1025-1035, Oct. 1985) is considered. By defining a certain function it is possible to calculate an upper bound on the number of connections to be moved...

  1. Brönsted Acid of Keggin Type Polyoxometalate Catalyzed Pinacol Rearrangement

    Directory of Open Access Journals (Sweden)

    Aldes Lesbani

    2014-07-01

    Full Text Available Keggin type polyoxometalates K4[a-SiW12O40] was synthesized and transformed to H4[a-SiW12O40]. Both catalysts have been used for pinacol rearrangement in toluene at 373 oK. The results showed that reaction of pinacol rearrangement did not proceed using K4[a-SiW12O40] as catalyst. The extent reac-tion time until 20 h also did not produce pinacolone as main product. By using H4[a-SiW12O40] as cata-lyst at 1 h reaction time gave conversion 100% with formation of pinacolone 72%. The reaction produce 27% of 2,3-dimethyl-1,3-butadiene as byproduct and 99% carbon balance for the reaction. This phe-nomenon indicated the Brönsted acid is a key role for catalytic reaction of pinacol rearrangement to pinacolone. © 2014 BCREC UNDIP. All rightsSubmitted: 21st January 2014; Revised: 21st April 2014; Accepted: 3rd May 2014[ How to Cite: Lesbani, A., Mohadi, R., (2014. Brönsted Acid of Keggin Type Polyoxometalate Catalyzed Pinacol Rearrangement. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (2: 136-141. (doi:10.9767/bcrec.9.2.6074.136-141 ][ Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.2.6074.136-141

  2. Cross sections for particle-rearrangement in ion-molecule collisions. 1. Hydrogen and helium species

    Energy Technology Data Exchange (ETDEWEB)

    Ichihara, Akira; Sataka, Masao; Shirai, Toshizo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Hayakawa, Shigeo

    1994-11-01

    Experimental cross sections for particle-rearrangement in the ion-molecule collisions between primary plasma constituents have been collected for edge plasma studies. Total and partial cross sections are compiled in graphical forms. Brief comments on the cross-section measurements are given for each reaction. The literature has been surveyed through March 1994. (author).

  3. Cross sections for particle-rearrangement in ion-molecule collisions. 1. Hydrogen and helium species

    International Nuclear Information System (INIS)

    Experimental cross sections for particle-rearrangement in the ion-molecule collisions between primary plasma constituents have been collected for edge plasma studies. Total and partial cross sections are compiled in graphical forms. Brief comments on the cross-section measurements are given for each reaction. The literature has been surveyed through March 1994. (author)

  4. Submicrosecond rearrangeable nonblocking silicon-on-insulator thermo-optic 4x4 switch matrix.

    Science.gov (United States)

    Li, Yuntao; Yu, Jinzhong; Chen, Shaowu; Li, Yanping; Chen, Yuanyuan

    2007-03-15

    A rearrangeable nonblocking silicon-on-insulator-based thermo-optic 4x4 switch matrix is designed and fabricated. A spot-size converter is integrated to reduce the insertion loss, and a new driving circuit is designed to improve the response speed. The insertion loss is less than 10 dB, and the response time is 950 ns. PMID:17308574

  5. Dynamic surface rearrangement and thermal stability of nitrogen functional groups on carbon nanotubes

    OpenAIRE

    R. Arrigo; Hävecker, M.; Schlögl, R.; Su, D.

    2008-01-01

    Dynamic surface rearrangement and thermal stability of N-functional groups on carbon nanotubes (CNTs), obtained by functionalization of pristine CNTs with NH3, were studied by temperature-programmed XPS and MS: a link between the stability of the functional group and decomposition temperature have been established and a conversion into graphitic nitrogen was observed.

  6. Synthesis of N-protected Galactosamine Building Blocks from D-Tagatose via the Heyns Rearrangement

    DEFF Research Database (Denmark)

    Wrodnigg, Tanja M.; Lundt, Inge; Stütz, Arnold E.

    2006-01-01

    N-Acetyl-D-galactosamine (11), a very important naturally occurring building block of oligosaccharides, is easily accessible via the Heyns rearrangement of D-tagatose (3) with benzylamine. The short and efficient synthesis of various differently N-protected D-galactosamine derivatives is reported....

  7. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    DEFF Research Database (Denmark)

    Andersson, Anna K; Ma, Jing; Wang, Jianmin;

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  8. Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

    DEFF Research Database (Denmark)

    Buysse, Karen; Crepel, An; Menten, Björn;

    2008-01-01

    BACKGROUND: Recent molecular studies of breakpoints of recurrent chromosome rearrangements revealed the role of genomic architecture in their formation. In particular, segmental duplications representing blocks of >1 kb with >90% sequence homology were shown to mediate non-allelic homologous reco...

  9. A DFT exploration of the enantioselective rearrangement of cyclohexene oxide to cyclohexenol

    DEFF Research Database (Denmark)

    Brandt, Peter; Norrby, Per-Ola; Andersson, Pher G.

    2003-01-01

    In this paper, we present computational results for the (1S,3R,4R)-3-(pyrrolidinyl)-methyl-2-azabicyclo[2.2.1]heptane mediated rearrangement of cyclohexene oxide. The results nicely explain the differences in enantioselectivities between catalytic and stoichiometric mode between different ligands...

  10. Cycloaddition-Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones.

    Science.gov (United States)

    Padwa, Albert; Brodney, Michael A.; Satake, Kyosuke; Straub, Christopher S.

    1999-06-25

    A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels-Alder cycloaddition (IMDAF) reaction of 2-amido substituted furans. The initially formed [4 + 2] cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The reaction rate and product yield were found to be markedly dependent upon the electronic properties of the alkenyl pi-bond. 2-[2-(tert-Butoxycarbonylfuran-2-yl-amino)ethyl]acrylic acid methyl ester was synthesized from 3-chlorocarbonyl-but-3-enoic acid methyl ester. Thermolysis of the carbomethoxy activated furanamide occurred at 80 degrees C to produce a rearranged hexahydroindolinone. When Me(3)Al or (MeO)(3)Al was used as a Lewis acid to promote the cycloaddition, a rearranged alcohol was obtained. The initially formed [4 + 2] cycloadduct undergoes ring opening in the presence of the Lewis acid, and the resulting aluminum intermediate delivers the substituent group from the same face as the neighboring oxygen to ultimately furnish a rearranged cis-alcohol. In contrast to this result, a mixture of diastereomeric methoxy alcohols was isolated when the IMDAF cycloaddition was carried out in methanol. The major isomer corresponds to the trans-diastereomer that results from trapping of the iminium ion from the less crowded face of the pi-bond. PMID:11674531

  11. Structure of Salvioccidentalin, a Diterpenoid with a Rearranged neo-Clerodane Skeleton from Salvia occidentalis

    Directory of Open Access Journals (Sweden)

    Jorge Cárdenas

    2011-10-01

    Full Text Available From the aerial parts of Salvia occidentalis (Labiatae a new diterpenoid with a rearranged neo-clerodane skeleton was isolated. This new compound was named salvioccidentalin and its structure was established by spectroscopic means. A probable biogenetic relationship with salvigenolide from S. fulgens and salvileucalin A and spiroleucantholide from Salvia leucantha is proposed.

  12. Structure of Salvioccidentalin, a Diterpenoid with a Rearranged neo-Clerodane Skeleton from Salvia occidentalis

    OpenAIRE

    Jorge Cárdenas; José Antonio Morales-Serna; Bernardo Antonio Frontana-Uribe; Manuel Salmón; Miguel Ángel Jaime-Vasconcelos

    2011-01-01

    From the aerial parts of Salvia occidentalis (Labiatae) a new diterpenoid with a rearranged neo-clerodane skeleton was isolated. This new compound was named salvioccidentalin and its structure was established by spectroscopic means. A probable biogenetic relationship with salvigenolide from S. fulgens and salvileucalin A and spiroleucantholide from Salvia leucantha is proposed.

  13. Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, J.Y.; Zheng, J.; Chen, X.; Zhou, J.Y. [Zhejiang University, Department of Respiratory Disease, Thoracic Disease Center, First Affiliated Hospital, College of Medicine, Hangzhou (China); Yu, Z.F.; Xiao, W.B.; Jiang, L.N. [Zhejiang University, Department of Radiology, First Affiliated Hospital, College of Medicine, Hangzhou (China); Zhao, J.; Sun, K.; Wang, B.; Ding, W. [Zhejiang University, Department of Pathology, First Affiliated Hospital, College of Medicine, Hangzhou (China)

    2015-05-01

    To compare the clinicoradiologic features of tumours with echinoderm anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, or wild type (WT) for both genes in a cohort of patients with lung adenocarcinoma to identify useful characteristics of different gene statuses. In 346 lung adenocarcinoma patients, ALK rearrangements were confirmed with fluorescence in situ hybridisation, and EGFR mutations were determined by pyrosequencing assay. Patients were divided into three groups: ALK rearrangement (ALK+ group, n = 48), EGFR mutation (EGFR+ group, n = 166), and WT for both genes (WT group, n = 132). Chest computed tomography (CT) examinations were performed in all patients. The percentages of ground-glass opacity volume (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi-automated nodule assessment software. The pGGO was significantly lower in the ALK+ group (25.1 % ± 24.3) than in the EGFR+ group (37.2 % ± 25.7, p < 0.001) and the WT group (36.1 % ± 24.6, p = 0.001). The TDR in the ALK+ group (17.3 % ± 25.1) was significantly lower than in the EGFR+ group (26.8 % ± 24.9, p = 0.002) and the WT group (25.7 % ± 24.6, p = 0.003). Solid pattern with lower incidence of lobulated border, finely spiculated margins, pleural retraction, and bubble-like lucency on CT imaging are the main characteristics of ALK rearrangement tumours. (orig.)

  14. Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

    Directory of Open Access Journals (Sweden)

    Bernhard Westermann

    2011-04-01

    Full Text Available Enantiomerically highly enriched unsaturated β-ketoesters bearing a quaternary stereocenter can be utilized as building blocks for the synthesis of natural occurring terpenes, i. a., trisporic acid and its derivatives. An advanced building block has been synthesized in a short reaction sequence, which involves an oxidative allylic rearrangement initiated by pyridinium dichromate (PDC as the key step.

  15. Total Synthesis of (±)-Strychnine via a [4+2]-Cycloaddition/Rearrangement Cascade

    OpenAIRE

    Zhang, Hongjun; Boonsombat, Jutatip; Padwa, Albert

    2007-01-01

    A new strategy for the synthesis of the Strychnos alkaloid (±)-strychnine has been developed and is based on an intramolecular [4+2]-cycloaddition/rearrangement cascade of an indolyl substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide.

  16. Design of Intelligent Cloud Guide System

    Directory of Open Access Journals (Sweden)

    Jintao Jiao

    2013-01-01

    Full Text Available In order to deliver accurate services to tourists’ phone, intelligent guide system based on the Android platform solution is proposed. First describes the system architecture, including cloud service center, sensor networks and cell phone; then describes the function of each tier; last proposed the three-tier implementation. The testing results show that the system can provide better guide service.

  17. Generation of genetically stable recombinant rotaviruses containing novel genome rearrangements and heterologous sequences by reverse genetics.

    Science.gov (United States)

    Navarro, Aitor; Trask, Shane D; Patton, John T

    2013-06-01

    The rotavirus (RV) genome consists of 11 segments of double-stranded RNA (dsRNA). Typically, each segment contains 5' and 3' untranslated regions (UTRs) that flank an open reading frame (ORF) encoding a single protein. RV variants with segments of atypical size owing to sequence rearrangements have been described. In many cases, the rearrangement originates from a partial head-to-tail sequence duplication that initiates after the stop codon of the ORF, leaving the protein product of the segment unaffected. To probe the limits of the RV genome to accommodate additional genetic sequence, we used reverse genetics to insert duplications (analogous to synthetic rearrangements) and heterologous sequences into the 3' UTR of the segment encoding NSP2 (gene 8). The approach allowed the recovery of recombinant RVs that contained sequence duplications (up to 200 bp) and heterologous sequences, including those for FLAG, the hepatitis C virus E2 epitope, and the internal ribosome entry site of cricket paralysis virus. The recombinant RVs grew to high titer (>10(7) PFU/ml) and remained genetically stable during serial passage. Despite their longer 3' UTRs, rearranged RNAs of recombinant RVs expressed wild-type levels of protein in vivo. Competitive growth experiments indicated that, unlike RV segments with naturally occurring sequence duplications, genetically engineered segments were less efficiently packaged into progeny viruses. Thus, features of naturally occurring rearranged segments, other than their increased length, contribute to their enhanced packaging phenotype. Our results define strategies for developing recombinant RVs as expression vectors, potentially leading to next-generation RV vaccines that induce protection against other infectious agents. PMID:23536662

  18. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Tsien, F.; Shapira, E. [Tulane Univ. School of Medicine, New Orleans, LA (United States); Carvalho, T. [Hospital Sarah Kubitschek, Brasilia (Brazil)] [and others

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  19. Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells

    Directory of Open Access Journals (Sweden)

    Rong Jian-hui

    2009-05-01

    Full Text Available Abstract Background Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng's effects remain to be investigated. We hypothesize some biological effects of ginseng are due to its anti-inflammatory effects. Methods Human promonocytic U937 cells were used to investigate the immunomodulatory effects of ginseng following TNF-α treatment. A global gene expression profile was obtained by using genechip analysis, and specific cytokine expression was measured by quantitative RT-PCR and ELISA. HPLC was used to define the composition of ginsenosides in 70% ethanol-water extracts of ginseng. Activation of signalling kinases was examined by Western blot analysis. Results Seventy percent ethanol-water extracts of ginseng significantly inhibited the transcription and secretion of CXCL-10 following TNF-α stimulation. Nine ginsenosides including Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3 and Rh1 were identified in our extract by HPLC. Seven out of nine ginsenosides could significantly inhibit TNF-α-induced CXCL-10 expression in U937 cells and give comparable inhibition of CXCL-10 transcription to those with the extract. However, the CXCL-10 suppressive effect of individual ginsenosides was less than that of the crude extract or the mixture of ginsenosides. The CXCL-10 suppression can be correlated with the inactivation of ERK1/2 pathways by ginseng. Conclusion We showed ginseng suppressed part of the TNF-α-inducible cytokines and signalling proteins in promonocytic cells, suggesting that it exerts its anti-inflammatory property targeting at different levels of TNF-α activity. The anti-inflammatory role of ginseng may be due to the combined effects of ginsenosides, contributing in part to the diverse actions of ginseng in humans.

  20. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    International Nuclear Information System (INIS)

    Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated. After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option

  1. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    Directory of Open Access Journals (Sweden)

    Zhu Jun

    2013-01-01

    Full Text Available Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER at a willingness-to-pay (WTP threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP was evaluated. Results After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP. The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. Conclusions These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

  2. Large Genomic Rearrangements of BRCA1 and BRCA2 among Patients Referred for Genetic Analysis in Galicia (NW Spain): Delimitation and Mechanism of Three Novel BRCA1 Rearrangements

    OpenAIRE

    Fachal, Laura; Blanco, Ana; Santamariña, Marta; Carracedo, Angel; Vega, Ana

    2014-01-01

    In the Iberian Peninsula, which includes mainly Spain and Portugal, large genomic rearrangements (LGRs) of BRCA1 and BRCA2 have respectively been found in up to 2.33% and 8.4% of families with hereditary breast and/or ovarian cancer (HBOC) that lack point mutations and small indels. In Galicia (Northwest Spain), the spectrum and frequency of BRCA1/BRCA2 point mutations differs from the rest of the Iberian populations. However, to date there are no Galician frequency reports of BRCA1/BRCA2 LGR...

  3. REARRANGEMENT IN THE B-GENOME FROM DIPLOID PROGENITOR TO WHEAT ALLOPOLYPOLID

    Directory of Open Access Journals (Sweden)

    Salina E.A.

    2012-08-01

    Full Text Available Three key periods that were accompanied by considerable rearrangements in the B genome of wheat and its progenitor can be considered. The first period covers the period from the divergence of diploid Triticum and Aegilops species from their common progenitor (2.5–6 million years ago to formation of the tetraploid T. diccocoides (about 500 thousand years ago. Significant genomic rearrangements in the diploid progenitor of the B genome, Ae. speltoides (SS genome, involved a considerable amplification of repeated DNA sequences, which led to an increase in the number of heterochromatin blocks on chromosomes relative to other diploid Aegilops and Triticum species. Our analysis has demonstrated that during this period the Spelt1 repeats intensively amplified as well as several mobile elements proliferated, in particular, the genome-specific gypsy LTR-retrotransposon Fatima and CACTA DNA-transposon Caspar. The second period in the B-genome evolution was associated with the emergence of tetraploid (BBAA genome and its subsequent evolution. The third most important event leading to the next rearrangement of the B genome took place relatively recently, 7000–9500 years ago, being associated with the emergence of hexaploid wheat with the genomic formula BBAADD. The evolution of the B/S genome involved intergenomic and intragenomic translocations and chromosome inversions. So far, five rearrangements in the B-genome chromosomes of polyploid wheats has been observed and described; the majority of them took place during the formation and evolution of tetraploid species. The mapping of the S-genome chromosomes and comparison with the B-genome chromosome maps have demonstrated that individual rearrangements pre-existed in Ae. speltoides; moreover, Ae. speltoides is polymorphic for these rearrangements.Chromosome 5B is nearly 870 Mbp (5BL = 580 Mbp and 5BS = 290 Mbp and is known to carry important genes controlling the key aspects of wheat biology, in

  4. Human age estimation from blood using mRNA, DNA methylation, DNA rearrangement, and telomere length.

    Science.gov (United States)

    Zubakov, Dmitry; Liu, Fan; Kokmeijer, Iris; Choi, Ying; van Meurs, Joyce B J; van IJcken, Wilfred F J; Uitterlinden, André G; Hofman, Albert; Broer, Linda; van Duijn, Cornelia M; Lewin, Jörn; Kayser, Manfred

    2016-09-01

    Establishing the age of unknown persons, or persons with unknown age, can provide important leads in police investigations, disaster victim identification, fraud cases, and in other legal affairs. Previous methods mostly relied on morphological features available from teeth or skeletal parts. The development of molecular methods for age estimation allowing to use human specimens that possess no morphological age information, such as bloodstains, is extremely valuable as this type of samples is commonly found at crime scenes. Recently, we introduced a DNA-based approach for human age estimation from blood based on the quantification of T-cell specific DNA rearrangements (sjTRECs), which achieves accurate assignment of blood DNA samples to one of four 20-year-interval age categories. Aiming at improving the accuracy of molecular age estimation from blood, we investigated different types of biomarkers. We started out by systematic genome-wide surveys for new age-informative mRNA and DNA methylation markers in blood from the same young and old individuals using microarray technologies. The obtained candidate markers were validated in independent samples covering a wide age range using alternative technologies together with previously proposed DNA methylation, sjTREC, and telomere length markers. Cross-validated multiple regression analysis was applied for estimating and validating the age predictive power of various sets of biomarkers within and across different marker types. We found that DNA methylation markers outperformed mRNA, sjTREC, and telomere length in age predictive power. The best performing model included 8 DNA methylation markers derived from 3 CpG islands reaching a high level of accuracy (cross-validated R(2)=0.88, SE±6.97 years, mean absolute deviation 5.07 years). However, our data also suggest that mRNA markers can provide independent age information: a model using a combined set of 5 DNA methylation markers and one mRNA marker could provide

  5. A method for VVER-1000 fuel rearrangement optimization taking into account both fuel cladding durability and burnup

    Energy Technology Data Exchange (ETDEWEB)

    Pelykh, S.N., E-mail: 1@pelykh.net [Odessa National Polytechnic University, Shevchenko av., 1, Odessa 65044 (Ukraine); Maksimov, M.V. [Odessa National Polytechnic University, Shevchenko av., 1, Odessa 65044 (Ukraine); Parks, G.T. [University of Cambridge, Engineering Department, Trumpington str., Cambridge, CB2 1PZ (United Kingdom)

    2013-04-15

    Highlights: ► Fuel cladding life and burnup determine fuel rearrangement optimization. ► The proposed rearrangement optimization criterion is universal. ► Robust optimization conservatively confirms the outcome of deterministic optimization. ► Robust optimization reveals the trade-off between mean performance and consistency of performance in the face of uncertainties in operational conditions. -- Abstract: A method for VVER-1000 fuel rearrangement optimization that takes into account both cladding durability and fuel burnup and which is suitable for any regime of normal reactor operation has been established. The main stages involved in solving the problem of fuel rearrangement optimization are discussed in detail. Using the proposed fuel rearrangement efficiency criterion, a simple example VVER-1000 fuel rearrangement optimization problem is solved under deterministic and uncertain conditions. It is shown that the deterministic and robust (in the face of uncertainty) solutions of the rearrangement optimization problem are similar in principle, but the robust solution is, as might be anticipated, more conservative.

  6. A method for VVER-1000 fuel rearrangement optimization taking into account both fuel cladding durability and burnup

    International Nuclear Information System (INIS)

    Highlights: ► Fuel cladding life and burnup determine fuel rearrangement optimization. ► The proposed rearrangement optimization criterion is universal. ► Robust optimization conservatively confirms the outcome of deterministic optimization. ► Robust optimization reveals the trade-off between mean performance and consistency of performance in the face of uncertainties in operational conditions. -- Abstract: A method for VVER-1000 fuel rearrangement optimization that takes into account both cladding durability and fuel burnup and which is suitable for any regime of normal reactor operation has been established. The main stages involved in solving the problem of fuel rearrangement optimization are discussed in detail. Using the proposed fuel rearrangement efficiency criterion, a simple example VVER-1000 fuel rearrangement optimization problem is solved under deterministic and uncertain conditions. It is shown that the deterministic and robust (in the face of uncertainty) solutions of the rearrangement optimization problem are similar in principle, but the robust solution is, as might be anticipated, more conservative

  7. Towards a Catalytic Asymmetric Cope Rearrangement and the Synthesis and Self-Assembly of Metal-Coordinated Hosts

    OpenAIRE

    Moehlig, Melissa Padilla

    2013-01-01

    The Cope rearrangement has been used as the key step of several natural products but to date there is only one limited example in the literature that is capable of performing an asymmetric variant of this reaction. The first half of this dissertation focuses on our efforts towards performing a catalytic asymmetric Cope rearrangement to access remote stereocenters. The rearrangement of 2-formyl-1,5-dienes was achieved with both Brønsted and Lewis acid catalysts. The best Lewis acid catalyst wa...

  8. An aniline dication-like transition state in the Bamberger rearrangement

    Directory of Open Access Journals (Sweden)

    Shinichi Yamabe

    2013-06-01

    Full Text Available A Bamberger rearrangement of N-phenylhydroxylamine, Ph–N(OHH, to p-aminophenol was investigated by DFT calculations for the first time. The nitrenium ion, C6H5–NH+, suggested and seemingly established as an intermediate was calculated to be absent owing to the high nucleophilicity of the water cluster around it. First, a reaction of the monoprotonated system, Ph–N(OHH + H3O+(H2On (n = 4 and 14 was examined. However, the rate-determining transition states involving proton transfers were calculated to have much larger activation energies than the experimental one. Second, a reaction of the diprotonated system, Ph–N(OHH + (H3O+2(H2O13, was traced. An activation energy similar to the experimental one was obtained. A new mechanism of the rearrangement including the aniline dication-like transition state was proposed.

  9. Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled `Nanozyme

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Courntey J.; Fiedler, Dorothea; Bergman, Robert G.; Raymond, Kenneth N.

    2008-02-27

    The tetrahedral [Ga{sub 4}L{sub 6}]{sup 12-} assembly (L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) encapsulates a variety of cations, including propargyl enammonium cations capable of undergoing the aza Cope rearrangement. For propargyl enammonium substrates that are encapsulated in the [Ga{sub 4}L{sub 6}]{sup 12-} assembly, rate accelerations of up to 184 are observed when compared to the background reaction. After rearrangement, the product iminium ion is released into solution and hydrolyzed allowing for catalytic turnover. The activation parameters for the catalyzed and uncatalyzed reaction were determined, revealing that a lowered entropy of activation is responsible for the observed rate enhancements. The catalyzed reaction exhibits saturation kinetics; the rate data obey the Michaelis-Menten model of enzyme kinetics, and competitive inhibition using a non-reactive guest has been demonstrated.

  10. Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

    Directory of Open Access Journals (Sweden)

    Maroš Bella

    2014-08-01

    Full Text Available The Grignard reaction of 2,3-O-isopropylidene-α-D-lyxo-pentodialdo-1,4-furanoside and benzylmagnesium chloride (or bromide afforded a non-separable mixture of diastereomeric benzyl carbinols and diastereomeric o-tolyl carbinols. The latter resulted from an unexpected benzyl to o-tolyl rearrangement. The proportion of benzyl versus o-tolyl derivatives depended on the reaction conditions. Benzylmagnesium chloride afforded predominantly o-tolyl carbinols while the application of benzylmagnesium bromide led preferably to the o-tolyl carbinols only when used in excess or at higher temperatures. The structures of the benzyl and o-tolyl derivatives were confirmed unambiguously by NMR spectral data and X-ray crystallographic analysis of their 5-ketone analogues obtained by oxidation of the corresponding mixture of diastereomeric carbinols. A possible mechanism for the Grignard reaction leading to the benzyl→o-tolyl rearrangement is also proposed.

  11. Complex distal 10q rearrangement in a girl with mild intellectual disability

    DEFF Research Database (Denmark)

    Sarri, Catherine; Douzgou, Sofia; Gyftodimou, Yolanda;

    2011-01-01

    several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q......We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites....... By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region...

  12. Dynamic force measurement of rearrangements in a 2D network of droplets

    Science.gov (United States)

    Barkley, Solomon; Backholm, Matilda; Dalnoki-Veress, Kari

    2015-03-01

    The interaction between two liquid droplets in an immiscible liquid is well understood. However, the emulsions relevant to biological and industrial processes involve high concentrations of these droplets, and multi-body effects cannot be ignored. As droplets rearrange in response to a disturbance, the importance of individual pair-wise interactions between droplets changes with the geometry of neighbours. Here we report on an experimental setup consisting of a two- dimensional network of monodisperse droplets stabilized with a surfactant. The system is studied with micropipette deflection, which permits direct measurement of forces along with simultaneous imaging of the droplet network. One micropipette is used to apply a tensile or compressive force to the droplet cluster, while a second pipette acts as a force-transducing cantilever, deflecting in response to rearrangements of the droplets.

  13. Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia.

    Science.gov (United States)

    Iaccarino, Licia; Ottone, Tiziana; Divona, Mariadomenica; Cicconi, Laura; Cairoli, Roberto; Voso, Maria Teresa; Lo-Coco, Francesco

    2016-03-01

    Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance. PMID:26728337

  14. Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement.

    Science.gov (United States)

    David, Nadège; Pasceri, Raffaele; Kitson, Russell R A; Pradal, Alexandre; Moody, Christopher J

    2016-07-25

    A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A. PMID:27346186

  15. Preparation of C14-labelled tetrazolium salts and tracer study of the tetrazene-formazan rearrangement

    International Nuclear Information System (INIS)

    The preparation of [5-C14]-TTC, [5, 5'-di-C14]NT (neotetrazolium) and [5, 5'-di-C14]-BT (tetrazolium blue) starting from benzaldehyde- [1-C14] has been accomplished. The yields for both mono- and ditetrazolium salts are high, and the products can be obtained with high sp. activity. The purity of the samples was investigated by paper chromatography. In the case of ditetrazolium salts some impurities could be detected and conclusions drawn as to their structure and quantity. A method has been developed to prepare C14- labelled ditetrazolium salts of high purity. The formation of the formazan, the precursor of the tetrazolium salt, goes through an unstable intermediate of tetrazene-type structure which rearranges rapidly in basic medium, to yield the formazan. The tetrazene intermediate can be isolated under suitable conditions. By using C14-labelled benzaldehyde phenylhydrazone this rearrangement was investigated and a verification of its intramolecular character given. (author)

  16. Oxygen vacancy defects in Ta2O5 showing long-range atomic re-arrangements

    Science.gov (United States)

    Guo, Yuzheng; Robertson, John

    2014-03-01

    The structure, formation energy, and energy levels of the various oxygen vacancies in Ta2O5 have been calculated using the λ phase model. The intra-layer vacancies give rise to unusual, long-range bonding rearrangements, which are different for each defect charge state. The 2-fold coordinated intra-layer vacancy is the lowest cost vacancy and forms a deep level 1.5 eV below the conduction band edge. The 3-fold intra-layer vacancy and the 2-fold inter-layer vacancy are higher cost defects, and form shallower levels. The unusual bonding rearrangements lead to low oxygen migration barriers, which are useful for resistive random access memory applications.

  17. Divergent Gold(I)-Catalyzed Skeletal Rearrangements of 1,7-Enynes.

    Science.gov (United States)

    Meiß, Rebecca; Kumar, Kamal; Waldmann, Herbert

    2015-09-21

    The gold(I) complex catalyzed cycloisomerization and skeletal rearrangement of 1,n-enynes (n=5-7) is a powerful methodology for the efficient synthesis of complex molecular architectures. In contrast to 1,6-enynes, readily accessible homologous 1,7-enynes are largely unexplored in such transformations. Here, the divergent skeletal rearrangement of all-carbon 1,7-enynes by catalysis with a cationic gold(I) complex is reported. Depending on electronic and steric factors, differently substituted 1,7-enynes react via different carbocations formed from a common gold carbene intermediate to yield on the one hand novel exocyclic allenes and on the other hand tricyclic hexahydro-anthracenes through a novel dehydrogenative Diels-Alder reaction. PMID:26356499

  18. A symplectic rearrangement of the four dimensional non-geometric scalar potential

    CERN Document Server

    Shukla, Pramod

    2015-01-01

    We present a symplectic rearrangement of the effective four-dimensional non-geometric scalar potential resulting from the type IIB superstring compactification on Calabi Yau orientifolds. The strategy has two main steps. In the first step, we rewrite the four dimensional scalar potential utilizing some interesting flux combinations which we call {\\it new generalized flux orbits}. After invoking a couple of non-trivial symplectic relations, in the second step, we further rearrange all the pieces of scalar potential into a completely `symplectic-formulation' which involves only the symplectic ingredients (such as period matrix etc.) without the need of knowing Calabi Yau metric. Moreover, the scalar potential under consideration is induced by a generic tree level K\\"{a}hler potential and (non-geometric) flux superpotential for arbitrary numbers of complex structure moduli, K\\"ahler moduli and odd-axions. Finally, we exemplify our symplectic formulation for the two well known toroidal examples based on type IIB ...

  19. Hapmnioides A-C, Rearranged Labdane-Type Diterpenoids from the Chinese Liverwort Haplomitrium mnioides.

    Science.gov (United States)

    Zhou, Jinchuan; Zhang, Jiaozhen; Li, Ruijuan; Liu, Jun; Fan, Peihong; Li, Yi; Ji, Mei; Dong, Yiwen; Yuan, Huiqing; Lou, Hongxiang

    2016-09-01

    Many exceptional labdane-type diterpenoids have been exclusively found in liverworts, which serve as taxonomic molecules or play important ecological roles in interactions among organisms. Three unprecedented labdane-type diterpenoids hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the Chinese liverwort Haplomitrium mnioides are reported. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction, and their anti-inflammatory activities were also preliminarily tested. PMID:27513610

  20. The constitutional t(11;22): implications for a novel mechanism responsible for gross chromosomal rearrangements

    OpenAIRE

    Kurahashi, H; Inagaki, H; Ohye, T; Kogo, H.; Tsutsumi, M.; Kato, T.; Tong, M.; Emanuel, BS

    2010-01-01

    The constitutional t(11;22)(q23;q11) is the most common recurrent non-Robertsonian translocation in humans. The breakpoint sequences of both chromosomes are characterized by several hundred base pairs of palindromic AT-rich repeats (PATRRs). Similar PATRRs have also been identified at the breakpoints of other nonrecurrent translocations, suggesting that PATRR-mediated chromosomal translocation represents one of the universal pathways for gross chromosomal rearrangement in the human genome. We...

  1. A transgenic system for generation of transposon Ac/Ds-induced chromosome rearrangements in rice

    OpenAIRE

    Yu, Chuanhe; Han, FangPu; Zhang, Jianbo; Birchler, James; Peterson, Thomas

    2012-01-01

    The maize Activator (Ac)/Dissociation (Ds) transposable element system has been used in a variety of plants for insertional mutagenesis. Ac/Ds elements can also generate genome rearrangements via alternative transposition reactions which involve the termini of closely linked transposons. Here, we introduced a transgene containing reverse-oriented Ac/Ds termini together with an Ac transposase gene into rice (Oryza sativa ssp. japonica cv. Nipponbare). Among the transgenic progeny, we identifie...

  2. Prenatally diagnosed de novo complex chromosome rearrangements: Two new cases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, C.; Grubs, R.E.; Jewett, T. [and others

    1994-09-01

    Complex chromosome rearrangements (CCR) are rare structural rearrangements involving at least three chromosomes with three or more breakpoints. Although there have been numerous reports of individuals with CCR, most have been ascertained through the presence of multiple congenital anomalies, recurrent pregnancy loss, or infertility. Few cases have been ascertained prenatally. We present two new cases of prenatally ascertained CCR. In the first case, an amniocentesis revealed an apparently balanced de novo rearrangement in which chromosomes 5, 6 and 11 were involved in a three-way translocation: 46,XY,t(6;5)(5;11)(q23;p14.3;q15;p13). The pregnancy was unevenful. Recently, at the age of 9 months, a physical and developmental evaluation were normal but, height, weight, and head circumference were below the 5th percentile. In the second case an amniocentesis revealed an unbalanced de novo rearrangement involving separate translocations and an interstitial deletion: 46,XY,del(6)(q25.3q27),t(3;8)(p13;q21.3),t(6;18)(p11.2;q11.2). A meconium plug was present at birth and at 6 months of age surgery for Hirschsprung`s disease was required. Currently, at 10 months of age, the patient has hypotonia and developmental delay. The paucity of information regarding prenatally diagnosed CCR poses a problem in counseling families. Of the four prenatally diagnosed balanced de novo CCR cases, three had abnormal outcomes. In a review of the literature, approximately 70% of the postnatally ascertained balanced de novo CCR cases were associated with congenital anomalies, growth retardation and/or mental retardation. More information regarding the outcome of prenatally ascertained balanced de novo CCR is required for accurate risk assessment.

  3. Rearrangement of a phosphosilicate glass network induced by the 193-nm radiation

    International Nuclear Information System (INIS)

    The IR absorption and Raman spectra of phosphosilicate glass (PSG) are measured during its exposure to radiation at a wavelength of 193 nm. The obtained data demonstrate the complicated rearrangement dynamics of the glass network around phosphor atoms and of the glass network as a whole. The experimental dependences are explained by the model of the PSG network based on the concepts of the theory of rigidity percolation. (interaction of laser radiation with matter)

  4. BRCA sequencing and large rearrangement testing in young Black women with breast cancer

    OpenAIRE

    Pal, Tuya; Bonner, Devon; Cragun, Deborah; Johnson, Sharland; Akbari, Mohammad; Servais, Lily; Narod, Steven; Vadaparampil, Susan

    2013-01-01

    Young Black women in the United States are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. In a cancer registry-based sample of young Black women with breast cancer, we evaluated: (1) the prevalence of BRCA mutations detected through full gene sequencing and large rearrangements testing and (2) proportions that accessed genetic services pre-dating study enrollment. Black women diagnosed with invasive breast cancer ≤ag...

  5. Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

    Directory of Open Access Journals (Sweden)

    Meller Jaroslaw

    2007-03-01

    Full Text Available Abstract Background Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes. Results We present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance. In particular, Cinteny provides: i integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii flexibility to adjust the parameters and re-compute the results on-the-fly; iii ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre-loaded and available for analysis at http://cinteny.cchmc.org. Conclusion Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances

  6. Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

    OpenAIRE

    Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

    2009-01-01

    Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human g...

  7. The effect of substrate size in the Beckmann rearrangement: MOFs vs. zeolites

    Czech Academy of Sciences Publication Activity Database

    Opanasenko, Maksym; Shamzhy, Mariya; Lamač, Martin; Čejka, Jiří

    2013-01-01

    Roč. 204, APR 2013 (2013), s. 94-100. ISSN 0920-5861 R&D Projects: GA ČR GBP106/12/G015 Grant ostatní: European Commission(XE) FP7/2007-2013, contract 228862 Institutional support: RVO:61388955 Keywords : Beckmann rearrangement * oximes * CuBTC Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.309, year: 2013

  8. Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen-Cope rearrangement.

    Science.gov (United States)

    Mei, Qinggang; Wang, Chun; Zhao, Zhigang; Yuan, Weicheng; Zhang, Guolin

    2015-01-01

    The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4'-OH methylation of kaempferol, the 8-prenylation of 3-O-methoxymethyl-4'-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen-Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the glycosylation of icaritin (3) are the key steps. PMID:26425179

  9. Hadronic J/psi and charmed particle production and correlating quark rearrangement model

    International Nuclear Information System (INIS)

    On the basis of the correlating quark rearrangement model, the exclusive and inclusive production cross sections of J/psi and charmed particles in hadron collisions are calculated. It is shown that the inclusive production cross section of charmed particles is several tens of μb at p sub( l) -- 100 GeV/c in hadron collisions. The OZI rule is discussed in connection with the production mechanism of J/psi particles. (author)

  10. Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience

    Science.gov (United States)

    van Karnebeek, C D M; Koevoets, C; Sluijter, S; Bijlsma, E; Smeets, D; Redeker, E; Hennekam, R; Hoovers, J

    2002-01-01

    Objective: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre. Methods: Inclusion criteria were: age <18 years at referral, IQ<85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB). Results: In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies. Conclusions: The total frequency of cytogenetic anomalies in this prospective study was high (1:10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre. PMID:12161591

  11. Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system

    OpenAIRE

    Morishita, Maki; Muramatsu, Tomoki; Suto, Yumiko; Hirai, Momoki; Konishi, Teruaki; Hayashi, Shin; Shigemizu, Daichi; Tsunoda, Tatsuhiko; Moriyama, Keiji; Inazawa, Johji

    2016-01-01

    Chromothripsis is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event, rather than an accumulation of a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and is thought to be associated with increased malignancy and carcinogenesis. However, the causes and consequences of chromothripsis remain unclear. Therefore, to identify the mechanism underlying the generation of chromothripsis, we invest...

  12. Influence of the dispersity of anthracite on the rearrangement of its structure during heat treatment

    Energy Technology Data Exchange (ETDEWEB)

    Fialkov, A.S.; Abramov, A.V.; Chuparova, L.D.; Kirilin, N.S.; Semenov, M.V.; Suslina, V.I.; Yurkovskii, I.M.

    1983-01-01

    The influence of the dispersity of anthracite on the rearrangement of its structure and its absorption capacity with respect to a binder has been investigated. It has been shown that a composition based on anthracite with a high degree of ordering of the structure can be obtained if the specific surface of the powder is not less than 14 m/sup 2//g but not more than 20 m/sup 2//g.

  13. An alignment-free method to find and visualise rearrangements between pairs of DNA sequences

    OpenAIRE

    Pratas, Diogo; Silva, Raquel M; Pinho, Armando J.; Ferreira, Paulo J.S.G.

    2015-01-01

    Species evolution is indirectly registered in their genomic structure. The emergence and advances in sequencing technology provided a way to access genome information, namely to identify and study evolutionary macro-events, as well as chromosome alterations for clinical purposes. This paper describes a completely alignment-free computational method, based on a blind unsupervised approach, to detect large-scale and small-scale genomic rearrangements between pairs of DNA sequences. To illustrat...

  14. Computational strategies and improvements in the linear algebraic variational approach to rearrangement scattering

    Science.gov (United States)

    Schwenke, David W.; Mladenovic, Mirjana; Zhao, Meishan; Truhlar, Donald G.; Sun, Yan

    1988-01-01

    The computational steps in calculating quantum mechanical reactive scattering amplitudes by the L2 generalized Newton variational principle are discussed with emphasis on computational strategies and recent improvements that make the calculations more efficient. Special emphasis is placed on quadrature techniques, storage management strategies, use of symmetry, and boundary conditions. It is concluded that an efficient implementation of these procedures provides a powerful algorithm for the accurate solution of the Schroedinger equation for rearrangements.

  15. Role of Host Reticulon Proteins in Rearranging Membranes for Positive-strand RNA Virus Replication

    OpenAIRE

    Diaz, Arturo; Ahlquist, Paul

    2012-01-01

    Positive-strand RNA [(+)RNA] viruses are responsible for numerous human, animal, and plant diseases. Because of the limiting coding capacity of (+)RNA viruses, their replication requires a complex orchestration of interactions between the viral genome, viral proteins and exploited host factors. To replicate their genomic RNAs, (+)RNA viruses induce membrane rearrangements that create membrane-linked RNA replication compartments. Along with substantial advances on the ultrastructure of the mem...

  16. Detection of monoclonal immunoglobulin heavy chain gene rearrangement (FR3 in Thai malignant lymphoma by High Resolution Melting curve analysis

    Directory of Open Access Journals (Sweden)

    Pongpruttipan Tawatchai

    2010-05-01

    Full Text Available Abstract Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Detection of antigen receptor gene rearrangement including T cell receptor (TCR and immunoglobulin heavy chain (IgH by polymerase chain reaction followed by heteroduplex has currently become standard whereas fluorescent fragment analysis (GeneScan has been used for confirmation test. In this study, three techniques had been compared: thermocycler polymerase chain reaction (PCR followed by heteroduplex and polyacrylamide gel electrophoresis, GeneScan analysis, and real time PCR with High Resolution Melting curve analysis (HRM. The comparison was carried out with DNA extracted from paraffin embedded tissues diagnosed as B- cell non-Hodgkin lymphoma. Specific PCR primers sequences for IgH gene variable region 3, including fluorescence labeled IgH primers were used and results were compared with HRM. In conclusion, the detection IgH gene rearrangement by HRM in the LightCycler System showed potential for distinguishing monoclonality from polyclonality in B-cell non-Hodgkin lymphoma. Introduction Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The incidence rate as reported by Ministry of Public Health is 3.1 per 100,000 population in female whereas the rate in male is 4.5 per 100,000 population 1. At Siriraj Hospital, the new cases diagnosed as malignant lymphoma were 214.6 cases/year 2. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Therefore, detection of antigen receptor gene rearrangement including T cell receptor (TCR and immunoglobulin heavy chain (IgH by polymerase chain reaction (PCR assay has recently become a standard laboratory test for discrimination of reactive from malignant clonal

  17. Symmetry Breaking in NMR Spectroscopy: The Elucidation of Hidden Molecular Rearrangement Processes

    Directory of Open Access Journals (Sweden)

    Michael J. McGlinchey

    2014-08-01

    Full Text Available Variable-temperature NMR spectroscopy is probably the most convenient and sensitive technique to monitor changes in molecular structure in solution. Rearrangements that are rapid on the NMR time-scale exhibit simplified spectra, whereby non-equivalent nuclear environments yield time-averaged resonances. At lower temperatures, when the rate of exchange is sufficiently reduced, these degeneracies are split and the underlying “static” molecular symmetry, as seen by X-ray crystallography, becomes apparent. Frequently, however, such rearrangement processes are hidden, even when they become slow on the NMR time-scale, because the molecular point group remains unchanged. Judicious symmetry breaking, such as by substitution of a molecular fragment by a similar, but not identical moiety, or by the incorporation of potentially diastereotopic (chemically non-equivalent nuclei, allows the elucidation of the kinetics and energetics of such processes. Examples are chosen that include a wide range of rotations, migrations and other rearrangements in organic, inorganic and organometallic chemistry.

  18. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

    Science.gov (United States)

    Zody, Michael C; Garber, Manuel; Adams, David J; Sharpe, Ted; Harrow, Jennifer; Lupski, James R; Nicholson, Christine; Searle, Steven M; Wilming, Laurens; Young, Sarah K; Abouelleil, Amr; Allen, Nicole R; Bi, Weimin; Bloom, Toby; Borowsky, Mark L; Bugalter, Boris E; Butler, Jonathan; Chang, Jean L; Chen, Chao-Kung; Cook, April; Corum, Benjamin; Cuomo, Christina A; de Jong, Pieter J; DeCaprio, David; Dewar, Ken; FitzGerald, Michael; Gilbert, James; Gibson, Richard; Gnerre, Sante; Goldstein, Steven; Grafham, Darren V; Grocock, Russell; Hafez, Nabil; Hagopian, Daniel S; Hart, Elizabeth; Norman, Catherine Hosage; Humphray, Sean; Jaffe, David B; Jones, Matt; Kamal, Michael; Khodiyar, Varsha K; LaButti, Kurt; Laird, Gavin; Lehoczky, Jessica; Liu, Xiaohong; Lokyitsang, Tashi; Loveland, Jane; Lui, Annie; Macdonald, Pendexter; Major, John E; Matthews, Lucy; Mauceli, Evan; McCarroll, Steven A; Mihalev, Atanas H; Mudge, Jonathan; Nguyen, Cindy; Nicol, Robert; O'Leary, Sinéad B; Osoegawa, Kazutoyo; Schwartz, David C; Shaw-Smith, Charles; Stankiewicz, Pawel; Steward, Charles; Swarbreck, David; Venkataraman, Vijay; Whittaker, Charles A; Yang, Xiaoping; Zimmer, Andrew R; Bradley, Allan; Hubbard, Tim; Birren, Bruce W; Rogers, Jane; Lander, Eric S; Nusbaum, Chad

    2006-04-20

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. PMID:16625196

  19. Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting.

    Science.gov (United States)

    Nie, W; Wang, J; Su, W; Wang, D; Tanomtong, A; Perelman, P L; Graphodatsky, A S; Yang, F

    2012-01-01

    Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID:22086079

  20. Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting

    Science.gov (United States)

    Nie, W; Wang, J; Su, W; Wang, D; Tanomtong, A; Perelman, P L; Graphodatsky, A S; Yang, F

    2012-01-01

    Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID:22086079