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Sample records for gene translocation accelerate

  1. Zinc translocation accelerates infarction after mild transient focal ischemia.

    Science.gov (United States)

    Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

    2002-01-01

    Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

  2. Mitochondrial tRNA gene translocations in highly eusocial bees

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    Daniela Silvestre

    2006-01-01

    Full Text Available Mitochondrial gene rearrangement events, especially involving tRNA genes, have been described more frequently as more complete mitochondrial genome sequences are becoming available. In the present work, we analyzed mitochondrial tRNA gene rearrangements between two bee species belonging to the tribes Apini and Meliponini within the "corbiculate Apidae". Eleven tRNA genes are in different genome positions or strands. The molecular events responsible for each translocation are explained. Considering the high number of rearrangements observed, the data presented here contradict the general rule of high gene order conservation among closely related organisms, and also represent a powerful molecular tool to help solve questions about phylogeny and evolution in bees.

  3. Myeloid translocation genes differentially regulate colorectal cancer programs

    Science.gov (United States)

    Parang, Bobak; Bradley, Amber M.; Mittal, Mukul K.; Short, Sarah P.; Thompson, Joshua J.; Barrett, Caitlyn W.; Naik, Rishi D.; Bilotta, Anthony J.; Washington, Mary K.; Revetta, Frank L.; Smith, Jesse J.; Chen, Xi; Wilson, Keith T.; Hiebert, Scott W.; Williams, Christopher S.

    2016-01-01

    Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1−/− mice have progressive depletion of all intestinal secretory cells, and Mtg16−/− mice have a decrease in goblet cells. Furthermore, both Mtgr1−/− and Mtg16−/− mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1−/− mice, but not Mtg16−/− mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of ChIP-seq datasets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1−/− tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context dependent effect on intestinal tumorigenesis. PMID:27270437

  4. Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4 Protein Translocation

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    Abu Sadat Md Sayem

    2018-01-01

    Full Text Available Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4 from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature.

  5. Robertsonian translocation 13/14 associated with rRNA genes ...

    African Journals Online (AJOL)

    Robertsonian translocation 13/14 associated with rRNA genes overexpression and intellectual disability. Alexander A. Dolskiy, Natalya A. Lemskaya, Yulia V. Maksimova, Asia R. Shorina, Irina S. Kolesnikova, Dmitry V. Yudkin ...

  6. TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription.

    Science.gov (United States)

    Gómez-Herreros, Fernando; Zagnoli-Vieira, Guido; Ntai, Ioanna; Martínez-Macías, María Isabel; Anderson, Rhona M; Herrero-Ruíz, Andrés; Caldecott, Keith W

    2017-08-10

    DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation 'hotspot', MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.DNA double-strand breaks (DSBs) induced by topoisomerase II (TOP2) are rejoined by TDP2-dependent non-homologous end-joining (NHEJ) but whether this promotes or suppresses translocations is not clear. Here the authors show that TDP2 suppresses chromosome translocations from DSBs introduced during gene transcription.

  7. Genetic markers, translocations and sexing genes on chromosome 2 of Ceratitis capitata

    International Nuclear Information System (INIS)

    Cladera, J.L.

    1997-01-01

    A review is presented of results obtained in a search for genetic markers, translocations and selectable genes obtained at the Instituto de Genetica, Castelar, Argentina, with special reference to chromosome 2 linked mutations and genes useful for developing self-sexing strains in Ceratitis capitata. (author)

  8. A Search for Gene Fusions/Translocations in Breast Cancer

    Science.gov (United States)

    2009-10-01

    Freemont PS, Solomon E . Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science 1991;254:1371–1374...characterization of gene f usions potentially provides novel di agnostic a nd t herapeutic markers, as e xemplified by th e successful application of BCR-ABL1...or e xons) are nominated a s c andidate g ene f usion partners (Figure 1). Further an alysis o f C NT loci b y s pectral k aryotyping ( SKY

  9. Transfer of alien genes by means of induced translocation in oats and other crop species

    International Nuclear Information System (INIS)

    Thomas, H.; Taing Aung

    1977-01-01

    Some of the best sources of resistance to mildew, which is the most important disease of the oat crop in the United Kingdom, occur in related weed species. The mildew resistance found in a genotype of the tetraploid species Avena barbata has been transferred into the germ plasm of the cultivated hexaploid species A. sativa by means of an induced translocation. The procedures adopted to isolate the desirable translocation and to determine its breeding behaviour are described. A number of alien genes have been transferred into wheat by means of induced translocations and genetic induction, but their successful introduction into commercial varieties has been limited. In this paper, the use and limitations of alien transfers as breeding material are discussed. (author)

  10. A Search for Gene Fusions/Translocations in Breast Cancer

    Science.gov (United States)

    2013-11-01

    2008). The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320, 1344–1349. Palanisamy, N., Ateeq, B., Kalyana-Sundaram...census of human cancer genes. Nat Rev Cancer 4, 177–183. [2] Santarius T, Shipley J, Brewer D, Stratton MR, and Cooper CS (2010). A census of amplified

  11. Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

    International Nuclear Information System (INIS)

    Gué, Michaël; Sun, Jian-Sheng; Boudier, Thomas

    2006-01-01

    Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static 'contact first' model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic 'breakage first' model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static 'contact first' model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static 'contact first' model of translocation. The recently proposed dynamic 'breakage first' model offers an attractive alternative explanation

  12. A cohort of balanced reciprocal translocations associated with dyslexia: identification of two putative candidate genes at DYX1

    DEFF Research Database (Denmark)

    Buonincontri, Roberta; Bache, Iben; Silahtaroglu, Asli

    2011-01-01

    Dyslexia is one of the most common neurodevelopmental disorders where likely many genes are involved in the pathogenesis. So far six candidate dyslexia genes have been proposed, and two of these were identified by rare chromosomal translocations in affected individuals. By systematic re......-examination of all translocation carriers in Denmark, we have identified 16 different translocations associated with dyslexia. In four families, where the translocation co-segregated with the phenotype, one of the breakpoints concurred (at the cytogenetic level) with either a known dyslexia linkage region--at 15q21...... (DYX1), 2p13 (DYX3) and 1p36 (DYX8)--or an unpublished linkage region at 19q13. As a first exploitation of this unique cohort, we identify three novel candidate dyslexia genes, ZNF280D and TCF12 at 15q21, and PDE7B at 6q23.3, by molecular mapping of the familial translocation with the 15q21 breakpoint....

  13. Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

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    Sun Jian-Sheng

    2006-01-01

    Full Text Available Abstract Background Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL, considers the spatial proximity of loci in interphase nuclei (static "contact first" model. The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model. Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4 and a less frequent partner gene (ENL, should elucidate the MLL translocation mechanism. Methods Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. Results In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value loci would indicate a greater probability of the occurrence of t(11;19(q23;p13.3 compared to t(4;11(q21;q23. However this is in contradiction to the epidemiology of 11q23 translocation. Conclusion The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation.

  14. Genome Wide Identification of Orthologous ZIP Genes Associated with Zinc and Iron Translocation in Setaria italica.

    Science.gov (United States)

    Alagarasan, Ganesh; Dubey, Mahima; Aswathy, Kumar S; Chandel, Girish

    2017-01-01

    Genes in the ZIP family encode transcripts to store and transport bivalent metal micronutrient, particularly iron (Fe) and or zinc (Zn). These transcripts are important for a variety of functions involved in the developmental and physiological processes in many plant species, including most, if not all, Poaceae plant species and the model species Arabidopsis. Here, we present the report of a genome wide investigation of orthologous ZIP genes in Setaria italica and the identification of 7 single copy genes. RT-PCR shows 4 of them could be used to increase the bio-availability of zinc and iron content in grains. Of 36 ZIP members, 25 genes have traces of signal peptide based sub-cellular localization, as compared to those of plant species studied previously, yet translocation of ions remains unclear. In silico analysis of gene structure and protein nature suggests that these two were preeminent in shaping the functional diversity of the ZIP gene family in S. italica . NAC, bZIP and bHLH are the predominant Fe and Zn responsive transcription factors present in SiZIP genes. Together, our results provide new insights into the signal peptide based/independent iron and zinc translocation in the plant system and allowed identification of ZIP genes that may be involved in the zinc and iron absorption from the soil, and thus transporting it to the cereal grain underlying high micronutrient accumulation.

  15. Genome Wide Identification of Orthologous ZIP Genes Associated with Zinc and Iron Translocation in Setaria italica

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    Ganesh Alagarasan

    2017-05-01

    Full Text Available Genes in the ZIP family encode transcripts to store and transport bivalent metal micronutrient, particularly iron (Fe and or zinc (Zn. These transcripts are important for a variety of functions involved in the developmental and physiological processes in many plant species, including most, if not all, Poaceae plant species and the model species Arabidopsis. Here, we present the report of a genome wide investigation of orthologous ZIP genes in Setaria italica and the identification of 7 single copy genes. RT-PCR shows 4 of them could be used to increase the bio-availability of zinc and iron content in grains. Of 36 ZIP members, 25 genes have traces of signal peptide based sub-cellular localization, as compared to those of plant species studied previously, yet translocation of ions remains unclear. In silico analysis of gene structure and protein nature suggests that these two were preeminent in shaping the functional diversity of the ZIP gene family in S. italica. NAC, bZIP and bHLH are the predominant Fe and Zn responsive transcription factors present in SiZIP genes. Together, our results provide new insights into the signal peptide based/independent iron and zinc translocation in the plant system and allowed identification of ZIP genes that may be involved in the zinc and iron absorption from the soil, and thus transporting it to the cereal grain underlying high micronutrient accumulation.

  16. Tyrosine kinase chromosomal translocations mediate distinct and overlapping gene regulation events

    International Nuclear Information System (INIS)

    Kim, Hani; Gillis, Lisa C; Jarvis, Jordan D; Yang, Stuart; Huang, Kai; Der, Sandy; Barber, Dwayne L

    2011-01-01

    Leukemia is a heterogeneous disease commonly associated with recurrent chromosomal translocations that involve tyrosine kinases including BCR-ABL, TEL-PDGFRB and TEL-JAK2. Most studies on the activated tyrosine kinases have focused on proximal signaling events, but little is known about gene transcription regulated by these fusions. Oligonucleotide microarray was performed to compare mRNA changes attributable to BCR-ABL, TEL-PDGFRB and TEL-JAK2 after 1 week of activation of each fusion in Ba/F3 cell lines. Imatinib was used to control the activation of BCR-ABL and TEL-PDGFRB, and TEL-JAK2-mediated gene expression was examined 1 week after Ba/F3-TEL-JAK2 cells were switched to factor-independent conditions. Microarray analysis revealed between 800 to 2000 genes induced or suppressed by two-fold or greater by each tyrosine kinase, with a subset of these genes commonly induced or suppressed among the three fusions. Validation by Quantitative PCR confirmed that eight genes (Dok2, Mrvi1, Isg20, Id1, gp49b, Cxcl10, Scinderin, and collagen Vα1(Col5a1)) displayed an overlapping regulation among the three tested fusion proteins. Stat1 and Gbp1 were induced uniquely by TEL-PDGFRB. Our results suggest that BCR-ABL, TEL-PDGFRB and TEL-JAK2 regulate distinct and overlapping gene transcription profiles. Many of the genes identified are known to be involved in processes associated with leukemogenesis, including cell migration, proliferation and differentiation. This study offers the basis for further work that could lead to an understanding of the specificity of diseases caused by these three chromosomal translocations

  17. Fine mapping of the EDA gene: A translocation breakpoint is associated with a CpG island that is transcribed

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, A.K.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); Montonen, O. [Univ. of Helsinki (Finland)] [and others

    1996-01-01

    In order to identify the gene for human X-linked anhidrotic ectodermal dysplasia (EDA), a translocation breakpoint in a female with t(X;1)(q13.1;p36.3) and EDA (patient AK) was finely mapped. The EDA region contains five groups of rare-cutter restriction sites that define CpG islands. The two more centromeric of these islands are associated with transcripts of 3.5 kb and 1.8 kb. The third CpG island maps within <1 kb of the translocation breakpoint in patient AK, as indicated by a genomic rearrangement, and {approximately}100 kb centromeric from another previously mapped translocation breakpoint (patient AnLy). Northern analysis with a probe from this CpG island detected an {approximately}6-kb mRNA in several fetal tissues tested. An extended YAC contig of 1,200 kb with an average of fivefold coverage was constructed. The two most telomeric CpG islands map 350 kb telomeric of the two translocations. Taken together, the results suggest that the CpG island just proximal of the AK translocation breakpoint lies at the 5{prime} end of a candidate gene for EDA. 26 refs., 4 figs., 1 tab.

  18. The transcriptional co-repressor myeloid translocation gene 16 inhibits glycolysis and stimulates mitochondrial respiration.

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    Parveen Kumar

    Full Text Available The myeloid translocation gene 16 product MTG16 is found in multiple transcription factor-containing complexes as a regulator of gene expression implicated in development and tumorigenesis. A stable Tet-On system for doxycycline-dependent expression of MTG16 was established in B-lymphoblastoid Raji cells to unravel its molecular functions in transformed cells. A noticeable finding was that expression of certain genes involved in tumor cell metabolism including 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4 (PFKFB3 and PFKFB4, and pyruvate dehydrogenase kinase isoenzyme 1 (PDK1 was rapidly diminished when MTG16 was expressed. Furthermore, hypoxia-stimulated production of PFKFB3, PFKFB4 and PDK1 was inhibited by MTG16 expression. The genes in question encode key regulators of glycolysis and its coupling to mitochondrial metabolism and are commonly found to be overexpressed in transformed cells. The MTG16 Nervy Homology Region 2 (NHR2 oligomerization domain and the NHR3 protein-protein interaction domain were required intact for inhibition of PFKFB3, PFKFB4 and PDK1 expression to occur. Expression of MTG16 reduced glycolytic metabolism while mitochondrial respiration and formation of reactive oxygen species increased. The metabolic changes were paralleled by increased phosphorylation of mitogen-activated protein kinases, reduced levels of amino acids and inhibition of proliferation with a decreased fraction of cells in S-phase. Overall, our findings show that MTG16 can serve as a brake on glycolysis, a stimulator of mitochondrial respiration and an inhibitor of cell proliferation. Hence, elevation of MTG16 might have anti-tumor effect.

  19. Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for mapping of neuroblastoma genes

    NARCIS (Netherlands)

    van Roy, N.; Laureys, G.; van Gele, M.; Opdenakker, G.; Miura, R.; van der Drift, P.; Chan, A.; Versteeg, R.; Speleman, F.

    1997-01-01

    Deletions and translocations resulting in loss of distal 1p-material are known to occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation (FISH) showed that 17q was most frequently involved in chromosome 1p translocations. A review of the literature shows that 10 of 27 cell

  20. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

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    Pierce Levi CT

    2009-01-01

    Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

  1. Disruption of the APC gene by t(5;7) translocation in a Turcot family.

    Science.gov (United States)

    Sahnane, Nora; Bernasconi, Barbara; Carnevali, Ileana; Furlan, Daniela; Viel, Alessandra; Sessa, Fausto; Tibiletti, Maria Grazia

    2016-03-01

    Turcot syndrome (TS) refers to the combination of colorectal polyps and primary tumours of the central nervous system. TS is a heterogeneous genetic condition due to APC and/or mismatch repair germline mutations. When APC is involved the vast majority of mutations are truncating, but in approximately 20%-30% of patients with familial polyposis no germline mutation can be found. A 30-year-old Caucasian woman with a positive pedigree for TS was referred to our Genetic Counselling Service. She was negative for APC and MUTYH but showed a reciprocal balanced translocation t(5;7)(q22;p15) at chromosome analysis. FISH analysis using specific BAC probes demonstrated that 5q22 breakpoint disrupted the APC gene. Transcript analysis by MLPA and digital PCR revealed that the cytogenetic rearrangement involving the 3' end of the APC gene caused a defective expression of a truncated transcript. This result allowed cytogenetic analysis to be offered to all the other family members and segregation analysis clearly demonstrated that all the carriers were affected, whereas non-carriers did not have the polyposis. A cytogenetic approach permitted the identification of the mutation-causing disease in this family, and the segregation analysis together with the transcript study supported the pathogenetic role of this mutation. Karyotype analysis was used as a predictive test in all members of this family. This family suggests that clinically positive TS and FAP cases, which test negative with standard molecular analysis, could be easily and cost-effectively resolved by a classical and molecular cytogenetic approach. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; Daenen, S.; de Jong, B.; Fonatsch, C.; Heinze, B.; Bartram, C.; Hagemeijer, A.; Grosveld, G.

    1992-01-01

    Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and

  3. Glycogen synthase kinase-3β facilitates cell apoptosis induced by high fluence low-power laser irradiation through acceleration of Bax translocation

    Science.gov (United States)

    Huang, Lei; Wu, Shengnan; Xing, Da

    2011-03-01

    Glycogen synthase kinase-3β (GSK-3β) is a critical activator of cell apoptosis induced by a diverse array of insults. However, the effects of GSK-3β on the human lung adenocarcinoma cell (ASTC-a-1) apoptosis induced by high fluence low-power laser irradiation (HF-LPLI) are not clear. Here, we showed that GSK-3β was constantly translocated from cytoplasm to nucleus and activated during HF-LPLI-induced cell apoptosis. In addition, we found that co-overexpression of YFP-GSK-3β and CFP-Bax in ASTC-a-1 cells accelerated both Bax translocations to mitochondria and cell apoptosis, compared to the cells expressed CFP-Bax only under HF-LPLI treatment, indicating that GSK-3β facilitated ASTC-a-1 cells apoptosis through acceleration mitochondrial translocation of Bax. Our results demonstrate that GSK-3β exerts some of its pro-apoptotic effects in ASTC-a-1 cells by regulating the mitochondrial localization of Bax, a key component of the intrinsic apoptotic cascade.

  4. Characterization of a heavy metal translocating P-type ATPase gene from an environmental heavy metal resistance Enterobacter sp. isolate.

    Science.gov (United States)

    Chien, Chih-Ching; Huang, Chia-Hsuan; Lin, Yi-Wei

    2013-03-01

    Heavy metals are common contaminants found in polluted areas. We have identified a heavy metal translocating P-type ATPase gene (hmtp) via fosmid library and in vitro transposon mutagenesis from an Enterobacter sp. isolate. This gene is believed to participate in the bacterium's heavy metal resistance traits. The complete gene was identified, cloned, and expressed in a suitable Escherichia coli host cell. E. coli W3110, RW3110 (zntA::Km), GG48 (ΔzitB::Cm zntA::Km), and GG51 (ΔzitB::Cm) were used to study the possible effects of this gene for heavy metal (cadmium and zinc in particular) resistance. Among the E. coli strains tested, RW3110 and GG48 showed more sensitivity to cadmium and zinc compared to the wild-type E. coli W3110 and strain GG51. Therefore, strains RW3110 and GG48 were chosen for the reference hosts for further evaluation of the gene's effect. The results showed that expression of this heavy metal translocating P-type ATPase gene could increase the ability for zinc and cadmium resistance in the tested microorganisms.

  5. MODY-like diabetes associated with an apparently balanced translocation: possible involvement of MPP7 gene and cell polarity in the pathogenesis of diabetes

    Directory of Open Access Journals (Sweden)

    Bartov Guy

    2009-02-01

    Full Text Available Abstract Background Characterization of disease-associated balanced translocations has led to the discovery of genes responsible for many disorders, including syndromes that include various forms of diabetes mellitus. We studied a man with unexplained maturity onset diabetes of the young (MODY-like diabetes and an apparently balanced translocation [46,XY,t(7;10(q22;p12] and sought to identify a novel diabetes locus by characterizing the translocation breakpoints. Results Mutations in coding exons and splice sites of known MODY genes were first ruled out by PCR amplification and DNA sequencing. Fluorescent in situ hybridization (FISH studies demonstrated that the translocation did not disrupt two known diabetes-related genes on 10p12. The translocation breakpoints were further mapped to high resolution using FISH and somatic cell hybrids and the junctions PCR-amplified and sequenced. The translocation did not disrupt any annotated transcription unit. However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 (MPP7 gene, which encodes a protein required for proper cell polarity. This biological function is shared by HNF4A, a known MODY gene. Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. The translocation did not appear to alter lymphoblastoid expression of MPP7 or other genes near the breakpoints. Conclusion The balanced translocation and MODY-like diabetes in the proband could be coincidental. Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study.

  6. Application of DNA RFLP procedures in interspecific gene transfer: The Lr19 translocation of wheat

    International Nuclear Information System (INIS)

    Prins, R.; Marais, G.F.; Marais, A.S.; Pretorius, Z.A.; Janse, B.J.H.

    1998-01-01

    Twenty-nine lines with deletions in the Lr19 ('Indis') translocated chromosome segment were used to physically map Thinopyrum Restriction Fragment Length Polymorphism (RFLP) loci as well as the Sr25 and Sdl loci. The relative distances between marker loci on the translocation were then calculated. The information was then used as an aid to characterize several recombined forms of the translocation. The data confirmed the reported homoeology between the Lr19 segment and chromosome arm 7DL of wheat. Also, it seems that the Lr19 translocation in 'Indis' is very similar to the Lr19 segment in the T4 source and that the former may not derive from Thinopyrum distichum. Near-isogenic lines of the recombined segments were derived and used to study their expression of leaf rust resistance. It became evident that only one potentially useful recombinant was obtained in an earlier attempt to induce allosyndetic pairing between the Lr19 translocation and 7DL of wheat. (author)

  7. A new 2DS·2RL Robertsonian translocation transfers stem rust resistance gene Sr59 into wheat.

    Science.gov (United States)

    Rahmatov, Mahbubjon; Rouse, Matthew N; Nirmala, Jayaveeramuthu; Danilova, Tatiana; Friebe, Bernd; Steffenson, Brian J; Johansson, Eva

    2016-07-01

    A new stem rust resistance gene Sr59 from Secale cereale was introgressed into wheat as a 2DS·2RL Robertsonian translocation. Emerging new races of the wheat stem rust pathogen (Puccinia graminis f. sp. tritici), from Africa threaten global wheat (Triticum aestivum L.) production. To broaden the resistance spectrum of wheat to these widely virulent African races, additional resistance genes must be identified from all possible gene pools. From the screening of a collection of wheat-rye (Secale cereale L.) chromosome substitution lines developed at the Swedish University of Agricultural Sciences, we described the line 'SLU238' 2R (2D) as possessing resistance to many races of P. graminis f. sp. tritici, including the widely virulent race TTKSK (isolate synonym Ug99) from Africa. The breakage-fusion mechanism of univalent chromosomes was used to produce a new Robertsonian translocation: T2DS·2RL. Molecular marker analysis and stem rust seedling assays at multiple generations confirmed that the stem rust resistance from 'SLU238' is present on the rye chromosome arm 2RL. Line TA5094 (#101) was derived from 'SLU238' and was found to be homozygous for the T2DS·2RL translocation. The stem rust resistance gene on chromosome 2RL arm was designated as Sr59. Although introgressions of rye chromosome arms into wheat have most often been facilitated by irradiation, this study highlights the utility of the breakage-fusion mechanism for rye chromatin introgression. Sr59 provides an additional asset for wheat improvement to mitigate yield losses caused by stem rust.

  8. CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene.

    Science.gov (United States)

    Uchida, Shusaku; Teubner, Brett J W; Hevi, Charles; Hara, Kumiko; Kobayashi, Ayumi; Dave, Rutu M; Shintaku, Tatsushi; Jaikhan, Pattaporn; Yamagata, Hirotaka; Suzuki, Takayoshi; Watanabe, Yoshifumi; Zakharenko, Stanislav S; Shumyatsky, Gleb P

    2017-01-10

    Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3-N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB, and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Robertsonian translocation 13/14 associated with rRNA genes ...

    African Journals Online (AJOL)

    Alexander A. Dolskiy

    2017-12-01

    Dec 1, 2017 ... Results: We describe a family case of a translocation rob (13; 14) and elevated rRNA expression in the proband with ..... Clin Genet 2010;78:299–309. ... [9] Bertini V, Fogli A, Bruno R, Azzarà A, Michelucci A, Mattina T, et al.

  10. Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas.

    Science.gov (United States)

    Bianchini, Laurence; Birtwisle, Loïc; Saâda, Esma; Bazin, Audrey; Long, Elodie; Roussel, Jean-François; Michiels, Jean-François; Forest, Fabien; Dani, Christian; Myklebost, Ola; Birtwisle-Peyrottes, Isabelle; Pedeutour, Florence

    2013-06-01

    Most lipomas are characterized by translocations involving the HMGA2 gene in 12q14.3. These rearrangements lead to the fusion of HMGA2 with an ectopic sequence from the translocation chromosome partner. Only five fusion partners of HMGA2 have been identified in lipomas so far. The identification of novel fusion partners of HMGA2 is important not only for diagnosis in soft tissue tumors but also because these genes might have an oncogenic role in other tumors. We observed that t(1;12)(p32;q14) was the second most frequent translocation in our series of lipomas after t(3;12)(q28;q14.3). We detected overexpression of HMGA2 mRNA and protein in all t(1;12)(p32;q14) lipomas. We used a fluorescence in situ hybridization-based positional cloning strategy to characterize the 1p32 breakpoint. In 11 cases, we identified PPAP2B, a member of the lipid phosphate phosphatases family as the 1p32 target gene. Reverse transcription-polymerase chain reaction analysis followed by nucleotide sequencing of the fusion transcript indicated that HMGA2 3' untranslated region (3'UTR) fused with exon 6 of PPAP2B in one case. In other t(1;12) cases, the breakpoint was extragenic, located in the 3'region flanking PPAP2B 3'UTR. Moreover, in one case showing a t(1;6)(p32;p21) we observed a rearrangement of PPAP2B and HMGA1, which suggests that HMGA1 might also be a fusion partner for PPAP2B. Our results also revealed that adipocytic differentiation of human mesenchymal stem cells derived from adipose tissue was associated with a significant decrease in PPAP2B mRNA expression suggesting that PPAP2B might play a role in adipogenesis. Copyright © 2013 Wiley Periodicals, Inc.

  11. Nuclear translocation of Nrf2 and expression of antioxidant defence genes in THP-1 cells exposed to carbon nanotubes.

    Science.gov (United States)

    Brown, David M; Donaldson, Kenneth; Stone, Vicki

    2010-06-01

    Carbon nanotubes have a wide range of applications in various industries and their use is likely to rise in the future. Currently, a major concern is that with the increasing use and production of these materials, there may be increased health risks to exposed workers. Long (> 15 microm) straight nanotubes may undergo frustrated phagocytosis which is likely to result in reduced clearance. We examine here the effects of multiwalled carbon nanotubes of different sizes on monocytic THP-1 cells, with regard to their ability to stimulate increased expression of the HO-1 and GST genes and their ability to produce nuclear translocation of the transcription factor, Nrf2, as well as the release of several pro-inflammatory cytokines and mediators of inflammation. Our results suggest that long (50 microm) carbon nanotubes (62.5 microg/ml for 4 hours) produce increased nuclear translocation of Nrf2 and increased HO-1 gene expression compared with shorter entangled nanotubes. There was no increased gene expression for GST. The long nanotubes (NT1) caused increased release of the proinflammatory cytokine IL-1beta, an effect which was diminished by the antioxidant trolox, suggesting a role of oxidative stress in the upregulation of this cytokine. Tentatively, our study suggests that long carbon nanotubes may exert their effect in THP-1 cells in part via an oxidative stress mechanism.

  12. A 45 X male patient with 7q distal deletion and rearrangement with SRY gene translocation: a case report.

    Science.gov (United States)

    Bilen, S; Okten, A; Karaguzel, G; Ikbal, M; Aslan, Y

    2013-01-01

    Here we present a male newborn with multiple congenital anomalies who also has an extremely rare form of testicular disorder of sex development (DSD). His karyotype was 45X, without any mosaicism. SRY gene was positive by polymerase chain reaction (PCR), and rearranged on distal part of the 7th chromosome by fluorescence in situ hybridization (FISH) analysis. SRY, normally located on the Y chromosome, is the most important gene that plays a role in the development of male sex. SRY gen may be translocated onto another chromosome, mostly X chromosome in the XX testicular DSD. On the other hand very few cases of 45 X testicular DSD were published to date. Other clinical manifestations of our patient were compatible with distal 7 q deletion syndrome. To the best of our knowledge this is the first case of 45 X testicular DSD with SRY gene rearranged on the 7th autosomal chromosome.

  13. Transcriptional expression analysis of genes involved in regulation of calcium translocation and storage in finger millet (Eleusine coracana L. Gartn.).

    Science.gov (United States)

    Mirza, Neelofar; Taj, Gohar; Arora, Sandeep; Kumar, Anil

    2014-10-25

    Finger millet (Eleusine coracana) variably accumulates calcium in different tissues, due to differential expression of genes involved in uptake, translocation and accumulation of calcium. Ca(2+)/H(+) antiporter (CAX1), two pore channel (TPC1), CaM-stimulated type IIB Ca(2+) ATPase and two CaM dependent protein kinase (CaMK1 and 2) homologs were studied in finger millet. Two genotypes GP-45 and GP-1 (high and low calcium accumulating, respectively) were used to understand the role of these genes in differential calcium accumulation. For most of the genes higher expression was found in the high calcium accumulating genotype. CAX1 was strongly expressed in the late stages of spike development and could be responsible for accumulating high concentrations of calcium in seeds. TPC1 and Ca(2+) ATPase homologs recorded strong expression in the root, stem and developing spike and signify their role in calcium uptake and translocation, respectively. Calmodulin showed strong expression and a similar expression pattern to the type IIB ATPase in the developing spike only and indicating developing spike or even seed specific isoform of CaM affecting the activity of downstream target of calcium transportation. Interestingly, CaMK1 and CaMK2 had expression patterns similar to ATPase and TPC1 in various tissues raising a possibility of their respective regulation via CaM kinase. Expression pattern of 14-3-3 gene was observed to be similar to CAX1 gene in leaf and developing spike inferring a surprising possibility of CAX1 regulation through 14-3-3 protein. Our results provide a molecular insight for explaining the mechanism of calcium accumulation in finger millet. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Cloning of the ω-secalin gene family in a wheat 1BL/1RS translocation line using BAC clone sequencing

    Directory of Open Access Journals (Sweden)

    Meng Jun Li

    2016-05-01

    Conclusion: The ω-secalin gene family consisted of at least 18 members in the 1BL/1RS translocation line cv. Shimai 15. Eight ω-secalin genes were expressed during seed development. Eighteen members may originate from a progenitor with a 1,074-bp ORF. The spacers differed in length and sequence conservation.

  15. RCSD1-ABL1 Translocation Associated with IKZF1 Gene Deletion in B-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Shawana Kamran

    2015-01-01

    Full Text Available The RCSD1 gene has recently been identified as a novel gene fusion partner of the ABL1 gene in cases of B-cell Acute Lymphoblastic Leukemia (B-ALL. The RCSD1 gene is located at 1q23 and ABL1 is located at 9q34, so that the RCSD1-ABL1 fusion typically arises through a rare reciprocal translocation t(1;9(q23;q34. Only a small number of RCSD1-ABL1 positive cases of B-ALL have been described in the literature, and the full spectrum of clinical, morphological, immunophenotypic, and molecular features associated with this genetic abnormality has not been defined. We describe extensive genetic characterization of a case of B-ALL with RCSD1-ABL1 fusion, by using conventional cytogenetic analysis, Fluorescence In Situ Hybridization (FISH studies, and Chromosomal Microarray Analysis (CMA. The use of CMA resulted in detection of an approximately 70 kb deletion at 7p12.2, which caused a disruption of the IKZF1 gene. Deletions and mutations of IKZF1 are recurring abnormalities in B-ALL and are associated with a poor prognosis. Our findings highlight the association of the deletion of IKZF1 gene with the t(1;9(q24;q34 and illustrate the importance of comprehensive cytogenetic and molecular evaluation for accurate prediction of prognosis in patients with B-cell ALL.

  16. CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

    Directory of Open Access Journals (Sweden)

    Shusaku Uchida

    2017-01-01

    Full Text Available Summary: Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3-N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB, and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets. : Uchida et al. link CRTC1 synapse-to-nucleus shuttling in memory. Weak and strong training induce CRTC1 nuclear transport and transient Fgf1b transcription by a complex including CRTC1, CREB, and histone acetyltransferase CBP, whereas strong training alone maintains Fgf1b transcription through CRTC1-dependent substitution of KAT5 for CBP, leading to memory enhancement. Keywords: memory enhancement, long-term potentiation, hippocampus, nuclear transport, epigenetics, FGF1, CRTC1, KAT5/Tip60, HDAC3, CREB

  17. Structural and functional studies of FKHR-PAX3, a reciprocal fusion gene of the t(2;13 chromosomal translocation in alveolar rhabdomyosarcoma.

    Directory of Open Access Journals (Sweden)

    Qiande Hu

    Full Text Available Alveolar rhabdomyosarcoma (ARMS is an aggressive pediatric cancer of skeletal muscle. More than 70% of ARMS tumors carry balanced t(2;13 chromosomal translocation that leads to the production of two novel fusion genes, PAX3-FKHR and FKHR-PAX3. While the PAX3-FKHR gene has been intensely studied, the reciprocal FKHR-PAX3 gene has rarely been described. We report here the cloning and functional characterization of the FKHR-PAX3 gene as the first step towards a better understanding of its potential impact on ARMS biology. From RH30 ARMS cells, we detected and isolated three versions of FKHR-PAX3 cDNAs whose C-terminal sequences corresponded to PAX3c, PAX3d, and PAX3e isoforms. Unlike the nuclear-specific localization of PAX3-FKHR, the reciprocal FKHR-PAX3 proteins stayed predominantly in the cytoplasm. FKHR-PAX3 potently inhibited myogenesis in both non-transformed myoblast cells and ARMS cells. We showed that FKHR-PAX3 was not a classic oncogene but could act as a facilitator in oncogenic pathways by stabilizing PAX3-FKHR expression, enhancing cell proliferation, clonogenicity, anchorage-independent growth, and matrix adhesion in vitro, and accelerating the onset of tumor formation in xenograft mouse model in vivo. In addition to these pro-oncogenic behaviors, FKHR-PAX3 also negatively affected cell migration and invasion in vitro and lung metastasis in vivo. Taken together, these functional characteristics suggested that FKHR-PAX3 might have a critical role in the early stage of ARMS development.

  18. A constitutional translocation t(1;17(p36.2;q11.2 in a neuroblastoma patient disrupts the human NBPF1 and ACCN1 genes.

    Directory of Open Access Journals (Sweden)

    Karl Vandepoele

    Full Text Available The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17(p36.2;q11.2 may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types.

  19. Cloning of the anhidrotic ectodermal dysplasia gene: Identification of cDNAs associated with CpG islands mapped near translocation breakpoint in two female patients

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, A.K.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); Kere, J. [Univ. of Helsinki (Finland)] [and others

    1994-09-01

    The gene for the X chromosomal developmental disorder anhidrotic ectodermal dysplasia (EDA) has been mapped to Xq12-q13 by linkage analysis and is expressed in a few females with chromosomal translocations involving band Xq12-q13. A yeast artificial chromosome (YAC) contig (2.0 Mb) spanning two translocation breakpoints has been assembled by sequence-tagged site (STS)-based chromosomal walking. The two translocation breakpoints (X:autosome translocations from the affected female patients) have been mapped less than 60 kb apart within a YAC contig. Unique probes and intragenic STSs (mapped between the two translocations) have been developed and a somatic cell hybrid carrying the translocated X chromosome from the AK patient has been analyzed by isolating unique probes that span the breakpoint. Several STSs made from intragenic sequences have been found to be conserved in mouse, hamster and monkey, but we have detected no mRNAs in a number of tissues tested. However, a probe and STS developed from the DNA spanning the AK breakpoint is conserved in mouse, hamster and monkey, and we have detected expressed sequences in skin cells and cDNA libraries. In addition, unique sequences have been obtained from two CpG islands in the region that maps proximal to the breakpoints. cDNAs containing these sequences are being studied as candidates for the gene affected in the etiology of EDA.

  20. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells.

    Directory of Open Access Journals (Sweden)

    Christiane Bumke-Vogt

    Full Text Available The flavones apigenin (4',5,7,-trihydroxyflavone and luteolin (3',4',5,7,-tetrahydroxyflavone are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1, an important mediator of insulin signal transduction. Insulin reversed the translocation of FOXO1 as shown by live cell imaging. The impact on the expression of target genes was evaluated in HepG2 (human hepatoma cells. The mRNA-expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK and glucose-6-phosphatase (G6Pc, the lipogenic enzymes fatty-acid synthase (FASN and acetyl-CoA-carboxylase (ACC were down-regulated by both flavones with smaller effective dosages of apigenin than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced by apigenin and luteolin but not that of the insulin-like growth factor receptor IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1 nuclear translocation induced by apigenin and luteolin, suggesting that these flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT, sirtuin1 (SIRT1, and nuclear factor (erythroid-derived2-like2 (NRF2, investigated by siRNA knockdown, showed differential patterns of signal pathways involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression. We conclude that these flavones show an antidiabetic potential due to reduction of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway which justifies detailed investigation in vivo.

  1. Regulation of expression of Na+ -translocating NADH:quinone oxidoreductase genes in Vibrio harveyi and Klebsiella pneumoniae.

    Science.gov (United States)

    Fadeeva, Maria S; Yakovtseva, Evgenia A; Belevich, Galina A; Bertsova, Yulia V; Bogachev, Alexander V

    2007-10-01

    The expression of genes encoding sodium-translocating NADH:quinone oxidoreductase (Na(+)-NQR) was studied in the marine bacterium Vibrio harveyi and in the enterobacterium Klebsiella pneumoniae. It has been shown that such parameters as NaCl concentration, pH value, and presence of an uncoupler in the growth media do not influence significantly the level of nqr expression. However, nqr expression depends on the growth substrates used by these bacteria. Na(+)-NQR is highly repressed in V. harveyi during anaerobic growth, and nqr expression is modulated by electron acceptors and values of their redox potentials. The latter effect was shown to be independent of the ArcAB regulatory system.

  2. High rate of translocation-based gene birth on the Drosophila Y chromosome.

    Science.gov (United States)

    Tobler, Ray; Nolte, Viola; Schlötterer, Christian

    2017-10-31

    The Y chromosome is a unique genetic environment defined by a lack of recombination and male-limited inheritance. The Drosophila Y chromosome has been gradually acquiring genes from the rest of the genome, with only seven Y-linked genes being gained over the past 63 million years (0.12 gene gains per million years). Using a next-generation sequencing (NGS)-powered genomic scan, we show that gene transfers to the Y chromosome are much more common than previously suspected: at least 25 have arisen across three Drosophila species over the past 5.4 million years (1.67 per million years for each lineage). The gene transfer rate is significantly lower in Drosophila melanogaster than in the Drosophila simulans clade, primarily due to Y-linked retrotranspositions being significantly more common in the latter. Despite all Y-linked gene transfers being evolutionarily recent (Drosophila Y chromosome to be more dynamic than previously appreciated. Our analytical method provides a powerful means to identify Y-linked gene transfers and will help illuminate the evolutionary dynamics of the Y chromosome in Drosophila and other species. Copyright © 2017 the Author(s). Published by PNAS.

  3. Expression pattern of a nuclear encoded mitochondrial arginine-ornithine translocator gene from Arabidopsis

    Directory of Open Access Journals (Sweden)

    Schneider Anja

    2003-01-01

    Full Text Available Abstract Background Arginine and citrulline serve as nitrogen storage forms, but are also involved in biosynthetic and catabolic pathways. Metabolism of arginine, citrulline and ornithine is distributed between mitochondria and cytosol. For the shuttle of intermediates between cytosol and mitochondria transporters present on the inner mitochondrial membrane are required. Yeast contains a mitochondrial translocator for ornithine and arginine, Ort1p/Arg11p. Ort1p/Arg11p is a member of the mitochondrial carrier family (MCF essential for ornithine export from mitochondria. The yeast arg11 mutant, which is deficient in Ort1p/Arg11p grows poorly on media lacking arginine. Results High-level expression of a nuclear encoded Arabidopsis thaliana homolog (AtmBAC2 of Ort1p/Arg11p was able to suppress the growth deficiency of arg11. RT-PCR analysis demonstrated expression of AtmBAC2 in all tissues with highest levels in flowers. Promoter-GUS fusions showed preferential expression in flowers, i.e. pollen, in the vasculature of siliques and in aborted seeds. Variable expression was observed in leaf vasculature. Induction of the promoter was not observed during the first two weeks in seedlings grown on media containing NH4NO3, arginine or ornithine as sole nitrogen sources. Conclusion AtmBAC2 was isolated as a mitochondrial transporter for arginine in Arabidopsis. The absence of expression in developing seeds and in cotyledons of seedlings indicates that other transporters are responsible for storage and mobilization of arginine in seeds.

  4. Bridge-Induced Translocation between NUP145 and TOP2 Yeast Genes Models the Genetic Fusion between the Human Orthologs Associated With Acute Myeloid Leukemia

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    Valentina Tosato

    2017-09-01

    Full Text Available In mammalian organisms liquid tumors such as acute myeloid leukemia (AML are related to spontaneous chromosomal translocations ensuing in gene fusions. We previously developed a system named bridge-induced translocation (BIT that allows linking together two different chromosomes exploiting the strong endogenous homologous recombination system of the yeast Saccharomyces cerevisiae. The BIT system generates a heterogeneous population of cells with different aneuploidies and severe aberrant phenotypes reminiscent of a cancerogenic transformation. In this work, thanks to a complex pop-out methodology of the marker used for the selection of translocants, we succeeded by BIT technology to precisely reproduce in yeast the peculiar chromosome translocation that has been associated with AML, characterized by the fusion between the human genes NUP98 and TOP2B. To shed light on the origin of the DNA fragility within NUP98, an extensive analysis of the curvature, bending, thermostability, and B-Z transition aptitude of the breakpoint region of NUP98 and of its yeast ortholog NUP145 has been performed. On this basis, a DNA cassette carrying homologous tails to the two genes was amplified by PCR and allowed the targeted fusion between NUP145 and TOP2, leading to reproduce the chimeric transcript in a diploid strain of S. cerevisiae. The resulting translocated yeast obtained through BIT appears characterized by abnormal spherical bodies of nearly 500 nm of diameter, absence of external membrane and defined cytoplasmic localization. Since Nup98 is a well-known regulator of the post-transcriptional modification of P53 target genes, and P53 mutations are occasionally reported in AML, this translocant yeast strain can be used as a model to test the constitutive expression of human P53. Although the abnormal phenotype of the translocant yeast was never rescued by its expression, an exogenous P53 was recognized to confer increased vitality to the translocants, in

  5. Genome-Wide Identification and Characterization of Four Gene Families Putatively Involved in Cadmium Uptake, Translocation and Sequestration in Mulberry

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    Wei Fan

    2018-06-01

    Full Text Available The zinc-regulated transporters, iron-regulated transporter-like proteins (ZIPs, the natural resistance and macrophage proteins (NRAMP, the heavy metal ATPases (HMAs and the metal tolerance or transporter proteins (MTPs families are involved in cadmium (Cd uptake, translocation and sequestration in plants. Mulberry (Morus L., one of the most ecologically and economically important (as a food plant for silkworm production genera of perennial trees, exhibits excellent potential for remediating Cd-contaminated soils. However, there is no detailed information about the genes involved in Cd2+ transport in mulberry. In this study, we identified 31 genes based on a genome-wide analysis of the Morus notabilis genome database. According to bioinformatics analysis, the four transporter gene families in Morus were distributed in each group of the phylogenetic tree, and the gene exon/intron structure and protein motif structure were similar among members of the same group. Subcellular localization software predicted that these transporters were mainly distributed in the plasma membrane and the vacuolar membrane, with members of the same group exhibiting similar subcellular locations. Most of the gene promoters contained abiotic stress-related cis-elements. The expression patterns of these genes in different organs were determined, and the patterns identified, allowing the categorization of these genes into four groups. Under low or high-Cd2+ concentrations (30 μM or 100 μM, respectively, the transcriptional regulation of the 31 genes in root, stem and leaf tissues of M. alba seedlings differed with regard to tissue and time of peak expression. Heterologous expression of MaNRAMP1, MaHMA3, MaZIP4, and MaIRT1 in Saccharomyces cerevisiae increased the sensitivity of yeast to Cd, suggested that these transporters had Cd transport activity. Subcellular localization experiment showed that the four transporters were localized to the plasma membrane of yeast and

  6. Novel gene fusion of PRCC-MITF defines a new member of MiT family translocation renal cell carcinoma: clinicopathological analysis and detection of the gene fusion by RNA sequencing and FISH.

    Science.gov (United States)

    Xia, Qiu-Yuan; Wang, Xiao-Tong; Ye, Sheng-Bing; Wang, Xuan; Li, Rui; Shi, Shan-Shan; Fang, Ru; Zhang, Ru-Song; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Bao, Wei; Zhou, Xiao-Jun; Rao, Qiu

    2018-04-01

    MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. © 2017 John Wiley & Sons Ltd.

  7. Expression study of GLUT4 translocation-related genes in a porcine pre-diabetic model

    DEFF Research Database (Denmark)

    Kristensen, Thea; Fredholm, Merete; Cirera Salicio, Susanna

    2015-01-01

    Obesity is a world-wide exponentially growing health problem that increases the risk of co-morbidities including metabolic syndrome, pre-diabetes, Type 2 Diabetes Mellitus (T2DM), and cancer. These co-morbidities are all complex conditions constituting a big challenge when searching for susceptib......Obesity is a world-wide exponentially growing health problem that increases the risk of co-morbidities including metabolic syndrome, pre-diabetes, Type 2 Diabetes Mellitus (T2DM), and cancer. These co-morbidities are all complex conditions constituting a big challenge when searching...... for susceptibility genes. Identification of relevant genes, which could contribute to an earlier identification of individuals prone to develop diabetes, is urgently needed as many long-term complications can be avoided by preventive measures. Pre-diabetes is mainly associated with hyperglycemia; thus studying...... this phenotype might provide knowledge on relevant genes implicated in molecular mechanisms underlying pre-diabetes, and contributing to the development of T2DM. In the present study, two groups of pigs with high (HGG, N = 6) and low (NGG, N = 6) fasting plasma glucose level respectively were selected from...

  8. Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiao; Zhou, Hao; Duan, Na; Liu, Yongkang; Wang, Zhongqiu [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Zhu, Qingqiang [Medical School of Yangzhou University, Department of Medical Imaging, Subei People' s Hospital, Yangzhou (China); Li, Baoxin [Gulou Hospital, Department of Radiology, Nanjing (China); Cui, Wenjing [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Nanjing University Medical School, Department of Radiology, Jinling Hospital, Nanjing (China); Kundra, Vikas [The University of Texas, M.D. Anderson Cancer Center, Department of Radiology, Houston, TX (United States)

    2017-02-15

    To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. (orig.)

  9. The nT1 translocation separates vulval regulatory elements from the egl-18 and elt-6 GATA factor genes.

    Science.gov (United States)

    Koh, Kyunghee; Bernstein, Yelena; Sundaram, Meera V

    2004-03-01

    egl-18 and elt-6 are partially redundant, adjacent genes encoding GATA factors essential for viability, seam cell development, and vulval development in Caenorhabditis elegans. The nT1 reciprocal translocation causes a strong Vulvaless phenotype, and an nT1 breakpoint was previously mapped to the left arm of LGIV, where egl-18/elt-6 are located. Here we present evidence that the nT1 vulval phenotype is due to a disruption of egl-18/elt-6 function specifically in the vulva. egl-18 mutations do not complement nT1 for vulval defects, and the nT1 breakpoint on LGIV is located within approximately 800 bp upstream of a potential transcriptional start site of egl-18. In addition, we have identified a approximately 350-bp cis-regulatory region sufficient for vulval expression just upstream of the nT1 breakpoint. By examining the fusion state and division patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of vulval development.

  10. Entropic effects in formation of chromosome territories: towards understanding of radiation-induced gene translocation frequency

    Science.gov (United States)

    Gudowska-Nowak, Ewa; Ritter, Sylvia; Durante, Marco; Deperas-Standylo, Joanna; Ciesla, Michal

    2012-07-01

    A detailed understanding of structural organization of biological target, such as geometry of an inter-phase chromosome, is an essential prerequisite for gaining deeper insight into relationship between radiation track structure and radiation-induced biological damage [1]. In particular, coupling of biophysical models aimed to describe architecture of chromosomes and their positioning in a cell nucleus [2-4] with models of local distribution of ionizations caused by passing projectiles, are expected to result in more accurate estimates of aberration induction caused by radiation. There is abundant experimental evidence indicating that arrangements of chromosomes in eukaryotic cell nucleus is non-random and has been evolutionary conserved in specific cell types. Moreover, the radial position of a given chromosome territory (CT) within the cell nucleus has been shown to correlate with its size and gene density. Usually it is assumed that chromosomal geometry and positioning result from the action of specific forces acting locally, such as hydrogen bonds, electrostatic, Van der Waals or hydrophobic interactions operating between nucleosomes and within their interiors. However, it is both desirable and instructive to learn to what extend organization of inter-phase chromosomes is affected by nonspecific entropic forces. In this study we report results of a coarse-grained analysis of a chromatin structure modeled by two distinct approaches. In the first method, we adhere to purely statistical analysis of chromatin packing within a chromosome territory. On the basis of the polymer theory, the chromatin fiber of diameter 30nm is approximated by a chain of spheres, each corresponding to about 30 kbp. Random positioning of the center of the domain is repeated for 1000 spherical nuclei. Configuration of the domain is determined by a random packing of a polymer (a string of identical beads) in estimated fraction of space occupied by a chromosome of a given length and mass

  11. Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes.

    Science.gov (United States)

    Scriber, Jon Mark

    2013-12-24

    Comprising 50%-75% of the world's fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience) may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including "invasive species" in various ecosystems as they may become disrupted in different ways by rapid climate change. "Invasive genes" (into new species and populations) need to be recognized for their positive creative potential and addressed in conservation programs. "Genetic rescue" via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae) with their long-term historical data base (phylogeographical diversity changes) and recent (3-decade) climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced "reshuffling" (recombinations) of species composition, genotypes, and genomes may become

  12. The mitochondrial genome of the stingless bee Melipona bicolor (Hymenoptera, Apidae, Meliponini: sequence, gene organization and a unique tRNA translocation event conserved across the tribe Meliponini

    Directory of Open Access Journals (Sweden)

    Daniela Silvestre

    2008-01-01

    Full Text Available At present a complete mtDNA sequence has been reported for only two hymenopterans, the Old World honey bee, Apis mellifera and the sawfly Perga condei. Among the bee group, the tribe Meliponini (stingless bees has some distinction due to its Pantropical distribution, great number of species and large importance as main pollinators in several ecosystems, including the Brazilian rain forest. However few molecular studies have been conducted on this group of bees and few sequence data from mitochondrial genomes have been described. In this project, we PCR amplified and sequenced 78% of the mitochondrial genome of the stingless bee Melipona bicolor (Apidae, Meliponini. The sequenced region contains all of the 13 mitochondrial protein-coding genes, 18 of 22 tRNA genes, and both rRNA genes (one of them was partially sequenced. We also report the genome organization (gene content and order, gene translation, genetic code, and other molecular features, such as base frequencies, codon usage, gene initiation and termination. We compare these characteristics of M. bicolor to those of the mitochondrial genome of A. mellifera and other insects. A highly biased A+T content is a typical characteristic of the A. mellifera mitochondrial genome and it was even more extreme in that of M. bicolor. Length and compositional differences between M. bicolor and A. mellifera genes were detected and the gene order was compared. Eleven tRNA gene translocations were observed between these two species. This latter finding was surprising, considering the taxonomic proximity of these two bee tribes. The tRNA Lys gene translocation was investigated within Meliponini and showed high conservation across the Pantropical range of the tribe.

  13. Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients

    International Nuclear Information System (INIS)

    Walker, B A; Wardell, C P; Brioli, A; Boyle, E; Kaiser, M F; Begum, D B; Dahir, N B; Johnson, D C; Ross, F M; Davies, F E; Morgan, G J

    2014-01-01

    Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype

  14. Single nucleotide polymorphisms at erythropoietin, superoxide dismutase 1, splicing factor, arginine/serin-rich 15 and plasmacytoma variant translocation genes association with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Maisaa Alwohhaib

    2014-01-01

    Full Text Available A number of genes have been identified in diabetic nephropathy. Association between diabetes-associated nephropathy and polymorphisms in the erythropoietin (EPO gene, variants in the superoxide dismutase 1 (SOD1 gene and plasmacytoma variant translocation 1 (PVT1 gene have been identified. The EPO, SOD1:SFRS15 and PVT1 genes were genotyped using the single nucleotide polymorphism (SNP technique in 38 diabetic nephropathy patients (Group 1 compared with 64 diabetic type 2 subjects without nephropathy (Group 2 at the Mubarak Alkabeer Hospital, Kuwait. The frequency of the risk allele T of the EPO (rs1617640 gene was high in both groups (0.96 in Group 1 and 0.92 in Group 2. Similarly, SNPs of the PVT1 (rs2720709 gene showed a higher frequency of the risk allele G in both groups (0.70 in the Group 1 and 0.68 in Group 2. Although the frequency of the risk allele A was higher than the frequency of the non-risk allele C of the SOD1:SFRS15 gene in both groups, the lowest probability value was observed in those gene SNPs (P = 0.05. We observed that the A allele of the SOD1:SFRS15 gene (rs17880135 was more frequently present in Group 1 (0.75 compared with Group 2 (0.62. Susceptibility to diabetes-associated nephropathy is partially mediated by genetic predisposition, and screening tests may open the gate for new therapeutic approaches.

  15. Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations.

    Science.gov (United States)

    Sotomatsu, M; Hayashi, Y; Kawamura, M; Yugami, S; Shitara, T

    1993-10-01

    A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.

  16. The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia.

    Science.gov (United States)

    Zerrouki, Rachid; Benhassine, Traki; Bensaada, Mustapha; Lauzon, Patricia; Trabzi, Anissa

    2016-03-01

    Many subtypes of acute lymphoblastic leukemia (ALL) are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14), a variant of the translocation (14;14)(q11;q32), is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH) and CCAAT enhancer-binding protein (CEBPE) genes in B-lineage ALL (B-ALL) and may represent a new B-ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE.

  17. The complex translocation (9;14;14 involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Rachid Zerrouki

    2016-03-01

    Full Text Available Abstract Many subtypes of acute lymphoblastic leukemia (ALL are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14, a variant of the translocation (14;14(q11;q32, is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH and CCAAT enhancer-binding protein (CEBPE genes in B-lineage ALL (B-ALL and may represent a new B-ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9(p21,t(14;14(q11;q32. FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC probes showed a complex t(9;14;14 associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A and paired box gene 5 (PAX5 at 9p21-13 and duplication of the fusion gene IGH-CEBPE.

  18. The clinical impact of chromosomal rearrangements with breakpoints upstream of the SOX9 gene: two novel de novo balanced translocations associated with acampomelic campomelic dysplasia.

    Science.gov (United States)

    Fonseca, Ana Carolina S; Bonaldi, Adriano; Bertola, Débora R; Kim, Chong A; Otto, Paulo A; Vianna-Morgante, Angela M

    2013-05-07

    The association of balanced rearrangements with breakpoints near SOX9 [SRY (sex determining region Y)-box 9] with skeletal abnormalities has been ascribed to the presumptive altering of SOX9 expression by the direct disruption of regulatory elements, their separation from SOX9 or the effect of juxtaposed sequences. We report on two sporadic apparently balanced translocations, t(7;17)(p13;q24) and t(17;20)(q24.3;q11.2), whose carriers have skeletal abnormalities that led to the diagnosis of acampomelic campomelic dysplasia (ACD; MIM 114290). No pathogenic chromosomal imbalances were detected by a-CGH. The chromosome 17 breakpoints were mapped, respectively, 917-855 kb and 601-585 kb upstream of the SOX9 gene. A distal cluster of balanced rearrangements breakpoints on chromosome 17 associated with SOX9-related skeletal disorders has been mapped to a segment 932-789 kb upstream of SOX9. In this cluster, the breakpoint of the herein described t(17;20) is the most telomeric to SOX9, thus allowing the redefining of the telomeric boundary of the distal breakpoint cluster region related to skeletal disorders to 601-585 kb upstream of SOX9. Although both patients have skeletal abnormalities, the t(7;17) carrier presents with relatively mild clinical features, whereas the t(17;20) was detected in a boy with severe broncheomalacia, depending on mechanical ventilation. Balanced and unbalanced rearrangements associated with disorders of sex determination led to the mapping of a regulatory region of SOX9 function on testicular differentiation to a 517-595 kb interval upstream of SOX9, in addition to TESCO (Testis-specific enhancer of SOX9 core). As the carrier of t(17;20) has an XY sex-chromosome constitution and normal male development for his age, the segment of chromosome 17 distal to the translocation breakpoint should contain the regulatory elements for normal testis development. These two novel translocations illustrate the clinical variability in carriers of balanced

  19. Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome.

    Science.gov (United States)

    Patel, Chirag; Cooper-Charles, Lisa; McMullan, Dominic J; Walker, Judith M; Davison, Val; Morton, Jenny

    2011-06-01

    Gilles de la Tourette syndrome is a complex neuropsychiatric disorder with a strong genetic basis. We identified a male patient with Tourette syndrome-like tics and an apparently balanced de novo translocation [46,XY,t(2;7)(p24.2;q31)]. Further analysis using array comparative genomic hybridisation (CGH) revealed a cryptic deletion at 7q31.1-7q31.2. Breakpoints disrupting this region have been reported in one isolated and one familial case of Tourette syndrome. In our case, IMMP2L, a gene coding for a human homologue of the yeast inner mitochondrial membrane peptidase subunit 2, was disrupted by the breakpoint on 7q31.1, with deletion of exons 1-3 of the gene. The IMMP2L gene has previously been proposed as a candidate gene for Tourette syndrome, and our case provides further evidence of its possible role in the pathogenesis. The deleted region (7q31.1-7q31.2) of 7.2 Mb of genomic DNA also encompasses numerous genes, including FOXP2, associated with verbal dyspraxia, and the CFTR gene.

  20. Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15(q27;q11.2 associated with Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Slater Howard R

    2005-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (MIM #176270; PWS is caused by lack of the paternally-derived copies, or their expression, of multiple genes in a 4 Mb region on chromosome 15q11.2. Known mechanisms include large deletions, maternal uniparental disomy or mutations involving the imprinting center. De novo balanced reciprocal translocations in 5 reported individuals had breakpoints clustering in SNRPN intron 2 or exon 20/intron 20. To further dissect the PWS phenotype and define the minimal critical region for PWS features, we have studied a 22 year old male with a milder PWS phenotype and a de novo translocation t(4;15(q27;q11.2. Methods We used metaphase FISH to narrow the breakpoint region and molecular analyses to map the breakpoints on both chromosomes at the nucleotide level. The expression of genes on chromosome 15 on both sides of the breakpoint was determined by RT-PCR analyses. Results Pertinent clinical features include neonatal hypotonia with feeding difficulties, hypogonadism, short stature, late-onset obesity, learning difficulties, abnormal social behavior and marked tolerance to pain, as well as sticky saliva and narcolepsy. Relative macrocephaly and facial features are not typical for PWS. The translocation breakpoints were identified within SNRPN intron 17 and intron 10 of a spliced non-coding transcript in band 4q27. LINE and SINE sequences at the exchange points may have contributed to the translocation event. By RT-PCR of lymphoblasts and fibroblasts, we find that upstream SNURF/SNRPN exons and snoRNAs HBII-437 and HBII-13 are expressed, but the downstream snoRNAs PWCR1/HBII-85 and HBII-438A/B snoRNAs are not. Conclusion As part of the PWCR1/HBII-85 snoRNA cluster is highly conserved between human and mice, while no copy of HBII-438 has been found in mouse, we conclude that PWCR1/HBII-85 snoRNAs is likely to play a major role in the PWS- phenotype.

  1. Circadian clock gene aryl hydrocarbon receptor nuclear translocator-like polymorphisms are associated with seasonal affective disorder: An Indian family study.

    Science.gov (United States)

    Rajendran, Bhagya; Janakarajan, Veeramahali Natarajan

    2016-01-01

    Polymorphisms in aryl hydrocarbon receptor nuclear translocator-like (ARNTL) gene, the key component of circadian clock manifests circadian rhythm abnormalities. As seasonal affective disorder (SAD) is associated with disrupted circadian rhythms, the main objective of this study was to screen an Indian family with SAD for ARNTL gene polymorphisms. In this study, 30 members of close-knit family with SAD, 30 age- and sex-matched controls of the same caste with no prior history of psychiatric illness and 30 age- and sex-matched controls belonging to 17 different castes with no prior history of psychiatric illness were genotyped for five different single nucleotide polymorphisms (SNPs) in ARNTL gene by TaqMan allele-specific genotyping assay. Statistical significance was assessed by more powerful quasi-likelihood score test-XM. Most of the family members carried the risk alleles and we observed a highly significant SNP rs2279287 (A/G) in ARNTL gene with an allelic frequency of 0.75. Polymorphisms in ARNTL gene disrupt circadian rhythms causing SAD and genetic predisposition becomes more deleterious in the presence of adverse environment.

  2. The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera.

    Science.gov (United States)

    Grohmann, L; Brennicke, A; Schuster, W

    1992-01-01

    The Oenothera mitochondrial genome contains only a gene fragment for ribosomal protein S12 (rps12), while other plants encode a functional gene in the mitochondrion. The complete Oenothera rps12 gene is located in the nucleus. The transit sequence necessary to target this protein to the mitochondrion is encoded by a 5'-extension of the open reading frame. Comparison of the amino acid sequence encoded by the nuclear gene with the polypeptides encoded by edited mitochondrial cDNA and genomic sequences of other plants suggests that gene transfer between mitochondrion and nucleus started from edited mitochondrial RNA molecules. Mechanisms and requirements of gene transfer and activation are discussed. Images PMID:1454526

  3. Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).

    Science.gov (United States)

    Machida, Junichiro; Félix, Têmis M; Murray, Jeffrey C; Yoshiura, Koh-ichiro; Tanemura, Mitsuyo; Kamamoto, Munefumi; Shimozato, Kazuo; Sonta, Shin-ichi; Ono, Takao

    2009-09-01

    Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate. We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations. Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17. The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.

  4. Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes

    Directory of Open Access Journals (Sweden)

    Brzezinska Agnieszka A

    2006-12-01

    Full Text Available Abstract Background Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. Results Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX domain of p47phox localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47phox, is translocated to the membrane of mature phagosomes. Conclusion We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils.

  5. Accelerators

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    The talk summarizes the principles of particle acceleration and addresses problems related to storage rings like LEP and LHC. Special emphasis will be given to orbit stability, long term stability of the particle motion, collective effects and synchrotron radiation.

  6. DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation

    International Nuclear Information System (INIS)

    Li, C.-C.; Lii, C.-K.; Liu, K.-L.; Yang, J.-J.; Chen, H.-W.

    2007-01-01

    The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation by n-6 and n-3 PUFAs of PB-induced CYP 2B1 expression in rat primary hepatocytes. We used 100 μM arachidonic acid, linoleic acid, eicosapentaenoic acid, and DHA to test this hypothesis. PB triggered the translocation of CAR from the cytosol into the nucleus in a dose-dependent and time-dependent manner in our hepatocyte system, and the CAR distribution in rat primary hepatocytes was significantly affected by DHA. DHA treatment decreased PB-inducible accumulation of CAR in the nuclear fraction and increased it in the cytosolic fraction in a dose-dependent manner. The down-regulation of CYP 2B1 expression by DHA occurred in a dose-dependent manner, and a similar pattern was found for the nuclear accumulation of CAR. The results of immunoprecipitation showed a CAR/RXR heterodimer bound to nuclear receptor binding site 1 (NR-1) of the PB-responsive enhancer module (PBREM) of the CYP 2B1gene. The EMSA results showed that PB-induced CAR binding to NR-1 was attenuated by DHA. Taken together, these results suggest that attenuation of CAR translocation and decreased subsequent binding to NR-1 are involved in DHA's down-regulation of PB-induced CYP 2B1 expression

  7. Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes

    Directory of Open Access Journals (Sweden)

    Jon Mark Scriber

    2013-12-01

    Full Text Available Comprising 50%–75% of the world’s fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including “invasive species” in various ecosystems as they may become disrupted in different ways by rapid climate change. “Invasive genes” (into new species and populations need to be recognized for their positive creative potential and addressed in conservation programs. “Genetic rescue” via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae with their long-term historical data base (phylogeographical diversity changes and recent (3-decade climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced “reshuffling” (recombinations of species composition, genotypes

  8. Nance-Horan syndrome in females due to a balanced X;1 translocation that disrupts the NHS gene: Familial case report and review of the literature.

    Science.gov (United States)

    Gómez-Laguna, Laura; Martínez-Herrera, Alejandro; Reyes-de la Rosa, Alejandra Del Pilar; García-Delgado, Constanza; Nieto-Martínez, Karem; Fernández-Ramírez, Fernando; Valderrama-Atayupanqui, Tania Yanet; Morales-Jiménez, Ariadna Berenice; Villa-Morales, Judith; Kofman, Susana; Cervantes, Alicia; Morán-Barroso, Verónica Fabiola

    2018-01-01

    The Nance-Horan syndrome is an X-linked disorder characterized by congenital cataract, facial features, microcornea, microphthalmia, and dental anomalies; most of the cases are due to NHS gene mutations on Xp22.13. Heterozygous carrier females generally present less severe features, and up to 30% of the affected males have intellectual disability. We describe two patients, mother and daughter, manifesting Nance-Horan syndrome. The cytogenetic and molecular analyses demonstrated a 46,X,t(X;1)(p22.13;q22) karyotype in each of them. No copy-number genomic imbalances were detected by high-density microarray analysis. The mother had a preferential inactivation of the normal X chromosome; expression analysis did not detect any mRNA isoform of NHS. This is the first report of Nance-Horan syndrome due to a skewed X chromosome inactivation resulting from a balanced translocation t(X;1) that disrupts the NHS gene expression, with important implications for clinical presentation and genetic counseling.

  9. Expression of tomato prosystemin gene in Arabidopsis reveals systemic translocation of its mRNA and confers necrotrophic fungal resistance.

    Science.gov (United States)

    Zhang, Haiyan; Yu, Pengli; Zhao, Jiuhai; Jiang, Hongling; Wang, Haiyang; Zhu, Yingfang; Botella, Miguel A; Šamaj, Jozef; Li, Chuanyou; Lin, Jinxing

    2018-01-01

    Systemin (SYS), an octadecapeptide hormone processed from a 200-amino-acid precursor (prosystemin, PS), plays a central role in the systemic activation of defense genes in tomato in response to herbivore and pathogen attacks. However, whether PS mRNA is transferable and its role in systemic defense responses remain unknown. We created the transgenic tomato PS gene tagged with the green fluorescent protein (PS-GFP) using a shoot- or root-specific promoter, and the constitutive 35S promoter in Arabidopsis. Subcellular localization of PS-/SYS-GFP was observed using confocal laser scanning microscopy and gene transcripts were determined using quantitative real-time PCR. In Arabidopsis, PS protein can be processed and SYS is secreted. Shoot-/root-specific expression of PS-GFP in Arabidopsis, and grafting experiments, revealed that the PS mRNA moves in a bi-directional manner. We also found that ectopic expression of PS improves Arabidopsis resistance to the necrotrophic fungus Botrytis cinerea, consistent with substantial upregulation of the transcript levels of specific pathogen-responsive genes. Our results provide novel insights into the multifaceted mechanism of SYS signaling transport and its potential application in genetic engineering for increasing pathogen resistance across diverse plant families. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  10. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22(q24.13;q11.21 in a young girl with dysgerminoma

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    Fiorio Patrizia

    2009-07-01

    Full Text Available Abstract Background RNF139/TRC8 is a potential tumor suppressor gene with similarity to PTCH, a tumor suppressor implicated in basal cell carcinomas and glioblastomas. TRC8 has the potential to act in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control and has been identified in families with hereditary renal (RCC and thyroid cancers. Haploinsufficiency of TRC8 may facilitate development of clear cell-RCC in association with VHL mutations, and may increase risk for other tumor types. We report a paternally inherited balanced translocation t(8;22 in a proposita with dysgerminoma. Methods The translocation was characterized by FISH and the breakpoints cloned, sequenced, and compared. DNA isolated from normal and tumor cells was checked for abnormalities by array-CGH. Expression of genes TRC8 and TSN was tested both on dysgerminoma and in the proposita and her father. Results The breakpoints of the translocation are located within the LCR-B low copy repeat on chromosome 22q11.21, containing the palindromic AT-rich repeat (PATRR involved in recurrent and non-recurrent translocations, and in an AT-rich sequence inside intron 1 of the TRC8 tumor-suppressor gene at 8q24.13. TRC8 was strongly underexpressed in the dysgerminoma. Translin is underexpressed in the dysgerminoma compared to normal ovary. TRC8 is a target of Translin (TSN, a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells. Conclusion A role for TRC8 in dysgerminoma may relate to its interaction with Translin. We propose a model in which one copy of TRC8 is disrupted by a palindrome-mediated translocation followed by complete loss of expression through suppression, possibly mediated by miRNA.

  11. Selected lactic acid-producing bacterial isolates with the capacity to reduce Salmonella translocation and virulence gene expression in chickens.

    Directory of Open Access Journals (Sweden)

    Xiaojian Yang

    Full Text Available BACKGROUND: Probiotics have been used to control Salmonella colonization/infection in chickens. Yet the mechanisms of probiotic effects are not fully understood. This study has characterized our previously-selected lactic acid-producing bacterial (LAB isolates for controlling Salmonella infection in chickens, particularly the mechanism underlying the control. METHODOLOGY/PRINCIPAL FINDINGS: In vitro studies were conducted to characterize 14 LAB isolates for their tolerance to low pH (2.0 and high bile salt (0.3-1.5% and susceptibility to antibiotics. Three chicken infection trials were subsequently carried out to evaluate four of the isolates for reducing the burden of Salmonella enterica serovar Typhimurium in the broiler cecum. Chicks were gavaged with LAB cultures (10(6-7 CFU/chick or phosphate-buffered saline (PBS at 1 day of age followed by Salmonella challenge (10(4 CFU/chick next day. Samples of cecal digesta, spleen, and liver were examined for Salmonella counts on days 1, 3, or 4 post-challenge. Salmonella in the cecum from Trial 3 was also assessed for the expression of ten virulence genes located in its pathogenicity island-1 (SPI-1. These genes play a role in Salmonella intestinal invasion. Tested LAB isolates (individuals or mixed cultures were unable to lower Salmonella burden in the chicken cecum, but able to attenuate Salmonella infection in the spleen and liver. The LAB treatments also reduced almost all SPI-1 virulence gene expression (9 out of 10 in the chicken cecum, particularly at the low dose. In vitro treatment with the extracellular culture fluid from a LAB culture also down-regulated most SPI-1 virulence gene expression. CONCLUSIONS/SIGNIFICANCE: The possible correlation between attenuation of Salmonella infection in the chicken spleen and liver and reduction of Salmonella SPI-1 virulence gene expression in the chicken cecum by LAB isolates is a new observation. Suppression of Salmonella virulence gene expression in

  12. A novel Robertsonian translocation event leads to transfer of a stem rust resistance gene (Sr52) effective against race Ug99 from Dasypyrum villosum into bread wheat.

    Science.gov (United States)

    Qi, L L; Pumphrey, M O; Friebe, Bernd; Zhang, P; Qian, C; Bowden, R L; Rouse, M N; Jin, Y; Gill, B S

    2011-06-01

    Stem rust (Puccinia graminis f. sp. tritici Eriks. & E. Henn.) (the causal agent of wheat stem rust) race Ug99 (also designated TTKSK) and its derivatives have defeated several important stem rust resistance genes widely used in wheat (Triticum aestivum L.) production, rendering much of the worldwide wheat acreage susceptible. In order to identify new resistance sources, a large collection of wheat relatives and genetic stocks maintained at the Wheat Genetic and Genomic Resources Center was screened. The results revealed that most accessions of the diploid relative Dasypyrum villosum (L.) Candargy were highly resistant. The screening of a set of wheat-D. villosum chromosome addition lines revealed that the wheat-D. villosum disomic addition line DA6V#3 was moderately resistant to race Ug99. The objective of the present study was to produce and characterize compensating wheat-D. villosum whole arm Robertsonian translocations (RobTs) involving chromosomes 6D of wheat and 6V#3 of D. villosum through the mechanism of centric breakage-fusion. Seven 6V#3-specific EST-STS markers were developed for screening F(2) progeny derived from plants double-monosomic for chromosomes 6D and 6V#3. Surprisingly, although 6D was the target chromosome, all recovered RobTs involved chromosome 6A implying a novel mechanism for the origin of RobTs. Homozygous translocations (T6AS·6V#3L and T6AL·6V#3S) with good plant vigor and full fertility were selected from F(3) families. A stem rust resistance gene was mapped to the long arm 6V#3L in T6AS·6V#3L and was designated as Sr52. Sr52 is temperature-sensitive and is most effective at 16°C, partially effective at 24°C, and ineffective at 28°C. The T6AS·6V#3L stock is a new source of resistance to Ug99, is cytogenetically stable, and may be useful in wheat improvement.

  13. Gene gun bombardment-mediated expression and translocation of EGFP-tagged GLUT4 in skeletal muscle fibres in vivo

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M M; Reynet, Christine; Schjerling, Peter

    2002-01-01

    the enhanced green fluorescent protein (EGFP) labelling technique with physical transfection methods in vivo: intramuscular plasmid injection or gene gun bombardment. During optimisation experiments with plasmid coding for the EGFP reporter alone EGFP-positive muscle fibres were counted after collagenase...... treatment of in vivo transfected flexor digitorum brevis (FDB) muscles. In contrast to gene gun bombardment, intramuscular injection produced EGFP expression in only a few fibres. Regardless of the transfection technique, EGFP expression was higher in muscles from 2-week-old rats than in those from 6-week......Cellular protein trafficking has been studied to date only in vitro or with techniques that are invasive and have a low time resolution. To establish a gentle method for analysis of glucose transporter-4 (GLUT4) trafficking in vivo in fully differentiated rat skeletal muscle fibres we combined...

  14. Insertional translocation leading to a 4q13 duplication including the EPHA5 gene in two siblings with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Matoso, Eunice; Melo, Joana B; Ferreira, Susana I; Jardim, Ana; Castelo, Teresa M; Weise, Anja; Carreira, Isabel M

    2013-08-01

    An insertional translocation (IT) can result in pure segmental aneusomy for the inserted genomic segment allowing to define a more accurate clinical phenotype. Here, we report on two siblings sharing an unbalanced IT inherited from the mother with a history of learning difficulty. An 8-year-old girl with developmental delay, speech disability, and attention-deficit hyperactivity disorder (ADHD), showed by GTG banding analysis a subtle interstitial alteration in 21q21. Oligonucleotide array comparative genomic hybridization (array-CGH) analysis showed a 4q13.1-q13.3 duplication spanning 8.6 Mb. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones confirmed the rearrangement, a der(21)ins(21;4)(q21;q13.1q13.3). The duplication described involves 50 RefSeq genes including the EPHA5 gene that encodes for the EphA5 receptor involved in embryonic development of the brain and also in synaptic remodeling and plasticity thought to underlie learning and memory. The same rearrangement was observed in a younger brother with behavioral problems and also exhibiting ADHD. ADHD is among the most heritable of neuropsychiatric disorders. There are few reports of patients with duplications involving the proximal region of 4q and a mild phenotype. To the best of our knowledge this is the first report of a duplication restricted to band 4q13. This abnormality could be easily missed in children who have nonspecific cognitive impairment. The presence of this behavioral disorder in the two siblings reinforces the hypothesis that the region involved could include genes involved in ADHD. Copyright © 2013 Wiley Periodicals, Inc.

  15. B-cell translocation gene 3 overexpression inhibits proliferation and invasion of colorectal cancer SW480 cells via Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Mao, D; Qiao, L; Lu, H; Feng, Y

    2016-01-01

    Increasing evidences have shown that B-cell translocation gene 3 (BTG3) inhibits metastasis of multiple cancer cells. However, the role of BTG3 in colorectal cancer (CRC) and its possible mechanism have not yet been reported. In our study, we evaluated BTG3 expression in several CRC cell lines. Then, pcDNA3.1-BTG3 was transfected into SW480 cells. We found that BTG3 was upregulated in SW480 cells after overexpression plasmid transfection. BTG3 overexpression significantly inhibited cell growth and decreased PCNA (proliferating cell nuclear antigen) and Ki67 levels. BTG3 overexpression markedly downregulated Cyclin D1 and Cyclin E1 levels, whereas elevated p27. Overexpression of BTG3 arrested the cell cycle at G1 phase, which was abrogated by p27 silencing. Furthermore, migration, invasion and EMT of SW480 cells were significantly suppressed by BTG3 overexpression. Further investigations showed the inhibition of Wnt/β-catenin signaling pathway. We then used GSK3β specific inhibitor SB-216763 to activate the Wnt/β-catenin signaling pathway. We found that Wnt/β-catenin signaling pathway activation reversed the effect of BTG3 overexpression on cell proliferation, cell cycle progression, invasion and EMT. In conclusion, BTG3 overexpression inhibited cell growth, induced cell cycle arrest and suppressed the metastasis of SW480 cells via the Wnt/β-catenin signaling pathway. BTG3 may be considered as a therapeutic target in CRC treatment.

  16. Accelerating Innovation in the Creation of Biovalue: The Cell and Gene Therapy Catapult.

    Science.gov (United States)

    Gardner, John; Webster, Andrew

    2017-09-01

    The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to "accelerate" innovation. This article examines in detail one such agency, the United Kingdom's Cell and Gene Therapy Catapult (CGTC). We describe CGTC's role as an accelerator agency and its value narrative, which combines both "health and wealth." Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field.

  17. Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. I. Results obtained after hybridization of human cells carrying reciprocal translocations involving chromosome 1.

    Science.gov (United States)

    Jongsma, A P; Burgerhout, W G

    1977-01-01

    Regional localization studies of genes coding for human PGD, PPH1, PGM1, UGPP, GuK1, Pep-C, and FH, which have been assigned to chromosome 1, were performed with man-Chinese hamster somatic cell hybrids, Informative hybrids that retained fragments of the human chromosome 1 were produced by fusion of hamster cells with human cells carrying reciprocal translocations involving chromosome 1. Analysis of the hybrids that retained one of the translocation chromosomes or de novo rearrangements involving the human 1 revealed the following gene positions: PGD and PPH1 in 1pter leads to 1p32, PGM1 in 1p32 leads to 1p22, UGPP and GuK1 in 1q21 leads to 1q42, FH in 1qter leads to 1q42, and Pep-C probably in 1q42.

  18. Cloning of the gene encoding the δ subunit of the human T-cell receptor reveals its physical organization within the α-subunit locus and its involvement in chromosome translocations in T-cell malignancy

    International Nuclear Information System (INIS)

    Isobe, M.; Russo, G.; Haluska, F.G.; Croce, C.M.

    1988-01-01

    By taking advantage of chromosomal walking techniques, the authors have obtained clones that encompass the T-cell receptor (TCR) δ-chain gene. They analyzed clones spanning the entire J α region extending 115 kilobases 5' of the TCR α-chain constant region and have shown that the TCR δ-chain gene is located over 80 kilobases 5' of C α . TCR δ-chain gene is rearranged in the γ/δ-expressing T-cell line Peer and is deleted in α/β-expressing T-cell lines. Sequence analysis of portions of this genomic region demonstrates its identity with previously described cDNA clones corresponding to the C δ and J δ segments. Furthermore, they have analyzed a t(8;14)-(q24;q11) chromosome translocation from a T-cell leukemia and have shown that the J δ segment is rearranged in cells deriving from this tumor and probably directly involved in the translocation. Thus, the newly clones TCR δ chain is implicated in the genesis of chromosome translocations in T-cell malignancies carrying cytogenetic abnormalities of band 14q11

  19. The multislice CT findings of renal carcinoma associated with XP11.2 translocation/TFE gene fusion and collecting duct carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Qingqiang; Zhu Wenrong; Chen Wenxin; Wu Jingtao [Subei People' s Hospital, Clinical School of Medical Coll., Yangzhou (China)], e-mail: wujingtaodoctor@163.com; Wang Zhongqiu [Dept. of Radiology, East Hospital, Tongji Univ. School of Medicine, Shanghai (China)

    2013-04-15

    Background: Renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusion (Xp11.2/TFE RCC), and collecting duct carcinoma (CDC) are uncommon subtypes of renal cell carcinomas. Purpose: To investigate the multislice CT (MSCT) characteristics of these two tumor types. Material and Methods Nine patients with Xp11.2/TFE RCC and 10 patients with CDC were studied retrospectively. MSCT was undertaken to investigate differences in tumor characteristics and enhancement patterns. Results: All patients had single tumors centered in the renal medulla. Two patients with each tumor type had lymph node involvement and there was a single case of hepatic metastasis (Xp11.2/TFE RCC). The mean tumor diameter of Xp11.2/TFE RCC tumors was significantly larger than for CDC tumors. Two patients with Xp11.2/TFE RCC had cystic components as did eight patients with CDC (P < 0.05). Calcifications were present in six patients, each with CDC. Clear tumor boundaries were visible in two patients with CDC and in nine with Xp11.2/TFE RCC (P < 0.05). The density of Xp11.2/TFE RCC tumors was greater than that of CDC tumors, normal renal cortex, or medulla on unenhanced CT. Enhancement was higher with Xp11.2/TFE RCC than with CDC tumors during all phases. Xp11.2/TFE RCC enhancement was higher than in the renal medulla during cortical and medullary phase but lower than in normal renal medulla during the delayed phase. CDC tumor enhancement was lower than that for normal renal medulla during all enhanced phases. Conclusion: Both tumor types originated from the renal medulla. Distinguishing features included density on unenhanced CT, enhancement patterns, and capsule signs. Identifying these differences may aid diagnosis.

  20. Effector genomics accelerates discovery and functional profiling of potato disease resistance and phytophthora infestans avirulence genes.

    Directory of Open Access Journals (Sweden)

    Vivianne G A A Vleeshouwers

    Full Text Available Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R genes into potato (Solanum tuberosum is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties.

  1. Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9;14)(p21-22;q11) in an acute lymphoblastic leukemia of B-cell type.

    Science.gov (United States)

    Duro, D; Bernard, O; Della Valle, V; Leblanc, T; Berger, R; Larsen, C J

    1996-02-15

    We have reported previously a preliminary study of a t(9;14)(p21-22; q11) in B-cell acute lymphoblastic leukemia. This translocation had rearranged the TCRA/D locus on chromosome band 14q11 and the locus encoding the tumor suppressor gene P16INK4/MTS1 (P16) on band 9p21 (D. Duro et al., Oncogene, 11: 21-29, 1995). In the present report, the breakpoints were precisely localized on each chromosome partner. On the 14q- derivative, the sequence derived from chromosome 9 was interrupted at 1.0 kb upstream of the first exon of P16, close to a consensus recombination heptamer, CACTGTG. In addition, the chromosome 14 breakpoint was localized at the end of the TCRD2 (delta 2) segment, and 22 residues with unknown origin were present at the translocation junction. On the 9p+ derivative, chromosome 9 sequences were in continuity with those displaced onto chromosome 14, and the 14q11 breakpoint was located within TCRJA29 segment. These features are consistent with aberrant activity of the TCR gene recombinase complex. Although all three coding exons of P16 were displaced onto the chromosome 14q-derivative, no P16 transcript was detected in the leukemic cells. Because the region spanning the P16 exon 1 was not inactivated by methylation and because the other P16 allele was deleted, the implication is that the chromosome breakpoint was likely to disrupt regulatory elements involved in the normal expression of the gene. As a whole, then, our results show that translocations affecting band 9p21 can participate to the inactivation of P16, thus justifying a systematic survey of translocations of the 9p21 band in acute lymphoblastic leukemia.

  2. Chromosomal Translocations: Chicken or Egg? | Center for Cancer Research

    Science.gov (United States)

    Many tumor cells have abnormal chromosomes. Some of these abnormalities are caused by chromosomal translocations, which occur when two chromosomes break and incorrectly rejoin, resulting in an exchange of genetic material. Translocations can activate oncogenes, silence tumor suppressor genes, or result in the creation of completely new fusion gene products. While there is

  3. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Directory of Open Access Journals (Sweden)

    Natalay Kouprina

    2004-05-01

    Full Text Available Primary microcephaly (MCPH is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  4. FastGCN: a GPU accelerated tool for fast gene co-expression networks.

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    Meimei Liang

    Full Text Available Gene co-expression networks comprise one type of valuable biological networks. Many methods and tools have been published to construct gene co-expression networks; however, most of these tools and methods are inconvenient and time consuming for large datasets. We have developed a user-friendly, accelerated and optimized tool for constructing gene co-expression networks that can fully harness the parallel nature of GPU (Graphic Processing Unit architectures. Genetic entropies were exploited to filter out genes with no or small expression changes in the raw data preprocessing step. Pearson correlation coefficients were then calculated. After that, we normalized these coefficients and employed the False Discovery Rate to control the multiple tests. At last, modules identification was conducted to construct the co-expression networks. All of these calculations were implemented on a GPU. We also compressed the coefficient matrix to save space. We compared the performance of the GPU implementation with those of multi-core CPU implementations with 16 CPU threads, single-thread C/C++ implementation and single-thread R implementation. Our results show that GPU implementation largely outperforms single-thread C/C++ implementation and single-thread R implementation, and GPU implementation outperforms multi-core CPU implementation when the number of genes increases. With the test dataset containing 16,000 genes and 590 individuals, we can achieve greater than 63 times the speed using a GPU implementation compared with a single-thread R implementation when 50 percent of genes were filtered out and about 80 times the speed when no genes were filtered out.

  5. Cutaneous hidradenocarcinoma: a clinicopathological, immunohistochemical, and molecular biologic study of 14 cases, including Her2/neu gene expression/amplification, TP53 gene mutation analysis, and t(11;19) translocation.

    Science.gov (United States)

    Kazakov, Dmitry V; Ivan, Doina; Kutzner, Heinz; Spagnolo, Dominic V; Grossmann, Petr; Vanecek, Tomas; Sima, Radek; Kacerovska, Denisa; Shelekhova, Ksenia V; Denisjuk, Natalja; Hillen, Uwe; Kuroda, Naoto; Mukensnabl, Petr; Danis, Dusan; Michal, Michal

    2009-05-01

    , in 2 cases, a minority of the neoplastic cells (10%-20%) demonstrated nuclear staining, whereas the remaining 4 cases were negative. Of 9 specimens of hidradenocarcinoma studied for TP53 mutations, 2 harbored mutations, whereas the remaining 7 specimens showed the wild-type sequence. Of 11 specimens studied for translocation t(11;19), 2 cases harbored the translocation. It is concluded that cutaneous hidradenocarcinomas show some microscopic heterogeneity and comprise both low- and high-grade lesions that cytologically are similar to their benign counterpart, the hidradenoma. Within the spectrum of low-grade lesions, there seem to exist tumors almost indistinguishable from hidradenomas but still being capable of regional or distant metastasis. Similar to hidradenomas, hidradenocarcinomas show a t(11;19) translocation, but it is a significantly rarer event. Even rarer is the amplification of the Her2/neu gene. Of note is the relatively low frequency of TP53 mutations despite a high rate of p53 protein expression at the immunohistochemical level.

  6. Plastid-Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae.

    Science.gov (United States)

    Weng, Mao-Lun; Ruhlman, Tracey A; Jansen, Robert K

    2016-06-27

    Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid-nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (ω) were accelerated in both plastid- (CpRP) and nuclear-encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased ω in CpRP was mainly due to intensified positive selection whereas increased ω in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Plastid–Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae

    Science.gov (United States)

    Weng, Mao-Lun; Ruhlman, Tracey A.; Jansen, Robert K.

    2016-01-01

    Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid–nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (ω) were accelerated in both plastid- (CpRP) and nuclear-encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased ω in CpRP was mainly due to intensified positive selection whereas increased ω in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. PMID:27190001

  8. cudaMap: a GPU accelerated program for gene expression connectivity mapping.

    Science.gov (United States)

    McArt, Darragh G; Bankhead, Peter; Dunne, Philip D; Salto-Tellez, Manuel; Hamilton, Peter; Zhang, Shu-Dong

    2013-10-11

    Modern cancer research often involves large datasets and the use of sophisticated statistical techniques. Together these add a heavy computational load to the analysis, which is often coupled with issues surrounding data accessibility. Connectivity mapping is an advanced bioinformatic and computational technique dedicated to therapeutics discovery and drug re-purposing around differential gene expression analysis. On a normal desktop PC, it is common for the connectivity mapping task with a single gene signature to take > 2h to complete using sscMap, a popular Java application that runs on standard CPUs (Central Processing Units). Here, we describe new software, cudaMap, which has been implemented using CUDA C/C++ to harness the computational power of NVIDIA GPUs (Graphics Processing Units) to greatly reduce processing times for connectivity mapping. cudaMap can identify candidate therapeutics from the same signature in just over thirty seconds when using an NVIDIA Tesla C2050 GPU. Results from the analysis of multiple gene signatures, which would previously have taken several days, can now be obtained in as little as 10 minutes, greatly facilitating candidate therapeutics discovery with high throughput. We are able to demonstrate dramatic speed differentials between GPU assisted performance and CPU executions as the computational load increases for high accuracy evaluation of statistical significance. Emerging 'omics' technologies are constantly increasing the volume of data and information to be processed in all areas of biomedical research. Embracing the multicore functionality of GPUs represents a major avenue of local accelerated computing. cudaMap will make a strong contribution in the discovery of candidate therapeutics by enabling speedy execution of heavy duty connectivity mapping tasks, which are increasingly required in modern cancer research. cudaMap is open source and can be freely downloaded from http://purl.oclc.org/NET/cudaMap.

  9. Problem-elephant translocation: translocating the problem and the elephant?

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    Prithiviraj Fernando

    Full Text Available Human-elephant conflict (HEC threatens the survival of endangered Asian elephants (Elephas maximus. Translocating "problem-elephants" is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: "homers" returned to the capture site, "wanderers" ranged widely, and "settlers" established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals.

  10. Simulations of polymer translocation

    NARCIS (Netherlands)

    Vocks, H.

    2008-01-01

    Transport of molecules across membranes is an essential mechanism for life processes. These molecules are often long, and the pores in the membranes are too narrow for the molecules to pass through as a single unit. In such circumstances, the molecules have to squeeze --- i.e., translocate ---

  11. Dek-can rearrangement in translocation (6;9)(p23;q34)

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; van der Plas, D. C.; Selleri, L.; Bartram, C. R.; Martiat, P.; Culligan, D.; Padua, R. A.; Hasper-Voogt, K. P.; Hagemeijer, A.

    1992-01-01

    The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated

  12. [The influence of combinations of alien translocations on in vitro androgenesis in near-isogenic lines of spring bread wheat].

    Science.gov (United States)

    Sibikeeva, Yu E; Sibikeev, S N

    2014-07-01

    The features of in vitro androgenesis were studied in Cultured anthers of spring bread wheats L503 and Dobrynya, having 7DS-7DL-7Ae#1 L translocation with genes Lrl9/Sr25 (Lrl9 translocation) from Agropyron elongatum (Host.) P.B. and their near-isogenic lines carrying combinations of Lrl9 translocation with translocations: 1BL-IR#1S with genes Pm8/Sr31/Lr26/Yr9 (Lr26translocation) from Secale cereal L., 4BS-4BL-2R#1L with genes Lr25/Pm7 (Lr25 translocation) from Secale cereal, 3DS-3DL-3Ae#1L with genes Lr24/Sr24 (Lr24 translocation) from Agropyron elongatum and 6BS-6BL-6U#1L with gene Lr9 (Lr9 translocation) from Aegilops umbellulata Zhuk. In comparison with those varieties having received the Lrl9 translocation, the following was established: (1) the combination of translocations Lr19+26 increased embryo frequency and green plant regeneration; (2) the combination of translocations Lr19+9 decreased embryo frequency but increased green plant regeneration; (3) the combination of translocations Lr19+24 decreased embryo frequency but increased green and albino plant regeneration; (4) the combination of translocations Lr19+25 increased embryo frequency and green plant regeneration but decreased albino plant regeneration. Thus, on near-isogenic lines of spring bread wheat, the influences of genotypes of four alien translocation combinations on in vitro androgenesis were determined.

  13. Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

    Directory of Open Access Journals (Sweden)

    Duda Marlena

    2012-11-01

    Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

  14. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis.

    Science.gov (United States)

    Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank

    2008-01-01

    In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). In early severe sepsis a gene expression pattern with

  15. Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-κB pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.M.; Pang, A.X., E-mail: zhaoliming515@126.com [Department of Nuclear Medicine, Linyi People' s Hospital, Linyi (China); Department of Urology, Linyi People' s Hospital, Linyi (China)

    2017-10-01

    Iodine-131 ({sup 131}I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following {sup 131}I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with {sup 131}I. They were then assessed for {sup 131}I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and {sup 131}I or with a NF-kB inhibitor of BMS-345541 and {sup 131}I, non-transfected SW579 cells were assessed in JNK/NFkB pathways. It was observed that {sup 131}I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G{sub 0}/G{sub 1} phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and {sup 131}I, the non transfected SW579 cell lines significantly inhibited JNK pathway, NF-kB pathway and the expression of BTG2. However, when treated with BMS-345541 and {sup 131}I, only the NF-kB pathway was suppressed. {sup 131}I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF--κB pathways. (author)

  16. Mapping of Leaf Rust Resistance Genes and Molecular Characterization of the 2NS/2AS Translocation in the Wheat Cultivar Jagger.

    Science.gov (United States)

    Xue, Shulin; Kolmer, James A; Wang, Shuwen; Yan, Liuling

    2018-04-19

    Winter wheat cultivar 'Jagger' was recently found to have an alien chromosomal segment 2NS that has Lr37 , a gene conferring resistance against leaf rust caused by Puccinia triticina The objective of this study was to map and characterize the gene(s) for seedling leaf rust resistance in Jagger. The recombinant inbred line (RIL) population of Jagger × '2174' was inoculated with leaf rust pathogen THBJG and BBBDB, and evaluated for infection type (IT) response. A major quantitative trait locus (QTL) for THBJG and BBBDB was coincidently mapped to chromosome arm 2AS, and the QTL accounted for 56.6% - 66.2% of total phenotypic variation in infection type (IT) response to THBJG, and 72.1% - 86.9% to BBBDB. The causal gene for resistance to these rust races was mapped to the 2NS segment in Jagger. The 2NS segment was located in a region of approximately 27.8 Mb starting from the telomere of chromosome arm 2AS, based on the sequences of the A genome in tetraploid wheat. The Lr17a gene on chromosome arm 2AS was delimited to 3.1 Mb in the genomic region, which was orthologous to the 2NS segment. Therefore, the Lr37 gene in the 2NS segment can be pyramided with other effective resistance genes, rather than Lr17a in wheat, to improve resistance to rust diseases. Copyright © 2018, G3: Genes, Genomes, Genetics.

  17. Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern.

    Directory of Open Access Journals (Sweden)

    Moisés Selman

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is characterized by the insidious onset of dyspnea or cough. However, a subset of patients has a short duration of symptoms with rapid progression to end-stage disease. In this study, we evaluated clinical and molecular features of "rapid" and "slow" progressors with IPF. METHODS AND FINDINGS: 26 patients with 24 months of symptoms [slow progressors] were studied. Survival was analyzed by the Kaplan-Meyer method and proportional hazard's model. Lung microarrays and tissue proteins were measured in a subset of patients. No differences were found in age, physiologic impairment and bronchoalveolar lavage (BAL cellular profile. There were more males (OR = 6.5; CI:1.4-29.5; p = 0.006 and smokers (OR = 3.04; CI:1.1-8.3; p = 0.04 in the rapid progressors group. Survival from the beginning of symptoms was significantly reduced in rapid progressors (HR = 9.0; CI:4.48-18.3; p2-fold increase of active matrix metalloproteinase-9, and induced a higher fibroblast migration compared with slow progressors and controls [238+/-98% versus 123+/-29% (p<0.05 and 30+/-17% (p<0.01]. CONCLUSIONS/SIGNIFICANCE: A subgroup of IPF patients, predominantly smoking males, display an accelerated clinical course and have a gene expression pattern that is different from those with slower progression and longer survival. These findings highlight the variability in the progression of IPF, and may explain, in part, the difficulty in obtaining significant and reproducible results in studies of therapeutic interventions in patients with IPF.

  18. HRAS1-selected chromosome transfer generates markers that colocalize aniridia- and genitourinary dysplasia-associated translocation breakpoints and the Wilms tumor gene within band 11p13.

    OpenAIRE

    Porteous, D J; Bickmore, W; Christie, S; Boyd, P A; Cranston, G; Fletcher, J M; Gosden, J R; Rout, D; Seawright, A; Simola, K O

    1987-01-01

    We show that chromosome-mediated gene transfer can provide an enriched source of DNA markers for predetermined, subchromosomal regions of the human genome. Forty-four human DNA recombinants isolated from a HRAS1-selected chromosome-mediated gene transformant map exclusively to chromosome 11, with several sublocalizing to the Wilms tumor region at 11p13. We present a detailed molecular map of the deletion chromosomes 11 from five WAGR (Wilms tumor/aniridia/genitourinary abnormalities/mental re...

  19. Familial cryptic translocation in Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Weyerts, L.K.; Wiley, J.E.; Loud, K.M. [ECU School of Medicine, Greenville, NC (United States)] [and others

    1994-09-01

    The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

  20. Sorting genomes by reciprocal translocations, insertions, and deletions.

    Science.gov (United States)

    Qi, Xingqin; Li, Guojun; Li, Shuguang; Xu, Ying

    2010-01-01

    The problem of sorting by reciprocal translocations (abbreviated as SBT) arises from the field of comparative genomics, which is to find a shortest sequence of reciprocal translocations that transforms one genome Pi into another genome Gamma, with the restriction that Pi and Gamma contain the same genes. SBT has been proved to be polynomial-time solvable, and several polynomial algorithms have been developed. In this paper, we show how to extend Bergeron's SBT algorithm to include insertions and deletions, allowing to compare genomes containing different genes. In particular, if the gene set of Pi is a subset (or superset, respectively) of the gene set of Gamma, we present an approximation algorithm for transforming Pi into Gamma by reciprocal translocations and deletions (insertions, respectively), providing a sorting sequence with length at most OPT + 2, where OPT is the minimum number of translocations and deletions (insertions, respectively) needed to transform Pi into Gamma; if Pi and Gamma have different genes but not containing each other, we give a heuristic to transform Pi into Gamma by a shortest sequence of reciprocal translocations, insertions, and deletions, with bounds for the length of the sorting sequence it outputs. At a conceptual level, there is some similarity between our algorithm and the algorithm developed by El Mabrouk which is used to sort two chromosomes with different gene contents by reversals, insertions, and deletions.

  1. Search for major genes with progeny test data to accelerate the development of genetically superior loblolly pine

    Energy Technology Data Exchange (ETDEWEB)

    NCSU

    2003-12-30

    This research project is to develop a novel approach that fully utilized the current breeding materials and genetic test information available from the NCSU-Industry Cooperative Tree Improvement Program to identify major genes that are segregating for growth and disease resistance in loblolly pine. If major genes can be identified in the existing breeding population, they can be utilized directly in the conventional loblolly pine breeding program. With the putative genotypes of parents identified, tree breeders can make effective decisions on management of breeding populations and operational deployment of genetically superior trees. Forest productivity will be significantly enhanced if genetically superior genotypes with major genes for economically important traits could be deployed in an operational plantation program. The overall objective of the project is to develop genetic model and analytical methods for major gene detection with progeny test data and accelerate the development of genetically superior loblolly pine. Specifically, there are three main tasks: (1) Develop genetic models for major gene detection and implement statistical methods and develop computer software for screening progeny test data; (2) Confirm major gene segregation with molecular markers; and (3) Develop strategies for using major genes for tree breeding.

  2. BCR translocation to derivative chromosome 2, a new case of chronic myeloid leukemia with complex variant translocation and Philadelphia chromosome

    International Nuclear Information System (INIS)

    Al-Achkar, W.; Wafa, A.; Al-Medani, S.

    2011-01-01

    The well-known typical fusion gene BCR/ABL can be observed in connection with a complex translocation event in only 5-8% of cases with chronic myeloid leukemia (CML). Herein we report an exceptional CML case with complex chromosomal aberrations not observed before, translocated BCR to the derivative chromosome 2 [der(2)], additional to involving a four chromosomes translocation implying chromosomal regions such as 1p32 and 2q21 besides 9q34 and 22q11.2. Which were characterized by molecular cytogenetics. (author)

  3. Efficient induction of Wheat-agropyron cristatum 6P translocation lines and GISH detection.

    Directory of Open Access Journals (Sweden)

    Liqiang Song

    Full Text Available The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by (60Co-γirradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes.

  4. Isolation of Hox cluster genes from insects reveals an accelerated sequence evolution rate.

    Directory of Open Access Journals (Sweden)

    Heike Hadrys

    Full Text Available Among gene families it is the Hox genes and among metazoan animals it is the insects (Hexapoda that have attracted particular attention for studying the evolution of development. Surprisingly though, no Hox genes have been isolated from 26 out of 35 insect orders yet, and the existing sequences derive mainly from only two orders (61% from Hymenoptera and 22% from Diptera. We have designed insect specific primers and isolated 37 new partial homeobox sequences of Hox cluster genes (lab, pb, Hox3, ftz, Antp, Scr, abd-a, Abd-B, Dfd, and Ubx from six insect orders, which are crucial to insect phylogenetics. These new gene sequences provide a first step towards comparative Hox gene studies in insects. Furthermore, comparative distance analyses of homeobox sequences reveal a correlation between gene divergence rate and species radiation success with insects showing the highest rate of homeobox sequence evolution.

  5. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.

    Science.gov (United States)

    Platt, Adam; Morten, John; Ji, Qunsheng; Elvin, Paul; Womack, Chris; Su, Xinying; Donald, Emma; Gray, Neil; Read, Jessica; Bigley, Graham; Blockley, Laura; Cresswell, Carl; Dale, Angela; Davies, Amanda; Zhang, Tianwei; Fan, Shuqiong; Fu, Haihua; Gladwin, Amanda; Harrod, Grace; Stevens, James; Williams, Victoria; Ye, Qingqing; Zheng, Li; de Boer, Richard; Herbst, Roy S; Lee, Jin-Soo; Vasselli, James

    2015-03-23

    To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment. Archival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients. The prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3-1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n = 26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4-6 copies in ≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). Of RET-rearrangement-positive patients, none had an objective response in the vandetanib arm and one patient responded in the comparator arm. Radiologic evidence of tumor shrinkage was observed in two patients treated with vandetanib and one treated with comparator drug. The objective response rate was similar in the vandetanib and comparator arms for patients positive for RET copy number gains or RET protein expression. We have identified prevalence for three RET biomarkers in a population predominated by non-Asians and smokers. RET rearrangement prevalence was lower than previously reported. We found no evidence of a differential benefit for efficacy by IHC and RET gene copy number gains. The low prevalence of RET rearrangements (0.7%) prevents firm conclusions regarding association of vandetanib treatment with

  6. Abdominal radiation causes bacterial translocation

    International Nuclear Information System (INIS)

    Guzman-Stein, G.; Bonsack, M.; Liberty, J.; Delaney, J.P.

    1989-01-01

    The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa

  7. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...

  8. SIGNIFICANCE OF ETV6-RUNX1 FUSION GENE TRANSCRIPT DETECTION IN PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA WITH TRANSLOCATION t(12;21(p13;q22

    Directory of Open Access Journals (Sweden)

    G. A. Tsaur

    2017-01-01

    Full Text Available Introduction. Translocation t(12;21(p13;q22 is one of the most common structural genetic abnormalities in childhood acute lymphoblastic leukemia (ALL. It cannot be detected by conventional G-banding, so a reverse-transcriptase polymerase chain reaction (RT-PCR or fluorescent in situ hybridization are used for this purpose.The aim of the study was to evaluate the prognostic significance of qualitative and quantitative detection of ETV6-RUNX1 fusion gene transcript at various time points in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL patients.Materials and methods. ETV6-RUNX1 fusion gene transcript was revealed by both reverse-transcriptase PCR and quantitative real-time PCR (RQ-PCR in 34 out of 166 (20.5 % children with BCP-ALL. Qualitative ETV6-RUNX1-positivity at days 36 and 85 led to unfavorable outcome (lower event-free survival –EFS and higher cumulative incidence of relapse – CIR. While ETV6-RUNX1 status at day 15 did not allow to divide patients with different outcomes. By ROC curve analysis we determined threshold levels (TL for ETV6-RUNX1/ABL1 ratio at days 0, 15, 36 and 85. Afterwards we adjusted obtained results to 10-fold scale.Results. So practically applicable TL were as follows 500.0 %, 1 %, 0.1 % и 0.01 % for days 0, 15, 36 and 85, respectively. EFS and CIR were both worse in patients with ETV6-RUNX1/ABL1 ratio equal or above defined TL. Moreover, initial ratio ≥500,0 % corresponded to delayed blast clearance at days 15 and 36. We showed good qualitative (84.8 % and quantitative (R2 = 0.953 concordance between ETV6-RUNX1/ABL1 ratio and MRD data obtained by flow cytometry at days 15, 36, 85. Of note, defined TL for ETV6-RUNX1/ABL1 at days 15, 36, 85 were equal to prognostically important levels for flow cytometry MRD.Conclusion. Thus, qualitative detection and quantitative value of ETV6-RUNX1 fusion gene transcript showed prognostic significance in the course of treatment in children with BCP-ALL. Based

  9. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

    Science.gov (United States)

    Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

    2015-07-01

    A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

  10. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    Science.gov (United States)

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Hyperthermophilic Composting Accelerates the Removal of Antibiotic Resistance Genes and Mobile Genetic Elements in Sewage Sludge

    NARCIS (Netherlands)

    Liao, Hanpeng; Lu, Xiaomei; Rensing, Christopher; Friman, Ville Petri; Geisen, Stefan; Chen, Zhi; Yu, Zhen; Wei, Zhong; Zhou, Shungui; Zhu, Yongguan

    2018-01-01

    Composting is an efficient way to convert organic waste into fertilizers. However, waste materials often contain large amounts of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) that can reduce the efficacy of antibiotic treatments when transmitted to humans. Because

  12. CHROMOSOMAL SUBLOCALIZATION OF THE 2 13 TRANSLOCATION BREAKPOINT IN ALVEOLAR RHABDOMYOSARCOMA

    NARCIS (Netherlands)

    SHAPIRO, DN; VALENTINE, MB; SUBLETT, JE; SINCLAIR, AE; TEREBA, AM; SCHEFFER, H; BUYS, CHCM; LOOK, AT

    A characteristic balanced reciprocal chromosomal translocation [t(2;13)(q35;q14)] has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first step in characterization of the genes involved in this translocation, we constructed somatic cell hybrids that retained either the

  13. TFE3-positive renal cell carcinomas are not always Xp11 translocation carcinomas: Report of a case with a TPM3-ALK translocation.

    Science.gov (United States)

    Thorner, Paul Scott; Shago, Mary; Marrano, Paula; Shaikh, Furqan; Somers, Gino R

    2016-10-01

    Translocation-associated renal cell carcinoma (RCC) is a distinct subtype of RCC with gene rearrangements of the TFE3 or TFEB loci. The TFE3 gene is located at Xp11 and can fuse to a number of translocation partners, resulting in high nuclear expression of TFE3 protein. TFE3 immunostaining is often used as a surrogate marker for a TFE3 translocation. We report a case of an RCC that expressed TFE3 but showed only gain of TFE3 rather than a translocation. Moreover, this case had a t(1;2) translocation fusing ALK and TMP3, identical to that seen in inflammatory myofibroblastic tumour. There was resulting overexpression of ALK protein in a cytoplasmic and membranous pattern. The patient was not treated with chemotherapy but following regional nodal recurrence, an ALK inhibitor was added and the patient remains alive one year later. There are only rare reports of RCC with an ALK-TMP3 fusion, and these tumours can express TFE3 on some unknown basis not related to a TFE3 translocation. Any RCC positive for TFE3 and lacking a translocation should be tested for ALK expression and translocation. Recognition of this subtype of RCC will allow ALK inhibitor therapy to be added, in the hope of improving patient outcome. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. Complex three-way translocation involving MLL, ELL, RREB1, and CMAHP genes in an infant with acute myeloid leukemia and t(6;19;11)(p22.2;p13.1;q23.3)

    DEFF Research Database (Denmark)

    Tuborgh, A; Meyer, C; Marschalek, R

    2013-01-01

    until progression to acute myeloid leukemia, AML-M5. The leukemic cells harbored a novel apparent 3-way translocation t(6;19;11)(p22.2;p13.1;q23.3). We utilized advanced molecular cytogenetic methods including 24-color karyotyping, high-resolution array comparative genomic hybridization (aCGH) and DNA...... in the initial stages of disease before clear morphological signs of bone marrow involvement. The patient responded well to therapy and remains in remission>6 years from diagnosis. This apparent 3-way translocation is remarkable because of its rarity and presentation with myeloid sarcoma, and may, as more cases...

  15. Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS.

    Directory of Open Access Journals (Sweden)

    Ping An

    2007-06-01

    Full Text Available Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA, is incorporated into the HIV type 1 (HIV-1 virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4 in perfect linkage disequilibrium were associated with more rapid CD4(+ T-cell loss (relative hazard = 3.7, p = 0.003 in African Americans. Among European Americans, these alleles were also associated with a significant trend to more rapid progression to AIDS in a multi-point categorical analysis (p = 0.005. Both SNPs showed differential nuclear protein-binding efficiencies in a gel shift assay. In addition, one SNP (SNP5 located in the 5' UTR previously shown to be associated with higher ex vivo HIV-1 replication was found to be more frequent in HIV-1-positive individuals than in those highly exposed uninfected individuals. These results implicate regulatory PPIA polymorphisms as a component of genetic susceptibility to HIV-1 infection or disease progression, affirming the important role of PPIA in HIV-1 pathogenesis.

  16. Relation Between Motility, Accelerated Aging and Gene Expression in Selected Drosophila Strains under Hypergravity Conditions

    Science.gov (United States)

    Serrano, Paloma; van Loon, Jack J. W. A.; Medina, F. Javier; Herranz, Raúl

    2013-02-01

    Motility and aging in Drosophila have proven to be highly modified under altered gravity conditions (both in space and ground simulation facilities). In order to find out how closely connected they are, five strains with altered geotactic response or survival rates were selected and exposed to an altered gravity environment of 2 g. By analysing the different motile and behavioural patterns and the median survival rates, we show that altered gravity leads to changes in motility, which will have a negative impact on the flies' survival. Previous results show a differential gene expression between sessile samples and adults and confirm that environmentally-conditioned behavioural patterns constrain flies' gene expression and life span. Therefore, hypergravity is considered an environmental stress factor and strains that do not respond to this new environment experience an increment in motility, which is the major cause for the observed increased mortality also under microgravity conditions. The neutral-geotaxis selected strain (strain M) showed the most severe phenotype, unable to respond to variations in the gravitational field. Alternatively, the opposite phenotype was observed in positive-geotaxis and long-life selected flies (strains B and L, respectively), suggesting that these populations are less sensitive to alterations in the gravitational load. We conclude that the behavioural response has a greater contribution to aging than the modified energy consumption in altered gravity environments.

  17. Analysis of mutations in the human HPRT gene induced by accelerated heavy-ion irradiation

    International Nuclear Information System (INIS)

    Kagawa, Yasuhiro; Yatagai, Fumio; Hanaoka, Fumio; Suzuki, Masao; Kase, Youko; Kobayashi, Akiko; Hirano, Masahiko; Kato, Takesi; Watanabe, Masami.

    1995-01-01

    Multiplex PCR analysis of HPRT(-) mutations in human embryo (HE) cells induced by 230 keV/μm carbon-ion irradiation showed no large deletion around the exon regions of the locus gene in contrast to the irradiations at different LETs. To identify these mutations, the sequence alterations in a cDNA of hprt gene were determined for 18 mutant clones in this study. Missing of exon 6 was the most frequent mutational event (10 clones), and missing of both exons 6 and 8 was next most frequent event (6 clones), then base substitutions (2 clones). These characteristics were not seen in a similar analysis of spontaneous mutations, which showed base substitution (5 clones), frameshift (2 clones), missing of both exons 2 and 3 (2 clones), and a single unidentified clone. Direct sequencing and restriction enzyme digestion of the genomic DNA of the mutants which showed missing of exons 6 and 8 in the cDNA, supports the possibility that they were induced by aberrant mRNA splicing. (author)

  18. Leading tip drives soma translocation via forward F-actin flow during neuronal migration.

    Science.gov (United States)

    He, Min; Zhang, Zheng-hong; Guan, Chen-bing; Xia, Di; Yuan, Xiao-bing

    2010-08-11

    Neuronal migration involves coordinated extension of the leading process and translocation of the soma, but the relative contribution of different subcellular regions, including the leading process and cell rear, in driving soma translocation remains unclear. By local manipulation of cytoskeletal components in restricted regions of cultured neurons, we examined the molecular machinery underlying the generation of traction force for soma translocation during neuronal migration. In actively migrating cerebellar granule cells in culture, a growth cone (GC)-like structure at the leading tip exhibits high dynamics, and severing the tip or disrupting its dynamics suppressed soma translocation within minutes. Soma translocation was also suppressed by local disruption of F-actin along the leading process but not at the soma, whereas disrupting microtubules along the leading process or at the soma accelerated soma translocation. Fluorescent speckle microscopy using GFP-alpha-actinin showed that a forward F-actin flow along the leading process correlated with and was required for soma translocation, and such F-actin flow depended on myosin II activity. In migrating neurons, myosin II activity was high at the leading tip but low at the soma, and increasing or decreasing this front-to-rear difference accelerated or impeded soma advance. Thus, the tip of the leading process actively pulls the soma forward during neuronal migration through a myosin II-dependent forward F-actin flow along the leading process.

  19. Gene Amplification on Demand Accelerates Cellobiose Utilization in Engineered Saccharomyces cerevisiae.

    Science.gov (United States)

    Oh, Eun Joong; Skerker, Jeffrey M; Kim, Soo Rin; Wei, Na; Turner, Timothy L; Maurer, Matthew J; Arkin, Adam P; Jin, Yong-Su

    2016-06-15

    Efficient microbial utilization of cellulosic sugars is essential for the economic production of biofuels and chemicals. Although the yeast Saccharomyces cerevisiae is a robust microbial platform widely used in ethanol plants using sugar cane and corn starch in large-scale operations, glucose repression is one of the significant barriers to the efficient fermentation of cellulosic sugar mixtures. A recent study demonstrated that intracellular utilization of cellobiose by engineered yeast expressing a cellobiose transporter (encoded by cdt-1) and an intracellular β-glucosidase (encoded by gh1-1) can alleviate glucose repression, resulting in the simultaneous cofermentation of cellobiose and nonglucose sugars. Here we report enhanced cellobiose fermentation by engineered yeast expressing cdt-1 and gh1-1 through laboratory evolution. When cdt-1 and gh1-1 were integrated into the genome of yeast, the single copy integrant showed a low cellobiose consumption rate. However, cellobiose fermentation rates by engineered yeast increased gradually during serial subcultures on cellobiose. Finally, an evolved strain exhibited a 15-fold-higher cellobiose fermentation rate. To identify the responsible mutations in the evolved strain, genome sequencing was performed. Interestingly, no mutations affecting cellobiose fermentation were identified, but the evolved strain contained 9 copies of cdt-1 and 23 copies of gh1-1 We also traced the copy numbers of cdt-1 and gh1-1 of mixed populations during the serial subcultures. The copy numbers of cdt-1 and gh1-1 in the cultures increased gradually with similar ratios as cellobiose fermentation rates of the cultures increased. These results suggest that the cellobiose assimilation pathway (transport and hydrolysis) might be a rate-limiting step in engineered yeast and copies of genes coding for metabolic enzymes might be amplified in yeast if there is a growth advantage. This study indicates that on-demand gene amplification might be an

  20. GAMUT: GPU accelerated microRNA analysis to uncover target genes through CUDA-miRanda

    Science.gov (United States)

    2014-01-01

    Background Non-coding sequences such as microRNAs have important roles in disease processes. Computational microRNA target identification (CMTI) is becoming increasingly important since traditional experimental methods for target identification pose many difficulties. These methods are time-consuming, costly, and often need guidance from computational methods to narrow down candidate genes anyway. However, most CMTI methods are computationally demanding, since they need to handle not only several million query microRNA and reference RNA pairs, but also several million nucleotide comparisons within each given pair. Thus, the need to perform microRNA identification at such large scale has increased the demand for parallel computing. Methods Although most CMTI programs (e.g., the miRanda algorithm) are based on a modified Smith-Waterman (SW) algorithm, the existing parallel SW implementations (e.g., CUDASW++ 2.0/3.0, SWIPE) are unable to meet this demand in CMTI tasks. We present CUDA-miRanda, a fast microRNA target identification algorithm that takes advantage of massively parallel computing on Graphics Processing Units (GPU) using NVIDIA's Compute Unified Device Architecture (CUDA). CUDA-miRanda specifically focuses on the local alignment of short (i.e., ≤ 32 nucleotides) sequences against longer reference sequences (e.g., 20K nucleotides). Moreover, the proposed algorithm is able to report multiple alignments (up to 191 top scores) and the corresponding traceback sequences for any given (query sequence, reference sequence) pair. Results Speeds over 5.36 Giga Cell Updates Per Second (GCUPs) are achieved on a server with 4 NVIDIA Tesla M2090 GPUs. Compared to the original miRanda algorithm, which is evaluated on an Intel Xeon E5620@2.4 GHz CPU, the experimental results show up to 166 times performance gains in terms of execution time. In addition, we have verified that the exact same targets were predicted in both CUDA-miRanda and the original mi

  1. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Bacterial translocation: impact of probiotics

    OpenAIRE

    Jeppsson, Bengt; Mangell, Peter; Adawi, Diya; Molin, Göran

    2004-01-01

    There is a considerable amount of data in humans showing that patients who cannot take in nutrients enterally have more organ failure in the intensive care unit, a less favourable prognosis, and a higher frequency of septicaemia, in particular involving bacterial species from the intestinal tract. However, there is little evidence that this is connected with translocation of bacterial species in humans. Animal data more uniformly imply the existence of such a connection. The main focus of thi...

  3. Suitability of amphibians and reptiles for translocation.

    Science.gov (United States)

    Germano, Jennifer M; Bishop, Phillip J

    2009-02-01

    Translocations are important tools in the field of conservation. Despite increased use over the last few decades, the appropriateness of translocations for amphibians and reptiles has been debated widely over the past 20 years. To provide a comprehensive evaluation of the suitability of amphibians and reptiles for translocation, we reviewed the results of amphibian and reptile translocation projects published between 1991 and 2006. The success rate of amphibian and reptile translocations reported over this period was twice that reported in an earlier review in 1991. Success and failure rates were independent of the taxonomic class (Amphibia or Reptilia) released. Reptile translocations driven by human-wildlife conflict mitigation had a higher failure rate than those motivated by conservation, and more recent projects of reptile translocations had unknown outcomes. The outcomes of amphibian translocations were significantly related to the number of animals released, with projects releasing over 1000 individuals being most successful. The most common reported causes of translocation failure were homing and migration of introduced individuals out of release sites and poor habitat. The increased success of amphibian and reptile translocations reviewed in this study compared with the 1991 review is encouraging for future conservation projects. Nevertheless, more preparation, monitoring, reporting of results, and experimental testing of techniques and reintroduction questions need to occur to improve translocations of amphibians and reptiles as a whole.

  4. Markovian description of unbiased polymer translocation

    International Nuclear Information System (INIS)

    Mondaini, Felipe; Moriconi, L.

    2012-01-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

  5. Markovian description of unbiased polymer translocation

    Energy Technology Data Exchange (ETDEWEB)

    Mondaini, Felipe [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil); Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, UnED Angra dos Reis, Angra dos Reis, 23953-030, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil)

    2012-10-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

  6. Primary vitreoretinal dysplasia resembling Norrie's disease in a female: association with X autosome chromosomal translocation.

    OpenAIRE

    Ohba, N.; Yamashita, T.

    1986-01-01

    A female infant with the typical clinical and histopathological features of vitreoretinal dysplasia is described. She had an apparently balanced reciprocal chromosomal translocation 46XX,t(X;10) with the X chromosome breakpoint being on the short arm. Since the parents' karyotypes were normal, it is most plausible that a de novo chromosomal translocation disrupted the vitreoretinal dysplasia gene itself. The severe clinical symptoms of this heterozygous female patient were explained by non-ra...

  7. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  8. Identification of genome-specific transcripts in wheat–rye translocation lines

    Directory of Open Access Journals (Sweden)

    Tong Geon Lee

    2015-09-01

    Full Text Available Studying gene expression in wheat–rye translocation lines is complicated due to the presence of homeologs in hexaploid wheat and high levels of synteny between wheat and rye genomes (Naranjo and Fernandez-Rueda, 1991 [1]; Devos et al., 1995 [2]; Lee et al., 2010 [3]; Lee et al., 2013 [4]. To overcome limitations of current gene expression studies on wheat–rye translocation lines and identify genome-specific transcripts, we developed a custom Roche NimbleGen Gene Expression microarray that contains probes derived from the sequence of hexaploid wheat, diploid rye and diploid progenitors of hexaploid wheat genome (Lee et al., 2014. Using the array developed, we identified genome-specific transcripts in a wheat–rye translocation line (Lee et al., 2014. Expression data are deposited in the NCBI Gene Expression Omnibus (GEO under accession number GSE58678. Here we report the details of the methods used in the array workflow and data analysis.

  9. Tourette syndrome in a pedigree with a 7;18 translocation: Identification of a YAC spanning the translocation breakpoint at 18q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Boghosian-Sell, L.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Comings, D.E. [City of Hope Medical Center, Duarte, CA (United States)

    1996-11-01

    Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pathologies include attention deficit disorder and obsessive-compulsive disorder (OCD). Extensive linkage analysis based on an autosomal dominant mode of transmission with reduced penetrance has failed to show linkage with polymorphic markers, suggesting either locus heterogeneity or a polygenic origin for Tourette syndrome. An individual diagnosed with Tourette syndrome has been described carrying a constitutional chromosome translocation. Other family members carrying the translocation exhibit features seen in Tourette syndrome including motor tics, vocal tics, and OCD. Since the disruption of specific genes by a chromosomal rearrangement can elicit a particular phenotype, we have undertaken the physical mapping of the 7;18 translocation such that genes mapping at the site of the breakpoint can be identified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18), a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventual identification of genes that map to chromosomes 7 and 18 at the site of the translocation. 41 refs., 3 figs., 1 tab.

  10. Energetics of Ortho-7 (oxime drug translocation through the active-site gorge of tabun conjugated acetylcholinesterase.

    Directory of Open Access Journals (Sweden)

    Vivek Sinha

    Full Text Available Oxime drugs translocate through the 20 Å active-site gorge of acetylcholinesterase in order to liberate the enzyme from organophosphorus compounds' (such as tabun conjugation. Here we report bidirectional steered molecular dynamics simulations of oxime drug (Ortho-7 translocation through the gorge of tabun intoxicated enzyme, in which time dependent external forces accelerate the translocation event. The simulations reveal the participation of drug-enzyme hydrogen bonding, hydrophobic interactions and water bridges between them. Employing nonequilibrium theorems that recovers the free energy from irreversible work done, we reconstruct potential of mean force along the translocation pathway such that the desired quantity represents an unperturbed system. The potential locates the binding sites and barriers for the drug to translocate inside the gorge. Configurational entropic contribution of the protein-drug binding entity and the role of solvent translational mobility in the binding energetics is further assessed.

  11. Translocality in Global Software Development

    DEFF Research Database (Denmark)

    Bjørn, Pernille; Søderberg, Anne-Marie; Krishna, S.

    2017-01-01

    . We explored how agile processes in global outsourcing impacts work conditions of the Indian IT developers, and were surprised to find that agile methodologies, even after 3 years of implementation, created a stressful and inflexible work environment negatively impacting their personal lives. Many......What happens when agile methods are introduced in global outsourcing set-ups? Agile methods are designed to empower IT developers in decision-making through self-managing collocated teams. We studied how agile methods were introduced into global outsourcing from the Indian IT vendor’s perspective...... of the negative aspects of work, which agile methodologies were developed to reduce, were evident in the global agile outsourcing set-up. We propose translocality to repudiate the dichotomy of global/local reminding us that methodologies and technologies must be understood as immediately localized and situated...

  12. Effects of an attractive wall on the translocation of polymer under driving

    International Nuclear Information System (INIS)

    Cao Weiping; Wang Chao; Sun Lizhen; Luo Mengbo

    2012-01-01

    The effects of an attractive wall at the trans side on the translocation of an eight-site bond-fluctuation model (BFM) polymer through a pore in a membrane under driving are simulated by the dynamic Monte Carlo method. The attractive wall shows two contrary effects: its excluded volume effect reduces configuration entropy and thus hinders the translocation of the polymer, while its attraction decreases the energy and thus accelerates the translocation. At a critical polymer-wall interaction ε* ≈- 1, we find that the two effects compensate each other and the translocation time τ is roughly independent of the separation distance between the wall and the pore. The value ε* ≈- 1 is roughly equal to the critical adsorption point for the BFM polymer. Moreover, the value of the critical attraction is roughly independent of chain length N and chemical potential difference Δμ. At last, a scaling relation τ ∼ N α is observed for polymer translocation at a high value of NΔμ. Though the translocation time is highly dependent on the polymer-wall interaction and pore-wall separation distance, the exponent α is always about 1.30 ± 0.05 so long as NΔμ is large enough. (paper)

  13. Mechanical design of translocating motor proteins.

    Science.gov (United States)

    Hwang, Wonmuk; Lang, Matthew J

    2009-01-01

    Translocating motors generate force and move along a biofilament track to achieve diverse functions including gene transcription, translation, intracellular cargo transport, protein degradation, and muscle contraction. Advances in single molecule manipulation experiments, structural biology, and computational analysis are making it possible to consider common mechanical design principles of these diverse families of motors. Here, we propose a mechanical parts list that include track, energy conversion machinery, and moving parts. Energy is supplied not just by burning of a fuel molecule, but there are other sources or sinks of free energy, by binding and release of a fuel or products, or similarly between the motor and the track. Dynamic conformational changes of the motor domain can be regarded as controlling the flow of free energy to and from the surrounding heat reservoir. Multiple motor domains are organized in distinct ways to achieve motility under imposed physical constraints. Transcending amino acid sequence and structure, physically and functionally similar mechanical parts may have evolved as nature's design strategy for these molecular engines.

  14. Complex Variant t(9;22 Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Valencia

    2009-01-01

    Full Text Available The Philadelphia (Ph1 chromosome arising from the reciprocal t(9;22 translocation is found in more than 90% of chronic myeloid leukemia (CML patients and results in the formation of the chimeric fusion gene BCR-ABL. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. We report five CML cases carrying variant Ph translocations involving both chromosomes 9 and 22 as well as chromosomes 3, 5, 7, 8, or 10. G-banding showed a reciprocal three-way translocation involving 3q21, 5q31, 7q32, 8q24, and 10q22 bands. BCR-ABL fusion signal on der(22 was found in all of the cases by FISH.

  15. Production and identification of wheat - Agropyron cristatum (1.4P) alien translocation lines.

    Science.gov (United States)

    Liu, Wei-Hua; Luan, Yang; Wang, Jing-Chang; Wang, Xiao-Guang; Su, Jun-Ji; Zhang, Jin-Peng; Yang, Xin-Ming; Gao, Ai-Nong; Li, Li-Hui

    2010-06-01

    The P genome of Agropyron Gaertn., a wild relative of wheat, contains an abundance of desirable genes that can be utilized as genetic resources to improve wheat. In this study, wheat - Aegilops cylindrica Host gametocidal chromosome 2C addition lines were crossed with wheat - Agropyron cristatum (L.) Gaertn. disomic addition line accession II-21 with alien recombinant chromosome (1.4)P. We successfully induced wheat - A. cristatum alien chromosomal translocations for the first time. The frequency of translocation in the progeny was 3.75%, which was detected by molecular markers and genomic in situ hybridization (GISH). The translocation chromosomes were identified by dual-color GISH /fluorescence in situ hybridization (FISH). The P genomic DNA was used as probe to detect the (1.4)P chromosome fragment, and pHvG39, pAs1, or pSc119.2 repeated sequences were used as probes to identify wheat translocated chromosomes. The results showed that six types of translocations were identified in the three wheat - A. cristatum alien translocation lines, including the whole arm or terminal portion of a (1.4)P chromosome. The (1.4)P chromosome fragments were translocated to wheat chromosomes 1B, 2B, 5B, and 3D. The breakpoints were located at the centromeres of 1B and 2B, the pericentric locations of 5BS, and the terminals of 5BL and 3DS. In addition, we obtained 12 addition-deletion lines that contained alien A. cristatum chromosome (1.4)P in wheat background. All of these wheat - A. cristatum alien translocation lines and addition-deletion lines would be valuable for identifying A. cristatum chromosome (1.4)P-related genes and providing genetic resources and new germplasm accessions for the genetic improvement of wheat. The specific molecular markers of A. cristatum (1.4)P chromosome have been developed and used to track the (1.4)P chromatin.

  16. Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells

    International Nuclear Information System (INIS)

    Kutsuzawa, K.; Chowdhury, E.H.; Nagaoka, M.; Maruyama, K.; Akiyama, Y.; Akaike, T.

    2006-01-01

    Stem cells holding great promises in regenerative medicine have the potential to be differentiated to a specific cell type through genetic manipulation. However, conventional ways of gene transfer to such progenitor cells suffer from a number of disadvantages particularly involving safety and efficacy issues. Here, we report on the development of a bio-functionalized inorganic nano-carrier of DNA by embedding fibronectin and E-cadherin chimera on the carrier, leading to its high affinity interactions with embryonic stem cell surface and accelerated trans-gene delivery for subsequent expression. While only apatite nano-particles were very inefficient in transfecting embryonic stem cells, fibronectin-anchored particles and to a more significant extent, fibronectin and E-cadherin-Fc-associated particles dramatically enhanced trans-gene delivery with a value notably higher than that of commercially available lipofection system. The involvement of both cell surface integrin and E-cadherin in mediating intracellular localization of the hybrid carrier was verified by blocking integrin binding site with excess free fibronectin and up-regulating both integrin and E-cadherin through PKC activation. Thus, the new establishment of a bio-functional hybrid gene-carrier would promote and facilitate development of stem cell-based therapy in regenerative medicine

  17. Carbon and nitrogen translocation between seagrass ramets

    NARCIS (Netherlands)

    Marbà, N.; Hemminga, M.A.; Mateo, M.A.; Duarte, C.M.; Maas, Y.E.M.; Terrados, J.; Gacia, E.

    2002-01-01

    The spatial scale and the magnitude of carbon and nitrogen translocation was examined in 5 tropical (Cymodocea serrulata, Halophila stipulacea, Halodule uninervis, Thalassodendron ciliatum, Thalassia hemprichii) and 3 temperate (Cymodocea nodosa, Posidonia oceanica, Zostera noltii) seagrass species

  18. Dudleya Variegata Translocation - San Diego [ds654

    Data.gov (United States)

    California Department of Resources — At Mission Trails Regional Park, a translocation project of Dudleya variegata was conducted in efforts to save the population from a private property undergoing...

  19. Comparative Genomics of Interreplichore Translocations in Bacteria: A Measure of Chromosome Topology?

    Science.gov (United States)

    Khedkar, Supriya; Seshasayee, Aswin Sai Narain

    2016-06-01

    Genomes evolve not only in base sequence but also in terms of their architecture, defined by gene organization and chromosome topology. Whereas genome sequence data inform us about the changes in base sequences for a large variety of organisms, the study of chromosome topology is restricted to a few model organisms studied using microscopy and chromosome conformation capture techniques. Here, we exploit whole genome sequence data to study the link between gene organization and chromosome topology in bacteria. Using comparative genomics across ∼250 pairs of closely related bacteria we show that: (a) many organisms show a high degree of interreplichore translocations throughout the chromosome and not limited to the inversion-prone terminus (ter) or the origin of replication (oriC); (b) translocation maps may reflect chromosome topologies; and (c) symmetric interreplichore translocations do not disrupt the distance of a gene from oriC or affect gene expression states or strand biases in gene densities. In summary, we suggest that translocation maps might be a first line in defining a gross chromosome topology given a pair of closely related genome sequences. Copyright © 2016 Khedkar and Seshasayee.

  20. Comparative Genomics of Interreplichore Translocations in Bacteria: A Measure of Chromosome Topology?

    Directory of Open Access Journals (Sweden)

    Supriya Khedkar

    2016-06-01

    Full Text Available Genomes evolve not only in base sequence but also in terms of their architecture, defined by gene organization and chromosome topology. Whereas genome sequence data inform us about the changes in base sequences for a large variety of organisms, the study of chromosome topology is restricted to a few model organisms studied using microscopy and chromosome conformation capture techniques. Here, we exploit whole genome sequence data to study the link between gene organization and chromosome topology in bacteria. Using comparative genomics across ∼250 pairs of closely related bacteria we show that: (a many organisms show a high degree of interreplichore translocations throughout the chromosome and not limited to the inversion-prone terminus (ter or the origin of replication (oriC; (b translocation maps may reflect chromosome topologies; and (c symmetric interreplichore translocations do not disrupt the distance of a gene from oriC or affect gene expression states or strand biases in gene densities. In summary, we suggest that translocation maps might be a first line in defining a gross chromosome topology given a pair of closely related genome sequences.

  1. Acceleration of gene transfection efficiency in neuroblastoma cells through polyethyleneimine/poly(methyl methacrylate core-shell magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Tencomnao T

    2012-06-01

    Full Text Available Tewin Tencomnao,1,* Kewalin Klangthong,2,* Nuttaporn Pimpha,3 Saowaluk Chaleawlert-umpon,3 Somsak Saesoo,3 Noppawan Woramongkolchai,3 Nattika Saengkrit,31Center for Excellence in Omics-Nano Medical Technology Development Project, 2Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 3National Nanotechnology Center, National Science and Technology Development Agency, Pathumthani, Thailand*Both authors contributed equally to this workBackground: The purpose of this study was to demonstrate the potential of magnetic poly(methyl methacrylate (PMMA core/polyethyleneimine (PEI shell (mag-PEI nanoparticles, which possess high saturation magnetization for gene delivery. By using mag-PEI nanoparticles as a gene carrier, this study focused on evaluation of transfection efficiency under magnetic induction. The potential role of this newly synthesized nanosphere for therapeutic delivery of the tryptophan hydroxylase-2 (TPH-2 gene was also investigated in cultured neuronal LAN-5 cells.Methods: The mag-PEI nanoparticles were prepared by one-step emulsifier-free emulsion polymerization, generating highly loaded and monodispersed magnetic polymeric nanoparticles bearing an amine group. The physicochemical properties of the mag-PEI nanoparticles and DNA-bound mag-PEI nanoparticles were investigated using the gel retardation assay, atomic force microscopy, and zeta size measurements. The gene transfection efficiencies of mag-PEI nanoparticles were evaluated at different transfection times. Confocal laser scanning microscopy confirmed intracellular uptake of the magnetoplex. The optimal conditions for transfection of TPH-2 were selected for therapeutic gene transfection. We isolated the TPH-2 gene from the total RNA of the human medulla oblongata and cloned it into an expression vector. The plasmid containing TPH-2 was subsequently bound onto the

  2. Genetic analysis of γ-ray induced W-translocation strain on Bombyx nori

    International Nuclear Information System (INIS)

    Onuma, Akio; Murakami, Akio

    1976-01-01

    In the process of analyzing a γ-ray induced mutant of Bombyx nori oo cyte, new type translocation strains of W chromosomes and No.5 chromosomes were detected. The constitution of their translocated chromosomes was assumed to be Z/(W-V) + sup(pe)-V + sup(oc)/v. Owing to such chromosome constitution, it was considered that non-disjunction was induced at meiosis, and Z/(W-V) + sup(pe)/V, Z/(W-V) + sup(pe), V/V were produced besides Z/(W-V) + sup(pe)-V + sup(oc)/V in the female chromosomes (gene) of the next progeny, while V/V and Z/Z, V + sup(oc)/V were produced besides Z/Z, V/V in male. Death of some male eggs in this translocation strain was also observed. No dissociated individual of translocated chromosomes was segregated in the next progeny of the female moth with Z/(W-V) + sup(pe), V/V chromosome constitution and the marker stock male moth, while a few dissociated individuals appeared in the next progeny of Z/(W-V) + sup(pe)-V + sup(oc)/V female moth group. This fact seemed to be resulted from the complicated translocated chromosome constitution of the translocation strain. (Kobatake, H.)

  3. Recombinase, chromosomal translocations and lymphoid neoplasia: targeting mistakes and repair failures.

    Science.gov (United States)

    Marculescu, Rodrig; Vanura, Katrina; Montpellier, Bertrand; Roulland, Sandrine; Le, Trang; Navarro, Jean-Marc; Jäger, Ulrich; McBlane, Fraser; Nadel, Bertrand

    2006-09-08

    A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory element. Due to the unique feature of lymphoid cells to somatically rearrange and mutate receptor genes, and to the corresponding strong activity of the immune enhancers/promoters at that stage of cell development, B- and T-cell differentiation pathways represent propitious targets for chromosomal translocations and oncogene activation. Recent progress in the understanding of the V(D)J recombination process has allowed a more accurate definition of the translocation mechanisms involved, and has revealed that V(D)J-mediated translocations result both from targeting mistakes of the recombinase, and from illegitimate repair of the V(D)J recombination intermediates. Surprisingly, V(D)J-mediated translocations turn out to be restricted to two specific sub-types of lymphoid malignancies, T-cell acute lymphoblastic leukemias, and a restricted set of mature B-cell Non-Hodgkin's lymphomas.

  4. Can Accelerators Accelerate Learning?

    International Nuclear Information System (INIS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-01-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  5. Can Accelerators Accelerate Learning?

    Science.gov (United States)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  6. High-performance analysis of single interphase cells with custom DNA probes spanning translocation break points

    Science.gov (United States)

    Weier, Heinz-Ulli G.; Munne, S.; Lersch, Robert A.; Marquez, C.; Wu, J.; Pedersen, Roger A.; Fung, Jingly

    1999-06-01

    The chromatin organization of interphase cell nuclei, albeit an object of intense investigation, is only poorly understood. In the past, this has hampered the cytogenetic analysis of tissues derived from specimens where only few cells were actively proliferating or a significant number of metaphase cells could be obtained by induction of growth. Typical examples of such hard to analyze cell systems are solid tumors, germ cells and, to a certain extent, fetal cells such as amniocytes, blastomeres or cytotrophoblasts. Balanced reciprocal translocations that do not disrupt essential genes and thus do not led to disease symptoms exit in less than one percent of the general population. Since the presence of translocations interferes with homologue pairing in meiosis, many of these individuals experience problems in their reproduction, such as reduced fertility, infertility or a history of spontaneous abortions. The majority of translocation carriers enrolled in our in vitro fertilization (IVF) programs carry simple translocations involving only two autosomes. While most translocations are relatively easy to spot in metaphase cells, the majority of cells biopsied from embryos produced by IVF are in interphase and thus unsuitable for analysis by chromosome banding or FISH-painting. We therefore set out to analyze single interphase cells for presence or absence of specific translocations. Our assay, based on fluorescence in situ hybridization (FISH) of breakpoint-spanning DNA probes, detects translocations in interphase by visual microscopic inspection of hybridization domains. Probes are prepared so that they span a breakpoint and cover several hundred kb of DNA adjacent to the breakpoint. On normal chromosomes, such probes label a contiguous stretch of DNA and produce a single hybridization domain per chromosome in interphase cells. The translocation disrupts the hybridization domain and the resulting two fragments appear as physically separated hybridization domains in

  7. Plasma accelerators

    International Nuclear Information System (INIS)

    Bingham, R.; Angelis, U. de; Johnston, T.W.

    1991-01-01

    Recently attention has focused on charged particle acceleration in a plasma by a fast, large amplitude, longitudinal electron plasma wave. The plasma beat wave and plasma wakefield accelerators are two efficient ways of producing ultra-high accelerating gradients. Starting with the plasma beat wave accelerator (PBWA) and laser wakefield accelerator (LWFA) schemes and the plasma wakefield accelerator (PWFA) steady progress has been made in theory, simulations and experiments. Computations are presented for the study of LWFA. (author)

  8. Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells.

    Science.gov (United States)

    Schwer, Bjoern; Wei, Pei-Chi; Chang, Amelia N; Kao, Jennifer; Du, Zhou; Meyers, Robin M; Alt, Frederick W

    2016-02-23

    High-throughput, genome-wide translocation sequencing (HTGTS) studies of activated B cells have revealed that DNA double-strand breaks (DSBs) capable of translocating to defined bait DSBs are enriched around the transcription start sites (TSSs) of active genes. We used the HTGTS approach to investigate whether a similar phenomenon occurs in primary neural stem/progenitor cells (NSPCs). We report that breakpoint junctions indeed are enriched around TSSs that were determined to be active by global run-on sequencing analyses of NSPCs. Comparative analyses of transcription profiles in NSPCs and B cells revealed that the great majority of TSS-proximal junctions occurred in genes commonly expressed in both cell types, possibly because this common set has higher transcription levels on average than genes transcribed in only one or the other cell type. In the latter context, among all actively transcribed genes containing translocation junctions in NSPCs, those with junctions located within 2 kb of the TSS show a significantly higher transcription rate on average than genes with junctions in the gene body located at distances greater than 2 kb from the TSS. Finally, analysis of repair junction signatures of TSS-associated translocations in wild-type versus classical nonhomologous end-joining (C-NHEJ)-deficient NSPCs reveals that both C-NHEJ and alternative end-joining pathways can generate translocations by joining TSS-proximal DSBs to DSBs on other chromosomes. Our studies show that the generation of transcription-associated DSBs is conserved across divergent cell types.

  9. (q24: q12) translocation is common in Ewing's sarcoma/peripheral ...

    Indian Academy of Sciences (India)

    The Ewing's sarcoma family can present diagnostic difficulties. In the past the basis of diagnosis has been a exclusion. Identification of a specific translocation especially t(11; 22) (EWS-FLI 1 fusion gene), which is seen in nearly 85% of Ewing's sarcoma cases can help in precise diagnosis. We have carried out a study on ...

  10. Assessing the ability of Salmonella enterica to translocate Type III effectors into plant cells

    Science.gov (United States)

    Salmonella enterica, a human enteric pathogen, has the ability to multiply and survive endophytically in plants, and mutations in genes encoding the type III secretion system (T3SS) or its effectors (T3Es) may contribute to this colonization. Two reporter plasmids for T3E translocation into plant ce...

  11. Linear Accelerators

    International Nuclear Information System (INIS)

    Vretenar, M

    2014-01-01

    The main features of radio-frequency linear accelerators are introduced, reviewing the different types of accelerating structures and presenting the main characteristics aspects of linac beam dynamics

  12. Flowering Without Vernalization in Winter Canola (Brassica napus: use of Virus-Induced Gene Silencing (VIGS to accelerate genetic gain

    Directory of Open Access Journals (Sweden)

    Raúl Álvarez-Venegas

    2010-01-01

    Full Text Available Ciclos de reproducción cortos y la oportunidad de incrementar la ganancia genética, junto con el estudio de las bases moleculares de la vernalización, son áreas esenciales de investigación dentro de la biología de plantas. Varios métodos se han empleado para lograr el silenciamiento génico en plantas, pero ninguno reportado a la fecha para canola (Brassica napus, y en particular para inducir la floración sin vernalización en líneas de invierno a través del uso de secuencias sentido de DNA en vectores diseñados para el silenciamiento génico inducido por virus (VIGS. La presente investigación provee los métodos para transitoriamente regular a la baja, por medio de VIGS, genes de la vernalización en plantas anuales de invierno, específicamente la familia de genes de Flowering Locus C (FLC en canola de invierno (BnFLC1 a BnFLC5. La regulación a la baja de estos genes permite a las plantas anuales de invierno florecer sin vernalización y, consecuentemente, provee los medios para acelerar la ganancia genética. El sistema de silenciamiento propuesto puede ser utilizado para regular a la baja familias de genes, para determinar la función génica, y para inducir la floración sin la vernalización en líneas de invierno tanto del género Brassica como de muchos cultivos importantes de invierno.

  13. Stochastic resonance during a polymer translocation process

    International Nuclear Information System (INIS)

    Mondal, Debasish; Muthukumar, M.

    2016-01-01

    We have studied the occurrence of stochastic resonance when a flexible polymer chain undergoes a single-file translocation through a nano-pore separating two spherical cavities, under a time-periodic external driving force. The translocation of the chain is controlled by a free energy barrier determined by chain length, pore length, pore-polymer interaction, and confinement inside the donor and receiver cavities. The external driving force is characterized by a frequency and amplitude. By combining the Fokker-Planck formalism for polymer translocation and a two-state model for stochastic resonance, we have derived analytical formulas for criteria for emergence of stochastic resonance during polymer translocation. We show that no stochastic resonance is possible if the free energy barrier for polymer translocation is purely entropic in nature. The polymer chain exhibits stochastic resonance only in the presence of an energy threshold in terms of polymer-pore interactions. Once stochastic resonance is feasible, the chain entropy controls the optimal synchronization conditions significantly.

  14. Nuclear translocation and retention of growth hormone

    DEFF Research Database (Denmark)

    Mertani, Hichem C; Raccurt, Mireille; Abbate, Aude

    2003-01-01

    We have previously demonstrated that GH is subject to rapid receptor-dependent nuclear translocation. Here, we examine the importance of ligand activation of the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization for hormone internalization and nuclear translocation by use...... of cells stably transfected with cDNA for the GHR. Staurosporine and herbimycin A treatment of cells did not affect the ability of GH to internalize but resulted in increased nuclear accumulation of hormone. Similarly, receptor mutations, which prevent the association and activation of JAK2, did not affect...... the ability of the hormone to internalize or translocate to the nucleus but resulted in increased nuclear accumulation of GH. These results were observed both by nuclear isolation and confocal laser scanning microscopy. Staurosporine treatment of cells in which human GH (hGH) was targeted to the cytoplasm...

  15. Accelerator Service

    International Nuclear Information System (INIS)

    Champelovier, Y.; Ferrari, M.; Gardon, A.; Hadinger, G.; Martin, J.; Plantier, A.

    1998-01-01

    Since the cessation of the operation of hydrogen cluster accelerator in July 1996, four electrostatic accelerators were in operation and used by the peri-nuclear teams working in multidisciplinary collaborations. These are the 4 MV Van de Graaff accelerator, 2,5 MV Van de Graaff accelerator, 400 kV ion implanter as well as the 120 kV isotope separator

  16. Garlic accelerates red blood cell turnover and splenic erythropoietic gene expression in mice: evidence for erythropoietin-independent erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Bünyamin Akgül

    2010-12-01

    Full Text Available Garlic (Allium sativum has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic

  17. In vitro studies on the translocation of acid phosphatase into the endoplasmic reticulum of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Krebs, H O; Hoffschulte, H K; Müller, M

    1989-05-01

    We demonstrate here the in vitro translocation of yeast acid phosphatase into rough endoplasmic reticulum. The precursor of the repressible acid phosphatase from Saccharomyces cerevisiae encoded by the PHO5 gene, was synthesized in a yeast lysate programmed with in vitro transcribed PHO5 mRNA. In the presence of yeast rough microsomes up to 16% of the acid phosphatase synthesized was found to be translocated into the microsomes, as judged by proteinase resistance, and fully core-glycosylated. The translocation efficiency however, decreased to 3% if yeast rough microsomes were added after synthesis of acid phosphatase had been terminated. When a wheat-germ extract was used for in vitro synthesis, the precursor of acid phosphatase was translocated into canine pancreatic rough microsomes and thereby core-glycosylated in a signal-recognition-particle-dependent manner. Replacing canine with yeast rough microsomes in the wheat-germ translation system, however, resulted in a significant decrease in the ability to translocate and glycosylate the precursor. Translocation and glycosylation were partially restored by a high-salt extract prepared from yeast ribosomes. The results presented here suggest that yeast-specific factors are needed to translocate and glycosylate acid phosphatase efficiently in vitro.

  18. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    Science.gov (United States)

    Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

    2012-01-01

    Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

  19. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    Directory of Open Access Journals (Sweden)

    Marcelo Razera Baruffi

    2012-01-01

    Full Text Available Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19(p21.2;q13.4. Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY. Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

  20. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    a duplication (Dp) of the translocated segment and four inviable (white, W) ascospores with .... of this work, namely, the definition of breakpoint junction sequences of 12 ..... then our results would place supercontig 10.9 in distal. LG VIR. A third ...

  1. Nitrogen uptake and translocation by Chara

    NARCIS (Netherlands)

    Vermeer, C.P.; Escher, M.; Portielje, R.; Klein, de J.J.M.

    2003-01-01

    The potential for above-ground and below-ground uptake and subsequent internal translocation of ammonium (NH4+) and nitrate (NO3-) by the macroalga Chara spp. was investigated. In a two compartment experimental set-up separating above-ground and below-ground algal parts, the charophytes were exposed

  2. 11C-methionine translocation in barley

    International Nuclear Information System (INIS)

    Nakanishi, Hiromi; Bughio, Naimatullah; Shigeta Ishioka, Noriko

    2000-01-01

    11 C-methionine was supplied to barley plants through a single leaf or via the roots and real time 11 C movement was monitored using a PETIS (positron emitting tracer imaging system). In Fe-deficient plants, 11 C-methionine was translocated from the tip of the absorbing leaf to the discrimination center' at the basal part of the shoot and then retranslocated to all the chlorotic leaves, while a negligible amount was retranslocated to the roots. In Fe-sufficient plants, methionine was translocated from the absorbing leaf to the discrimination center and then only to the newest leaf on the main shoot. A negligible amount was also retranslocated to the roots. Although, in Fe-sufficient plants, methionine translocation was observed from absorbing roots to shoots, in Fe-deficient plants, only a little amount was translocated from roots to shoots. In conclusion, methionine from the upper portion of a plant is not used as a precursor of mugineic acid under Fe-deficiency conditions. (author)

  3. Inactivation of the host lipin gene accelerates RNA virus replication through viral exploitation of the expanded endoplasmic reticulum membrane.

    Directory of Open Access Journals (Sweden)

    Chingkai Chuang

    2014-02-01

    Full Text Available RNA viruses take advantage of cellular resources, such as membranes and lipids, to assemble viral replicase complexes (VRCs that drive viral replication. The host lipins (phosphatidate phosphatases are particularly interesting because these proteins play key roles in cellular decisions about membrane biogenesis versus lipid storage. Therefore, we examined the relationship between host lipins and tombusviruses, based on yeast model host. We show that deletion of PAH1 (phosphatidic acid phosphohydrolase, which is the single yeast homolog of the lipin gene family of phosphatidate phosphatases, whose inactivation is responsible for proliferation and expansion of the endoplasmic reticulum (ER membrane, facilitates robust RNA virus replication in yeast. We document increased tombusvirus replicase activity in pah1Δ yeast due to the efficient assembly of VRCs. We show that the ER membranes generated in pah1Δ yeast is efficiently subverted by this RNA virus, thus emphasizing the connection between host lipins and RNA viruses. Thus, instead of utilizing the peroxisomal membranes as observed in wt yeast and plants, TBSV readily switches to the vastly expanded ER membranes in lipin-deficient cells to build VRCs and support increased level of viral replication. Over-expression of the Arabidopsis Pah2p in Nicotiana benthamiana decreased tombusvirus accumulation, validating that our findings are also relevant in a plant host. Over-expression of AtPah2p also inhibited the ER-based replication of another plant RNA virus, suggesting that the role of lipins in RNA virus replication might include several more eukaryotic viruses.

  4. Microscopy of bacterial translocation during small bowel obstruction and ischemia in vivo – a new animal model

    Directory of Open Access Journals (Sweden)

    Hafner Mathias

    2002-08-01

    Full Text Available Abstract Background Existing animal models provide only indirect information about the pathogenesis of infections caused by indigenous gastrointestinal microflora and the kinetics of bacterial translocation. The aim of this study was to develop a novel animal model to assess bacterial translocation and intestinal barrier function in vivo. Methods In anaesthetized male Wistar rats, 0.5 ml of a suspension of green fluorescent protein-transfected E. coli was administered by intraluminal injection in a model of small bowel obstruction. Animals were randomly subjected to non-ischemic or ischemic bowel obstruction. Ischemia was induced by selective clamping of the terminal mesenteric vessels feeding the obstructed bowel loop. Time intervals necessary for translocation of E. coli into the submucosal stroma and the muscularis propria was assessed using intravital microscopy. Results Bacterial translocation into the submucosa and muscularis propria took a mean of 36 ± 8 min and 80 ± 10 min, respectively, in small bowel obstruction. Intestinal ischemia significantly accelerated bacterial translocation into the submucosa (11 ± 5 min, p E. coli were visible in frozen sections of small bowel, mesentery, liver and spleen taken two hours after E. coli administration. Conclusions Intravital microscopy of fluorescent bacteria is a novel approach to study bacterial translocation in vivo. We have applied this technique to define minimal bacterial transit time as a functional parameter of intestinal barrier function.

  5. Adenine nucleotide translocator transports haem precursors into mitochondria.

    Directory of Open Access Journals (Sweden)

    Motoki Azuma

    2008-08-01

    Full Text Available Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT, the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

  6. Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

    DEFF Research Database (Denmark)

    Aristidou, Constantia; Koufaris, Costas; Theodosiou, Athina

    2017-01-01

    Familial apparently balanced translocations (ABTs) segregating with discordant phenotypes are extremely challenging for interpretation and counseling due to the scarcity of publications and lack of routine techniques for quick investigation. Recently, next generation sequencing has emerged...... and non-affected members carrying the same translocations. PTCD1, ATP5J2-PTCD1, CADPS2, and STPG1 were disrupted by the translocations in three families, rendering them initially as possible disease candidate genes. However, subsequent mutation screening and structural variant analysis did not reveal any...... can also be used in routine clinical investigation of ABT cases. Unlike de novo translocations, no associations were determined here between familial two-way ABTs and the phenotype of the affected members, in which the presence of cryptic imbalances and complex chromosomal rearrangements has been...

  7. Future accelerators (?)

    Energy Technology Data Exchange (ETDEWEB)

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  8. Translocation heterozygosity in southern African species of Viscum

    Directory of Open Access Journals (Sweden)

    D. Wiens

    1980-11-01

    Full Text Available Sex-associated and floating translocation complexes are characteristic of dioecious species of  Viscum,  but are virtually absent in monoecious species. The majority of dioecious species has fixed sex-associated translocation complexes with the male being the heterozygous sex. The sex-associated multivalent is usually O4 (ring-of-four or O6 , rarely O8 . Dioecious species without sex-associated translocations are much less common. Most of the dioecious species are also polymorphic for floating translocations, producing one or more additional multivalents ranging from O4 to O12. Floating translocations may be more frequent in species that do not have sex-associated translocations. Supernumerary chromosomes are also present in several species. Sex ratios are at unity in most dioecious species, but female-biased ratios may occur in some species. The high correlation between dioecy and translocation heterozygosity suggests that translocations are primarily associated with the origin and establishment of dioecy. Any róle in the maintenance of biased sex ratios through meiotic drive is probably secondary. Sex-associated translocations may serve to stabilize dioecy by bringing the sex factors into close linkage. Subsequent structural rearrangements within a sex-associated translocation complex may bring the sex factors together in one chromosome pair, releasing floating translocations. The high frequencies of floating translocation heterozygosity in some species indicate that such heterozygosity also has adaptive value.

  9. Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations.

    Science.gov (United States)

    Moysés-Oliveira, Mariana; Guilherme, Roberta Dos Santos; Dantas, Anelisa Gollo; Ueta, Renata; Perez, Ana Beatriz; Haidar, Mauro; Canonaco, Rosane; Meloni, Vera Ayres; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-05-01

    To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility. Retrospective and case-control study. University-based research laboratory. Three women with balanced X-autosome translocation and primary amenorrhea. Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction. Karyotype, copy number variation, breakpoint mapping, and gene expression levels. All patients presented with breakpoints in the Xq13q21 region. In two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. The ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. The break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. In the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. The FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region. The etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. The fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier's embryos- preliminary observations of two robertsonian translocation carrier families.

    Science.gov (United States)

    Shamash, Jana; Rienstein, Shlomit; Wolf-Reznik, Haike; Pras, Elon; Dekel, Michal; Litmanovitch, Talia; Brengauz, Masha; Goldman, Boleslav; Yonath, Hagith; Dor, Jehoshua; Levron, Jacob; Aviram-Goldring, Ayala

    2011-01-01

    Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation genetic haplotyping (PGH) that can identify and distinguish between all forms of the translocation status in cleavage stage embryos prior to implantation. Polymorphic markers were used to identify and differentiate between the alleles that carry the translocation and those that are the normal homologous chromosomes. Embryos from two families of robertsonian translocation carriers were successfully analyzed using polymorphic markers haplotyping. Our preliminary results indicate that the PGH is capable of distinguishing between normal, balanced and unbalanced translocation carrier embryos. This method will improve PGD and will enable translocation carriers to avoid transmission of the translocation and the associated medical complications to offspring.

  11. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.

    Science.gov (United States)

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-11-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase. The t(5;8;17)(p15;q13;q21) three‑way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in‑frame fusions AHRR‑NCOA2 and NCOA2‑ETV4 as well as an out‑of‑frame ETV4‑AHRR transcript. In the AHRR‑NCOA2 protein, the C‑terminal part of AHRR is replaced by the C‑terminal part of NCOA2 which contains two activation domains. The NCOA2‑ETV4 protein would contain the helix‑loop‑helix, PAS_9 and PAS_11, CITED domains, the SRC‑1 domain of NCOA2 and the ETS DNA‑binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR‑NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

  12. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M

    2009-08-13

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

  13. Accelerator Physics Section progress report

    International Nuclear Information System (INIS)

    Coote, G.E.

    1986-05-01

    This report summarizes the work of the Accelerator Physics Section of the Institute of Nuclear Sciences during the period January-December 1985. Applications of the EN-tandem accelerator included 13 N production for tracer experiments in plants and animals, hydrogen profiling with a 19 F beam and direct detection of heavy ions with a surface barrier detector. Preparations for accelerator mass spectrometry continued steadily, with the commissioning of the pulsed EHT supply which selects the isotope to be accelerated, routine detection of 14 C ions, and completion of a sputter ion source with an eight position target wheel. It was shown that the hydrogen content of a material could be derived from a simultaneous measurement of the transmission of neutrons and gamma rays from a neutron source or accelerator target. The 11 CO 2 produced at the 3 MV accelerator was used in two studies of translocation in a large number of plant species: the effects of small quantities of SO 2 in the air, and the effect of cooling a short length of the stem. The nuclear microprobe was applied to studies of carbon pickup during welding of stainless steel, determination of trace elements in soil and vegetation and the measurement of sodium depth profiles in obsidian - in particular the effect of rastering the incident proton beams

  14. Obstructive jaundice promotes bacterial translocation in humans.

    Science.gov (United States)

    Kuzu, M A; Kale, I T; Cöl, C; Tekeli, A; Tanik, A; Köksoy, C

    1999-01-01

    Significant bacterial translocation was demonstrated following experimental biliary obstruction, however very little is known about the importance and the prevalence of gut-origin sepsis in obstructive jaundice patients. Therefore, the aim of this study was to investigate the concept of gut-origin sepsis in obstructive jaundiced patients and its clinical importance. Twenty-one patients requiring laparotomy for obstructive jaundice (group I) and thirty patients operated on electively mainly for chronic cholecystitis (group II) were studied. Peritoneal swab, mesenteric lymph node, portal venous blood, liver wedge biopsy and bile were sampled for culture immediately after opening the peritoneum. Additionally, peripheral blood samples were taken pre- and post-operatively from all patients. Post-operatively, patients were monitored for infectious complications. The mean serum bilirubin concentration, gamma glutamyl transferase and alkaline phosphatase levels in jaundiced patients before therapeutic intervention were significantly higher than in control patients. Five patients demonstrated bacterial translocation in group I (24%), whereas only one did so in group II (3.5%, p jaundice significantly promotes bacterial translocation in humans, however, its clinical importance has yet to be defined.

  15. Radiation induced reciprocal translocations and inversions in anopheles albimanus

    International Nuclear Information System (INIS)

    Kaiser, P.E.; Seawright, J.A.; Benedict, M.Q.; Narang, S.

    1982-01-01

    Reciprocal translocations and inversions were induced in Anopheles albimanus Wiedemann by irradiation of males with X rays. A total of 1669 sperm were assayed, and 175 new aberrations were identified as follows: 102 reciprocal translocations (67 autosomal and 35 sex-linked), 45 pericentric inversions, and 28 paracentric inversions. Eleven of the translocations were nearly whole-arm interchanges, and these were selected for the construction of 'capture systems' for compound chromosomes. Two double-heterozygous translocation strains and four homozygous translocation strains were established. Anopheles albimanus females were irradiated, and a pseudolinkage scheme involving mutant markers was employed to identify reciprocal translocations. The irradiation of females was very inefficient; only one translocation was recovered from 1080 ova tested

  16. Financial costs of large carnivore translocations--accounting for conservation.

    Directory of Open Access Journals (Sweden)

    Florian J Weise

    Full Text Available Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars. Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23, and $2,108 per leopard (n = 6. One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%, followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4% of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown with a strong species bias. Four leopards (66.7% were successfully translocated but only eight of the 20 cheetahs (40.0% with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis.

  17. Financial costs of large carnivore translocations--accounting for conservation.

    Science.gov (United States)

    Weise, Florian J; Stratford, Ken J; van Vuuren, Rudolf J

    2014-01-01

    Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars). Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23), and $2,108 per leopard (n = 6). One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%), followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4%) of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards (66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%) with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC) and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis.

  18. Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?

    Science.gov (United States)

    Rego, Eduardo M; Pandolfi, Pier Paolo

    2002-08-01

    Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene lead to the formation of two fusion genes: X-RARalpha and RARalpha-X (where X is the alternative RARalpha fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X-RARalpha fusion protein is indeed oncogenic. However, recent data indicate that the RARalpha-X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.

  19. Electrostatic accelerators

    OpenAIRE

    Hinterberger, F

    2006-01-01

    The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We ...

  20. Electrostatic accelerators

    CERN Document Server

    Hinterberger, F

    2006-01-01

    The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We sketch possible applications and the progress in the development of electrostatic accelerators.

  1. Accelerator development

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    Because the use of accelerated heavy ions would provide many opportunities for new and important studies in nuclear physics and nuclear chemistry, as well as other disciplines, both the Chemistry and Physics Divisions are supporting the development of a heavy-ion accelerator. The design of greatest current interest includes a tandem accelerator with a terminal voltage of approximately 25 MV injecting into a linear accelerator with rf superconducting resonators. This combined accelerator facility would be capable of accelerating ions of masses ranging over the entire periodic table to an energy corresponding to approximately 10 MeV/nucleon. This approach, as compared to other concepts, has the advantages of lower construction costs, lower operating power, 100 percent duty factor, and high beam quality (good energy resolution, good timing resolution, small beam size, and small beam divergence). The included sections describe the concept of the proposed heavy-ion accelerator, and the development program aiming at: (1) investigation of the individual questions concerning the superconducting accelerating resonators; (2) construction and testing of prototype accelerator systems; and (3) search for economical solutions to engineering problems. (U.S.)

  2. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  3. Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene.

    Science.gov (United States)

    Shinoda, K; Nakamura, Y; Matsushita, K; Shimoda, K; Okita, H; Fukuma, M; Yamada, T; Ohde, H; Oguchi, Y; Hata, J; Umezawa, A

    2001-10-01

    EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. EAT transgenic mice incorporating the EF-1alpha promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (pstatistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95% confidence interval (CI) 0.0347-0.0500) than in littermates (0. 0199/mouse/week; 95% CI 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI 0-0.0120) and 0.0419/mouse/week in the EAT mice (95% CI 0.0286-0.0500). Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.

  4. Measurement of background translocation frequencies in individuals with clones

    Energy Technology Data Exchange (ETDEWEB)

    Wade, Marcelle J. [California State Univ. (CalState), Hayward, CA (United States)

    1996-08-01

    In the leukemia case the unseparated B and T lymphocytes had a high translocation frequency even after 0.0014, respectively. After purging all clones from the data, the translocation frequencies for Bio 8 and Bio 23 were 0.00750.0014 and 0.0073 metaphases were scored for chromosomal aberrations,, specifically reciprocal translocations, using fluorescence in situ hybridization (FISH). Metaphase spreads were used from two healthy, unexposed individuals (not exposed to radiation, chemotherapy or radiotherapy) and one early B- precursor acute lymphocytic leukemia (ALL) patient (metaphase spreads from both separated T lymphocytes and unseparated B and T lymphocytes were scored). All three individuals had an abnormally high translocation frequency. The high translocation frequencies resulted from clonal expansion of specific translocated chromosomes. I show in this thesis that by purging (discounting or removing) clones from the data of unexposed individuals, one can obtain true background translocation frequencies. In two cases, Bio 8 and Bio 23, the measured translocation frequency for chromosomes 1, 2 and 4 was 0.0124 purging all of the clones from the data. This high translocation frequency may be due to a low frequency of some clones and may not be recognized. The separated T lymphocytes had a higher translocation frequency than expected.

  5. RECIRCULATING ACCELERATION

    International Nuclear Information System (INIS)

    BERG, J.S.; GARREN, A.A.; JOHNSTONE, C.

    2000-01-01

    This paper compares various types of recirculating accelerators, outlining the advantages and disadvantages of various approaches. The accelerators are characterized according to the types of arcs they use: whether there is a single arc for the entire recirculator or there are multiple arcs, and whether the arc(s) are isochronous or non-isochronous

  6. LIBO accelerates

    CERN Multimedia

    2002-01-01

    The prototype module of LIBO, a linear accelerator project designed for cancer therapy, has passed its first proton-beam acceleration test. In parallel a new version - LIBO-30 - is being developed, which promises to open up even more interesting avenues.

  7. Accelerating Inspire

    CERN Document Server

    AUTHOR|(CDS)2266999

    2017-01-01

    CERN has been involved in the dissemination of scientific results since its early days and has continuously updated the distribution channels. Currently, Inspire hosts catalogues of articles, authors, institutions, conferences, jobs, experiments, journals and more. Successful orientation among this amount of data requires comprehensive linking between the content. Inspire has lacked a system for linking experiments and articles together based on which accelerator they were conducted at. The purpose of this project has been to create such a system. Records for 156 accelerators were created and all 2913 experiments on Inspire were given corresponding MARC tags. Records of 18404 accelerator physics related bibliographic entries were also tagged with corresponding accelerator tags. Finally, as a part of the endeavour to broaden CERN's presence on Wikipedia, existing Wikipedia articles of accelerators were updated with short descriptions and links to Inspire. In total, 86 Wikipedia articles were updated. This repo...

  8. Contribution of Interstitial Deletion of 21q22.2-3 per se to Prostate Cancer Progression in Tumors Harboring TMPRSS2-ERG Translocations

    Science.gov (United States)

    2015-12-01

    harboring TMPRSS2- ERG translocations PRINCIPAL INVESTIGATOR: Yan Dong CONTRACTING ORGANIZATION: Tulane University New Orleans, LA 70112...0485 to prostate cancer progression in tumors harboring TMPRSS2- ERG translocations 5b. GRANT NUMBER W81XWH-14-1-0485 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT TMPRSS2- ERG gene fusions are present in close to 50% of human prostate cancers. Approximately half of the

  9. Longing Itineraries: Building the Translocal Community

    Directory of Open Access Journals (Sweden)

    Gustavo López Angel

    2017-06-01

    Full Text Available Migration has reshaped social practices, the sense of belonging has been rethought, and the membership is renegotiated and contended; this is why strategies for their sustainability have been generated. The translocal community operates through multilocated relationships that reveal the ways in which migrants are adapting to the new demands of the community. We emphasize the emotional impulse of nostalgia as one of the vehicles of sustainability for the community. The community is redefined and understood in a set of socio-cultural relationships its members generate, and where the locality is not central, but the connection. A new dimension of the social community space is not just the community gathered in a specific place, but also that agreements, commitments, and acknowledgments are exhibited and settled in the cyberspace; this cyberspace gives cohesion and brings a dynamic element to preserve the community, despite the fact that it is even less concrete than the spatial notion of territory. Facebook, YouTube and a blog are the web platforms of the virtual space where "neighbors, compatriots and citizens" (categories of ascription from the migration get together, where there is a reproduction of social practices (even the most ancient and fundamental ones, to give a new dimension to a translocal, multilocated and ciberlocated community.

  10. Another reptile translocation to a national park

    Directory of Open Access Journals (Sweden)

    W.R. Branch

    1990-10-01

    Full Text Available On 4 May 1988 a sub-adult (50 mm snout-vent length, 42 mm tail Jones' girdled lizard Cordylus tropidosternum jonesi was collected in a pile of wood being off-loaded at the new restcamp in the Karoo National Park, Beaufort West. The wood had been transported by lorry from the Kruger National Park. The specimen is deposited in the herpetological collection of the Port Elizabeth Museum (PEM R 4584. Jones' girdled lizard is a small, arboreal cordylid that shelters under tree bark and in hollow logs. It is common and widely-distributed in the Kruger National Park (Pienaar, Haacke & Jacobsen 1983, The Reptiles of the Kruger National Park, 3rd edition. Pretoria: National Parks Board and adjacent lowveld, being replaced in northern Zimbabwe and East Africa by the nominate race. Hewitt & Power (1913, Transactions of the Royal Society of South Africa 3: 147-176, 1913 reported a similar translocation of the species to Kimberley in association with timber brought to the diamond mining camps. One of us noted recently the ease and danger of the unwitting spread of commensal reptile species into conservation areas (Branch 1978, Koedoe 30: 165, and this is confirmed by this additional example. We recommend that should similar shipments of wood be considered essential, then they be fumigated to prevent the translocation of other alien organisms that may potentially have more dangerous consequences.

  11. Arsenic Uptake and Translocation in Plants.

    Science.gov (United States)

    Li, Nannan; Wang, Jingchao; Song, Won-Yong

    2016-01-01

    Arsenic (As) is a highly toxic metalloid that is classified as a non-threshold class-1 carcinogen. Millions of people worldwide suffer from As toxicity due to the intake of As-contaminated drinking water and food. Reducing the As concentration in drinking water and food is thus of critical importance. Phytoremediation of soil contaminated with As and the reduction of As contamination in food depend on a detailed understanding of As uptake and transport in plants. As transporters play essential roles in As uptake, translocation and accumulation in plant cells. In this review, we summarize the current understanding of As transport in plants, with an emphasis on As uptake, mechanisms of As resistance and the long-distance translocation of As, especially the accumulation of As in grains through phloem-mediated transport. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Factors affecting translocation and sclerotial formation in Morchella esculenta

    International Nuclear Information System (INIS)

    Amir, R.; Levanon, D.; Hadar, Y.; Chet, I.

    1995-01-01

    Amir, R., Levanon, D., Hadar, Y., and Chet, I. 1995. Factors affecting translocation and sclerotial formation in Morchella esculenta. Experimental Mycology 19, 61-70. Morchella esculenta was grown on square split plates, forming sclerotia on one side and mycelium on the other. After the fungus ceased to colonize and before sclerotial initials appeared, [ 14 C]3-O-methyl glucose was added to the edge of the plate on the mycelial side. The effect of various activities in the mycelium (source) and sclerotia (sink) on sclerotial formation and translocation were examined using inhibitors and water potential changes of the media. Sodium azide or cycloheximide applied separately to both sides inhibited both sclerotial formation and translocation, showing that processes in the source and sink depend on metabolic activities as well as protein synthesis. The use of nikkomycin inhibited sclerotial formation, without affecting translocation to the sclerotia. Since the hyphal tips swelled and burst, the translocated compounds were lost to the media. In a strain defective in sclerotial formation, used as a control, no translocation took place, showing that there is a connection between sclerotial formation and translocation. Reversal of the water potential gradient between the two media (lower on the mycelial side), reduced the formation of sclerotia and translocation to them. Translocation to Morchella sclerotia takes place via turgor driven mass flow, but is nevertheless affected by activities in both the source and the sink. (author)

  13. Label Free Chromosome Translocation Detection with Silicon nanowires

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Andersen, Karsten Brandt; Frøhling, Kasper Bayer

    HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method is a Fluore......HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method...

  14. Transfer of Hessian fly resistance from rye to wheat via radiation-induced terminal and intercalary chromosomal translocations

    International Nuclear Information System (INIS)

    Friebe, B.; Hatchett, J.H.; Gill, B.S.; Mukai, Y.; Sebesta, E.E.

    1991-01-01

    A new Hessian fly (Mayetiola destructor) resistance gene derived from 'Balbo' rye and its transfer to hexaploid wheat via radiation-induced terminal and intercalary chromosomal translocations are described. Crosses between resistant 'Balbo' rye and susceptible 'Suwon 92' wheat and between the F1 amphidiploids and susceptible 'TAM 106' and 'Amigo' wheats produced resistant BC2F3 lines that were identified by C-banding analysis as being 6RL telocentric addition lines. Comparative chromosomal analyses and resistance tests revealed that the resistance gene is located on the 6RL telocentric chromosome. X-irradiated pollen of 6RL addition plants was used to fertilize plants of susceptible wheats 'TAM 106,' 'TAM 101,' and 'Vona.' After several generations of selection for resistance, new sublines were obtained that were homogeneous for resistance. Thirteen of these lines were analyzed by C-banding, and three different wheat-6RL chromosomal translocations (T) were identified. Wheat chromosomes involved in the translocations were 6B, 4B, and 4A. Almost the complete 6RL arm is present in T6BS · 6BL-6RL. Only the distal half of 6RL is present in T4BS · 4BL-6RL, which locates the resistance gene in the distal half of 6RL. Only a very small segment (ca 1.0 μm) of the distal region of 6RL is present in an intercalary translocation (Ti) Ti4AS · 4AL-6RL-4AL. The 6RL segment is inserted in the intercalary region between the centromere of chromosome 4A and the large proximal C-band of 4AL. The break-points of the translocations are outside the region of the centromere, indicating that they were induced by the X-ray treatment. All three translocations are cytologically stable and can be used directly in wheat breeding programs

  15. FMIT accelerator

    International Nuclear Information System (INIS)

    Armstrong, D.D.

    1983-01-01

    A 35-MeV 100-mA cw linear accelerator is being designed by Los Alamos for use in the Fusion Materials Irradiation Test (FMIT) Facility. Essential to this program is the design, construction, and evaluation of performance of the accelerator's injector, low-energy beam transport, and radio-frequency quadrupole sections before they are shipped to the facility site. The installation and testing of some of these sections have begun as well as the testing of the rf, noninterceptive beam diagnostics, computer control, dc power, and vacuum systems. An overview of the accelerator systems and the performance to date is given

  16. Electron accelerator

    International Nuclear Information System (INIS)

    Abramyan.

    1981-01-01

    The USSR produces an electron accelerator family of a simple design powered straight from the mains. The specifications are given of accelerators ELITA-400, ELITA-3, ELT-2, TEUS-3 and RIUS-5 with maximum electron energies of 0.3 to 5 MeV, a mean power of 10 to 70 kW operating in both the pulsed and the continuous (TEUS-3) modes. Pulsed accelerators ELITA-400 and ELITA-3 and RIUS-5 in which TESLA resonance transformers are used are characterized by their compact size. (Ha)

  17. A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay.

    Science.gov (United States)

    Ozantürk, Ayşegül; Davis, Erica E; Sabo, Aniko; Weiss, Marjan M; Muzny, Donna; Dugan-Perez, Shannon; Sistermans, Erik A; Gibbs, Richard A; Özgül, Köksal R; Yalnızoglu, Dilek; Serdaroglu, Esra; Dursun, Ali; Katsanis, Nicholas

    2016-03-01

    Genetic studies grounded on monogenic paradigms have accelerated both gene discovery and molecular diagnosis. At the same time, complex genomic rearrangements are also appreciated as potent drivers of disease pathology. Here, we report two male siblings with a dysmorphic face, ambiguous genitalia, intellectual disability, and speech delay. Through quad-based whole-exome sequencing and concomitant molecular cytogenetic testing, we identified two copy-number variants (CNVs) in both affected individuals likely arising from a balanced translocation: a 13.5-Mb duplication on Chromosome 16 (16q23.1 → 16qter) and a 7.7-Mb deletion on Chromosome 5 (5p15.31 → 5pter), as well as a hemizygous missense variant in CXorf36 (also known as DIA1R). The 5p terminal deletion has been associated previously with speech delay, whereas craniofacial dysmorphia and genital/urinary anomalies have been reported in patients with a terminal duplication of 16q. However, dosage changes in either genomic region alone could not account for the overall clinical presentation in our family; functional testing of CXorf36 in zebrafish did not induce defects in neurogenesis or the craniofacial skeleton. Notably, literature and database analysis revealed a similar dosage disruption in two siblings with extensive phenotypic overlap with our patients. Taken together, our data suggest that dosage perturbation of genes within the two chromosomal regions likely drives the syndromic manifestations of our patients and highlight how multiple genetic lesions can contribute to complex clinical pathologies.

  18. MicroRNA-125b-1 and BLID upregulation resulting from a novel IGH translocation in childhood B-Cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Tassano, Elisa; Acquila, Maura; Tavella, Elisa; Micalizzi, Concetta; Panarello, Claudio; Morerio, Cristina

    2010-08-01

    Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus are common abnormalities in mature B-cell neoplasms. Recent findings have also revealed their significant role in B-cell precursor acute lymphoblastic leukemia. As a rule, IGH translocations generate transcriptional activation of the oncogene localized in the proximity of the breakpoint. In this study, we describe a pediatric case of B-cell precursor acute lymphoblastic leukemia showing microRNA-125b-1 (MIR125B1) and BLID gene overexpression, resulting from a novel t(11;14)(q24.1;q32) translocation involving IGH. This is the first report describing the upregulation of a microRNA due to its juxtaposition to protein-coding gene regulatory elements and the overexpression of two neighboring genes as a consequence of transcriptional enhancers localized in the vicinity of the IGH gene.

  19. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M; Uwimpuhwe, H; Ballo, R; Kaur, M; Bajic, Vladimir B.; Prince, S

    2009-01-01

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular

  20. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  1. Horizontal Accelerator

    Data.gov (United States)

    Federal Laboratory Consortium — The Horizontal Accelerator (HA) Facility is a versatile research tool available for use on projects requiring simulation of the crash environment. The HA Facility is...

  2. Acceleration theorems

    International Nuclear Information System (INIS)

    Palmer, R.

    1994-06-01

    Electromagnetic fields can be separated into near and far components. Near fields are extensions of static fields. They do not radiate, and they fall off more rapidly from a source than far fields. Near fields can accelerate particles, but the ratio of acceleration to source fields at a distance R, is always less than R/λ or 1, whichever is smaller. Far fields can be represented as sums of plane parallel, transversely polarized waves that travel at the velocity of light. A single such wave in a vacuum cannot give continuous acceleration, and it is shown that no sums of such waves can give net first order acceleration. This theorem is proven in three different ways; each method showing a different aspect of the situation

  3. LINEAR ACCELERATOR

    Science.gov (United States)

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  4. Translocation of cell-penetrating peptides into Candida fungal pathogens.

    Science.gov (United States)

    Gong, Zifan; Karlsson, Amy J

    2017-09-01

    Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

  5. An Updated View of Translocator Protein (TSPO

    Directory of Open Access Journals (Sweden)

    Nunzio Denora

    2017-12-01

    Full Text Available Decades of study on the role of mitochondria in living cells have evidenced the importance of the 18 kDa mitochondrial translocator protein (TSPO, first discovered in the 1977 as an alternative binding site for the benzodiazepine diazepam in the kidneys. This protein participates in a variety of cellular functions, including cholesterol transport, steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and cell proliferation. Thus, TSPO has become an extremely attractive subcellular target for the early detection of disease states that involve the overexpression of this protein and the selective mitochondrial drug delivery. This special issue was programmed with the aim of summarizing the latest findings about the role of TSPO in eukaryotic cells and as a potential subcellular target of diagnostics or therapeutics. A total of 9 papers have been accepted for publication in this issue, in particular, 2 reviews and 7 primary data manuscripts, overall describing the main advances in this field.

  6. Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Pedersen, Julie S.; Tavenier, Juliette

    2018-01-01

    .4), and MELD score 12 (±3.9). Patients received rifaximin 550 mg BD (n=36) or placebo BD (n=18). Blood and faecal (n=15) sampling were conducted at baseline and after four weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in faeces was analysed......BACKGROUND & AIMS: Decompensated cirrhosis is characterized by disturbed haemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination...... with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. In a randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. METHODS: Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (±8...

  7. Delayed reproduction of translocated red-cockaded woodpeckers

    Science.gov (United States)

    James R. McCormick; Richard N. Conner; Daniel Saenz; Brent Burt

    2001-01-01

    Twelve pairs of Red-cockaded Woodpeckers were translocated to the Angelina National Forest from 21 October 1998 to 17 December 1998. Five breeding pairs (consisting of at least one trnnslocated bird) produced eggs/nestlings within the first breeding season after translocation. Clutch initiation dates for all five pairs were later than those of resident breeders. The...

  8. Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line.

    Science.gov (United States)

    Peeters, B W M M; Ruigt, G S F; Craighead, M; Kitchener, P

    2008-12-01

    Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist-GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021-012 and RTI3021-022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone-induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 x 10(-7) M) did not induce GR translocation, but was able to block corticosterone (3 x 10(-8) M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.

  9. The ATOMKI Accelerator Center

    International Nuclear Information System (INIS)

    Biri, S.; Kormany, Z.; Berzi, I.; Hunyadi, M.

    2009-01-01

    In 2009 a new division was established in our institute: the ATOMKI Accelerator Center (AAC). Before this time the facilities and staff of AAC belonged to other departments of the institute. The re-organization however, was necessary. It was understood that the translocation of all the accelerators into a centralized unit is advantageous in numerous fields. Here we just mention some of them. The submission of any instrumentation type proposal (EU or domestic) will be easier and has a higher chance to be supported. The organization and distribution of the beamtimes will be more equal and optimal. The usage of the maintenance and spare tools can became better and cheaper. The operating staff (cca. 20 person) can serve at more than one accelerator and the teams can help each other. The accelerator center actually became a fourth new basic unit of the institute besides the three traditional scientific divisions (see the Atomki homepage for the organization chart). The following six main facilities belong to the accelerator center: Cyclotron; VdG-5 accelerator; VdG-1 accelerator; ECR ion source; Isotope separator; Tandetron (under installation). In figure 1 the placements of these machines are shown in an artistic 3D map of the Atomki. The table 1 summarizes the main parameters of the accelerators. More detailed technical specification of the machines can be found in the new homepage of the center. In 2009 all the accelerators operated as scheduled, safely and without major breakdowns. After the experiences in the first months it can be concluded that the new center works well both for technical and human point of views. In the next sub-chapters the 2009 operation and development details of the individual accelerators are summarized. Cyclotron operation. The operation of the cyclotron in 2009 was concentrated to the usual 9 months; January, July and August were reserved for maintenance and holidays. The overall working time of the accelerator was 2009 hours; the time

  10. Multistep Current Signal in Protein Translocation through Graphene Nanopores

    KAUST Repository

    Bonome, Emma Letizia

    2015-05-07

    © 2015 American Chemical Society. In nanopore sensing experiments, the properties of molecules are probed by the variation of ionic currents flowing through the nanopore. In this context, the electronic properties and the single-layer thickness of graphene constitute a major advantage for molecule characterization. Here we analyze the translocation pathway of the thioredoxin protein across a graphene nanopore, and the related ionic currents, by integrating two nonequilibrium molecular dynamics methods with a bioinformatic structural analysis. To obtain a qualitative picture of the translocation process and to identify salient features we performed unsupervised structural clustering on translocation conformations. This allowed us to identify some specific and robust translocation intermediates, characterized by significantly different ionic current flows. We found that the ion current strictly anticorrelates with the amount of pore occupancy by thioredoxin residues, providing a putative explanation of the multilevel current scenario observed in recently published translocation experiments.

  11. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  12. Minimizing the cost of translocation failure with decision-tree models that predict species' behavioral response in translocation sites.

    Science.gov (United States)

    Ebrahimi, Mehregan; Ebrahimie, Esmaeil; Bull, C Michael

    2015-08-01

    The high number of failures is one reason why translocation is often not recommended. Considering how behavior changes during translocations may improve translocation success. To derive decision-tree models for species' translocation, we used data on the short-term responses of an endangered Australian skink in 5 simulated translocations with different release conditions. We used 4 different decision-tree algorithms (decision tree, decision-tree parallel, decision stump, and random forest) with 4 different criteria (gain ratio, information gain, gini index, and accuracy) to investigate how environmental and behavioral parameters may affect the success of a translocation. We assumed behavioral changes that increased dispersal away from a release site would reduce translocation success. The trees became more complex when we included all behavioral parameters as attributes, but these trees yielded more detailed information about why and how dispersal occurred. According to these complex trees, there were positive associations between some behavioral parameters, such as fight and dispersal, that showed there was a higher chance, for example, of dispersal among lizards that fought than among those that did not fight. Decision trees based on parameters related to release conditions were easier to understand and could be used by managers to make translocation decisions under different circumstances. © 2015 Society for Conservation Biology.

  13. Accelerator microanalysis

    International Nuclear Information System (INIS)

    Tuniz, C.

    1997-01-01

    Particle accelerators have been developed more than sixty years ago to investigate nuclear and atomic phenomena. A major shift toward applications of accelerators in the study of materials structure and composition in inter-disciplinary projects has been witnessed in the last two decades. The Australian Nuclear Science and Technology Organisation (ANSTO) has developed advanced research programs based on the use of particle and photon beams. Atmospheric pollution problems are investigated at the 3 MV Van de Graff accelerator using ion beam analysis techniques to detect toxic elements in aerosol particles. High temperature superconductor and semiconductor materials are characterised using the recoil of iodine and other heavy ions produced at ANTARES, the 10-MV Tandem accelerator. A heavy-ion microprobe is presently being developed at ANTARES to map elemental concentrations of specific elements with micro-size resolution. An Accelerator mass Spectrometry (AMS) system has been developed at ANSTO for the ultra-sensitive detection of Carbon-14, Iodine-129 and other long-lived radioisotopes. This AMS spectrometer is a key instrument for climate change studies and international safeguards. ANSTO is also managing the Australian Synchrotron Research program based on facilities developed at the Photon Factory (Japan) and at the Advanced Photon Source (USA). Advanced projects in biology, materials chemistry, structural condensed matter and other disciplines are being promoted by a consortium involving Australian universities and research institutions. This paper will review recent advances in the use of particle accelerators, with a particular emphasis on applications developed at ANSTO and related to problems of international concern, such as global environmental change, public health and nuclear proliferation

  14. Familial X/Y Translocation Encompassing ARSE in Two Moroccan Siblings with Sensorineural Deafness.

    Science.gov (United States)

    Amasdl, Saadia; Smaili, Wiam; Natiq, Abdelhafid; Hassani, Amale; Sbiti, Aziza; Agadr, Aomar; Sanlaville, Damien; Sefiani, Abdelaziz

    2017-01-01

    Unbalanced translocations involving X and Y chromosomes are rare and associated with a contiguous gene syndrome. The clinical phenotype is heterogeneous including mainly short stature, chondrodysplasia punctata, ichthyosis, hypogonadism, and intellectual disability. Here, we report 2 brothers with peculiar gestalt, short stature, and hearing loss, who harbor an X/Y translocation. Physical examination, brainstem acoustic potential evaluation, bone age, hormonal assessment, and X-ray investigations were performed. Because of their dysmorphic features, karyotyping, FISH, and aCGH were carried out. The probands had short stature, hypertelorism, midface hypoplasia, sensorineural hearing loss, normal intelligence as well as slight radial and ulnar bowing with brachytelephalangy. R-banding identified a derivative X chromosome with an abnormally expanded short arm. The mother was detected as a carrier of the same aberrant X chromosome. aCGH disclosed a 3.1-Mb distal deletion of chromosome region Xp22.33pter. This interval encompasses several genes, especially the short stature homeobox (SHOX) and arylsulfatase (ARSE) genes. The final karyotype of the probands was: 46,Y,der(X),t(X;Y)(p22;q12).ish der(X)(DXYS129-,DXYS153-)mat.arr[hg19] Xp22.33(61091_2689408)×1mat,Xp22.33(2701273_3258404)×0mat,Yq11.222q12 (21412851_59310245)×2. Herein, we describe a Moroccan family with a maternally inherited X/Y translocation and discuss the genotype-phenotype correlations according to the deleted genes. © 2017 S. Karger AG, Basel.

  15. The ribosome as a molecular machine: the mechanism of tRNA-mRNA movement in translocation.

    Science.gov (United States)

    Rodnina, Marina V; Wintermeyer, Wolfgang

    2011-04-01

    Translocation of tRNA and mRNA through the ribosome is one of the most dynamic events during protein synthesis. In the cell, translocation is catalysed by EF-G (elongation factor G) and driven by GTP hydrolysis. Major unresolved questions are: how the movement is induced and what the moving parts of the ribosome are. Recent progress in time-resolved cryoelectron microscopy revealed trajectories of tRNA movement through the ribosome. Driven by thermal fluctuations, the ribosome spontaneously samples a large number of conformational states. The spontaneous movement of tRNAs through the ribosome is loosely coupled to the motions within the ribosome. EF-G stabilizes conformational states prone to translocation and promotes a conformational rearrangement of the ribosome (unlocking) that accelerates the rate-limiting step of translocation: the movement of the tRNA anticodons on the small ribosomal subunit. EF-G acts as a Brownian ratchet providing directional bias for movement at the cost of GTP hydrolysis.

  16. Accelerator operations

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    This section is concerned with the operation of both the tandem-linac system and the Dynamitron, two accelerators that are used for entirely different research. Developmental activities associated with the tandem and the Dynamitron are also treated here, but developmental activities associated with the superconducting linac are covered separately because this work is a program of technology development in its own right

  17. CNSTN Accelerator

    International Nuclear Information System (INIS)

    Habbassi, Afifa; Trabelsi, Adel

    2010-01-01

    This project give a big idea about the measurement of the linear accelerator in the CNSTN. During this work we control dose distribution for different product. For this characterisation we have to make an installation qualification ,operational qualification,performance qualification and of course for every step we have to control temperature and the dose ,even the distribution of the last one.

  18. Accelerators course

    CERN Multimedia

    CERN. Geneva HR-RFA; Métral, E

    2006-01-01

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges

  19. Accelerator operations

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Operations of the SuperHILAC, the Bevatron/Bevalac, and the 184-inch Synchrocyclotron during the period from October 1977 to September 1978 are discussed. These include ion source development, accelerator facilities, the Heavy Ion Spectrometer System, and Bevelac biomedical operations

  20. Accelerator update

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    When the Accelerator Conference, combined International High Energy and US Particle versions, held in Dallas in May, was initially scheduled, progress nearby for the US Superconducting Supercollider was high on the preliminary agenda. With the SSC voted down by Congress in October 1993, this was no longer the case. However the content of the meeting, in terms of both its deep implications for ambitious new projects and the breadth of its scope, showed that the worldwide particle accelerator field is far from being moribund. A traditional feature of such accelerator conferences is the multiplicity of parallel sessions. No one person can attend all sessions, so that delegates can follow completely different paths and emerge with totally different impressions. Despite this overload, and despite the SSC cancellation, the general picture is one of encouraging progress over a wide range of major new projects throughout the world. At the same time, spinoff from, and applications of, accelerators and accelerator technology are becoming increasingly important. Centrestage is now CERN's LHC proton-proton collider, where a test string of superconducting magnets is operating over long periods at the nominal LHC field of 8.36 tesla or more. The assignment of the underground areas in the existing 27- kilometre LEP tunnel is now quasidefinitive (see page 3). For CERN's existing big machine, the LEP electron-positron collider, ongoing work concentrates on boosting performance using improved optics and bunch trains. But the main objective is the LEP2 scheme using superconducting accelerating cavities to boost the beam energy (see page 6). After some initial teething problems, production and operation of these cavities appears to have been mastered, at least under test conditions. A highlight at CERN last year was the first run with lead ions (December 1994, page 15). Handling these heavy particles with systems originally designed for protons calls for ingenuity. The SPS

  1. Accelerator update

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1995-09-15

    When the Accelerator Conference, combined International High Energy and US Particle versions, held in Dallas in May, was initially scheduled, progress nearby for the US Superconducting Supercollider was high on the preliminary agenda. With the SSC voted down by Congress in October 1993, this was no longer the case. However the content of the meeting, in terms of both its deep implications for ambitious new projects and the breadth of its scope, showed that the worldwide particle accelerator field is far from being moribund. A traditional feature of such accelerator conferences is the multiplicity of parallel sessions. No one person can attend all sessions, so that delegates can follow completely different paths and emerge with totally different impressions. Despite this overload, and despite the SSC cancellation, the general picture is one of encouraging progress over a wide range of major new projects throughout the world. At the same time, spinoff from, and applications of, accelerators and accelerator technology are becoming increasingly important. Centrestage is now CERN's LHC proton-proton collider, where a test string of superconducting magnets is operating over long periods at the nominal LHC field of 8.36 tesla or more. The assignment of the underground areas in the existing 27- kilometre LEP tunnel is now quasidefinitive (see page 3). For CERN's existing big machine, the LEP electron-positron collider, ongoing work concentrates on boosting performance using improved optics and bunch trains. But the main objective is the LEP2 scheme using superconducting accelerating cavities to boost the beam energy (see page 6). After some initial teething problems, production and operation of these cavities appears to have been mastered, at least under test conditions. A highlight at CERN last year was the first run with lead ions (December 1994, page 15). Handling these heavy particles with systems originally designed for protons calls for ingenuity. The SPS has managed

  2. Forced Translocation of Polymer through Nanopore: Deterministic Model and Simulations

    Science.gov (United States)

    Wang, Yanqian; Panyukov, Sergey; Liao, Qi; Rubinstein, Michael

    2012-02-01

    We propose a new theoretical model of forced translocation of a polymer chain through a nanopore. We assume that DNA translocation at high fields proceeds too fast for the chain to relax, and thus the chain unravels loop by loop in an almost deterministic way. So the distribution of translocation times of a given monomer is controlled by the initial conformation of the chain (the distribution of its loops). Our model predicts the translocation time of each monomer as an explicit function of initial polymer conformation. We refer to this concept as ``fingerprinting''. The width of the translocation time distribution is determined by the loop distribution in initial conformation as well as by the thermal fluctuations of the polymer chain during the translocation process. We show that the conformational broadening δt of translocation times of m-th monomer δtm^1.5 is stronger than the thermal broadening δtm^1.25 The predictions of our deterministic model were verified by extensive molecular dynamics simulations

  3. [Clinical characteristics and preimplantation genetic diagnosis for male Robertsonian translocations].

    Science.gov (United States)

    Huang, Jin; Lian, Ying; Qiao, Jie; Liu, Ping

    2012-08-18

    To explore the clinical characteristics and the preimplantation genetic diagnosis (PGD) for male Robertsonian translocations. From Jan 2005 to Oct 2011, 96 PGD cycles of 80 male Robertsonian translocations were performed at the Center of Reproductive Medicine of Peking University Third Hospital, Beijing. All the couples were involved in assisted reproductive therapy because of oligozoospermia or repeated abortions. Pregnancy results and clinical characteristics were analyzed in this study. Of all the 80 Robertsonian translocation couples, 62 (77.50%, 62/80) couples suffered from primary infertility due to severe oligoospermia and 8 (10%, 8/80) couples suffered from secondary infertility due to oligoospermia. Moreover, 10 (12.50%, 10/80) couples had recurrent spontaneous abortion. Of all the 80 male Robertsonian translocations, 50 were (13; 14) translocations and 15 (14; 21) translocations. The study showed that 79 PGD cycles had the balanced embryos to transfer and 25 cycles resulted in clinical pregnancies. The clinical pregnancy rate per transfer cycle was 31.65% (25 of 79). Now, 18 couples had 21 viable infants and 3 were ongoing pregnant. Oligozoospermia is the main factor for the infertility of the male Robertsonian translocations. Artificial reproductive techniques can solve their reproductive problems. Moreover, PGD will decrease the risk of recurrent spontaneous abortion and the malformations.

  4. Genetic outcomes from the translocations of the critically endangered woylie

    Directory of Open Access Journals (Sweden)

    Carlo PACIONI, Adrian F.WAYNE, Peter B.S.SPENCER

    2013-06-01

    Full Text Available Translocations are an important conservation strategy for many species. However simply observing demographic growth of a translocated population is not sufficient to infer species recovery. Adequate genetic representation of the source population(s and their long-term viability should also be considered. The woylie Bettongia penicillata ogilbyi has been subject to more formal translocations for conservation than any other marsupial that, up until recently, has resulted in one of the most successful species recoveries in Australia. We used mitochondrial and nuclear DNA markers to assess the genetic outcomes of translocated woylie populations. These populations have lost genetic variability, differentiated from their source population and the supplementation program on two island populations appears to have failed. We discuss the conservation implications that our results have for managing threatened species, outline some general recommendations for the management of present and future translocations and discuss the appropriate sampling design for the establishment of new populations or captive breeding programs that may mitigate the genetic ‘erosion’ seen in our study species. This research provides some practical outcomes and a pragmatic understanding of translocation biology. The findings are directly applicable to other translocation programs [Current Zoology 59 (3: 294-310, 2013].

  5. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  6. Translocation of threatened plants as a conservation measure in China.

    Science.gov (United States)

    Liu, Hong; Ren, Hai; Liu, Qiang; Wen, XiangYing; Maunder, Michael; Gao, JiangYun

    2015-12-01

    We assessed the current status of plant conservation translocation efforts in China, a topic poorly reported in recent scientific literature. We identified 222 conservation translocation cases involving 154 species, of these 87 were Chinese endemic species and 101 (78%) were listed as threatened on the Chinese Species Red List. We categorized the life form of each species and, when possible, determined for each case the translocation type, propagule source, propagule type, and survival and reproductive parameters. A surprisingly large proportion (26%) of the conservation translocations in China were conservation introductions, largely implemented in response to large-scale habitat destruction caused by the Three-Gorge Dam and another hydropower project. Documentation and management of the translocations varied greatly. Less than half the cases had plant survival records. Statistical analyses showed that survival percentages were significantly correlated with plant life form and the type of planting materials. Thirty percent of the cases had records on whether or not individuals flowered or fruited. Results of information theoretic model selection indicated that plant life form, translocation type, propagule type, propagule source, and time since planting significantly influenced the likelihood of flowering and fruiting on the project level. We suggest that the scientific-based application of species conservation translocations should be promoted as part of a commitment to species recovery management. In addition, we recommend that the common practice of within and out of range introductions in nature reserves to be regulated more carefully due to its potential ecological risks. We recommend the establishment of a national office and database to coordinate conservation translocations in China. Our review effort is timely considering the need for a comprehensive national guideline for the newly announced nation-wide conservation program on species with extremely

  7. Absorption and translocation of phosphorus-32 in guava leaves

    International Nuclear Information System (INIS)

    Natale, William

    1997-01-01

    Phosphorus is easily absorbed by the leaves and translocated. The objective of this work was to evaluate the absorption and translocation of P by guava leaves, with time. When a solution containing 2% MAP and specific activity 0.15 μCi/ml was applied. MAP labelled with 32 P was applied in the 3 rd pair of leaves. These and other leaves, roots and stem were collected separately and analyzed accordingly. The results showed that 20 days after application 12% of the applied P was absorbed by the guava leaves. The translocation of P started immediately after its absorption reaching 20% 2fter 20 days. (author). 19 refs., 4 tabs

  8. Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression.

    Science.gov (United States)

    Karlsson, Asa; Deb-Basu, Debabrita; Cherry, Athena; Turner, Stephanie; Ford, James; Felsher, Dean W

    2003-08-19

    DNA repair mechanisms are essential for the maintenance of genomic integrity. Disruption of gene products responsible for DNA repair can result in chromosomal damage. Improperly repaired chromosomal damage can result in the loss of chromosomes or the generation of chromosomal deletions or translocations, which can lead to tumorigenesis. The MYC protooncogene is a transcription factor whose overexpression is frequently associated with human neoplasia. MYC has not been previously implicated in a role in DNA repair. Here we report that the overexpression of MYC disrupts the repair of double-strand DNA breaks, resulting in a several-magnitude increase in chromosomal breaks and translocations. We found that MYC inhibited the repair of gamma irradiation DNA breaks in normal human cells and blocked the repair of a single double-strand break engineered to occur in an immortal cell line. By spectral karyotypic analysis, we found that MYC even within one cell division cycle resulted in a several-magnitude increase in the frequency of chromosomal breaks and translocations in normal human cells. Hence, MYC overexpression may be a previously undescribed example of a dominant mutator that may fuel tumorigenesis by inducing chromosomal damage.

  9. Accelerating Value Creation with Accelerators

    DEFF Research Database (Denmark)

    Jonsson, Eythor Ivar

    2015-01-01

    and developing the best business ideas and support the due diligence process. Even universities are noticing that the learning experience of the action learning approach is an effective way to develop capabilities and change cultures. Accelerators related to what has historically been associated...

  10. Nuclear translocation and regulation of intranuclear distribution of cytoplasmic poly(A-binding protein are distinct processes mediated by two Epstein Barr virus proteins.

    Directory of Open Access Journals (Sweden)

    Richard Park

    Full Text Available Many viruses target cytoplasmic polyA binding protein (PABPC to effect widespread inhibition of host gene expression, a process termed viral host-shutoff (vhs. During lytic replication of Epstein Barr Virus (EBV we observed that PABPC was efficiently translocated from the cytoplasm to the nucleus. Translocated PABPC was diffusely distributed but was excluded from viral replication compartments. Vhs during EBV infection is regulated by the viral alkaline nuclease, BGLF5. Transfection of BGLF5 alone into BGLF5-KO cells or uninfected 293 cells promoted translocation of PAPBC that was distributed in clumps in the nucleus. ZEBRA, a viral bZIP protein, performs essential functions in the lytic program of EBV, including activation or repression of downstream viral genes. ZEBRA is also an essential replication protein that binds to viral oriLyt and interacts with other viral replication proteins. We report that ZEBRA also functions as a regulator of vhs. ZEBRA translocated PABPC to the nucleus, controlled the intranuclear distribution of PABPC, and caused global shutoff of host gene expression. Transfection of ZEBRA alone into 293 cells caused nuclear translocation of PABPC in the majority of cells in which ZEBRA was expressed. Co-transfection of ZEBRA with BGLF5 into BGLF5-KO cells or uninfected 293 cells rescued the diffuse intranuclear pattern of PABPC seen during lytic replication. ZEBRA mutants defective for DNA-binding were capable of regulating the intranuclear distribution of PABPC, and caused PABPC to co-localize with ZEBRA. One ZEBRA mutant, Z(S186E, was deficient in translocation yet was capable of altering the intranuclear distribution of PABPC. Therefore ZEBRA-mediated nuclear translocation of PABPC and regulation of intranuclear PABPC distribution are distinct events. Using a click chemistry-based assay for new protein synthesis, we show that ZEBRA and BGLF5 each function as viral host shutoff factors.

  11. Chemiosmotic Energy Conservation in Dinoroseobacter shibae: Proton Translocation Driven by Aerobic Respiration, Denitrification, and Photosynthetic Light Reaction

    Directory of Open Access Journals (Sweden)

    Christian Kirchhoff

    2018-05-01

    Full Text Available Dinoroseobacter shibae is an aerobic anoxygenic phototroph and able to utilize light energy to support its aerobic energy metabolism. Since the cells can also grow anaerobically with nitrate and nitrite as terminal electron acceptor, we were interested in how the cells profit from photosynthesis during denitrification and what the steps of chemiosmotic energy conservation are. Therefore, we conducted proton translocation experiments and compared O2-, NO3-, and NO2- respiration during different light regimes and in the dark. We used wild type cells and transposon mutants with knocked-out nitrate- and nitrite- reductase genes (napA and nirS, as well as a mutant (ppsR impaired in bacteriochlorophyll a synthesis. Light had a positive impact on proton translocation, independent of the type of terminal electron acceptor present. In the absence of an electron acceptor, however, light did not stimulate proton translocation. The light-driven add-on to proton translocation was about 1.4 H+/e- for O2 respiration and about 1.1 H+/e- for NO3- and NO2-. We could see that the chemiosmotic energy conservation during aerobic respiration involved proton translocation, mediated by the NADH dehydrogenase, the cytochrome bc1 complex, and the cytochrome c oxidase. During denitrification the last proton translocation step of the electron transport was missing, resulting in a lower H+/e- ratio during anoxia. Furthermore, we studied the type of light-harvesting and found that the cells were able to channel light from the green–blue spectrum most efficiently, while red light has only minor impact. This fits well with the depth profiles for D. shibae abundance in the ocean and the penetration depth of light with different wavelengths into the water column.

  12. Laser acceleration

    Science.gov (United States)

    Tajima, T.; Nakajima, K.; Mourou, G.

    2017-02-01

    The fundamental idea of Laser Wakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wakefields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ˜ c and ultrafastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nanomaterials is also emerging.

  13. Laser acceleration

    International Nuclear Information System (INIS)

    Tajima, T.; Nakajima, K.; Mourou, G.

    2017-01-01

    The fundamental idea of LaserWakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wake fields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ∼ c and ultra fastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nano materials is also emerging.

  14. Accelerating networks

    International Nuclear Information System (INIS)

    Smith, David M D; Onnela, Jukka-Pekka; Johnson, Neil F

    2007-01-01

    Evolving out-of-equilibrium networks have been under intense scrutiny recently. In many real-world settings the number of links added per new node is not constant but depends on the time at which the node is introduced in the system. This simple idea gives rise to the concept of accelerating networks, for which we review an existing definition and-after finding it somewhat constrictive-offer a new definition. The new definition provided here views network acceleration as a time dependent property of a given system as opposed to being a property of the specific algorithm applied to grow the network. The definition also covers both unweighted and weighted networks. As time-stamped network data becomes increasingly available, the proposed measures may be easily applied to such empirical datasets. As a simple case study we apply the concepts to study the evolution of three different instances of Wikipedia, namely, those in English, German, and Japanese, and find that the networks undergo different acceleration regimes in their evolution

  15. A case of posttraumatic splenic translocation into the thorax

    International Nuclear Information System (INIS)

    Sosnowski, P.; Sikorski, L.; Ziemianski, A.

    1993-01-01

    A case of the left diaphragmatic hernia due to blunt thoracic and abdominal trauma is presented. Characteristic radiological signs of splenic translocation into the thorax contributed to quick diagnosis and immediate surgical intervention. (author)

  16. Multistep Current Signal in Protein Translocation through Graphene Nanopores

    KAUST Repository

    Bonome, Emma Letizia; Lepore, Rosalba; Raimondo, Domenico; Cecconi, Fabio; Tramontano, Anna; Chinappi, Mauro

    2015-01-01

    of graphene constitute a major advantage for molecule characterization. Here we analyze the translocation pathway of the thioredoxin protein across a graphene nanopore, and the related ionic currents, by integrating two nonequilibrium molecular dynamics

  17. Microbial translocation and cardiometabolic risk factors in HIV infection

    DEFF Research Database (Denmark)

    Trøseid, Marius; Manner, Ingjerd W; Pedersen, Karin K

    2014-01-01

    of microbial translocation are closely associated with several cardiovascular risk factors such as dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis. Future studies should investigate whether associations between microbial...

  18. Isolated Norrie disease in a female caused by a balanced translocation t(X,6).

    Science.gov (United States)

    Meire, F M; Lafaut, B A; Speleman, F; Hanssens, M

    1998-12-01

    This is the second report of Norrie disease in a female patient with a de-novo balanced translocation t(X,6) with breakpoint at the location of the Norrie gene. At the age of 3 months, a girl was referred for suspected congenital glaucoma. The right eye was microphthalmic and ultrasonography was compatible with persistent hyperplasia of the primary vitreous. The left eye was also microphthalmic. The left cornea was larger than the right. The anterior chamber was virtual and leukocoria was evident. The eye felt hard digitally. Ultrasonography indicated an organized retinal detachment. The pathologic findings are reported and are compatible with Norrie disease.

  19. Carbon translocation in zooanthaellae-coelenterate symbioses

    International Nuclear Information System (INIS)

    Battey, J.F.

    1985-01-01

    When host and algal triglycerides synthesized in the symbiotic sea anemone Condylactis gigantea during light and dark incubations in 14 C-bicarbonate and 14 C-acetate were deacylated, more then 80% of the radioactivity was found in the fatty acid moiety. In contrast, triglycerides isolated from zooxanthellae and host incubated in 14 C-glycerol in the dark were found to have more then 95% of their radioactivity in the glycerol moiety. During 14 C-glycerol incubations in the light, radioactivity in the fatty acid moiety of zooxanthellae triglyceride fatty acid moiety stayed below 5% during 14 C-glycerol incubations in the light. These results show neither the zooxanthellae nor host can rapidly convert glycerol to fatty acid. Radioactivity from 14 C-glycerol that does eventually appear in host lipid may have been respired to 14 CO 2 then photosynthetically fixed by the zooxanthellae and synthesized into lipid fatty acid. The isolated zooxanthellae of C. gigantea contained 3.62 +/- 0.33 mM glycerol, which was 26x the 0.141 +/- 0.02 mM found in the coelenterate tissue. Aposymbiotic coelenterate tissue contained 0.169 +/- 0.05 mM glycerol. The metabolic inhibitors, sodium cyanide, aminooxyacetic acid and cerulenin were used to try and uncouple the production of glycerol by the zooxanthellae from its utilization by the coelenterate host. 10 -5 M NaCN increased the ratio of cross photosynthesis to respiration in both intact tentacles and isolated zooxanthellae, increased translocation from 17.7 +/- 3.5% of total fixed carbon in controls to 43.5 +/- 5.79%, and doubled the amount of photosynthetically fixed carbon accumulating in the coelenterate host over that in controls

  20. Bacterial translocation in clinical intestinal transplantation.

    Science.gov (United States)

    Cicalese, L; Sileri, P; Green, M; Abu-Elmagd, K; Kocoshis, S; Reyes, J

    2001-05-27

    Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after small bowel transplantation (SBTx). Bacterial overgrowth, alteration of the mucosal barrier function as a consequence of preservation injury or acute rejection (AR), and potent immunosuppression are all associated with BT. The aim of this study was to evaluate and quantify the correlation of BT with these events. Fifty pediatric SBTx recipients on tacrolimus and prednisone immunosuppression were analyzed. Blood, stool, and liver biopsies and peritoneal fluid were cultured (circa 4000 total specimens) when infection was clinically suspected or as part of follow-up. BT episodes were considered when microorganisms were found simultaneously in blood or liver biopsy and stool. BT (average of 2.0 episodes/patient) was evident in 44% of patients and was most frequently caused by Enterococcus, Staphylococcus, Enterobacter, and Klebsiella. The presence of a colon allograft was associated with a higher rate of BT (75% vs. 33.3%). Furthermore, the transplantation procedure (colon vs. no colon) affected the rate of BT: SBTx=40% vs. 25%, combined liver and SBTx=100% vs. 30%, multivisceral transplantation=25% vs. 50%. AR was associated with 39% of BT episodes. BT followed AR in 9.6% of the cases. In 5.2% of the cases, positive blood cultures without stool confirmation of the bacteria were seen. Prolonged cold ischemia time (CIT) affected BT rate significantly (CIT>9 hr 76% vs. CIT<9 hr 20.8%). This study shows that 1) a substantial percentage of, but not all, BT is associated with AR, 2) the presence of a colon allograft increases the risk for BT, and 3) a long CIT is associated with a high incidence of BT after SBTx.

  1. Meiotic delay of translocation carrying spermatocytes responsible for reduced transmission

    International Nuclear Information System (INIS)

    Buul, P.P.W. van

    1991-01-01

    Using in vivo pulse labelling of spermatocytes from mice irradiated with different doses of X-rays (6 and 7 Gy). The authors demonstrated that cells having translocations derived from irradiated stem cells tend to spend longer time at the meiotic prophase than normal cells. At the 2 Gy level this effect is much less pronounced. The recorded delay forms a good explanation for the reduced transmission of translocations to the next generation observed by others. (author)

  2. Advanced concepts for acceleration

    International Nuclear Information System (INIS)

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations

  3. Uptake, translocation, and debromination of polybrominated diphenyl ethers in maize

    Institute of Scientific and Technical Information of China (English)

    Moming Zhao; Shuzhen Zhang; Sen Wang; Honglin Huang

    2012-01-01

    Uptake,translocation and debromination of three polybrominated diphenyl ethers(PBDEs),BDE-28,-47 and-99,in maize were studied in a hydroponic experiment.Roots took up most of the PBDEs in the culture solutions and more highly brominated PBDEs had a stronger uptake capability.PBDEs were detected in the stems and leaves of maize after exposure but rarely detected in the blank control plants.Furthermore,PBDE concentrations decreased from roots to stems and then to leaves,and a very clear decreasing gradient was found in segments upwards along the stem.These altogether provide substantiating evidence for the acropetal translocation of PBDEs in maize.More highly brominated PBDEs were translocated with more difficulty.Radial translocation of PBDEs from nodes to sheath inside maize was also observed.Both acropetal and radial translocations were enhanced at higher transpiration rates,suggesting that PBDE transport was probably driven by the transpiration stream.Debromination of PBDEs occurred in all parts of the maize,and debromination patterns of different parent PBDEs and in different parts of a plant were similar but with some differences.This study for the first time provides direct evidence for the acropetal translocation of PBDEs within plants,elucidates the process of PBDE transport and clarifies the debromination products of PBDEs in maize.

  4. The Unexplored Mechanisms and Regulatory Functions of Ribosomal Translocation

    Science.gov (United States)

    Alejo, Jose Luis

    In every cell, protein synthesis is carried out by the ribosome, a complex macromolecular RNA-protein assembly. Decades of structural and kinetic studies have increased our understanding of ribosome initiation, decoding, translocation and termination. Yet, the underlying mechanism of these fundamental processes has yet to be fully delineated. Hence, the molecular basis of regulation remains obscure. Here, single-molecule fluorescence methods are applied to decipher the mechanism and regulatory roles of the multi-step process of directional substrate translocation on the ribosome that accompanies every round of protein synthesis. In Chapter 1, single-molecule fluorescence resonance energy transfer (smFRET) is introduced as a tool for studying bacterial ribosome translocation. Chapter 2 details the experimental methods. In Chapter 3, the elongation factor G(EF-G)-catalyzed movement of substrates through the ribosome is examined from several perspectives or signals reporting on various degrees of freedom of ribosome dynamics. Two ribosomal states interconvert in the presence of EF-G(GDP), displaying novel head domain motions, until relocking takes place. In Chapter 4, in order to test if the mentioned fluctuations leading to relocking are correlated to the engagement of the P-site by the peptidyl-tRNA, the translocation of miscoded tRNAs is studied. Severe defects in the relocking stages of translocation reveal the correlation between this new stage of translocation and P-site tRNA engagement.

  5. Cloning of the chromosome translocation breakpoint junction of the t(14;19) in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    McKeithan, T.W.; Rowley, J.D.; Shows, T.B.; Diaz, M.O.

    1987-01-01

    The authors' laboratory has reported that t(14;19)(q32;q13.1) is a recurring translocation in the neoplastic cells of patients with chronic lymphocytic leukemia. In the present study, they have analyzed the leukemic cells from one such patient with probes from the immunoglobulin heavy-chain locus, which is present on band q32 of chromosome 14. Using a probe for the α constant-region gene segments, they detected a rearranged band by Southern blot analysis. This rearranged band was cloned and mapped. A subclone free of repetitive sequences was shown to be from chromosome 19 by analysis of human-mouse somatic cell hybrids, confirming that the rearranged band contains the translocation breakpoint junction. This probe may be used to identify a gene on chromosome 19 adjacent to the breakpoint that can contribute to the malignant development of B lymphocytes

  6. Accelerators and the Accelerator Community

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  7. Accelerators and the Accelerator Community

    International Nuclear Information System (INIS)

    Malamud, Ernest; Sessler, Andrew

    2008-01-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process

  8. Menopause accelerates biological aging

    Science.gov (United States)

    Levine, Morgan E.; Lu, Ake T.; Chen, Brian H.; Hernandez, Dena G.; Singleton, Andrew B.; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E.; Quach, Austin; Kusters, Cynthia D. J.; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E.; Widschwendter, Martin; Ritz, Beate R.; Absher, Devin; Assimes, Themistocles L.; Horvath, Steve

    2016-01-01

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  9. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Science.gov (United States)

    Mukesh; Sharma, Lalit Kumar; Charoo, Samina Amin; Sathyakumar, Sambandam

    2015-01-01

    The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  10. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Directory of Open Access Journals (Sweden)

    Mukesh

    Full Text Available The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  11. Ring accelerators

    International Nuclear Information System (INIS)

    Gisler, G.; Faehl, R.

    1983-01-01

    We present two-dimensional simulations in (r-z) and r-theta) cylinderical geometries of imploding-liner-driven accelerators of rings of charged particles. We address issues of azimuthal and longitudinal stability of the rings. We discuss self-trapping designs in which beam injection and extraction is aided by means of external cusp fields. Our simulations are done with the 2-1/2-D particle-in-cell plasma simulation code CLINER, which combines collisionless, electromagnetic PIC capabilities with a quasi-MHD finite element package

  12. accelerating cavity

    CERN Multimedia

    On the inside of the cavity there is a layer of niobium. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment.

  13. Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole.

    Directory of Open Access Journals (Sweden)

    Hayley J Newton

    Full Text Available The human pathogen Coxiella burnetii encodes a type IV secretion system called Dot/Icm that is essential for intracellular replication. The Dot/Icm system delivers bacterial effector proteins into the host cytosol during infection. The effector proteins delivered by C. burnetii are predicted to have important functions during infection, but when these proteins are needed during infection has not been clearly defined. Here, we use a reporter system consisting of fusion proteins that have a β-lactamase enzyme (BlaM fused to C. burnetii effector proteins to study protein translocation by the Dot/Icm system. Translocation of BlaM fused to the effector proteins CBU0077, CBU1823 and CBU1524 was not detected until 8-hours after infection of HeLa cells, which are permissive for C. burnetii replication. Translocation of these effector fusion proteins by the Dot/Icm system required acidification of the Coxiella-containing vacuole. Silencing of the host genes encoding the membrane transport regulators Rab5 or Rab7 interfered with effector translocation, which indicates that effectors are not translocated until bacteria traffic to a late endocytic compartment in the host cell. Similar requirements for effector translocation were discerned in bone marrow macrophages derived from C57BL/6 mice, which are primary cells that restrict the intracellular replication of C. burnetii. In addition to requiring endocytic maturation of the vacuole for Dot/Icm-mediated translocation of effectors, bacterial transcription was required for this process. Thus, translocation of effector proteins by the C. burnetii Dot/Icm system occurs after acidification of the CCV and maturation of this specialized organelle to a late endocytic compartment. This indicates that creation of the specialized vacuole in which C. burnetii replicates represents a two-stage process mediated initially by host factors that regulate endocytic maturation and then by bacterial effectors delivered into

  14. Cosmic ray acceleration mechanisms

    International Nuclear Information System (INIS)

    Cesarsky, C.J.

    1982-09-01

    We present a brief summary of some of the most popular theories of cosmic ray acceleration: Fermi acceleration, its application to acceleration by shocks in a scattering medium, and impulsive acceleration by relativistic shocks

  15. Transcuticular translocation of radionuclides on plant leaf surfaces

    International Nuclear Information System (INIS)

    Matsumoto, Ken-ichi; Watanabe, Tadakazu; Ambe, Shizuko; Yamaguchi, Isamu

    1996-01-01

    The cuticle covering all the outermost surfaces of the aerial parts of plants could play a selective role in uptake and translocation of radionuclides from air into plants. In this study, we investigated the transcuticular uptake and translocation behavior via water droplets of various radionuclides in red clover, orchard grass, Japanese radish and mung bean. Ten μl of an aqueous solution of the multitracer generated from Au was applied to the upper surface of the 2nd leaf of the plants at the 5th leaf stage. The plants were then grown for 14 days at 25degC and 70% RH under illumination of artificial solar lights. The transcuticular uptake and translocation throughout the plant were periodically assayed by determining the radioactivity in the surface residue, the cuticle layer beneath the applied site, the leaf area outside the applied site, the other aerial parts and the root of the plant, using an HPGe detector. The applied radionuclides were absorbed into, in turn, the cuticle layer beneath the applied site and then translocated through the cuticle to the inner tissue and eventually to the other aerial parts and finally to the roots, of the plant. The distribution and accumulation in the plant seems to depend upon the characteristics of each radionuclide and plant species. Ca * and Te * tended to remain on leaf surfaces without being absorbed into the cuticle. On the other hand, Sc * , Co * , Zn * , Se * , Rb * , and Eu * were easily absorbed and translocated to every part of the plant including the root. The other radionuclides such as Be * , Mn * , Sr * , Y * , Ba * , Ce * , Pm * , Gd * , Hf * , Yb * , Lu * , Os * , Ir * , and Pt * remained in the region close to the site of their application. The above results possibly indicate the existence of mechanisms common to these plants for selective transcuticular uptake and translocation of radionuclides within plant tissues, though their translocation was considerably influenced by the plant species. (author)

  16. High-speed detection of DNA translocation in nanopipettes

    Science.gov (United States)

    Fraccari, Raquel L.; Ciccarella, Pietro; Bahrami, Azadeh; Carminati, Marco; Ferrari, Giorgio; Albrecht, Tim

    2016-03-01

    We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface.We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface. Electronic supplementary information (ESI) available: Gel electrophoresis confirming lengths and purity of DNA samples, comparison between Axopatch 200B and custom-built setup, comprehensive low-noise amplifier characterization, representative I-V curves of nanopipettes used, typical scatter plots of τ vs. peak amplitude for the four LDNA's used, table of most probable τ values, a comparison between different fitting models for the DNA translocation time distribution, further details on the stochastic numerical simulation of the scaling statistics and the derivation of the extended

  17. Role of non-equilibrium conformations on driven polymer translocation.

    Science.gov (United States)

    Katkar, H H; Muthukumar, M

    2018-01-14

    One of the major theoretical methods in understanding polymer translocation through a nanopore is the Fokker-Planck formalism based on the assumption of quasi-equilibrium of polymer conformations. The criterion for applicability of the quasi-equilibrium approximation for polymer translocation is that the average translocation time per Kuhn segment, ⟨τ⟩/N K , is longer than the relaxation time τ 0 of the polymer. Toward an understanding of conditions that would satisfy this criterion, we have performed coarse-grained three dimensional Langevin dynamics and multi-particle collision dynamics simulations. We have studied the role of initial conformations of a polyelectrolyte chain (which were artificially generated with a flow field) on the kinetics of its translocation across a nanopore under the action of an externally applied transmembrane voltage V (in the absence of the initial flow field). Stretched (out-of-equilibrium) polyelectrolyte chain conformations are deliberately and systematically generated and used as initial conformations in translocation simulations. Independent simulations are performed to study the relaxation behavior of these stretched chains, and a comparison is made between the relaxation time scale and the mean translocation time (⟨τ⟩). For such artificially stretched initial states, ⟨τ⟩/N K polymers including single stranded DNA (ssDNA), double stranded DNA (dsDNA), and synthetic polymers. Even when these data are rescaled assuming a constant effective velocity of translocation, it is found that for flexible (ssDNA and synthetic) polymers with N K Kuhn segments, the condition ⟨τ⟩/N K polymers such as ssDNA, a crossover from quasi-equilibrium to non-equilibrium behavior would occur at N K ∼ O(1000).

  18. Jumping translocations in hematological malignancies: a cytogenetic study of five cases.

    Science.gov (United States)

    Manola, Kalliopi N; Georgakakos, Vasileios N; Stavropoulou, Chryssa; Spyridonidis, Alexandros; Angelopoulou, Maria K; Vlachadami, Ioanna; Katsigiannis, Andreas; Roussou, Paraskevi; Pantelias, Gabriel E; Sambani, Constantina

    2008-12-01

    Jumping translocations (JT) are rare cytogenetic aberrations in hematological malignancies that include unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to two or more different recipient chromosomes in different cell lines. We report five cases associated with different hematologic disorders and JT to contribute to the investigation of the origin, pathogenesis, and clinical significance of JT. These cases involve JT of 1q in a case of acute myeloblastic leukemia (AML)-M1, a case of Burkitt lymphoma, and a case of BCR/ABL-positive acute lymphoblastic leukemia, as well as a JT of 13q in a case of AML-M5, and a JT of 11q segment in a case of undifferentiated leukemia. To our knowledge, with regard to hematologic malignancies, this study presents the first case of JT associated with AML-M1, the first case of JT involving 13q as a donor chromosome, and the first report of JT involving a segment of 11q containing two copies of the MLL gene, jumping on to two recipient chromosomes in each cell line and resulting in six copies of the MLL gene. Our investigation suggests that JT may not contribute to the pathogenesis but rather to the progression of the disease, and it demonstrates that chromosome band 1q10 as a breakpoint of the donor chromosome 1q is also implicated in AML, not only in multiple myeloma as it has been known until now.

  19. An Arabidopsis thaliana knock-out mutant of the chloroplast triose phosphate/phosphate translocator is severely compromised only when starch synthesis, but not starch mobilisation is abolished

    DEFF Research Database (Denmark)

    Schneider, Anja; Häusler, Rainer E; Kolukisaoglu, Uner

    2002-01-01

    The Arabidopsis thaliana tpt-1 mutant which is defective in the chloroplast triose phosphate/phosphate translocator (TPT) was isolated by reverse genetics. It contains a T-DNA insertion 24 bp upstream of the start ATG of the TPT gene. The mutant lacks TPT transcripts and triose phosphate (TP)-spe...

  20. GeneYenta: a phenotype-based rare disease case matching tool based on online dating algorithms for the acceleration of exome interpretation.

    Science.gov (United States)

    Gottlieb, Michael M; Arenillas, David J; Maithripala, Savanie; Maurer, Zachary D; Tarailo Graovac, Maja; Armstrong, Linlea; Patel, Millan; van Karnebeek, Clara; Wasserman, Wyeth W

    2015-04-01

    Advances in next-generation sequencing (NGS) technologies have helped reveal causal variants for genetic diseases. In order to establish causality, it is often necessary to compare genomes of unrelated individuals with similar disease phenotypes to identify common disrupted genes. When working with cases of rare genetic disorders, finding similar individuals can be extremely difficult. We introduce a web tool, GeneYenta, which facilitates the matchmaking process, allowing clinicians to coordinate detailed comparisons for phenotypically similar cases. Importantly, the system is focused on phenotype annotation, with explicit limitations on highly confidential data that create barriers to participation. The procedure for matching of patient phenotypes, inspired by online dating services, uses an ontology-based semantic case matching algorithm with attribute weighting. We evaluate the capacity of the system using a curated reference data set and 19 clinician entered cases comparing four matching algorithms. We find that the inclusion of clinician weights can augment phenotype matching. © 2015 WILEY PERIODICALS, INC.

  1. A somatic origin of homologous Robertsonian translocations and isochromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A. (Univ. of Zurich (Switzerland)); Basaran, S.; Yueksel-Apak, M. (Univ. of Istanbul (Turkey)); Neri, G. (Universita Cattolica, Rome (Italy)); Serville, F. (Hopital d' Enfants Pellegrin, Bordeaux (France)); Balicek, P.; Haluza, R. (Univ. Hospital of Hradeck Kralove, Hradec Kralove (Czech Republic)); Farah, L.M.S. (Escuola Paulista de Medicina, Sao Paulo (Brazil)) (and others)

    1994-02-01

    One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.

  2. Electrostatics of polymer translocation events in electrolyte solutions.

    Science.gov (United States)

    Buyukdagli, Sahin; Ala-Nissila, T

    2016-07-07

    We develop an analytical theory that accounts for the image and surface charge interactions between a charged dielectric membrane and a DNA molecule translocating through the membrane. Translocation events through neutral carbon-based membranes are driven by a competition between the repulsive DNA-image-charge interactions and the attractive coupling between the DNA segments on the trans and the cis sides of the membrane. The latter effect is induced by the reduction of the coupling by the dielectric membrane. In strong salt solutions where the repulsive image-charge effects dominate the attractive trans-cis coupling, the DNA molecule encounters a translocation barrier of ≈10 kBT. In dilute electrolytes, the trans-cis coupling takes over image-charge forces and the membrane becomes a metastable attraction point that can trap translocating polymers over long time intervals. This mechanism can be used in translocation experiments in order to control DNA motion by tuning the salt concentration of the solution.

  3. Nonabsorbable Antibiotics Reduce Bacterial and Endotoxin Translocation in Hepatectomised Rats

    Directory of Open Access Journals (Sweden)

    S. K. Kakkos

    1997-01-01

    Full Text Available There is increasing evidence that septic complications, occurring after major hepatectomies, may be caused by gram negative bacteria, translocating from the gut. We investigated in rats, the effect of extended hepatectomy on the structure and morphology of the intestinal mucosa as well as on the translocation of intestinal bacteria and endotoxins. We also examined the effect of nonabsorbable antibiotics on reducing the intestinal flora and consequently the phenomenon of translocation by administering neomycin sulphate and cefazoline. Hepatectomy was found to increase translocation, while administration of nonabsorbable antibiotics decreased it significantly. In addition, hepatectomy increased the aerobic cecal bacterial population, which normalised in the group receiving antibiotics. Among the histological parameters evaluated, villus height demonstrated a significant reduction after hepatectomy, while the number of villi per cm and the number of mitoses per crypt, remained unchanged. Our results indicate that administration of nonabsorbable antibiotics presents a positive effect on bacterial and endotoxin translocation after extended hepatectomy, and this may be related to reduction of colonic bacterial load as an intraluminal effect of antibiotics.

  4. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    Directory of Open Access Journals (Sweden)

    Jingjing eMeng

    2015-06-01

    Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

  5. Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

    Science.gov (United States)

    Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

    2015-01-14

    In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

  6. Mechanism for translocation of fluoroquinolones across lipid membranes

    DEFF Research Database (Denmark)

    Cramariuc, O.; Rog, T.; Javanainen, M.

    2012-01-01

    Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone...... antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins....... Subsequent QM analysis of the observed molecular stacking shows the important role of partial charge neutralization in the stacks, highlighting how the zwitterionic form of the drug is neutralized for translocation. The findings propose a translocation mechanism in which zwitterionic CPFX molecules approach...

  7. Biological mechanisms and translocation kinetics of particulate plutonium

    International Nuclear Information System (INIS)

    Bruenger, F.W.; Stevens, W.; Atherton, D.R.; Roswell, R.L.; Smith, J.M.

    1981-01-01

    The dissolution and elimination of particulate 239 Pu from its initial sites of deposition in phagocytic organs (the liver, spleen, and lung), as well as its translocation and redeposition in soft tissue organs and skeleton have been investigated. Beagles were injected intravenously with particulate Pu and sacrificed sequentially at times ranging from 33 to 830 days after injection. Equations that describe the overall retention of Pu in liver, spleen, lung, and bone were calculated. Plutonium mobilized from these organs either re-entered the blood stream and redeposited in the skeleton and liver parenchyma or was excreted. The protracted translocation of Pu to bone surfaces potentially exposes all cells involved in osteogenesis to continuous α-radiation, a situation that could enhance the hazard of developing osteosarcoma. A kinetic model that describes the translocation of Pu from the phagocytic compartments to blood and its subsequent redistribution to bone, liver, and other organs was formulated

  8. Evaluating descriptors for the lateral translocation of membrane proteins.

    Science.gov (United States)

    Domanova, Olga; Borbe, Stefan; Mühlfeld, Stefanie; Becker, Martin; Kubitz, Ralf; Häussinger, Dieter; Berlage, Thomas

    2011-01-01

    Microscopic images of tissue sections are used for diagnosis and monitoring of therapy, by analysis of protein patterns correlating to disease states. Spatial protein distribution is influenced by protein translocation between different membrane compartments and quantified by comparison of microscopic images of biological samples. Cholestatic liver diseases are characterized by translocation of transport proteins, and quantification of their dislocation offers new diagnostic options. However, reliable and unbiased tools are lacking. The nowadays used manual method is slow, subjective and error-prone. We have developed a new workflow based on automated image analysis and improved it by the introduction of scale-free descriptors for the translocation quantification. This fast and unbiased method can substitute the manual analysis, and the suggested descriptors perform better than the earlier used statistical variance.

  9. Crystallographic snapshot of cellulose synthesis and membrane translocation.

    Science.gov (United States)

    Morgan, Jacob L W; Strumillo, Joanna; Zimmer, Jochen

    2013-01-10

    Cellulose, the most abundant biological macromolecule, is an extracellular, linear polymer of glucose molecules. It represents an essential component of plant cell walls but is also found in algae and bacteria. In bacteria, cellulose production frequently correlates with the formation of biofilms, a sessile, multicellular growth form. Cellulose synthesis and transport across the inner bacterial membrane is mediated by a complex of the membrane-integrated catalytic BcsA subunit and the membrane-anchored, periplasmic BcsB protein. Here we present the crystal structure of a complex of BcsA and BcsB from Rhodobacter sphaeroides containing a translocating polysaccharide. The structure of the BcsA-BcsB translocation intermediate reveals the architecture of the cellulose synthase, demonstrates how BcsA forms a cellulose-conducting channel, and suggests a model for the coupling of cellulose synthesis and translocation in which the nascent polysaccharide is extended by one glucose molecule at a time.

  10. Overexpression of Adenylyl Cyclase Encoded by the Mycobacterium tuberculosis Rv2212 Gene Confers Improved Fitness, Accelerated Recovery from Dormancy and Enhanced Virulence in Mice

    Directory of Open Access Journals (Sweden)

    Margarita O. Shleeva

    2017-08-01

    Full Text Available Earlier we demonstrated that the adenylyl cyclase (AC encoded by the MSMEG_4279 gene plays a key role in the resuscitation and growth of dormant Mycobacterium smegmatis and that overexpression of this gene leads to an increase in intracellular cAMP concentration and prevents the transition of M. smegmatis from active growth to dormancy in an extended stationary phase accompanied by medium acidification. We surmised that the homologous Rv2212 gene of M. tuberculosis (Mtb, the main cAMP producer, plays similar physiological roles by supporting, under these conditions, the active state and reactivation of dormant bacteria. To test this hypothesis, we established Mtb strain overexpressing Rv2212 and compared its in vitro and in vivo growth characteristics with a control strain. In vitro, the AC-overexpressing pMindRv2212 strain demonstrated faster growth in a liquid medium, prolonged capacity to form CFUs and a significant delay or even prevention of transition toward dormancy. AC-overexpressing cells exhibited easier recovery from dormancy. In vivo, AC-overexpressing bacteria demonstrated significantly higher growth rates (virulence in the lungs and spleens of infected mice compared to the control strain, and, unlike the latter, killed mice in the TB-resistant strain before month 8 of infection. Even in the absence of selecting hygromycin B, all pMindRv2212 CFUs retained the Rv2212 insert during in vivo growth, strongly suggesting that AC overexpression is beneficial for bacteria. Taken together, our results indicate that cAMP supports the maintenance of Mtb cells vitality under unfavorable conditions in vitro and their virulence in vivo.

  11. Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

    DEFF Research Database (Denmark)

    Gartland, Alison; Skarratt, Kristen K; Hocking, Lynne J

    2012-01-01

    The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether th...... publication, 11 January 2012; doi:10.1038/ejhg.2011.245....

  12. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies

    DEFF Research Database (Denmark)

    Kim, Hyung-Goo; Kim, Hyun-Taek; Leach, Natalia T

    2012-01-01

    development, and suppression of the latter led to both craniofacial abnormalities and neuronal apoptosis. Along with lysine-specific demethylase 1 (LSD1), PHF21A, also known as BHC80, is a component of the BRAF-histone deacetylase complex that represses target-gene transcription. In lymphoblastoid cell lines...... from two translocation subjects in whom PHF21A was directly disrupted by the respective breakpoints, we observed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional...

  13. De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome.

    Science.gov (United States)

    Sagar, Angela; Pinto, Dalila; Najjar, Fedra; Guter, Stephen J; Macmillan, Carol; Cook, Edwin H

    2017-06-01

    Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. (2011) Neuron 70: 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. (2010) Pediatrics 125: e727-735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. (2002) Circulation 102: 432-437]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. (1997) Journal of Medical Genetics 34: 719-728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. (2008) The American Journal of Human Genetics 82: 477-488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al. (1997)]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints. © 2017 Wiley Periodicals, Inc.

  14. Scintigraphic visualization of bacterial translocation in experimental strangulated intestinal obstruction

    International Nuclear Information System (INIS)

    Galeev, Yu.M.; Popov, M.V.; Salato, O.V.; Lishmanov, Yu.B.; Grigorev, E.G.; Aparcin, K.A.

    2009-01-01

    The purpose of this study was to obtain scintigraphic images depicting translocation of 99m Tc-labelled Escherichia coli bacteria through the intestinal barrier and to quantify this process using methods of nuclear medicine. Thirty male Wistar rats (including 20 rats with modelled strangulated intestinal obstruction and 10 healthy rats) were used for bacterial scintigraphy. 99m Tc-labelled E. coli bacteria ( 99m Ts-E. coli) with an activity of 7.4-11.1 MBq were administered into a section of the small intestine. Scintigraphic visualization of bacterial translocation into organs and tissues of laboratory animals was recorded in dynamic (240 min) and static (15 min) modes. The number of labelled bacteria, which migrated through the intestinal barrier, was quantified by calculating the translocation index (TI). Control indicated no translocation of 99m Ts-E. coli administered into the intestine through the parietes of the small intestine's distal part in healthy animals. Animals with strangulated obstruction demonstrated different migration strength and routes of labelled bacteria from strangulated and superior to strangulation sections of the small intestine. 99m Ts-E. coli migrated from the strangulated loop into the peritoneal cavity later causing systemic bacteraemia through peritoneal resorption. The section of the small intestine, which was superior to the strangulation, demonstrated migration of labelled bacteria first into the portal and then into the systemic circulation. The strangulated section of the small intestine was the main source of bacteria dissemination since the number of labelled bacteria, which migrated from this section significantly, exceeded that of the area superior to the strangulation section of the small intestine (p = 0.0003). Bacterial scintigraphy demonstrated the possibility of visualizing migration routes of labelled bacteria and quantifying their translocation through the intestinal barrier. This approach to study bacterial

  15. Dopaminergic expression of the Parkinsonian gene LRRK2-G2019S leads to non-autonomous visual neurodegeneration, accelerated by increased neural demands for energy

    Science.gov (United States)

    Hindle, Samantha; Afsari, Farinaz; Stark, Meg; Middleton, C. Adam; Evans, Gareth J.O.; Sweeney, Sean T.; Elliott, Christopher J.H.

    2013-01-01

    Parkinson's disease (PD) is associated with loss of dopaminergic signalling, and affects not just movement, but also vision. As both mammalian and fly visual systems contain dopaminergic neurons, we investigated the effect of LRRK2 mutations (the most common cause of inherited PD) on Drosophila electroretinograms (ERGs). We reveal progressive loss of photoreceptor function in flies expressing LRRK2-G2019S in dopaminergic neurons. The photoreceptors showed elevated autophagy, apoptosis and mitochondrial disorganization. Head sections confirmed extensive neurodegeneration throughout the visual system, including regions not directly innervated by dopaminergic neurons. Other PD-related mutations did not affect photoreceptor function, and no loss of vision was seen with kinase-dead transgenics. Manipulations of the level of Drosophila dLRRK suggest G2019S is acting as a gain-of-function, rather than dominant negative mutation. Increasing activity of the visual system, or of just the dopaminergic neurons, accelerated the G2019S-induced deterioration of vision. The fly visual system provides an excellent, tractable model of a non-autonomous deficit reminiscent of that seen in PD, and suggests that increased energy demand may contribute to the mechanism by which LRRK2-G2019S causes neurodegeneration. PMID:23396536

  16. The Genetics of a Probable Insertional Translocation in SORDARIA BREVICOLLIS.

    Science.gov (United States)

    Bond, D J

    1979-05-01

    A chromosome rearrangement has been isolated and characterized in Sordaria brevicollis. Crosses to spore color mutants on each of the seven linkage groups have enabled the breakpoints to be mapped. The simplest hypothesis to account for the results is that a piece of linkage group VI has been translocated to linkage group V and inserted 2.7 map units from its centromere. Previous reports of markers on this linkage group with centromere distances greater than 2.7 units make it unlikely that the translocation is quasiterminal.

  17. Free energy evaluation in polymer translocation via Jarzynski equality

    Energy Technology Data Exchange (ETDEWEB)

    Mondaini, Felipe, E-mail: fmondaini@if.ufrj.br [Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, Petrópolis, 25.620-003, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970, Rio de Janeiro, RJ (Brazil)

    2014-05-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations, which provide free energy estimates for unbiased three-dimensional polymer translocation. We employ the Jarzynski equality in its rigorous setting, to compute the variation of the free energy in single monomer translocation events. In our three-dimensional Langevin simulations, the excluded-volume and van der Waals interactions between beads (monomers and membrane atoms) are modeled through a repulsive Lennard-Jones (LJ) potential and consecutive monomers are subject to the Finite-Extension Nonlinear Elastic (FENE) potential. Analysing data for polymers with different lengths, the free energy profile is noted to have interesting finite-size scaling properties.

  18. Free energy evaluation in polymer translocation via Jarzynski equality

    International Nuclear Information System (INIS)

    Mondaini, Felipe; Moriconi, L.

    2014-01-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations, which provide free energy estimates for unbiased three-dimensional polymer translocation. We employ the Jarzynski equality in its rigorous setting, to compute the variation of the free energy in single monomer translocation events. In our three-dimensional Langevin simulations, the excluded-volume and van der Waals interactions between beads (monomers and membrane atoms) are modeled through a repulsive Lennard-Jones (LJ) potential and consecutive monomers are subject to the Finite-Extension Nonlinear Elastic (FENE) potential. Analysing data for polymers with different lengths, the free energy profile is noted to have interesting finite-size scaling properties.

  19. The action spectrum in chloroplast translocation in multilayer leaf cells

    Directory of Open Access Journals (Sweden)

    Zbigniew Lechowski

    2015-01-01

    Full Text Available By measurement of light transmittance through a leaf as criterion of chloroplast translocation, the action spectrum of Ajuga reptans was established. In the spectrum obtained, a correction was introduced for leaf autoabsorption calculated on the basis of the Beer-Lambert law. The action spectrum has two maxima: at λ= 375 nm and λ= 481 nm. The range above 502 nm has no significant effect on chloroplast translocation. Comparison with other objects examined demonstrated that in multilayer leaf cells riboflavin seems also to be a photoreceptor active in this process.

  20. Occupational exposure to pesticides and occurrence of the chromosomal translocation t(14;18 among farmers in Jordan

    Directory of Open Access Journals (Sweden)

    Bara’a M. Qaqish

    Full Text Available Background: An increased incidence of non-Hodgkin’s lymphoma (NHL has been reported in farmers and other occupational groups working with pesticides. In these individuals, an increased prevalence of the chromosomal translocation t(14;18(q32;q21, one of the most common chromosomal abnormalities in NHL, has been detected in peripheral blood lymphocytes. This translocation juxtaposes the antiapoptotic BCL2 protein to the immunoglobulin heavy chain gene locus (IGH leading to overexpression of BCL2. This causes an increase in cell survival, paving the way for malignant transformation. Aim of the study: The present study aimed to evaluate the association between the occurrence of the chromosomal translocation t(14;18 and occupational exposure to pesticides among a group of Jordanian farmers. Methods: A total of 192 male subjects including 96 agricultural workers and 96 control subjects participated in this study. BCL2-IGH t(14;18 fusions were detected by a nested polymerase chain reaction (PCR assay targeting the major breakpoint region (MBR. Results: We found that occupational exposure to pesticides in open-field farming and insecticide used on animals increased the frequency of the chromosomal translocation t(14;18. Farmers occupationally exposed to pesticides and insecticide were 13.5 times more likely to harbor t(14;18. 63.5% (61 of 96 of farmers compared to 11.5% (11 of 96 of controls carried the translocation (odds ratio: 13.5; 95% confidence interval (CI = 6.3–28.6. We ruled out the influence of possible confounding factors such as age, duration of sun exposure, alcohol intake, smoking, and use of personal protective equipment. Conclusion: Our results indicate that pesticides increased the frequency of chromosomal translocation in the 14q32 region. Accordingly, the presented data agrees with previous suggestions from the literature that pesticides might be involved in the development of NHL through the t(14;18 pathway. Keywords

  1. Functional and RNA-sequencing analysis revealed expression of a novel stay-green gene from Zoysia japonica (ZjSGR caused chlorophyll degradation and accelerated senescence in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Ke Teng

    2016-12-01

    Full Text Available Senescence is not only an important developmental process, but also a responsive regulation to abiotic and biotic stress for plants. Stay-green protein plays crucial roles in plant senescence and chlorophyll degradation. However, the underlying mechanisms were not well studied, particularly in non-model plants. In this study, a novel stay-green gene, ZjSGR, was isolated from Zoysia japonica. Subcellular localization result demonstrated that ZjSGR was localized in the chloroplasts. Quantitative real-time PCR results together with promoter activity determination using transgenic Arabidopsis confirmed that ZjSGR could be induced by darkness, ABA and MeJA. Its expression levels could also be up-regulated by natural senescence, but suppressed by SA treatments. Overexpression of ZjSGR in Arabidopsis resulted in a rapid yellowing phenotype; complementary experiments proved that ZjSGR was a functional homologue of AtNYE1 from Arabidopsis thaliana. Overexpression of ZjSGR accelerated chlorophyll degradation and impaired photosynthesis in Arabidopsis. Transmission electron microscopy observation revealed that overexpression of ZjSGR decomposed the chloroplasts structure. RNA sequencing analysis showed that ZjSGR could play multiple roles in senescence and chlorophyll degradation by regulating hormone signal transduction and the expression of a large number of senescence and environmental stress related genes. Our study provides a better understanding of the roles of SGRs, and new insight into the senescence and chlorophyll degradation mechanisms in plants.

  2. Sector ring accelerator ''RESATRON''

    International Nuclear Information System (INIS)

    Schwabe, E.

    1980-01-01

    Project of sector ring accelerator RESATRON is described. The curiosity of this accelerator is the second cycle of acceleration of the beam after stripping it on the foil. In such an accelerator heavy ions with a different ratio Z to A can be accelerated. (S.B.)

  3. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    Energy Technology Data Exchange (ETDEWEB)

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd [Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg (Germany); Schaefer, Tobias, E-mail: tobias.schaefer@uniklinik-freiburg.de [Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg (Germany)

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  4. Caspase 3 inactivates biologically active full length interleukin-33 as a classical cytokine but does not prohibit nuclear translocation

    International Nuclear Information System (INIS)

    Ali, Shafaqat; Nguyen, Dang Quan; Falk, Werner; Martin, Michael Uwe

    2010-01-01

    IL-33 is a member of the IL-1 family of cytokines with dual function which either activates cells via the IL-33 receptor in a paracrine fashion or translocates to the nucleus to regulate gene transcription in an intracrine manner. We show that full length murine IL-33 is active as a cytokine and that it is not processed by caspase 1 to mature IL-33 but instead cleaved by caspase 3 at aa175 to yield two products which are both unable to bind to the IL-33 receptor. Full length IL-33 and its N-terminal caspase 3 breakdown product, however, translocate to the nucleus. Finally, bioactive IL-33 is not released by cells constitutively or after activation. This suggests that IL-33 is not a classical cytokine but exerts its function in the nucleus of intact cells and only activates others cells via its receptor as an alarm mediator after destruction of the producing cell.

  5. Intratracheally instilled titanium dioxide nanoparticles translocate to heart and liver and activate complement cascade in the heart of C57BL/6 mice

    DEFF Research Database (Denmark)

    Husain, Mainul; Wu, Dongmei; Saber, Anne T.

    2015-01-01

    translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 mu g of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed...... of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following...... at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early...

  6. Multiperiodic accelerator structures for linear particle accelerators

    International Nuclear Information System (INIS)

    Tran, D.T.

    1975-01-01

    High efficiency linear accelerator structures, comprised of a succession of cylindrical resonant cavities for acceleration, are described. Coupling annular cavities are located at the periphery, each being coupled to two adjacent cylindrical cavities. (auth)

  7. Pros and cons of characterising an optical translocation setup

    CSIR Research Space (South Africa)

    Maphanga, Charles

    2017-02-01

    Full Text Available an optical translocation setup Charles Maphanga 1, 2 , Rudzani Malabi 1, 2 , Saturnin Ombinda-Lemboumba 1 , Malik Maaza 2 , Patience Mthunzi-Kufa 1, 2* 1 Council for Scientific and Industrial Research, National Laser Centre, P O BOX 395, Pretoria...

  8. Centrifugally driven microfluidic disc for detection of chromosomal translocations

    DEFF Research Database (Denmark)

    Brøgger, Anna Line; Kwasny, Dorota; Bosco, Filippo G.

    2012-01-01

    and prognosis of patients. In this work we demonstrate a novel, centrifugally-driven microfluidic system for controlled manipulation of oligonucleotides and subsequent detection of chromosomal translocations. The device is fabricated in the form of a disc with capillary burst microvalves employed to control...

  9. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Science.gov (United States)

    2010-07-01

    ... fertile animals for cytological confirmation as translocation heterozygotes. (3) Animal selection—(i... administration include oral, inhalation, admixture with food or water, and IP or IV injection. (e) Test.... Criteria for determining normal and semisterile males are usually established for each new strain because...

  10. Polymer translocation through a nanopore: a showcase of anomalous diffusion.

    Science.gov (United States)

    Milchev, A; Dubbeldam, Johan L A; Rostiashvili, Vakhtang G; Vilgis, Thomas A

    2009-04-01

    We investigate the translocation dynamics of a polymer chain threaded through a membrane nanopore by a chemical potential gradient that acts on the chain segments inside the pore. By means of diverse methods (scaling theory, fractional calculus, and Monte Carlo and molecular dynamics simulations), we demonstrate that the relevant dynamic variable, the transported number of polymer segments, s(t), displays an anomalous diffusive behavior, both with and without an external driving force being present. We show that in the absence of drag force the time tau, needed for a macromolecule of length N to thread from the cis into the trans side of a cell membrane, scales as tauN(2/alpha) with the chain length. The anomalous dynamics of the translocation process is governed by a universal exponent alpha= 2/(2nu + 2 - gamma(1)), which contains the basic universal exponents of polymer physics, nu (the Flory exponent) and gamma(1) (the surface entropic exponent). A closed analytic expression for the probability to find s translocated segments at time t in terms of chain length N and applied drag force f is derived from the fractional Fokker-Planck equation, and shown to provide analytic results for the time variation of the statistical moments and . It turns out that the average translocation time scales as tau proportional, f(-1)N(2/alpha-1). These results are tested and found to be in perfect agreement with extensive Monte Carlo and molecular dynamics computer simulations.

  11. Selective bowel decontamination results in gram-positive translocation.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Rowe, M I

    1990-05-01

    Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

  12. Toponomics method for the automated quantification of membrane protein translocation.

    Science.gov (United States)

    Domanova, Olga; Borbe, Stefan; Mühlfeld, Stefanie; Becker, Martin; Kubitz, Ralf; Häussinger, Dieter; Berlage, Thomas

    2011-09-19

    Intra-cellular and inter-cellular protein translocation can be observed by microscopic imaging of tissue sections prepared immunohistochemically. A manual densitometric analysis is time-consuming, subjective and error-prone. An automated quantification is faster, more reproducible, and should yield results comparable to manual evaluation. The automated method presented here was developed on rat liver tissue sections to study the translocation of bile salt transport proteins in hepatocytes. For validation, the cholestatic liver state was compared to the normal biological state. An automated quantification method was developed to analyze the translocation of membrane proteins and evaluated in comparison to an established manual method. Firstly, regions of interest (membrane fragments) are identified in confocal microscopy images. Further, densitometric intensity profiles are extracted orthogonally to membrane fragments, following the direction from the plasma membrane to cytoplasm. Finally, several different quantitative descriptors were derived from the densitometric profiles and were compared regarding their statistical significance with respect to the transport protein distribution. Stable performance, robustness and reproducibility were tested using several independent experimental datasets. A fully automated workflow for the information extraction and statistical evaluation has been developed and produces robust results. New descriptors for the intensity distribution profiles were found to be more discriminative, i.e. more significant, than those used in previous research publications for the translocation quantification. The slow manual calculation can be substituted by the fast and unbiased automated method.

  13. Bladder calculus resulting from an intravesical translocation of ...

    African Journals Online (AJOL)

    Although perforation of the uterus by an intrauterine contraceptive device (IUCD) is commonly encountered, intravesical translocation and secondary calculus formation is a very rare complication.We report a case of a 60-year old multiparous woman in whom an intrauterine contraceptive Copper-T device inserted 12 years ...

  14. Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

    2005-01-01

    Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

  15. Resource Control: A Translocation Of The Scramble For Africa ...

    African Journals Online (AJOL)

    Adopting a theoretical framework successfully adapted from the biological and medical sciences, namely; translocation analysis, the paper traces the ancestry of the present resource control problem to the scramble, first, and then, the use of fiscal and revenue allocation commissions during the colonial era, and the ...

  16. Single-Molecule Studies of Bacterial Protein Translocation

    NARCIS (Netherlands)

    Kedrov, Alexej; Kusters, Ilja; Driessen, Arnold J. M.

    2013-01-01

    In prokaryotes, a large share of the proteins are secreted from the cell through a process that requires their translocation across the cytoplasmic membrane. This process is mediated by the universally conserved Sec system with homologues in the endoplasmic reticulum and thylakoid membranes of

  17. Introduction: translocal development, development corridors and development chains.

    NARCIS (Netherlands)

    Zoomers, E.B.; Westen, A.C.M. van

    2011-01-01

    This paper offers an introduction to this Special Issue of International Development Planning Review. It uses the concepts of translocal development, development corridors and development chains to secure a better grasp of what development means in the context of globalisation and how ‘local

  18. Concentration Polarization in Translocation of DNA through Nanopores and Nanochannels

    NARCIS (Netherlands)

    Das, S.; Dubsky, P.; van den Berg, Albert; Eijkel, Jan C.T.

    2012-01-01

    In this Letter we provide a theory to show that high-field electrokinetic translocation of DNA through nanopores or nanochannels causes large transient variations of the ionic concentrations in front and at the back of the DNA due to concentration polarization (CP). The CP causes strong local

  19. Putative cruciform DNA structures at BCL6 breakpoint region may explain BCL6 translocation in diffuse large B-Cell lymphoma

    International Nuclear Information System (INIS)

    Bhatelia, Khyati D.; Nambiar, Mridula; Choudhary, Bibha; Raghvan, Sathees C.

    2010-01-01

    Cancer is a disease characterized by uncontrolled proliferation of cells, caused by genetic alterations such as chromosomal translocations, which are present in almost all hematological malignancies. Diffuse Large B-cell Lymphoma (DLBL) is the most common non-Hodgkin's lymphoma, comprising 40-50% of all lymphomas both in India and worldwide, and is characterized by BCL6 chromosomal translocation. However, the mechanism of this translocation is completely unknown. By mapping of translocation breakpoints from patients, we have identified three breakpoint cluster regions at 5' UTR of BCL6 gene. Bioinformatics analysis of cluster II, which possesses majority of breakpoints, this region may form cruciform DNA structures. Gel mobility shift assays using oligomeric DNA from the region suggested that a portion of cluster II folded into hairpin structures. Mutations to the wild type sequences disrupted hairpin formation. Circular dichroism studies on BCL6 oligomers resulted in a spectra containing two overlapping peaks at 265 nm and 285 nm, confirming hairpin structure. Further, the structure was destroyed upon heating, and reformed when appropriate conditions were provided. P1 nuclease assay in conjunction with KMnO 4 probing suggested that the structure possessed an eight nucleotide double-stranded stem and a nine nucleotide loop. To further understand the mechanism of BCL6 translocation in vivo, human cells were transfected with episomes harboring cluster II region and the results obtained will be discussed. Hence, our results suggest the formation of a putative cruciform DNA structure at BCL6 breakpoint region and that may facilitate breakage at BCL6 gene explaining chromosomal translocations in DLBL. (author)

  20. Accelerators of atomic particles

    International Nuclear Information System (INIS)

    Sarancev, V.

    1975-01-01

    A brief survey is presented of accelerators and methods of accelerating elementary particles. The principle of collective accelerating of elementary particles is clarified and the problems are discussed of its realization. (B.S.)

  1. Transcuticular translocation of radionuclides on plant leaf surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Ken-ichi; Watanabe, Tadakazu; Ambe, Shizuko; Yamaguchi, Isamu [Institute of Physical and Chemical Research, Wako, Saitama (Japan)

    1996-12-31

    The cuticle covering all the outermost surfaces of the aerial parts of plants could play a selective role in uptake and translocation of radionuclides from air into plants. In this study, we investigated the transcuticular uptake and translocation behavior via water droplets of various radionuclides in red clover, orchard grass, Japanese radish and mung bean. Ten {mu}l of an aqueous solution of the multitracer generated from Au was applied to the upper surface of the 2nd leaf of the plants at the 5th leaf stage. The plants were then grown for 14 days at 25degC and 70% RH under illumination of artificial solar lights. The transcuticular uptake and translocation throughout the plant were periodically assayed by determining the radioactivity in the surface residue, the cuticle layer beneath the applied site, the leaf area outside the applied site, the other aerial parts and the root of the plant, using an HPGe detector. The applied radionuclides were absorbed into, in turn, the cuticle layer beneath the applied site and then translocated through the cuticle to the inner tissue and eventually to the other aerial parts and finally to the roots, of the plant. The distribution and accumulation in the plant seems to depend upon the characteristics of each radionuclide and plant species. Ca{sup *} and Te{sup *} tended to remain on leaf surfaces without being absorbed into the cuticle. On the other hand, Sc{sup *}, Co{sup *}, Zn{sup *}, Se{sup *}, Rb{sup *}, and Eu{sup *} were easily absorbed and translocated to every part of the plant including the root. The other radionuclides such as Be{sup *}, Mn{sup *}, Sr{sup *}, Y{sup *}, Ba{sup *}, Ce{sup *}, Pm{sup *}, Gd{sup *}, Hf{sup *}, Yb{sup *}, Lu{sup *}, Os{sup *}, Ir{sup *}, and Pt{sup *} remained in the region close to the site of their application. The above results possibly indicate the existence of mechanisms common to these plants for selective transcuticular uptake and translocation of radionuclides within plant

  2. Adaptation of Clostridium difficile toxin A for use as a protein translocation system

    Energy Technology Data Exchange (ETDEWEB)

    Kern, Stephanie M. [Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202 (United States); Feig, Andrew L., E-mail: afeig@chem.wayne.edu [Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202 (United States)

    2011-02-25

    Research highlights: {yields} Catalytic domain of TcdA was replaced by a luciferase reporter. {yields} Each functional domain retains activity in the context of the fusion protein. {yields} We provide evidence that reporter proteins are delivered into vero cells. {yields} System releases cargo into the cytosol, providing a powerful new biotechnology tool. -- Abstract: A cellular delivery system is a useful biotechnology tool, with many possible applications. Two derivatives of Clostridium difficile toxin A (TcdA) have been constructed (GFP-TcdA and Luc-TcdA), by fusing reporter genes to functional domains of TcdA, and evaluated for their ability to translocate their cargo into mammalian cells. The cysteine protease and receptor binding domains of TcdA have been examined and found to be functional when expressed in the chimeric construct. Whereas GFP failed to internalize in the context of the TcdA fusion, significant cellular luciferase activity was detected in vero cell lysates after treatment with Luc-TcdA. Treatment with bafilomycin A1, which inhibits endosomal acidification, traps the luciferase activity within endosomes. To further understand these results, clarified lysates were subjected to molecular weight sieving, demonstrating that active luciferase was released from Luc-TcdA after translocation and internal processing.

  3. Adaptation of Clostridium difficile toxin A for use as a protein translocation system

    International Nuclear Information System (INIS)

    Kern, Stephanie M.; Feig, Andrew L.

    2011-01-01

    Research highlights: → Catalytic domain of TcdA was replaced by a luciferase reporter. → Each functional domain retains activity in the context of the fusion protein. → We provide evidence that reporter proteins are delivered into vero cells. → System releases cargo into the cytosol, providing a powerful new biotechnology tool. -- Abstract: A cellular delivery system is a useful biotechnology tool, with many possible applications. Two derivatives of Clostridium difficile toxin A (TcdA) have been constructed (GFP-TcdA and Luc-TcdA), by fusing reporter genes to functional domains of TcdA, and evaluated for their ability to translocate their cargo into mammalian cells. The cysteine protease and receptor binding domains of TcdA have been examined and found to be functional when expressed in the chimeric construct. Whereas GFP failed to internalize in the context of the TcdA fusion, significant cellular luciferase activity was detected in vero cell lysates after treatment with Luc-TcdA. Treatment with bafilomycin A1, which inhibits endosomal acidification, traps the luciferase activity within endosomes. To further understand these results, clarified lysates were subjected to molecular weight sieving, demonstrating that active luciferase was released from Luc-TcdA after translocation and internal processing.

  4. Moderate Light-Induced Degeneration of Rod Photoreceptors with Delayed Transducin Translocation in shaker1 Mice

    Science.gov (United States)

    Zallocchi, Marisa; Wang, Wei-Min; Delimont, Duane; Cosgrove, Dominic

    2011-01-01

    Purpose. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. Methods. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. Results. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. Conclusions. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light. PMID:21447681

  5. Breaching Biological Barriers: Protein Translocation Domains as Tools for Molecular Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Benjamin L. Franc

    2003-10-01

    Full Text Available The lipid bilayer of a cell presents a significant barrier for the delivery of many molecular imaging reagents into cells at target sites in the body. Protein translocation domains (PTDs are peptides that breach this barrier. Conjugation of PTDs to imaging agents can be utilized to facilitate the delivery of these agents through the cell wall, and in some cases, into the cell nucleus, and have potential for in vitro and in vivo applications. PTD imaging conjugates have included small molecules, peptides, proteins, DNA, metal chelates, and magnetic nanoparticles. The full potential of the use of PTDs in novel in vivo molecular probes is currently under investigation. Cells have been labeled in culture using magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess trafficking patterns relative to cells expressing a target antigen. In vivo imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated in living animals. Here we review several natural and synthetic PTDs that have evolved in the quest for easier translocation across biological barriers and the application of these peptide domains to in vivo delivery of imaging agents.

  6. Embryos, genes, and birth defects

    National Research Council Canada - National Science Library

    Ferretti, Patrizia

    2006-01-01

    ... Structural anomalies The genesis of chromosome abnormalities Embryo survival The cause of high levels of chromosome abnormality in human embryos Relative parental risks - age, translocations, inversions, gonadal and germinal mosaics 33 33 34 35 36 44 44 45 4 Identification and Analysis of Genes Involved in Congenital Malformation Syndromes Peter J. Scambler Ge...

  7. Cold-inhibited phloem translocation in sugar beet

    International Nuclear Information System (INIS)

    Grusak, M.A.

    1985-01-01

    Experimental studies were undertaken on a simplified single source leaf-single sink leaf, or single source leaf-double sink leaf sugar beet system to investigate the responsive nature of the long-distance phloem translocation system to localized cooling perturbations on the source leaf petiole. Experiments were performed by using a steady state [ 14 C]-labelling system for the source leaf, and translocation into the sink leaf (leaves) was monitored with a Geiger-Mueller system. A specially designed Peltier apparatus enabled cooling of the source petiole to 1 0 C (or other desired temperatures) at various positions on the petiole, over different lengths, and at different rates of cooling. Initial experiment were designed to test the predictions of a mathematical recovery model of translocation inhibited by cold. The results did not support the mathematical model, but did suggest that vascular anastomoses may be involved in the recovery response. Selective petiolar incision/excision experiments showed that anastomoses were capable of re-establishing translocation following a disruption of flow. Studies with two monitored sink levels suggested that the inhibition to slow-coolings was not due to reduced translocation through the cooled source petiole region, but rather, was due to a repartitioning of flow among the terminal sinks (sink leaves and hypocotyl/crown region above the heat-girdled root). This repartitioning occurred via a redirection of flow through the vascular connections in the crown region of the plant, and appeared to be promoted by rapid, physical signals originating from the cooled region of the petiole

  8. E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

    International Nuclear Information System (INIS)

    Hao, Hongying; Dong, Yanbin; Bowling, Maria T; Gomez-Gutierrez, Jorge G; Zhou, H Sam; McMasters, Kelly M

    2007-01-01

    PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

  9. Atlas of alien and translocated indigenous aquatic animals in southern Africa

    CSIR Research Space (South Africa)

    De Moor, IJ

    1988-01-01

    Full Text Available This report serves as an introduction to the problem of alien and translocated aquatic animals in southern Africa is given followed by checklists of the different species which have been introduced into or translocated within the subcontinent...

  10. Identification of copy number variations and translocations in cancer cells from Hi-C data.

    Science.gov (United States)

    Chakraborty, Abhijit; Ay, Ferhat

    2017-10-18

    Eukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e.g., Hi-C), which are originally developed for decoding the 3D structure of the chromatin, provide a great opportunity to simultaneously identify the locations of genomic rearrangements and to investigate the 3D genome organization in cancer cells. Even though Hi-C data has been used for validating known rearrangements, computational methods that can distinguish rearrangement signals from the inherent biases of Hi-C data and from the actual 3D conformation of chromatin, and can precisely detect rearrangement locations de novo have been missing. In this work, we characterize how intra and inter-chromosomal Hi-C contacts are distributed for normal and rearranged chromosomes to devise a new set of algorithms (i) to identify genomic segments that correspond to CNV regions such as amplifications and deletions (HiCnv), (Nurtdinov et al.) to call inter-chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments, and (iii) to simulate Hi-C data from genomes with desired rearrangements and abnormalities (AveSim) in order to select optimal parameters for and to benchmark the accuracy of our methods. Our results on 10 different cancer cell lines with Hi-C data show that we identify a total number of 105 amplifications and 45 deletions together with 90 translocations, whereas we identify virtually no such events for two karyotypically normal cell lines. Our CNV predictions correlate very well with whole genome sequencing (WGS) data among chromosomes

  11. Translocation Study of Some Zooxanthellae Clade to the Survival and Growth of Goniastrea Aspera After Bleaching

    OpenAIRE

    Purnomo, Pujiono W

    2014-01-01

    Inter-host translocation technique of zooxanthellae was attempted to prove Buddemier and Futin's (1993) theory on adaptation. The recent trend of coral products trading must be anticipated by its mass production through artificial techniques, the alternation of natural resources. Translocation bio-technique of zooxanthellae on coral was expected to resolve the problem and the translocation study should provide fundamental answer to coral recovery. The study of zooxanthellae translocation was ...

  12. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Pedersen, Karin Kaereby; Pedersen, Maria; Trøseid, Marius

    2013-01-01

    Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals.......Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals....

  13. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Science.gov (United States)

    2010-07-01

    ... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable translocation test in Drosophila measures the induction of chromosomal translocations in germ cells of insects...

  14. Translocation as a conservation tool for Agassiz's desert tortoises: Survivorship, reproduction, and movements

    Science.gov (United States)

    K. E. Nussear; C. R. Tracy; P. A. Medica; D. S. Wilson; R. W. Marlow; P. S. Corn

    2012-01-01

    We translocated 120 Agassiz's desert tortoises to 5 sites in Nevada and Utah to evaluate the effects of translocation on tortoise survivorship, reproduction, and habitat use. Translocation sites included several elevations, and extended to sites with vegetation assemblages not typically associated with desert tortoises in order to explore the possibility of moving...

  15. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    NARCIS (Netherlands)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. It is generally accepted that, when no chromosomal rearrangements are involved, man

  16. Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells.

    Science.gov (United States)

    Walker, Brian A; Wardell, Christopher P; Johnson, David C; Kaiser, Martin F; Begum, Dil B; Dahir, Nasrin B; Ross, Fiona M; Davies, Faith E; Gonzalez, David; Morgan, Gareth J

    2013-04-25

    Translocations in myeloma are thought to occur solely in mature B cells in the germinal center through class switch recombination (CSR). We used a targeted captured technique followed by massively parallel sequencing to determine the exact breakpoints in both the immunoglobulin heavy chain (IGH) locus and the partner chromosome in 61 presentation multiple myeloma samples. The majority of samples (62%) have a breakpoint within the switch regions upstream of the IGH constant genes and are generated through CSR in a mature B cell. However, the proportion of CSR translocations is not consistent between cytogenetic subgroups. We find that 100% of t(4;14) are CSR-mediated; however, 21% of t(11;14) and 25% of t(14;20) are generated through DH-JH recombination activation gene-mediated mechanisms, indicating they occur earlier in B-cell development at the pro-B-cell stage in the bone marrow. These 2 groups also generate translocations through receptor revision, as determined by the breakpoints and mutation status of the segments used in 10% and 50% of t(11;14) and t(14;20) samples, respectively. The study indicates that in a significant number of cases the translocation-based etiological events underlying myeloma may arise at the pro-B-cell hematological progenitor cell level, much earlier in B-cell development than was previously thought.

  17. Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset.

    Science.gov (United States)

    Guo, Yongjun; Ma, Jie; Lyu, Xiaodong; Liu, Hai; Wei, Bing; Zhao, Jiuzhou; Fu, Shuang; Ding, Lu; Zhang, Jihong

    2014-11-18

    The translocations of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene on chromosome 2p have been identified in non-small-cell lung cancers (NSCLCs) as oncogenic driver mutations. It has been suggested that EML4-ALK fusion is associated with the resistance in NSCLCs to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib. In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK. Thus, characterization of EML4-ALK fusion genes and clinical features of resulting carcinomas would be a great benefit to disease diagnosis and designing customized treatment plans. Studies have suggested that EML4-ALK translocation occurs more frequently in never-smokers with NSCLC, especially in female patients. However, it is not clear whether this is the case in male patients, too. In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients. The clinical features associated with EML4-ALK translocation were also investigated. A cohort of 95 Chinese male never-smokers with NSCLC was enrolled in this study. EML4-ALK fusion genes were detected using one-step real time RT-PCR and DNA sequencing. We further determined the expression levels of ALK mRNA by RT-PCR and ALK protein by immunohistochemistry in these specimens. The clinical features of EML4-ALK-positive carcinomas were also determined. We have identified EML4-ALK fusion genes in 8 out of 95 carcinoma cases, accounting for 8.42% in Chinese male never-smokers with NSCLC. It is significantly higher than that in all Chinese male patients (3.44%) regardless smoking habit. It is also significantly higher than that in all Chinese smokers (8/356 or 2.25%) or in smokers worldwide (2.9%) by comparing to published data. Interestingly, EML4-ALK fusion genes are more frequently found in

  18. Plant P4-ATPases: lipid translocators with a role in membrane traficking

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    a large family of membrane proteins involved in pumping different physiologically-relevant substrates across biological membranes [4]. The members of the P4 subfamily (also known as flippases) catalyze the energy-driven translocation of lipids necessary for establishing transbilayer lipid asymmetry [5......], a feature necessary for correct functioning of the cells [6,7]. Deletion of one or more P4-ATPase genes causes defects in vesicle budding in various organisms [8-10] and some members of the yeast family have been shown to interact with the vesiculation machinery [11,12]. Thus, unraveling the key features...... of P4-ATPase functioning is crucial to understand the mechanisms underlying the whole secretory and endocytic pathways. In the model plant Arabidopsis, 12 members of the P4-ATPase family have been described (ALA1-ALA12, for Aminophospholipid ATPase) [4]. In the past years, we have characterized several...

  19. Accelerators of future generation

    International Nuclear Information System (INIS)

    Kolomenskij, A.A.

    1983-01-01

    A brief review of the prospects of development of various of types accelerator over next 10 to 15 years is given. The following directions are considered: superhign energy proton accelerators and storage rings, electron-positron colliding beams, heavy ion accelerators, medium energy, high-current proton accelerators superhigh power particle beams (electrons light- and heavy ions) for inertial fusion

  20. Future accelerator technology

    International Nuclear Information System (INIS)

    Sessler, A.M.

    1986-05-01

    A general discussion is presented of the acceleration of particles. Upon this foundation is built a categorization scheme into which all accelerators can be placed. Special attention is devoted to accelerators which employ a wake-field mechanism and a restricting theorem is examined. It is shown how the theorem may be circumvented. Comments are made on various acceleration schemes

  1. Probiotic Mixture Golden Bifido Prevents Neonatal Escherichia coli K1 Translocation via Enhancing Intestinal Defense

    Directory of Open Access Journals (Sweden)

    Qing Zeng

    2017-09-01

    Full Text Available Escherichia coli (E. coli K1 sepsis and meningitis is a severe infection characterized by high mortality in neonates. Successful colonization and translocation across the intestinal mucosa have been regarded as the critical steps for E. coli K1 sepsis and meningitis. We recently reported that the probiotic mixture, Golden Bifido (containing live Lactobacillus bulgaricus, Bifidobacterium, and Streptococcus thermophilus, LBS has a preventive role against neonatal E. coli K1 bacteremia and meningitis. However, the interaction between the neonatal gut barrier, probiotics and E. coli K1 is still not elucidated. The present study aims to investigate how LBS exerts its protective effects on neonatal gut barrier during E. coli K1 infection. The beneficial effects of LBS were explored in vitro and in vivo using human colon carcinoma cell lines HT-29 and rat model of neonatal E. coli K1 infection, respectively. Our results showed that stimulation with E. coli K1 was able to cause intestinal barrier dysfunction, which were reflected by E. coli K1-induced intestinal damage and apoptosis of intestinal epithelial cells, reduction of mucin, immunoglobulin A (IgA and tight junction proteins expression, as well as increase in intestinal permeability, all these changes facilitate E. coli K1 intestinal translocation. However, these changes were alleviated when HT-29 cells were treated with LBS before E. coli K1 infection. Furthermore, we found that LBS-treated neonatal rats (without E. coli K1 infection have showed higher production of mucin, ZO-1, IgA, Ki67 in intestinal mucosa as well as lower intestinal permeability than that of non-treated rats, indicating that LBS could accelerate the development of neonatal intestinal defense. Taken together, our results suggest that enhancement of the neonatal intestinal defense to fight against E. coli K1 translocation could be the potential mechanism to elucidate how LBS confers a protective effect against neonatal E

  2. Enhanced targeted integration mediated by translocated I-SceI during the Agrobacterium mediated transformation of yeast.

    Science.gov (United States)

    Rolloos, Martijn; Hooykaas, Paul J J; van der Zaal, Bert J

    2015-02-09

    Agrobacterium mediated transformation (AMT) has been embraced by biotechnologists as the technology of choice to introduce or alter genetic traits of plants. However, in plants it is virtually impossible to predetermine the integration site of the transferred T-strand unless one is able to generate a double stranded break (DSB) in the DNA at the site of interest. In this study, we used the model organism Saccharomyces cerevisiae to investigate whether the Agrobacterium mediated translocation of site-specific endonucleases via the type IV secretion system (T4SS), concomitantly with T-DNA transfer is possible and whether this can improve the gene targeting efficiency. In addition to that, the effect of different chromatin states on targeted integration, was investigated. It was found that Agrobacterium mediated translocation of the homing endonuclease I-SceI has a positive effect on the integration of T-DNA via the homologous repair (HR) pathway. Furthermore, we obtained evidence that nucleosome removal has a positive effect on I-SceI facilitated T-DNA integration by HR. Reversely; inducing nucleosome formation at the site of integration removes the positive effect of translocated I-SceI on T-DNA integration.

  3. MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

    International Nuclear Information System (INIS)

    Yu, Teng; Ji, Jiang; Guo, Yong-li

    2013-01-01

    Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

  4. DNA Physical Mapping via the Controlled Translocation of Single Molecules through a 5-10nm Silicon Nitride Nanopore

    Science.gov (United States)

    Stein, Derek; Reisner, Walter; Jiang, Zhijun; Hagerty, Nick; Wood, Charles; Chan, Jason

    2009-03-01

    The ability to map the binding position of sequence-specific markers, including transcription-factors, protein-nucleic acids (PNAs) or deactivated restriction enzymes, along a single DNA molecule in a nanofluidic device would be of key importance for the life-sciences. Such markers could give an indication of the active genes at particular stage in a cell's transcriptional cycle, pinpoint the location of mutations or even provide a DNA barcode that could aid in genomics applications. We have developed a setup consisting of a 5-10 nm nanopore in a 20nm thick silicon nitride film coupled to an optical tweezer setup. The translocation of DNA across the nanopore can be detected via blockades in the electrical current through the pore. By anchoring one end of the translocating DNA to an optically trapped microsphere, we hope to stretch out the molecule in the nanopore and control the translocation speed, enabling us to slowly scan across the genome and detect changes in the baseline current due to the presence of bound markers.

  5. MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Teng, E-mail: tengyu33@yahoo.com [Department of Dermatology, Shandong Ji-ning No. 1 People’s Hospital, Shandong Province 272011 (China); Ji, Jiang [Department of Dermatology, The Second Hospital Affiliated of Soochow University, SuZhou, Jiangsu Province 215000 (China); Guo, Yong-li [Department of Oncology, Shandong Ji-ning No. 1 People’s Hospital, Shandong Province 272011 (China)

    2013-11-08

    Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.

  6. Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents.

    Science.gov (United States)

    Christmann, M; Kaina, B

    2000-11-17

    Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gene activity. Cells expressing the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT), thus having the ability to repair O(6)-methylguanine, showed no translocation of MutSalpha, whereas inhibition of MGMT by O(6)-benzylguanine provoked the translocation. The results demonstrate that O(6)-methylguanine lesions are involved in triggering nuclear accumulation of MSH2 and MSH6. The finding that treatment of cells with O(6)-methylguanine-generating mutagens results in an increase of MutSalpha and GT binding activity in the nucleus indicates a novel type of genotoxic stress response.

  7. A t(3;9)(q25.1;q34.3) translocation leading to OLFM1 fusion transcripts in Gilles de la Tourette syndrome, OCD and ADHD

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Melchior, Linea; Jensen, Lars Riff

    2015-01-01

    Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with a strong genetic etiology; however, finding of candidate genes is hampered by its genetic heterogeneity and the influence of non-genetic factors on disease pathogenesis. We report a case of a male patient with GTS, obsessive...... compulsive disorder, attention-deficit/hyperactivity-disorder, as well as other comorbidities, and a translocation t(3;9)(q25.1;q34.3) inherited from a mother with tics. Mate-pair sequencing revealed that the translocation breakpoints truncated the olfactomedin 1 (OLFM1) gene and two uncharacterized...

  8. Markers of immunity and bacterial translocation in cirrhosis

    DEFF Research Database (Denmark)

    Mortensen, Christian

    2015-01-01

    to be correlated to portal hypertension, a clinically relevant haemodynamic alteration, and appeared to be associated with increased mortality. To assess the consequences of BT on immunity, we developed an assay for the detection of bacterial DNA (bDNA), a novel marker of BT. Using the assay in the second study......Bacterial translocation (BT), the migration of enteric bacteria to extraintestinal sites, is related to immune stimulation and haemodynamic changes in experimental cirrhosis. These changes may be highly relevant to patients with cirrhosis, where changes in the circulation cause serious......, in 38 patients with ascites, we found no association between bDNA and immunity, in contrast to some previous findings. In the final paper, exploring one possible translocation route, we hypothesized a difference in bDNA levels between the blood from the veins draining the gut on one hand and the liver...

  9. Regulation of Neuronal Protein Trafficking and Translocation by SUMOylation

    Directory of Open Access Journals (Sweden)

    Jeremy M. Henley

    2012-05-01

    Full Text Available Post-translational modifications of proteins are essential for cell function. Covalent modification by SUMO (small ubiquitin-like modifier plays a role in multiple cell processes, including transcriptional regulation, DNA damage repair, protein localization and trafficking. Factors affecting protein localization and trafficking are particularly crucial in neurons because of their polarization, morphological complexity and functional specialization. SUMOylation has emerged as a major mediator of intranuclear and nucleo-cytoplasmic translocations of proteins involved in critical pathways such as circadian rhythm, apoptosis and protein degradation. In addition, SUMO-regulated re-localization of extranuclear proteins is required to sustain neuronal excitability and synaptic transmission. Thus, SUMOylation is a key arbiter of neuronal viability and function. Here, we provide an overview of recent advances in our understanding of regulation of neuronal protein localization and translocation by SUMO and highlight exciting areas of ongoing research.

  10. Sex Chromosome Translocations in the Evolution of Reproductive Isolation

    Science.gov (United States)

    Tracey, Martin L.

    1972-01-01

    Haldane's rule states that in organisms with differentiated sex chromosomes, hybrid sterility or inviability is generally expressed more frequently in the heterogametic sex. This observation has been variously explained as due to either genic or chromosomal imbalance. The fixation probabilities and mean times to fixation of sex-chromosome translocations of the type necessary to explain Haldane's rule on the basis of chromosomal imbalance have been estimated in small populations of Drosophila melanogaster. The fixation probability of an X chromosome carrying the long arm of the Y(X·YL) is approximately 30% greater than expected under the assumption of no selection. No fitness differences associated with the attached YL segment were detected. The fixation probability of a deficient Y chromosome is 300% greater than expected when the X chromosome contains the deleted portion of the Y. It is suggested that sex-chromosome translocations may play a role in the establishment of reproductive isolation. PMID:4630586

  11. Analysis of photosynthate translocation velocity and measurement of weighted average velocity in transporting pathway of crops

    International Nuclear Information System (INIS)

    Ge Cailin; Luo Shishi; Gong Jian; Zhang Hao; Ma Fei

    1996-08-01

    The translocation profile pattern of 14 C-photosynthate along the transporting pathway in crops were monitored by pulse-labelling a mature leaf with 14 CO 2 . The progressive spreading of translocation profile pattern along the sheath or stem indicates that the translocation of photosynthate along the sheath or stem proceed with a range of velocities rather than with just a single velocity. The method for measuring the weighted average velocity of photosynthate translocation along the sheath or stem was established in living crops. The weighted average velocity and the maximum velocity of photosynthate translocation along the sheath in rice and maize were measured actually. (4 figs., 3 tabs.)

  12. A strategy for generation and balancing of autosome: Y chromosome translocations.

    Science.gov (United States)

    Joshi, Sonal S; Cheong, Han; Meller, Victoria H

    2014-01-01

    We describe a method for generation and maintenance of translocations that move large autosomal segments onto the Y chromosome. Using this strategy we produced ( 2;Y) translocations that relocate between 1.5 and 4.8 Mb of the 2nd chromosome.. All translocations were easily balanced over a male-specific lethal 1 (msl-1) mutant chromosome. Both halves of the translocation carry visible markers, as well as P-element ends that enable molecular confirmation. Halves of these translocations can be separated to produce offspring with duplications and with lethal second chromosome deficiencies . Such large deficiencies are otherwise tedious to generate and maintain.

  13. Polymer translocation in the presence of excluded volume and explicit hydrodynamic interactions

    International Nuclear Information System (INIS)

    Guillouzic, Steve; Slater, Gary W.

    2006-01-01

    Molecular Dynamics simulations of polymer translocation are hereby reported. No external force was applied to the polymer during translocation, and the dynamics was dominated by polymer-pore interactions. It was found that hydrodynamic interactions play an important role in the relaxation of the polymer on each side of the membrane but have a negligible impact on the translocation process itself. Also, the scaling laws obtained for the relaxation and translocation times indicate that long translocating polymers may be considered to be following a quasi-equilibrium anomalous diffusion process in the absence of external forces

  14. International study of factors affecting human chromosome translocations

    Czech Academy of Sciences Publication Activity Database

    Sigurdson, A.J.; Ha, M.; Hauptmann, M.; Bhatti, P.; Šrám, Radim; Beskid, Olena; Tawn, E.J.; Whitehouse, C.A.; Lindholm, C.; Nakano, M.; Kodama, Y.; Nakamura, N.; Vorobtsova, I.; Oestreicher, U.; Stephan, G.; Yong, L.C.; Bauchinger, M.; Schmid, E.; Chung, H.W.; Darroudi, F.; Roy, L.; Voisin, P.; Barquinero, J.F.; Livingston, G.; Blakey, D.; Hayata, I.; Zhang, W.; Wang, Ch.; Benett, L.M.; Littlefield, L.G.; Edwards, A.A.; Kleinerman, R.A.; Tucker, J.D.

    2008-01-01

    Roč. 652, č. 2 (2008), s. 112-121 ISSN 1383-5718 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SI/340/2/00; GA MŽP SL/740/5/03 Institutional research plan: CEZ:AV0Z50390512 Keywords : Chromosome translocations * FISH * Background frequency Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.363, year: 2008

  15. "Translocal Express" juba täna! / Rael Artel

    Index Scriptorium Estoniae

    Artel, Rael, 1980-

    2009-01-01

    27. märtsil algab Kumu Kunstimuuseumis "Public Preparation'i" ("Avalik ettevalmistus") sarja rahvusvaheline seminar "Translocal Express. Golden Age" ("Translokaalne ekspress. Kuldaeg"), kus on kõne all ajalookirjutamise ja kollektiivse mälu roll praegu domineerivas natsionalistlikus diskursuses ja selle käsitlemine kaasaegses kunstis. Seminaril on lähtutud eelkõige kunstnike Martin Krenni (Viin) ja Kristina Normani teoste tutvustamisest

  16. Yersinia enterocolitica and Photorhabdus asymbiotica β-lactamases BlaA are exported by the twin-arginine translocation pathway.

    Science.gov (United States)

    Schriefer, Eva-Maria; Hoffmann-Thoms, Stephanie; Schmid, Franz X; Schmid, Annika; Heesemann, Jürgen

    2013-01-01

    In general, β-lactamases of medically important Gram-negative bacteria are Sec-dependently translocated into the periplasm. In contrast, β-lactamases of Mycobacteria spp. (BlaC, BlaS) and the Gram-negative environmental bacteria Stenotrophomonas maltophilia (L2) and Xanthomonas campestris (Bla(XCC-1)) have been reported to be secreted by the twin-arginine translocation (Tat) system. Yersinia enterocolitica carries 2 distinct β-lactamase genes (blaA and blaB) encoding BlaA(Ye) and the AmpC-like β-lactamase BlaB, respectively. By using the software PRED-TAT for prediction and discrimination of Sec from Tat signal peptides, we identified a functional Tat signal sequence for Yersinia BlaA(Ye). The Tat-dependent translocation of BlaA(Ye) could be clearly demonstrated by using a Y. enterocolitica tatC-mutant and cell fractionation. Moreover, we could demonstrate a unique unusual temperature-dependent activity profile of BlaA(Ye) ranging from 15 to 60 °C and a high 'melting temperature' (T(M)=44.3°) in comparison to the related Sec-dependent β-lactamase TEM-1 (20-50°C, T(M)=34.9 °C). Strikingly, the blaA gene of Y. enterocolitica is present in diverse environmental Yersinia spp. and a blaA homolog gene could be identified in the closely related Photorhabdus asymbiotica (BlaA(Pa); 69% identity to BlaA(Ye)). For BlaA(Pa) of P. asymbiotica, we could also demonstrate Tat-dependent secretion. These results suggest that Yersinia BlaA-related β-lactamases may be the prototype of a large Tat-dependent β-lactamase family, which originated from environmental bacteria. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Apoptotic role of TGF-β mediated by Smad4 mitochondria translocation and cytochrome c oxidase subunit II interaction.

    Science.gov (United States)

    Pang, Lijuan; Qiu, Tao; Cao, Xu; Wan, Mei

    2011-07-01

    Smad4, originally isolated from the human chromosome 18q21, is a key factor in transducing the signals of the TGF-β superfamily of growth hormones and plays a pivotal role in mediating antimitogenic and proapoptotic effects of TGF-β, but the mechanisms by which Smad4 induces apoptosis are elusive. Here we report that Smad4 directly translocates to the mitochondria of apoptotic cells. Smad4 gene silencing by siRNA inhibits TGF-β-induced apoptosis in Hep3B cells and UV-induced apoptosis in PANC-1 cells. Cell fractionation assays demonstrated that a fraction of Smad4 translocates to mitochondria after long time TGF-β treatment or UV exposure, during which the cells were under apoptosis. Smad4 mitochondria translocation during apoptosis was also confirmed by fluorescence observation of Smad4 colocalization with MitoTracker Red. We searched for mitochondria proteins that have physical interactions with Smad4 using yeast two-hybrid screening approach. DNA sequence analysis identified 34 positive clones, five of which encoded subunits in mitochondria complex IV, i.e., one clone encoded cytochrome c oxidase COXII, three clones encoded COXIII and one clone encoded COXVb. Strong interaction between Smad4 with COXII, an important apoptosis regulator, was verified in yeast by β-gal activity assays and in mammalian cells by immunoprecipitation assays. Further, mitochondrial portion of cells was isolated and the interaction between COXII and Smad4 in mitochondria upon TGF-β treatment or UV exposure was confirmed. Importantly, targeting Smad4 to mitochondria using import leader fusions enhanced TGF-β-induced apoptosis. Collectively, the results suggest that Smad4 promote apoptosis of the cells through its mitochondrial translocation and association with mitochondria protein COXII. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity.

    Directory of Open Access Journals (Sweden)

    Heather C Whalley

    Full Text Available Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1 is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11 (q42.1;q14.3.Within the original pedigree, we examined the effects of the t(1;11 translocation on white matter integrity, measured by fractional anisotropy (FA. This included family members with (n = 7 and without (n = 13 the translocation, along with a clinical control sample of patients with psychosis (n = 34, and a group of healthy controls (n = 33.We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity.We demonstrate that the t(1;11 translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis.

  19. Single-strand DNA molecule translocation through nanoelectrode gaps

    International Nuclear Information System (INIS)

    Zhao Xiongce; Payne, Christina M; Cummings, Peter T; Lee, James W

    2007-01-01

    Molecular dynamics simulations were performed to investigate the translocation of single-strand DNA through nanoscale electrode gaps under the action of a constant driving force. The application behind this theoretical study is a proposal to use nanoelectrodes as a screening gap as part of a rapid genomic sequencing device. Preliminary results from a series of simulations using various gap widths and driving forces suggest that the narrowest electrode gap that a single-strand DNA can pass is ∼1.5 nm. The minimum force required to initiate the translocation within nanoseconds is ∼0.3 nN. Simulations using DNA segments of various lengths indicate that the minimum initiation force is insensitive to the length of DNA. However, the average threading velocity of DNA varies appreciably from short to long DNA segments. We attribute such variation to the different nature of drag force experienced by the short and long DNA segments in the environment. It is found that DNA molecules deform significantly to fit in the shape of the nanogap during the translocation

  20. Spatial behaviour and survival of translocated wild brown hares

    Directory of Open Access Journals (Sweden)

    Fischer, C.

    2012-01-01

    Full Text Available The fragility of many populations of brown hares in Western Europe is a concern for managers, hunters and naturalists. We took advantage of a locally high density population to use wild individuals to restock areas where the species had disappeared or was close to disappearing. The aim of the project was to assess the evolution of the spatial behaviour after release using radio–tracking. Over 150 wild brown hares were translocated, one third of which were fitted with radio collars. In addition, fifteen individuals were radio–tagged and released back into the source population as a control. Most individuals settled in less than two months and their seasonal home range, once settled, was similar to that observed in the source population. Mean duration of tracking was not significantly different between the two groups. Moreover, two years after the last translocation, tagged individuals can still be observed, but most hares present are not tagged, which indicates natural reproduction of the released individuals. The translocation of wild individuals thus appears to give encouraging results.

  1. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  2. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  3. Black bears in Arkansas: Characteristics of a successful translocation

    Science.gov (United States)

    Smith, Kimberly G.; Clark, Joseph D.

    1994-01-01

    In 1958, the Arkansas Game and Fish Commission began translocating black bears (Ursus americanus) from Minnesota to the Interior Highlands (Ozark and Ouachita mountains) of Arkansas where bears had been extirpated early in this century. This project continued for 11 years with little public imput, during which time an estimated 254 bears were released. We estimate there are now >2,500 bears in the Interior Highlands of Arkansas, Missouri, and Oklahoma, making it one of the most successful translocations of a Carnivora. Factors that contributed to the success include use of wild-captured animals, elimination of major factors associated with extirpation, release into prime habitats within the former range, multiple release sites, release of 20–40 animals/year for eight years, and release of mostly males prior to release of mostly females. Studies on two allopatric populations demonstrate that they are now diverging in some demographic characteristics, including litter size, cub survivorship, and adult sex-ratio. Translocation of black bears to the Interior Highlands is successful in terms of numbers of animals, but it will not be truly successful until people accept black bears as part of the regional fauna. To that end, those associated with management and research of bears in Arkansas are now focussing on public education and control of nuisance bears.

  4. Translocation of 11C from leaves of Helianthus: preliminary results

    International Nuclear Information System (INIS)

    Fensom, D.S.; Aikman, D.; Scobie, J.; Drinkwater, A.; Ledingham, K.W.O.

    1977-01-01

    11 C fed to leaves as 11 CO 2 was used to study the dynamics of short-term translocation of photosynthate in Helianthus. As in 14 C studies small amounts of tracer were often detected in the stem close to the fed leaf in th first 5 min, followed by a larger mass flow after 15 min. The speed of mass flow of tracer movement was calculated to be 60 to 400 cm.h -1 depending on the method of calculation. There was no evidence in the premass flow for discrete spots along the stem or petiole where tracer accumulated. Neither was there firm evidence for pulses of tracer moving steadily forward, but there were point fluctuations of greater variability than would be expected by chance alone, which suggest the possibility of aberrations of movement superimposed on the mass flow. Details of these aberrations could not be assessed with certainty from these preliminary experiments owing to the rather low tracer activity. The translocation profiles were sensitive to the prior light conditioning of the plant and above all to chilling. In Helianthus the latter produced temporary restrictions in translocation which lasted for some 10-12 min. (author)

  5. MiR-520b suppresses proliferation of hepatoma cells through targeting ten-eleven translocation 1 (TET1) mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weiying; Lu, Zhanping; Gao, Yuen [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Ye, Lihong [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin (China); Song, Tianqiang, E-mail: tjchi@hotmai.com [Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China)

    2015-05-08

    Accumulating evidence indicates that microRNAs are able to act as oncogenes or tumor suppressor genes in human cancer. We previously reported that miR-520b was down-regulated in hepatocellular carcinoma (HCC) and its deregulation was involved in hepatocarcinogenesis. In the present study, we report that miR-520b suppresses cell proliferation in HCC through targeting the ten-eleven translocation 1 (TET1) mRNA. Notably, we identified that miR-520b was able to target 3′-untranslated region (3′UTR) of TET1 mRNA by luciferase reporter gene assays. Then, we revealed that miR-520b was able to reduce the expression of TET1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blotting analysis. In terms of function, 5-ethynyl-2-deoxyuridine (EdU) incorporation and colony formation assays demonstrated that the forced miR-520b expression remarkably inhibited proliferation of hepatoma cells, but TET1 overexpression could rescue the inhibition of cell proliferation mediated by miR-520b. Furthermore, anti-miR-520b enhanced proliferation of hepatoma cells, whereas silencing of TET1 abolished anti-miR-520b-induced acceleration of cell proliferation. Then, we validated that the expression levels of miR-520b were negatively related to those of TET1 mRNA in clinical HCC tissues. Thus, we conclude that miR-520b depresses proliferation of liver cancer cells through targeting 3′UTR of TET1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • TET1 is a novel target gene of miR-520b. • TET1 is upregulated in clinical HCC tissues. • MiR-520b is negatively correlated with TET1 in clinical HCC tissues. • MiR-520b depresses the proliferation of HCC cells through targeting TET1 mRNA.

  6. Induction of transposon TN1 translocation under the action of different mutagens

    International Nuclear Information System (INIS)

    Kubanejshvili, M.G.; Smirnov, S.P.; Tarasov, V.A.

    1983-01-01

    Migration of ampicillin transposon Tn1 under normal conditions in Escherichia coli cells proceeds with low frequency (10 -4 transpositions for cell). The low transposition frequency is conditioned by the transposition repression, realized by the gene-repressor in transposon structure and, probably, by other regulating genes of the bacterium-host. E. coli cell treatment by physical and chemical mutagens resulted in induction of translocation of ampicillin transposon Tn1 from plasmid RP4 into other replicons. Mitomycin C and ultraviolet radiation produced stronger inducing effect as compared to nitroso-guanidine (NG). The effect of the given mutagens on transposition Tn1 correlated with their activating capacity with respect to inducible SOS-functions of E coli. The mutation of rec A didn't influence on spontaneous Tn1 transposition, but blocked completely the induction of transposition process under mutagen effect. The relationship of inducible transposition with SOS-functions in E. coli cells, controlled by recA and lexA genes, as well as the possible role of the process in genetic microorganism variability are discussed in the paper

  7. 2014 CERN Accelerator Schools: Plasma Wake Acceleration

    CERN Multimedia

    2014-01-01

    A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at: http://cas.web.cern.ch/cas/PlasmaWake2014/CERN-advert.html http://indico.cern.ch/event/285444/

  8. Can gene fusions serve for fingerprints of radiogenic cancers?

    International Nuclear Information System (INIS)

    Nakamura, Nori

    2016-01-01

    It has been recognized that malignancies in blood cells often bear specific chromosome translocations or gene fusions. In recent years, the presence of fusion genes became to be known also among solid cancers as driver mutations. However, representative solid cancers bearing specific gene fusions are limited to cancers of thyroid, prostate, and sarcomas among which only thyroid cancer risk is known to be related to radiation exposures. On the other hand, it is extremely rare to find recurrent reciprocal translocations among common cancers such as in the lung, stomach, breast, and colon, which form a major component of radiation risks. It is therefore unlikely that radiation increases the risk of cancer by inducing specific translocations (gene fusions) but more likely through induction of mutations (including deletions). Although gene fusions could play a role in radiation carcinogenesis, it does not seem good enough to serve for a radiation fingerprint. (author)

  9. Other people's accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1987-06-15

    The first report from the Washington Accelerator Conference concentrated on news from the particle physics centres. But the bulk of the Conference covered the use of accelerators in other fields, underlining this valuable spinoff from particle physics.

  10. Improved plasma accelerator

    Science.gov (United States)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  11. The electron accelerator Ridgetron

    International Nuclear Information System (INIS)

    Hayashizaki, N.; Hattori, T.; Odera, M.; Fujisawa, T.

    1999-01-01

    Many electron accelerators of DC or RF type have been widely used for electron beam irradiation (curing, crosslinking of polymers, sterilization of medical disposables, preservation of food, etc.). Regardless of the acceleration energy, the accelerators to be installed in industrial facilities, have to satisfy the requires of compact size, low power consumption and stable operation. The DC accelerator is realized very compact in the energy under 300 keV, however, it is large to prevent the discharge of an acceleration column in the energy over 300 keV. The RF electron accelerator Ridgetron has been developed to accelerate the continuous beam of the 0.5-10 MeV range in compact space. It is the first example as an electron accelerator incorporated a ridged RF cavity. A prototype system of final energy of 2.5 MeV has been studied to confirm the feasibility at present

  12. High brightness electron accelerator

    International Nuclear Information System (INIS)

    Sheffield, R.L.; Carlsten, B.E.; Young, L.M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of accelerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electrons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electrons as the electrons enter the first cavity. 5 figs

  13. Unified accelerator libraries

    International Nuclear Information System (INIS)

    Malitsky, Nikolay; Talman, Richard

    1997-01-01

    A 'Universal Accelerator Libraries' (UAL) environment is described. Its purpose is to facilitate program modularity and inter-program and inter-process communication among heterogeneous programs. The goal ultimately is to facilitate model-based control of accelerators

  14. YEREVAN: Acceleration workshop

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    Sponsored by the Yerevan Physics Institute in Armenia, a Workshop on New Methods of Charged Particle Acceleration in October near the Nor Amberd Cosmic Ray Station attracted participants from most major accelerator centres in the USSR and further afield

  15. San Francisco Accelerator Conference

    International Nuclear Information System (INIS)

    Southworth, Brian

    1991-01-01

    'Where are today's challenges in accelerator physics?' was the theme of the open session at the San Francisco meeting, the largest ever gathering of accelerator physicists and engineers

  16. Large tandem accelerators

    International Nuclear Information System (INIS)

    Jones, C.M.

    1976-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of tandem accelerators designed to operate at maximum terminal potentials in the range 14 to 30 MV. In addition, a number of older tandem accelerators are now being significantly upgraded to improve their heavy ion performance. Both of these developments have reemphasized the importance of negative heavy ion sources. The new large tandem accelerators are described, and the requirements placed on negative heavy ion source technology by these and other tandem accelerators used for the acceleration of heavy ions are discussed. First, a brief description is given of the large tandem accelerators which have been completed recently, are under construction, or are funded for construction, second, the motivation for construction of these accelerators is discussed, and last, criteria for negative ion sources for use with these accelerators are presented

  17. Vp x B acceleration

    International Nuclear Information System (INIS)

    Sugihara, Ryo.

    1987-05-01

    A unique particle acceleration by an electrostatic (ES) wave, a magnetosonic shock wave as well as an electromagnetic (EM) wave is reviewed. The principle of the acceleration is that when a charged particle is carried across an external magnetic field the charge feels a DC field (the Lorentz force) and is accelerated. The theory for the ES wave acceleration is experimentally verified thought it is semi-quantitative. The shock acceleration is extensively studied theoretically and in a particle simulation method and the application is extended to phenomena in interplanetary space. The EM wave acceleration is based on a trapping in a moving neutral sheet created by the wave magnetic field and the external magnetic field, and the particle can be accelerated indefinitely. A brief sketch on a slow-wave-structure for this acceleration will be given. (author)

  18. Accelerator-timing system

    International Nuclear Information System (INIS)

    Timmer, E.; Heine, E.

    1985-01-01

    Along the NIKHEF accelerator in Amsterdam (Netherlands), at several places a signal is needed for the sychronisation of all devices with the acceleration process. In this report, basic principles and arrangements of this timing system are described

  19. Linear accelerator: A concept

    Science.gov (United States)

    Mutzberg, J.

    1972-01-01

    Design is proposed for inexpensive accelerometer which would work by applying pressure to fluid during acceleration. Pressure is used to move shuttle, and shuttle movement is sensed and calibrated to give acceleration readings.

  20. Heavy ion accelerators

    International Nuclear Information System (INIS)

    Schmelzer, C.

    1974-01-01

    This review of the present state of work on heavy-ion accelerators pays particular attention to the requirements for nuclear research. It is divided into the following sections: single-particle versus collective acceleration, heavy-ion accelerators, beam quality, and a status report on the UNILAC facility. Among the topics considered are the recycling cyclotron, linacs with superconducting resonators, and acceleration to the GeV/nucleon range. (8 figures, 2 tables) (U.S.)

  1. Accelerators at school

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    Latest subject covered by the CERN Accelerator School was 'Applied Geodesy of Particle Accelerators', which attracted an impressive number of outside participants to CERN for a week in April. Since the forerunners of today's particle accelerators were demonstrated over 50 years ago, the positioning of accelerator components has progressed from the laboratory bench-top to tunnels tens of kilometres long. Despite this phenomenal growth in size, sub-millimetre accuracy is still required

  2. Accelerators at school

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-06-15

    Latest subject covered by the CERN Accelerator School was 'Applied Geodesy of Particle Accelerators', which attracted an impressive number of outside participants to CERN for a week in April. Since the forerunners of today's particle accelerators were demonstrated over 50 years ago, the positioning of accelerator components has progressed from the laboratory bench-top to tunnels tens of kilometres long. Despite this phenomenal growth in size, sub-millimetre accuracy is still required.

  3. Accelerators for Medicine

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    This lecture will review the different applications of particle accelerators to the medical field, from cancer treatment with beams of accelerator-produced particles (photons, electrons, protons, ions and neutrons) to the generation of radioactive isotopes used in medical diagnostics, in cancer therapy and in the new domain of theragnostics. For each application will be outlined the state of the art, the potential, and the accelerator challenges to be faced to meet the increasing demand for therapeutic procedures based on accelerators.

  4. Large electrostatic accelerators

    International Nuclear Information System (INIS)

    Jones, C.M.

    1984-01-01

    The paper is divided into four parts: a discussion of the motivation for the construction of large electrostatic accelerators, a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year

  5. Particle beam accelerator

    International Nuclear Information System (INIS)

    Turner, N.L.

    1982-01-01

    A particle beam accelerator is described which has several electrodes that are selectively short circuited together synchronously with changes in the magnitude of a DC voltage applied to the accelerator. By this method a substantially constant voltage gradient is maintained along the length of the unshortened electrodes despite variations in the energy applied to the beam by the accelerator. The invention has particular application to accelerating ion beams that are implanted into semiconductor wafers. (U.K.)

  6. Superconducting accelerator technology

    International Nuclear Information System (INIS)

    Grunder, H.A.; Hartline, B.K.

    1986-01-01

    Modern and future accelerators for high energy and nuclear physics rely increasingly on superconducting components to achieve the required magnetic fields and accelerating fields. This paper presents a practical overview of the phenomenon of superconductivity, and describes the design issues and solutions associated with superconducting magnets and superconducting rf acceleration structures. Further development and application of superconducting components promises increased accelerator performance at reduced electric power cost

  7. Applications of particle accelerators

    International Nuclear Information System (INIS)

    Barbalat, O.

    1994-01-01

    Particle accelerators are now widely used in a variety of applications for scientific research, applied physics, medicine, industrial processing, while possible utilisation in power engineering is envisaged. Earlier presentations of this subject, given at previous CERN Accelerator School sessions have been updated with papers contributed to the first European Conference on Accelerators in Applied Research and Technology (ECAART) held in September 1989 in Frankfurt and to the Second European Particle Accelerator Conference in Nice in June 1990. (orig.)

  8. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong

    2015-01-01

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd 2+ . Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals

  9. The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells

    International Nuclear Information System (INIS)

    Salim, Tavga; Sand-Dejmek, Janna; Sjölander, Anita

    2014-01-01

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D 4 (LTD 4 ) exerts its effects through the CysLT 1 receptor. We previously reported an upregulation of CysLT 1 R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD 4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD 4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD 4 significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD 4 can be blocked by the inhibition of CysLT 1 R. Furthermore, LTD 4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT 1 and the Wnt/β-catenin pathway. In conclusion, LTD 4 , which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D 4 (LTD 4 ) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD 4 triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD 4 also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells

  10. Interchromosomal insertional translocation at Xq26.3 alters SOX3 expression in an individual with XX male sex reversal.

    Science.gov (United States)

    Haines, Bryan; Hughes, James; Corbett, Mark; Shaw, Marie; Innes, Josie; Patel, Leena; Gecz, Jozef; Clayton-Smith, Jill; Thomas, Paul

    2015-05-01

    46,XX male sex reversal occurs in approximately 1: 20 000 live births and is most commonly caused by interchromosomal translocations of the Y-linked sex-determining gene, SRY. Rearrangements of the closely related SOX3 gene on the X chromosome are also associated with 46,XX male sex reversal. It has been hypothesized that sex reversal in the latter is caused by ectopic expression of SOX3 in the developing urogenital ridge where it triggers male development by acting as an analog of SRY. However, altered regulation of SOX3 in individuals with XX male sex reversal has not been demonstrated. Here we report a boy with SRY-negative XX male sex reversal who was diagnosed at birth with a small phallus, mixed gonads, and borderline-normal T. Molecular characterization of the affected individual was performed using array comparative genomic hybridization, fluorescent in situ hybridization of metaphase chromosomes, whole-genome sequencing, and RT-PCR expression analysis of lymphoblast cell lines. The affected male carries ∼774-kb insertion translocation from chromosome 1 into a human-specific palindromic sequence 82 kb distal to SOX3. Importantly, robust SOX3 expression was identified in cells derived from the affected individual but not from control XX or XY cells, indicating that the translocation has a direct effect on SOX3 regulation. This is the first demonstration of altered SOX3 expression in an individual with XX male sex reversal and suggests that SOX3 can substitute for SRY to initiate male development in humans.

  11. Molecular cytogenetic identification of a novel wheat-Agropyron elongatum chromosome translocation line with powdery mildew resistance.

    Science.gov (United States)

    Li, Xiaojun; Jiang, Xiaoling; Chen, Xiangdong; Song, Jie; Ren, Cuicui; Xiao, Yajuan; Gao, Xiaohui; Ru, Zhengang

    2017-01-01

    Agropyron elongatum (Host.) Neviski (synonym, Thinopyrum ponticum Podp., 2n = 70) has been used extensively as a valuable source for wheat breeding. Numerous chromosome fragments containing valuable genes have been successfully translocated into wheat from A. elongatum. However, reports on the transfer of powdery mildew resistance from A. elongatum to wheat are rare. In this study, a novel wheat-A. elongatum translocation line, 11-20-1, developed and selected from the progenies of a sequential cross between wheat varieties (Lankaoaizaoba, Keyu 818 and BainongAK 58) and A. elongatum, was evaluated for disease resistance and characterized using molecular cytogenetic methods. Cytological observations indicated that 11-20-1 had 42 chromosomes and formed 21 bivalents at meiotic metaphase I. Genomic in situ hybridization analysis using whole genomic DNA from A. elongatum as a probe showed that the short arms of a pair of wheat chromosomes were replaced by a pair of A. elongatum chromosome arms. Fluorescence in situ hybridization, using wheat D chromosome specific sequence pAs1 as a probe, suggested that the replaced chromosome arms of 11-20-1 were 5DS. This was further confirmed by wheat SSR markers specific for 5DS. EST-SSR and EST-STS multiple loci markers confirmed that the introduced A. elongatum chromosome arms belonged to homoeologous group 5. Therefore, it was deduced that 11-20-1 was a wheat-A. elongatum T5DL∙5AgS translocation line. Both resistance observation and molecular marker analyses using two specific markers (BE443538 and CD452608) of A. elongatum in a F2 population from a cross between line 11-20-1 and a susceptible cultivar Yannong 19 verified that the A. elongatum chromosomes were responsible for the powdery mildew resistance. This work suggests that 11-20-1 likely contains a novel resistance gene against powdery mildew. We expect this line to be useful for the genetic improvement of wheat.

  12. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong, E-mail: dayongw@seu.edu.cn

    2015-02-11

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd{sup 2+}. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals.

  13. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

    Introduction to accelerator physics The CERN Accelerator School: Introduction to Accelerator Physics, which should have taken place in Istanbul, Turkey, later this year has now been relocated to Budapest, Hungary.  Further details regarding the new hotel and dates will be made available as soon as possible on a new Indico site at the end of May.

  14. Angular Acceleration without Torque?

    Science.gov (United States)

    Kaufman, Richard D.

    2012-01-01

    Hardly. Just as Robert Johns qualitatively describes angular acceleration by an internal force in his article "Acceleration Without Force?" here we will extend the discussion to consider angular acceleration by an internal torque. As we will see, this internal torque is due to an internal force acting at a distance from an instantaneous center.

  15. Accelerators and Dinosaurs

    CERN Multimedia

    Turner, Michael Stanley

    2003-01-01

    Using naturally occuring particles on which to research might have made accelerators become extinct. But in fact, results from astrophysics have made accelerator physics even more important. Not only are accelerators used in hospitals but they are also being used to understand nature's inner workings by searching for Higgs bosons, CP violation, neutrino mass and dark matter (2 pages)

  16. Far field acceleration

    International Nuclear Information System (INIS)

    Fernow, R.C.

    1995-07-01

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail

  17. Hyaluronan synthase mediates dye translocation across liposomal membranes

    Directory of Open Access Journals (Sweden)

    Medina Andria P

    2012-01-01

    Full Text Available Abstract Background Hyaluronan (HA is made at the plasma membrane and secreted into the extracellular medium or matrix by phospolipid-dependent hyaluronan synthase (HAS, which is active as a monomer. Since the mechanism by which HA is translocated across membranes is still unresolved, we assessed the presence of an intraprotein pore within HAS by adding purified Streptococcus equisimilis HAS (SeHAS to liposomes preloaded with the fluorophore Cascade Blue (CB. Results CB translocation (efflux was not observed with mock-purified material from empty vector control E. coli membranes, but was induced by SeHAS, purified from membranes, in a time- and dose-dependent manner. CB efflux was eliminated or greatly reduced when purified SeHAS was first treated under conditions that inhibit enzyme activity: heating, oxidization or cysteine modification with N-ethylmaleimide. Reduced CB efflux also occurred with SeHAS K48E or K48F mutants, in which alteration of K48 within membrane domain 2 causes decreased activity and HA product size. The above results used liposomes containing bovine cardiolipin (BCL. An earlier study testing many synthetic lipids found that the best activating lipid for SeHAS is tetraoleoyl cardiolipin (TO-CL and that, in contrast, tetramyristoyl cardiolipin (TM-CL is an inactivating lipid (Weigel et al, J. Biol. Chem. 281, 36542, 2006. Consistent with the effects of these CL species on SeHAS activity, CB efflux was more than 2-fold greater in liposomes made with TO-CL compared to TM-CL. Conclusions The results indicate the presence of an intraprotein pore in HAS and support a model in which HA is translocated to the exterior by HAS itself.

  18. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    Energy Technology Data Exchange (ETDEWEB)

    Ponnusamy, Rajesh [Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal); Lebedev, Andrey A. [Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); Pahlow, Steffen [University of Hamburg, Ohnhorststrasse 18, 22609 Hamburg (Germany); Lohkamp, Bernhard, E-mail: bernhard.lohkamp@ki.se [Karolinska Institutet, Tomtebodavägen 6, 4tr, 17177 Stockholm (Sweden); Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal)

    2014-06-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs.

  19. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    International Nuclear Information System (INIS)

    Ponnusamy, Rajesh; Lebedev, Andrey A.; Pahlow, Steffen; Lohkamp, Bernhard

    2014-01-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs

  20. VEDs for charged particle accelerators: Indian scenario

    International Nuclear Information System (INIS)

    Bhandari, R.K.

    2012-01-01

    In the initial times after their invention, the charged particle accelerators have, primarily, been used for fundamental studies on nuclei and atoms. From the first modern accelerator, the cathode ray tube, used by J.J. Thomson for the discovery of electron, very recently the gigantic 27 km circumference Large Hadron Collider (LHC) is operational in the search of Higg's boson and related physics issues. Particle accelerators have emerged as powerful microscopes for investigating the finest details of cells, genes, molecules, atoms, protons, neutrons, muons, electrons, quarks and, possibly, still undiscovered even more fundamental constituents of the universe, such as dark matter and dark energy. Several noble prize winning discoveries have been made using accelerators. Accelerators are now being used in a wide area of industrial and medical applications. They are used for the production of radioisotopes for medical imaging, cancer therapy, food sterilization, treatment of waste water, sterilization of medical equipment, material modification, mass spectroscopy, cargo scanning, fabrication of semiconductors etc. Ongoing effort towards the development of accelerators with megawatt beam power is showing hope for a cleaner source of nuclear energy and treatment of nuclear waste. Several tens of thousands of accelerators are presently operational in the world for basic research and applications. Development of new accelerators has several times been driven by new technologies and materials and sometimes they have driven the technological developments towards cutting edge. Some examples are ultra-high vacuum in large volumes, superfluid helium in cryogenics, cryocoolers, superconducting magnets and RF cavities, high power vacuum electronic devices, global control systems, superfast computing and communication networks, giant data storage/processing systems etc. India has been pursuing a fairly robust programme of accelerator development at various institutions. It

  1. Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Kere, J. [Washington Univ. School of Medicine, St. Louis, MO (United States)]|[Univ. of Helsinki (Finland); Grzeschik, K.H. [Univ. of Marburg (Germany); Limon, J. [Medical Academy, Gdansk (Poland); Gremaud, M.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); De La Chapelle, A. [Univ. of Helsinki (Finland)

    1993-05-01

    Anhidrotic ectodermal dysplasia (EDA), an X-chromosomal recessive disorder, is expressed in a few females with chromosomal translocations involving bands Xq12-q13. Using available DNA markers from the region and somatic cell hybrids the authors mapped the X-chromosomal breakpoints in two such translocations. The breakpoints were further mapped within a yeast artificial chromosome contig constructed by chromosome walking techniques. Genomic DNA markers that map between the two translocation breakpoints were recovered representing putative portions of the EDA gene. 32 refs., 3 figs., 1 tab.

  2. Absorption and translocation of arsenate arsenic by coffee plants

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, J F; Yamaguchi, S

    1964-01-01

    Studies on arsenate arsenic absorption and translocation in coffee plants were carried out using arsenic-77 applied either to leaves or to roots through the nutrient solution. The youngest leaves were unable to export arsenic and only an acropetal movement in the transpiration stream was observed. From the second pair of leaves, it moved into the growing leaves. From the fourth pair it moved downward through the stem and into the roots. Roots absorbed high amounts of arsenate once absorbed it moved via the xylem of the transpiration stream into the leaves. 7 references, 2 figures.

  3. The use of alien gene transfers

    International Nuclear Information System (INIS)

    Bhatia, C.R.

    1976-01-01

    The present status of the gene transfers from alien species belonging to the sub-tribe Triticanae into wheat is reviewed, and the advantages and disadvantages of the different methods available for such transfers are examined. In general, the alien genes provide a high degree of resistance against a notably wide range of physiological races of wheat rusts, powdery mildew and other diseases. The alien resistance, like other sources of resistance, is known to break down for certain new races. This may happen more often when alien genes of resistance are widely incorporated in commercial cultivars and grown over large areas. So far, few of the available induced translocation stocks have contributed to the development of agronomically superior commercial cultivars, mainly due to the associated undesirable effects of the translocations on agronomic characters of the recipient variety. The deleterious effects appear in some genetic backgrounds and not in others. Extensive hybridization of translocation stocks with different genotypes has been emphasized by most investigators. Such programmes have led to the release of three commercial cultivars - 2 in Australia and 1 in the USA. On the other hand, spontaneous wheat-rye translocations carrying gene(s) for disease resistance have been unconsciously incorporated into several wheat cultivars, some of them are widely cultivated and were top in ranking based on grain yield. (author)

  4. Virtual Accelerator for Accelerator Optics Improvement

    CERN Document Server

    Yan Yi Ton; Decker, Franz Josef; Ecklund, Stanley; Irwin, John; Seeman, John; Sullivan, Michael K; Turner, J L; Wienands, Ulrich

    2005-01-01

    Through determination of all quadrupole strengths and sextupole feed-downs by fitting quantities derivable from precision orbit measurement, one can establish a virtual accelerator that matches the real accelerator optics. These quantities (the phase advances, the Green's functions, and the coupling eigen-plane ellipses tilt angles and axis ratios) are obtained by analyzing turn-by-turn Beam Position Monitor (BPM) data with a model-independent analysis (MIA). Instead of trying to identify magnet errors, a limited number of quadrupoles are chosen for optimized strength adjustment to improve the virtual accelerator optics and then applied to the real accelerator accordingly. These processes have been successfully applied to PEP-II rings for beta beating fixes, phase and working tune adjustments, and linear coupling reduction to improve PEP-II luminosity.

  5. Partial deletions of the W chromosome due to reciprocal translocation in the silkworm Bombyx mori.

    Science.gov (United States)

    Abe, H; Seki, M; Ohbayashi, F; Tanaka, N; Yamashita, J; Fujii, T; Yokoyama, T; Takahashi, M; Banno, Y; Sahara, K; Yoshido, A; Ihara, J; Yasukochi, Y; Mita, K; Ajimura, M; Suzuki, M G; Oshiki, T; Shimada, T

    2005-08-01

    In the silkworm, Bombyx mori (female, ZW; male, ZZ), femaleness is determined by the presence of a single W chromosome, irrespective of the number of autosomes or Z chromosomes. The W chromosome is devoid of functional genes, except the putative female-determining gene (Fem). However, there are strains in which chromosomal fragments containing autosomal markers have been translocated on to W. In this study, we analysed the W chromosomal regions of the Zebra-W strain (T(W;3)Ze chromosome) and the Black-egg-W strain (T(W;10)+(w-2) chromosome) at the molecular level. Initially, we undertook a project to identify W-specific RAPD markers, in addition to the three already established W-specific RAPD markers (W-Kabuki, W-Samurai and W-Kamikaze). Following the screening of 3648 arbitrary 10-mer primers, we obtained nine W-specific RAPD marker sequences (W-Bonsai, W-Mikan, W-Musashi, W-Rikishi, W-Sakura, W-Sasuke, W-Yukemuri-L, W-Yukemuri-S and BMC1-Kabuki), almost all of which contained the border regions of retrotransposons, namely portions of nested retrotransposons. We confirmed the presence of eleven out of twelve W-specific RAPD markers in the normal W chromosomes of twenty-five silkworm strains maintained in Japan. These results indicate that the W chromosomes of the strains in Japan are almost identical in type. The Zebra-W strain (T(W;3)Ze chromosome) lacked the W-Samurai and W-Mikan RAPD markers and the Black-egg-W strain (T(W;10)+(w-2) chromosome) lacked the W-Mikan RAPD marker. These results strongly indicate that the regions containing the W-Samurai and W-Mikan RAPD markers or the W-Mikan RAPD marker were deleted in the T(W;3)Ze and T(W;10)+(w-2) chromosomes, respectively, due to reciprocal translocation between the W chromosome and the autosome. This deletion apparently does not affect the expression of Fem; therefore, this deleted region of the W chromosome does not contain the putative Fem gene.

  6. The Accelerator Reliability Forum

    CERN Document Server

    Lüdeke, Andreas; Giachino, R

    2014-01-01

    A high reliability is a very important goal for most particle accelerators. The biennial Accelerator Reliability Workshop covers topics related to the design and operation of particle accelerators with a high reliability. In order to optimize the over-all reliability of an accelerator one needs to gather information on the reliability of many different subsystems. While a biennial workshop can serve as a platform for the exchange of such information, the authors aimed to provide a further channel to allow for a more timely communication: the Particle Accelerator Reliability Forum [1]. This contribution will describe the forum and advertise it’s usage in the community.

  7. Notes on Laser Acceleration

    International Nuclear Information System (INIS)

    Tajima, T.

    2008-01-01

    This note intends to motivate our effort toward the advent of new methods of particle acceleration, utilizing the fast rising laser technology. By illustrating the underlying principles in an intuitive manner and thus less jargon-clad fashion, we seek a direction in which we shall be able to properly control and harness the promise of laser acceleration. First we review the idea behind the laser wakefield. We then go on to examine ion acceleration by laser. We examine the sheath acceleration in particular and look for the future direction that allows orderly acceleration of ions in high energies

  8. Use of chromosome translocations for measuring prior environment exposures in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J. D.

    1997-05-01

    Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.

  9. Akt phosphorylation is essential for nuclear translocation and retention in NGF-stimulated PC12 cells

    International Nuclear Information System (INIS)

    Truong Le Xuan Nguyen; Choi, Joung Woo; Lee, Sang Bae; Ye, Keqiang; Woo, Soo-Dong; Lee, Kyung-Hoon; Ahn, Jee-Yin

    2006-01-01

    Nerve growth factor (NGF) elicits Akt translocation into the nucleus, where it phosphorylates nuclear targets. Here, we describe that Akt phosphorylation can promote the nuclear translocation of Akt and is necessary for its nuclear retention. Overexpression of Akt-K179A, T308A, S473A-mutant failed to show either nuclear translocation or nuclear Akt phosphorylation, whereas expression of wild-type counterpart elicited profound Akt phosphorylation and induced nuclear translocation under NGF stimulation. Employing the PI3K inhibitor and a variety of mutants PI3K, we showed that nuclear translocation of Akt was mediated by activation of PI3K, and Akt phosphorylation status in the nucleus required PI3K activity. Thus the activity of PI3K might contribute to the nuclear translocation of Akt, and that Akt phosphorylation is essential for its nuclear retention under NGF stimulation conditions

  10. Polymer translocation under a pulling force: Scaling arguments and threshold forces

    Science.gov (United States)

    Menais, Timothée

    2018-02-01

    DNA translocation through nanopores is one of the most promising strategies for next-generation sequencing technologies. Most experimental and numerical works have focused on polymer translocation biased by electrophoresis, where a pulling force acts on the polymer within the nanopore. An alternative strategy, however, is emerging, which uses optical or magnetic tweezers. In this case, the pulling force is exerted directly at one end of the polymer, which strongly modifies the translocation process. In this paper, we report numerical simulations of both linear and structured (mimicking DNA) polymer models, simple enough to allow for a statistical treatment of the pore structure effects on the translocation time probability distributions. Based on extremely extended computer simulation data, we (i) propose scaling arguments for an extension of the predicted translocation times τ ˜N2F-1 over the moderate forces range and (ii) analyze the effect of pore size and polymer structuration on translocation times τ .

  11. Industrial Application of Accelerators

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    At CERN, we are very familiar with large, high energy particle accelerators. However, in the world outside CERN, there are more than 35000 accelerators which are used for applications ranging from treating cancer, through making better electronics to removing harmful micro-organisms from food and water. These are responsible for around $0.5T of commerce each year. Almost all are less than 20 MeV and most use accelerator types that are somewhat different from what is at CERN. These lectures will describe some of the most common applications, some of the newer applications in development and the accelerator technology used for them. It will also show examples of where technology developed for particle physics is now being studied for these applications. Rob Edgecock is a Professor of Accelerator Science, with a particular interest in the medical applications of accelerators. He works jointly for the STFC Rutherford Appleton Laboratory and the International Institute for Accelerator Applications at the Univer...

  12. Industrial Application of Accelerators

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    At CERN, we are very familiar with large, high energy particle accelerators. However, in the world outside CERN, there are more than 35000 accelerators which are used for applications ranging from treating cancer, through making better electronics to removing harmful micro-organisms from food and water. These are responsible for around $0.5T of commerce each year. Almost all are less than 20 MeV and most use accelerator types that are somewhat different from what is at CERN. These lectures will describe some of the most common applications, some of the newer applications in development and the accelerator technology used for them. It will also show examples of where technology developed for particle physics is now being studied for these applications. Rob Edgecock is a Professor of Accelerator Science, with a particular interest in the medical applications of accelerators. He works jointly for the STFC Rutherford Appleton Laboratory and the International Institute for Accelerator Applications at the Uni...

  13. Accelerations in Flight

    Science.gov (United States)

    Doolittle, J H

    1925-01-01

    This work on accelerometry was done at McCook Field for the purpose of continuing the work done by other investigators and obtaining the accelerations which occur when a high-speed pursuit airplane is subjected to the more common maneuvers. The accelerations obtained in suddenly pulling out of a dive with well-balanced elevators are shown to be within 3 or 4 per cent of the theoretically possible accelerations. The maximum acceleration which a pilot can withstand depends upon the length of time the acceleration is continued. It is shown that he experiences no difficulty under the instantaneous accelerations as high as 7.8 G., but when under accelerations in excess of 4.5 G., continued for several seconds, he quickly loses his faculties.

  14. Accelerators for energy

    International Nuclear Information System (INIS)

    Inoue, Makoto

    2000-01-01

    A particle accelerator is a device to consume energy but not to produce it. Then, the titled accelerator seems to mean an accelerator for using devices related to nuclear energy. For an accelerator combined to nuclear fissionable fuel, neutron sources are D-T type, (gamma, n) reaction using electron beam type spallation type, and so forth. At viewpoints of powers of incident beam and formed neutron, a spallation type source using high energy proton is told to be effective but others have some advantages by investigation on easy operability, easy construction, combustion with target, energy and directivity of neutron, and so forth. Here were discussed on an accelerator for research on accelerator driven energy system by dividing its researching steps, and on kind, energy, beam intensity, and so forth of an accelerator suitable for it. And, space electric charge effect at beam propagation direction controlled by beam intensity of cyclotron was also commented. (G.K.)

  15. Resistance to Wheat Curl Mite in Arthropod-Resistant Rye-Wheat Translocation Lines

    Directory of Open Access Journals (Sweden)

    Lina Maria Aguirre-Rojas

    2017-11-01

    Full Text Available The wheat curl mite, Aceria toschiella (Keifer, and a complex of viruses vectored by A. toschiella substantially reduce wheat yields in every wheat-producing continent in the world. The development of A. toschiella-resistant wheat cultivars is a proven economically and ecologically viable method of controlling this pest. This study assessed A. toschiella resistance in wheat genotypes containing the H13, H21, H25, H26, H18 and Hdic genes for resistance to the Hessian fly, Mayetiola destructor (Say and in 94M370 wheat, which contains the Dn7 gene for resistance to the Russian wheat aphid, Diuraphis noxia (Kurdjumov. A. toschiella populations produced on plants containing Dn7 and H21 were significantly lower than those on plants of the susceptible control and no different than those on the resistant control. Dn7 resistance to D. noxia and H21 resistance to M. destructor resulted from translocations of chromatin from rye into wheat (H21—2BS/2RL, Dn7—1BL/1RS. These results provide new wheat pest management information, indicating that Dn7 and H21 constitute resources that can be used to reduce yield losses caused by A. toschiella, M. destructor, D. noxia, and wheat streak mosaic virus infection by transferring multi-pest resistance to single sources of germplasm.

  16. Cell Biological Mechanisms of Activity-Dependent Synapse to Nucleus Translocation of CRTC1 in Neurons

    Directory of Open Access Journals (Sweden)

    Toh Hean eCh'ng

    2015-09-01

    Full Text Available Previous studies have revealed a critical role for CREB-regulated transcriptional coactivator (CRTC1 in regulating neuronal gene expression during learning and memory. CRTC1 localizes to synapses but undergoes activity-dependent nuclear translocation to regulate the transcription of CREB target genes. Here we investigate the long-distance retrograde transport of CRTC1 in hippocampal neurons. We show that local elevations in calcium, triggered by activation of synaptic glutamate receptors and L-type voltage-gated calcium channels, initiate active, dynein-mediated retrograde transport of CRTC1 along microtubules. We identify a nuclear localization signal within CRTC1, and characterize three conserved serine residues whose dephosphorylation is required for nuclear import. Domain analysis reveals that the amino-terminal third of CRTC1 contains all of the signals required for regulated nucleocytoplasmic trafficking. We fuse this region to Dendra2 to generate a reporter construct and perform live-cell imaging coupled with local uncaging of glutamate and photoconversion to characterize the dynamics of stimulus-induced retrograde transport and nuclear accumulation.

  17. Mating type regulates the radiation-associated stimulation of reciprocal translocation events in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Fasullo, M.; Dave, P.

    1994-01-01

    Both ultraviolet (UV) and ionizing radiation were observed to stimulate mitotic, ectopic recombination between his3 recombinational substrates, generating reciprocal translocations in Saccharomyces cervisiae (yeast). The stimulation was greatest in diploid strains competent for sporulation and depends upon both the ploidy of the strain and heterozygosity at the MATlocus. The difference in levels of stimulation between MATa/MATalpha diploid and MATalpha haploid strains increases when cells are exposed to higher levels of UV radiation (sevenfold at 150 J/square metre), whereas when cells are exposed to higher levels of ionizing radiation (23.4 krad), only a twofold difference is observed. When the MATalpha gene was introduced by DNA transformation into a MATa/matalpha: LEU2 + diploid, the levels of radiation-induced ectopic recombination approach those obtained in a strain that is heterozygous at MAT. Conversely, when the MATa gene was introduced by DNA transformation into a MATalpha haploid, no enhanced stimulation of ectopic recombination was observed when cells were irradiated with ionizing radiation but a threefold enhancement was observed when cells were irradiated with UV. The increase in radiation stimulated ectopic recombination resulting from heterozygosity at MAT correlated with greater spontaneous ectopic recombination and higher levels of viability after irradiation. It is suggested that MAT functions that have been previously shown to control the level of mitotic, allelic recombination (homolog recombination) also control the level of mitotic, radiation-stimulated ectopic recombination between short dispersed repetitive sequences on non-homologous chromosomes

  18. Phosphorylation inhibits DNA-binding of alternatively spliced aryl hydrocarbon receptor nuclear translocator

    International Nuclear Information System (INIS)

    Kewley, Robyn J.; Whitelaw, Murray L.

    2005-01-01

    The basic helix-loop-helix/PER-ARNT-SIM homology (bHLH/PAS) transcription factor ARNT (aryl hydrocarbon receptor nuclear translocator) is a key component of various pathways which induce the transcription of cytochrome P450 and hypoxia response genes. ARNT can be alternatively spliced to express Alt ARNT, containing an additional 15 amino acids immediately N-terminal to the DNA-binding basic region. Here, we show that ARNT and Alt ARNT proteins are differentially phosphorylated by protein kinase CKII in vitro. Phosphorylation had an inhibitory effect on DNA-binding to an E-box probe by Alt ARNT, but not ARNT, homodimers. This inhibitory phosphorylation occurs through Ser77. Moreover, a point mutant, Alt ARNT S77A, shows increased activity on an E-box reporter gene, consistent with Ser77 being a regulatory site in vivo. In contrast, DNA binding by an Alt ARNT/dioxin receptor heterodimer to the xenobiotic response element is not inhibited by phosphorylation with CKII, nor does Alt ARNT S77A behave differently from wild type Alt ARNT in the context of a dioxin receptor heterodimer

  19. Insulin-induced translocation of IR to the nucleus in insulin responsive cells requires a nuclear translocation sequence.

    Science.gov (United States)

    Kesten, Dov; Horovitz-Fried, Miriam; Brutman-Barazani, Tamar; Sampson, Sanford R

    2018-04-01

    Insulin binding to its cell surface receptor (IR) activates a cascade of events leading to its biological effects. The Insulin-IR complex is rapidly internalized and then is either recycled back to the plasma membrane or sent to lysosomes for degradation. Although most of the receptor is recycled or degraded, a small amount may escape this pathway and migrate to the nucleus of the cell where it might be important in promulgation of receptor signals. In this study we explored the mechanism by which insulin induces IR translocation to the cell nucleus. Experiments were performed cultured L6 myoblasts, AML liver cells and 3T3-L1 adipocytes. Insulin treatment induced a rapid increase in nuclear IR protein levels within 2 to 5 min. Treatment with WGA, an inhibitor of nuclear import, reduced insulin-induced increases nuclear IR protein; IR was, however, translocated to a perinuclear location. Bioinformatics tools predicted a potential nuclear localization sequence (NLS) on IR. Immunofluorescence staining showed that a point mutation on the predicted NLS blocked insulin-induced IR nuclear translocation. In addition, blockade of nuclear IR activation in isolated nuclei by an IR blocking antibody abrogated insulin-induced increases in IR tyrosine phosphorylation and nuclear PKCδ levels. Furthermore, over expression of mutated IR reduced insulin-induced glucose uptake and PKB phosphorylation. When added to isolated nuclei, insulin induced IR phosphorylation but had no effect on nuclear IR protein levels. These results raise questions regarding the possible role of nuclear IR in IR signaling and insulin resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function

    OpenAIRE

    Thomson, Pippa A; Duff, Barbara; Blackwood, Douglas H R; Romaniuk, Liana; Watson, Andrew; Whalley, Heather C; Li, Xiang; Dauvermann, Maria R; Moorhead, T William J; Bois, Catherine; Ryan, Niamh M; Redpath, Holly; Hall, Lynsey; Morris, Stewart W; van Beek, Edwin J R

    2016-01-01

    Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorde...

  1. Survival of translocated sharp-tailed grouse: Temporal threshold and age effects

    Science.gov (United States)

    Mathews, Steven; Coates, Peter S.; Delehanty, David J.

    2016-01-01

    Context: The Columbian sharp-tailed grouse (Tympanuchus phasianellus columbianus) is a subspecies of conservation concern in the western United States, currently occupying ≤10% of its historic range. Land and management agencies are employing translocation techniques to restore Columbian sharp-tailed grouse (CSTG) populations. However, establishing self-sustaining populations by translocating grouse often is unsuccessful, owing, in part, to low survivorship of translocated grouse following release.Aims: We measured and modelled patterns of CSTG mortality for 150 days following translocation into historic range, to better understand patterns and causes of success or failure in conservation efforts to re-establish grouse populations.Methods: We conducted two independent multi-year translocations and evaluated individual and temporal factors associated with CSTG survival up to 150 days following their release. Both translocations were reintroduction attempts in Nevada, USA, to establish viable populations of CSTG into their historic range.Key results: We observed a clear temporal threshold in survival probability, with CSTG mortality substantially higher during the first 50 days following release than during the subsequent 100 days. Additionally, translocated yearling grouse exhibited higher overall survival (0.669 ± 0.062) than did adults (0.420 ± 0.052) across the 150-day period and higher survival than adults both before and after the 50-day temporal threshold.Conclusions: Translocated CSTG are especially vulnerable to mortality for 50 days following release, whereas translocated yearling grouse are more resistant to mortality than are adult grouse. On the basis of the likelihood of survival, yearling CSTG are better candidates for population restoration through translocation than are adult grouse.Implications: Management actions that ameliorate mortality factors for 50 days following translocation and translocations that employ yearling grouse will

  2. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    International Nuclear Information System (INIS)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. As an exogeneous factor of possible influence, the meiotic effects of two types of radiation (fission neutrons and X-rays) administered at relatively low doses 2 and 3 hours before prometaphase-metaphase II (probably during metaphase-anaphase I), were determined in Rb4Bnr/+-males. (Auth.)

  3. Occurence of translocations between irradiated and intact chromosomes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Myasnyankina, E.N.; Abeleva, Eh.A.; Generalova, M.V.

    1980-01-01

    Two translocations between irradiated father and intact mother autosomes are obtained in Drosophila melanogaster. Five out of 283 regular translocations (between the second and the third chromosomes of an irradiated male) are accompanied by a recombination over the second or the third chromosomes. Nine flies out of twenty considered to be recombinants, could originate due to mutations. The data obtained prove that intact female autosomes can take part in the exchange with homologic (recombinations) and heterologic (translocations) irradiated male autosomes

  4. Translocation of photoassimilates in γ-irradiated soybean plants

    International Nuclear Information System (INIS)

    Ursino, D.J.; Schefski, H.; Latour, P.W.

    1977-01-01

    Young soybean plants received on a single occasion a dose of 3.75 krads of γ-radiation after which they were allowed to photoassimilate 14 CO 2 so that the magnitude of translocation and distribution pattern of exported 14 C could be determined. In comparison to the non-irradiated controls, plants exposed to ionizing radiation showed a large reduction, almost 70%, in the magnitude of 14 C exported from the source leaf in a one hour period. Furthermore, the pattern of distribution of exported 14 C was altered such that less was exported to the shoot apex region and more to the region below the node of the source leaf. Replacement of the shoot apex with 20 ppm IAA immediately following irradiation completely restored the pattern of distribution but was able to only partially increase the magnitude of translocation. These results are interpreted with reference to the results from the author's previous study with soybean showing radiation effects on photosynthesis and shoot development. (author)

  5. [Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects].

    Science.gov (United States)

    Podoprigora, G I; Kafarskaya, L I; Bainov, N A; Shkoporov, A N

    2015-01-01

    Bacterial translocation (BT) is both pathology and physiology phenomenon. In healthy newborns it accompanies the process of establishing the autochthonous intestinal microbiota and the host microbiome. In immunodeficiency it can be an aethio-pathogenetic link and a manifestation of infection or septic complications. The host colonization resistance to exogenous microbic colonizers is provided by gastrointestinal microbiota in concert with complex constitutional and adaptive defense mechanisms. BT may be result of barrier dysfunction and self-purification mechanisms involving the host myeloid cell phagocytic system and opsonins. Dynamic cell humoral response to microbial molecular patterns that occurs on the mucous membranes initiates receptorsignalingpathways and cascade ofreactions. Their vector and results are largely determined by cross-reactivity between microbiome and the host genome. Enterocyte barriers interacting with microbiota play leading role in providing adaptive, homeostatic and stress host reactivity. Microcirculatory ischemic tissue alterations and inflammatory reactions increase the intestinal barrier permeability and BT These processes a well as mechanisms for apoptotic cells and bacteria clearance are justified to be of prospective research interest. The inflammatory and related diseases caused by alteration and dysfunction of the intestinal barrier are reasonably considered as diseases of single origin. Maternal microbiota affects theformation of the innate immune system and the microbiota of the newborn, including intestinal commensal translocation during lactation. Deeper understanding of intestinal barrier mechanisms needs complex microbiological, immunological, pathophysiological, etc. investigations using adequate biomodels, including gnotobiotic animals.

  6. Translocation of the neonicotinoid seed treatment clothianidin in maize.

    Science.gov (United States)

    Alford, Adam; Krupke, Christian H

    2017-01-01

    Neonicotinoid seed treatments, typically clothianidin or thiamethoxam, are routinely applied to >80% of maize (corn) seed grown in North America where they are marketed as a targeted pesticide delivery system. Despite this widespread use, the amount of compound translocated into plant tissue from the initial seed treatment to provide protection has not been reported. Our two year field study compared concentrations of clothianidin seed treatments in maize to that of maize without neonicotinoid seed treatments and found neonicotinoids present in root tissues up to 34 days post planting. Plant-bound clothianidin concentrations followed an exponential decay pattern with initially high values followed by a rapid decrease within the first ~20 days post planting. A maximum of 1.34% of the initial seed treatment was successfully recovered from plant tissues in both study years and a maximum of 0.26% was recovered from root tissue. Our findings show neonicotinoid seed treatments may provide protection from some early season secondary maize pests. However, the proportion of the neonicotinoid seed treatment clothianidin translocated into plant tissues throughout the growing season is low overall and this observation may provide a mechanism to explain reports of inconsistent efficacy of this pest management approach and increasing detections of environmental neonicotinoids.

  7. Translocation of the neonicotinoid seed treatment clothianidin in maize.

    Directory of Open Access Journals (Sweden)

    Adam Alford

    Full Text Available Neonicotinoid seed treatments, typically clothianidin or thiamethoxam, are routinely applied to >80% of maize (corn seed grown in North America where they are marketed as a targeted pesticide delivery system. Despite this widespread use, the amount of compound translocated into plant tissue from the initial seed treatment to provide protection has not been reported. Our two year field study compared concentrations of clothianidin seed treatments in maize to that of maize without neonicotinoid seed treatments and found neonicotinoids present in root tissues up to 34 days post planting. Plant-bound clothianidin concentrations followed an exponential decay pattern with initially high values followed by a rapid decrease within the first ~20 days post planting. A maximum of 1.34% of the initial seed treatment was successfully recovered from plant tissues in both study years and a maximum of 0.26% was recovered from root tissue. Our findings show neonicotinoid seed treatments may provide protection from some early season secondary maize pests. However, the proportion of the neonicotinoid seed treatment clothianidin translocated into plant tissues throughout the growing season is low overall and this observation may provide a mechanism to explain reports of inconsistent efficacy of this pest management approach and increasing detections of environmental neonicotinoids.

  8. Novel Class of Potential Therapeutics that Target Ricin Retrograde Translocation

    Directory of Open Access Journals (Sweden)

    Veronika Redmann

    2013-12-01

    Full Text Available Ricin toxin, an A-B toxin from Ricinus communis, induces cell death through the inhibition of protein synthesis. The toxin binds to the cell surface via its B chain (RTB followed by its retrograde trafficking through intracellular compartments to the ER where the A chain (RTA is transported across the membrane and into the cytosol. Ricin A chain is transported across the ER membrane utilizing cellular proteins involved in the disposal of aberrant ER proteins by a process referred to as retrograde translocation. Given the current lack of therapeutics against ricin intoxication, we developed a high-content screen using an enzymatically attenuated RTA chimera engineered with a carboxy-terminal enhanced green fluorescent protein (RTAE177Qegfp to identify compounds that target RTA retrograde translocation. Stabilizing RTAE177Qegfp through the inclusion of proteasome inhibitor produced fluorescent peri-nuclear granules. Quantitative analysis of the fluorescent granules provided the basis to discover compounds from a small chemical library (2080 compounds with known bioactive properties. Strikingly, the screen found compounds that stabilized RTA molecules within the cell and several compounds limited the ability of wild type RTA to suppress protein synthesis. Collectively, a robust high-content screen was developed to discover novel compounds that stabilize intracellular ricin and limit ricin intoxication.

  9. Molecular determinants of nucleolar translocation of RNA helicase A

    International Nuclear Information System (INIS)

    Liu Zhe; Kenworthy, Rachael; Green, Christopher; Tang, Hengli

    2007-01-01

    RNA helicase A (RHA) is a member of the DEAH-box family of DNA/RNA helicases involved in multiple cellular processes and the life cycles of many viruses. The subcellular localization of RHA is dynamic despite its steady-state concentration in the nucleoplasm. We have previously shown that it shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus. Here, we investigate the molecular determinants for its translocation within the nucleus and, more specifically, its redistribution from the nucleoplasm to nucleolus or the perinucleolar region. We found that low temperature treatment, transcription inhibition or replication of hepatitis C virus caused the intranuclear redistribution of the protein, suggesting that RHA shuttles between the nucleolus and nucleoplasm and becomes trapped in the nucleolus or the perinucleolar region upon blockade of transport to the nucleoplasm. Both the NTD and ATPase activity were essential for RHA's transport to the nucleolus or perinucleolar region. One of the double-stranded RNA binding domains (dsRBD II) was also required for this nucleolar translocation (NoT) phenotype. RNA interference studies revealed that RHA is essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role

  10. Translocation of cesium in plants after foliar deposition - Experiments and models

    International Nuclear Information System (INIS)

    Proehl, G.; Voigt, G.; Mueller, H.

    1991-01-01

    The translocation of cesium from the foliage to the edible parts as function of the time period between deposition and harvest has been determined for cereals, potatoes, green beans and carrots. From the results the following conclusions can be drawn: 1. The maximum of the cesium translocation is 40 to 50 and 70 to 90 days before harvest for cereals and potatoes respectively. For green beans a maximum was observed after deposition 15 days before harvest; 2. The variations of the translocation factors are less if the translocation is normalized to the yield; 3. The translocation factors are in good agreement with those of other investigators. The agreement between the experimental series is better for a normalization of the translocation factor on the yield; 4. For cereals and potatoes the translocation can be described with gaussian functions which are consistent with the physiological development of cereals and potatoes. Although the approach in ECOSYS tends to over predict slightly the translocation for barley and potatoes there is a good overall agreement between the experiments and this model; 5. According to the investigations available the translocation of cesium can be predicted within a factor of 3 for cereals and a factor of 4 for potatoes. Sources of the uncertainties besides the biological variability and the inherent experimental error are differences in the development of the plants due to weather conditions, farm management and plant diseases. (9 refs., 5 figs.)

  11. Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

    Science.gov (United States)

    Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

    2012-01-01

    Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

  12. Use of wild–caught individuals as a key factor for success in vertebrate translocations

    Energy Technology Data Exchange (ETDEWEB)

    Rummel, L.; MartInez-AbraIn, A.; Mayol, J.; Ruiz-Olmo, J.; Mañas, F.; Jimenez, J.; Gomez, J.A.; Oro, D.

    2016-07-01

    Success of vertebrate translocations is crucial to improve efficacy and efficiency of conservation actions but it is often difficult to assess because negative results (failed translocations) are seldom published. We developed surveys and sent them to heads of conservation services in three major Spanish Mediterranean regions. The purpose of our surveys was to determine which methodological factor, that could easily be implemented in practice, was more influential for translocation success. These factors included the origin of translocated individuals (captive or wild) and translocation effort (propagule size and program duration). After analyzing 83 programs, corresponding to 34 different vertebrate species, by means of generalized linear mixed modelling, we found that ‘origin’ was more relevant for translocation success than ‘effort’, although we could not rule out some role of translocation effort. Variance in success of translocation programs involving individuals from wild sources was smaller and consequently results more predictable. Origin interacted with taxa so that success was higher when using wild birds and especially wild fish and mammals, but not when releasing reptiles. Hence, we suggest that, for any given effort, translocation results will be better for most vertebrate taxa if individuals from wild sources are used. When this is not feasible, managers should release captive–reared individuals for a long number of years rather than a short number of years. (Author)

  13. Can Characteristics of Reciprocal Translocations Predict the Chance of Transferable Embryos in PGD Cycles?

    Directory of Open Access Journals (Sweden)

    Elsbeth Dul

    2014-04-01

    Full Text Available Translocation carriers have an increased risk of miscarriage or the birth of a child with congenital anomalies. Preimplantation genetic diagnosis (PGD is performed in translocation carriers to select for balanced embryos and, thus, increase the chance of an ongoing pregnancy. However, a common experience is that reciprocal translocation carriers produce a high percentage of unbalanced embryos, which cannot be transferred. Therefore, the pregnancy rates in PGD in this patient group are low. In a cohort of 85 reciprocal translocation carriers undergoing PGD we have searched for cytogenetic characteristics of the translocations that can predict the percentage of balanced embryos. Using shape algorithms, the most likely segregation mode per translocation was determined. Shape algorithm, breakpoint location, and relative chromosome segment sizes proved not to be independent predictors of the percentage of balanced embryos. The ratio of the relative sizes of the translocated segments of both translocation chromosomes can give some insight into the chance of transferable embryos: Very asymmetrical translocations have a higher risk of unbalanced products (p = 0.048. Counseling of the couples on the pros and cons of all their reproductive options remains very important.

  14. Use of wild–caught individuals as a key factor for success in vertebrate translocations

    Directory of Open Access Journals (Sweden)

    Rummel, L.

    2016-06-01

    Full Text Available Success of vertebrate translocations is crucial to improve efficacy and efficiency of conservation actions but it is often difficult to assess because negative results (failed translocations are seldom published. We developed surveys and sent them to heads of conservation services in three major Spanish Mediterranean regions. The purpose of our surveys was to determine which methodological factor, that could easily be implemented in practice, was more influential for translocation success. These factors included the origin of translocated individuals (captive or wild and translocation effort (propagule size and program duration. After analyzing 83 programs, corresponding to 34 different vertebrate species, by means of generalized linear mixed modelling, we found that ‘origin’ was more relevant for translocation success than ‘effort’, although we could not rule out some role of translocation effort. Variance in success of translocation programs involving individuals from wild sources was smaller and consequently results more predictable. Origin interacted with taxa so that success was higher when using wild birds and especially wild fish and mammals, but not when releasing reptiles. Hence, we suggest that, for any given effort, translocation results will be better for most vertebrate taxa if individuals from wild sources are used. When this is not feasible, managers should release captive–reared individuals for a long number of years rather than a short number of years.

  15. Translocation of reindeer from South Georgia to the Falkland Islands

    Directory of Open Access Journals (Sweden)

    Cameron M. Bell

    2010-03-01

    Full Text Available This report describes the first translocation of reindeer Rangifer tarandus from South Georgia to the Falkland Islands, in the South Atlantic Ocean. Reindeer were introduced from Norway to the subantarctic island of South Georgia on three occasions in the early 1900s by Norwegian whalers, and today they exist as two discrete herds, numbering approximately 2600 individuals in total. Because of concerns over the impact on native vegetation, the long-term eradication of reindeer from South Georgia has recently been proposed. A translocation of reindeer to the Falkland Islands was undertaken in 2001 by the Falkland Island Government with two objectives: (1 to preserve the genetic resources of at least one of the South Georgia herds; and (2 to facilitate the diversification of the agricultural sector of the Falkland Islands by establishing a commercial reindeer herd. Techniques developed and used in North America for the successful relocation of large numbers of calves were adopted for the translocation. A total of 59 calves (26 females and 33 males were successfully translocated from South Georgia to the Falklands Islands in 2001, and subsequently produced their first offspring in 2003. Good husbandry practices and an understanding of biology and behaviour are essential for the successful translocation of reindeer.Flytting av rein fra Sør-Georgia til FalklandsøyeneAbstract in Norwegian / Sammendrag: Artikkelen beskriver den første overføring av rein Rangifer tarandus fra Sør-Georgia til Falklandsøyene i søratlanteren. Tamrein fra Norge ble flyttet til den subarktiske øya Sør-Georgia ved tre anledninger i perioden 1911 til 1925 i forbindelse med den norske hvalfangsten der. I dag består bestanden av rundt regnet 2600 dyr fordelt på to geografisk atskilte flokker. Av hensyn til den naturlige vegetasjonen på øya er det forslag om å på sikt utrydde reinbestanden på øya. Regjeringen på Falklandsøyene foretok en første overføring av

  16. Cell-cycle dependent expression of a translocation-mediated fusion oncogene mediates checkpoint adaptation in rhabdomyosarcoma.

    Directory of Open Access Journals (Sweden)

    Ken Kikuchi

    2014-01-01

    Full Text Available Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by alveolar or embryonal histology. The alveolar subtype harbors a translocation-mediated PAX3:FOXO1A fusion gene and has an extremely poor prognosis. However, tumor cells have heterogeneous expression for the fusion gene. Using a conditional genetic mouse model as well as human tumor cell lines, we show that that Pax3:Foxo1a expression is enriched in G2 and triggers a transcriptional program conducive to checkpoint adaptation under stress conditions such as irradiation in vitro and in vivo. Pax3:Foxo1a also tolerizes tumor cells to clinically-established chemotherapy agents and emerging molecularly-targeted agents. Thus, the surprisingly dynamic regulation of the Pax3:Foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells.

  17. Molecular cytogenetic characterization of a new wheat-rye 4R chromosome translocation line resistant to powdery mildew.

    Science.gov (United States)

    An, Diaoguo; Zheng, Qi; Zhou, Yilin; Ma, Pengtao; Lv, Zhenling; Li, Lihui; Li, Bin; Luo, Qiaoling; Xu, Hongxing; Xu, Yunfeng

    2013-07-01

    Rye is an important and valuable gene resource for wheat improvement. However, due to extensive growing of cultivars with disease resistance genes from short arm of rye chromosome 1R and coevolution of pathogen virulence and host resistance, these cultivars successively lost resistance to pathogens. Identification and deployment of new resistance gene sources in rye are, therefore, of especial importance and urgency. A new wheat-rye line, designated as WR41-1, was produced through distant hybridization and chromosome engineering protocols between common wheat cultivar Xiaoyan 6 and rye cultivar German White. It was proved to be a new wheat-rye T4BL·4RL and T7AS·4RS translocation line using sequential genomic in situ hybridization (GISH), multicolor fluorescence in situ hybridization (mc-FISH), and expressed sequence tag-simple sequence repeat (EST-SSR) marker analysis. WR41-1 showed high levels of resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) pathogens prevalent in China at the adult growth stage and 13 of 23 Bgt isolates tested at the seedling stage. According to its resistant pattern to 23 different Bgt isolates, WR41-1 may possess new gene(s) for resistance to powdery mildew, which differed from previously identified and known powdery mildew genes from rye (Pm7, Pm8, Pm17, and Pm20). In addition, WR41-1 was cytologically stable, had a desirable fertility, and is expected to be useful in wheat improvement.

  18. Particle-accelerator decommissioning

    International Nuclear Information System (INIS)

    Opelka, J.H.; Mundis, R.L.; Marmer, G.J.; Peterson, J.M.; Siskind, B.; Kikta, M.J.

    1979-12-01

    Generic considerations involved in decommissioning particle accelerators are examined. There are presently several hundred accelerators operating in the United States that can produce material containing nonnegligible residual radioactivity. Residual radioactivity after final shutdown is generally short-lived induced activity and is localized in hot spots around the beam line. The decommissioning options addressed are mothballing, entombment, dismantlement with interim storage, and dismantlement with disposal. The recycle of components or entire accelerators following dismantlement is a definite possibility and has occurred in the past. Accelerator components can be recycled either immediately at accelerator shutdown or following a period of storage, depending on the nature of induced activation. Considerations of cost, radioactive waste, and radiological health are presented for four prototypic accelerators. Prototypes considered range from small accelerators having minimal amounts of radioactive mmaterial to a very large accelerator having massive components containing nonnegligible amounts of induced activation. Archival information on past decommissionings is presented, and recommendations concerning regulations and accelerator design that will aid in the decommissioning of an accelerator are given

  19. An introduction to acceleration mechanisms

    International Nuclear Information System (INIS)

    Palmer, R.B.

    1987-05-01

    This paper discusses the acceleration of charged particles by electromagnetic fields, i.e., by fields that are produced by the motion of other charged particles driven by some power source. The mechanisms that are discussed include: Ponderamotive Forces, Acceleration, Plasma Beat Wave Acceleration, Inverse Free Electron Laser Acceleration, Inverse Cerenkov Acceleration, Gravity Acceleration, 2D Linac Acceleration and Conventional Iris Loaded Linac Structure Acceleration

  20. FRAS1-related extracellular matrix 3 (FREM3) single-nucleotide polymorphism effects on gene expression, amygdala reactivity and perceptual processing speed: An accelerated aging pathway of depression risk

    Science.gov (United States)

    Nikolova, Yuliya S.; Iruku, Swetha P.; Lin, Chien-Wei; Conley, Emily Drabant; Puralewski, Rachel; French, Beverly; Hariri, Ahmad R.; Sibille, Etienne

    2015-01-01

    The A allele of the FRAS1-related extracellular matrix protein 3 (FREM3) rs7676614 single nucleotide polymorphism (SNP) was linked to major depressive disorder (MDD) in an early genome-wide association study (GWAS), and to symptoms of psychomotor retardation in a follow-up investigation. In line with significant overlap between age- and depression-related molecular pathways, parallel work has shown that FREM3 expression in postmortem human brain decreases with age. Here, we probe the effect of rs7676614 on amygdala reactivity and perceptual processing speed, both of which are altered in depression and aging. Amygdala reactivity was assessed using a face-matching BOLD fMRI paradigm in 365 Caucasian participants in the Duke Neurogenetics Study (DNS) (192 women, mean age 19.7 ± 1.2). Perceptual processing speed was indexed by reaction times in the same task and the Trail Making Test (TMT). The effect of rs7676614 on FREM3 mRNA brain expression levels was probed in a postmortem cohort of 169 Caucasian individuals (44 women, mean age 50.8 ± 14.9). The A allele of rs7676614 was associated with blunted amygdala reactivity to faces, slower reaction times in the face-matching condition (p < 0.04), as well as marginally slower performance on TMT Part B (p = 0.056). In the postmortem cohort, the T allele of rs6537170 (proxy for the rs7676614 A allele), was associated with trend-level reductions in gene expression in Brodmann areas 11 and 47 (p = 0.066), reminiscent of patterns characteristic of older age. The low-expressing allele of another FREM3 SNP (rs1391187) was similarly associated with reduced amygdala reactivity and slower TMT Part B speed, in addition to reduced BA47 activity and extraversion (p < 0.05). Together, these results suggest common genetic variation associated with reduced FREM3 expression may confer risk for a subtype of depression characterized by reduced reactivity to environmental stimuli and slower perceptual processing speed, possibly suggestive of

  1. Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in ApcMin/+ mice

    Directory of Open Access Journals (Sweden)

    Brudvik Kristoffer W

    2011-12-01

    Full Text Available Abstract Background The adenomatous polyposis coli (APC protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer. The destruction complex is inhibited by Wnt-Frz and prostaglandin E2 (PGE2 - PI-3 kinase pathways. Recent reports show that PGE2-induced phosphorylation of β-catenin by protein kinase A (PKA increases nuclear translocation indicating two mechanisms of action of PGE2 on β-catenin homeostasis. Findings Treatment of ApcMin/+ mice that spontaneously develop intestinal adenomas with a PKA antagonist (Rp-8-Br-cAMPS selectively targeting only the latter pathway reduced tumor load, but not the number of adenomas. Immunohistochemical characterization of intestines from treated and control animals revealed that expression of β-catenin, β-catenin nuclear translocation and expression of the β-catenin target genes c-Myc and COX-2 were significantly down-regulated upon Rp-8-Br-cAMPS treatment. Parallel experiments in a human colon cancer cell line (HCT116 revealed that Rp-8-Br-cAMPS blocked PGE2-induced β-catenin phosphorylation and c-Myc upregulation. Conclusion Based on our findings we suggest that PGE2 act through PKA to promote β-catenin nuclear translocation and tumor development in ApcMin/+ mice in vivo, indicating that the direct regulatory effect of PKA on β-catenin nuclear translocation is operative in intestinal cancer.

  2. Reviews of accelerator science and technology

    CERN Document Server

    Chou, Weiren

    2008-01-01

    Particle accelerators are a major invention of the 20th century. In the last eight decades, they have evolved enormously and have fundamentally changed the way we live, think and work. Accelerators are the most powerful microscopes for viewing the tiniest inner structure of cells, genes, molecules, atoms and their constituents such as protons, neutrons, electrons, neutrinos and quarks. This opens up a whole new world for materials science, chemistry and molecular biology.Accelerators with megawatt beam power may ultimately solve a critical problem faced by our society, namely, the treatment of nuclear waste and the supply of an alternative type of energy. There are also tens of thousands of small accelerators all over the world. They are used every day for medical imaging, cancer therapy, radioisotope production, high-density chip-making, mass spectrometry, cargo x-ray/gamma-ray imaging, detection of explosives and illicit drugs, and weapons. This volume provides a comprehensive review of this driving and fas...

  3. Accelerator and radiation physics

    CERN Document Server

    Basu, Samita; Nandy, Maitreyee

    2013-01-01

    "Accelerator and radiation physics" encompasses radiation shielding design and strategies for hadron therapy accelerators, neutron facilities and laser based accelerators. A fascinating article describes detailed transport theory and its application to radiation transport. Detailed information on planning and design of a very high energy proton accelerator can be obtained from the article on radiological safety of J-PARC. Besides safety for proton accelerators, the book provides information on radiological safety issues for electron synchrotron and prevention and preparedness for radiological emergencies. Different methods for neutron dosimetry including LET based monitoring, time of flight spectrometry, track detectors are documented alongwith newly measured experimental data on radiation interaction with dyes, polymers, bones and other materials. Design of deuteron accelerator, shielding in beam line hutches in synchrotron and 14 MeV neutron generator, various radiation detection methods, their characteriza...

  4. 2014 Accelerators meeting, Grenoble

    International Nuclear Information System (INIS)

    Lucotte, Arnaud; Lamy, Thierry; De Conto, Jean-Marie; Fontaine, Alain; Revol, Jean-Luc; Nadolski, Laurent S.; Kazamias, Sophie; Vretenar, Maurizio; Ferrando, Philippe; Laune, Bernard; Vedrine, Pierre

    2014-10-01

    The Accelerators meeting is organised every two years by the Accelerators division of the French Society of Physics (SFP). It brings together about 50 participants during a one-day meeting. The morning sessions are devoted to scientific presentations while the afternoon is dedicated to technical visits of facilities. This document brings together the available presentations (slides): 1 - Presentation of the Laboratory of subatomic physics and cosmology - LPSC-Grenoble (Lucotte, Arnaud; Lamy, Thierry); 2 - Presentation of the Accelerators division of the French Society of Physics (Fontaine, Alain; Revol, Jean-Luc); 3 - Presentation of Grenoble's master diplomas in Accelerator physics (Nadolski, Laurent S.); 4 - Presentation of Paris' master diplomas in big instruments (Kazamias, Sophie); 5 - Particle accelerators and European Union's projects (Vretenar, Maurizio); 6 - French research infrastructures (Ferrando, Philippe); 7 - Coordination of accelerators activity in France (Laune, Bernard; Vedrine, Pierre)

  5. Accelerator reliability workshop

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, L; Duru, Ph; Koch, J M; Revol, J L; Van Vaerenbergh, P; Volpe, A M; Clugnet, K; Dely, A; Goodhew, D

    2002-07-01

    About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop.

  6. Accelerator reliability workshop

    International Nuclear Information System (INIS)

    Hardy, L.; Duru, Ph.; Koch, J.M.; Revol, J.L.; Van Vaerenbergh, P.; Volpe, A.M.; Clugnet, K.; Dely, A.; Goodhew, D.

    2002-01-01

    About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop

  7. Acceleration of radioactive ions

    International Nuclear Information System (INIS)

    Laxdal, R.E.

    2003-01-01

    There is an intense interest world-wide in the use of radioactive ion beams (RIBs) for experiment. In many existing or proposed facilities ions are produced or collected at source potential, ionized and re-accelerated. Within the past year three new ISOL based facilities have added dedicated post-accelerators to deliver accelerated RIBs to experiment. The paper gives an overview of RIB accelerators present and future, and explores the inherent features in the various acceleration methods with an emphasis on heavy ion linacs. The ISAC-I and ISAC-II post-accelerators are discussed as examples. Commissioning results and initial operating experience with ISAC-I will be presented

  8. Nuclear physics accelerator facilities

    International Nuclear Information System (INIS)

    1988-12-01

    This paper describes many of the nuclear physics heavy-ion accelerator facilities in the US and the research programs being conducted. The accelerators described are: Argonne National Laboratory--ATLAS; Brookhaven National Laboratory--Tandem/AGS Heavy Ion Facility; Brookhaven National Laboratory--Relativistic Heavy Ion Collider (RHIC) (Proposed); Continuous Electron Beam Accelerator Facility; Lawrence Berkeley Laboratory--Bevalac; Lawrence Berkeley Laboratory--88-Inch Cyclotron; Los Alamos National Laboratory--Clinton P. Anderson Meson Physics Facility (LAMPF); Massachusetts Institute of Technology--Bates Linear Accelerator Center; Oak Ridge National Laboratory--Holifield Heavy Ion Research Facility; Oak Ridge National Laboratory--Oak Ridge Electron Linear Accelerator; Stanford Linear Accelerator Center--Nuclear Physics Injector; Texas AandM University--Texas AandM Cyclotron; Triangle Universities Nuclear Laboratory (TUNL); University of Washington--Tandem/Superconducting Booster; and Yale University--Tandem Van de Graaff

  9. Experience with FISH-detected translocations as an indicator in retrospective dose reconstructions

    International Nuclear Information System (INIS)

    Pressl, S.; Romm, H.; Ganguly, B.B.; Stephan, G.

    2000-01-01

    The prerequisite for the use of translocations as an indicator in retrospective dose reconstructions, is knowledge of the background level, persistence, and the availability of dose response curves for the conversion of translocation frequencies into doses. The results obtained in these areas are summarised. Cells with complete painted chromosome material are evaluated. Those showing any aberrations which involve painted material are stored in a computerised system, and described in detail. The simultaneous painting of whole chromosomes and centromeres has proved to provide a better level of discrimination between translocations and dicentrics. Following irradiation, direct proportionality was observed between DNA content covered by the painted chromosomes (11-19%) and the translocation frequency. The background level of translocations was determined in 42 healthy subjects, aged between 21 and 73 years of age. The statistical analyses of the data revealed no influence from sex and smoking habits on the translocation frequency. A clear increase in translocation yield was, however, observed for age. For the whole genome the frequency is at a level of 3 to 11 per 1000 cells, for all types of translocations. In a radiation accident victim (Estonia) the frequency of translocations was determined over a post-exposure time of four years. For two-way translocations, the half-time was calculated to be 7.0 years, and that for one-way translocations 5.2 years. On the basis of our control data and our dose response curve, the lowest detectable radiation dose is about 0.3 Gy in subjects under 40 years of age, and about 0.5 Gy for those older than 40 years of age. (author)

  10. Translocation of iodine-129 in soil and transfer to vegetation

    International Nuclear Information System (INIS)

    Handl, J.

    1989-01-01

    The translocation of I-129 in the soil and its long-term transfer from soil to plant have been investigated using an undisturbed soil column and a pasture on a river bank. The I-129 profiles in the soils of the monolith and the pasture exhibit clear differences in the distribution of radioiodine after 52 and 47 months, respectively. At those times after surface contamination of both soil types 88% (monolith) and 66% (pasture) of the total I-129 activity were found in the top soil layer of 10 cm, indicating that translocation in the pasture soil is faster than in the monolith. Apart from soil-specific parameters this behaviour may be explained by anaerobic conditions created in the soil due to high water levels in the nearby river attecting the chemical form of iodine. The distribution of stable iodine was found rather homogeneous in both soils with mean contents of 3 mg I-127 kg -1 d.w. in the upper 15 cm and 4 mg I-127 kg -1 d.w. in deeper layers in case of the monolith. For the pasture soil the corresponding values are about 4 and 5 mg I-127 kg -1 d.w. Transfer factors plant/soil (dry weight basis) of I-129 obtained from the monolith 39 g and 52 months after contamination are 1.5x10 -3 and 2.1x10 -3 , respectively. Data from the pasture 35 and 47 months after contamination show values of 9.0x10 -3 and 8.4x10 -3 , respectively. Transfer factors of stable iodine are significantly higher in both soils yielding an average value of 1.0 for the monolith and 0.3 for the pasture. Delay constants (related to a top soil layer of 10 cm) calculated for I-129 using data obtained from the long-term translocation processes to deeper soil layers in the monolith and in the pasture show values of 1x10 -9 s -1 and 4x10 -9 s -1 , respectively. (orig.) [de

  11. Cd translocation into generative organs of linseed (Linum usitatissimum L.)

    Energy Technology Data Exchange (ETDEWEB)

    Becher, M.; Woerner, A.; Schubert, S. [Giessen Univ. (Germany). Inst. fuer Pflanzenernaehrung

    1997-12-31

    Linseed is able to accumulate considerably high concentrations of Cd in generative organs, the dietary critical value of 0.3 {mu}g Cd/g seed often being exceeded. Differences between genotypes of linseed in this respect, however, have been observed but the underlying mechanisms responsible for these differences are unknown. The aim of the present work was to identify these mechanisms by studying the Cd accumulation of the linseed genotypes Antares and McGregor which differ in their ability to accumulate Cd in the seeds. Cultivar Antares is a high and cv. McGregor is low Cd accumulator which was confirmed in a pot experiment. It was found that the differences between these genotypes were Cd-specific and were caused neither by single seed weight nor by Cd translocation into the shoot. The distribution pattern of Cd within mature capsules between the pericarp and the seeds differed from that of Ca which was used as a phloem-immobile reference ion. From these results we conclude that Cd was translocated from the pericarp into the seeds via the phloem. This conclusion was supported by direct Cd determination in collected phloem sap from linseed stems. As sources of seed-Cd we identified the pericarps of capsules and the leaves. The genotype differences concerning the Cd concentrations in the seeds may be explained in terms of differences in phloem translocation of Cd. (orig.) [Deutsch] Oellein vermag Cd in betraechtlichen Konzentrationen in den Samen zu akkumulieren. Aus diesem Grund wird der Grenzwert fuer Diaetlein von 0,3 {mu}g/g Samen im Anbau haeufig ueberschritten. Es gibt jedoch genotypische Unterschiede, deren zugrundeliegende Mechanismen nicht bekannt sind. Das Ziel der vorliegenden Arbeit bestand darin, diese Mechanismen an den Oelleinsorten Antares und McGregor zu untersuchen. Antares akkumuliert grosse, McGregor hingegen geringe Mengen Cd in den Samen. Diese Beobachtungen konnten in einem Gefaessversuch bestaetigt werden. Es wurde gezeigt, dass die

  12. Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation.

    Science.gov (United States)

    Stefanova, Margarita; Zemke, Katrin; Dimitrov, Boyan; Has, Christina; Kern, Johannes S; Bruckner-Tuderman, Leena; Kutsche, Kerstin

    2005-10-01

    Mutations in the type VII collagen gene (COL7A1) cause autosomal recessive and autosomal dominant inherited dystrophic epidermolysis bullosa (DEB). We report a family with three individuals who present blistering, scarring, hypo- and hyperpigmentation, and nail dystrophy suggestive for DEB. Whereas father and son carry a 5;13 translocation, the daughter shows a normal karyotype. Segregation analysis revealed that all affected family members inherited the same COL7A1 allele. Mutation analysis disclosed a heterozygous missense mutation, c.6227G > A (p.G2076D), in COL7A1 in all affected individuals. Delineation of the translocation breakpoints showed that the ERBB2IP (erbb2 interacting protein or Erbin) gene is disrupted in 5q13.1 and GPC6 in 13q32. GPC6 encodes glypican 6 belonging to a family of cell surface heparan sulfate proteoglycans. The binding partners of Erbin, BP230 (BPAG1) and the integrin beta4 subunit, both involved in hemidesmosome (HD) function, and the presence of Erbin in HD suggested that it plays a role in establishment and maintenance of cell-basement membrane adhesions. However, loss of function of one ERBB2IP copy or expression of a putative novel ERBB2IP fusion protein did not apparently modulate the DEB phenotype in both translocation patients. Nonetheless, one cannot yet exclude that ERBB2IP is a candidate for human blistering disorders such as epidermolysis bullosa.

  13. Development of a high-throughput method for the systematic identification of human proteins nuclear translocation potential

    Directory of Open Access Journals (Sweden)

    Kawai Jun

    2009-09-01

    Full Text Available Abstract Background Important clues to the function of novel and uncharacterized proteins can be obtained by identifying their ability to translocate in the nucleus. In addition, a comprehensive definition of the nuclear proteome undoubtedly represents a key step toward a better understanding of the biology of this organelle. Although several high-throughput experimental methods have been developed to explore the sub-cellular localization of proteins, these methods tend to focus on the predominant localizations of gene products and may fail to provide a complete catalog of proteins that are able to transiently locate into the nucleus. Results We have developed a method for examining the nuclear localization potential of human gene products at the proteome scale by adapting a mammalian two-hybrid system we have previously developed. Our system is composed of three constructs co-transfected into a mammalian cell line. First, it contains a PCR construct encoding a fusion protein composed of a tested protein, the PDZ-protein TIP-1, and the transactivation domain of TNNC2 (referred to as ACT construct. Second, our system contains a PCR construct encoding a fusion protein composed of the DNA binding domain of GAL4 and the PDZ binding domain of rhotekin (referred to as the BIND construct. Third, a GAL4-responsive luciferase reporter is used to detect the reconstitution of a transcriptionally active BIND-ACT complex through the interaction of TIP-1 and rhotekin, which indicates the ability of the tested protein to translocate into the nucleus. We validated our method in a small-scale feasibility study by comparing it to green fluorescent protein (GFP fusion-based sub-cellular localization assays, sequence-based computational prediction of protein sub-cellular localization, and current sub-cellular localization data available from the literature for 22 gene products. Conclusion Our reporter-based system can rapidly screen gene products for their ability

  14. Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression

    International Nuclear Information System (INIS)

    Ivanov, Vladimir N.; Hei, Tom K.

    2006-01-01

    AP-1/cJun, NF-κB and STAT3 transcription factors control expression of numerous genes, which regulate critical cell functions including proliferation, survival and apoptosis. Sodium arsenite is known to suppress both the IKK-NF-κB and JAK2-STAT3 signaling pathways and to activate the MAPK/JNK-cJun pathways, thereby committing some cancers to undergo apoptosis. Indeed, sodium arsenite is an effective drug for the treatment of acute promyelocytic leukemia with little nonspecific toxicity. Malignant melanoma is highly refractory to conventional radio- and chemotherapy. In the present study, we observed strong effects of sodium arsenite treatment on upregulation of TRAIL-mediated apoptosis in human and mouse melanomas. Arsenite treatment upregulated surface levels of death receptors, TRAIL-R1 and TRAIL-R2, through increased translocation of these proteins from cytoplasm to the cell surface. Furthermore, activation of cJun and suppression of NF-κB by sodium arsenite resulted in upregulation of the endogenous TRAIL and downregulation of the cFLIP gene expression (which encodes one of the main anti-apoptotic proteins in melanomas) followed by cFLIP protein degradation and, finally, by acceleration of TRAIL-induced apoptosis. Direct suppression of cFLIP expression by cFLIP RNAi also accelerated TRAIL-induced apoptosis in these melanomas, while COX-2 suppression substantially increased levels of both TRAIL-induced and arsenite-induced apoptosis. In contrast, overexpression of permanently active AKTmyr inhibited TRAIL-mediated apoptosis via downregulation of TRAIL-R1 levels. Finally, AKT overactivation increased melanoma survival in cell culture and dramatically accelerated growth of melanoma transplant in vivo, highlighting a role of AKT suppression for effective anticancer treatment

  15. Japan Accelerator Conference

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    At the international level, the high energy accelerator scene evolves rapidly and the International Conference on High Energy Accelerators is where its strong pulse can best be felt. This year, the Conference was held for the first time in Japan, with the 14th meeting in the series having been hosted in August by the Japanese KEK National Laboratory for High Energy Physics, Tsukuba. The venue was a recognition of the premier accelerator physics and technology status achieved by this diligent nation

  16. Accelerator shielding benchmark problems

    International Nuclear Information System (INIS)

    Hirayama, H.; Ban, S.; Nakamura, T.

    1993-01-01

    Accelerator shielding benchmark problems prepared by Working Group of Accelerator Shielding in the Research Committee on Radiation Behavior in the Atomic Energy Society of Japan were compiled by Radiation Safety Control Center of National Laboratory for High Energy Physics. Twenty-five accelerator shielding benchmark problems are presented for evaluating the calculational algorithm, the accuracy of computer codes and the nuclear data used in codes. (author)

  17. Plasma particle accelerators

    International Nuclear Information System (INIS)

    Dawson, J.M.

    1988-01-01

    The Superconducting Supercollider (SSC) will require an 87-kilometer accelerator ring to boost particles to 40 TeV. The SSC's size is due in part to the fact that its operating principle is the same one that has dominated accelerator design for 50 years: it guides particles by means of magnetic fields and propels them by strong electric fields. If one were to build an equally powerful but smaller accelerator, one would need to increase the strength of the guiding and propelling fields. Actually, however, conventional technology may not be able to provide significant increases in field strength. There are two reasons. First, the forces from magnetic fields are becoming greater than the structural forces that hold a magnetic material together; the magnets that produce these fields would themselves be torn apart. Second, the energy from electric fields is reaching the energies that bind electrons to atoms; it would tear electrons from nuclei in the accelerator's support structures. It is the electric field problem that plasma accelerators can overcome. Plasma particle accelerators are based on the principle that particles can be accelerated by the electric fields generated within a plasma. Because the plasma has already been ionized, plasma particle accelerators are not susceptible to electron dissociation. They can in theory sustain accelerating fields thousands of times stronger that conventional technologies. So far two methods for creating plasma waves for accelerators have been proposed and tested: the wakefield and the beat wave. Although promising electric fields have been produced, more research is necessary to determine whether plasma particle accelerators can compete with the existing accelerators. 7 figs

  18. Wake field accelerators

    International Nuclear Information System (INIS)

    Wilson, P.B.

    1986-02-01

    In a wake field accelerator a high current driving bunch injected into a structure or plasma produces intense induced fields, which are in turn used to accelerate a trailing charge or bunch. The basic concepts of wake field acceleration are described. Wake potentials for closed cavities and periodic structures are derived, as are wake potentials on a collinear path with a charge distribution. Cylindrically symmetric structures excited by a beam in the form of a ring are considered

  19. CONFERENCE: Computers and accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1984-01-15

    In September of last year a Conference on 'Computers in Accelerator Design and Operation' was held in West Berlin attracting some 160 specialists including many from outside Europe. It was a Europhysics Conference, organized by the Hahn-Meitner Institute with Roman Zelazny as Conference Chairman, postponed from an earlier intended venue in Warsaw. The aim was to bring together specialists in the fields of accelerator design, computer control and accelerator operation.

  20. Japan Accelerator Conference

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1989-11-15

    At the international level, the high energy accelerator scene evolves rapidly and the International Conference on High Energy Accelerators is where its strong pulse can best be felt. This year, the Conference was held for the first time in Japan, with the 14th meeting in the series having been hosted in August by the Japanese KEK National Laboratory for High Energy Physics, Tsukuba. The venue was a recognition of the premier accelerator physics and technology status achieved by this diligent nation.

  1. CERN Accelerator School

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    The CERN Accelerator School (CAS) recently held its Advanced Accelerator Physics course in Greece on the island of Rhodes. Complementing the general course in Finland last year, this course was organized together with the University of Athens and NCSR. Demokritos. Accelerator specialists from Europe, CIS, Japan and USA followed two weeks of ''state-of-theart'' lectures designed to complete their education in the field

  2. Applying the accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Barbalat, Oscar

    1989-12-15

    Originally developed as tools for frontier physics, particle accelerators provide valuable spinoff benefits in applied research and technology. These accelerator applications are the subject of a biennial meeting in Denton, Texas, but the increasing activity in this field resulted this year (5-9 September) in the first European Conference on Accelerators in Applied Research and Technology, organized by K. Bethge of Frankfurt's Goethe University. The meeting reflected a wide range of applications - ion beam analysis, exploitation of nuclear microbeams, accelerator mass spectrometry, applications of photonuclear reactions, ion beam processing, synchrotron radiation for semiconductor technology, specialized technology.

  3. Laser-driven accelerators

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Several devices for using laser fields have been proposed and they can be classified in three broad categories - 'far-field' accelerators (such as the principle of inverse free electron lasers), 'media' accelerators (which, for example, use the inverse Cherenkov effect or laser-controlled plasma waves), and 'near-field' accelerators (using a loaded guiding structure such as cavities or gratings). These different approaches come from the fact that a particle cannot be accelerated by the absorption of single photons (because of momentum conservation) and thus some other element has to intervene. (orig./HSI).

  4. Illinois Accelerator Research Center

    Science.gov (United States)

    Kroc, Thomas K.; Cooper, Charlie A.

    The Illinois Accelerator Research Center (IARC) hosts a new accelerator development program at Fermi National Accelerator Laboratory. IARC provides access to Fermi's state-of-the-art facilities and technologies for research, development and industrialization of particle accelerator technology. In addition to facilitating access to available existing Fermi infrastructure, the IARC Campus has a dedicated 36,000 ft2 Heavy Assembly Building (HAB) with all the infrastructure needed to develop, commission and operate new accelerators. Connected to the HAB is a 47,000 ft2 Office, Technology and Engineering (OTE) building, paid for by the state, that has office, meeting, and light technical space. The OTE building, which contains the Accelerator Physics Center, and nearby Accelerator and Technical divisions provide IARC collaborators with unique access to world class expertise in a wide array of accelerator technologies. At IARC scientists and engineers from Fermilab and academia work side by side with industrial partners to develop breakthroughs in accelerator science and translate them into applications for the nation's health, wealth and security.

  5. High Gradient Accelerator Research

    International Nuclear Information System (INIS)

    Temkin, Richard

    2016-01-01

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  6. Interacting with accelerators

    International Nuclear Information System (INIS)

    Dasgupta, S.

    1994-01-01

    Accelerators are research machines which produce energetic particle beam for use as projectiles to effect nuclear reactions. These machines along with their services and facilities may occupy very large areas. The man-machine interface of accelerators has evolved with technological changes in the computer industry and may be partitioned into three phases. The present paper traces the evolution of man-machine interface from the earliest accelerators to the present computerized systems incorporated in modern accelerators. It also discusses the advantages of incorporating expert system technology for assisting operators. (author). 8 ref

  7. FFAGS for muon acceleration

    International Nuclear Information System (INIS)

    Berg, J. Scott; Kahn, Stephen; Palmer, Robert; Trbojevic, Dejan; Johnstone, Carol; Keil, Eberhard; Aiba, Masamitsu; Machida, Shinji; Mori, Yoshiharu; Ogitsu, Toru; Ohmori, Chihiro; Sessler, Andrew; Koscielniak, Shane

    2003-01-01

    Due to their finite lifetime, muons must be accelerated very rapidly. It is challenging to make the magnets ramp fast enough to accelerate in a synchrotron, and accelerating in a linac is very expensive. One can use a recirculating accelerator (like CEBAF), but one needs a different arc for each turn, and this limits the number of turns one can use to accelerate, and therefore requires significant amounts of RF to achieve the desired energy gain. An alternative method for muon acceleration is using a fixed field alternating gradient (FFAG) accelerator. Such an accelerator has a very large energy acceptance (a factor of two or three), allowing one to use the same arc with a magnetic field that is constant over time. Thus, one can in principle make as many turns as one can tolerate due to muon decay, therefore reducing the RF cost without increasing the arc cost. This paper reviews the current status of research into the design of FFAGs for muon acceleration. Several current designs are described and compared. General design considerations are also discussed

  8. Accelerator-based BNCT.

    Science.gov (United States)

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases. © 2013 Elsevier Ltd. All rights reserved.

  9. Applying the accelerator

    International Nuclear Information System (INIS)

    Barbalat, Oscar

    1989-01-01

    Originally developed as tools for frontier physics, particle accelerators provide valuable spinoff benefits in applied research and technology. These accelerator applications are the subject of a biennial meeting in Denton, Texas, but the increasing activity in this field resulted this year (5-9 September) in the first European Conference on Accelerators in Applied Research and Technology, organized by K. Bethge of Frankfurt's Goethe University. The meeting reflected a wide range of applications - ion beam analysis, exploitation of nuclear microbeams, accelerator mass spectrometry, applications of photonuclear reactions, ion beam processing, synchrotron radiation for semiconductor technology, specialized technology

  10. Superconducting linear accelerator cryostat

    International Nuclear Information System (INIS)

    Ben-Zvi, I.; Elkonin, B.V.; Sokolowski, J.S.

    1984-01-01

    A large vertical cryostat for a superconducting linear accelerator using quarter wave resonators has been developed. The essential technical details, operational experience and performance are described. (author)

  11. Tailoring particle translocation via dielectrophoresis in pore channels

    Science.gov (United States)

    Tanaka, Shoji; Tsutsui, Makusu; Theodore, Hu; Yuhui, He; Arima, Akihide; Tsuji, Tetsuro; Doi, Kentaro; Kawano, Satoyuki; Taniguchi, Masateru; Kawai, Tomoji

    2016-01-01

    Understanding and controlling electrophoretic motions of nanoscopic objects in fluidic channels are a central challenge in developing nanopore technology for molecular analyses. Although progress has been made in slowing the translocation velocity to meet the requirement for electrical detections of analytes via picoampere current measurements, there exists no method useful for regulating particle flows in the transverse directions. Here, we report the use of dielectrophoresis to manipulate the single-particle passage through a solid-state pore. We created a trap field by applying AC voltage between electrodes embedded in a low-aspect-ratio micropore. We demonstrated a traffic control of particles to go through center or near side surface via the voltage frequency. We also found enhanced capture efficiency along with faster escaping speed of particles by virtue of the AC-mediated electroosmosis. This method is compatible with nanopore sensing and would be widely applied for reducing off-axis effects to achieve single-molecule identification. PMID:27527126

  12. Physical insights into the blood-brain barrier translocation mechanisms

    Science.gov (United States)

    Theodorakis, Panagiotis E.; Müller, Erich A.; Craster, Richard V.; Matar, Omar K.

    2017-08-01

    The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood-brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB. Moreover, we discuss various numerical and simulation approaches used to study the BBB, and possible future directions based on multi-scale methods. We anticipate that this review will motivate multi-disciplinary research on the BBB aiming at the design of effective drug therapies.

  13. Translocation of labelled fertilizer nitrogen in soil columns

    International Nuclear Information System (INIS)

    Haunold, E.; Zvara, J.

    1975-01-01

    The translocation of 15 labeled ammonium and nitrate fertilizer was studied under normal weather conditions for two years in columns filled with different soils. At the end of the experimental period, which usually lasted for 9 months, between 5.9-10.3% of the ammonium fertilizer was leached out, 33.7-50.1% remained in the soil and 39.5-59.7% was lost as gas. For nitrate nitrogen the figures were: 22.6-47.3% leached out, 16.7-40% remaining in the soil, 12.7-60.0% lost as gas. The ammonium fertilizer moving through the soil interchanged with 1-13% of the soil nitrogen, the nitrate fertilizer with only 0.5-2%

  14. Real-time analysis of nitrogen translocation in plants

    International Nuclear Information System (INIS)

    Hayashi, Hiroaki

    2000-01-01

    Nitrogen absorbed by roots is transported to the leaves through xylem vessels and then retranslocated to the new leaves, such as root and storage organs through sieve tubes. It is very important to know how this nitrogen movement occurs in the plants and what mechanisms are involved in controlling this movement in order to increase the efficiency of fertilizer. In this experiments, 13 N and 15 N was used to detect the nitrogen circulation in plants, in combination with the technique for positron detection in real time and for collection of sap in sieve tubes and analysis of 15 N in it. By using 13 N, nitrogen movement from root to shoot was analyzed within 10 min after 13 N was applied to the roots. On the other hand, nitrogen retranslocation through sieve tubes was detected by the analysis of 15 N in the phloem sap over 6 hrs. All data suggest the dynamic translocation of nitrogen in rice plants. (author)

  15. Translocation of integron-associated resistance in a natural system: Acquisition of resistance determinants by Inc P and Inc W Plasmids from Salmonella enterica Typhimurium DT104

    DEFF Research Database (Denmark)

    Sandvang, Dorthe; Diggle, M.; Platt, D.J.

    2002-01-01

    to determinate the genetic content. Translocation to R751 and R388 was associated with the loss of the indigenous trimethoprim cassette to both plasmids and also acquisition of sulfonamide resistance by R751 and RP4::Tn7, which indicated movement of the 3' terminus of one or both of the DT104 integrons......Salmonella enterica Typhimurium DT104, 961368, a veterinary field isolate that encodes a chromosomal cluster of resistance genes as well as two integrons, was used to study the mobility of resistance cassettes (aadA2 and pse-1) and nonintegron-associated resistance determinants (chloramphenicol...... and tetracycline). A range of natural plasmids was used as targets for the translocation of resistance. Plasmids that acquired resistance from the DT104 chromosome were segregated by conjugation into Escherichia coli K12. Plasmids R751, R388, and RP4::Tn7 acquired several combinations of resistance determinant...

  16. Translocation t(11;14 (q13;q32 and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study

    Directory of Open Access Journals (Sweden)

    Ivyna Bong Pau Ni

    2012-09-01

    Full Text Available More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR-based translocation detection assay to detect BCL1/JH t(11;14 (q13;q32 in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14 (q13;q32 translocation (n=15 of 105. We found no significant correlation between this translocation with age (P=0.420, gender (P=0.317, ethnicity (P=0.066 or new/relapsed status of multiple myeloma (P=0.412 at 95% confidence interval level by x2 test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14(q13;q32 translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14 (q13;q32 translocation.

  17. Translocation of Cell Penetrating Peptide Engrafted Nanoparticles Across Skin Layers

    Science.gov (United States)

    Patlolla, Ram R; Desai, Pinaki; Belay, Kalayu; Singh, Mandip

    2010-01-01

    The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24 h, fluorescence was observed upto a depth of 120 µm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 µm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24 h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers. PMID:20413152

  18. Distribution and Translocation of 141Ce (III) in Horseradish

    Science.gov (United States)

    Guo, Xiaoshan; Zhou, Qing; Lu, Tianhong; Fang, Min; Huang, Xiaohua

    2007-01-01

    Background and Aims Rare earth elements (REEs) are used in agriculture and a large amount of them contaminate the environment and enter foods. The distribution and translocation of 141Ce (III) in horseradish was investigated in order to help understand the biochemical behaviour and toxic mechanism of REEs in plants. Method The distribution and translocation of 141Ce (III) in horseradish were investigated using autoradiography, liquid scintillation counting (LSC) and electron microscopic autoradiography (EMARG) techniques. The contents of 141Ce (III) and nutrient elements were analysed using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). Results The results from autoradiography and LSC indicated that 141Ce (III) could be absorbed by horseradish and transferred from the leaf to the leaf-stalk and then to the root. The content of 141Ce (III) in different parts of horseradish was as follows: root > leaf-stalk > leaf. The uptake rates of 141Ce (III) in horseradish changed with the different organs and time. The content of 141Ce (III) in developing leaves was greater than that in mature leaves. The results from EMARG indicated that 141Ce (III) could penetrate through the cell membrane and enter the mesophyll cells, being present in both extra- and intra-cellular deposits. The contents of macronutrients in horseradish were decreased by 141Ce (III) treatment. Conclusions 141Ce (III) can be absorbed and transferred between organs of horseradish with time, and the distribution was found to be different at different growth stages. 141Ce (III) can enter the mesophyll cells via apoplast and symplast channels or via plasmodesmata. 141Ce (III) can disturb the metabolism of macronutrients in horseradish. PMID:17921527

  19. Muscle contraction increases carnitine uptake via translocation of OCTN2

    International Nuclear Information System (INIS)

    Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

    2012-01-01

    Highlights: ► Muscle contraction augmented carnitine uptake into rat hindlimb muscles. ► An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. ► Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. ► OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL uptake ) of L-[ 3 H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL uptake of [ 14 C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL uptake of L-[ 3 H]carnitine in the contracting muscles increased 1.4–1.7-fold as compared to that in the contralateral resting muscles (p uptake of [ 14 C]IAP was much higher than that of L-[ 3 H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  20. The Enzymology of Protein Translocation across the Escherichia coli Plasma Membrane

    NARCIS (Netherlands)

    Wickner, William; Driessen, Arnold J.M.; Hartl, Franz-Ulrich

    1991-01-01

    Converging physiological, genetic, and biochemical studies have established the salient features of preprotein translocation across the plasma membrane of Escherichia coli. Translocation is catalyzed by two proteins, a soluble chaperone and a membrane-bound translocase. SecB, the major chaperone for

  1. Most Uv-Induced Reciprocal Translocations in SORDARIA MACROSPORA Occur in or near Centromere Regions.

    Science.gov (United States)

    Leblon, G; Zickler, D; Lebilcot, S

    1986-02-01

    In fungi, translocations can be identified and classified by the patterns of ascospore abortion in asci from crosses of rearrangement x normal sequence. Previous studies of UV-induced rearrangements in Sordaria macrospora revealed that a major class (called type III) appeared to be reciprocal translocations that were anomalous in producing an unexpected class of asci with four aborted ascospores in bbbbaaaa linear sequence (b = black; a = abortive). The present study shows that the anomalous type III rearrangements are, in fact, reciprocal translocations having both breakpoints within or adjacent to centromeres and that bbbbaaaa asci result from 3:1 disjunction from the translocation quadrivalent.-Electron microscopic observations of synaptonemal complexes enable centromeres to be visualized. Lengths of synaptonemal complexes lateral elements in translocation quadrivalents accurately reflect chromosome arm lengths, enabling breakpoints to be located reliably in centromere regions. All genetic data are consistent with the behavior expected of translocations with breakpoints at centromeres.-Two-thirds of the UV-induced reciprocal translocations are of this type. Certain centromere regions are involved preferentially. Among 73 type-III translocations, there were but 13 of the 21 possible chromosome combinations and 20 of the 42 possible combinations of chromosome arms.

  2. Comparative study of the reciprocal translocation rate in spermatocytes after irradiation of newborn and adult mice

    International Nuclear Information System (INIS)

    Pomerantseva, M.D.

    1978-01-01

    The yield of reciprocal translocations was investigated in spermatocytes of the CBA male mice irradiated immediately after their brith or after the irradiation of the stem spermatogonia at the age of 3 months. The irradiation doses were 100, 200, 400 R X-rays 300 R gamma-rays 60 Co. The yield of translocations in both groups was the same

  3. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria

    KAUST Repository

    Houben, Diane; Demangel, Caroline; Van Ingen, Jakko; Perez, Jorge; Baldeó n, Lucy R.; Abdallah, Abdallah; Caleechurn, Laxmee; Bottai, Daria; Van Zon, Maaike; De Punder, Karin; Van Der Laan, Tridia; Kant, Arie; Bossers-De Vries, Ruth; Willemsen, Peter Th J; Bitter, Wilbert M.; Van Soolingen, Dick; Brosch, Roland; Van Der Wel, Nicole N.; Peters, Peter J.

    2012-01-01

    Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. As yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. In this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacterial virulence. Pathogenic, patient-derived mycobacteria species were found to translocate to the cytosol, while non-pathogenic species did not. We were further able to link cytosolic translocation with pathogenicity by introducing the ESX-1 (type VII) secretion system into the non-virulent, exclusively phagolysosomal Mycobacterium bovis BCG. Furthermore, we show that translocation is dependent on the C-terminus of the early-secreted antigen ESAT-6. The C-terminal truncation of ESAT-6 was shown to result in attenuation in mice, again linking translocation to virulence. Together, these data demonstrate the molecular mechanism facilitating translocation of mycobacteria. The ability to translocate from the phagolysosome to the cytosol is with this study proven to be biologically significant as it determines mycobacterial virulence. © 2012 Blackwell Publishing Ltd.

  4. Comparative sensitivity of photosynthesis and translocation to sulfur dioxide damage in Phaseolus vulgaris L

    International Nuclear Information System (INIS)

    Noyes, R.D.

    1978-01-01

    The inhibiting effect of sulfur dioxide on photosynthesis in a mature bean leaf and, simultaneously, on the rate of carbohydrate translocation from this same leaf has been examined. The results show a reduction of 0, 13, and 73% in net photosynthesis and 39, 44, and 69% in translocation, at concentrations of 0.1, 1, and 3 ppm sulfur dioxide, respectively. The inhibition of translocation at 0.1 ppm sulfur dioxide without any accompanying inhibition of net photosynthesis indicates that translocation is considerably more sensitive to sulfur dioxide damage. The mechanism of translocation inhibition at 1 ppm sulfur dioxide or less is shown to be independent of photosynthetic inhibition. Whereas, it is suggested that at higher concentrations significant inhibition of photosynthesis causes an additive reduction of translocation due to reduced levels of transport sugars. Autoradiograms of 14 C-labeled source leaves indicate that one possible mechanism of sulfur dioxide damage to translocation is the inhibition of sieve-tube loading. Inhibition of phloem translocation at common ambient levels (0.1 ppm) of sulfur dioxide is important to the overall growth and yield of major agricultural crops sensitive to sulfur dioxide

  5. Live birth from a patient with a three-way balanced translocation t(5 ...

    African Journals Online (AJOL)

    Objectives: Array comparative genomic hybridisation (array-CGH) was used to screen embryos for chromosome imbalances. Methods: Embryo biopsy, preimplantation genetic diagnosis using a 24sure+ kit to detect translocations in embryos. Results: Of 10 embryos tested, 2 were found to have an unbalanced translocation, ...

  6. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria

    KAUST Repository

    Houben, Diane

    2012-05-08

    Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. As yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. In this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacterial virulence. Pathogenic, patient-derived mycobacteria species were found to translocate to the cytosol, while non-pathogenic species did not. We were further able to link cytosolic translocation with pathogenicity by introducing the ESX-1 (type VII) secretion system into the non-virulent, exclusively phagolysosomal Mycobacterium bovis BCG. Furthermore, we show that translocation is dependent on the C-terminus of the early-secreted antigen ESAT-6. The C-terminal truncation of ESAT-6 was shown to result in attenuation in mice, again linking translocation to virulence. Together, these data demonstrate the molecular mechanism facilitating translocation of mycobacteria. The ability to translocate from the phagolysosome to the cytosol is with this study proven to be biologically significant as it determines mycobacterial virulence. © 2012 Blackwell Publishing Ltd.

  7. Preimplantation genetic diagnosis by fluorescence in situ hybridization of reciprocal and Robertsonian translocations

    Directory of Open Access Journals (Sweden)

    Chun-Kai Chen

    2014-03-01

    Conclusion: There is a trend whereby the outcome for Robertsonian translocation group carriers is better than that for reciprocal translocation group carriers. Aneuploidy screening may possibly be added in order to improve the outcome, especially for individuals with an advanced maternal age. The emergence of an array-based technology should help improve this type of analysis.

  8. Comparison of experimentally determined translocation of 134Cs in potatoes with the radioecological code CHECOSYS

    International Nuclear Information System (INIS)

    Riesen, T.; Egli, J.; Andres, R.

    1997-01-01

    The verification and adoption of radioecological models is a continuous process. Greenhouse trials on the translocation of radiocaesium from leaves to potato tubers showed a 4-12 times higher translocation rate compared to the radioecological code CHECOSYS. The possible reasons for the differences are discussed. (author) 1 tab., 3 refs

  9. Translocations of chromosome end-segments and facultative heterochromatin promote meiotic ring formation in evening primroses.

    Science.gov (United States)

    Golczyk, Hieronim; Massouh, Amid; Greiner, Stephan

    2014-03-01

    Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories.

  10. Accelerator Modeling with MATLAB Accelerator Toolbox

    International Nuclear Information System (INIS)

    2002-01-01

    This paper introduces Accelerator Toolbox (AT)--a collection of tools to model storage rings and beam transport lines in the MATLAB environment. The objective is to illustrate the flexibility and efficiency of the AT-MATLAB framework. The paper discusses three examples of problems that are analyzed frequently in connection with ring-based synchrotron light sources

  11. Identification of 2nd chromosome region translocated onto the W chromosome by RFLP with EST-cDNA clones in the Gensei-kouken strains of the mulberry silkworm, Bombyx mori L

    Directory of Open Access Journals (Sweden)

    Sivaramakurup Sreekumar

    2010-01-01

    Full Text Available In silkworms, sex-limited strains are either obtained spontaneously or induced by X-rays or gamma rays. When a fragment of an autosome carrying a dominant allele of those genes responsible for certain characters is translocated onto a W chromosome, the female of the successive generations will express these phenotypic characters and sex discrimination can be facilitated. Gensei-kouken strains are sex-limited strains of silkworms developed by irradiating the pupae with gamma rays, by which a portion of the second chromosome is translocated onto the W chromosome. In these improved strains, the females are yellow-blooded and spin yellow cocoons. By using the EST-cDNA clones mapped on the Z chromosome, we identified the sex according to the polymorphic banding pattern or intensity of the signals. Furthermore, by using the clones on the second chromosome, the region of the second chromosome translocated onto the W chromosome was also defined. In both the A95 and A 96 strains selected for the present study, only the mid-portion of the second chromosome was translocated. The differences in length of the fragments translocated in these strains are discussed.

  12. Meiotic chromosomal translocations in male mice induced by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

    1983-01-01

    The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

  13. Translocation of 14C in adventitiously rooting Calluna vulgaris on peat

    International Nuclear Information System (INIS)

    Wallen, B.

    1983-01-01

    Seasonal variation in translocation of 14 C-labelled assimilates showed that 14 C-translocation within woody tissue was mainly limited to the phytomass produced during the last eight years. Independent of overgrowth of basal stem segments or decumbent sections by Sphagnum, or of subsequent adventitious rooting, the allocation followed a negative exponential from the assimilating units down the plant, and reached negligible values in 8-yr-old wood. Translocation to fine roots was however, mainly restricted to the shallow roots. Already at ca. 10 cm depth, the fine roots contained only about 5% of the concentration in the fine roots in the surface. During spring and autumn translocation to below ground parts dominated. During summer the main translocation was within the above ground green shoots and flowers. Here most of the allocated 14 C was irreversibly bound. There were only weak indications of accumulation of moblie 14 C-compounds in the woody parts near the soil surface. (author)

  14. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

    Science.gov (United States)

    Shan, Liang; Siliciano, Robert F.

    2014-01-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  15. Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) but not PPAR-interacting protein (PRIP) is required for nuclear translocation of constitutive androstane receptor in mouse liver

    International Nuclear Information System (INIS)

    Guo Dongsheng; Sarkar, Joy; Ahmed, Mohamed R.; Viswakarma, Navin; Jia Yuzhi; Yu Songtao; Sambasiva Rao, M.; Reddy, Janardan K.

    2006-01-01

    The constitutive androstane receptor (CAR) regulates transcription of phenobarbital-inducible genes that encode xenobiotic-metabolizing enzymes in liver. CAR is localized to the hepatocyte cytoplasm but to be functional, it translocates into the nucleus in the presence of phenobarbital-like CAR ligands. We now demonstrate that adenovirally driven EGFP-CAR, as expected, translocates into the nucleus of normal wild-type hepatocytes following phenobarbital treatment under both in vivo and in vitro conditions. Using this approach we investigated the role of transcription coactivators PBP and PRIP in the translocation of EGFP-CAR into the nucleus of PBP and PRIP liver conditional null mouse hepatocytes. We show that coactivator PBP is essential for nuclear translocation of CAR but not PRIP. Adenoviral expression of both PBP and EGFP-CAR restored phenobarbital-mediated nuclear translocation of exogenously expressed CAR in PBP null livers in vivo and in PBP null primary hepatocytes in vitro. CAR translocation into the nucleus of PRIP null livers resulted in the induction of CAR target genes such as CYP2B10, necessary for the conversion of acetaminophen to its hepatotoxic intermediate metabolite, N-acetyl-p-benzoquinone imine. As a consequence, PRIP-deficiency in liver did not protect from acetaminophen-induced hepatic necrosis, unlike that exerted by PBP deficiency. These results establish that transcription coactivator PBP plays a pivotal role in nuclear localization of CAR, that it is likely that PBP either enhances nuclear import or nuclear retention of CAR in hepatocytes, and that PRIP is redundant for CAR function

  16. Santa Fe Accelerator Conference

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    The 10th USA National Particle Accelerator Conference was hosted this year by the Los Alamos National Laboratory in Santa Fe from 21-23 March. It was a resounding success in emphasizing the ferment of activity in the accelerator field. About 900 people registered and about 500 papers were presented in invited and contributed talks and poster sessions

  17. Relativistic Shock Acceleration

    International Nuclear Information System (INIS)

    Duffy, P.; Downes, T.P.; Gallant, Y.A.; Kirk, J.G.

    1999-01-01

    In this paper we briefly review the basic theory of shock waves in relativistic hydrodynamics and magneto-hydrodynamics, emphasising some astrophysically interesting cases. We then present an overview of the theory of particle acceleration at such shocks describing the methods used to calculate the spectral indices of energetic particles. Recent results on acceleration at ultra-relativistic shocks are discussed. (author)

  18. CERN Accelerator School

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-01-15

    The CERN Accelerator School (CAS) offers a regular course on general accelerator physics. The first basic course was given in September 1984 at Orsay, France, and last September the advanced course was jointly organized by CAS, Oxford's Nuclear Physics Laboratory and the Rutherford Appleton Laboratory, and held at The Queen's College, Oxford.

  19. Accelerator for nuclear transmutation

    International Nuclear Information System (INIS)

    Schapira, J.P.

    1984-01-01

    A review on nuclear transmutation of radioactive wastes using particle accelerators is given. Technical feasibility, nuclear data, costs of various projects are discussed. It appears that one high energy accelerator (1500 MeV, 300 mA proton) could probably handle the amount of actinides generated by the actual French nuclear program [fr

  20. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960's to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore's Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail

  1. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1997-01-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at Lawrence Livermore National Laboratory (LLNL) from the early 1960s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400-ns pulses. The Advanced Test Accelerator (ATA) built at Livermore close-quote s Site 300 produced 10,000-Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and Lawrence Berkeley National Laboratory (LBNL). This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high-current, short-pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail. copyright 1997 American Institute of Physics

  2. Hamburg Accelerator Conference (2)

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Edmund J.N. [CERN Accelerator School (Switzerland)

    1992-11-15

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). The HEACC Conference traditionally reviews the status of all major accelerator projects whether they are already running like clockwork, still in the construction phase, or waiting impatiently for financial approval.

  3. Charged particle accelerator

    International Nuclear Information System (INIS)

    Arakawa, Kazuo.

    1969-01-01

    An accelerator is disclosed having a device which permits the electrodes of an accelerator tube to be readily conditioned in an uncomplicated manner before commencing operation. In particle accelerators, it is necessary to condition the accelerator electrodes before a stable high voltage can be applied. Large current accelerators of the cockcroft-walton type require a complicated manual operation which entails applying to the electrodes a low voltage which is gradually increased to induce a vacuum discharge and then terminated. When the discharge attains an extremely low level, the voltage is again impressed and again raised to a high value in low current type accelerators, a high voltage power supply charges the electrodes once to induce discharge followed by reapplying the voltage when the vacuum discharge reaches a low level, according to which high voltage is automatically applied. This procedure, however, requires that the high voltage power supply be provided with a large internal resistance to limit the current to within several milliamps. The present invention connects a high voltage power supply and an accelerator tube through a discharge current limiting resistor wired in parallel with a switch. Initially, the switch is opened enabling the power supply to impress a voltage limited to a prescribed value by a suitably chosen resistor. Conditioning is effected by allowing the voltage between electrodes to increase and is followed by closing the switch through which high voltage is applied directly to the accelerator for operation. (K.J. Owens)

  4. Asia honours accelerator physicists

    CERN Multimedia

    2010-01-01

    "Steve Meyers of Cern and Jie Wei of Beijing's Tsinghua University are the first recipients of a new prize for particle physics. The pair were honoured for their contributions to numerous particle-accelerator projects - including Cern's Large Hadron Collider - by the Asian Committee for Future Accelerators (ACFA)..." (1 paragraph)

  5. Accelerators Beyond The Tevatron?

    Energy Technology Data Exchange (ETDEWEB)

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  6. CERN Accelerator School

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    The CERN Accelerator School (CAS) offers a regular course on general accelerator physics. The first basic course was given in September 1984 at Orsay, France, and last September the advanced course was jointly organized by CAS, Oxford's Nuclear Physics Laboratory and the Rutherford Appleton Laboratory, and held at The Queen's College, Oxford

  7. Thoughts on accelerator tubes

    International Nuclear Information System (INIS)

    Larson, J.D.

    1978-01-01

    A brief, subjective review is given of mechanisms that may be limiting electrostatic accelerator tubes to present levels of performance. Suggestions are made for attacking these limitations with the purpose of stimulating the thinking of designers and users of electrostatic accelerators

  8. KEK digital accelerator

    Directory of Open Access Journals (Sweden)

    T. Iwashita

    2011-07-01

    Full Text Available The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  9. Thoughts of accelerator tubes

    International Nuclear Information System (INIS)

    Larson, J.D.

    1977-01-01

    A brief, subjective review is given of mechanisms that may be limiting electrostatic accelerator tubes to present levels of performance. Suggestions are made for attacking these limitations with the purpose of stimulating the thinking of designers and users of electrostatic accelerators

  10. Racetrack linear accelerators

    International Nuclear Information System (INIS)

    Rowe, C.H.; Wilton, M.S. de.

    1979-01-01

    An improved recirculating electron beam linear accelerator of the racetrack type is described. The system comprises a beam path of four straight legs with four Pretzel bending magnets at the end of each leg to direct the beam into the next leg of the beam path. At least one of the beam path legs includes a linear accelerator. (UK)

  11. Linear Accelerator (LINAC)

    Science.gov (United States)

    ... uses microwave technology (similar to that used for radar) to accelerate electrons in a part of the accelerator called the "wave guide," then allows ... risk of accidental exposure is extremely low. top of page This page was ... No Please type your comment or suggestion into the following text ...

  12. Hamburg Accelerator Conference (2)

    International Nuclear Information System (INIS)

    Wilson, Edmund J.N.

    1992-01-01

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). The HEACC Conference traditionally reviews the status of all major accelerator projects whether they are already running like clockwork, still in the construction phase, or waiting impatiently for financial approval

  13. Optimization of accelerator control

    International Nuclear Information System (INIS)

    Vasiljev, N.D.; Mozin, I.V.; Shelekhov, V.A.; Efremov, D.V.

    1992-01-01

    Expensive exploitation of charged particle accelerators is inevitably concerned with requirements of effectively obtaining of the best characteristics of accelerated beams for physical experiments. One of these characteristics is intensity. Increase of intensity is hindered by a number of effects, concerned with the influence of the volume charge field on a particle motion dynamics in accelerator's chamber. However, ultimate intensity, determined by a volume charge, is almost not achieved for the most of the operating accelerators. This fact is caused by losses of particles during injection, at the initial stage of acceleration and during extraction. These losses are caused by deviations the optimal from real characteristics of the accelerating and magnetic system. This is due to a number of circumstances, including technological tolerances on structural elements of systems, influence of measuring and auxiliary equipment and beam consumers' installations, placed in the closed proximity to magnets, and instability in operation of technological systems of accelerator. Control task consists in compensation of deviations of characteristics of magnetic and electric fields by optimal selection of control actions. As for technical means, automatization of modern accelerators allows to solve optimal control problems in real time. Therefore, the report is devoted to optimal control methods and experimental results. (J.P.N.)

  14. Accelerator breeder concept

    International Nuclear Information System (INIS)

    Bartholomew, G.A.; Fraser, J.S.; Garvey, P.M.

    1978-10-01

    The principal components and functions of an accelerator breeder are described. The role of the accelerator breeder as a possible long-term fissile production support facility for CANDU (Canada Deuterium Uranium) thorium advanced fuel cycles and the Canadian research and development program leading to such a facility are outlined. (author)

  15. Semiconductor acceleration sensor

    Science.gov (United States)

    Ueyanagi, Katsumichi; Kobayashi, Mitsuo; Goto, Tomoaki

    1996-09-01

    This paper reports a practical semiconductor acceleration sensor especially suited for automotive air bag systems. The acceleration sensor includes four beams arranged in a swastika structure. Two piezoresistors are formed on each beam. These eight piezoresistors constitute a Wheatstone bridge. The swastika structure of the sensing elements, an upper glass plate and a lower glass plate exhibit the squeeze film effect which enhances air dumping, by which the constituent silicon is prevented from breakdown. The present acceleration sensor has the following features. The acceleration force component perpendicular to the sensing direction can be cancelled. The cross-axis sensitivity is less than 3 percent. And, the erroneous offset caused by the differences between the thermal expansion coefficients of the constituent materials can be canceled. The high aspect ratio configuration realized by plasma etching facilitates reducing the dimensions and improving the sensitivity of the acceleration sensor. The present acceleration sensor is 3.9 mm by 3.9 mm in area and 1.2 mm in thickness. The present acceleration sensor can measure from -50 to +50 G with sensitivity of 0.275 mV/G and with non-linearity of less than 1 percent. The acceleration sensor withstands shock of 3000 G.

  16. Molecular ion acceleration using tandem accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Yuichi; Mizuhashi, Kiyoshi; Tajima, Satoshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1996-12-01

    In TIARA compound beam radiation system, cluster beams have been produced using 3 MV tandem accelerator (9SDH-2) to supply them to various radiation on injection experiments. Till now, productions of C{sub 2-8}, Si{sub 2-4} and O{sub 2} and their accelerations up to 6 MeV have been succeeded. This study aimed at production and acceleration of B{sub 2-4} and LiF. Anion clusters were produced using the conventional ion source of cesium sputter type. The proportions of atoms, molecules and clusters elicited from the ion source were varied depending on the material`s properties and the operating conditions of ion source such as sample temperature, sputter voltage and the shape of sample. The anion clusters were accelerated toward the high voltage terminal in the center of tandem accelerator, leading to cations through losing their electrons by the collision to N{sub 2} gas in a charge conversion cell at the terminal. Positively charged cluster ions could be obtained by modulating the pressure of N{sub 2} gas. Thus, B{sub 2} (64 nA), B{sub 3} (4.4 nA) and B{sub 4} (2.7 nA) have been produced and their maximum survival probabilities were higher than those of carbon or silicon clusters. In addition, the relationship between beam current and gas pressure was investigated for Bn (n = 2-4) and LiF. (M.N.)

  17. Plasma based accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, Allen [Max-Planck-Institut fuer Physik, Muenchen (Germany)

    2015-05-01

    The concept of laser-induced plasma wakefields as a technique to accelerate charged particles was introduced 35 years ago as a means to go beyond the accelerating gradients possible with metallic cavities supporting radio frequency electromagnetic fields. Significant developments in laser technology have made possible the pulse intensity needed to realize this concept, and rapid progress is now underway in the realization of laser-driven plasma wakefield acceleration. It has also been realized that similar accelerating gradients can be produced by particle beams propagating in plasmas, and experimental programs have also been undertaken to study this possibility. Positive results have been achieved with electron-driven plasma wakefields, and a demonstration experiment with proton-driven wakefields is under construction at CERN. The concepts behind these different schemes and their pros and cons are described, as well as the experimental results achieved. An outlook for future practical uses of plasma based accelerators will also be given.

  18. TIARA electrostatic accelerator facility

    International Nuclear Information System (INIS)

    Tajima, Satoshi; Takada, Isao; Mizuhashi, Kiyoshi; Uno, Sadanori; Ohkoshi, Kiyonori; Nakajima, Yoshinori; Saitoh, Yuichi; Ishii, Yasuyuki; Kamiya, Tomihiro

    1996-07-01

    In order to promote the Advanced Radiation Technology Project, Japan Atomic Energy Research Institute constructed TIARA facility composed of four ion accelerators at Takasaki Radiation Chemistry Research Establishment for the period from 1988 to 1993. A 3MV tandem accelerator and an AVF cycrotron were completed in 1991 as the first phase of the construction, and a 3MV single-ended accelerator and a 400kV ion implanter were completed in 1993 as the second phase. Three electrostatic accelerators, the tandem, the single-ended and the implanter, were installed in the Multiple-beam facility of TIARA and have been operated for various experiments with using single, dual and triple beams without any serious trouble. This report describes the constructive works, machine performances, control systems, safety systems and accessory equipments of the electrostatic accelerators. (author)

  19. 2016 Accelerators meeting

    International Nuclear Information System (INIS)

    Spiro, Michel; Revol, Jean-Luc; Biarrotte, Jean-Luc; Napoly, Olivier; Jardin, Pascal; Chautard, Frederic; Thomas, Jean Charles; Petit, Eric

    2016-09-01

    The Accelerators meeting is organised every two years by the Accelerators division of the French Society of Physics (SFP). It brings together about 50 participants during a one-day meeting. The morning sessions are devoted to scientific presentations while the afternoon is dedicated to technical visits of facilities. This document brings together the available presentations (slides): 1 - Presentation of the Ganil - Grand accelerateur national d'ions lourds/Big national heavy-ion accelerator, Caen (Jardin, Pascal); 2 - Presentation of the Accelerators division of the French Society of Physics (Revol, Jean-Luc); 3 - Forward-looking and Prospective view (Napoly, Olivier); 4 - Accelerators at the National Institute of Nuclear and particle physics, situation, Forward-looking and Prospective view (Biarrotte, Jean-Luc); 5 - GANIL-SPIRAL2, missions and goals (Thomas, Jean Charles); 6 - The SPIRAL2 project (Petit, Eric)

  20. Collinear wake field acceleration

    International Nuclear Information System (INIS)

    Bane, K.L.F.; Chen, P.; Wilson, P.B.

    1985-04-01

    In the Voss-Weiland scheme of wake field acceleration a high current, ring-shaped driving bunch is used to accelerate a low current beam following along on axis. In such a structure, the transformer ratio, i.e., the ratio of maximum voltage that can be gained by the on-axis beam and the voltage lost by the driving beam, can be large. In contrast, it has been observed that for an arrangement in which driving and driven bunches follow the same path, and where the current distribution of both bunches is gaussian, the transformer ratio is not normally greater than two. This paper explores some of the possibilities and limitations of a collinear acceleration scheme. In addition to its application to wake field acceleration in structures, this study is also of interest for the understanding of the plasma wake field accelerator. 11 refs., 4 figs