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Sample records for chromosome instability results

  1. Telomere dysfunction and chromosome instability

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    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  2. Radiation-induced chromosomal instability

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    Ritter, S. [GSI, Biophysics, Darmstadt (Germany)

    1999-03-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/{mu}m) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  3. Early embryonic chromosome instability results in stable mosaic pattern in human tissues.

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    Hasmik Mkrtchyan

    Full Text Available The discovery of copy number variations (CNV in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations.

  4. Delayed chromosomal instability induced by DNA damage.

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    Marder, B A; Morgan, W. F.

    1993-01-01

    DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamster-human hybrid cell line by means of fluorescence in situ hybridization. We examined ...

  5. Chromosomal instability determines taxane response

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    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C.; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells....

  6. Radiation induced chromosome instability in human fibroblasts

    International Nuclear Information System (INIS)

    Evidence has been arising that some biological effects can manifest many cell divisions after irradiation. We have demonstrated that de novo chromosome instability can be detected 10- 15 mean population doubling after heavy ion irradiations. This chromosome instability is characterized by end to end fusions between specific chromosomes. The specificity of the instability may differ from one donor to another but for the same donor, the same instability should be observed after irradiation, during the senescence process and after SV40 transfection (before crisis). In irradiated primary culture fibroblasts, the expression of the delayed chromosomal instability lasts for several cell divisions without inducing cell death. Several rounds of fusions- breakage-fusions can be performed and unbalanced clones emerge (gain or loss of chromosomes with the shorter telomeres would become unstable first.. The difference in the chromosomal instability among donors could be due to a polymorphism in telomere lengths. This could induce large variation in long term response to irradiation among individuals. (author)

  7. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

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    Bakheet, Saleh A.; Attia, Sabry M.

    2011-01-01

    We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cell...

  8. Chromosomal instability determines taxane response.

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    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang; Howell, Michael; Ried, Thomas; Habermann, Jens K; Auer, Gert; Brenton, James D; Szallasi, Zoltan; Downward, Julian

    2009-05-26

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival" genes is associated with poor outcome in estrogen receptor-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents. PMID:19458043

  9. Cancer chromosomal instability: therapeutic and diagnostic challenges

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    McGranahan, Nicholas; Burrell, Rebecca A.; Endesfelder, David; Novelli, Marco R; Swanton, Charles

    2012-01-01

    This review provides a much-needed translational perspective into the issue of aneuploidy and chromosomal instability, discussing the prognostic value of CIN assessment in human tumours, methods to analyze it and how it could be therapeutically targeted.

  10. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

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    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  11. A computer simulation of chromosomal instability

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    Goodwin, E.; Cornforth, M.

    The transformation of a normal cell into a cancerous growth can be described as a process of mutation and selection occurring within the context of clonal expansion. Radiation, in addition to initial DNA damage, induces a persistent and still poorly understood genomic instability process that contributes to the mutational burden. It will be essential to include a quantitative description of this phenomenon in any attempt at science-based risk assessment. Monte Carlo computer simulations are a relatively simple way to model processes that are characterized by an element of randomness. A properly constructed simulation can capture the essence of a phenomenon that, as is often the case in biology, can be extraordinarily complex, and can do so even though the phenomenon itself is incompletely understood. A simple computer simulation of one manifestation of genomic instability known as chromosomal instability will be presented. The model simulates clonal expansion of a single chromosomally unstable cell into a colony. Instability is characterized by a single parameter, the rate of chromosomal rearrangement. With each new chromosome aberration, a unique subclone arises (subclones are defined as having a unique karyotype). The subclone initially has just one cell, but it can expand with cell division if the aberration is not lethal. The computer program automatically keeps track of the number of subclones within the expanding colony, and the number of cells within each subclone. Because chromosome aberrations kill some cells during colony growth, colonies arising from unstable cells tend to be smaller than those arising from stable cells. For any chosen level of instability, the computer program calculates the mean number of cells per colony averaged over many runs. These output should prove useful for investigating how such radiobiological phenomena as slow growth colonies, increased doubling time, and delayed cell death depend on chromosomal instability. Also of

  12. Cancer chromosomal instability: therapeutic and diagnostic challenges.

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    McGranahan, Nicholas; Burrell, Rebecca A; Endesfelder, David; Novelli, Marco R; Swanton, Charles

    2012-06-01

    Chromosomal instability (CIN)-which is a high rate of loss or gain of whole or parts of chromosomes-is a characteristic of most human cancers and a cause of tumour aneuploidy and intra-tumour heterogeneity. CIN is associated with poor patient outcome and drug resistance, which could be mediated by evolutionary adaptation fostered by intra-tumour heterogeneity. In this review, we discuss the clinical consequences of CIN and the challenges inherent to its measurement in tumour specimens. The relationship between CIN and prognosis supports assessment of CIN status in the clinical setting and suggests that stratifying tumours according to levels of CIN could facilitate clinical risk assessment. PMID:22595889

  13. Chromosomal instability determines taxane sensitivity - supplementary materials

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    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C.; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells....

  14. Radiation-induced chromosomal instability in human mammary epithelial cells

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    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  15. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

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    Saleh A. Bakheet

    2011-01-01

    Full Text Available We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients.

  16. The TP53 dependence of radiation-induced chromosome instability in human lymphoblastoid cells

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    Schwartz, Jeffrey L.; Jordan, Robert; Evans, Helen H.; Lenarczyk, Marek; Liber, Howard

    2003-01-01

    The dose and TP53 dependence for the induction of chromosome instability were examined in cells of three human lymphoblastoid cell lines derived from WIL2 cells: TK6, a TP53-normal cell line, NH32, a TP53-knockout created from TK6, and WTK1, a WIL2-derived cell line that spontaneously developed a TP53 mutation. Cells of each cell line were exposed to (137)Cs gamma rays, and then surviving clones were isolated and expanded in culture for approximately 35 generations before the frequency and characteristics of the instability were analyzed. The presence of dicentric chromosomes, formed by end-to-end fusions, served as a marker of chromosomal instability. Unexposed TK6 cells had low levels of chromosomal instability (0.002 +/- 0.001 dicentrics/cell). Exposure of TK6 cells to doses as low as 5 cGy gamma rays increased chromosome instability levels nearly 10-fold to 0.019 +/- 0.008 dicentrics/cell. There was no further increase in instability levels beyond 5 cGy. In contrast to TK6 cells, unexposed cultures of WTK1 and NH32 cells had much higher levels of chromosome instability of 0.034 +/- 0.007 and 0.041 +/- 0.009, respectively, but showed little if any effect of radiation on levels of chromosome instability. The results suggest that radiation exposure alters the normal TP53-dependent cell cycle checkpoint controls that recognize alterations in telomere structure and activate apoptosis.

  17. Mechanisms of ring chromosome formation, ring instability and clinical consequences

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    Guilherme Roberta S

    2011-12-01

    Full Text Available Abstract Background The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Methods Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification and FISH (Fluorescent in situ Hybridization. Results The ring chromosomes of patients I to XIV were determined to be, respectively: r(3(p26.1q29, r(4(p16.3q35.2, r(10(p15.3q26.2, r(10(p15.3q26.13, r(13(p13q31.1, r(13(p13q34, r(14(p13q32.33, r(15(p13q26.2, r(18(p11.32q22.2, r(18(p11.32q21.33, r(18(p11.21q23, r(22(p13q13.33, r(22(p13q13.2, and r(22(p13q13.2. These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV; a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II; a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X; fusion of two subtelomeric regions (patient VII; and telomere-telomere fusion (patient XII. Thus, the r(14 and one r(22 can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI with r(13 showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV. Conclusions We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14 and r(22.

  18. The Relationship Between Spontaneous Telomere Loss and Chromosome Instability in a Human Tumor Cell Line

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    Bijan Fouladi

    2000-01-01

    Full Text Available Chromosome instability plays an important role in cancer by promoting the alterations in the genome required for tumor cell progression. The loss of telomeres that protect the ends of chromosomes and prevent chromosome fusion has been proposed as one mechanism for chromosome instability in cancer cells, however, there is little direct evidence to support this hypothesis. To investigate the relationship between spontaneous telomere loss and chromosome instability in human cancer cells, clones of the EJ-30 tumor cell line were isolated in which a herpes simplex virus thymidine kinase (HSV-tk gene was integrated immediately adjacent to a telomere. Selection for HSV-tkdeficient cells with ganciclovir demonstrated a high rate of loss of the end these "marked" chromosomes (10-4 events/cell per generation. DNA sequence and cytogenetic analysis suggests that the loss of function of the HSV-tk gene most often involves telomere loss, sister chromatid fusion, and prolonged periods of chromosome instability. In some HSV-tk-deficient cells, telomeric repeat sequences were added on to the end of the truncated HSV-tk gene at a new location, whereas in others, no telomere was detected on the end of the marked chromosome. These results suggest that spontaneous telomere loss is a mechanism for chromosome instability in human cancer cells.

  19. Mitotic Origins of Chromosomal Instability in Colorectal Cancer

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    Dalton, W. Brian; Yang, Vincent W.

    2007-01-01

    Mitosis is a crucial part of the cell cycle. A successful mitosis requires the proper execution of many complex cellular behaviors. Thus, there are many points at which mitosis may be disrupted. In cancer cells, chronic disruption of mitosis can lead to unequal segregation of chromosomes, a phenomenon known as chromosomal instability. A majority of colorectal tumors suffer from this instability, and recent studies have begun to reveal the specific ways in which mitotic defects promote chromos...

  20. Chromosomal instability in patients with Fanconi anemia from Serbia

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    Ćirković Sanja

    2014-01-01

    Full Text Available Background/Aim. Fanconi anemia (FA is a rare hereditary disease in a heterogeneous group of syndromes, so-called chromosome breakage disorders. Specific hypersensitivity of its cells to chemical agents, such as diepoxybutane (DEB, was used as a part of screening among patients with clinical suspicion of FA. The aim of this study was to determine chromosomal instability in patients with FA symptoms in Serbia. Methods. A total of 70 patients with phenotypic symptoms of FA, diagnosed at the Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić”, Belgrade and University Children’s Hospital, Belgrade from February 2004 to September 2011, were included in this study. Cytogenetic instability analysis was performed on untreated and DEBtreated 72 h-cultures of peripheral blood. Results. Ten patients in the group of 70 suspected of FA, showed increased DEB induced chromosome breakage and were classified into the FA group. The range of DEB induced aberrant cells percentages in the FA group was from 32% to 82%. DEB sensitivity of 58 tested patients were bellow FA values (range: 0-6% (non-FA group, with no overlapping. The remaining two patients showed borderline sensitivity (borderline FA group - FA*, comparing to the healthy controls. Conclusion. This study revealed 10 patients with FA on the basis of cytogenetic analysis of DEB induced chromosome aberrations. Our results are in consistency with those from the literature. Early and precise diagnosis of FA is very important in further treatment of these patients, considering its cancer prone and lethal effects. [Projekat Ministarstva nauke Republike Srbije, br. 173046

  1. Chromosomal instability in multiple endocrine neoplasia type 1. Cytogenetic evaluation with DEB test.

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    Tomassetti, P; Cometa, G; Del Vecchio, E; Baserga, M; Faccioli, P; Bosoni, D; Paolucci, G; Barbara, L

    1995-02-01

    Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant condition with high penetrance and variable expressivity, in which tumors or hyperplasia occur in two or more endocrine organs. Some authors have investigated chromosomal instability in MEN 1 and MEN 2; the results are controversial. Chromosome analyses were performed on lymphocytes from seven patients with MEN 1, four healthy first-degree relatives (three of whom were children), six phenotypically normal volunteers, and three patients with Fanconi's anemia. To evaluate chromosomal instability we analyzed phytohemagglutinin-stimulated lymphocyte cultures with and without diepoxibutane. We observed an increase in the frequency of spontaneous chromosomal alterations in four patients. After the DEB test we found an increase in chromatid breakages, gaps, and exchange figures. These findings support the inclusion of the MEN 1 syndrome among the disorders with "chromosomal instability." PMID:7889502

  2. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

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    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2011-01-14

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  3. Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.

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    Clemente-Ruiz, Marta; Murillo-Maldonado, Juan M; Benhra, Najate; Barrio, Lara; Pérez, Lidia; Quiroga, Gonzalo; Nebreda, Angel R; Milán, Marco

    2016-02-01

    Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID:26859353

  4. Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice.

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    Rabindra N Bhattacharjee

    Full Text Available BACKGROUND: Telomeres are essential to maintain chromosomal stability. Cells derived from mice lacking telomerase RNA component (mTERC-/- mice display elevated telomere-mediated chromosome instability. Age-dependent telomere shortening and associated chromosome instability reduce the capacity to respond to cellular stress occurring during inflammation and cancer. Inflammation is one of the important risk factors in cancer progression. Controlled innate immune responses mediated by Toll-like receptors (TLR are required for host defense against infection. Our aim was to understand the role of chromosome/genome instability in the initiation and maintenance of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of TLR4 in telomerase deficient mTERC-/- mice harbouring chromosome instability which did not develop any overt immunological disorder in pathogen-free condition or any form of cancers at this stage. Chromosome instability was measured in metaphase spreads prepared from wildtype (mTERC+/+, mTERC+/- and mTERC-/- mouse splenocytes. Peritoneal and/or bone marrow-derived macrophages were used to examine the responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells derived from telomerase-null (mTERC-/- mice and lipopolysaccharide, a natural ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating ATF-3 in mTERC-/- macrophages. CONCLUSIONS/SIGNIFICANCE: Our findings implied that background chromosome instability in the cellular level stabilises the action of TLR4-induced NF-kappaB action and sensitises cells to produce excess pro-inflammatory mediators. Chromosome/genomic instability data raises optimism for controlling inflammation by non-toxic TLR antagonists among high-risk groups.

  5. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

    International Nuclear Information System (INIS)

    Folic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the 'normal' physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P < 0.0001, P = 0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy γ-rays) on day 9 relative to un-irradiated controls (P < 0.05). Folic acid deficiency and γ-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P 0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend < 0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage

  6. The evolution of chromosomal instability in Chinese hamster cells: a changing picture?

    Science.gov (United States)

    Ponnaiya, B.; Limoli, C. L.; Corcoran, J.; Kaplan, M. I.; Hartmann, A.; Morgan, W. F.

    1998-01-01

    PURPOSE: To investigate the kinetics of chromosomal instability induced in clones of Chinese hamster cells following X-irradiation. MATERIALS AND METHODS: X-irradiated clones of GM10115, human-hamster hybrid cells containing a single human chromosome 4 (HC4), have been previously established. These clones were defined as unstable if they contained > or = three subpopulations of cells with unique rearrangements of HC4 as detected by FISH. Stable and unstable clones were analysed by FISH and Giemsa staining at various times post-irradiation. RESULTS: While most of the stable clones continued to show chromosomal stability of HC4 over time, one became marginally unstable at approximately 45 population doublings post-irradiation. Clones exhibiting chromosomal instability had one of several fates. Many of the unstable clones were showed similar levels of instability over time. However, one unstable clone became stable with time in culture, while another became even more unstable over time. Cytogenetic analyses of all clones after Giemsa staining indicated that in some clones the hamster chromosomes were rearranged independent of HC4, demonstrating increased frequencies of chromatid breaks and dicentric chromosomes. The majority of the unstable clones also had higher yields of chromatid gaps. CONCLUSIONS: These data demonstrate the dynamic nature of chromosomal instability as measured by two different cytogenetic assays.

  7. Functions of spindle check-point and its relationship to chromosome instability

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is generally believed that the equal distribution of genetic materials to two daughter cells during mitosis is the key to cell health and development. During the dynamic process, spindle checkpoint plays a very important role in chromosome movements and final sister chromatid separation. The equal and precise segregation of chromosomes contributes to the genomic stability while aberrant separations result in chromosome instability that causes pathogenesis of certain diseases such as Down's syndrome and cancers. Kinetochore and its regulatory proteins consist of the spindle checkpoint and determine the spatial and temporal orders of chromosome segregation.

  8. Topoisomerase IIα in chromosome instability and personalized cancer therapy.

    Science.gov (United States)

    Chen, T; Sun, Y; Ji, P; Kopetz, S; Zhang, W

    2015-07-30

    Genome instability is a hallmark of cancer cells. Chromosome instability (CIN), which is often mutually exclusive from hypermutation genotypes, represents a distinct subtype of genome instability. Hypermutations in cancer cells are due to defects in DNA repair genes, but the cause of CIN is still elusive. However, because of the extensive chromosomal abnormalities associated with CIN, its cause is likely a defect in a network of genes that regulate mitotic checkpoints and chromosomal organization and segregation. Emerging evidence has shown that the chromosomal decatenation checkpoint, which is critical for chromatin untangling and packing during genetic material duplication, is defective in cancer cells with CIN. The decatenation checkpoint is known to be regulated by a family of enzymes called topoisomerases. Among them, the gene encoding topoisomerase IIα (TOP2A) is commonly altered at both gene copy number and gene expression level in cancer cells. Thus, abnormal alterations of TOP2A, its interacting proteins, and its modifications may have a critical role in CIN in human cancers. Clinically, a large arsenal of topoisomerase inhibitors has been used to suppress DNA replication in cancer. However, they often lead to the secondary development of leukemia because of their effect on the chromosomal decatenation checkpoint. Therefore, topoisomerase drugs must be used judiciously and administered on an individual basis. In this review, we highlight the biological function of TOP2A in chromosome segregation and the mechanisms that regulate this enzyme's expression and activity. We also review the roles of TOP2A and related proteins in human cancers, and raise a perspective for how to target TOP2A in personalized cancer therapy. PMID:25328138

  9. Chromosomal Instability Confers Intrinsic Multidrug Resistance

    DEFF Research Database (Denmark)

    Lee, Alvin J. X.; Endesfelder, David; Rowan, Andrew J.;

    2011-01-01

    . Identification of distinct therapeutic agents that target tumor karyotypic complexity has important clinical implications. To identify distinct therapeutic approaches to specifically limit the growth of CIN tumors, we focused on a panel of colorectal cancer (CRC) cell lines, previously classified as either...... progression-free or disease-free survival relative to patients with CIN- disease. Our results suggest that stratifying tumor responses according to CIN status should be considered within the context of clinical trials to minimize the confounding effects of tumor CIN status on drug sensitivity. Cancer Res; 71...

  10. Hexavalent chromium induces chromosome instability in human urothelial cells.

    Science.gov (United States)

    Wise, Sandra S; Holmes, Amie L; Liou, Louis; Adam, Rosalyn M; Wise, John Pierce

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. PMID:26908176

  11. Chromosomal duplication strains of Aspergillus nidulans and their instability

    International Nuclear Information System (INIS)

    Strains of Aspergillus nidulans with chromosomal duplication were obtained after gamma irradiation followed by crossing of the translocated strains with normal strains. From 20 analysed colonies, 12 have shown translocations induced by irradiation. Segregants from four of these translocation strains crossed to normal strains have shown to be unstable although presenting normal morphology. Two segregants were genetically analysed. The first one has shown a duplication of part of linkage groups VIII and the second one presented a duplication of a segment of linkage group V. These new duplication strains in A. nidulans open new perspectives of a more detailed study of the instability phenomenon in this fungus. (Author)

  12. Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome.

    OpenAIRE

    Maraschio, P; Zuffardi, O; Dalla Fior, T; Tiepolo, L

    1988-01-01

    Instability of the heterochromatic centromeric regions of chromosomes 1, 9, and 16 associated with immunodeficiency was found in a four year old girl. Similar phenotypic and chromosomal abnormalities were described in a previous patient studied by us and in four other published cases. All these patients have facial anomalies in addition to combined immunodeficiency and chromosomal instability. Stretching of the heterochromatic centromeric regions of chromosomes 1, 16, and to a lesser extent, ...

  13. Evidence of increased chromosomal instability in infertile males after exposure to mitomycin C and caffeine

    Institute of Scientific and Technical Information of China (English)

    Fotini Papachristou; Theodore Lialiaris; Stavros Touloupidis; Christos Kalaitzis; Constantinos Simopoulos; Nikolaos Sofikitis

    2006-01-01

    Aim: To evaluate the genetic instability of 11 fertile and 25 infertile men. Methods: The methodology of sister chromatid exchanges (SCEs) was applied to cultures of peripheral blood lymphocytes, and the levels of SCEss were analyzed as a quantitative index of genotoxicity, along with the values of the mitotic index (MI) and the proliferation rate index (PRI) as qualitative indices of cytotoxicity and cytostaticity, respectively. The genotoxic and antineoplastic agent, mitomycin C (MMC), and caffeine (CAF) - both well-known inhibitors of DNA repair mechanism - were used in an attempt to induce chromosomal instability in infertile men, so as to more easily detect the probable underlying damage on DNA. Results: Our experiments illustrated that infertile men, compared with fertile ones, demonstrated a statistically significant DNA instability in peripheral blood lymphocytes after being exposed simultaneously to MMC and CAF. Conclusion: The current study showed vividly that there was genetic instability in infertile men which probably contributes to the development of an impaired reproductive capacity.

  14. Chromosomal instability as a prognostic marker in cervical cancer

    International Nuclear Information System (INIS)

    Cervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients. The ability to predict which patients are likely to experience distant relapse would allow clinicians to better tailor treatment. Previous studies have investigated the role of chromosomal instability (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of human malignancies. In this study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients, to determine if this CIN signature associated with patient outcome. Cervical cancer samples were collected from 79 patients, treated between 2000–2007 at the PM, prior to undergoing curative chemo-radiation. Total RNA was extracted from each patient sample and analyzed using the GeneChip Human Genome U133 Plus 2.0 array (Affymetrix). High CIN70 scores were significantly related to increased chromosomal alterations in TCGA cervical cancer patients, including a higher percentage of genome altered and a higher number of copy number alterations. In addition, this same CIN70 signature was shown to be predictive of para-aortic nodal relapse in the PM Cancer Centre cohort. These findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer

  15. Chromosomal instability selects gene copy number variants encoding core regulators of proliferation in ER+ breast cancer

    OpenAIRE

    Endesfelder, David; Burrell, Rebecca; Kanu, Nnennaya; McGranahan, Nicholas; Howell, Mike; Parker, Peter J.; Downward, Julian; Swanton, Charles; Kschischo, Maik

    2014-01-01

    Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER+) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context-dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesised ...

  16. Comparison of instability theory with simulation results

    International Nuclear Information System (INIS)

    The results of a quantitative comparison between linear instability theory and simulation results for a third order charge fluctuation mode in a quadrupole - focused beam are summarized. The theory is found to provide a good account of the initial instability exhibited by the simulation computations

  17. Reprogramming to pluripotency can conceal somatic cell chromosomal instability.

    Directory of Open Access Journals (Sweden)

    Masakazu Hamada

    Full Text Available The discovery that somatic cells are reprogrammable to pluripotency by ectopic expression of a small subset of transcription factors has created great potential for the development of broadly applicable stem-cell-based therapies. One of the concerns regarding the safe use of induced pluripotent stem cells (iPSCs in therapeutic applications is loss of genomic integrity, a hallmark of various human conditions and diseases, including cancer. Structural chromosome defects such as short telomeres and double-strand breaks are known to limit reprogramming of somatic cells into iPSCs, but whether defects that cause whole-chromosome instability (W-CIN preclude reprogramming is unknown. Here we demonstrate, using aneuploidy-prone mouse embryonic fibroblasts (MEFs in which chromosome missegregation is driven by BubR1 or RanBP2 insufficiency, that W-CIN is not a barrier to reprogramming. Unexpectedly, the two W-CIN defects had contrasting effects on iPSC genomic integrity, with BubR1 hypomorphic MEFs almost exclusively yielding aneuploid iPSC clones and RanBP2 hypomorphic MEFs karyotypically normal iPSC clones. Moreover, BubR1-insufficient iPSC clones were karyotypically unstable, whereas RanBP2-insufficient iPSC clones were rather stable. These findings suggest that aneuploid cells can be selected for or against during reprogramming depending on the W-CIN gene defect and present the novel concept that somatic cell W-CIN can be concealed in the pluripotent state. Thus, karyotypic analysis of somatic cells of origin in addition to iPSC lines is necessary for safe application of reprogramming technology.

  18. Radiation induced chromosomal instability in lymphocytes of cancer patients

    International Nuclear Information System (INIS)

    Full text: Cytokinesis-blocked micronucleus (CBMN) assay has been extensively used to evaluate the radiation sensitivity of human individuals. Using the CBMN assay, Scott et al (1998, 1999) demonstrated that a fraction of radiosensitive individuals in breast cancer case population was larger than in normal individual population. However, Vral et al were very skeptical about the Scott et al's findings (2002). Under the approval from the ethical committee of NIRS, peripheral blood was obtained from 46 normal healthy females, 131 breast cancer patients, 32 cervical cancer patients and 7 female head and neck cancer patients. Radiosensitivity of T-lymphocytes was assessed by using a CBMN assay. The frequencies of MN per binucleated cell in healthy donors were 0.031(±0.010) and 0.151(±0.066) for cells treated before and after X-ray-irradiation (2Gy), respectively. Spontaneous MN frequencies in cancer patients were significantly higher than healthy donors (p < 0.001). Radiation sensitivities of breast- and head and neck-cancer patients were significantly higher than normal individuals (p < 0.001). Cervical cancer patients were more resistant to irradiation than healthy donors, though the number of cases for statistical analysis was small. (p < 0.001). We are considering that the HPV infection affected the radiosensitivity of cervical cancer cases. Because it is widely believed that one key mechanism which leads to spontaneous micronucleus formation involves an imbalance of chromosomal segregation and a chromosomal instability in patients' lymphocytes might be greater than that in normal individuals' lymphocytes. Recently, Kuschel et al (2002) demonstrated that ratios in two SNPs on XRCC3 were significantly different between cancer patients and healthy females. Then, we can suppose that the radiation-related genes with low penetrance may be involved in tumorigenesis of mammary- and head and neck-cells, and also, in patients' radiation susceptibility

  19. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  20. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    International Nuclear Information System (INIS)

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

  1. Tolerance whole of genome doubling propagates chromosomal instability and accelerates cancer genome evolution

    OpenAIRE

    Dewhurst, Sally M; McGranahan, Nicholas; Burrell, Rebecca A.; Rowan, Andrew J.; Grönroos, Eva; Endesfelder, David; Joshi, Tejal; Mouradov, Dmitri; Gibbs, Peter; Ward, Robyn L.; Hawkins, Nicholas J.; Szallasi, Zoltan; Sieber, Oliver M.; Swanton, Charles

    2014-01-01

    The contribution of whole genome doubling to chromosomal instability (CIN) and tumour evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, t...

  2. Persistent Increase in Chromosome Instability in Lung Cancer : Possible Indirect Involvement of p53 Inactivation

    OpenAIRE

    Haruki, Nobuhiro; Harano, Tomoko; Masuda, Akira; Kiyono, Tohru; TAKAHASHI, TAKAO; Tatematsu, Yoshio; Shimizu, Shigeki; Mitsudomi, Tetsuya; Konishi, Hiroyuki; Osada, Hirotaka; Fujii, Yoshitaka; Takahashi, Takashi

    2001-01-01

    Karyotype and fluorescence in situ hybridization analyses have demonstrated the frequent presence of an altered static state of the number of chromosomes (ie, aneuploidy) in lung cancer, but it has not been directly established whether aneuploidy is in fact associated with a persistent increase in the rate of chromosomal losses and gains (ie, chromosome instability, or CIN). The study presented here used a panel of 10 lung cancer cell lines to provide for the first time direct evidence that C...

  3. Deregulation of the Replisome Factor MCMBP Prompts Oncogenesis in Colorectal Carcinomas through Chromosomal Instability

    Directory of Open Access Journals (Sweden)

    Mauricio Quimbaya

    2014-09-01

    Full Text Available Genetic instability has emerged as an important hallmark of human neoplasia. Although most types of cancers exhibit genetic instability to some extent, in colorectal cancers genetic instability is a distinctive characteristic. Recent studies have shown that deregulation of genes involved in sister chromatid cohesion can result in chromosomal instability in colorectal cancers. Here, we show that the replisome factor minichromosome maintenance complex–binding protein (MCMBP, which is directly involved in the dynamics of the minichromosome maintenance complex and contributes to maintaining sister chromatid cohesion, is transcriptionally misregulated in different types of carcinomas. Cellular studies revealed that both MCMBP knockdown and overexpression in different breast and colorectal cell lines is associated with the emergence of a subpopulation of cells with abnormal nuclear morphology that likely arise as a consequence of aberrant cohesion events. Association analysis integrating gene expression data with clinical information revealed that enhanced MCMBP transcript levels correlate with an increased probability of relapse risk in colorectal cancers and different types of carcinomas. Moreover, a detailed study of a cohort of colorectal tumors showed that the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma.

  4. Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer

    DEFF Research Database (Denmark)

    Birkbak, Nicolai Juul; Eklund, Aron Charles; Li, Qiyuan;

    2011-01-01

    70 scores. These results suggest a nonmonotonic relationship between gene signature expression and HR for survival outcome, which may explain the difficulties encountered in the identification of prognostic expression signatures in ER- breast cancer. Furthermore, the data are consistent with the...... cancer cell biological fitness and its relationship with clinical outcome, we applied the CIN70 expression signature, which correlates with DNA-based measures of structural chromosomal complexity and numerical CIN in vivo, to gene expression profiles of 2,125 breast tumors from 13 published cohorts...... intolerance of excessive CIN in carcinomas and provide a plausible strategy to define distinct prognostic patient cohorts with ER- breast cancer. Inclusion of a surrogate measurement of CIN may improve cancer risk stratification and future therapeutic approaches. Cancer Res; 71(10); 3447-52. (C) 2011 AACR....

  5. Numerical chromosomal instability mediates susceptibility to radiation treatment

    Science.gov (United States)

    Bakhoum, Samuel F.; Kabeche, Lilian; Wood, Matthew D.; Laucius, Christopher D.; Qu, Dian; Laughney, Ashley M.; Reynolds, Gloria E.; Louie, Raymond J.; Phillips, Joanna; Chan, Denise A.; Zaki, Bassem I.; Murnane, John P.; Petritsch, Claudia; Compton, Duane A.

    2015-01-01

    The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which chromosome missegregation rates have been reduced are rendered markedly more resistant to IR, exhibiting diminished markers of cell death in response to treatment. This work identifies a novel mitotic pathway for radiation-induced genome damage, which occurs outside of the primary nucleus and augments chromosomal breaks. This relationship between radiation treatment and whole-chromosome missegregation can be exploited to modulate therapeutic response in a clinically relevant manner. PMID:25606712

  6. Alternative Splicing of CHEK2 and Codeletion with NF2 Promote Chromosomal Instability in Meningioma

    Directory of Open Access Journals (Sweden)

    Hong Wei Yang

    2012-01-01

    Full Text Available Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.

  7. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    formation, respectively. It indicates that from chromosome instability proceeding to tumorigenesis, the simultaneous action of Aurora-A with activated oncogenic factor or inactivated tumor suppressor is required. In summary, we hypothesize that low concentration (0.5-1 μM) of arsenic-induced E2F1-Aurora-A signaling pathway results in aberrant chromosome distribution during cell mitosis, the abnormal mitotic cells proceed to cancer cells only after acquiring additional tumorigenic factors. Our studies suggest that inhibition of low concentration of arsenic induced Aurora-A expression may provide a new theraputical strategy for the prevention and treatment of arsenic-related cancers.

  8. Gene Expression Signature TOPFOX Reflecting Chromosomal Instability Refines Prediction of Prognosis in Grade 2 Breast Cancer

    DEFF Research Database (Denmark)

    Szasz, A.; Li, Qiyuan; Sztupinszki, Z.; Tokes, A. M.; Szekely, B.; Szendroi, M.; Gyorffy, B.; Szallasi, Z.; Swanton, C.; Kulkal, J.

    Purpose: To assess the ability of genes selected from those reflecting chromosomal instability to identify good and poor prognostic subsets of Grade 2 breast carcinomas. Methods: We selected genes for splitting grade 2 tumours into low and high grade type groups by using public databases. Patients...... immunophenotypical characterization of tumours. 1509 samples were in silico analyzed for further validation of the selected genes. Results: Grade 1 and 3 groups were used as training set for the selected genes. The 4-gene signature was able to split grade 2 carcinomas (n = 62) into a good and a poor prognosis group...... (RFS: 83.8±4.9 months and 69.4±8.2 months, respectively, p = 0.016). Furthermore, independent of grade, the identified signature containing only TOP2A and FOXM1 (TOPFOX) was able to separate ER+ tumours in an efficient manner (p = 0.009), which is further supported by validation in a dataset containing...

  9. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

    DEFF Research Database (Denmark)

    Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.; Rowan, Andrew J.; Grönroos, Eva; Endesfelder, David; Joshi, Tejal; Mouradov, Dmitri; Gibbs, Peter; Ward, Robyn L.; Hawkins, Nicholas J.; Szallasi, Zoltan Imre; Sieber, Oliver M.; Swanton, Charles

    2014-01-01

    The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells ...

  10. Distinct Patterns of Structural and Numerical Chromosomal Instability Characterize Sporadic Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jane Bayani

    2008-10-01

    Full Text Available Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN, which can generate both numerical [(N-CIN] and structural chromosomal instability [(S-CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels of both (N-CIN and (S-CIN. Six tumors had a near-diploid chromosome number, two were near-tetraploid, and two were near-triploid. (N-CIN levels increased as a function of overall tumor genomic content, with near-diploid tumors exhibiting numerical instability indices ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S-CIN was generally more evident in the diploid tumors compared with the near-tetraploid tumors. To determine whether the associated chromosomal constitution and/or ploidy changes were influenced by mitotic segregation errors, centrosome analyses were performed on all 10 tumors. The near-diploid tumors, with the lowest numerical change, were observed to possess fewer cells with centrosome abnormalities (5.5% to 14.0%, whereas the near-tetraploid tumors possessed much higher levels of (N-CIN and were characterized by a trend of elevating percentages of cells with abnormal centrosomes (16.0% to 20.5%. These observations suggest that two distinct processes governing genome stability may be disrupted in ovarian cancer: those that impact on numerical segregation and ploidy of chromosomes and those that affect the fidelity of DNA repair and lead to structural aberrations.

  11. A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Marshall Wallace F

    2005-05-01

    Full Text Available Abstract Background The role of centrioles in mitotic spindle function remains unclear. One approach to investigate mitotic centriole function is to ask whether mutation of centriole-associated proteins can cause genomic instability. Results We addressed the role of the centriole-associated EF-hand protein centrin in genomic stability using a Chlamydomonas reinhardtii centrin mutant that forms acentriolar bipolar spindles and lacks the centrin-based rhizoplast structures that join centrioles to the nucleus. Using a genetic assay for loss of heterozygosity, we found that this centrin mutant showed increased genomic instability compared to wild-type cells, and we determined that the increase in genomic instability was due to a 100-fold increase in chromosome loss rates compared to wild type. Live cell imaging reveals an increased rate in cell death during G1 in haploid cells that is consistent with an elevated rate of chromosome loss, and analysis of cell death versus centriole copy number argues against a role for multipolar spindles in this process. Conclusion The increased chromosome loss rates observed in a centrin mutant that forms acentriolar spindles suggests a role for centrin protein, and possibly centrioles, in mitotic fidelity.

  12. Correlation of chromosomal instability, telomere length and telomere maintenance in microsatellite stable rectal cancer: a molecular subclass of rectal cancer.

    Directory of Open Access Journals (Sweden)

    Lisa A Boardman

    Full Text Available INTRODUCTION: Colorectal cancer (CRC tumor DNA is characterized by chromosomal damage termed chromosomal instability (CIN and excessively shortened telomeres. Up to 80% of CRC is microsatellite stable (MSS and is historically considered to be chromosomally unstable (CIN+. However, tumor phenotyping depicts some MSS CRC with little or no genetic changes, thus being chromosomally stable (CIN-. MSS CIN- tumors have not been assessed for telomere attrition. EXPERIMENTAL DESIGN: MSS rectal cancers from patients ≤50 years old with Stage II (B2 or higher or Stage III disease were assessed for CIN, telomere length and telomere maintenance mechanism (telomerase activation [TA]; alternative lengthening of telomeres [ALT]. Relative telomere length was measured by qPCR in somatic epithelial and cancer DNA. TA was measured with the TRAPeze assay, and tumors were evaluated for the presence of C-circles indicative of ALT. p53 mutation status was assessed in all available samples. DNA copy number changes were evaluated with Spectral Genomics aCGH. RESULTS: Tumors were classified as chromosomally stable (CIN- and chromosomally instable (CIN+ by degree of DNA copy number changes. CIN- tumors (35%; n=6 had fewer copy number changes (<17% of their clones with DNA copy number changes than CIN+ tumors (65%; n=13 which had high levels of copy number changes in 20% to 49% of clones. Telomere lengths were longer in CIN- compared to CIN+ tumors (p=0.0066 and in those in which telomerase was not activated (p=0.004. Tumors exhibiting activation of telomerase had shorter tumor telomeres (p=0.0040; and tended to be CIN+ (p=0.0949. CONCLUSIONS: MSS rectal cancer appears to represent a heterogeneous group of tumors that may be categorized both on the basis of CIN status and telomere maintenance mechanism. MSS CIN- rectal cancers appear to have longer telomeres than those of MSS CIN+ rectal cancers and to utilize ALT rather than activation of telomerase.

  13. Chromosome instability in human hepatocellular carcinoma depends on p53 status and aflatoxin exposure.

    Science.gov (United States)

    Pineau, Pascal; Marchio, Agnès; Battiston, Carlo; Cordina, Emilie; Russo, Alessandro; Terris, Benoît; Qin, Lun-Xiu; Turlin, Bruno; Tang, Zhao-You; Mazzaferro, Vincenzo; Dejean, Anne

    2008-05-31

    Hepatocellular carcinoma (HCC) is a heterogeneous disease triggered by various risk factors and frequently characterized by chromosome instability. This instability is considered to be caused primarily by Hepatitis B virus (HBV), although aflatoxin B1 (AFB1), a potent fungal mutagen is also suspected to influence chromosomal repair. We studied 90 HCCs from Italy, the country with the highest incidence of hepatocellular carcinoma in Europe, 81 samples from France and 52 specimens from Shanghai, in a region where intake of AFB1 via the diet is known to be high. All 223 tumours were characterized for 15 different genomic targets, including allelic loss at 13 chromosome arms and mutations of beta-catenin and p53 genes. Despite disparity in risk-factor distribution, Italian and French cases did not significantly differ for 14 of the 15 targets tested. beta-Catenin and p53 displayed moderate and similar mutation rates (18-29% of cases) in European series. By contrast, tumours from Shanghai were significantly different, with a lower mutation rate for beta-catenin (4% vs. 26%, p<0.0003) and a higher mutation rate for p53 (48% vs. 22%, p<0.0001) when compared with tumours of European origin. The Arg249Ser mutation, hallmark of exposure to AFB1, represented half of the changes in p53 in Shanghai. Furthermore, when stratified for the presence of HBV or p53 mutations, chromosome instability was always higher in Chinese than in European patients. This difference was particularly strong in p53-wildtype tumours (fractional allelic loss, 29.4% vs. 16.7%, p<0.0001). We suggest that AFB1-associated mutagenesis represents a plausible cause for the higher chromosome instability observed in Chinese HCCs, when compared with European primary liver carcinomas. PMID:18467159

  14. Aberrant Wnt/β-catenin signaling can induce chromosomal instability in colon cancer

    OpenAIRE

    Hadjihannas, Michel V; Brückner, Martina; Jerchow, Boris; Birchmeier, Walter; Dietmaier, Wolfgang; Behrens, Jürgen

    2006-01-01

    Chromosomal instability (CIN), a hallmark of most colon tumors, may promote tumor progression by increasing the rate of genetic aberrations. CIN is thought to arise as a consequence of improper mitosis and spindle checkpoint activity, but its molecular basis remains largely elusive. The majority of colon tumors develop because of mutations in the tumor suppressor APC that lead to Wnt/β-catenin signaling activation and subsequent transcription of target genes, including conductin/AXIN2. Here w...

  15. Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Sawyer, J.R.; North, P.E.; Hassed, S.J. [Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States)] [and others

    1997-04-14

    We describe the cytogenetic evolution of multiple cell lines in the gonadal tissue of a 10-year-old girl with mosaic Ullrich-Turner syndrome (UTS) involving clonal telomeric associations (tas) of the Y chromosome. G-band analysis of all tissues showed at least 2 cell lines; 45,X and 46,X,tas(Y;21)(q12;p13). However, analysis of left gonadal tissue of this patient showed the evolution of 2 additional cell lines, one designated 45,X,tas(Y;21)(q12;p13),-22 and the other 46,X,tas(Y;21)(q12;p13),+tas(Y;14)(q12;p13),-22. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei from uncultured gonadal tissue confirmed the findings of aneuploidy in the left gonadal tissue and extended the findings of aneuploidy to the tissue of the right gonad. The chromosome findings in the gonadal tissue of this patient suggest a preneoplastic karyotype relating to several distinct tumor associations. The clonal evolution of telomeric fusions indicates chromosome instability and suggests the extra copy of the Y chromosome may have resulted from a fusion-related malsegregation. In addition, the extra Y suggests low-level amplification of a putative gonadoblastoma gene, while the loss of chromosome 22 suggests the loss of heterozygosity for genes on chromosome 22. This case demonstrates the utility of the study of gonadal tissue in 45X46,XY UTS patients, and provides evidence that clonal telomeric fusions may, in rare cases, be associated with chromosomal malsegregation and with the subsequent evolution of unstable karyotypes. 27 refs., 3 figs.

  16. Cytokinesis-block micronucleus assay evolves into a 'cytome' assay of chromosomal instability, mitotic dysfunction and cell death

    International Nuclear Information System (INIS)

    The cytokinesis-block micronucleus (CBMN) assay was originally developed as an ideal system for measuring micronuclei (MNi) however it can also be used to measure nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (necrosis or apoptosis) and nuclear division rate. Current evidence suggests that (a) NPBs originate from dicentric chromosomes in which the centromeres have been pulled to the opposite poles of the cell at anaphase and are therefore indicative of DNA mis-repair, chromosome rearrangement or telomere end-fusions, (b) NPBs may break to form MNi, (c) the nuclear budding process is the mechanism by which cells remove amplified and/or excess DNA and is therefore a marker of gene amplification and/or altered gene dosage, (d) cell cycle checkpoint defects result in micronucleus formation and (e) hypomethylation of DNA, induced nutritionally or by inhibition of DNA methyl transferase can lead to micronucleus formation either via chromosome loss or chromosome breakage. The strong correlation between micronucleus formation, nuclear budding and NPBs (r = 0.75-0.77, P < 0.001) induced by either folic acid deficiency or exposure to ionising radiation is supportive of the hypothesis that folic acid deficiency and/or ionising radiation cause genomic instability and gene amplification by the initiation of breakage-fusion-bridge cycles. In its comprehensive mode, the CBMN assay measures all cells including necrotic and apoptotic cells as well as number of nuclei per cell to provide a measure of cytotoxicity and mitotic activity. The CBMN assay has in fact evolved into a 'cytome' method for measuring comprehensively chromosomal instability phenotype and altered cellular viability caused by genetic defects and/or nutrional deficiencies and/or exogenous genotoxins thus opening up an exciting future for the use of this methodology in the emerging fields of nutrigenomics and toxicogenomics and their combinations

  17. Chromosomal instability selects gene copy number variants encoding core regulators of proliferation in ER+ breast cancer

    Science.gov (United States)

    Endesfelder, David; McGranahan, Nicholas; Howell, Mike; Parker, Peter J.; Downward, Julian; Swanton, Charles; Kschischo, Maik

    2014-01-01

    Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER+) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context-dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesised that CIN permits accelerated genomic evolution through the generation of diverse DNA copy number events that may be selected during disease development. In support of this hypothesis, we found evidence for selection of gene amplification of core regulators of proliferation in CIN-associated cancer genomes. Stable DNA copy number amplifications of the core regulators TPX2 and UBE2C were associated with expression of a gene module involved in proliferation. The module genes were enriched within prognostic signature gene sets for ER+ breast cancer, providing a logical connection between CIN and prognostic signature expression. Our results provide a framework to decipher the impact of intratumor heterogeneity on key cancer phenotypes, and they suggest that CIN provides a permissive landscape for selection of copy number alterations which drive cancer proliferation. PMID:24970479

  18. HIPK2 deficiency causes chromosomal instability by cytokinesis failure and increases tumorigenicity

    Science.gov (United States)

    Valente, Davide; Bossi, Gianluca; Moncada, Alice; Tornincasa, Mara; Indelicato, Stefania; Piscuoglio, Salvatore; Karamitopoulou, Eva Diamantis; Bartolazzi, Armando; Pierantoni, Giovanna Maria; Fusco, Alfredo; Soddu, Silvia; Rinaldo, Cinzia

    2015-01-01

    HIPK2, a cell fate decision kinase inactivated in several human cancers, is thought to exert its oncosuppressing activity through its p53-dependent and -independent apoptotic function. However, a HIPK2 role in cell proliferation has also been described. In particular, HIPK2 is required to complete cytokinesis and impaired HIPK2 expression results in cytokinesis failure and tetraploidization. Since tetraploidy may yield to aneuploidy and chromosomal instability (CIN), we asked whether unscheduled tetraploidy caused by loss of HIPK2 might contribute to tumorigenicity. Here, we show that, compared to Hipk2+/+ mouse embryo fibroblasts (MEFs), hipk2-null MEFs accumulate subtetraploid karyotypes and develop CIN. Accumulation of these defects inhibits proliferation and spontaneous immortalization of primary MEFs whereas increases tumorigenicity when MEFs are transformed by E1A and Harvey-Ras oncogenes. Upon mouse injection, E1A/Ras-transformed hipk2-null MEFs generate tumors with genetic alterations resembling those of human cancers derived by initial tetraploidization events, such as pancreatic adenocarcinoma. Thus, we evaluated HIPK2 expression in different stages of pancreatic transformation. Importantly, we found a significant correlation among reduced HIPK2 expression, high grade of malignancy, and high nuclear size, a marker of increased ploidy. Overall, these results indicate that HIPK2 acts as a caretaker gene, whose inactivation increases tumorigenicity and causes CIN by cytokinesis failure. PMID:25868975

  19. Alternative Lengthening of Telomeres-An Enhanced Chromosomal Instability in Aggressive Non-MYCN Amplified and Telomere Elongated Neuroblastomas

    NARCIS (Netherlands)

    G. Lundberg; D. Sehic; J.K. Lansberg; I. Ora; A. Frigyesi; V. Castel; S. Navarro; M. Piqueras; T. Martinsson; R. Noguera; D. Gisselsson

    2011-01-01

    Telomere length alterations are known to cause genomic instability and influence clinical course in several tumor types, but have been little investigated in neuroblastoma (NB), one of the most common childhood tumors. In the present study, telomere-dependent chromosomal instability and telomere len

  20. Duration of the hidden chromosome instability persistence in peripheral blood lymphocytes of persons occupationally exposed to ionizing radiation

    International Nuclear Information System (INIS)

    With compatible use of tests 'G2-bleomycin sensitivity assay' and two-term (48 and 100 h) cultivation of human peripheral blood lymphocytes, the voluntary cytogenetic examination of persons who have occupational contact with ionizing radiation is carried out. The results are compared with those obtained in a similar observation of the unexposed group. Principal differences between the groups in the manifestation and the dynamics of the hidden chromosome instability (HCI) in time are found. Its indicators were significantly higher in the occupational group. The possibility of the persistence of radiation-associated HCI in successive generations of human somatic cells with significant interindividual differences is established

  1. Influence of gamma irradiation on chromosomal instability in seeds of welsh onion (Allium fistulosum L.) at storage

    International Nuclear Information System (INIS)

    The levels of chromosomal instability and germinating capacity of welsh onion (Allium fistulosum L.) seeds were studied in control and gamma-irradiated (5 and 10 Gy) groups of seeds. We compared relative chromosome destabilizing effects of the seed age at the moment of irradiation and the time period of storage after irradiation to germination. The second factor was significantly more effective than the first one. It increased the rate of chromosomal aberration and decreased the germinative capacity of seeds. (authors)

  2. Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells

    OpenAIRE

    Kim, Jung Hyun; Lee, Hee Sheung; Lee, Nicholas C.O.; Goncharov, Nikolay V.; Kumeiko, Vadim; Masumoto, Hiroshi; Earnshaw, William C.; Kouprina, Natalay; Larionov, Vladimir

    2016-01-01

    Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" a...

  3. Meiotic chromosomal variation resulting from irradiation of pollen in maize

    International Nuclear Information System (INIS)

    The objective of this study was to standardize an induction strategy of chromosome aberrations in maize inbred line L-869. Pollen grains irradiated with 0, 36 and 72 Gy were used for fertilization. Resulting seeds were planted in a greenhouse to assess the number of abnormal meiotic cells. Germination, height, sterility and mortality were verified. Cells with delayed separation of chromosomes, translocation, deficiency, abnormal pairing, later condensation and anaphase bridges were observed. The number of abnormalities increased as the dosage increased but chromosome aberration types were the same regardless of the dosages used. Various chromosome-altered plants were obtained without viability loss. (author)

  4. Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas

    Directory of Open Access Journals (Sweden)

    Gilson S. Baia

    2008-06-01

    Full Text Available The Notch signaling cascade is deregulated in diverse cancer types. Specific Notch function in cancer is dependent on the cellular context, the particular homologs expressed, and cross-talk with other signaling pathways. We have previously shown that components of the Notch signaling pathway are deregulated in meningiomas. How-ever, the functional consequence of abnormal Notch signaling to meningiomas is unknown. Here, we report that exogenous expression of the Notch pathway effector, HES1, is associated with tetraploid cells in meningioma cell lines. Activated Notch1 and Notch2 receptors induced endogenous HES1 expression and were associated with tetraploidy in meningiomas. Tetraploid meningioma cells exhibited nuclear features of chromosomal instability and increased frequency of nuclear atypia, such as multipolar mitotic spindles and accumulation of cells with large nuclei. FACS-sorted tetraploid cells are viable but have higher rates of spontaneous apoptosis when compared with diploid cells. We have used spectral karyotyping to show that, in contrast to diploid cells, tetraploid cells develop a higher number of both numerical and structural chromosomal abnormalities. Our findings identify a novel function for the Notch signaling pathway in generating tetraploidy and contributing to chromosomal instability. We speculate that abnormal Notch signaling pathway is an initiating genetic mechanism for meningioma and potentially promotes tumor development.

  5. 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH

    Directory of Open Access Journals (Sweden)

    Jaime Gosálvez

    2013-02-01

    Full Text Available We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH. A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL, 10 with high-grade SIL (HG-SIL, and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

  6. Centrosome amplification, chromosomal instability and cancer: mechanistic, clinical and therapeutic issues.

    Science.gov (United States)

    Cosenza, Marco Raffaele; Krämer, Alwin

    2016-01-01

    Centrosomes, the main microtubule-organizing centers in most animal cells, are of crucial importance for the assembly of a bipolar mitotic spindle and subsequent faithful segregation of chromosomes into two daughter cells. Centrosome abnormalities can be found in virtually all cancer types and have been linked to chromosomal instability (CIN) and tumorigenesis. Although our knowledge on centrosome structure, replication, and amplification has greatly increased within recent years, still only very little is known on nature, causes, and consequences of centrosome aberrations in primary tumor tissues. In this review, we summarize our current insights into the mechanistic link between centrosome aberrations, aneuploidy, CIN and tumorigenesis. Mechanisms of induction and cellular consequences of aneuploidy, tetraploidization and CIN, as well as origin and effects of supernumerary centrosomes will be discussed. In addition, animal models for both CIN and centrosome amplification will be outlined. Finally, we describe approaches to exploit centrosome amplification, aneuploidy and CIN for novel and specific anticancer treatment strategies based on the modulation of chromosome missegregation rates. PMID:26645976

  7. Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

    KAUST Repository

    Kashuba, Elena

    2015-05-12

    We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells. Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.

  8. Chromosome instability and X-ray hypersensitivity in a microcephalic and growth-retarded child

    International Nuclear Information System (INIS)

    The authors report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. They propose that their patient belongs to the expanding category of AT-related genetic disorders, probably to the Nijmegen breakage syndrome

  9. Radiation induced chromosomal instability in peripheral blood lymphocytes obtained from breast cancer patients

    International Nuclear Information System (INIS)

    If the breast cancer patients include a disproportionately large number of radiosensitive persons, some radiation-related genes may be involved in the mammary tumorigenesis. To test this hypothesis, the in vitro radiation sensitivities of peripheral blood lymphocytes obtained from 48 normal females and 131 breast cancer patients were measured with a cytokinesis-blocking micronucleus assay. Both the spontaneous- and the X-ray-induced-micronucleus frequencies in patients' blood were significantly higher than those in normal individuals. Our data demonstrate that the chromosomal instability is higher in patients' cells than in normal individuals' cells, and that the radiation-related genes with low penetrance may be involved in mammary tumorigenesis and also, in patients' radiation susceptibility. (author)

  10. Instability of Multiple Sex Chromosomes Systems in Fish: The Case of Erythrinus erythrinus (Bloch & Schneider, 1801) (Characiformes, Erythrinidae).

    Science.gov (United States)

    Bueno, Vanessa; Moresco, Rafaela Maria; Konerat, Jocicléia Thums; Moreira-Filho, Orlando; Margarido, Vladimir Pavan

    2016-02-01

    The fish species Erythrinus erythrinus belongs to the family Erythrinidae (order Characiformes, superorder Teleostei) and is considered a species complex because of the considerable differences between the karyotypes of analyzed populations. Whereas some populations present a sex chromosome system with male heterogamety, others do not show differentiated sex chromosomes. In this article, two novel karyotypes of E. erythrinus with the occurrence of male and female heterogamety are described, and a discussion of the stability of multiple sex chromosome systems is provided. A possible cause for sex chromosomes instability is that the Robertsonian rearrangements that originated the multiple systems did not prevent recombination with ancestral chromosomes, which also did not pass through a heterochromatinization process, the opposite of what usually happens with simple systems, especially of the ZZ/ZW or XX/XY type. It is suggested that multiple sex chromosome systems would not act as an effective postzygotic barrier, especially when there are hybridization zones between distinct karyomorphs that bear and that do not bear sex chromosome systems, allowing the generation of hybrids. This finding is important both for the comprehension of sex chromosomes evolution in fish and for conservation biology since the contact between populations with and without multiple sex chromosomes may compromise the regional biodiversity. PMID:26618235

  11. Two siblings with immunodeficiency, facial abnormalities and chromosomal instability without mutation in DNMT3B gene but liability towards malignancy; a new chromatin disorder delineation?

    Directory of Open Access Journals (Sweden)

    Neitzel Heidemarie

    2010-03-01

    Full Text Available Abstract Background ICF syndrome (standing for Immunodeficiency, Centromere instability and Facial anomalies syndrome is a very rare autosomal recessive immune disorder caused by mutations of the gene de novo DNA-methyltransferase 3B (DNMT3B. However, in the literature similar clinical cases without such mutations are reported, as well. Results We report on a family in which the unrelated spouses had two female siblings sharing similar phenotypic features resembling ICF-syndrome, i.e. congenital abnormalities, immunodeficiency, developmental delay and high level of chromosomal instability, including high frequency of centromeric/pericentromeric rearrangements and breaks, chromosomal fragments despiralization or pulverization. However, mutations in DNMT3B could not be detected. Conclusion The discovery of a new so-called 'chromatin disorder' is suggested. Clinical, molecular genetic and cytogenetic characteristics are reported and compared to other 'chromatin disorders'.

  12. Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell carcinoma.

    Science.gov (United States)

    Peng, Jingtao; Ma, Jian; Li, Weiguo; Mo, Ren; Zhang, Pingzhao; Gao, Kun; Jin, Xiaofeng; Xiao, Jiantao; Wang, Chenji; Fan, Jie

    2015-12-01

    Characterization of the exome and genome of carcinoma (ccRCC) by next-generation sequencing identified numerous genetic alternations. BRCA1-associated protein-1 (BAP1) was identified as one of the most frequently mutated genes in ccRCC, suggesting that BAP1 is a potential key driver for ccRCC cancer initiation and progression. However, how BAP1 mutations contribute to ccRCC remains to be elucidated. BAP1 is a nuclear de-ubiquitinating enzyme and cleaves the ubiquitin chain from the substrates. Here, we identified MCRS1 as a bona fide substrate for BAP1. MCRS1 is a component of the centrosome proteins, and plays an essential role in spindle assembly. BAP1 binds to MCRS1 and stabilizes MCRS1 by de-ubiquitination. BAP1 contributes to chromosome stability partially via MCRS1. A positive correlation was identified between BAP1 and MCRS1 expression in ccRCC tissues. Both BAP1 loss and MCRS1 down-regulation in ccRCC were associated with adverse clinicopathological features. This study revealed a novel mechanism for BAP1 involved in MCRS1 stability regulation, and provided insight in understanding the relationship between BAP1 mutations and chromosome instability in ccRCC. PMID:26300492

  13. Misregulation of Scm3p/HJURP causes chromosome instability in Saccharomyces cerevisiae and human cells.

    Directory of Open Access Journals (Sweden)

    Prashant K Mishra

    2011-09-01

    Full Text Available The kinetochore (centromeric DNA and associated proteins is a key determinant for high fidelity chromosome transmission. Evolutionarily conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast. Overexpression of HJURP, the mammalian homolog of budding yeast Scm3p, has been observed in lung and breast cancers and is associated with poor prognosis; however, the physiological relevance of these observations is not well understood. We overexpressed SCM3 and HJURP in Saccharomyces cerevisiae and HJURP in human cells and defined domains within Scm3p that mediate its chromosome loss phenotype. Our results showed that the overexpression of SCM3 (GALSCM3 or HJURP (GALHJURP caused chromosome loss in a wild-type yeast strain, and overexpression of HJURP led to mitotic defects in human cells. GALSCM3 resulted in reduced viability in kinetochore mutants, premature separation of sister chromatids, and reduction in Cse4p and histone H4 at centromeres. Overexpression of CSE4 or histone H4 suppressed chromosome loss and restored levels of Cse4p at centromeres in GALSCM3 strains. Using mutant alleles of scm3, we identified a domain in the N-terminus of Scm3p that mediates its interaction with CEN DNA and determined that the chromosome loss phenotype of GALSCM3 is due to centromeric association of Scm3p devoid of Cse4p/H4. Furthermore, we determined that similar to other systems the centromeric association of Scm3p is cell cycle regulated. Our results show that altered stoichiometry of Scm3p/HJURP, Cse4p, and histone H4 lead to defects in chromosome segregation. We conclude that stringent regulation of HJURP and SCM3 expression are critical for genome stability.

  14. Transgenerational genomic instability in children of irradiated parents as a result of the Chernobyl Nuclear Accident

    International Nuclear Information System (INIS)

    The study of families irradiated as a result of the accident at the Chernobyl Nuclear Power Plant revealed significantly increased aberrant genomes frequencies (AGFs) not only in irradiated parents (n = 106, p 137Cs) of peripheral blood samples from the children and their parents at doses of 0.1, 0.2 and 0.3 Gy. The spectrum and frequency of chromosome aberrations were studied in the 1st and 2nd cell generations. The average AGF was significantly increased at all doses (except 0.1 Gy) in children of irradiated parents, as compared to children born from non-irradiated parents. Amplification of cells with single-break chromosome aberrations in mitosis 2, as compared to mitosis 1, suggests the replication mechanism of realization of potential damage in DNA and the occurrence of genomic instability in succeeding cell generations.

  15. Heterozygosity of Knob-Associated Tandem Repeats and Knob Instability in Mitotic Chromosomes of Zea (Zea mays L. and Z. diploperennis Iltis Doebley)

    Institute of Scientific and Technical Information of China (English)

    Zhi-Yong XIONG; Yong LIU; Yong-Gang HE; Yun-Chun SONG; Ke-Xiu LI; Guan-Yuan HE

    2005-01-01

    Knobs are blocks of heterochromatin present on chromosomes of maize (Zea mays L.) and its relatives that have effects on the frequency of genetic recombination, as well as on chromosome behavior.Knob heterozygosity and instability in six maize inbred lines and one Z. diploperennis Iltis Doebley line were investigated using the fluorescence in situ hybridization (FISH) technique with knob-associated tandem repeats (180 bp and 350 bp (TR-1)) as probes. Signals of seven heterozygous knobs containing 180-bp repeats and of one heterozygous knob containing TR- 1 were captured in chromosomes of all materials tested according to the results of FISH, which demonstrates that the 180-bp repeat is the main contributor to knob heterozygosity compared with the TR-1 element. In addition, one target cell with two TR-1 signals on one homolog of chromosome 2L, which was different from the normal cells in the maize inbred line GB57,was observed, suggesting knob duplication and an instability phenomenon in the maize genome.

  16. Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white

    Science.gov (United States)

    Ponnaiya, B.; Cornforth, M. N.; Ullrich, R. L.

    1997-01-01

    Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.

  17. Instability of chromosome number and DNA methylation variation induced by hybridization and amphidiploid formation between Raphanus sativus L. and Brassica alboglabra Bailey

    Directory of Open Access Journals (Sweden)

    Wang Yanjie

    2010-09-01

    Full Text Available Abstract Background Distant hybridization can result genome duplication and allopolyploid formation which may play a significant role in the origin and evolution of many plant species. It is unclear how the two or more divergent genomes coordinate in one nucleus with a single parental cytoplasm within allopolyploids. We used cytological and molecular methods to investigate the genetic and epigenetic instabilities associated with the process of distant hybridization and allopolyploid formation, measuring changes in chromosome number and DNA methylation across multiple generations. Results F1 plants from intergeneric hybridization between Raphanus sativus L. (2n = 18, RR and Brassica alboglabra Bailey (2n = 18, CC were obtained by hand crosses and subsequent embryo rescue. Random amplification of polymorphic DNA (RAPD markers were used to identify the F1 hybrid plants. The RAPD data indicated that the hybrids produced specific bands similar to those of parents and new bands that were not present in either parent. Chromosome number variation of somatic cells from allotetraploids in the F4 to F10 generations showed that intensive genetic changes occurred in the early generations of distant hybridization, leading to the formation of mixopolyploids with different chromosome numbers. DNA methylation variation was revealed using MSAP (methylation-sensitive amplification polymorphism, which showed that cytosine methylation patterns changed markedly in the process of hybridization and amphidiploid formation. Differences in cytosine methylation levels demonstrated an epigenetic instability of the allopolyploid of Raphanobrassica between the genetically stable and unstable generations. Conclusions Our results showed that chromosome instability occurred in the early generations of allopolyploidy and then the plants were reverted to largely euploidy in later generations. During this process, DNA methylation changed markedly. These results suggest that

  18. Cascades of genetic instability resulting from compromised break-induced replication.

    Science.gov (United States)

    Vasan, Soumini; Deem, Angela; Ramakrishnan, Sreejith; Argueso, Juan Lucas; Malkova, Anna

    2014-02-01

    Break-induced replication (BIR) is a mechanism to repair double-strand breaks (DSBs) that possess only a single end that can find homology in the genome. This situation can result from the collapse of replication forks or telomere erosion. BIR frequently produces various genetic instabilities including mutations, loss of heterozygosity, deletions, duplications, and template switching that can result in copy-number variations (CNVs). An important type of genomic rearrangement specifically linked to BIR is half-crossovers (HCs), which result from fusions between parts of recombining chromosomes. Because HC formation produces a fused molecule as well as a broken chromosome fragment, these events could be highly destabilizing. Here we demonstrate that HC formation results from the interruption of BIR caused by a damaged template, defective replisome or premature onset of mitosis. Additionally, we document that checkpoint failure promotes channeling of BIR into half-crossover-initiated instability cascades (HCC) that resemble cycles of non-reciprocal translocations (NRTs) previously described in human tumors. We postulate that HCs represent a potent source of genetic destabilization with significant consequences that mimic those observed in human diseases, including cancer. PMID:24586181

  19. Cascades of genetic instability resulting from compromised break-induced replication.

    Directory of Open Access Journals (Sweden)

    Soumini Vasan

    2014-02-01

    Full Text Available Break-induced replication (BIR is a mechanism to repair double-strand breaks (DSBs that possess only a single end that can find homology in the genome. This situation can result from the collapse of replication forks or telomere erosion. BIR frequently produces various genetic instabilities including mutations, loss of heterozygosity, deletions, duplications, and template switching that can result in copy-number variations (CNVs. An important type of genomic rearrangement specifically linked to BIR is half-crossovers (HCs, which result from fusions between parts of recombining chromosomes. Because HC formation produces a fused molecule as well as a broken chromosome fragment, these events could be highly destabilizing. Here we demonstrate that HC formation results from the interruption of BIR caused by a damaged template, defective replisome or premature onset of mitosis. Additionally, we document that checkpoint failure promotes channeling of BIR into half-crossover-initiated instability cascades (HCC that resemble cycles of non-reciprocal translocations (NRTs previously described in human tumors. We postulate that HCs represent a potent source of genetic destabilization with significant consequences that mimic those observed in human diseases, including cancer.

  20. Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

    International Nuclear Information System (INIS)

    Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis. Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

  1. Expression of chromosome instability in children with thyroid pathology born to parents suffered from Chernobyl accident factors

    International Nuclear Information System (INIS)

    Under the usage of long-term human peripheral blood lymphocytes' cultures, the association between thyroid pathology in the children born to irradiated parents and the expression of the hidden cytogenetic effect in delayed cells' generations had been determined. The interindividual variability in the observed children as regard as the response of somatic cells' chromosomes to different terms of the lymphocytes cultivation had been revealed. The possible promotion of delayed chromosome instability on the realization of thyroid pathology in children with a hidden functional failure of the endocrine system has been assumed

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Ultraviolet-induced chromosomal instability in cultured fibroblasts of heterozygote carriers for xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Fibroblast cultures of seven patients with xeroderma pigmentosum (XP), 19 healthy sibs or parents of XP patients (XP-heterozygotes), and 24 healthy normal controls were studied for chromosome instability induced by ultraviolet rays (UV). We used a UV source that contained predominantly UV-A and UV-B at an intensity of 500 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). the XP homozygotes had a UV sensitivity that was clearly above that of all heterozygotes and normal controls. Heterozygotes had an increased rate of UV-induced MN (4.76 ± 1.96 vs. 1.82 ± 2.05, p less than 0.0001) and increased UV induction of SCE (13.21 ± 3.49 vs. 9.01 ± 1.25, p less than 0.001), as compared to normal controls. These data support epidemiologic findings that suggest that XP heterozygotes are particularly cancer prone. In addition, the determination of the UV sensitivity in vitro as described may be used for genetic counseling of asymptomatic relatives of XP patients

  4. Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma.

    Science.gov (United States)

    Plentz, Ruben R; Caselitz, Martin; Bleck, Joerg S; Gebel, Michael; Flemming, Peer; Kubicka, Stefan; Manns, Michael P; Rudolph, K Lenhard

    2004-07-01

    The telomere hypothesis of cancer initiation indicates that telomere shortening initiates cancer by induction of chromosomal instability. To test whether this hypothesis applies to human hepatocellular carcinoma (HCC), we analyzed the telomere length of hepatocytes in cytological smears of fine-needle biopsies of liver tumors from patients with cirrhosis (n = 39). The tumors consisted of 24 HCC and 15 regenerative nodules as diagnosed by combined histological and cytological diagnostics. In addition, we analyzed the telomere length of hepatocytes in HCC and surrounding noncancerous liver tissue within individual patients in another cohort of 10 patients with cirrhosis. Telomere length analysis of hepatocytes was correlated with tumor pathology and ploidy grade of the tumors, which was analyzed by cytophotometry. Telomeres were significantly shortened in hepatocytes of HCC compared to hepatocytes in regenerative nodules or surrounding noncancerous liver tissue. Hepatocyte telomere shortening in HCC was independent of the patient's age. There was no overlap in mean telomere lengths of individual samples when comparing HCC with regenerative nodules or noncancerous surrounding liver. Within the HCC group, telomeres were significantly shorter in hepatocytes of aneuploid tumors compared to diploid tumors. In conclusion, our data suggest that the telomere hypothesis of cancer initiation applies to human HCC and that cell type-specific telomere length analysis might indicate the risk of HCC development. PMID:15239089

  5. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables

    DEFF Research Database (Denmark)

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai Juul; Szallasi, Zoltan Imre; Kschischo, Maik; A. Graham, Trevor; Swanton, Charles

    2011-01-01

    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours...

  6. Chromosomal instability in Afrotheria: fragile sites, evolutionary breakpoints and phylogenetic inference from genome sequence assemblies

    Directory of Open Access Journals (Sweden)

    Ruiz-Herrera Aurora

    2007-10-01

    Full Text Available Abstract Background Extant placental mammals are divided into four major clades (Laurasiatheria, Supraprimates, Xenarthra and Afrotheria. Given that Afrotheria is generally thought to root the eutherian tree in phylogenetic analysis of large nuclear gene data sets, the study of the organization of the genomes of afrotherian species provides new insights into the dynamics of mammalian chromosomal evolution. Here we test if there are chromosomal bands with a high tendency to break and reorganize in Afrotheria, and by analyzing the expression of aphidicolin-induced common fragile sites in three afrotherian species, whether these are coincidental with recognized evolutionary breakpoints. Results We described 29 fragile sites in the aardvark (OAF genome, 27 in the golden mole (CAS, and 35 in the elephant-shrew (EED genome. We show that fragile sites are conserved among afrotherian species and these are correlated with evolutionary breakpoints when compared to the human (HSA genome. Inddition, by computationally scanning the newly released opossum (Monodelphis domestica and chicken sequence assemblies for use as outgroups to Placentalia, we validate the HSA 3/21/5 chromosomal synteny as a rare genomic change that defines the monophyly of this ancient African clade of mammals. On the other hand, support for HSA 1/19p, which is also thought to underpin Afrotheria, is currently ambiguous. Conclusion We provide evidence that (i the evolutionary breakpoints that characterise human syntenies detected in the basal Afrotheria correspond at the chromosomal band level with fragile sites, (ii that HSA 3p/21 was in the amniote ancestor (i.e., common to turtles, lepidosaurs, crocodilians, birds and mammals and was subsequently disrupted in the lineage leading to marsupials. Its expansion to include HSA 5 in Afrotheria is unique and (iii that its fragmentation to HSA 3p/21 + HSA 5/21 in elephant and manatee was due to a fission within HSA 21 that is probably shared

  7. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables.

    OpenAIRE

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai Juul; Szallasi, Zoltan Imre; Kschischo, Maik; A. Graham, Trevor; Swanton, Charles

    2011-01-01

    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to...

  8. Chromosomal instability selects gene copy-number variants encoding core regulators of proliferation in ER+ breast cancer.

    Science.gov (United States)

    Endesfelder, David; Burrell, Rebecca A; Kanu, Nnennaya; McGranahan, Nicholas; Howell, Mike; Parker, Peter J; Downward, Julian; Swanton, Charles; Kschischo, Maik

    2014-09-01

    Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies, including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER(+)) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesized that CIN permits accelerated genomic evolution through the generation of diverse DNA copy-number events that may be selected during disease development. In support of this hypothesis, we found evidence for selection of gene amplification of core regulators of proliferation in CIN-associated cancer genomes. Stable DNA copy-number amplifications of the core regulators TPX2 and UBE2C were associated with expression of a gene module involved in proliferation. The module genes were enriched within prognostic signature gene sets for ER(+) breast cancer, providing a logical connection between CIN and prognostic signature expression. Our results provide a framework to decipher the impact of intratumor heterogeneity on key cancer phenotypes, and they suggest that CIN provides a permissive landscape for selection of copy-number alterations that drive cancer proliferation. PMID:24970479

  9. Genetic control of chromosome instability in Aspergillus nidulans as a means for gene amplification in eukaryotic microorganisms

    International Nuclear Information System (INIS)

    A haploid strain of Aspergillus nidulans carrying I-II duplication homozygous for the leaky mutation adE20 shows improved growth on minimal medium. The duplication, though more stable than disomics, still shows instability. Several methods were used for detecting genetic control of improved stability. a) visual selection, using a duplicated strain which is very unstable due to UV sensitivity, (adE20, biAl/dp yA2; uvsB). One stable strain showed a deletion (or a lethal mutation) distal to biA on the segment at the original position (on chromosome I). This deletion reduces crossing-over frequency detween the two homologous segments. As the deletion of the non-translated segment (yellow sectors) must be preceded by crossing-over, the above reduces the frequency of yellow sectors. A deletion of the translocated segment (green sectors) results in non-viability due to the deletion, and such sectors do not appear. The net result is a stable duplication involving only 12 C.O. units carrying the gene in concern. b) Suppressors of UV sensitivity (su-uvsB) were attempted using the above uvs duplicated strain. Phenotypic revertants were easily obtained, but all were back mutations at the uvsB locus. c) Mutations for UV resistance higher than that of the wild type were not obtained, in spite of the strong selective pressure inserted. d) Recombination deficient mutations (rec), six altogether, all uvs+, did not have any effect on stability. (orig.)

  10. Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

    International Nuclear Information System (INIS)

    Purpose: To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. Methods and Materials: Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatment (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. Results: Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; -4 each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations. Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. Conclusions: An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients

  11. A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables.

    Science.gov (United States)

    Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai J; Szallasi, Zoltan; Kschischo, Maik; Graham, Trevor A; Swanton, Charles

    2011-07-01

    Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to address whether younger age at diagnosis is associated with increased tumour genome instability. We find that CIN, assessed by the two independently derived CIN expression signatures, is significantly associated with increased tumour size, ER negative or HER2 positive disease, higher tumour grade and younger age at diagnosis in ER negative breast cancer. These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome. PMID:21709316

  12. A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells

    International Nuclear Information System (INIS)

    Aneuploidy is a feature of most cancer cells that is often accompanied by an elevated rate of chromosome mis-segregation termed chromosome instability (CIN). While CIN can act as a driver of cancer genome evolution and tumor progression, recent findings point to the existence of a threshold level beyond which CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically. Drugs known to increase CIN beyond the therapeutic threshold are currently few in number, and the clinical promise of targeting the CIN phenotype warrants new screening efforts. However, none of the existing methods, including the in vitro micronuclei (MNi) assay, developed to quantify CIN, is entirely satisfactory. We have developed a new assay for measuring CIN. This quantitative assay for chromosome mis-segregation is based on the use of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Thus, cells that inherit the HAC display green fluorescence, while cells lacking the HAC do not. This allows the measurement of HAC loss rate by routine flow cytometry. Using the HAC-based chromosome loss assay, we have analyzed several well-known anti-mitotic, spindle-targeting compounds, all of which have been reported to induce micronuclei formation and chromosome loss. For each drug, the rate of HAC loss was accurately measured by flow cytometry as a proportion of non-fluorescent cells in the cell population which was verified by FISH analysis. Based on our estimates, despite their similar cytotoxicity, the analyzed drugs affect the rates of HAC mis-segregation during mitotic divisions differently. The highest rate of HAC mis-segregation was observed for the microtubule-stabilizing drugs, taxol and peloruside A. Thus, this new and simple assay allows for a quick and efficient screen of hundreds of drugs to identify those affecting chromosome mis-segregation. It also allows ranking of compounds with the same or similar mechanism of

  13. Evaluation of chromosome aberration frequency instable in individual groups residents at the municipality of Monte Alegre, Para, Brazil, exposed to radon

    International Nuclear Information System (INIS)

    The municipality of Monte Alegre is a region that presents natural radiation high due to the presence of the radionuclide uranium (238U) in its soil, which through its decay gives rise to element Rn, a gas. The radioactivity of the rocks has become a problem for the population of Monte Alegre, from the moment when the radioactive material began to be used in the construction of houses and paving of streets. Among all bio markers related to environmental exposures and its biological effects, the chromosomal aberrations are considered good bio markers as predictors of the risk of cancer. Studies suggest that the frequency of chromosomal aberrations may be related to the genetic instability individual and/or exposure to ionizing radiation. Our work aimed to evaluate the frequency of chromosomal aberrations in individuals in the region of high natural radioactivity in Monte Alegre-PA. As well as to correlate the cytogenetic analysis made in this study with the results of analysis of frequency of polymorphisms of genes of DNA repair carried out in another study that resulted in other dissertation. In accordance with the distribution of the data obtained in characterizing environmental radiological and in the calculation of dose, were chosen residents of homes with more and less exposure to radiation. The samples of peripheral blood of 85 individuals of the resident population of the region of Monte Alegre - PA were collected and examine provided two slides for individual was performed to verify the quality of the sample. Through this evaluation we decide that 33% of the material collected, or is, samples of 28 individuals were in suitable conditions for analysis of the frequency of chromosomal aberrations. After the collections lymphocytes present in the sample were cultivated in accordance with the methodology proposed for obtaining of cells in metaphase. were analyzed 6,177 metaphases of 28 individuals among which were found dicentric chromosomes 4 and 19 fragments

  14. Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.

    Science.gov (United States)

    Kim, Jung-Hyun; Lee, Hee-Sheung; Lee, Nicholas C O; Goncharov, Nikolay V; Kumeiko, Vadim; Masumoto, Hiroshi; Earnshaw, William C; Kouprina, Natalay; Larionov, Vladimir

    2016-03-22

    Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this "loss of signal" assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this "gain of signal" assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date. The "gain of signal" assay was also sensitive enough to detect increase of CIN after siRNA depletion of known genes controlling mitotic progression through distinct mechanisms. Hence this assay can be utilized in future experiments to uncover novel human CIN genes, which will provide novel insight into the pathogenesis of cancer. Also described is the possible conversion of this new assay into a high-throughput screen using a fluorescence microplate reader to characterize chemical libraries and identify new conditions that modulate CIN level. PMID:26943579

  15. Financial Instability - a Result of Excess Liquidity or Credit Cycles?

    DEFF Research Database (Denmark)

    Heebøll-Christensen, Christian

    financial crisis. Consistent with monetarist theory, the results suggest a stable money supply-demand relation in the period in question. However, the implied excess liquidity only resulted in financial destabilizing effect after year 2000. Meanwhile, the results also point to persistent cycles of real...... house prices and leverage, which appear to have been driven by real credit shocks, in accordance with post-Keynesian theories on financial instability. Importantly, however, these mechanisms of credit growth and excess liquidity are found to be closely related. In regards to the global financial crisis......, a prolonged credit cycle starting in the mid-1990s - and possibly initiated subprime mortgage innovations - appears to have created a long-run housing bubble. Further fuelled by expansionary monetary policy and excess liquidity, the bubble accelerated in period following the dot-com crash, until it...

  16. Instability of human societies as a result of conformity

    CERN Document Server

    Efros, A L

    2005-01-01

    We introduce a new model that mimics the strong and sudden effects induced by conformity in tightly interacting human societies. Such effects range from mere crowd phenomena to dramatic political turmoil. The model is a modified version of the Ising Hamiltonian. We have studied the properties of this Hamiltonian using both a Metropolis simulation and analytical derivations. Our study shows that increasing the value of the conformity parameter, results in a first order phase transition. As a result a majority of people begin honestly to support the idea that may contradict the moral principles of a normal human beings though each individual would support the moral principle without tight interaction with the society. Thus, above some critical level of conformity our society occurs to be instable with respect to ideas that might be doubtful. Our model includes, in a simplified way, human diversity with respect to loyalty to the moral principles.

  17. Chromosome instability and global gene expression patterns in proliferating human T-lymphocytes after low dose rate γ-irradiation, and genetic instability in cells from in vivo radiation-exposed persons

    International Nuclear Information System (INIS)

    Chromosomal instability (Cl), and radiation induced Cl in particular, as well as in a wider sense, genomic instability, has been of great interest lately, as it provides an explanation for the occurrence of multiple mutations during transformation of a normal cell to a malignant tumor cell. To explore this phenomenon, we developed an in vitro system to study the long term, cytogenetic effects of ionizing radiation in human T-lymphocytes. Irradiated or non-irradiated T-cells were grown for up to two months as monoclonal or bulk cell cultures in medium enriched with T-cell growth factors. Analysis of G-banded karyotypes at different time intervals demonstrated clonal aberrations in 65% of the clones derived from irradiated cells, and in only 5% of the clones from non-irradiated cells. Delayed occurrence of de novo aberrations, and a progressive development of subclones with karyotypic abnormalities of increasing complexity, was observed many cell generations after the radiation exposure. Moreover, cells exposed to γ-radiation at a low dose rate (LDR, 0.024 Gy h-1) for 5 days in G0-phase, e.g. a dose that gives the cells time to repair between subsequent hits, also demonstrated CI. Following a radiological accident in Estonia 1994, we studied the possible induction of CI in vivo. Both long term bulk cultures and single cell clones were established from one high and three low exposed persons, as well as control individuals from Estonia. Compared to our historical Swedish controls, we found CI to occur in both bulk cultures and clones, and the aberrations were more complex in the exposed individuals than in the controls, indicating that the aberrations were caused by the irradiation. However, due to the high frequency of CI in the Estonian controls, no conclusion with regard to chromosomal instability in vivo could be drawn from the study. In order to trace factors that induce and maintain the chromosomal instability, and clarify which steps are affected in the

  18. Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Tatsunari Sasada

    Full Text Available The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma--caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc(+/flox, abbreviated to CPC;Apc or microsatellite (CDX2P9.5-G19Cre;Apc(flox/flox and CDX2P9.5-G22Cre;Apc(flox/flox instability, respectively--were administered chlorinated (10.0 mg/L chlorine or tap (0.7 mg/L chlorine water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox and CDX2P9.5-G22Cre;Apc(flox/flox mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to

  19. The mean electromotive force resulting from magnetic buoyancy instability

    CERN Document Server

    Davies, C R

    2010-01-01

    Motivated both by considerations of the generation of large-scale astrophysical magnetic fields and by potential problems with mean magnetic field generation by turbulent convection, we investigate the mean electromotive force (emf) resulting from the magnetic buoyancy instability of a rotating layer of stratified magnetic field, considering both unidirectional and sheared fields. We discuss why the traditional decomposition into $\\alpha$ and $\\beta$ effects is inappropriate in this case, and that it is only consideration of the entire mean emf that is meaningful. By considering a weighted average of the unstable linear eigenmodes, and averaging over the horizontal plane, we obtain depth-dependent emfs. For the simplified case of isothermal, ideal MHD we are able to obtain an analytic expression for the emf; more generally the emf has to be determined numerically. We calculate how the emf depends on the various parameters of the problem, particularly the rotation rate and the latitude of the magnetic layer.

  20. The Mean Electromotive Force Resulting from Magnetic Buoyancy Instability

    Science.gov (United States)

    Davies, C. R.; Hughes, D. W.

    2011-02-01

    Motivated both by considerations of the generation of large-scale astrophysical magnetic fields and by potential problems with mean magnetic field generation by turbulent convection, we investigate the mean electromotive force (emf) resulting from the magnetic buoyancy instability of a rotating layer of stratified magnetic field, considering both unidirectional and sheared fields. We discuss why the traditional decomposition into α and β effects is inappropriate in this case, and that it is only consideration of the entire mean emf that is meaningful. By considering a weighted average of the unstable linear eigenmodes, and averaging over the horizontal plane, we obtain depth-dependent emfs. For the simplified case of isothermal, ideal MHD, we are able to obtain an analytic expression for the emf; more generally, the emf has to be determined numerically. We calculate how the emf depends on the various parameters of the problem, particularly the rotation rate and the latitude of the magnetic layer.

  1. The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription

    Directory of Open Access Journals (Sweden)

    Wael M. Abdel-Rahman

    2016-01-01

    Full Text Available All colorectal cancer cell lines except RKO displayed active β-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various β-catenin localizations as a surrogate marker for β-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1 confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors with membranous β-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.

  2. Chromosomal instability in Afrotheria: fragile sites, evolutionary breakpoints and phylogenetic inference from genome sequence assemblies

    OpenAIRE

    Ruiz-Herrera Aurora; Robinson Terence J

    2007-01-01

    Abstract Background Extant placental mammals are divided into four major clades (Laurasiatheria, Supraprimates, Xenarthra and Afrotheria). Given that Afrotheria is generally thought to root the eutherian tree in phylogenetic analysis of large nuclear gene data sets, the study of the organization of the genomes of afrotherian species provides new insights into the dynamics of mammalian chromosomal evolution. Here we test if there are chromosomal bands with a high tendency to break and reorgani...

  3. Colorectal Tumour Microsatellite Instability Test Results: Perspectives from Patients

    Directory of Open Access Journals (Sweden)

    Lindor Noralane M

    2004-05-01

    Full Text Available Abstract Purpose To determine which individuals with colorectal cancer (CRC were interested in knowing the results of their tumour microsatellite instability (MSI and immunohistochemistry (IHC testing. We were also interested in the patients' reasons for choosing to learn their results and in the impact of those results on overall self-assessed quality of life. Patients and Methods CRCs from 414 individuals were assayed for MSI and IHC for DNA mismatch repair gene products (MLH1, MSH2, MSH6. Individuals were invited to learn their MSI/IHC results. They randomly received either brief or extended educational materials about the testing and a pretest survey to learn reasons for their interest and to assess their pretest quality of life. Results Of the 414 individuals, 307 (74% chose to learn their results. There was no significant difference in interest in knowing test results according to gender, age, educational level, or family history of colon cancer. The level of detail in the information piece received by the patients did not influence their desire to know their test results. Self-assessed quality of life was not altered by receiving results and was not correlated with the test outcome. Conclusions Individuals with colorectal cancer had a high level of interest in learning their individual MSI/IHC test results and did not seem deterred by the inherent complexity or ambiguity of this information. Regardless of test outcome, results did not significantly affect self-assessed quality of life. Further studies are needed to assess comprehension of results and behavioural changes resulting from the learning of MSI/IHC results.

  4. Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients.

    Science.gov (United States)

    Halevy, Tomer; Akov, Shira; Bohndorf, Martina; Mlody, Barbara; Adjaye, James; Benvenisty, Nissim; Goldberg, Michal

    2016-08-30

    Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here, we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress, and abnormal cell-cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show downregulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed light on the molecular mechanisms underlying this severe syndrome, and further expand our knowledge of the genomic stress cells experience during the reprogramming process. PMID:27545893

  5. Determination of hidden chromosome instability in persons suffered from the action of factors of the Chernobyl accident by the modified 'G2 bleomycin sensitivity assay'

    International Nuclear Information System (INIS)

    With the help of the modified 'G2-bleomycin sensitivity assay' the voluntary investigation of hidden chromosome instability in 53 persons with different radiation exposures had been fulfilled. In all examined groups, the individual levels of chromosome injuries under identical bleomycin exposure varied in a wide range and didn't depend on their initial values in intact cultures. Among control donors and individuals with low radiation exposure, ∼ 33 % hypertensive persons had been identified that can be considered as a genetically caused phenomenon. In patients recovered from acute radiation, 57.9 % persons expressed the hidden chromosome instability. The data obtained allow us to assume that high doses of ionizing radiation can modify the inherited susceptibility of human chromosomes to a mutagen exposure.

  6. Telomerase reverse transcriptase expression protects transformed human cells against DNA-damaging agents, and increases tolerance to chromosomal instability.

    Science.gov (United States)

    Fleisig, H B; Hukezalie, K R; Thompson, C A H; Au-Yeung, T T T; Ludlow, A T; Zhao, C R; Wong, J M Y

    2016-01-14

    Reactivation of telomerase reverse transcriptase (TERT) expression is found in more than 85% of human cancers. The remaining cancers rely on the alternative lengthening of telomeres (ALT), a recombination-based mechanism for telomere-length maintenance. Prevalence of TERT reactivation over the ALT mechanism was linked to secondary TERT function unrelated to telomere length maintenance. To characterize this non-canonical function, we created a panel of ALT cells with recombinant expression of TERT and TERT variants: TERT-positive ALT cells showed higher tolerance to genotoxic insults compared with their TERT-negative counterparts. We identified telomere synthesis-defective TERT variants that bestowed similar genotoxic stress tolerance, indicating that telomere synthesis activity is dispensable for this survival phenotype. TERT expression improved the kinetics of double-strand chromosome break repair and reduced DNA damage-related nuclear division abnormalities, a phenotype associated with ALT tumors. Despite this reduction in cytological abnormalities, surviving TERT-positive ALT cells were found to have gross chromosomal instabilities. We sorted TERT-positive cells with cytogenetic changes and followed their growth. We found that the chromosome-number changes persisted, and TERT-positive ALT cells surviving genotoxic events propagated through subsequent generations with new chromosome numbers. Our data confirm that telomerase expression protects against double-strand DNA (dsDNA)-damaging events, and show that this protective function is uncoupled from its role in telomere synthesis. TERT expression promotes oncogene-transformed cell growth by reducing the inhibitory effects of cell-intrinsic (telomere attrition) and cell-extrinsic (chemical- or metabolism-induced genotoxic stress) challenges. These data provide the impetus to develop new therapeutic interventions for telomerase-positive cancers through simultaneous targeting of multiple telomerase activities. PMID

  7. Polytene chromosomes of Chironomidae (Diptera as a bioassay of trace-metal-induced genome instability

    Directory of Open Access Journals (Sweden)

    Paraskeva Vladimirova Michailova

    2012-10-01

    Full Text Available Chironomids are a ubiquitous group of aquatic insects that are very sensitive to environmental stress. Due to the presence of polytene (‘giant’ salivary gland chromosomes, it is possible to define the genome response of several Chironomid species to various stress agents. The aim of this study was to assess the genotoxic changes in populations of widely distributed chironomid species from aquatic basins in Bulgaria, Italy, Russia, U.K. and Poland, which were exposed to high concentrations of trace metals. We analyzed the structural and functional alterations of polytene chromosomes of the salivary glands of larvae belonging to three different cytocomplexes of the genus Chironomus (“thummi”, “lacunarius”, “pseudothummi”, and genera Glyptotendipes and Kiefferulus. Somatic structural chromosome rearrangements (para- and pericentric heterozygous inversions, deletions, deficiencies and amplifications were used to estimate a Somatic index (S for each population. The highest S indexes were detected in Chironomus riparius populations from locations with high concentrations of trace metals in the sediment. Each species showed specific genome responses to stress agents which we discussed in the light of the specific DNA structures and cytogenetic characteristics of the species. In larvae from polluted sediments two key structures of the salivary gland chromosomes (Balbiani Rings and Nucleolar Organizer sharply reduced their activity to levels below those observed under non-polluted conditions. It is concluded that polytene chromosomes can be used as tools for evaluating the genotoxicity of the aquatic environment. Structural and functional chromosome alterations provide cost-effective early-warning signals of genotoxic concentrations of environmental pollutants.doi: 10.5324/fn.v31i0.1355.Published online: 17 October 2012.

  8. Unexpected rates of chromosomal instabilities and alterations of hormone levels in Namibian uranium miners.

    Science.gov (United States)

    Zaire, R; Notter, M; Riedel, W; Thiel, E

    1997-05-01

    A common problem in determining the health consequences of radiation exposure is factoring out other carcinogenic influences. The conditions in Namibia provide a test case for distinguishing the effects of long-term low-dose exposure to uranium from the other environmental factors because of good air quality and the lack of other industries with negative health effects. Present records indicate a much higher prevalence of cancer among male workers in the open-pit uranium mine in Namibia compared with the general population. The objective of the present study was to determine whether long-term exposure to low doses of uranium increases the risk of a biological radiation damage which would lead to malignant diseases and to derive a dose-response model for these miners. To investigate this risk, we measured uranium excretion in urine, neutrophil counts and the serum level of FSH, LH and testosterone and analyzed chromosome aberrations in whole blood cells using fluorescence in situ hybridization. A representative cohort of 75 non-smoking, HIV-negative miners was compared to a control group of 31 individuals with no occupational history in mining. A sixfold increase in uranium excretion among the miners compared to the controls was recorded (P atomic bomb or the Chernobyl accident. We conclude that the miners exposed to uranium are at an increased risk to acquire various degrees of genetic damage, and that the damage may be associated with an increased risk for malignant transformation. As expected, the chronic radiation injury of the hematopoietic system resulted in low neutrophil counts. Also, low hormone levels probably reflect damage to the gonadal endocrine system. PMID:9146703

  9. Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers

    DEFF Research Database (Denmark)

    Gaasenbeek, Michelle; Howarth, Kimberley; Rowan, Andrew J;

    2006-01-01

    Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid with multiple large-scale gains/deletions, but the processes underlying CIN are unclear and different types of CIN might exist. We investigated colorectal cancer cell lines using array-comparative genomic hybridization ...

  10. Tumor suppressors, chromosomal instability and hepatitis C virus-associated liver cancer

    OpenAIRE

    McGivern, David R.; Lemon, Stanley M.

    2009-01-01

    Hepatitis C virus is the only known RNA virus with an exclusively cytoplasmic life cycle that is associated with cancer. The mechanisms by which it causes cancer are unclear, but chronic immune-mediated inflammation and associated oxidative chromosomal DNA damage are likely to play a role. Nonetheless, compelling data suggest that the path to hepatocellular carcinoma in chronic hepatitis C shares some important features with human papillomavirus-induced carcinogenesis. Interactions of viral p...

  11. Kinetic instabilities in Mercury's magnetosphere: Three-dimensional simulation results

    Czech Academy of Sciences Publication Activity Database

    Trávníček, Pavel M.; Hellinger, Petr; Schriver, D.; Herčík, David; Slavin, J.A.; Anderson, B.J.

    2009-01-01

    Roč. 36, - (2009), L07104/1-L07104/5. ISSN 0094-8276 R&D Projects: GA AV ČR IAA300030805 Grant ostatní: ESA PECS(XE) 98068 Institutional research plan: CEZ:AV0Z30420517; CEZ:AV0Z10030501 Keywords : Mercury * magnetosphere * instability * ion temperature anisotropy * plasma flow * magnetosheath Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.204, year: 2009

  12. Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: The Nijmegan breakage syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Chrzanowska, K.H.; Krajewska-Walasek, M.; Gutkowska, A. [Memorial Hospital-Child Health Center, Warsaw (Poland)] [and others

    1995-07-03

    We report on 11 patients with 8 independent families (3 pairs of sibs) with a complex clinical pattern including microcephaly, peculiar {open_quotes}bird-like{close_quotes} face, growth retardation, and, in some cases, mild-to-moderate mental deficiency. Most of the patients have recurring respiratory tract infections. One girl has developed B-cell lymphoma. A detailed anthropometric study of 15 physical parameters, including 3 cephalic traits, was performed. It was possible to study the chromosomes of PHA-stimulated lymphocytes in all of the patients. We found structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14 in a proportion of metaphases in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were hitherto studied in this respect. Our patients fulfill the criteria of the Nijmegen breakage syndrome, which belongs to the growing category of ataxia telangiectasia-related genetic disorders. In light of the increased predisposition to malignancy in this syndrome, an accurate diagnosis is important for the patient. 27 refs., 5 figs., 4 tabs.

  13. The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components.

    Directory of Open Access Journals (Sweden)

    Peter C Stirling

    2011-04-01

    Full Text Available Chromosome instability (CIN is observed in most solid tumors and is linked to somatic mutations in genome integrity maintenance genes. The spectrum of mutations that cause CIN is only partly known and it is not possible to predict a priori all pathways whose disruption might lead to CIN. To address this issue, we generated a catalogue of CIN genes and pathways by screening ∼ 2,000 reduction-of-function alleles for 90% of essential genes in Saccharomyces cerevisiae. Integrating this with published CIN phenotypes for other yeast genes generated a systematic CIN gene dataset comprised of 692 genes. Enriched gene ontology terms defined cellular CIN pathways that, together with sequence orthologs, created a list of human CIN candidate genes, which we cross-referenced to published somatic mutation databases revealing hundreds of mutated CIN candidate genes. Characterization of some poorly characterized CIN genes revealed short telomeres in mutants of the ASTRA/TTT components TTI1 and ASA1. High-throughput phenotypic profiling links ASA1 to TTT (Tel2-Tti1-Tti2 complex function and to TORC1 signaling via Tor1p stability, consistent with the role of TTT in PI3-kinase related kinase biogenesis. The comprehensive CIN gene list presented here in principle comprises all conserved eukaryotic genome integrity pathways. Deriving human CIN candidate genes from the list allows direct cross-referencing with tumor mutational data and thus candidate mutations potentially driving CIN in tumors. Overall, the CIN gene spectrum reveals new chromosome biology and will help us to understand CIN phenotypes in human disease.

  14. Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability--an implication in aneuploid human tumors.

    Directory of Open Access Journals (Sweden)

    Chunyan Dai

    Full Text Available Mitotic chromosomal instability (CIN plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis--two tumor microenvironmental factors--could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy.

  15. Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells.

    Science.gov (United States)

    Congras, Annabelle; Barasc, Harmonie; Canale-Tabet, Kamila; Plisson-Petit, Florence; Delcros, Chantal; Feraud, Olivier; Oudrhiri, Noufissa; Hadadi, Eva; Griscelli, Franck; Bennaceur-Griscelli, Annelise; Turhan, Ali; Afanassieff, Marielle; Ferchaud, Stéphane; Pinton, Alain; Yerle-Bouissou, Martine; Acloque, Hervé

    2016-01-01

    The pig is an emerging animal model, complementary to rodents for basic research and for biomedical and agronomical purposes. However despite the progress made on mouse and rat models to produce genuine pluripotent cells, it remains impossible to produce porcine pluripotent cell lines with germline transmission. Reprogramming of pig somatic cells using conventional integrative strategies remains also unsatisfactory. In the present study, we compared the outcome of both integrative and non-integrative reprogramming strategies on pluripotency and chromosome stability during pig somatic cell reprogramming. The porcine cell lines produced with integrative strategies express several pluripotency genes but they do not silence the integrated exogenes and present a high genomic instability upon passaging. In contrast, pig induced pluripotent-like stem cells produced with non-integrative reprogramming system (NI-iPSLCs) exhibit a normal karyotype after more than 12 months in culture and reactivate endogenous pluripotency markers. Despite the persistent expression of exogenous OCT4 and MYC, these cells can differentiate into derivatives expressing markers of the three embryonic germ layers and we propose that these NI-iPSLCs can be used as a model to bring new insights into the molecular factors controlling and maintaining pluripotency in the pig and other non-rodent mammalians. PMID:27245508

  16. Antagonizing pathways leading to differential dynamics in colon carcinogenesis in Shugoshin1 (Sgo1)-haploinsufficient chromosome instability model.

    Science.gov (United States)

    Rao, Chinthalapally V; Sanghera, Saira; Zhang, Yuting; Biddick, Laura; Reddy, Arun; Lightfoot, Stan; Dai, Wei; Yamada, Hiroshi Y

    2016-05-01

    Colon cancer is the second most lethal cancer. It is predicted to claim 50,310 lives in 2014. Chromosome Instability (CIN) is observed in 80-90% of colon cancers, and is thought to contribute to colon cancer progression and recurrence. However, there are no animal models of CIN that have been validated for studies of colon cancer development or drug testing. In this study, we sought to validate a mitotic error-induced CIN model mouse, the Shugoshin1 (Sgo1) haploinsufficient mouse, as a colon cancer study model. Wild-type and Sgo1(-/+) mice were treated with the colonic carcinogen, azoxymethane (AOM). We tracked colon tumor development 12, 24, and 36 wk after treatment to assess progression of colon tumorigenesis. Initially, more precancerous lesions, Aberrant Crypt Foci (ACF), developed in Sgo1(-/+) mice. However, the ACF did not develop straightforwardly into larger tumors. At the 36-wk endpoint, the number of gross tumors in Sgo1(-/+) mice was no different from that in wild-type controls. However, Copy Number Variation (CNV) analysis indicated that fully developed colon tumor in Sgo1(-/+) mice carried 13.75 times more CNV. Immunohistological analyses indicated that Sgo1(-/+) mice differentially expressed IL-6, Bcl2, and p16(INK4A) . We propose that formation of ACF in Sgo1(-/+) mice is facilitated by the IL6-STAT3-SOCS3 oncogenic pathway and by the Bcl2-anti-apoptotic pathway, yet further development of the ACF to tumors is inhibited by the p16(INK4A) tumor suppressor pathway. Manipulating these pathways would be beneficial for inhibiting development of colon cancer with CIN. © 2015 Wiley Periodicals, Inc. PMID:25773652

  17. Gene Expression Signature TOPFOX Reflecting Chromosomal Instability Refines Prediction of Prognosis in Grade 2 Breast Cancer

    DEFF Research Database (Denmark)

    Szasz, A.; Li, Qiyuan; Sztupinszki, Z.;

    2011-01-01

    were diagnosed between 1999–2002 at the Budai MA´ V Hospital. 187 formalinfixed, paraffin-embedded breast cancer samples were included in the qPCR-based measurement of expression of AURKA, FOXM1, TOP2A and TPX2 genes. The expression of the genes were correlated to recurrencefree survival (RFS) and...... immunophenotypical characterization of tumours. 1509 samples were in silico analyzed for further validation of the selected genes. Results: Grade 1 and 3 groups were used as training set for the selected genes. The 4-gene signature was able to split grade 2 carcinomas (n = 62) into a good and a poor prognosis group...

  18. Instability of Human Societies as a Result of Conformity

    Science.gov (United States)

    Efros, A. L.; Désesquelles, P.

    We introduce a new model that mimics the strong and sudden effects induced by conformity in tightly interacting human societies. Such effects range from mere crowd phenomena to dramatic political turmoil. The model is a modified version of the Ising Hamiltonian. We have studied the properties of this Hamiltonian using both a Metropolis simulation and analytical derivations. Our study shows that increasing the value of the conformity parameter, results in a first order phase transition. As a result a majority of people begin to honestly support the idea that may contradict the moral principles of a normal human beings though each individual would support the moral principle without tight interaction with the society. Thus, above some critical level of conformity our society destabilizes with respect to ideas that might be doubtful. Our model includes, in a simplified way, human diversity with respect to loyalty to the moral principles.

  19. Instability of human societies as a result of conformity

    OpenAIRE

    Efros, A. L.; P. Désesquelles

    2005-01-01

    We introduce a new model that mimics the strong and sudden effects induced by conformity in tightly interacting human societies. Such effects range from mere crowd phenomena to dramatic political turmoil. The model is a modified version of the Ising Hamiltonian. We have studied the properties of this Hamiltonian using both a Metropolis simulation and analytical derivations. Our study shows that increasing the value of the conformity parameter, results in a first order phase transition. As a r...

  20. Constitutional mosaicism for a chromosome 9 inversion resulting in recombinant aneusomy in an offspring

    Energy Technology Data Exchange (ETDEWEB)

    Shapira, S.K.; Gagos, S.; Shaffer, L.G. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1997-04-14

    We report on a case of constitutional mosaicism for a large pericentric inversion of chromosome 9 in a man whose daughter had recombinant aneusomy resulting in partial 9q duplication and partial 9p deletion. At age 6 months, the girl was evaluated because of dysmorphic congenital animal features and developmental delay. Chromosomal analysis on this infant showed a derivative chromosome 9 which was later determined to be a recombinant chromosome with trisomy of 9q34.1{r_arrow}qter and monosomy of pter{r_arrow}9p24. Chromosomal analysis in her father showed the presence of two cell lines; 75% of lymphocytes had a 46,XY pattern, and 25% had a 46,XY,inv(9)(p24q34.1) karyotype. The infant`s physical findings represent a composite of the reported cases of both trisomy 9q34.1{r_arrow}qter and monosomy pter{r_arrow}p24. The infant`s father was phenotypically and cognitively normal. This case broadens the spectrum of reported cases of mosaicism for an autosomal structural rearrangement generating unbalanced gametes, and further supports the tenet that constitutional mosaicism has clinical relevance for genetic counseling. 21 refs., 3 figs., 1 tab.

  1. Measurements of parametric instability near the critical density and the resultant electron heating: Final report

    International Nuclear Information System (INIS)

    Detailed studies of the ion acoustic parametric decay instability have been made. Theoretical and particle simulation results indicate these instabilities are important in long scale length plasma irradiated by moderate intensity laser light (10'' ≤ Iλ2/T/sub e/ (W/cm2) (μm2)/(keV) ≤ 5 x 1014). Laser light (λ0 ≅ 1/2 μm) is focused onto a CH target. The parametric decay instability has been measured by detecting the emission spectrum at frequencies near 2ω0. The experimental results clearly indicate that this parametric instability is important for short wavelength (1/2 μm) laser light irradiation. The threshold of the parametric instability (λ0 = 1/2 μm) was only slightly higher than that of 1 μm laser case. The measured wavelength shift of the Stokes component (λ0 = 1/2 μm) compared very well with the 1 μm laser results

  2. Ion-beam-driven lower-hybrid instability and resultant anomalous beam slowing

    International Nuclear Information System (INIS)

    A lower-hybrid instability with ion cyclotron harmonics is observed to be driven by an ion beam injected obliquely to the magnetic field confining the isothermal plasma of the Q-1 double plasma device. The instability occurs with the injection of a low density, low velocity beam and propagates normal to the field with phase velocity ω/k/sub perpendicular/ approximately equal to u/sub b//sub perpendicular/, the perpendicular velocity component of the spiraling ions. The frequency spectrum, propagation, and growth rate are all in good agreement with a numerical calculation based on linear kinetic theory. Pulsed beams are used to follow the instability from the linearly growing stage to nonlinear saturation. The anomalous perpendicular momentum loss of the beam is examined by both direct energy analysis and by measurements of the resultant beam orbit modifications. By varying the beam parameters, a transition of the nonlinear saturation mechanism from the quasilinear to the trapping regime is demonstrated

  3. Sexual dimorphism in white campion: deletion on the Y chromosome results in a floral asexual phenotype

    International Nuclear Information System (INIS)

    White campion is a dioecious plant with heteromorphic X and Y sex chromosomes. In male plants, a filamentous structure replaces the pistil, while in female plants the stamens degenerate early in flower development. Asexual (asx) mutants, cumulating the two developmental defects that characterize the sexual dimorphism in this species, were produced by gamma ray irradiation of pollen and screening in the M1 generation. The mutants harbor a novel type of mutation affecting an early function in sporogenous/parietal cell differentiation within the anther. The function is called stamen-promoting function (SPF). The mutants are shown to result from interstitial deletions on the Y chromosome. We present evidence that such deletions tentatively cover the central domain on the (p)-arm of the Y chromosome (Y2 region). By comparing stamen development in wild-type female and asx mutant flowers we show that they share the same block in anther development, which results in the production of vestigial anthers. The data suggest that the SPF, a key function(s) controlling the sporogenous/parietal specialization in premeiotic anthers, is genuinely missing in females (XX constitution). We argue that this is the earliest function in the male program that is Y-linked and is likely responsible for ''male dimorphism'' (sexual dimorphism in the third floral whorl) in white campion. More generally, the reported results improve our knowledge of the structural and functional organization of the Y chromosome and favor the view that sex determination in this species results primarily from a trigger signal on the Y chromosome (Y1 region) that suppresses female development. The default state is therefore the ancestral hermaphroditic state

  4. Complete paternal uniparental isodisomy of chromosome 1 resulting in Herlitz junctional epidermolysis bullosa.

    Science.gov (United States)

    Fassihi, H; Wessagowit, V; Ashton, G H S; Moss, C; Ward, R; Denyer, J; Mellerio, J E; McGrath, J A

    2005-01-01

    Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive mechanobullous disorder that results from loss-of-function mutations in the genes encoding the basement membrane component, laminin 5. Typically, there are frameshift, splice site or nonsense mutations on both alleles of either the LAMA3, LAMB3 or LAMC2 genes, with affected individuals inheriting one mutated allele from each parent. In this report, we describe a patient with Herlitz JEB in whom DNA analysis revealed homozygosity for the recurrent nonsense mutation R635X in LAMB3, located on chromosome 1q32.2. However, screening of parental DNA showed that although the patient's father was a heterozygous carrier of this mutation, the mother's DNA showed only wild-type sequence. Subsequent genotype analysis using 13 microsatellite markers spanning chromosome 1 revealed that the affected child was homozygous for the entire series of markers tested and that all of the alleles originated from the father. These results indicate that the Herlitz JEB phenotype in this patient is due to complete paternal isodisomy of chromosome 1 and reduction to homozygosity of the mutant LAMB3 gene locus. This is the fourth case of uniparental disomy to be described in Herlitz JEB, but it represents the first example of complete paternal isodisomy for chromosome 1 with a pathogenic mutation in the LAMB3 gene. These findings have important implications for mutation screening in JEB and for genetic counselling. PMID:15663509

  5. Dynamic Bcl-xL (S49) and (S62) Phosphorylation/Dephosphorylation during Mitosis Prevents Chromosome Instability and Aneuploidy in Normal Human Diploid Fibroblasts

    Science.gov (United States)

    Baruah, Prasamit Saurav; Beauchemin, Myriam; Hébert, Josée; Bertrand, Richard

    2016-01-01

    Bcl-xL proteins undergo dynamic phosphorylation/dephosphorylation on Ser49 and Ser62 residues during mitosis. The expression of Bcl-xL(S49A), (S62A) and dual (S49/62A) phosphorylation mutants in tumor cells lead to severe mitotic defects associated with multipolar spindle, chromosome lagging and bridging, and micro-, bi- and multi-nucleated cells. Because the above observations were made in tumor cells which already display genomic instability, we now address the question: will similar effects occur in normal human diploid cells? We studied normal human diploid BJ foreskin fibroblast cells expressing Bcl-xL (wild type), (S49A), (S49D), (S62A), (S62D) and the dual-site (S49/62A) and (S49/62D) mutants. Cells expressing S49 and/or S62 phosphorylation mutants showed reduced kinetics of cell population doubling. These effects on cell population doubling kinetics correlated with early outbreak of senescence with no impact on the cell death rate. Senescent cells displayed typical senescence-associated phenotypes including high-level of senescence-associated β-galactosidase activity, interleukin-6 (IL-6) secretion, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21Waf1/Cip1 activation as well as γH2A.X-associated nuclear chromatin foci. Fluorescence in situ hybridization analysis and Giemsa-banded karyotypes revealed that the expression of Bcl-xL phosphorylation mutants in normal diploid BJ cells provoked chromosome instability and aneuploidy. These findings suggest that dynamic Bcl-xL(S49) and (S62) phosphorylation/dephosphorylation cycles are important in the maintenance of chromosome integrity during mitosis in normal cells. They could impact future strategies aiming to develop and identify compounds that could target not only the anti-apoptotic domain of Bcl-xL protein, but also its mitotic domain for cancer therapy. PMID:27398719

  6. Instability of surface lenticular vortices: results from laboratory experiments and numerical simulations

    Science.gov (United States)

    Lahaye, Noé; Paci, Alexandre; Smith, Stefan Llewellyn

    2016-04-01

    We examine the instability of lenticular vortices -- or lenses -- in a stratified rotating fluid. The simplest configuration is one in which the lenses overlay a deep layer and have a free surface, and this can be studied using a two-layer rotating shallow water model. We report results from laboratory experiments and high-resolution direct numerical simulations of the destabilization of vortices with constant potential vorticity, and compare these to a linear stability analysis. The stability properties of the system are governed by two parameters: the typical upper-layer potential vorticity and the size (depth) of the vortex. Good agreement is found between analytical, numerical and experimental results for the growth rate and wavenumber of the instability. The nonlinear saturation of the instability is associated with conversion from potential to kinetic energy and weak emission of gravity waves, giving rise to the formation of coherent vortex multipoles with trapped waves. The impact of flow in the lower layer is examined. In particular, it is shown that the growth rate can be strongly affected and the instability can be suppressed for certain types of weak co-rotating flow.

  7. Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase–deficient mice and primary cells despite increased chromosomal instability

    OpenAIRE

    Samper, Enrique; Goytisolo, Fermín A.; Murcia, Josiane Ménissier-de; González-Suárez, Eva; Cigudosa, Juan C.; de Murcia, Gilbert; Blasco, María A

    2001-01-01

    Poly(ADP-ribose) polymerase (PARP)-1, a detector of single-strand breaks, plays a key role in the cellular response to DNA damage. PARP-1–deficient mice are hypersensitive to genotoxic agents and display genomic instability due to a DNA repair defect in the base excision repair pathway. A previous report suggested that PARP-1–deficient mice also had a severe telomeric dysfunction consisting of telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P. Hande, W.-M. Tong,...

  8. Cascades of Genetic Instability Resulting from Compromised Break-Induced Replication

    OpenAIRE

    Soumini Vasan; Angela Deem; Sreejith Ramakrishnan; Juan Lucas Argueso; Anna Malkova

    2014-01-01

    Break-induced replication (BIR) is a mechanism to repair double-strand breaks (DSBs) that possess only a single end that can find homology in the genome. This situation can result from the collapse of replication forks or telomere erosion. BIR frequently produces various genetic instabilities including mutations, loss of heterozygosity, deletions, duplications, and template switching that can result in copy-number variations (CNVs). An important type of genomic rearrangement specifically link...

  9. Rowe and Zarins technique in the reconstruction of chronic anterior knee instability and our results

    OpenAIRE

    Kuskucu, Mesih; Kral, Ahmet; Kaplan, Haluk; Arpacioglu, Omer; Cuhadar, Kemal

    2004-01-01

    Between the years 1986-1990 in the clinic of orthopaedics and traumatology of GATA Haydarpaşa Training Hospital combined Rowe and Zarins reconstruction, semimembranosusplasty, vastusplasty, sartoriusplasty and gracilisplasty has been performed in 15 cases with chronic anterior instability. The results are evaluated according to patients history. Clinical and radiological examination and percentage to return to preinjuries level of daily and sport activities. In general estimation we ha...

  10. JC Virus T-Antigen in Colorectal Cancer Is Associated with p53 Expression and Chromosomal Instability, Independent of CpG Island Methylator Phenotype

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    2009-01-01

    Full Text Available JC virus has a transforming gene encoding JC virus T-antigen (JCVT. JCVT may inactivate wild-type p53, cause chromosomal instability (CIN, and stabilize β-catenin. A link between JCVT and CpG island methylator phenotype (CIMP has been suggested. However, no large-scale study has examined the relations of JCVT with molecular alterations, clinical outcome, or prognosis in colon cancer. We detected JCVT expression (by immunohistochemistry in 271 (35% of 766 colorectal cancers. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1 and eight other loci (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, WRN by MethyLight. We examined loss of heterozygosity in 2p, 5q, 17q, and 18q. JCVT was significantly associated with p53 expression (P < .0001, p21 loss (P < .0001, CIN (≥2 chromosomal segments with LOH; P < .0001, nuclear β-catenin (P = .006, LINE-1 hypomethylation (P = .002, and inversely with CIMP-high (P = .0005 and microsatellite instability (MSI (P < .0001, but not with PIK3CA mutation. In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR, 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003, cyclin D1 (adjusted OR, 1.57; P = .02, LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03, BRAF mutation (adjusted OR, 2.20; P = .04, and family history of colorectal cancer (adjusted OR, 0.64; P = .04 remained statistically significant. However, JCVT was no longer significantly associated with CIMP, MSI, β-catenin, or cyclooxygenase-2 expression in multivariate analysis. JCVT was unrelated with patient survival. In conclusion, JCVT expression in colorectal cancer is independently associated with p53 expression and CIN, which may lead to uncontrolled cell proliferation.

  11. Saturation of the f-mode instability in neutron stars: II. Applications and results

    CERN Document Server

    Pnigouras, Pantelis

    2016-01-01

    We present the first results on the saturation of the f-mode instability in neutron stars, due to nonlinear mode coupling. Emission of gravitational waves drives the f-mode (fundamental mode) unstable in fast-rotating, newborn neutron stars. The initial growth phase of the mode is followed by its saturation, because of energy leaking to other modes of the star. The saturation point determines the strain of the generated gravitational-wave signal, which can then be used to extract information about the neutron star equation of state. The parent (unstable) mode couples via parametric resonances with pairs of daughter modes, with the triplets' evolution exhibiting a rich variety of behaviors. We study both supernova- and merger-derived neutron stars, simply modeled as polytropes in a Newtonian context, and show that the parent may couple to many different daughter pairs during the star's evolution through the instability window, with the saturation amplitude changing by orders of magnitude.

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

    OpenAIRE

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

    2015-01-01

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

  13. Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer

    DEFF Research Database (Denmark)

    Roylance, Rebecca; Endesfelder, David; Gorman, Patricia;

    2011-01-01

    reflect tumor CIN status, efficiently delineate outcome in estrogen receptor ER-positive reast cancer in contrast to ERnegative breast cancer, suggesting that the relationship of CIN with prognosis differs in these two breast cancer subtypes. Methods: Direct assessment of CIN requires single-cell analysis...... methods, such as centromeric FISH, aimed at determining the variation around the modal number of two or more chromosomes within individual tumor nuclei. Here, we document the frequency of tumor CIN by dual centromeric FISH analysis in a retrospective primary breast cancer cohort of 246 patients with...... in multivariate analysis. In contrast, a linear relationship of increasing CIN with poorer prognosis in ER-positive breast cancer was observed, using three independent measures of CIN. Conclusions: The paradoxical relationship between extreme CIN and cancer outcome in the ER-negative cohorts may...

  14. Aneuploid progeny of the American oyster, Crassostrea virginica, produced by tetraploid × diploid crosses: another example of chromosome instability in polyploid oysters.

    Science.gov (United States)

    de Sousa, Joana Teixeira; Allen, Standish K; Baker, Haley; Matt, Joseph L

    2016-05-01

    The commercial production of triploids, and the creation of tetraploid broodstock to support it, has become an important technique in aquaculture of the eastern oyster, Crassostrea virginica. Tetraploids are produced by cytogenetic manipulation of embryos and have been shown to undergo chromosome loss (to become a mosaic) with unknown consequences for breeding. Our objective was to determine the extent of aneuploidy in triploid progeny produced from both mosaic and non-mosaic tetraploids. Six families of triploids were produced using a single diploid female and crossed with three mosaic and non-mosaic tetraploid male oysters. A second set of crosses was performed with the reciprocals. Chromosome counts of the resultant embryos were tallied at 2-4 cell stage and as 6-hour(h)-old embryos. A significant level of aneuploidy was observed in 6-h-old embryos. For crosses using tetraploid males, aneuploidy ranged from 53% to 77% of observed metaphases, compared to 36% in the diploid control. For crosses using tetraploid females, 51%-71% of metaphases were aneuploidy versus 53% in the diploid control. We conclude that somatic chromosome loss may be a regular feature of early development in triploids, and perhaps polyploid oysters in general. Other aspects of chromosome loss in polyploid oysters are also discussed. PMID:27070368

  15. Long term results of arthroscopic bankart repair for traumatic anterior shoulder instability

    Directory of Open Access Journals (Sweden)

    Tan Andrew HC

    2011-06-01

    Full Text Available Abstract Background The arthroscopic method offers a less invasive technique of Bankart repair for traumatic anterior shoulder instability. We would like to report the 2 year clinical outcomes of bio-absorbable suture anchors used in traumatic anterior dislocations of the shoulder. Methods Data from 79 shoulders in 74 patients were collected over 4 years (2004 - 2008. Each patient was followed-up over a period of 2 years. The patients underwent arthroscopic Bankart repair using bio-absorbable suture anchors for their shoulder instability. These surgeries were performed at a single institution by a single surgeon over the time period. The patients were assessed with two different outcome measurement tools. The University of California at Los Angeles (UCLA shoulder rating scale and the Simple Shoulder Test (SST score. The scores were calculated before surgery and at the 2-year follow-up. The recurrence rates, range of motion as well post-operative function and return to sporting activities were evaluated. Results SST results from the 12 domains showed a significant improvement from a mean of 6.1 ± 3.1 to 11.1 ± 1.8 taken at the 2-year follow-up (p Conclusion Arthroscopic Bankart repair with the use of suture anchors is a reliable treatment method, with good clinical outcomes, excellent post-operative shoulder motion and low recurrence rates.

  16. Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities.

    OpenAIRE

    Sánchez-García, I; Rabbitts, T H

    1994-01-01

    Proteins that appear to participate in transcriptional control of gene expression are increasingly implicated in leukemias and malignant solid tumors. We report here that the N-terminal domains of the proteins TAL1 (ectopically activated in T-cell acute leukemias after chromosomal abnormalities caused by V-D-J recombinase error) (V, variable; D, diversity; J, joining) and FUS-CHOP (a liposarcoma tumor-specific fusion protein that is produced as a result of a chromosomal translocation) can fun...

  17. Instability of chromosome number and DNA methylation variation induced by hybridization and amphidiploid formation between Raphanus sativus L. and Brassica alboglabra Bailey

    OpenAIRE

    Wang Yanjie; Wei Lihua; Chen Honggao; Li Xiangsong; Wang Bing; Guo Weiwei; Li Xuanli; Wu Jiangsheng; Long Hong

    2010-01-01

    Abstract Background Distant hybridization can result genome duplication and allopolyploid formation which may play a significant role in the origin and evolution of many plant species. It is unclear how the two or more divergent genomes coordinate in one nucleus with a single parental cytoplasm within allopolyploids. We used cytological and molecular methods to investigate the genetic and epigenetic instabilities associated with the process of distant hybridization and allopolyploid formation...

  18. Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa.

    Science.gov (United States)

    Takizawa, Y; Pulkkinen, L; Shimizu, H; Lin, L; Hagiwara, S; Nishikawa, T; Uitto, J

    1998-05-01

    Herlitz junctional epidermolysis bullosa (OMIM#226700) is a lethal, autosomal recessive blistering disorder caused by mutations in one of the three genes LAMA3, LAMB3, or LAMC2, encoding the constitutive polypeptide subunits of laminin 5. In this study, we describe a patient homozygous for a novel nonsense mutation Q936X in exon 19 of LAMB3, which has been mapped to chromosome 1q32. The patient was born with extensive blistering and demonstrated negative immunofluorescence staining for laminin 5, and transmission electron microscopy revealed tissue separation within lamina lucida of the dermal-epidermal junction, diagnostic of Herlitz junctional epidermolysis bullosa. The mother of the proband was found to be a heterozygous carrier for this mutation, whereas the father demonstrated the wild-type LAMB3 allele only. Nonpaternity was excluded by 13 microsatellite markers in six different chromosomes. Genotype analysis using 28 microsatellite markers spanning chromosome 1 revealed that the patient had maternal primary heterodisomy, as well as meroisodisomy within two regions of chromosome 1, one on 1p and the other one on 1q, the latter region containing the maternal LAMB3 mutation. These results suggest that Herlitz junctional epidermolysis bullosa in this patient developed as a result of reduction to homozygosity of the maternal LAMB3 mutation on chromosome 1q32. PMID:9579554

  19. Partial Tetrasomy of Chromosome 22q11.1 Resulting from a Supernumerary Isodicentric Marker Chromosome in a Boy with Cat-eye Syndrome

    OpenAIRE

    Ko, Jung Min; Kim, Jun Bum; Pai, Ki Soo; Yun, Jun-No; Park, Sang-Jin

    2010-01-01

    The 22q11 region has been implicated in chromosomal rearrangements that result in altered gene dosage, leading to three different congenital malformation syndromes: DiGeorge syndrome, cat-eye syndrome (CES), and der(22) syndrome. Although DiGeorge syndrome is a common genomic disorder on 22q11, CES is quite rare, and there has been no report of Korean CES cases with molecular cytogenetic confirmation. In this study, we present the phenotypic and genetic characteristics of a 3-month-old boy wi...

  20. Chromosome evolution in Neotropical butterflies.

    Science.gov (United States)

    Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O; Brown, Keith S

    2013-06-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results in the context of chromosome numbers of over 1400 Neotropical butterfly species and subspecies derived from about 3000 populations published here and in earlier papers of a series. The overall results show that many Neotropical groups are characterized by karyotype instability with several derived modal numbers or none at all, while almost all taxa of Lepidoptera studied from the other parts of the world have one of n = 29-31 as modal numbers. Possibly chromosome number changes become fixed in the course of speciation driven by biotic interactions. Population subdivision and structuring facilitate karyotype change. Factors that stabilize chromosome numbers include hybridization among species sharing the same number, migration, sexual selection and possibly the distribution of chromosomes within the nucleus. PMID:23865963

  1. Volume nanograting formation in laser-silica interaction as a result of the 1D plasma-resonance ionization instability

    CERN Document Server

    Gildenburg, V B

    2016-01-01

    The initial stage of the small-scale ionization-induced instability developing inside the fused silica volume exposed to the femtosecond laser pulse is studied as a possible initial cause of the self-organized nanograting formation. We have calculated the spatial spectra of the instability with the electron-hole diffusion taken into account for the first time and have found that it results in the formation of some hybrid (diffusion-wave) 1D structure with the spatial period determined as geometrical mean of the laser wavelength and characteristic diffusion length of the process considered. Near the threshold of the instability this period occurs to be approximately equal to the laser half-wavelength in the silica, close to the one experimentally observed.

  2. Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping

    Directory of Open Access Journals (Sweden)

    Prabhat Ranjan

    2013-01-01

    Full Text Available The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have additional material from chromosome 6p arising from complex chromosomal rearrangement in the father. Karyotyping is the basic, cost-effective preliminary investigation in a child with mental subnormality or congenital anomalies.

  3. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

    Swanton, C.; Nicke, B.; Schuett, M.;

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting...

  4. Supernumerary Chromosome Marker Der(22)t(11;22) Resulting from a Maternal Balanced Translocation

    OpenAIRE

    Jia-Woei Hou

    2003-01-01

    Derivative 22 [der(22)] syndrome is a rare disorder associated with multiple congenitalanomalies including pre-auricular skin tags or pits, conotruncal heart defects, and profoundmental retardation. Der(22)t(11;22) is one of the causes of supernumerary chromosomemarkers (mar) in humans. We present a boy with developmental delay and multiple anomaliesconsistent with the supernumerary der(22) syndrome. Cytogenetic analysis showed anabnormal chromosome complement of 47, XY, +mar in all 50 cells ...

  5. Evaluation of chromosome aberration frequency instable in individual groups residents at the municipality of Monte Alegre, Para, Brazil, exposed to radon; Avaliacao da frequencia de aberracoes cromossomicas instaveis em grupos de individuos residentes no municipio de Monte Alegre - PA expostos diferencialmente ao radonio

    Energy Technology Data Exchange (ETDEWEB)

    Yunes, Samira Nogarol

    2010-07-01

    The municipality of Monte Alegre is a region that presents natural radiation high due to the presence of the radionuclide uranium ({sup 238}U) in its soil, which through its decay gives rise to element Rn, a gas. The radioactivity of the rocks has become a problem for the population of Monte Alegre, from the moment when the radioactive material began to be used in the construction of houses and paving of streets. Among all bio markers related to environmental exposures and its biological effects, the chromosomal aberrations are considered good bio markers as predictors of the risk of cancer. Studies suggest that the frequency of chromosomal aberrations may be related to the genetic instability individual and/or exposure to ionizing radiation. Our work aimed to evaluate the frequency of chromosomal aberrations in individuals in the region of high natural radioactivity in Monte Alegre-PA. As well as to correlate the cytogenetic analysis made in this study with the results of analysis of frequency of polymorphisms of genes of DNA repair carried out in another study that resulted in other dissertation. In accordance with the distribution of the data obtained in characterizing environmental radiological and in the calculation of dose, were chosen residents of homes with more and less exposure to radiation. The samples of peripheral blood of 85 individuals of the resident population of the region of Monte Alegre - PA were collected and examine provided two slides for individual was performed to verify the quality of the sample. Through this evaluation we decide that 33% of the material collected, or is, samples of 28 individuals were in suitable conditions for analysis of the frequency of chromosomal aberrations. After the collections lymphocytes present in the sample were cultivated in accordance with the methodology proposed for obtaining of cells in metaphase. were analyzed 6,177 metaphases of 28 individuals among which were found dicentric chromosomes 4 and 19

  6. GENETIC INSTABILITY IN CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    赵旻; 伍欣星; 邱小萍; 李晖; 戴天力; 谭云

    2002-01-01

    Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH) and microsatellite instability (MI). The aim of the present study was to investigate the genetic instability in cervical carcinoma tissues and provide evidence for discoveringnew tumor suppressor genes and screening diagnostic molecular marker of cervical carcinoma. Methods: Fifty primary cervical carcinoma samples from high-incidence area were analyzed by PCR for HPV16 infection, LOH and microsatellite instability. Results: HPV16 was detected in 88% of the cases. Sixty-six percent of total cases showed LOH with no more than 3 different loci per case. The highest frequency of the allelic loss was found in D18S474 (18q21, 40.5%). MI was detected in 4 cases (8%) only. Conclusion: Different percentages of LOH on specific chromosomal regions were found and MI was very infrequent in cervical carcinoma. The putative suppressor gene(s) could be located on specific chromosome regions such as 18q, and genetic instability could be involved in cervical tumorigenesis.

  7. Housing Instability among People Who Inject Drugs: Results from the Australian Needle and Syringe Program Survey

    OpenAIRE

    Topp, Libby; Iversen, Jenny; Baldry, Eileen; Maher, Lisa

    2012-01-01

    High rates of substance dependence are consistently documented among homeless people, and are associated with a broad range of negative outcomes among this population. Investigations of homelessness among drug users are less readily available. This study examined the prevalence and correlates of housing instability among clients of needle syringe programs (NSPs) via the Australian NSP Survey, annual cross-sectional seroprevalence studies among NSP attendees. Following self-completion of a bri...

  8. Long term results of arthroscopic bankart repair for traumatic anterior shoulder instability

    OpenAIRE

    Ee, Gerard WW; Mohamed, Sedeek; Tan, Andrew HC

    2011-01-01

    Background The arthroscopic method offers a less invasive technique of Bankart repair for traumatic anterior shoulder instability. We would like to report the 2 year clinical outcomes of bio-absorbable suture anchors used in traumatic anterior dislocations of the shoulder. Methods Data from 79 shoulders in 74 patients were collected over 4 years (2004 - 2008). Each patient was followed-up over a period of 2 years. The patients underwent arthroscopic Bankart repair using bio-absorbable suture ...

  9. Intraspecific crosses resulting in the first occurrence of eight and nine B chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae)

    OpenAIRE

    Tatiana Aparecida Voltolin; José Augusto Senhorini; Fausto Foresti; Jehud Bortolozzi; Fábio Porto-Foresti

    2011-01-01

    B chromosomes are supernumerary elements present in about 15% of eukaryotic species and are most frequently heterochromatic, behave parasitically, show a transmission rate higher than standard (A) chromosomes, and can provoke harmful effects on carriers. In the current work, Prochilodus lineatus individuals carrying eight and nine B chromosomes were obtained by induced crossing performed involving breeders with different B chromosome numbers in their cells. The high B chromosome numbers found...

  10. Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping

    OpenAIRE

    Prabhat Ranjan; Kundanbala Desai; Shailaja Gada Saxena

    2013-01-01

    The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have ...

  11. Supernumerary Chromosome Marker Der(22t(11;22 Resulting from a Maternal Balanced Translocation

    Directory of Open Access Journals (Sweden)

    Jia-Woei Hou

    2003-01-01

    Full Text Available Derivative 22 [der(22] syndrome is a rare disorder associated with multiple congenitalanomalies including pre-auricular skin tags or pits, conotruncal heart defects, and profoundmental retardation. Der(22t(11;22 is one of the causes of supernumerary chromosomemarkers (mar in humans. We present a boy with developmental delay and multiple anomaliesconsistent with the supernumerary der(22 syndrome. Cytogenetic analysis showed anabnormal chromosome complement of 47, XY, +mar in all 50 cells analyzed. The karyotypeof his mother showed a reciprocal translocation over the distal bands 11q23 and 22q11,respectively, i.e., 46,XX,t(11;22(q23.3;q11.2, and that of his father was 46,XY. Thus, thenature of the supernumerary chromosome markers was of der(22t(11;22(q23.3;q11.2. Theclinical features, including craniofacial dysmorphism, hypotonia, psychomotor retardation,heart defects, and urogenital anomalies, were the combined effects of partial trisomies forboth distal 11q and pericentromeric 22q.

  12. Scattering of electromagnetic waves by vortex density structures associated with interchange instability: Analytical and large scale plasma simulation results

    Energy Technology Data Exchange (ETDEWEB)

    Sotnikov, V.; Kim, T.; Lundberg, J. [Air Force Research Laboratory (AFRL/RY), Wright Patterson AFB, Ohio 45433 (United States); Paraschiv, I. [University of Nevada at Reno, Nevada 89557 (United States); Mehlhorn, T. A. [Naval Research Laboratory, Washington, District of Columbia 20375 (United States)

    2014-05-15

    The presence of plasma turbulence can strongly influence propagation properties of electromagnetic signals used for surveillance and communication. In particular, we are interested in the generation of low frequency plasma density irregularities in the form of coherent vortex structures. Interchange or flute type density irregularities in magnetized plasma are associated with Rayleigh-Taylor type instability. These types of density irregularities play an important role in refraction and scattering of high frequency electromagnetic signals propagating in the earth ionosphere, in high energy density physics, and in many other applications. We will discuss scattering of high frequency electromagnetic waves on low frequency density irregularities due to the presence of vortex density structures associated with interchange instability. We will also present particle-in-cell simulation results of electromagnetic scattering on vortex type density structures using the large scale plasma code LSP and compare them with analytical results.

  13. Analysis of chromosome lesions in women with gynecological disorders, residing in territories contaminated as a result of the Chernobyl accident

    International Nuclear Information System (INIS)

    Spontaneous levels of chromosome aberrations in peripheral lymphocytes of 95 women were analyzed in the course of medical examination of residents of Bryansk region territories (Klintsy district, and the town of Klintsy) contaminated after the Chernobyl NPP accident. All recognizable chromosome lesion types were scored in the first in vitro division metaphases stained with azure-eosin. The mean total aberration frequency in the sample studied was 5.1±0.4 per 100 metaphases, the main contribution being made by chromatid deletions, which is typical for a normal spontaneous aberration pattern. Abnormal patterns, including significantly elevated aberration frequencies and/or presence of chromosome type exchange aberrations, were found in 13 women. The aim of the study was to evaluate a possible correlation between cytogenetic anomalies and reproductive system disorders and/or the level of radiation contamination of the territory. As a result of our estimation, it was shown that cytogenetic anomalies were in fact higher in subjects residing in territories with a higher radiation contamination; however, the difference was statistically insignificant. The frequency of cytogenetic anomalies was higher in women with gynecological disorders including hormone-dependent and inflammatory (17%) than in healthy women (7%). This difference was statistically significant for subjects with hormone-dependent diseases of the female reproductive system, but not in patients with inflammatory disorders

  14. Analysis of chromosome lesions in women with gynecological disorders, residing in territories contaminated as a result of the Chernobyl accident

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, T. I.; Kondrashova, T. V.; Krikunova, L. I.; Shenterva, N. I. [Medical Radiological Research Center, RAMS, Obninsk (Russian Federation); Song, Jie Young; Han, Young Soo; Yun, Yeon Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    Spontaneous levels of chromosome aberrations in peripheral lymphocytes of 95 women were analyzed in the course of medical examination of residents of Bryansk region territories (Klintsy district, and the town of Klintsy) contaminated after the Chernobyl NPP accident. All recognizable chromosome lesion types were scored in the first in vitro division metaphases stained with azure-eosin. The mean total aberration frequency in the sample studied was 5.1{+-}0.4 per 100 metaphases, the main contribution being made by chromatid deletions, which is typical for a normal spontaneous aberration pattern. Abnormal patterns, including significantly elevated aberration frequencies and/or presence of chromosome type exchange aberrations, were found in 13 women. The aim of the study was to evaluate a possible correlation between cytogenetic anomalies and reproductive system disorders and/or the level of radiation contamination of the territory. As a result of our estimation, it was shown that cytogenetic anomalies were in fact higher in subjects residing in territories with a higher radiation contamination; however, the difference was statistically insignificant. The frequency of cytogenetic anomalies was higher in women with gynecological disorders including hormone-dependent and inflammatory (17%) than in healthy women (7%). This difference was statistically significant for subjects with hormone-dependent diseases of the female reproductive system, but not in patients with inflammatory disorders.

  15. Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast

    OpenAIRE

    Paek, Andrew L.; Kaochar, Salma; Jones, Hope; Elezaby, Aly; Shanks, Lisa; Weinert, Ted

    2009-01-01

    Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a p...

  16. Quasilinear diffusion as a result of modulational instability in the pulsar plasma

    International Nuclear Information System (INIS)

    Quasilinear diffusion due to modulational instability is considered in this paper. Interaction between the high-frequency, nearly transverse O mode (or the transverse X mode) and the low-frequency, nearly longitudinal L-O mode in a pulsar magnetospheric pair plasma can lead to modulational instability. The low-frequency L-O mode is superluminal, which is not subjected to usual Landau damping, and it is possible that excess wave energy is stored in this superluminal mode. The superluminal low-frequency L-O mode can dissipate in a way similar to the process of Langmuir wave collapse, that is, it cascades from the long- to short-wavelength regimes. When the phase speed becomes less than c, the waves can be damped through various resonances. We consider, in particular, damping through cyclotron resonance, which can lead to particle acceleration. The energetic beam particles, which have a very small spread initially, can develop a high-energy distribution tail, acquiring pitch angles through quasilinear diffusion. These particles can emit γ rays through synchrotron radiation, contributing to the observed pulsar high-energy emission

  17. Mitotic chromosome structure

    International Nuclear Information System (INIS)

    Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

  18. How chromosome mis-segregation leads to cancer: lessons from BubR1 mouse models.

    Science.gov (United States)

    Lee, Hyunsook

    2014-10-31

    Alteration in chromosome numbers and structures instigate and foster massive genetic instability. As Boveri has seen a hundred years ago (Boveri, 1914; 2008), aneuploidy is hallmark of many cancers. However, whether aneuploidy is the cause or the result of cancer is still at debate. The molecular mechanism behind aneuploidy includes the chromo-some mis-segregation in mitosis by the compromise of spindle assembly checkpoint (SAC). SAC is an elaborate network of proteins, which monitor that all chromosomes are bipolarly attached with the spindles. Therefore, the weakening of the SAC is the major reason for chromosome number instability, while complete compromise of SAC results in detrimental death, exemplified in natural abortion in embryonic stage. Here, I will review on the recent progress on the understanding of chromosome mis-segregation and cancer, based on the comparison of different mouse models of BubR1, the core component of SAC. PMID:25256220

  19. Buoyancy-driven instability in a vertical cylinder: Binary fluids with Soret effect. I - General theory and stationary stability results

    Science.gov (United States)

    Hardin, G. R.; Sani, R. L.; Henry, D.; Roux, B.

    1990-01-01

    The buoyancy-driven instability of a monocomponent or binary fluid completely contained in a vertical circular cylinder is investigated, including the influence of the Soret effect for the binary mixture. The Boussinesq approximation is used, and the resulting linear stability problem is solved using a Galerkin technique. The analysis considers fluid mixtures ranging from gases to liquid metals. The flow structure is found to depend strongly on both the cylinder aspect ratio and the magnitude of the Soret effect. The predicted stability limits are shown to agree closely with experimental observations.

  20. Simulation Results of a Feedback Control System to Damp Electron Cloud Single-Bunch Transverse Instabilities In The Cern SPS

    Energy Technology Data Exchange (ETDEWEB)

    Secondo, R.; Vay, J. L.; Venturini, M.; Fox, J. D.; Rivetta, C. H.; Hofle, W.

    2011-03-28

    Transverse Single-Bunch Instabilities due to the Electron Cloud effect are limiting the operation at high current of the SPS at CERN. Recently a high-bandwidth Feedback System has been proposed as a possible solution to stabilize the beam and is currently under study. We analyze the dynamics of the bunch actively damped with a simple model of the Feedback in the macro-particle code WARP, in order to investigate the limitations of the System such as the minimum amount of power required to maintain stability. We discuss the feedback model, report on simulation results and present our plans for further development of the numerical model.

  1. Lymphocytes with multiple chromosomal damages in a large cohort of West Siberia residents: Results of long-term monitoring.

    Science.gov (United States)

    Druzhinin, Vladimir; Bakanova, Maria; Fucic, Aleksandra; Golovina, Tatiana; Savchenko, Yana; Sinitsky, Maxim; Volobaev, Valentin

    2016-01-01

    Cells with specific multiple chromosome aberrations, defined as rogue cells (RC) have been described in different populations, predominantly those exposed to radiation. The frequency, etiology and related health risks have still not been elucidated due to their low frequency of occurrences and rarely performed studies. This study reports RC frequency using chromosome aberration (CA) assay in peripheral lymphocytes in the group of 3242 subjects, during a 30-year long follow-up study in a general rural and urban population, children environmentally exposed to radon, occupationally exposed population and lung cancer patients from the Kemerovo region (Siberia, Russian Federation). Results show that the highest RC frequency was present in children environmentally exposed to radon and the lowest in the general urban population. Total frequency of CA did not correlate with frequency of RC. Genotoxic analysis of air and water samples excluded anthropogenic pollution as a possible cause of genome damage and RC frequency. In 85% of RCs, double minutes, observed in a large number of human tumors, were present. Results of CA analysis suggested that radon and its decay products (alpha-emitters) were the leading factors causing RC in subjects exposed to high LET radiation. Thus, RC may be a candidate biomarker for exposure to this type of radiation. PMID:26731314

  2. HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an X-chromosome exome sequencing study

    Science.gov (United States)

    Friez, Michael J; Brooks, Susan Sklower; Stevenson, Roger E; Field, Michael; Basehore, Monica J; Adès, Lesley C; Sebold, Courtney; McGee, Stephen; Saxon, Samantha; Skinner, Cindy; Craig, Maria E; Murray, Lucy; Simensen, Richard J; Yap, Ying Yzu; Shaw, Marie A; Gardner, Alison; Corbett, Mark; Kumar, Raman; Bosshard, Matthias; van Loon, Barbara; Tarpey, Patrick S; Abidi, Fatima; Gecz, Jozef; Schwartz, Charles E

    2016-01-01

    Background X linked intellectual disability (XLID) syndromes account for a substantial number of males with ID. Much progress has been made in identifying the genetic cause in many of the syndromes described 20–40 years ago. Next generation sequencing (NGS) has contributed to the rapid discovery of XLID genes and identifying novel mutations in known XLID genes for many of these syndromes. Methods 2 NGS approaches were employed to identify mutations in X linked genes in families with XLID disorders. 1 involved exome sequencing of genes on the X chromosome using the Agilent SureSelect Human X Chromosome Kit. The second approach was to conduct targeted NGS sequencing of 90 known XLID genes. Results We identified the same mutation, a c.12928 G>C transversion in the HUWE1 gene, which gives rise to a p.G4310R missense mutation in 2 XLID disorders: Juberg-Marsidi syndrome (JMS) and Brooks syndrome. Although the original families with these disorders were considered separate entities, they indeed overlap clinically. A third family was also found to have a novel HUWE1 mutation. Conclusions As we identified a HUWE1 mutation in an affected male from the original family reported by Juberg and Marsidi, it is evident the syndrome does not result from a mutation in ATRX as reported in the literature. Additionally, our data indicate that JMS and Brooks syndromes are allelic having the same HUWE1 mutation. PMID:27130160

  3. Small chromosomes among Danish Candida glabrata isolates originated through different mechanisms

    DEFF Research Database (Denmark)

    Ahmad, Khadija Mohamed; Ishchuk, Olena P.; Hellborg, Linda;

    2013-01-01

    participate in their origin: (i) through a segmental duplication which covered the centromeric region, or (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of small chromosomes carrying duplicated genes...... chromosomes, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, these C. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to each other (i.e. they contained different sets of genes). We suggest that at least two mechanisms could...... exhibited mitotic instability, while the second type, which contained the corresponding genes in only one copy in the genome, was mitotically stable. Apparently, in patients C. glabrata chromosomes are frequently reshuffled resulting in new genetic configurations, including appearance of small chromosomes...

  4. Severe neonatal marfan syndrome resulting from a De Novo 3-bp insertion into the fibrillin gene on chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Milewicz, D.M.; Duvic, M. (Univ. of Texas Medical School, Houston, TX (United States))

    1994-03-01

    Severe neonatal Marfan syndrome has features of the Marfan syndrome and congenital contractural arachnodactyly present at birth, along with unique features such as loose, redundant skin and pulmonary emphysema. Since the Marfan syndrome and congenital contractural arachnodactyly are due to mutations in different genes, it has been uncertain whether neonatal Marfan syndrome is due to mutations in the fibrillin gene on chromosome 15 or in another gene. The authors studied an infant with severe neonatal Marfan syndrome. Dermal fibroblasts were metabolically labeled and found to secrete fibrillin inefficiently when compared with control cells. Reverse transcription and amplification of the proband's fibroblast RNA was used to identify a 3-bp insertion between nucleotides 480-481 or 481-482 of the fibrillin cDNA. The insertion maintains the reading frame of the protein and inserts a cysteine between amino acids 160 and 161 in an epidermal growth-factor-like motif of fibrillin. This 3-bp insertion was not found in the fibrillin gene in 70 unrelated, unaffected individuals and 11 unrelated individuals with the Maran syndrome. The authors conclude that neonatal Marfan syndrome is the result of mutations in the fibrillin gene on chromosome 15 and is part of the Marfan syndrome spectrum. 32 refs., 3 figs.

  5. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K; Tsai, Y C; Spruck, C H; Miyao, N; Nichols, P W; Hermann, G G; Horn, T; Steven, K

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chr...

  6. Intraspecific crosses resulting in the first occurrence of eight and nine B chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae).

    Science.gov (United States)

    Voltolin, Tatiana Aparecida; Senhorini, José Augusto; Foresti, Fausto; Bortolozzi, Jehud; Porto-Foresti, Fábio

    2011-04-01

    B chromosomes are supernumerary elements present in about 15% of eukaryotic species and are most frequently heterochromatic, behave parasitically, show a transmission rate higher than standard (A) chromosomes, and can provoke harmful effects on carriers. In the current work, Prochilodus lineatus individuals carrying eight and nine B chromosomes were obtained by induced crossing performed involving breeders with different B chromosome numbers in their cells. The high B chromosome numbers found in the offspring were recorded for the first time in this species. The use of cytogenetic techniques applied in the present study revealed that regardless of the increase in number of B chromosomes in the genome of these individuals, those elements did not presented active genes, and showed their normal heterochromatic characteristic. PMID:21734820

  7. Intraspecific crosses resulting in the first occurrence of eight and nine B chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae

    Directory of Open Access Journals (Sweden)

    Tatiana Aparecida Voltolin

    2011-01-01

    Full Text Available B chromosomes are supernumerary elements present in about 15% of eukaryotic species and are most frequently heterochromatic, behave parasitically, show a transmission rate higher than standard (A chromosomes, and can provoke harmful effects on carriers. In the current work, Prochilodus lineatus individuals carrying eight and nine B chromosomes were obtained by induced crossing performed involving breeders with different B chromosome numbers in their cells. The high B chromosome numbers found in the offspring were recorded for the first time in this species. The use of cytogenetic techniques applied in the present study revealed that regardless of the increase in number of B chromosomes in the genome of these individuals, those elements did not presented active genes, and showed their normal heterochromatic characteristic.

  8. Mre11 deficiency in Arabidopsis is associated with chromosomal instability in somatic cells and Spo11-dependent genome fragmentation during meiosis

    Czech Academy of Sciences Publication Activity Database

    Puizina, J.; Široký, Jiří; Schweizer, D.; Říha, K.

    2004-01-01

    Roč. 16, č. 8 (2004), s. 1968-1978. ISSN 1040-4651 R&D Projects: GA ČR GA522/03/0354; GA AV ČR IAA6004304 Grant ostatní: Austrian Science Foundation(AT) P16405 Institutional research plan: CEZ:AV0Z5004920 Keywords : MRE11 * Arabidopsis thaliana * chromosomes Subject RIV: BO - Biophysics Impact factor: 11.295, year: 2004

  9. Some indications from instability results about the effectiveness of wall heating as a control option for channel flow

    Indian Academy of Sciences (India)

    A Sameen; Rama Govindarajan

    2007-02-01

    This paper is a review of some of our recent work on the effect of wall heating on the stability of laminar flow in a channel. The summary of our results, some of them unexpected, is as follows. Viscosity stratification has very little effect on transient growth, whereas it results in linear mode stabilising or destabilising by an order of magnitude. It has hitherto been accepted that heat diffusivity does not affect stability. This is however true only for linear instability, transient growth is affected by an order of magnitude. Unusually, the growth is spanwise-independent and not in the form of streamwise vortices. It is also shown that flow is destabilised by secondary modes as the viscosity ratio increases. However, the viscosity ratio has no role in the selection of the pattern of vortices.

  10. Vibrio chromosomes share common history

    OpenAIRE

    Gevers Dirk; Chang Sarah; Chang LeeAnn; Kirkup Benjamin C; Polz Martin F

    2010-01-01

    Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II) were identified from 19 sequenced Vibrionales genomes ...

  11. Comparative analysis of cytogenetic manifestations of human genome instability

    International Nuclear Information System (INIS)

    The comparative analysis of cytogenetic manifestations of human genome instability was carried out. The studied parameters are the micronuclei rate (MNR), the level of single and double chromosome fragment and the level of premature chromatid division (PCD). PCD and chromosome fragments were chosen as anomalies that possibly result in MN formation. We analysed the MNR in buccal epithelium (BE) and peripheral blood lymphocytes (PBL), the level of single and double chromosome fragment as well as level PCD - in PBL only. Average MNR in BE was higher than in PBL. The studied parameters are independent ones and have to be considered altogether for more comprehensive evaluation of the level and peculiarities of manifestation of human genome instability

  12. Beam Instabilities

    CERN Document Server

    Rumolo, G

    2014-01-01

    When a beam propagates in an accelerator, it interacts with both the external fields and the self-generated electromagnetic fields. If the latter are strong enough, the interplay between them and a perturbation in the beam distribution function can lead to an enhancement of the initial perturbation, resulting in what we call a beam instability. This unstable motion can be controlled with a feedback system, if available, or it grows, causing beam degradation and loss. Beam instabilities in particle accelerators have been studied and analysed in detail since the late 1950s. The subject owes its relevance to the fact that the onset of instabilities usually determines the performance of an accelerator. Understanding and suppressing the underlying sources and mechanisms is therefore the key to overcoming intensity limitations, thereby pushing forward the performance reach of a machine.

  13. Instability results for the wave equation in the interior of Kerr black holes

    CERN Document Server

    Luk, Jonathan

    2015-01-01

    We prove that a large class of smooth solutions $\\psi$ to the linear wave equation $\\Box_g\\psi=0$ on subextremal rotating Kerr spacetimes which are regular and decaying along the event horizon become singular at the Cauchy horizon. More precisely, we show that assuming appropriate upper and lower bounds on the energy along the event horizon, the solution has infinite (non-degenerate) energy on any spacelike hypersurfaces intersecting the Cauchy horizon transversally. Extrapolating from known results in the Reissner--Nordstr\\"om case, the assumed upper and lower bounds required for our theorem are conjectured to hold for solutions arising from generic smooth and compactly supported initial data on a Cauchy hypersurface. This result is motivated by the strong cosmic censorship conjecture in general relativity.

  14. Chronic Myeloid Leukemia with Variant Chromosomal Translocations: Results of Treatment with Imatinib Mesylate

    Directory of Open Access Journals (Sweden)

    Rohan Bhise

    2013-01-01

    Full Text Available Objective: To evaluate the efficacy of imatinib in chronic myeloid leukemia patients with variant translocations. Methods: Forty eight chronic myeloid leukemia patients carrying variant translocations and treated with imatinib at our institute were considered for the study. Survival and response rates were evaluated. Results: The median follow up was 48 months(m. Forty three (89.58% patients achieved complete hematologic response. Thirty one (64.58% patients achieved complete cytogenetic response and 19(39.58% achieved major molecular response anytime during their follow up period. Only 18.75% of the patients achieved complete cytogenetic response and major molecular response within the stipulated time frames.The estimated overall survival at 48 m median follow up was 81.2%.The progression free survival was also 81.2% and the event free survival was 79.1%.There was no significant survival difference between low vs intermediate and high risk sokal group. Conclusion: We report suboptimal responses to imatinib in chronic myeloid leukemia with variant translocations. Further studies with imatinib and the newer more active drugs dasatinib and nilotinib are justified.

  15. Vertical Instability in EAST: Comparison of Model Predictions with Experimental Results

    Institute of Scientific and Technical Information of China (English)

    QIAN Jinping; WAN Baonian; SHEN Biao; XIAO Bingjia; SUN Youwen; SHI Yuejiang; LIN Shiyao; LI Jiangang; GONG Xianzu

    2008-01-01

    Growth rates of the axisymmetric mode in elongated plasmas in the experimental advanced superconducting tokamak (EAST) are measured with zero feedback gains and then compared with numerically calculated growth rates for the reconstructed shapes. The comparison is made after loss of vertical position control. The open-loop growth rates were scanned with the number of vessel eigenmodes, which up to 20 is enough to make the growth rates settled. The agreement between the growth rates measured experimentally and the growth rates determined numerically is good. The results show that a linear RZIP model is essentially good enough for the vertical position feedback control.

  16. Catastrophic chromosomal restructuring during genome elimination in plants.

    Science.gov (United States)

    Tan, Ek Han; Henry, Isabelle M; Ravi, Maruthachalam; Bradnam, Keith R; Mandakova, Terezie; Marimuthu, Mohan Pa; Korf, Ian; Lysak, Martin A; Comai, Luca; Chan, Simon Wl

    2015-01-01

    Genome instability is associated with mitotic errors and cancer. This phenomenon can lead to deleterious rearrangements, but also genetic novelty, and many questions regarding its genesis, fate and evolutionary role remain unanswered. Here, we describe extreme chromosomal restructuring during genome elimination, a process resulting from hybridization of Arabidopsis plants expressing different centromere histones H3. Shattered chromosomes are formed from the genome of the haploid inducer, consistent with genomic catastrophes affecting a single, laggard chromosome compartmentalized within a micronucleus. Analysis of breakpoint junctions implicates breaks followed by repair through non-homologous end joining (NHEJ) or stalled fork repair. Furthermore, mutation of required NHEJ factor DNA Ligase 4 results in enhanced haploid recovery. Lastly, heritability and stability of a rearranged chromosome suggest a potential for enduring genomic novelty. These findings provide a tractable, natural system towards investigating the causes and mechanisms of complex genomic rearrangements similar to those associated with several human disorders. PMID:25977984

  17. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    Science.gov (United States)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  18. Evaluating shoulder instability treatment

    OpenAIRE

    Linde, J. A.

    2016-01-01

    Shoulder instability common occurs. When treated nonoperatively, the resulting societal costs based on health care utilization and productivity losses are significant. Shoulder function can be evaluated using patient reported outcome measurements (PROMs). For shoulder instability, these include the Western Ontario Shoulder Instability index (WOSI) and the Oxford Shoulder Instability Score (OSIS). When translated and validated for the dutch population, both have good measurment properties. Sco...

  19. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres

    OpenAIRE

    Espejel, Silvia; Franco, Sonia; Rodríguez-Perales, Sandra; Bouffler, Simon D; Cigudosa, Juan C.; Blasco, María A.

    2002-01-01

    Here we analyze the functional interaction between Ku86 and telomerase at the mammalian telomere by studying mice deficient for both proteins. We show that absence of Ku86 prevents the end-to-end chromosomal fusions that result from critical telomere shortening in telomerase-deficient mice. In addition, Ku86 deficiency rescues the male early germ cell apoptosis triggered by short telomeres in these mice. Together, these findings define a role for Ku86 in mediating chromosomal instability and ...

  20. Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta)

    OpenAIRE

    Moore, Charleen M.; Dunn, Betty G.; McMahan, C. Alex; Lane, Mark A.; Roth, George S.; Ingram, Donald K.; Mattison, Julie A.

    2006-01-01

    The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the mos...

  1. [The retrospective cytogenetic dosimetry using the results of conventional chromosomal analysis in Chernobyl clean-up workers].

    Science.gov (United States)

    Maznik, N A; Vinnikov, V A

    2005-01-01

    The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up workers, who were surveyed with the conventional cytogenetic technique in terms from several days to 10 years after the end of their duties in the Chernobyl accident exclusive zone. An empirical model of the aberrant cell dynamics was utilized for the calculation of mean initial yields of dicentrics and centric rings in groups with different terms and duration of staying in the Chernobyl zone. Corresponding protracted irradiation doses estimated from aberration levels ranged from 79 to 670 mGy. The probabilistic distribution of the radiation doses was constructed by the applying the Bayesian analysis to initial individual chromosome exchange yields extrapolated to the exposure termination moment. This distribution was characterized by the mean dose about 460 mGy and maximum of probability density in the interval of 50-300 mGy. For the late somatic risk assessment in clean-up workers the probabilistic distribution of equivalentally-acute radiation doses was proposed; that had the mean value about 270 mGy, modal classes of 250-350 mGy and 99.8% of the probability density concentrated within the dose range from 0 to 1000 mGy. PMID:16454338

  2. Surgical Correction of Posttraumatic Scapulothoracic Bursitis, Rhomboid Major Muscle Injury, Ipsilateral Glenohumeral Instability, and Headaches Resulting from Circus Acrobatic Maneuvers

    Directory of Open Access Journals (Sweden)

    John G. Skedros

    2015-01-01

    Full Text Available We report the case of a 28-year-old transgender (male-to-female patient that had a partial tear of the rhomboid major tendon, scapulothoracic bursitis, and glenohumeral instability on the same side. These conditions resulted from traumatic events during circus acrobatic maneuvers. Additional aspects of this case that make it unique include (1 the main traumatic event occurred during a flagpole exercise, where the patient’s trunk was suspended horizontally while a vertical pole was grasped with both hands, (2 headaches were associated with the periscapular injury and they improved after scapulothoracic bursectomy and rhomboid tendon repair, (3 surgical correction was done during the same operation with an open anterior capsular-labral reconstruction, open scapulothoracic bursectomy without bone resection, and rhomboid tendon repair, (4 a postoperative complication of tearing of the serratus anterior and rhomboid muscle attachments with recurrent scapulothoracic pain occurred from patient noncompliance, and (5 the postoperative complication was surgically corrected and ultimately resulted in an excellent outcome at the one-year final follow-up.

  3. False Negative NIPT Results: Risk Figures for Chromosomes 13, 18 and 21 Based on Chorionic Villi Results in 5967 Cases and Literature Review.

    Directory of Open Access Journals (Sweden)

    Diane Van Opstal

    Full Text Available Non-invasive prenatal testing (NIPT demonstrated a small chance for a false negative result. Since the "fetal" DNA in maternal blood originates from the cytotrophoblast of chorionic villi (CV, some false negative results will have a biological origin. Based on our experience with cytogenetic studies of CV, we tried to estimate this risk. 5967 CV samples of pregnancies at high risk for common aneuplodies were cytogenetically investigated in our centre between January 2000 and December 2011. All cases of fetal trisomy 13, 18 and 21 were retrospectively studied for the presence of a normal karyotype or mosaicism < 30% in short-term cultured (STC- villi. 404 cases of trisomies 13, 18 and 21 were found amongst 5967 samples (6,8%. Of these 404 cases, 14 (3,7% had a normal or low mosaic karyotype in STC-villi and therefore would potentially be missed with NIPT. It involved 2% (5/242 of all trisomy 21 cases and 7.3% (9/123 of all trisomy 18 cases. In 1:426 (14/5967 NIPT samples of patients at high risk for common aneuploidies, a trisomy 18 or 21 will potentially be missed due to the biological phenomenon of absence of the chromosome aberration in the cytotrophoblast.

  4. Chromosome Microarray.

    Science.gov (United States)

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  5. Tn5401 disruption of the spo0F gene, identified by direct chromosomal sequencing, results in CryIIIA overproduction in Bacillus thuringiensis.

    OpenAIRE

    Malvar, T.; Baum, J A

    1994-01-01

    The Bacillus thuringiensis spo0F gene was identified by chromosomal DNA sequencing of sporulation mutants derived from a B. thuringiensis transposon insertion library. A spo0F defect in B. thuringiensis, which was suppressed by multicopy hknA or kinA, resulted in the overproduction of the CryIIIA insecticidal crystal protein.

  6. Long-term quasi-periodicity of 4U 1636-536 resulting from accretion disc instability

    CERN Document Server

    Wisniewicz, Mateusz; Gondek-Rosinska, Dorota; Zdziarski, Andrzej A; Janiuk, Agnieszka

    2015-01-01

    We present the results of a study of the low-mass X-ray binary 4U 1636-536. We have performed temporal analysis of all available RXTE/ASM, Swift/BAT and MAXI data. We have confirmed the previously discovered quasi-periodicity of ~45 d present during ~2004, however we found it continued to 2006. At other epochs, the quasi-periodicity is only transient, and the quasi-period, if present, drifts. We have then applied a time-dependent accretion disc model to the interval with the significant X-ray quasi-periodicity. For our best model, the period and the amplitude of the theoretical light curve agree well with that observed. The modelled quasi-periodicity is due to the hydrogen thermal-ionization instability occurring in outer regions of the accretion disc. The model parameters are the average mass accretion rate (estimated from the light curves), and the accretion disc viscosity parameters, for the hot and cold phases. Our best model gives relatively low values of viscosity parameter for cold phase 0.01 and for h...

  7. Induction of chromosome instability and stomach cancer by altering the expression pattern of mitotic checkpoint genes in mice exposed to areca-nut

    International Nuclear Information System (INIS)

    developed cancer earlier, (b) perturbations in components of the chromosome segregation machinery could be involved in the initial process of carcinogenicity and (c) the importance of precocious anaphase as a screening marker for identification of mitotic checkpoint defects during early days

  8. Micromechanics of human mitotic chromosomes

    International Nuclear Information System (INIS)

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed

  9. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  10. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    DNA damages induced by space radiation, consisting of protons and high-LET charged particles, can be complex in nature, which are often left unrepaired and cause chromosomal aberrations. Increased level of genomic instability is attributed to tumorigenesis and increased cancer risks. To investigate genomic instability induced by charged particles, human lymphocytes ex vivo, human fibroblasts, and human mammary epithelial cells, as well as mouse bone marrow stem cells isolated from CBA/CaH and C57BL/6 strains were exposed to high energy protons and Fe ions. Metaphase chromosome spreads at different cell divisions after radiation exposure were collected and, chromosome aberrations were analyzed with fluorescence in situ hybridization with whole chromosome-specific probes for human cells. With proton irradiation, levels of chromosome aberrations decreased by about 50% in both lymphocytes and epithelial cells after multiple cell divisions, compared to initial chromosome aberrations at 48 hours post irradiation in both cell types. With Fe ion irradiation, however, the frequency of chromosome aberrations in lymphocytes after multiple cell divisions was significantly lower than that in epithelial cells at comparable cell divisions, while their initial chromosome aberrations were at similar levels. Similar to the human cells, after Fe ion irradiation, the frequency of late chromosome aberrations was similar to that of the early damages for radio-sensitive CBA cells, but different for radio-resistant C57 cells. Our results suggest that relative biological effectiveness (RBE) values are dependent not only on radiation sources, but also on cell types and cell divisions.

  11. Divergent actions of long noncoding RNAs on X-chromosome remodelling in mammals and Drosophila achieve the same end result: dosage compensation

    Indian Academy of Sciences (India)

    Subhash C. Lakhotia

    2015-12-01

    Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of the sex chromosome-linked genes that have somatic functions. In-depth cytological and subsequent biochemical and molecular studies on dosage compensation started with Mary F. Lyon’s proposal in early 1960s that the Barr body in female mammalian somatic cells represented one of the randomly inactivated and heterochromatinized X chromosomes. In contrast, Drosophila was soon shown to achieve dosage compensation through hypertranscription of single X in male whose chromatin remains more open. Identification of proteins that remodel chromatin either to cause one of the two X chromosomes in somatic cells of very early female mammalian embryos to become condensed and inactive or to remodel the single X in male Drosophila embryos to a more open state for hypertranscription provided important insights into the underlying cellular epigenetic processes. However, the most striking and unexpected discoveries were the identification of long noncoding RNAs (lncRNAs), X- inactive specific transcript (Xist) in mammals and roX1/2 in Drosophila, which were essential for achieving the contrasting chromatin organizations but leading to similar end result in terms of dosage compensation of X-linked genes in females and males. An overview of the processes of X inactivation or hyperactivation in mammals and Drosophila, respectively, and the roles played by Xist, roX1/2 and other lncRNAs in these events is presented.

  12. Experimental and numerical results on three-dimensional instabilities in a rotating disk-tall cylinder flow

    DEFF Research Database (Denmark)

    Sørensen, Jens Nørkær; Gelfgat, A. Yu; Naumov, I. V.; Mikkelsen, Robert Flemming

    2009-01-01

    The three-dimensional axisymmetry-breaking instability of axisymmetric flow between a rotating lid and a stationary cylinder is analyzed both numerically and experimentally for the case of tall cylinders with the height/radius aspect ratio between 3.3 and 5.5. A complete stability diagram for the...

  13. Causes of genome instability

    DEFF Research Database (Denmark)

    Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel;

    2015-01-01

    Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus......, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other...... chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling...

  14. Severe neonatal Marfan syndrome resulting from a de novo 3-bp insertion into the fibrillin gene on chromosome 15.

    OpenAIRE

    Milewicz, D.M.; Duvic, M

    1994-01-01

    Severe neonatal Marfan syndrome has features of the Marfan syndrome and congenital contractural arachnodactyly present at birth, along with unique features such as loose, redundant skin and pulmonary emphysema. Since the Marfan syndrome and congenital contractural arachnodactyly are due to mutations in different genes, it has been uncertain whether neonatal Marfan syndrome is due to mutations in the fibrillin gene on chromosome 15 or in another gene. We studied an infant with severe neonatal ...

  15. Inactivation of normal human fibroblasts by ionising irradiation results to a similar extent from chromosomal damage and p53-dependent G1-arrest

    International Nuclear Information System (INIS)

    After ionizing irradiation, fibroblasts lose clonogenicity (1) by non-repaired DNA double-strand breaks leading to lethal chromosome aberrations and (2) by permanent G1 arrest. The aim of this study was to determine the relative contribution of these two processes. 13 normal human fibroblast strains and 3 cell lines with non-functional p53 (LFS2800, FaDu, CHO). Cells were irradiated in plateau phase followed by immediate or delayed (14 h) plating. Lethal chromosome aberrations (CA) were measured by metaphase technique, the fraction of cells permanently arrested in G1 (fG1arr) by flow cytometry and cell survival by colony assay. For normal human fibroblasts, the number of lethal chromosome aberrations increased with dose but varied substantially among the strains studied. Only for delayed but not immediate plating the surviving fraction was correlated with the number of lethal aberrations (r2 =0.69, p2 =0.19, p=0.16). When survival was converted into lethal events the ratio between these events and the number of lethal aberrations amounted to 2.00±0.05:1, indicating that chromosomal damage accounted on average for only 50% of cell killing. The remainder was attributed to cell inactivation by the p53-dependent permanent G1-arrest, since cells lacking in functional p53 (LFS2800, FaDu, CHO) were characterised by a ratio of 1.01±0.02:1. In addition, there was a negative correlation between the extent of G1-arrest and the number of CA with those cell lines showing the highest G1-arrest having the lowest number of CA indicating that there is an interaction between these two processes. For normal human fibroblasts, cell inactivation results from chromosomal damage and permanent G1 arrest to a similar extent

  16. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  17. Tracking Code for Microwave Instability

    Energy Technology Data Exchange (ETDEWEB)

    Heifets, S.; /SLAC

    2006-09-21

    To study microwave instability the tracking code is developed. For bench marking, results are compared with Oide-Yokoya results [1] for broad-band Q = 1 impedance. Results hint to two possible mechanisms determining the threshold of instability.

  18. Nitric Oxide: Genomic Instability And Synthetic Lethality

    Directory of Open Access Journals (Sweden)

    Vasily A. Yakovlev

    2015-08-01

    Loss or inhibition of Poly(ADP-ribose polymerase 1 (PARP1 activity results in accumulation of DNA single-strand breaks, which are subsequently converted to DSB by the transcription machinery. In BRCA-positive cells, DSB are repaired by HRR, but they cannot be properly repaired in BRCA1-deficient cells, leading to genomic instability, chromosomal rearrangements, and cell death. Our data demonstrated that combination of NO-donors with PARP inhibitors significantly sensitized the BRCA1-positive cancer cells to DNA-damaging agents.

  19. Shoulder Instability

    Science.gov (United States)

    ... Risk Factors Is shoulder instability the same as shoulder dislocation? No. The signs of dislocation and instability might ... the same to you--weakness and pain. However, dislocation occurs when your shoulder goes completely out of place. The shoulder ligaments ...

  20. Partial Excision of the Chromosomal Cassette Containing the Methicillin Resistance Determinant Results in Methicillin-Susceptible Staphylococcus aureus

    Science.gov (United States)

    Donnio, Pierre-Yves; Oliveira, Duarte C.; Faria, Nuno A.; Wilhelm, Nathalie; Le Coustumier, Alain; de Lencastre, Herminia

    2005-01-01

    We report a detailed characterization of methicillin-susceptible Staphylococcus aureus isolates from five French hospitals negative for both the mecA and the ccrAB loci but positive for the IS431::pUB110::IS431::dcs structure, present in some Staphylococcus cassette chromosome mec (SCCmec) types. The presence of SCCmec-associated elements suggests that this unusual resistant phenotype is due to a partial excision of SCCmec from epidemic methicillin-resistant S. aureus. The hypothesis of a genetic relatedness is strengthened by common sequence and spa types and similar susceptibility patterns. PMID:16081974

  1. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  2. Induction of Genomic Instability In Vivo by Low Doses of 137Cs gamma rays

    International Nuclear Information System (INIS)

    The overall goal of this project is to determine if low doses (below or equal to the level traditionally requiring human radiation protection, i.e. less than or equal to 10 cGy) of low LET radiation can induce genomic instability. The magnitude of genomic instability was measured as delayed chromosome instability in bone marrow cells of exposed mice with different levels of endogenous DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, i.e. high (C57BL/6J mice), intermediate (BALB/cJ mice), and extremely low (Scid mice). In addition, at early time points (1 and 4 hrs) following irradiation, levels of activation of nuclear factor-kappa B (NF-κB), a transcription factor known to be involved in regulating the expression of genes responsible for cell protection following stimuli, were measured in these cells. Bone marrow cells were collected at different times following irradiation, i.e. 1 hr, 4 hrs, 1 month, and 6 months. A total of five mice per dose per strain were sacrificed at each time point for sample collection. As a result, a total of 80 mice from each strain were used. The frequency and the type of metaphase chromosome aberrations in bone marrow cells collected from exposed mice at different times following irradiation were used as markers for radiation-induced genomic instability. A three-color fluorescence in situ hybridization (FISH) protocol for mouse chromosomes 1, 2, and 3 was used for the analysis of delayed stable chromosomal aberrations in metaphase cells. All other visible chromatid-type aberrations and gross structural abnormalities involving non-painted chromosomes were also evaluated on the same metaphase cells used for scoring the stable chromosomal aberrations of painted chromosomes. Levels of nuclear factor-kappa B (NF-κB) activation were also determined in cells at 1 and 4 hrs following irradiation (indicative of early responses)

  3. Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst

    OpenAIRE

    Cerbone, Manuela; Wang, Jun; van der Maarel, Silvère M.; D’Amico, Alessandra; d’Agostino, Antonio; Romano, Alfonso; Brunetti-Pierri, Nicola

    2012-01-01

    The Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome is an autosomal recessive disease presenting with immunodeficiency secondary to hypo- or agammaglobulinemia, developmental delay, and facial anomalies. Centromeric instability is the cytogenetic hallmark of the disorder which results from targeted chromosomal rearrangements related to a genomic methylation defect. We describe a patient carrying a homozygous mutation of the ZBTB24 gene, which has been recently shown...

  4. Modelling Financial Instability

    OpenAIRE

    Franklin Allen

    2005-01-01

    Financial instability can have large adverse effects on an economy. One major cause of instability is asset price bubbles. This paper starts by considering how such bubbles can arise due to the expansion of money and credit. The ways in which subsequent financial instability occurs are then discussed. Banking crises can arise due to panics or as a result of the business cycle. Contagion and financial fragility can cause small disturbances to have large effects. Finally, policy issues are touc...

  5. Comparison of cell repair mechanisms by means of chromosomal aberration induced by proton and gamma irradiation - preliminary results

    Science.gov (United States)

    Kowalska, A.; Czerski, K.; Kaczmarski, M.; Lewocki, M.; Masojć, B.; Łukowiak, A.

    2015-03-01

    DNA damage of peripheral blood lymphocytes exposed to gamma and proton irradiation is studied by means of chromosome aberrations to validate the efficiency of the repair mechanisms of individual cells. A new method based on an observed deviation from the Poisson statistics of the chromosome aberration number is applied for estimation of a repair factor ( RF) defined as a ratio between originally damaged cells to the amount of finally observed aberrations. The repair factors are evaluated by studying the variance of individual damage factors in a collective of healthy persons at a given dose as well as by using the chi-square analysis for the dose-effect curves. The blood samples from fifteen donors have been irradiated by Co60 gamma rays and from nine persons by 150 MeV protons with different doses up to 2 Gy. A standard extraction of lymphocyte has been used whereby dicentrics, acentrics and rings have been scored under a microscope. The RF values determined for the proton radiation are slightly larger than for gamma rays, indicating that up to 70% DNA double strand breaks can be repaired.

  6. Self-consistent kinetic simulations of lower hybrid drift instability resulting in electron current driven by fusion products in tokamak plasmas

    CERN Document Server

    Cook, J W S; Dendy, R O

    2010-01-01

    We present particle-in-cell (PIC) simulations of minority energetic protons in deuterium plasmas, which demonstrate a collective instability responsible for emission near the lower hybrid frequency and its harmonics. The simulations capture the lower hybrid drift instability in a regime relevant to tokamak fusion plasmas, and show further that the excited electromagnetic fields collectively and collisionlessly couple free energy from the protons to directed electron motion. This results in an asymmetric tail antiparallel to the magnetic field. We focus on obliquely propagating modes under conditions approximating the outer mid-plane edge in a large tokamak, through which there pass confined centrally born fusion products on banana orbits that have large radial excursions. A fully self-consistent electromagnetic relativistic PIC code representing all vector field quantities and particle velocities in three dimensions as functions of a single spatial dimension is used to model this situation, by evolving the in...

  7. Shoulder instability

    International Nuclear Information System (INIS)

    In the shoulder, the advantages of range of motion are traded for the disadvantages of vulnerability to injury and the development of instability. Shoulder instability and the lesion it produces represent one of the main causes of shoulder discomfort and pain. Shoulder instability is defined as a symptomatic abnormal motion of the humeral head relative to the glenoid during active shoulder motion. Glenohumeral instabilities are classified according to their causative factors as the pathogenesis of instability plays an important role with respect to treatment options: instabilities are classified in traumatic and atraumatic instabilities as part of a multidirectional instability syndrome, and in microtraumatic instabilities. Plain radiographs ('trauma series') are performed to document shoulder dislocation and its successful reposition. Direct MR arthrography is the most important imaging modality for delineation the different injury patterns on the labral-ligamentous complex and bony structures. Monocontrast CT-arthrography with use of multidetector CT scanners may be an alternative imaging modality, however, regarding the younger patient age, MR imaging should be preferred in the diagnostic work-up of shoulder instabilities. (orig.)

  8. Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells.

    Science.gov (United States)

    Yamano, Noriko; Takahashi, Mai; Ali Haghparast, Seyed Mohammad; Onitsuka, Masayoshi; Kumamoto, Toshitaka; Frank, Jana; Omasa, Takeshi

    2016-08-01

    Chromosomal instability is a characteristic of Chinese hamster ovary (CHO) cells. Cultures of these cells gradually develop heterogeneity even if established from a single cell clone. We isolated cells containing different numbers of chromosomes from a CHO-DG44-based human granulocyte-macrophage colony stimulating factor (hGM-CSF)-producing cell line and found that high chromosome number cells showed higher hGM-CSF productivity. Therefore, we focused on the relationship between chromosome aneuploidy of CHO cells and high recombinant protein-producing cell lines. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. Both cell lines were stably transfected with a vector that expresses immunoglobulin G3 (IgG3), and specific antibody production rates were compared. Cells containing more than 30 chromosomes had higher specific antibody production rates than those with normal chromosome number. Single cell analysis of enhanced green fluorescent protein (Egfp)-gene transfected cells revealed that increased GFP expression was relative to the number of gene integration sites rather than the difference in chromosome numbers or vector locations. Our results suggest that CHO cells with high numbers of chromosomes contain more sites for vector integration, a characteristic that could be advantageous in biopharmaceutical production. PMID:26850366

  9. Effects on Genome Constitution and Novel Cell Wall Formation Caused by the Addition of 5RS Rye Chromosome to Common Wheat

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun Cheng; Minoru Murata; Sodmergen; Xiao-Mei Li; Hai Nian; Jian-Min Wan

    2008-01-01

    The cytological instability of common wheat-rye addition lines was investigated in the present study. The chromosome numbers of almost all addition lines were considerably stable, but those of CS + 5R were very variable. The rye chromosome added in this line was found to be much shorter than expected. Fluorescent in situ hybridization with 5S rDNA and the centromere-specific probes clearly revealed that the short rye chromosome contains only a short arm of chromosome 5R (5RS). In this line, chromosome numbers of both 5RS and common wheat were changeable. The chromosome numbers ranged from 2n = 36 to 2n = 44 in the cells carrying two 5RS, and ranged from 2n = 31 to 2n = 44 in one 5RS cells. In addition to the chromosome instability, the multicells wrapped in a sac-like structure were frequently observed in the root meristematic tissues of CS + 5RS after the enzyme treatment for chromosome preparation. Genomic in situ hybridization with rye DNA as a probe showed that all cells in sacs investigated were at the interphase stage and contained one or two 5RS chromosomes. An electron microscopic analysis revealed that the cells of CS + 5RS, particularly in sacs, have abnormal (irregular and curved) cell walls. These results indicate that 5RS has (a) specific factor(s) influencing the cell wall development as well as the genome stability.

  10. Fluidelastic instability in tube arrays

    International Nuclear Information System (INIS)

    When an array of tubes is subjected to crossflow, the tubes can experience dynamic instability, generally called fluidelastic instability. Instability initiates when the crossflow velocity exceeds a threshold value above which energy input from the flow exceeds that dissipated by system damping. Catastrophic failures of reactor and process plant equipment have been attributed to fluidelastic instability. As a result, extensive research studies have been conducted in the last 15 years with the objective of understanding the instability mechanisms and developing general design guidelines to avoid instability. Argonne National Laboratory has a continuing research program in this area which includes both mathematical model development and experimentation. This paper describes recent developments and accomplishments

  11. Hip instability.

    Science.gov (United States)

    Smith, Matthew V; Sekiya, Jon K

    2010-06-01

    Hip instability is becoming a more commonly recognized source of pain and disability in patients. Traumatic causes of hip instability are often clear. Appropriate treatment includes immediate reduction, early surgery for acetabular rim fractures greater than 25% or incarcerated fragments in the joint, and close follow-up to monitor for avascular necrosis. Late surgical intervention may be necessary for residual symptomatic hip instability. Atraumatic causes of hip instability include repetitive external rotation with axial loading, generalized ligamentous laxity, and collagen disorders like Ehlers-Danlos. Symptoms caused by atraumatic hip instability often have an insidious onset. Patients may have a wide array of hip symptoms while demonstrating only subtle findings suggestive of capsular laxity. Traction views of the affected hip can be helpful in diagnosing hip instability. Open and arthroscopic techniques can be used to treat capsular laxity. We describe an arthroscopic anterior hip capsular plication using a suture technique. PMID:20473129

  12. Characterization of genomic instability in Saccharomyces cerevisiae and engaging teaching strategies described in two curricula

    Science.gov (United States)

    Keller, Alexandra P.

    Cancer arises through an accumulation of mutations in the genome. In cancer cells, mutations are frequently caused by DNA rearrangements, which include chromosomal breakages, deletions, insertions, and translocations. Such events contribute to genomic instability, a known hallmark of cancer. To study cycles of chromosomal instability, we are using baker's yeast as a model organism. In yeast, a ChrVII system was previously developed (Admire et al., 2006), in which a disomic yeast strain was used to identify regions of instability on ChrVII. Using this system, a fragile site on the left arm of ChrVII (Admire et al., 2006) was identified and characterized. This study led to insight into mechanisms involved in chromosomal rearrangements and mutations that arise from them as well as to an understanding of mechanisms involved in genomic instability. To further our understanding of genomic instability, I devised a strategy to study instability on a different chromosome (ChrV) (Figure 3), so that we could determine whether lessons learned from the ChrVII system are applicable to other chromosomes, and/or whether other mechanisms of instability could be identified. A suitable strain was generated and analyzed, and our findings suggest that frequencies of instability on the right arm of ChrV are similar to those found in ChrVII. The results from the work in ChrV described in this paper support the idea that the instability found on ChrVII is not an isolated occurrence. My research was supported by an NSF GK-12 grant. The aim of this grant is to improve science education in middle schools, and as part of my participation in this program, I studied and practiced effective science communication methodologies. In attempts to explain my research to middle school students, I collaborated with others to develop methods for explaining genetics and the most important techniques I used in my research. While developing these methods, I learned more about what motivates people to learn

  13. Instability in evolutionary games.

    Directory of Open Access Journals (Sweden)

    Zimo Yang

    Full Text Available BACKGROUND: Phenomena of instability are widely observed in many dissimilar systems, with punctuated equilibrium in biological evolution and economic crises being noticeable examples. Recent studies suggested that such instabilities, quantified by the abrupt changes of the composition of individuals, could result within the framework of a collection of individuals interacting through the prisoner's dilemma and incorporating three mechanisms: (i imitation and mutation, (ii preferred selection on successful individuals, and (iii networking effects. METHODOLOGY/PRINCIPAL FINDINGS: We study the importance of each mechanism using simplified models. The models are studied numerically and analytically via rate equations and mean-field approximation. It is shown that imitation and mutation alone can lead to the instability on the number of cooperators, and preferred selection modifies the instability in an asymmetric way. The co-evolution of network topology and game dynamics is not necessary to the occurrence of instability and the network topology is found to have almost no impact on instability if new links are added in a global manner. The results are valid in both the contexts of the snowdrift game and prisoner's dilemma. CONCLUSIONS/SIGNIFICANCE: The imitation and mutation mechanism, which gives a heterogeneous rate of change in the system's composition, is the dominating reason of the instability on the number of cooperators. The effects of payoffs and network topology are relatively insignificant. Our work refines the understanding on the driving forces of system instability.

  14. Caffeine-Induced Premature Chromosome Condensation Results in the Apoptosis-Like Programmed Cell Death in Root Meristems of Vicia faba.

    Directory of Open Access Journals (Sweden)

    Dorota Rybaczek

    Full Text Available We have demonstrated that the activation of apoptosis-like programmed cell death (AL-PCD was a secondary result of caffeine (CF induced premature chromosome condensation (PCC in hydroxyurea-synchronized Vicia faba root meristem cells. Initiation of the apoptotic-like cell degradation pathway seemed to be the result of DNA damage generated by treatment with hydroxyurea (HU [double-stranded breaks (DSBs mostly] and co-treatment with HU/CF [single-stranded breaks (SSBs mainly]. A single chromosome comet assay was successfully used to study different types of DNA damage (neutral variant-DSBs versus alkaline-DSBs or SSBs. The immunocytochemical detection of H2AXS139Ph and PARP-2 were used as markers for DSBs and SSBs, respectively. Acridine orange and ethidium bromide (AO/EB were applied for quantitative immunofluorescence measurements of dead, dying and living cells. Apoptotic-type DNA fragmentation and positive TUNEL reaction finally proved that CF triggers AL-PCD in stressed V. faba root meristem cells. In addition, the results obtained under transmission electron microscopy (TEM further revealed apoptotic-like features at the ultrastructural level of PCC-type cells: (i extensive vacuolization; (ii abnormal chromatin condensation, its marginalization and concomitant degradation; (iii formation of autophagy-like vesicles (iv protoplast shrinkage (v fragmentation of cell nuclei and (vi extensive degeneration of the cells. The results obtained have been discussed with respect to the vacuolar/autolytic type of plant-specific AL-PCD.

  15. Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction

    Directory of Open Access Journals (Sweden)

    Despoina Sakellariou

    2013-11-01

    Full Text Available Human tumors using the alternative lengthening of telomeres (ALT exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth.

  16. Intra- and interindividual variability in lymphocyte chromosomal aberrations: implications for cancer risk assessment.

    Science.gov (United States)

    Peters, Susan; Portengen, Lützen; Bonassi, Stefano; Sram, Radim; Vermeulen, Roel

    2011-08-15

    Chromosomal aberration frequency in peripheral lymphocytes of healthy individuals has been found to be predictive of future cancer risk. The variability of chromosomal aberrations over time, which is largely unknown, should be clarified to interpret the strength of this association and to determine its use in cancer prediction. Intra- and interindividual variability in chromosomal aberration frequency was therefore determined. From a pooled database comprising 11 national cohorts (1965-2002), the authors included 9,433 blood samples from 3,550 subjects with at least one repeated chromosomal aberration measurement. The generalized concordance correlation coefficient of 0.19 was low, indicating high intraindividual variability compared with interindividual variability, resulting in a high likelihood of misclassification. The relation between chromosomal aberration frequency and future cancer risk has probably been underestimated in previous studies. A single chromosomal aberration measurement seems not to be representative of the whole lifespan level of chromosome instability and greatly limits the use of chromosomal aberration frequency-as measured with Giemsa staining-for individual risk assessment. PMID:21652601

  17. Alternative lengthening of telomeres: recurrent cytogenetic aberrations and chromosome stability under extreme telomere dysfunction.

    Science.gov (United States)

    Sakellariou, Despoina; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis

    2013-11-01

    Human tumors using the alternative lengthening of telomeres (ALT) exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN) in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines. We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted. We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs) were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth. PMID:24339742

  18. Mitotic instability of Pichia pinus diploid cells 2. Segregation induced by gamma-irradiation

    International Nuclear Information System (INIS)

    Two types of genetic damages resulted from gamma rays in diploid cells of yeasts Pichia pinus MH4: nonlethal damages resulting in increasing frequency of mitotic crossing-over and lethal damages leading to cell death or arising unstable clones have been described. Survaving irradiated cells with lethal damages (which nature is not established) originate ''grown'' colonies which instability is manifested in the increased frequency of segregation of lethal sections and aneuploid segregants; in such colonies segregants without one, two or three nonhomologous chromosomes are often found. It is concluded that losses of separate chromosomes are not those primary damages which result in radiation inactivation of cells

  19. Genomic instability following irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hacker-Klom, U.B.; Goehde, W. [Inst. fuer Strahlenbiologie, Muenster Univ. (Germany)

    2001-07-01

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  20. Genomic instability following irradiation

    International Nuclear Information System (INIS)

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  1. The three-in-one proximal and distal soft tissue patellar realignment procedure. Results, and its place in the management of patellofemoral instability

    DEFF Research Database (Denmark)

    Myers, P; Williams, Andrew Richard; Dodds, R;

    1999-01-01

    at a minimum 25-month follow-up (range, 25 to 85 months; mean, 44). Thirty-two of 42 knees (76%) with recurrent patellar dislocation had good or excellent results after surgery. Redislocation occurred in four knees (9.5%). Skeletal immaturity, chondral damage, and generalized ligament laxity did not...... patellar stabilization. We describe the place of the three-in-one operation in our surgical protocol for patellofemoral instability, which is based on the principle that a procedure should be selected to address the underlying pathologic features in an individual case rather than always using one operation...

  2. Hypersensitivity to ionizing radiation, in vitro, in a new chromosomal breakage disorder, the Nijmegen Breakage Syndrome

    International Nuclear Information System (INIS)

    The Nijmegen Breakage Syndrome (NBS) is a new chromosomal instability disorder different from ataxia telangiectasia (AT) and other chromosome-breakage syndromes. Cells from an NBS patient appeared hypersensitive to X-irradiation. X-rays induced significantly more chromosomal damage in NBS lymphocytes and fibroblasts than in normal cells. The difference was most pronounced after irradiation in G2. Further, NBS fibroblasts were more readily by X-rays than normal fibroblasts. In addition, the DNA synthesis in NBS cells was more resistant to X-rays and bleomycin than that in normal cells. The reaction of NBS cells to X-rays and bleomycin was similar to that of cells from patients with ataxia telangiectasia. Our results indicate that NBS and AT, which also have similar chromosomal characteristics, must be closely related. (orig.)

  3. Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22.

    Science.gov (United States)

    Aviv, H; Lieber, C; Yenamandra, A; Desposito, F

    1997-06-27

    Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment. PMID:9182781

  4. Chromosomal aberration

    International Nuclear Information System (INIS)

    Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G1 phase. (author)

  5. Sequential cloning of chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  6. [Chromosomal organization of the genomes of small-chromosome plants].

    Science.gov (United States)

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species. PMID:20058798

  7. Cancer morphology, carcinogenesis and genetic instability: a background.

    Science.gov (United States)

    Bignold, Leon P; Coghlan, B L D; Jersmann, H P A

    2006-01-01

    Morphological abnormalities of both the nuclei and the cell bodies of tumour cells were described by Müller in the late 1830s. Abnormalities of mitoses and chromosomes in tumour cells were described in the late 1880s. Von Hansemann, in the 1890s, suggested that tumour cells develop from normal cells because of a tendency to mal-distribution and other changes of chromosomes occurring during mitosis. In the first decades of the 20th century, Mendelian genetics and "gene mapping" of chromosomes were established, and the dominant or recessive bases of the familial predispositions to certain tumour types were recognised. In the same period, the carcinogenic effects of ionising radiations, of certain chemicals and of particular viruses were described. A well-developed "somatic gene-mutational theory" of tumours was postulated by Bauer in 1928. In support of this, in the next three decades, many environmental agents were found to cause mitotic and chromosomal abnormalities in normal cells as well as mutations in germ-line cells of experimental animals. Nevertheless, mitotic, chromosomal, and other mutational theories were not popular explanations of tumour pathogenesis in the first half of the 20th century. Only in the 1960s did somatic mutational mechanisms come to dominate theories of tumour formation, especially as a result of the discoveries of the reactivity of carcinogens with DNA, and that the mutation responsible for xeroderma pigmentosum causes loss of function of a gene involved in the repair of DNA after damage by ultraviolet light (Cleaver in 1968). To explain the complexity of tumourous phenomena, "multi-hit" models gained popularity over "single-hit" models of somatic mutation, and "epigenetic" mechanisms of gene regulation began to be studied in tumour cells. More recently, the documentation of much larger-than-expected numbers of genomic events in tumour cells (by Stoler and co-workers, in 1999) has raised the issue of somatic genetic instability in

  8. Chronic Ankle Instability

    Science.gov (United States)

    ... ankle surgeon will ask you about any previous ankle injuries and instability. Then s/he will examine your ankle ... Weak ankles may be a result of previous ankle injuries, but in some cases they are a congenital ( ...

  9. Genetic instability in urinary bladder cancer: An evolving hallmark

    Directory of Open Access Journals (Sweden)

    N Wadhwa

    2013-01-01

    Full Text Available Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA mismatch repair (MMR system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

  10. Baroclinic instabilities

    OpenAIRE

    Joly, Laurent; Chassaing, Patrick; Chapin, Vincent; Reinaud, Jean; Micallef, J; Suarez, Juan; Bretonnet, L

    2003-01-01

    1. Introduction - Illustrative examples from experiments and simulations 2. The baroclinic torque in high Froude number flows, its organization, scale and order of magnitude 3. Stability of the inhomogeneous mixing-layer 4. Transition of the inhomogeneous mixing-layer and the 2D secondary baroclinic instability 5. The strain field of 2D light jets 6. Transition to three-dimensionality in light jets and the question of side-jets 7. Baroclinic instability of heavy vortices and...

  11. Carpal instability

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, R.; Froehner, S.; Coblenz, G.; Christopoulos, G. [Institut fuer Diagnostische und Interventionelle Radiologie, Herz- und Gefaessklinik GmbH, Bad Neustadt an der Saale (Germany)

    2006-10-15

    This review addresses the pathoanatomical basics as well as the clinical and radiological presentation of instability patterns of the wrist. Carpal instability mostly follows an injury; however, other diseases, like CPPD arthropathy, can be associated. Instability occurs either if the carpus is unable to sustain physiologic loads (''dyskinetics'') or suffers from abnormal motion of its bones during movement (''dyskinematics''). In the classification of carpal instability, dissociative subcategories (located within proximal carpal row) are differentiated from non-dissociative subcategories (present between the carpal rows) and combined patterns. It is essential to note that the unstable wrist initially does not cause relevant signs in standard radiograms, therefore being ''occult'' for the radiologic assessment. This paper emphasizes the high utility of kinematographic studies, contrast-enhanced magnetic resonance imaging (MRI) and MR arthrography for detecting these predynamic and dynamic instability stages. Later in the natural history of carpal instability, static malalignment of the wrist and osteoarthritis will develop, both being associated with significant morbidity and disability. To prevent individual and socio-economic implications, the handsurgeon or orthopedist, as well as the radiologist, is challenged for early and precise diagnosis. (orig.)

  12. Genetic instability in Gynecological Cancer

    Institute of Scientific and Technical Information of China (English)

    ZHAO Qing-hua; ZHOU Hong-lin

    2003-01-01

    Defects of mismatch repair (MMR) genes also have beenidentified in many kinds of tumors. Loss of MMR functionhas been linked to genetic instability especially microsatelliteinstability that results in high mutation rate. In this review, wediscussed the microsatellite instability observed in thegynecological tumors. We also discussed defects in the DNAmismatch repair in these tumors and their correlation to themicrosatellite instability, as well as the gene mutations due tothe microsatellite instability in these tumors. From thesediscussion, we tried to understand the mechanism ofcarcinogenesis in gynecological tumors from the aspect ofgenetic instability due to mismatch repair defects.

  13. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes. PMID:26111960

  14. Fluorescence in situ hybridisation in chromosome aberration detection in subjects occupationally exposed to ionising radiation

    International Nuclear Information System (INIS)

    For more than two decades, chromosomal aberration analysis has been used to detect structural chromosomal aberrations as sensitive biodosimeters of occupational exposure to ionising radiation. Its use is also recommended by the World Health Organisation. Changes in chromosome structure detected by that method are considered to be early biomarkers of a possible malignant disease. Aberrations detected by the method are unstable and can be found in the lymphocytes of irradiated personnel only within a limited time after exposure. To detect stable chromosomal aberrations, which persist after exposure, multicolour fluorescent in situ hybridisation has to be used. Using DNA probes labelled with different fluorochromes, it dyes each pair of chromosomes with different colour. Due to the dynamic of unstable aberration formation, chromosomal aberration analysis is more suitable in genome damage assessment of recent exposures. On the other hand, fluorescence in situ hybridisation gives the information on chromosome instability caused by long-term occupational exposure to ionising radiation. Considering the high costs of fluorescence in situ hybridisation and the uncertainty of the result, it should be used in biodosimetry only when it is absolutely necessary.(author)

  15. Chromosome arm-specific long telomeres: a new clonal event in primary chronic myelogenous leukemia cells.

    Science.gov (United States)

    Samassekou, Oumar; Li, Huiyu; Hébert, Josée; Ntwari, Aimé; Wang, Haixia; Cliché, Catherine Grenier; Bouchard, Eric; Huang, Shiang; Yan, Ju

    2011-06-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32) of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp) with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation. PMID:21677878

  16. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Oumar Samassekou

    2011-06-01

    Full Text Available Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32 of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation.

  17. Rotor internal friction instability

    Science.gov (United States)

    Bently, D. E.; Muszynska, A.

    1985-01-01

    Two aspects of internal friction affecting stability of rotating machines are discussed. The first role of internal friction consists of decreasing the level of effective damping during rotor subsynchronous and backward precessional vibrations caused by some other instability mechanisms. The second role of internal frication consists of creating rotor instability, i.e., causing self-excited subsynchronous vibrations. Experimental test results document both of these aspects.

  18. Chromosomal mutation by fission neutrons and X-rays in higher plants. A review on results of the joint research program utilizing Kinki University reactor

    International Nuclear Information System (INIS)

    We have studied the efficiency of fission neutrons from the nuclear reactor of Kinki University (UTR-KINKI) and X-rays to chromosomes of higher plants for over 20 years. In this review, we described the development of bio-dosimeter using hyper-sensibility of germinating onion roots for irradiation, the analysis of chromosome structure in Haplopappus gracilis (Asteraceae), with the special reference of latent centromeres and survived telomeres throughout chromosomal evolution, the experimental studies on the induction of chromosomal rearrangement in Zebrina pendula (Commelinaceae), the behavior of chromosome fragments with non-localized centromeres in Carex and Eleocharis (Cyperaceae), and the possibility as a bio-dosimeter of pollen mother cells of Tradescantia paludosa (Commelinaceae) for the detection of low-dose radiation. (author)

  19. Shoulder instability

    International Nuclear Information System (INIS)

    Shoulder instability is a common clinical feature leading to recurrent pain and limitated range of motion within the glenohumeral joint. Instability can be due a single traumatic event, general joint laxity or repeated episodes of microtrauma. Differentiation between traumatic and atraumatic forms of shoulder instability requires careful history and a systemic clinical examination. Shoulder laxity has to be differentiated from true instability followed by the clinical assessment of direction and degree of glenohumeral translation. Conventional radiography and CT are used for the diagnosis of bony lesions. MR imaging and MR arthrography help in the detection of soft tissue affection, especially of the glenoid labrum and the capsuloligamentous complex. The most common lesion involving the labrum is the anterior labral tear, associated with capsuloperiostal stripping (Bankart lesion). A number of variants of the Bankart lesion have been described, such as ALPSA, SLAP or HAGL lesions. The purpose of this review is to highlight different forms of shoulder instability and its associated radiological findings with a focus on MR imaging. (orig.)

  20. Reference-assisted chromosome assembly

    OpenAIRE

    Kim, Jaebum; Larkin, Denis M; Cai, Qingle; Asan,; Zhang, Yongfen; Ge, Ri-Li; Auvil, Loretta; Capitanu, Boris; Zhang, Guojie; Lewin, Harris A.; Ma, Jian

    2013-01-01

    One of the most difficult problems in modern genomics is the assembly of full-length chromosomes using next generation sequencing (NGS) data. To address this problem, we developed “reference-assisted chromosome assembly” (RACA), an algorithm to reliably order and orient sequence scaffolds generated by NGS and assemblers into longer chromosomal fragments using comparative genome information and paired-end reads. Evaluation of results using simulated and real genome assemblies indicates that ou...

  1. Chronic γ-irradiation results in increased cell killing and chromosomal aberration with specific breakpoints in fibroblast cell strains derived from non-Hodgkin's lymphoma patients

    International Nuclear Information System (INIS)

    Cultured skin fibroblast cells from 16 NHL (non-Hodgkin's lymphoma) patients and 2 clinically normal subjects were compared for cell survival and chromosomal aberration after chronic γ-irradiation. Fibroblasts from an ataxia telangiectasia (AT) homozygote and an AT heterozygote were used as positive controls. Following irradiation, fibroblasts from all 16 NHL patients showed an increase in both cell death and chromosomal aberration (breaks and rearrangements) compared to normal subjects. The difference in frequency of chromosomal aberration between normals and NHL-patients remained virtually unchanged over a period of 24-72 h post irradiation incubation of cells. Cell cycle analysis by flow cytometry carried out in 1 normal and 1 NHL fibroblast cell strain showed that more cells representing the NHL patient were in G2/M phase compared to the normal at various times of cytogenetic analysis. While the AT homozygote appeared to be the most radiosensitive, the AT heterozygote showed a slightly higher incidence of cell death and chromosomal aberration than the normals. The cellular and chromosomal radiosensitivity of fibroblast cell lines from NHL-patients differed slightly from that of AT heterozygote but clearly occupied an intermediate position between the AT homozygote and the normal subjects. Cells from 3 of the NHL patients showed radiation-induced specific chromosomal breaks involving chromosomes 1, 2, 6, 8, 10 and 11 which correspond to known fragile sites. Such breakpoints associated with increased radiosensitivity may be indicative of predisposition to malignancy in the patients studied. (author). 30 refs., 2 figs., 4 tabs

  2. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae).

    Science.gov (United States)

    Lukhtanov, Vladimir A

    2014-01-01

    Lepidoptera (butterflies and moths), as many other groups of animals and plants, simultaneously represent preservation of ancestral karyotype in the majority of families with a high degree of chromosome number instability in numerous independently evolved phylogenetic lineages. However, the pattern and trends of karyotype evolution in some Lepidoptera families are poorly studied. Here I provide a survey of chromosome numbers in skippers (family Hesperiidae) based on intensive search and analysis of published data. I demonstrate that the majority of skippers preserve the haploid chromosome number n=31 that seems to be an ancestral number for the Hesperiidae and the order Lepidoptera at whole. However, in the tribe Baorini the derived number n=16 is the most typical state which can be used as a (syn)apomorphic character in further phylogenetic investigations. Several groups of skippers display extreme chromosome number variations on within-species (e.g. the representatives of the genus Carcharodus Hübner, [1819]) and between-species (e.g. the genus Agathymus Freeman, 1959) levels. Thus, these groups can be used as model systems for future analysis of the phenomenon of chromosome instability. Interspecific chromosomal differences are also shown to be useful for discovering and describing new cryptic species of Hesperiidae representing in such a way a powerful tool in biodiversity research. Generally, the skipper butterflies promise to be an exciting group that will significantly contribute to the growing knowledge of patterns and processes of chromosome evolution. PMID:25610542

  3. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae

    Directory of Open Access Journals (Sweden)

    Vladimir Lukhtanov

    2014-11-01

    Full Text Available Lepidoptera (butterflies and moths, as many other groups of animals and plants, simultaneously represent preservation of ancestral karyotype in the majority of families with a high degree of chromosome number instability in numerous independently evolved phylogenetic lineages. However, the pattern and trends of karyotype evolution in some Lepidoptera families are poorly studied. Here I provide a survey of chromosome numbers in skippers (family Hesperiidae based on intensive search and analysis of published data. I demonstrate that the majority of skippers preserve the haploid chromosome number n=31 that seems to be an ancestral number for the Hesperiidae and the order Lepidoptera at whole. However, in the tribe Baorini the derived number n=16 is the most typical state which can be used as a (synapomorphic character in further phylogenetic investigations. Several groups of skippers display extreme chromosome number variations on within-species (e.g. the representatives of the genus Carcharodus Hübner, [1819] and between-species (e.g. the genus Agathymus Freeman, 1959 levels. Thus, these groups can be used as model systems for future analysis of the phenomenon of chromosome instability. Interspecific chromosomal differences are also shown to be useful for discovering and describing new cryptic species of Hesperiidae representing in such a way a powerful tool in biodiversity research. Generally, the skipper butterflies promise to be an exciting group that will significantly contribute to the growing knowledge of patterns and processes of chromosome evolution.

  4. False negative NIPT results: Risk figures for chromosomes 13,18 and 21 based on chorionic villi results in 5967 cases and literature review

    NARCIS (Netherlands)

    A.R.M. van Opstal (Diane); M. Srebniak (Malgorzata); J. Polak (Joke); F.A.T. de Vries (Femke); L.C. Govaerts (Lutgarde); M. Joosten (Marieke); A. Go (Attie); M.F.C.M. Knapen (Maarten); C.D.F. van den Berg (Cardi); K.E.M. Diderich (Karin); R-J.H. Galjaard (Robert-Jan)

    2016-01-01

    textabstractNon-invasive prenatal testing (NIPT) demonstrated a small chance for a false negative result. Since the "fetal" DNA in maternal blood originates from the cytotrophoblast of chorionic villi (CV), some false negative results will have a biological origin. Based on our experience with cytog

  5. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation

    Directory of Open Access Journals (Sweden)

    Ilknur Erol

    2015-01-01

    Full Text Available West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9 (p11.2;p22 and presenting with macrocephaly, West syndrome, severe mental motor retardation and hypotonia. As far as we know, this is a new chromosomal anomaly associated with West syndrome.

  6. Endocrine abnormalities in ring chromosome 11: a case report and review of the literature

    OpenAIRE

    Lange, Renata; Von Linsingen, Caoê; Mata, Fernanda; Moraes, Aline Barbosa; Arruda, Mariana; Vieira Neto, Leonardo

    2015-01-01

    Summary Ring chromosomes (RCs) are uncommon cytogenetic findings, and RC11 has only been described in 19 cases in the literature. Endocrine abnormalities associated with RC11 were reported for two of these cases. The clinical features of RC11 can result from an alteration in the structure of the genetic material, ring instability, mosaicism, and various extents of genetic material loss. We herein describe a case of RC11 with clinical features of 11q-syndrome and endocrine abnormalities that h...

  7. Cell division patterns and chromosomal segregation defects in oral cancer stem cells.

    Science.gov (United States)

    Kaseb, Hatem O; Lewis, Dale W; Saunders, William S; Gollin, Susanne M

    2016-09-01

    Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc. PMID:27123539

  8. Early Clinical Results of Arthroscopic Remplissages in Patients with Anterior Shoulder Instability with Engaging Hill-Sachs Lesion in Iran

    Directory of Open Access Journals (Sweden)

    Hamid Reza Aslani

    2014-03-01

    Full Text Available Background:   To assess the outcome of the remplissage arthroscopic surgical method in patients with anterior shoulder dislocation associated with Hill-Sachs lesion.     Methods:   Ten patients with anterior shoulder dislocations and Hill-Sachs lesions were entered into this study and were operated on by the remplissage arthroscopic surgical method. They were followed up 22 months after surgery in   order to evaluate the outcome of the treatment, including recurrence of dislocation and motion limitation.     Results:   During the internal follow up period no case of recurrence was found. Motion limitation during the follow up   period was not significant (internal rotation limitation=5°±1°, and external rotation limitation=4°±1° Conclusions:   Our findings suggest that the remplissage arthroscopic surgical method is an acceptable, safe and   reliable treatment for anterior shoulder dislocation with engaging Hill-Sachs lesion.

  9. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation

    OpenAIRE

    Ilknur Erol; Semra Saygi; Senay Demir; Fusun Alehan; Feride Iffet Sahin

    2015-01-01

    West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9) (p11.2;p22) and presenting with macrocephaly, West syndrome, severe mental motor retardation and h...

  10. Material and structural instabilities of single-wall carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    J. Wu; K. C. Hwang; J. Song; Y. Huang

    2008-01-01

    The nonlinear atomistic interactions usually involve softening behavior. Instability resulting directly from this softening are called the material instability, while those unrelated to this softening are called the structural instability. We use the finite-deformation shell theory based on the interatomic potential to show that the tension instability of single-wall carbon nanotubes is the material instability, while the compression and torsion instabilities are structural instability.

  11. Genome organization, instabilities, stem cells, and cancer

    Directory of Open Access Journals (Sweden)

    Senthil Kumar Pazhanisamy

    2009-01-01

    Full Text Available It is now widely recognized that advances in exploring genome organization provide remarkable insights on the induction and progression of chromosome abnormalities. Much of what we know about how mutations evolve and consequently transform into genome instabilities has been characterized in the spatial organization context of chromatin. Nevertheless, many underlying concepts of impact of the chromatin organization on perpetuation of multiple mutations and on propagation of chromosomal aberrations remain to be investigated in detail. Genesis of genome instabilities from accumulation of multiple mutations that drive tumorigenesis is increasingly becoming a focal theme in cancer studies. This review focuses on structural alterations evolve to raise a variety of genome instabilities that are manifested at the nucleotide, gene or sub-chromosomal, and whole chromosome level of genome. Here we explore an underlying connection between genome instability and cancer in the light of genome architecture. This review is limited to studies directed towards spatial organizational aspects of origin and propagation of aberrations into genetically unstable tumors.

  12. Presencia de micronúcleos en células epiteliales de encías, como marcador de inestabilidad cromosomal: Revisión sistemática Presence of micronuclei in oral epithelium cells, as marker of chromosomal instability: Systematic review

    Directory of Open Access Journals (Sweden)

    A. Díaz Caballero

    2013-04-01

    environment, medical procedures such as radiation and chemical agents, nutrients deficiency like folic acid, habits as alcoholism, smoking, drug addiction, stress, lifestyle and genetic factors such as changes in metabolism and/or DNA repair. Objetive. To guide a critical analysis of the micronucleus test as a measure of genetic instability, its applicability from dentistry and its relationship with cancer development. Materials and methods. The most relevant papers were identifies through a systematic search on electronic databases such as Ovid, Ebsco Host, Science Direct and PubMed. Results. A total of 282872 articles were obtained of wich were selected wich fulfilled the criteria inclusion and were subsequently analyzed and discussed taking into account title, author, journal, year, volume, month and page. Conclusion. The results of this analysis of the literature review support the hypothesis that frequency of micronucleus is related to cancer development based on the fact that a substantial proportion of genetic instability of cancer cells is due to specific structural defects in chromosome segregation.

  13. Chromosomal Behavior during Meiosis in the Progeny of Triticum timopheevii × Hexaploid Wild Oat.

    Directory of Open Access Journals (Sweden)

    Hongzhou An

    Full Text Available The meiotic behavior of pollen mother cells (PMCs of the F2 and F3 progeny from Triticum timopheevii × hexaploid wild oat was investigated by cytological analysis and sequential C-banding-genomic in situ hybridization (GISH in the present study. A cytological analysis showed that the chromosome numbers of the F2 and F3 progeny ranged from 28 to 41. A large number of univalents, lagging chromosomes, chromosome bridges and micronuclei were found at the metaphase I, anaphase I, anaphase II and tetrad stages in the F2 and F3 progeny. The averages of univalents were 3.50 and 2.73 per cell, and those of lagging chromosomes were 3.37 and 1.87 in the F2 and F3 progeny, respectively. The PMC meiotic indices of the F2 and F3 progeny were 12.22 and 20.34, respectively, indicating considerable genetic instability. A sequential C-banding-GISH analysis revealed that some chromosomes and fragments from the hexaploid wild oat were detected at metaphase I and anaphase I in the progeny, showing that the progeny were of true intergeneric hybrid origin. The alien chromosomes 6A, 7A, 3C and 2D were lost during transmission from F2 to F3. In addition, partial T. timopheevii chromosomes appeared in the form of univalents or lagging chromosomes, which might result from large genome differences between the parents, and the wild oat chromosome introgression interfered with the wheat homologues' normally pairing.

  14. Chromosomal Behavior during Meiosis in the Progeny of Triticum timopheevii × Hexaploid Wild Oat.

    Science.gov (United States)

    An, Hongzhou; Hu, Mei; Li, Pengfei; Geng, Guangdong; Zhang, Qingqin; Zhang, Suqin

    2015-01-01

    The meiotic behavior of pollen mother cells (PMCs) of the F2 and F3 progeny from Triticum timopheevii × hexaploid wild oat was investigated by cytological analysis and sequential C-banding-genomic in situ hybridization (GISH) in the present study. A cytological analysis showed that the chromosome numbers of the F2 and F3 progeny ranged from 28 to 41. A large number of univalents, lagging chromosomes, chromosome bridges and micronuclei were found at the metaphase I, anaphase I, anaphase II and tetrad stages in the F2 and F3 progeny. The averages of univalents were 3.50 and 2.73 per cell, and those of lagging chromosomes were 3.37 and 1.87 in the F2 and F3 progeny, respectively. The PMC meiotic indices of the F2 and F3 progeny were 12.22 and 20.34, respectively, indicating considerable genetic instability. A sequential C-banding-GISH analysis revealed that some chromosomes and fragments from the hexaploid wild oat were detected at metaphase I and anaphase I in the progeny, showing that the progeny were of true intergeneric hybrid origin. The alien chromosomes 6A, 7A, 3C and 2D were lost during transmission from F2 to F3. In addition, partial T. timopheevii chromosomes appeared in the form of univalents or lagging chromosomes, which might result from large genome differences between the parents, and the wild oat chromosome introgression interfered with the wheat homologues' normally pairing. PMID:25950431

  15. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Tsien, F.; Shapira, E. [Tulane Univ. School of Medicine, New Orleans, LA (United States); Carvalho, T. [Hospital Sarah Kubitschek, Brasilia (Brazil)] [and others

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  16. Effect of exercise therapy combining electrical therapy and balance training on functional instability resulting from ankle sprain—focus on stability of jump landing

    OpenAIRE

    Yoshida, Takaki; Tanino, Yoshitsugu; Suzuki, Toshiaki

    2015-01-01

    [Purpose] Functional instability leads to a delay in the muscle reaction time and weakness of the peroneal muscles. The present study examined the effects of transcutaneous electrical nerve stimulation during balance exercise on patients with functional instability of the ankles, including the ability to land after jumping at the center of foot pressure. [Subjects] The subjects were seven males with a history of ankle sprain. All had a sprained ankle score of ≤80 points on Karlson’s functiona...

  17. 56Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo

    Science.gov (United States)

    DeCarolis, Nathan A.; Rivera, Phillip D.; Ahn, Francisca; Amaral, Wellington Z.; LeBlanc, Junie A.; Malhotra, Shveta; Shih, Hung-Ying; Petrik, David; Melvin, Neal R.; Chen, Benjamin P. C.; Eisch, Amelia J.

    2014-07-01

    The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreERT2/R26R:YFP mice, respectively). Mice were subjected to 56Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24 h), intermediate (7 d), and/or long time points (2-3 mo) post-irradiation. 56Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support

  18. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

    2016-01-01

    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  19. Nonlinear mirror instability

    CERN Document Server

    Rincon, F; Cowley, S C

    2014-01-01

    Slow dynamical changes in magnetic-field strength and invariance of the particles' magnetic moments generate ubiquitous pressure anisotropies in weakly collisional, magnetized astrophysical plasmas. This renders them unstable to fast, small-scale mirror and firehose instabilities, which are capable of exerting feedback on the macroscale dynamics of the system. By way of a new asymptotic theory of the early nonlinear evolution of the mirror instability in a plasma subject to slow shearing or compression, we show that the instability does not saturate quasilinearly at a steady, low-amplitude level. Instead, the trapping of particles in small-scale mirrors leads to nonlinear secular growth of magnetic perturbations, $\\delta B/B \\propto t^{2/3}$. Our theory explains recent collisionless simulation results, provides a prediction of the mirror evolution in weakly collisional plasmas and establishes a foundation for a theory of nonlinear mirror dynamics with trapping, valid up to $\\delta B/B =O(1)$.

  20. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells12

    Science.gov (United States)

    Samassekou, Oumar; Li, Huiyu; Hébert, Josée; Ntwari, Aimé; Wang, Haixia; Cliché, Catherine Grenier; Bouchard, Eric; Huang, Shiang; Yan, Ju

    2011-01-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32) of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp) with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation. PMID:21677878

  1. Photomultiplier time instability

    International Nuclear Information System (INIS)

    A short-time and slow instability of anode photocurrent in photoelectron multiplier is investigated. The analysis of sorption and desorption processes stimulated by electron excitation allowed to propose an adsorption-desorption mechanism of devices instability. Transient response and drift of photomultiplier anode photocurrent are measured as well as the curves of spent variations of spectral sensitivity of photocathode and individual amplifier cascades of the multiplying system depending on anode current. The results of calculating the proposed model are in good agreement with the experimental data

  2. Comparative analysis of sex chromosomes in Leporinus species (Teleostei, Characiformes) using chromosome painting

    Science.gov (United States)

    2013-01-01

    Background The Leporinus genus, belonging to the Anostomidae family, is an interesting model for studies of sex chromosome evolution in fish, particularly because of the presence of heteromorphic sex chromosomes only in some species of the genus. In this study we used W chromosome-derived probes in a series of cross species chromosome painting experiments to try to understand events of sex chromosome evolution in this family. Results W chromosome painting probes from Leporinus elongatus, L. macrocephalus and L. obtusidens were hybridized to each others chromosomes. The results showed signals along their W chromosomes and the use of L. elongatus W probe against L. macrocephalus and L. obtusidens also showed signals over the Z chromosome. No signals were observed when the later aforementioned probe was used in hybridization procedures against other four Anostomidae species without sex chromosomes. Conclusions Our results demonstrate a common origin of sex chromosomes in L. elongatus, L. macrocephalus and L. obtusidens but suggest that the L. elongatus chromosome system is at a different evolutionary stage. The absence of signals in the species without differentiated sex chromosomes does not exclude the possibility of cryptic sex chromosomes, but they must contain other Leporinus W sequences than those described here. PMID:23822802

  3. Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function.

    Directory of Open Access Journals (Sweden)

    Kaitlin M Stimpson

    Full Text Available The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA. The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2 causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair.

  4. Instability in Shocked Granular Gases

    CERN Document Server

    Sirmas, Nick; Radulescu, Matei

    2013-01-01

    Shocks in granular media, such as vertically oscillated beds, have been shown to develop instabilities. Similar jet formation has been observed in explosively dispersed granular media. Our previous work addressed this instability by performing discrete-particle simulations of inelastic media undergoing shock compression. By allowing finite dissipation within the shock wave, instability manifests itself as distinctive high density non-uniformities and convective rolls within the shock structure. In the present study we have extended this work to investigate this instability at the continuum level. We modeled the Euler equations for granular gases with a modified cooling rate to include an impact velocity threshold necessary for inelastic collisions. Our results showed a fair agreement between the continuum and discrete-particle models. Discrepancies, such as higher frequency instabilities in our continuum results may be attributed to the absence of higher order effects.

  5. Instability in shocked granular gases

    International Nuclear Information System (INIS)

    Shocks in granular media, such as vertically oscillated beds, have been shown to develop instabilities. Similar jet formation has been observed in explosively dispersed granular media. Our previous work addressed this instability by performing discrete-particle simulations of inelastic media undergoing shock compression. By allowing finite dissipation within the shock wave, instability manifests itself as distinctive high density non-uniformities and convective rolls within the shock structure. In the present study we have extended this work to investigate this instability at the continuum level. We modeled the Euler equations for granular gases with a modified cooling rate to include an impact velocity threshold necessary for inelastic collisions. Our results showed a fair agreement between the continuum and discrete-particle models. Discrepancies, such as higher frequency instabilities in our continuum results may be attributed to the absence of higher order effects.

  6. Early and Late Chromosome Damages in Human Lymphocytes Induced by Gamma Rays and Fe Ions

    Science.gov (United States)

    Sunagawa, Mayumi; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2014-01-01

    Chromosomal translocations and inversions are considered stable, and cells containing these types of chromosome aberrations can survive multiple cell divisions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. Detailed analysis of chromosome break ends participating in exchanges revealed a greater fraction of break ends involved in intrachromosome aberrations in the 7- and 14-day samples in comparison to the fraction at first mitosis. In particular, simple inversions were found at 7 and 14 days, but not at the first mitosis, suggesting that some of the aberrations might be formed days post irradiation. In contrast, at the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Comparison between low and high doses of Fe ion irradiation in the induction of late damages will also be discussed.

  7. Instability of liquid crystal elastomers

    Science.gov (United States)

    An, Ning; Li, Meie; Zhou, Jinxiong

    2016-01-01

    Nematic liquid crystal elastomers (LCEs) contract in the director direction but expand in other directions, perpendicular to the director, when heated. If the expansion of an LCE is constrained, compressive stress builds up in the LCE, and it wrinkles or buckles to release the stored elastic energy. Although the instability of soft materials is ubiquitous, the mechanism and programmable modulation of LCE instability has not yet been fully explored. We describe a finite element method (FEM) scheme to model the inhomogeneous deformation and instability of LCEs. A constrained LCE beam working as a valve for microfluidic flow, and a piece of LCE laminated with a nanoscale poly(styrene) (PS) film are analyzed in detail. The former uses the buckling of the LCE beam to occlude the microfluidic channel, while the latter utilizes wrinkling or buckling to measure the mechanical properties of hard film or to realize self-folding. Through rigorous instability analysis, we predict the critical conditions for the onset of instability, the wavelength and amplitude evolution of instability, and the instability patterns. The FEM results are found to correlate well with analytical results and reported experiments. These efforts shed light on the understanding and exploitation of the instabilities of LCEs.

  8. Whole chromosome painting of B chromosomes of the red-eye tetra Moenkhausia sanctaefilomenae (Teleostei, Characidae)

    Science.gov (United States)

    Scudeler, Patricia Elda Sobrinho; Diniz, Débora; Wasko, Adriane Pinto; Oliveira, Claudio; Foresti, Fausto

    2015-01-01

    Abstract B chromosomes are dispensable genomic elements found in different groups of animals and plants. In the present study, a whole chromosome probe was generated from a specific heterochromatic B chromosome occurring in cells of the characidae fish Moenkhausia sanctaefilomenae (Steindachner, 1907). The chromosome painting probes were used in fluorescence in situ hybridization (FISH) experiments for the assessment of metaphase chromosomes obtained from individuals from three populations of Moenkhausia sanctaefilomenae. The results revealed that DNA sequences were shared between a specific B chromosome and many chromosomes of the A complement in all populations analyzed, suggesting a possible intra-specific origin of these B chromosomes. However, no hybridization signals were observed in other B chromosomes found in the same individuals, implying a possible independent origin of B chromosome variants in this species. FISH experiments using 18S rDNA probes revealed the presence of non-active ribosomal genes in some B chromosomes and in some chromosomes of the A complement, suggesting that at least two types of B chromosomes had an independent origin. The role of heterochromatic segments and ribosomal sequences in the origin of B chromosomes were discussed. PMID:26753081

  9. Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

    Directory of Open Access Journals (Sweden)

    Sebastian Pita

    2013-05-01

    Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

  10. Overproduction of Bacillus amyloliquefaciens extracellular glutamyl-endopeptidase as a result of ectopic multi-copy insertion of an efficiently-expressed mpr gene into the Bacillus subtilis chromosome

    Directory of Open Access Journals (Sweden)

    Yomantas Yurgis AV

    2011-08-01

    Full Text Available Abstract Background Plasmid-less, engineered Bacillus strains have several advantages over plasmid-carrier variants. Specifically, their stability and potential ecological safety make them of use in industrial applications. As a rule, however, it is necessary to incorporate many copies of a key gene into a chromosome to achieve strain performance that is comparable to that of cells carrying multiple copies of a recombinant plasmid. Results A plasmid-less B. subtilis JE852-based strain secreting glutamyl-specific protease (GSP-the protein product of the mpr gene from B. amyloliquefaciens was constructed that exhibits decreased levels of other extracellular proteases. Ten copies of an mprB.amy cassette in which the GSP gene was placed between the promoter of the B. amyloliquefaciens rplU-rpmA genes and the Rho-independent transcription terminator were ectopically inserted into designated (3 copies and random (7 copies points in the recipient chromosome. The resulting strain produced approximately 0.5 g/L of secreted GSP after bacterial cultivation in flasks with starch-containing media, and its performance was comparable to an analogous strain in which the mprB.amy cassette was carried on a multi-copy plasmid. Conclusion A novel strategy for ectopically integrating a cassette into multiple random locations in the B. subtilis chromosome was developed. This new method is based on the construction of DNA fragments in which the desired gene, marked by antibiotic resistance, is sandwiched between "front" and "back" portions of random chromosomal DNA restriction fragments. These fragments were subsequently inserted into the targeted sites of the chromosome using double-cross recombination. The construction of a marker-free strain was achieved by gene conversion between the integrated marked gene and a marker-less variant carried by plasmid DNA, which was later removed from the cells.

  11. Measurements of fast transition instability in RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Ptitsyn, V.; Blaskiewicz, M.; Fischer, W.; Lee, R.; Zhang, S.Y.

    2010-05-23

    A fast transition instability presents a limiting factor for ion beam intensity in RHIC. Several pieces of evidence show that electron clouds play an important role in establishing the threshold of this instability. In RHIC Runs8 the measurements of the instability, using a button BPM, were done in order to observe details of the instability development on the scale over hundreds and thousands turns. The paper presents and discusses the results of those measurements in time and frequency domains.

  12. Temporal genomic evolution of bird sex chromosomes

    DEFF Research Database (Denmark)

    Wang, Zongji; Zhang, Jilin; Yang, Wei;

    2014-01-01

    driving forces of Z chromosome evolution, we analyze here 45 newly available bird genomes and four species' transcriptomes, over their course of recombination loss between the sex chromosomes. RESULTS: We show Z chromosomes in general have a significantly higher substitution rate in introns and synonymous...... evolved very recently. CONCLUSIONS: In conclusion, we uncover that the sequence and expression patterns of Z chromosome genes covary with their ages of becoming Z-linked. In contrast to the mammalian X chromosomes, such patterns are mainly driven by mutational bias and genetic drift in birds, due...... to the opposite sex-biased inheritance of Z vs. X....

  13. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    Directory of Open Access Journals (Sweden)

    Daniela Mierla

    2012-06-01

    Full Text Available Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, karyotype analysis by G-banding was performed from peripheral blood in 967 women infertility. Results: Chromosomal abnormalities were found to 79 women (8,17%. The percentage of chromosomal abnormalities in the studied population correlates with the data in the literature. Chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions.

  14. 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...

  15. Chromosome heteromorphism quantified by high-resolution bivariate flow karyotyping.

    Science.gov (United States)

    Trask, B; van den Engh, G; Mayall, B; Gray, J W

    1989-11-01

    Maternal and paternal homologues of many chromosome types can be differentiated on the basis of their peak position in Hoechst 33258 versus chromomycin A3 bivariate flow karyotypes. We demonstrate here the magnitude of DNA content differences among normal chromosomes of the same type. Significant peak-position differences between homologues were observed for an average of four chromosome types in each of the karyotypes of 98 different individuals. The frequency of individuals with differences in homologue peak positions varied among chromosome types: e.g., chromosome 15, 61%; chromosome 3, 4%. Flow karyotypes of 33 unrelated individuals were compared to determine the range of peak position among normal chromosomes. Chromosomes Y, 21, 22, 15, 16, 13, 14, and 19 were most heteromorphic, and chromosomes 2-8 and X were least heteromorphic. The largest chromosome 21 was 45% larger than the smallest 21 chromosome observed. The base composition of the variable regions differed among chromosome types. DNA contents of chromosome variants determined from flow karyotypes were closely correlated to measurements of DNA content made of gallocyanin chrome alum-stained metaphase chromosomes on slides. Fluorescence in situ hybridization with chromosome-specific repetitive sequences indicated that variability in their copy number is partly responsible for peak-position variability in some chromosomes. Heteromorphic chromosomes are identified for which parental flow karyotype information will be essential if de novo rearrangements resulting in small DNA content changes are to be detected with flow karyotyping. PMID:2479266

  16. Karyotyping of Chromosomes in Human Bronchial Epithelial Cells Transformed by High Energy Fe Ions

    Science.gov (United States)

    Yeshitla, Samrawit; Zhang, Ye; Park, Seongmi; Story, Michael D.; Wilson, Bobby; Wu, Honglu

    2015-01-01

    Lung cancer induced from exposures to space radiation is one of the most significant health risks for long-term space travels. Evidences show that low- and high- Linear energy transfer (LET)-induced transformation of normal human bronchial epithelial cells (HBEC) that are immortalized through the expression of Cdk4 and hTERT. The cells were exposed to gamma rays and high-energy Fe ions for the selection of transformed clones. Transformed HBEC are identified and analyzed chromosome aberrations (i.e. genomic instability) using the multi-color fluorescent in situ hybridization (mFISH), as well as the multi-banding in situ hybridization (mBAND) techniques. Our results show chromosomal translocations between different chromosomes and several of the breaks occurred in the q-arm of chromosome 3. We also identified copy number variations between the transformed and the parental HBEC regardless of the exposure conditions. We observed chromosomal aberrations in the lowand high-LET radiation-induced transformed clones and they are imperfectly different from clones obtain in spontaneous soft agar growth.

  17. Transient Microgeographic Clines during B Chromosome Invasion.

    Science.gov (United States)

    Camacho, Juan Pedro M; Shaw, Michael W; Cabrero, Josefa; Bakkali, Mohammed; Ruíz-Estévez, Mercedes; Ruíz-Ruano, Francisco J; Martín-Blázquez, Rubén; López-León, María Dolores

    2015-11-01

    The near-neutral model of B chromosome evolution predicts that the invasion of a new population should last some tens of generations, but the details on how it proceeds in real populations are mostly unknown. Trying to fill this gap, we analyze here a natural population of the grasshopper Eyprepocnemis plorans at three time points during the last 35 years. Our results show that B chromosome frequency increased significantly during this period and that a cline observed in 1992 had disappeared in 2012 once B chromosome frequency reached an upper limit at all sites sampled. This indicates that, during B chromosome invasion, transient clines for B chromosome frequency are formed at the invasion front on a microgeographic scale. Computer simulation experiments showed that the pattern of change observed for genotypic frequencies is consistent with the existence of B chromosome drive through females and selection against individuals with a high number of B chromosomes. PMID:26655780

  18. [The evolution of human Y chromosome].

    Science.gov (United States)

    Yang, Xianrong; Wang, Meiqin; Li, Shaohua

    2014-09-01

    The human Y chromosome is always intriguing for researchers, because of its role in gender determination and its unusual evolutionary history. The Y chromosome evolves from an autosome, and its evolution has been characterized by massive gene decay. The lack of recombination and protein-coding genes and high content of repetitive sequences have hindered the progress in our understanding of the Y chromosome biology. Recently, with the advances in comparative genomics and sequencing technology, the research on Y chromosome has become a hotspot, with an intensified debate about Y-chromosome final destination resulting from degeneration. This review focuses on the structure, inheritance characteristics, gene content, and the origin and evolution of Y chromosome. We also discuss the long-term destiny of Y chromosome. PMID:25252301

  19. Chromosome evolution in Neotropical butterflies

    OpenAIRE

    Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O.; Brown, Keith S., Jr.

    2013-01-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results i...

  20. Human Herpesvirus 6 Chromosomal Integration in Immunocompetent Patients Results in High Levels of Viral DNA in Blood, Sera, and Hair Follicles

    OpenAIRE

    Ward, Katherine N.; Leong, Hoe Nam; Elisabeth P. Nacheva; Howard, Julie; Atkinson, Claire E; Davies, Nicholas W. S.; Griffiths, Paul D; Clark, Duncan A.

    2006-01-01

    Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal integration had HHV-6 and β-globin DNA quantified in various samples by PCR. The mean HHV-6 DNA concentration (log10 copies/milliliter) in blood was 7.0 (≥1 HHV-6 DNA copies/leukocyte), and in serum it was 5.3 (≥1 HHV-6 DNA copies/lysed cell). The mean HHV-6 DNA load (log10 copies)/hair follicle was 4.2 (≥1 copies/hair follicle cell), demonstrating that viral integration is not confined to blood cells. The characteristi...

  1. Evolutionary interaction between W/Y chromosome and transposable elements.

    Science.gov (United States)

    Śliwińska, Ewa B; Martyka, Rafał; Tryjanowski, Piotr

    2016-06-01

    The W/Y chromosome is unique among chromosomes as it does not recombine in its mature form. The main side effect of cessation of recombination is evolutionary instability and degeneration of the W/Y chromosome, or frequent W/Y chromosome turnovers. Another important feature of W/Y chromosome degeneration is transposable element (TEs) accumulation. Transposon accumulation has been confirmed for all W/Y chromosomes that have been sequenced so far. Models of W/Y chromosome instability include the assemblage of deleterious mutations in protein coding genes, but do not include the influence of transposable elements that are accumulated gradually in the non-recombining genome. The multiple roles of genomic TEs, and the interactions between retrotransposons and genome defense proteins are currently being studied intensively. Small RNAs originating from retrotransposon transcripts appear to be, in some cases, the only mediators of W/Y chromosome function. Based on the review of the most recent publications, we present knowledge on W/Y evolution in relation to retrotransposable element accumulation. PMID:27000053

  2. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J;

    1983-01-01

    A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were...... unbalanced chromosome abnormality in group A (women with elevated risk) is significantly higher than in group B + C (women without elevated risk) (relative risk 2.4). Women with a known familial translocation and women 40 years or more have a relative risk of 5.7 of having an unbalanced chromosome......The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...

  3. Chromosomal bands affected by acute oil exposure and DNA repair errors.

    Directory of Open Access Journals (Sweden)

    Gemma Monyarch

    Full Text Available BACKGROUND: In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. OBJECTIVES: We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. METHODS: Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. RESULTS: Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016. CONCLUSION: The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

  4. The bar instability revisited

    OpenAIRE

    Chiodi, Filippo; Andreotti, Bruno; Claudin, Philippe

    2012-01-01

    The river bar instability is revisited, using a hydrodynamical model based on Reynolds averaged Navier-Stokes equations. The results are contrasted with the standard analysis based on shallow water Saint-Venant equations. We first show that the stability of both transverse modes (ripples) and of small wavelength inclined modes (bars) predicted by the Saint-Venant approach are artefacts of this hydrodynamical approximation. When using a more reliable hydrodynamical model, the dispersion relati...

  5. Gastric cancers of Western European and African patients show different patterns of genomic instability

    Directory of Open Access Journals (Sweden)

    Mulder Chris JJ

    2011-01-01

    Full Text Available Abstract Background Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK and South Africa (SA, in an attempt to support the African enigma hypothesis at the biological level. Methods DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis. Results Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p Conclusions Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.

  6. The role of chromosome missegregation in cancer development: a theoretical approach using agent-based modelling.

    Directory of Open Access Journals (Sweden)

    Arturo Araujo

    Full Text Available Many cancers are aneuploid. However, the precise role that chromosomal instability plays in the development of cancer and in the response of tumours to treatment is still hotly debated. Here, to explore this question from a theoretical standpoint we have developed an agent-based model of tissue homeostasis in which to test the likely effects of whole chromosome mis-segregation during cancer development. In stochastic simulations, chromosome mis-segregation events at cell division lead to the generation of a diverse population of aneuploid clones that over time exhibit hyperplastic growth. Significantly, the course of cancer evolution depends on genetic linkage, as the structure of chromosomes lost or gained through mis-segregation events and the level of genetic instability function in tandem to determine the trajectory of cancer evolution. As a result, simulated cancers differ in their level of genetic stability and in their growth rates. We used this system to investigate the consequences of these differences in tumour heterogeneity for anti-cancer therapies based on surgery and anti-mitotic drugs that selectively target proliferating cells. As expected, simulated treatments induce a transient delay in tumour growth, and reveal a significant difference in the efficacy of different therapy regimes in treating genetically stable and unstable tumours. These data support clinical observations in which a poor prognosis is correlated with a high level of chromosome mis-segregation. However, stochastic simulations run in parallel also exhibit a wide range of behaviours, and the response of individual simulations (equivalent to single tumours to anti-cancer therapy prove extremely variable. The model therefore highlights the difficulties of predicting the outcome of a given anti-cancer treatment, even in cases in which it is possible to determine the genotype of the entire set of cells within the developing tumour.

  7. Molecular Mechanisms of Radiation-Induced Genomic Instability in Human Cells

    Energy Technology Data Exchange (ETDEWEB)

    Howard L. Liber; Jeffrey L. Schwartz

    2005-10-31

    There are many different model systems that have been used to study chromosome instability. What is clear from all these studies is that conclusions concerning chromosome instability depend greatly on the model system and instability endpoint that is studied. The model system for our studies was the human B-lymphoblastoid cell line TK6. TK6 was isolated from a spontaneously immortalized lymphoblast culture. Thus there was no outside genetic manipulation used to immortalize them. TK6 is a relatively stable p53-normal immortal cell line (37). It shows low gene and chromosome mutation frequencies (19;28;31). Our general approach to studying instability in TK6 cells has been to isolate individual clones and analyze gene and chromosome mutation frequencies in each. This approach maximizes the possibility of detecting low frequency events that might be selected against in mass cultures.

  8. Intrinsic Instability of Coronal Streamers

    CERN Document Server

    Chen, Y; Song, H Q; Shi, Q Q; Feng, S W; Xia, L D; 10.1088/0004-637X/691/2/1936

    2009-01-01

    Plasma blobs are observed to be weak density enhancements as radially stretched structures emerging from the cusps of quiescent coronal streamers. In this paper, it is suggested that the formation of blobs is a consequence of an intrinsic instability of coronal streamers occurring at a very localized region around the cusp. The evolutionary process of the instability, as revealed in our calculations, can be described as follows: (1) through the localized cusp region where the field is too weak to sustain the confinement, plasmas expand and stretch the closed field lines radially outward as a result of the freezing-in effect of plasma-magnetic field coupling; the expansion brings a strong velocity gradient into the slow wind regime providing the free energy necessary for the onset of a subsequent magnetohydrodynamic instability; (2) the instability manifests itself mainly as mixed streaming sausage-kink modes, the former results in pinches of elongated magnetic loops to provoke reconnections at one or many loc...

  9. The Program of Sex Chromosome Pairing in Meiosis Is Highly Conserved Across Marsupial Species: Implications for Sex Chromosome Evolution

    OpenAIRE

    Page, Jesús; Berríos, Soledad; Parra, María Teresa; Viera, Alberto; Suja, José Ángel; Prieto, Ignacio; Barbero, José Luis; Rufas, Julio S; Fernández-Donoso, Raúl

    2005-01-01

    Marsupials present a series of genetic and chromosomal features that are highly conserved in very distant species. One of these features is the absence of a homologous region between X and Y chromosomes. According to this genetic differentiation, sex chromosomes do not synapse during the first meiotic prophase in males, and a special structure, the dense plate, maintains sex chromosome association. In this report we present results on the process of meiotic sex chromosome pairing obtained fro...

  10. Breast tumor copy number aberration phenotypes and genomic instability

    International Nuclear Information System (INIS)

    Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes. We applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability. We discriminated three breast tumor subtypes based on genomic DNA copy number alterations. The subtypes varied with respect to level of genomic instability. We find that shorter telomeres and altered telomere related gene expression are associated with amplification, implicating telomere attrition as a promoter of this type of aberration in breast cancer. On the other hand, the numbers of chromosomal alterations, particularly low level changes, are associated with altered expression of genes in other functional classes (mitosis, cell cycle, DNA replication and repair). Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability. Many of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. These observations are consistent with failure to find mutations in sporadic tumors in genes that have roles in maintenance or manipulation of the genome

  11. Chromosome Architecture and Genome Organization

    Science.gov (United States)

    Bernardi, Giorgio

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. PMID:26619076

  12. Cosmic ray driven instability

    International Nuclear Information System (INIS)

    The interaction between energetic charged particles and thermal plasma, which forms the basis of diffusive shock acceleration, leads also to interesting dynamical phenomena. For a compressional mode propagating in a system with homoeneous energetic particle pressure it is well known that friction with the energetic particles leads to damping. The linear theory of this effect has been analyzed in detail by Ptuskin. Not so obvious is that a non-uniform energetic particle pressure can in addition amplify compressional disturbances. If the pressure gradient is sufficiently steep this growth can dominate the frictional damping and lead to an instability. It is important to not that this effect results from the collective nature of the interaction between the energetic particles and the gas and is not connected with the Parker instability, nor with the resonant amplification of Alfven waves

  13. Photomultiplier short-term instability

    International Nuclear Information System (INIS)

    The present paper gives a description of the apparatus and method to measure PM gain short-term instability under the condition of pulsed light source simulating the operation at proton synchrotrons. Experimental results are presented for FEU-84, FEU-85, FEU-110, FEU-115 and XP2010 photomultipliers. It is shown that the short-term gain instability can be described by a simple mathematical model. (Auth.)

  14. Quantitative Proteomic Analysis of Mitochondrial Proteins Reveals Pro-Survival Mechanisms in the Perpetuation of Radiation-Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Stefani N.; Waters, Katrina M.; Morgan, William F.; Yang, Austin; Baulch, Janet E.

    2012-07-26

    Radiation induced genomic instability is a well-studied phenomenon that is measured as mitotically heritable genetic alterations observed in the progeny of an irradiated cell. The mechanisms that perpetuate this instability are unclear, however, a role for chronic oxidative stress has consistently been demonstrated. In the chromosomally unstable LS12 cell line, oxidative stress and genomic instability were correlated with mitochondrial dysfunction. To clarify this mitochondrial dysfunction and gain insight into the mechanisms underlying radiation induced genomic instability we have evaluated the mitochondrial sub-proteome and performed quantitative mass spectrometry (MS) analysis of LS12 cells. Of 98 quantified mitochondrial proteins, 17 met criteria for fold changes and reproducibility; and 11 were statistically significant in comparison with the stable parental GM10115 cell line. Previous observations implicated defects in the electron transport chain (ETC) in the LS12 cell mitochondrial dysfunction. Proteomic analysis supports these observations, demonstrating significantly reduced levels of mitochondrial cytochrome c, the intermediary between complexes III and IV of the ETC. Results also suggest that LS12 cells compensate for ETC dysfunction and oxidative stress through increased levels of tricarboxylic acid cycle enzymes and up-regulation of proteins that protect against oxidative stress and apoptosis. More than one cellular defect is likely to contribute to the genomic instability phenotype. These data suggest that LS12 cells have adapted mechanisms that allow survival under sub-optimal conditions of oxidative stress and compromised mitochondrial function to perpetuate genomic instability.

  15. Midcarpal instability: a radiological perspective

    International Nuclear Information System (INIS)

    Midcarpal instability (MCI) is the result of complex abnormal carpal motion at the midcarpal joint of the wrist. It is a form of non-dissociative carpal instability (CIND) and can be caused by various combinations of extrinsic ligament injuries that then result in one of several subtypes of MCI. The complex patterns of injury and the kinematics are further complicated by competing theories, terminology and classifications of MCI. Palmar, dorsal, ulna midcarpal instability, and capitolunate or chronic capitolunate instability are all descriptions of types of MCI with often overlapping features. Palmar midcarpal instability (PMCI) is the most commonly reported type of MCI. It has been described as resulting from deficiencies in the ulna limb of the palmar arcuate ligament (triquetrohamate-capitate) or the dorsal radiotriquetral ligaments, or both. Unstable carpal articulations can be treated with limited carpal arthrodesis or the ligamentous defects can be treated with capsulorrhaphy or ligament reconstruction. Conventional radiographic abnormalities are usually limited to volar intercalated segment instability (VISI) patterns of carpal alignment and are not specific. For many years stress view radiographs and videofluoroscopy have been the methods of choice for demonstrating carpal instability and abnormal carpal kinematics respectively. Dynamic US can be also used to demonstrate midcarpal dyskinesia including the characteristic triquetral ''catch-up'' clunk. Tears of the extrinsic ligaments can be demonstrated with MR arthrography, and probably with CT arthrography, but intact yet redundant ligaments are more difficult to identify. The exact role of these investigations in the diagnosis, categorisation and management of midcarpal instability has yet to be determined. (orig.)

  16. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

    Full Text Available Abstract Background The Characidium (a Neotropical fish group have a conserved diploid number (2n = 50, but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR. In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.

  17. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae)

    Science.gov (United States)

    2011-01-01

    Background The Characidium (a Neotropical fish group) have a conserved diploid number (2n = 50), but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR). In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH) using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish. PMID:21787398

  18. WELLBORE INSTABILITY: CAUSES AND CONSEQUENCES

    Directory of Open Access Journals (Sweden)

    Borivoje Pašić

    2007-12-01

    Full Text Available Wellbore instability is one of the main problems that engineers meet during drilling. The causes of wellbore instability are often classified into either mechanical (for example, failure of the rock around the hole because of high stresses, low rock strength, or inappropriate drilling practice or chemical effects which arise from damaging interaction between the rock, generally shale, and the drilling fluid. Often, field instances of instability are a result of a combination of both chemical and mechanical. This problem might cause serious complication in well and in some case can lead to expensive operational problems. The increasing demand for wellbore stability analyses during the planning stage of a field arise from economic considerations and the increasing use of deviated, extended reach and horizontal wells. This paper presents causes, indicators and diagnosing of wellbore instability as well as the wellbore stresses model.

  19. Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age

    OpenAIRE

    Živković, Lada; Spremo-Potparević, Biljana; Plećaš-Solarović, Bosiljka; Djelić, Ninoslav; Ocić, Gordana; Smiljković, Predrag; Siedlak, Sandra L.; Smith, Mark A.; Bajić, Vladan

    2010-01-01

    Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X ch...

  20. Chromosome Abnormalities

    Science.gov (United States)

    ... are two kinds of cell division, mitosis and meiosis. Mitosis results in two cells that are duplicates ... make up our body are made and replaced. Meiosis results in cells with half the number of ...

  1. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar

    2014-10-01

    Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

  2. Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy

    OpenAIRE

    Kohlhase, J; Schubert, L.; Liebers, M; Rauch, A; Becker, K.; Mohammed, S; Newbury-Ecob, R.; REARDON, W.

    2003-01-01

    We have recently shown that Okihiro syndrome results from mutation in the putative zinc finger transcription factor gene SALL4 on chromosome 20q13.13-13.2. There is considerable overlap of clinical features of Okihiro syndrome with other conditions, most notably Holt-Oram syndrome, a condition in part resulting from mutation of the TBX5 locus, as well as acro-renal-ocular syndrome. We analysed further families/patients with the clinical diagnosis of Holt-Oram syndrome and acro-renal-ocular sy...

  3. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    OpenAIRE

    Daniela Mierla; Viorica Radoi; Veronica Stoian

    2012-01-01

    Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, ka...

  4. Chromosome landmarks and autosome-sex chromosome translocations in Rumex hastatulus, a plant with XX/XY1Y2 sex chromosome system.

    Science.gov (United States)

    Grabowska-Joachimiak, Aleksandra; Kula, Adam; Książczyk, Tomasz; Chojnicka, Joanna; Sliwinska, Elwira; Joachimiak, Andrzej J

    2015-06-01

    Rumex hastatulus is the North American endemic dioecious plant with heteromorphic sex chromosomes. It is differentiated into two chromosomal races: Texas (T) race characterised by a simple XX/XY sex chromosome system and North Carolina (NC) race with a polymorphic XX/XY1Y2 sex chromosome system. The gross karyotype morphology in NC race resembles the derived type, but chromosomal changes that occurred during its evolution are poorly understood. Our C-banding/DAPI and fluorescence in situ hybridization (FISH) experiments demonstrated that Y chromosomes of both races are enriched in DAPI-positive sequences and that the emergence of polymorphic sex chromosome system was accompanied by the break of ancestral Y chromosome and switch in the localization of 5S rDNA, from autosomes to sex chromosomes (X and Y2). Two contrasting domains were detected within North Carolina Y chromosomes: the older, highly heterochromatinised, inherited from the original Y chromosome and the younger, euchromatic, representing translocated autosomal material. The flow-cytometric DNA estimation showed ∼3.5 % genome downsizing in the North Carolina race. Our results are in contradiction to earlier reports on the lack of heterochromatin within Y chromosomes of this species and enable unambiguous identification of autosomes involved in the autosome-heterosome translocation, providing useful chromosome landmarks for further studies on the karyotype and sex chromosome differentiation in this species. PMID:25394583

  5. Longitudinal instability of a bunched beam resulting from current loading of the accelerating system in an ultrahigh-energy proton synchrotron

    CERN Document Server

    Ivanov, S V

    1981-01-01

    Collective effects in the acceleration and storage of particles have recently attracted considerable interest. The authors discuss the theory of the longitudinal multipole instabilities of coupled modes of a bunched beam. Up to now, there has been no electrodynamic calculation of the excitation of the resonant elements around the beam, so that only impedances of a simple resonator type are used (the variations in the longitudinal component of the electric field on the resonator axis are not taken into account). Furthermore, and particularly significantly, elements of a waveguide nature have been ignored (the accelerating systems of the CERN SPS synchrotron in the working frequency band are examples of such elements). The authors' intention is to correct these deficiencies of the theory. (7 refs).

  6. mBAND Analysis of Late Chromosome Aberrations in Human Lymphocytes Induced by Gamma Rays and Fe Ions

    Science.gov (United States)

    Sunagawa, Mayumi; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2014-01-01

    Chromosomal translocations and inversions are considered stable, and cells containing these types of chromosome aberrations can survive multiple cell divisions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. Detailed analysis of chromosome break ends participating in exchanges revealed a greater fraction of break ends involved in intrachromosome aberrations in the 7- and 14-day samples in comparison to the fraction at first mitosis. In particular, simple inversions were found at 7 and 14 days, but not at the first mitosis, suggesting that some of the aberrations might be formed days post irradiation. In contrast, at the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Comparison between low and high doses of Fe ion irradiation in the induction of late damages will also be discussed.

  7. Development of cancer-initiating cells and immortalized cells with genomic instability.

    Science.gov (United States)

    Yoshioka, Ken-Ichi; Atsumi, Yuko; Nakagama, Hitoshi; Teraoka, Hirobumi

    2015-03-26

    Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells. PMID:25815132

  8. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  9. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li

    2009-01-01

    Objective: The progression of human cancer is characterized by the accumulation of genetic instability. An increasing number of experimental genetic molecular techniques have been used to detect chromosome aberrations. Previous studies on chromosome abnormalities often focused on identifying the frequent loci of chromosome alterations, but rarely addressed the issue of interrelationship of chromosomal abnormalities. In the last few years, several mathematical models have been employed to construct models of carcinogenesis, in an attempt to identify the time order and cause-and-effect relationship of chromosome aberrations. The principles and applications of these models are reviewed and compared in this paper. Mathematical modeling of carcinogenesis can contribute to our understanding of the molecular genetics of tumor development, and identification of cancer related genes, thus leading to improved clinical practice of cancer.

  10. Genomic heterogeneity and instability in colorectal cancer: spectral karyotyping, glutathione transferase-Ml and ras.

    Science.gov (United States)

    Bartos, Jeremy D; Stoler, Daniel L; Matsui, Sei-ichi; Swede, Helen; Willmott, Lyndsay J; Sait, Sheila N; Petrelli, Nicholas J; Anderson, Garth R

    2004-12-21

    Genomic instability in cancer is frequently described as being either chromosomal instability or microsatellite instability, although when events within chromosomes are monitored, extensive intrachromosomal instability is also found. Spectral karyotyping was used to visualize how extensively genomic instability gives rise to intratumor genomic heterogeneity in sporadic colorectal carcinomas. Two factors were then examined which might relate to intrachromosomal instability in colorectal cancers: the presence of the glutathione transferase-Ml gene to detoxify potential carcinogens, and the presence of activated ras which has been associated with chromosomal instability when first expressed. Intrachromosomal genomic instability was previously determined by inter-(simple sequence repeat) PCR (inter-SSR PCR) and by fractional allelic loss rate for 348 markers. GSTM1 status was determined for each of 49 tumors through use of specific PCR, and 28 of the tumors showed the GSTM1 null genotype. A significant association was found between GSTMl-null status and elevated inter-(simple sequence repeat) PCR instability. In contrast, no association was found with fractional allelic loss rate. The first exons of the K-ras and H-ras oncogenes were sequenced in 72 colorectal cancers; 19 of the tumors had a mutation in codon 12 of the K-ras gene (24.5%), but no H-ras mutations were found. A weak correlation (p=0.10) was observed between mutant K-ras and inter-(simple sequence repeat) PCR genomic instability, and no association existed with fractional allelic loss rate. PMID:15542115

  11. Genetic and Epigenetic Changes in Chromosomally Stable and Unstable Progeny of Irradiated Cells

    Energy Technology Data Exchange (ETDEWEB)

    Baulch, Janet E.; Aypar, Umut; Waters, Katrina M.; Yang, Austin; Morgan, William F.

    2014-09-24

    Radiation induced genomic instability is a well-studied phenomenon, the underlying mechanisms of which are poorly understood. Persistent oxidative stress, mitochondrial dysfunction, elevated cytokine levels and epigenetic changes are among the mechanisms invoked in the perpetuation of the phenotype. To determine whether epigenetic aberrations affect genomic instability we measured DNA methylation, mRNA and microRNA (miR) levels in well characterized chromosomally stable and unstable clonally expanded single cell survivors of irradiation. While no changes in DNA methylation were observed for the gene promoters evaluated, increased LINE-1 methylation was observed for two unstable clones (LS12, CS9) and decreased Alu element methylation was observed for the other two unstable clones (115, Fe5.0-8). These relationships also manifested for mRNA and miR expression. mRNA identified for the LS12 and CS9 clones were most similar to each other (261 mRNA), while the 115 and Fe5.0-8 clones were more similar to each other, and surprisingly also similar to the two stable clones, 114 and 118 (286 mRNA among these four clones). Pathway analysis showed enrichment for pathways involved in mitochondrial function and cellular redox, themes routinely invoked in genomic instability. The commonalities between the two subgroups of clones were also observed for miR. The number of miR for which anti-correlated mRNA were identified suggests that these miR exert functional effects in each clone. The results of this study demonstrate significant genetic and epigenetic changes in unstable cells, but similar changes almost equally common in chromosomally stable cells. Possible conclusions might be that the chromosomally stable clones have some other form of instability, or that some of the observed changes represent a sort of radiation signature for and that other changes are related to genomic instability. Irrespective, these findings again suggest that a spectrum of changes both drive genomic

  12. Genetic instability in nerve sheath cell tumors

    DEFF Research Database (Denmark)

    Rogatto, Silvia Regina; Casartelli, Cacilda; Rainho, Claudia Aparecida; Barbieri Neto, J

    1995-01-01

    After in vitro culture, we analyzed cytogenetically four acoustic nerve neurinomas, one intraspinal neurinoma and one neurofibroma obtainedfrom unrelated patients. Monosomy of chromosomes 22 and 16 was an abnormality common to all cases, followed in frequency by loss of chromosomes 18 (three cases......, reflected by the presence of polyploid cells with inconsistent abnormalities, endoreduplications and telomeric associations resulting in dicentric chromosomes. It is probable that these cytogenetic abnormalities represent some kind of evolutionary advantage for the in vitro progression of nerve sheath...

  13. Chromosome polymorphism in a population of ceratitis capitata

    International Nuclear Information System (INIS)

    A morphological chromosomal polymorphism along with the observation of B chromosomes in a natural population of Ceratitis capitata is reported. A variability affecting the centromere size of chromosome 3 is described. The observed B chromosome is minute, heterochromatic and telocentric. The B chromosome was found in the male and female germ cells and it exhibited, in the males, intra-individual numerical variation with OB and IB cells, which suggested a mitotic instability. It was also found, in both sexes, in somatic cells (cerebral ganglia tissue). Only males transmitted the B chromosomes to the progeny. The high rate of transmission suggested a differential utilization of the sperm carrying the B chromosomes or a preferential segregation into secondary spermatocytes. Previously reported linkage relationship between a pupal esterase gene (Est-1) and a pupa colour mutant (nig) has been extended to a line carrying a Y-chromosome (Y,B) shorter than the one previously studied (Y,A). Furthermore, an elaborate crossing scheme has been devised in order to estimate the recombination distances between these two genes and a third one affecting pupal length (lp-1). It is concluded that all three genes are in the same linkage group but Est-1 is far from the other two. In turn, nig and lp-1 are separated by 14.9 map units. It is confirmed that genetic recombination does not regularly occur at high frequency in the male and this frequency is not increased by the varying length of the Y-chromosome. Refs, figs, tabs

  14. Chromosomal aberrations in ore miners of Slovakia

    International Nuclear Information System (INIS)

    A pilot study was performed in which the incidence of chromosomal aberrations in lymphocytes of miners in ore mines located in Central Slovakia was monitored and related to lifetime underground radon exposure and to lifetime smoking. The conclusions drawn from the results of the study were as follows: the counts of chromosomal aberrations in lymphocytes of miners were significantly higher than in an age matched control group of white-collar staff; the higher counts of chromosomal aberrations could be ascribed to underground exposure of miners and to smoking; a dependence of chromosomal aberration counts on the exposure to radon could not be assessed. (A.K.)

  15. Amifostine Protection Against Mitomycin-induced Chromosomal Breakage in Fanconi Anaemia Lymphocytes

    OpenAIRE

    Lopes, Miriam T. P.; Salas, Carlos E.; Fernanda S. G. Kehdy; Camelo, Ricardo M.

    2008-01-01

    Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronucle...

  16. DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation.

    OpenAIRE

    Deniz Simsek; Erika Brunet; Sunnie Yan-Wai Wong; Sachin Katyal; Yankun Gao; McKinnon, Peter J.; Jacqueline Lou; Lei Zhang; James Li; Rebar, Edward J; Gregory, Philip D.; Michael C. Holmes; Maria Jasin

    2011-01-01

    International audience Nonhomologous end-joining (NHEJ) is the primary DNA repair pathway thought to underlie chromosomal translocations and other genomic rearrangements in somatic cells. The canonical NHEJ pathway, including DNA ligase IV (Lig4), suppresses genomic instability and chromosomal translocations, leading to the notion that a poorly defined, alternative NHEJ (alt-NHEJ) pathway generates these rearrangements. Here, we investigate the DNA ligase requirement of chromosomal translo...

  17. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    OpenAIRE

    Payne CM; Crowley-Skillicorn C; Bernstein C; Holubec H; Bernstein H

    2011-01-01

    Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated w...

  18. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells

    OpenAIRE

    Oumar Samassekou; Huiyu Li; Josée Hébert; Aimé Ntwari; Haixia Wang; Catherine Grenier Cliché; Eric Bouchard; Shiang Huang; Ju Yan

    2011-01-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found th...

  19. The CRO-1 gene of Saccharomyces cerevisiae controls mitotic crossing over, chromosomal stability and sporulation

    International Nuclear Information System (INIS)

    The properties of a novel temperature-sensitive recombination-defective mutant of Saccharomyces cerevisiae, cro1-1 is described. The cro1-1 mutant is the first instance of a rec mutation that reduces drastically the rates of spontaneous mitotic crossing-over events but not those of gene conversional events. The cro1-1 mutation thus provides evidence that mitotic crossing-over is dependent upon gene products that are not essential for gene conversional events. The cro1-1 mutation also results in enhanced mitotic-chromosomal instability and MATa/MATα cro1-1/cro1-1 mutants are sporulation deficient. These phenotypes indicate that the CRO1 gene modulates mitotic chromosomal integrity and is essential for normal meiosis. The cro1-1 mutant possesses Holliday junction resolvase activity, hence its recombinational defect does not involve failure to execute this putative final recombinational step. 7 refs., 1 fig., 5 tabs

  20. Mapping of human chromosomal regions related to neoplasia: evidence from chromosomes 1 and 17

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1977-12-01

    In clonal aberrations leading to an excess or partial excess of chromosome I, trisomy for bands 1q25-1q32 was noted in the myeloid cells from all of 34 patients who had various disorders such as acute leukemia, polycythemia vera, and myelofibrosis. This was not the result of a particularly fragile site in that region of the chromosome because the break points in reciprocal translocations that involve it occurred almost exclusively in the short arm. Two consistent rearrangements that have been observed in chromosome 17 produced either duplication of the entire long arm or a translocation of the distal portion of the long arm to chromosome 15. The nonrandom chromosomal changes found in hematologic disorders can now be correlated with the gene loci on these chromosomes or chromosomal segments. Seventy-five genes related to various metabolic enzymes have been mapped; it may be significant that chromosomes carrying gene loci related to nucleic acid metabolism are more frequently involved in hematologic disorders (and other malignancies as well) than are gene loci related to intermediary or carbohydrate metabolism. Furthermore, the known virus-human chromosome associations are closely correlated with the chromosomes affected in hematologic disorders. If one of the effects of carcinogens (including viruses) is to activate genes that regulate host cell DNA synthesis, and if translocations or duplications of specific chromosomal segments produce the same effect, then either of these mechanisms might provide the affected cell with a proliferative advantage.

  1. A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.

    OpenAIRE

    Estabrooks, L L; Lamb, A.N.; Kirkman, H N; Callanan, N P; Rao, K W

    1992-01-01

    We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in aff...

  2. Telomere Length on Chromosome 17q Shortens More than Global Telomere Length in the Development of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Fariborz Rashid-Kolvear

    2007-04-01

    Full Text Available It is known that total telomere length is shorter in invasive breast cancer than in normal breast tissue but the status of individual telomere lengths has not been studied. Part of the difficulty is that usually telomere length in interphase cells is measured on all chromosomes together. In this study we compared normal breast epithelium, duct carcinoma in situ (DCIS, and invasive duct carcinoma (IDC from 18 patients. Telomere length was specifically measured on chromosome 17q and was found to be shorter in DCIS and IDC than in normal breast epithelial cells, with more heterogeneity in telomere length in DCIS associated with IDC than in DCIS alone. More importantly, we found that the shortening of telomere on chromosome 17q is greater than the average shortening of all telomeres. This finding indicates that telomere shortening is not simply the result of the end replication problem; otherwise, all telomeres should be subjected to the same rate of telomere shortening. It seems there are mechanisms that preferentially erode some telomeres more than others or preferentially protect some chromosome ends. Our results suggest that the increased level of telomere shortening on 17q may be involved in chromosome instability and the progression of DCIS.

  3. Genomic instability of micronucleated cells revealed by single-cell comparative genomic hybridization.

    NARCIS (Netherlands)

    Imle, A.; Polzer, B.; Alexander, S.; Klein, C.A.; Friedl, P.H.A.

    2009-01-01

    Nuclear variation in size and shape and genomic instability are hallmarks of dedifferentiated cancer cells. Although micronuclei are a typical long-term consequence of DNA damage, their contribution to chromosomal instability and clonal diversity in cancer disease is unclear. We isolated cancer cell

  4. Systematics of shoulder instability

    International Nuclear Information System (INIS)

    Shoulder instability is defined as a symptomatic abnormal motion of the humeral head relative to the glenoid during active shoulder motion. Glenohumeral instabilities are classified according to the causative factors as the pathogenesis of instability plays an important role with respect to treatment options. Instabilities are classified into traumatic and atraumatic instabilities as part of a multidirectional instability syndrome and into microtraumatic instabilities. For diagnostics plain radiographs (''trauma series'') are performed to document shoulder dislocation and its successful repositioning. Direct magnetic resonance (MR) arthrography is the most important imaging modality for delineation of the different injury patterns of the labral-ligamentous complex and bony structures. Monocontrast computed tomography (CT) arthrography with the use of multidetector CT scanners represents an alternative imaging modality; however, MR imaging should be preferred in the work-up of shoulder instabilities due to the mostly younger age of patients. (orig.)

  5. X-chromosome workshop.

    Science.gov (United States)

    Paterson, A D

    1998-01-01

    Researchers presented results of ongoing research to the X-chromosome workshop of the Fifth World Congress on Psychiatric Genetics, covering a wide range of disorders: X-linked infantile spasms; a complex phenotype associated with deletions of Xp11; male homosexuality; degree of handedness; bipolar affective disorder; schizophrenia; childhood onset psychosis; and autism. This report summarizes the presentations, as well as reviewing previous studies. The focus of this report is on linkage findings for schizophrenia and bipolar disorder from a number of groups. For schizophrenia, low positive lod scores were obtained for markers DXS991 and DXS993 from two studies, although the sharing of alleles was greatest from brother-brother pairs in one study, and sister-sister in the other. Data from the Irish schizophrenia study was also submitted, with no strong evidence for linkage on the X chromosome. For bipolar disease, following the report of a Finnish family linked to Xq24-q27, the Columbia group reported some positive results for this region from 57 families, however, another group found no evidence for linkage to this region. Of interest, is the clustering of low positive linkage results that point to regions for possible further study. PMID:9686435

  6. Semi-automatic laser beam microdissection of the Y chromosome and analysis of Y chromosome DNA in a dioecious plant, Silene latifolia

    International Nuclear Information System (INIS)

    Silene latifolia has heteromorphic sex chromosomes, the X and Y chromosomes. The Y chromosome, which is thought to carry the male determining gene, was isolated by UV laser microdissection and amplified by degenerate oligonucleotide-primed PCR. In situ chromosome suppression of the amplified Y chromosome DNA in the presence of female genomic DNA as a competitor showed that the microdissected Y chromosome DNA did not specifically hybridize to the Y chromosome, but-hybridized to all chromosomes. This result suggests that the Y chromosome does not contain Y chromosome-enriched repetitive sequences. A repetitive sequence in the microdissected Y chromosome, RMY1, was isolated while screening repetitive sequences in the amplified Y chromosome. Part of the nucleotide sequence shared a similarity to that of X-43.1, which was isolated from microdissected X chromosomes. Since fluorescence in situ hybridization analysis with RMY1 demonstrated that RMY1 was localized at the ends of the chromosome, RMY1 may be a subtelomeric repetitive sequence. Regarding the sex chromosomes, RMY1 was detected at both ends of the X chromosome and at one end near the pseudoautosomal region of the Y chromosome. The different localization of RMY1 on the sex chromosomes provides a clue to the problem of how the sex chromosomes arose from autosomes

  7. Earnings instability and tenure

    OpenAIRE

    Cappellari, Lorenzo; Leonardi, Marco

    2007-01-01

    We study the effect of tenure on earnings instability in Italy using two alternative estimation strategies. First we use a descriptive measure of earnings instability and fixed effects regressions. Second, we develop a formal model of earnings dynamics distinguishing permanent from transitory earnings, and exploit variation of tenure and instability over time and across birth cohorts in estimation. We use the two approaches also to evaluate earnings instability associated with temporary contr...

  8. A dominant negative mutant of TLK1 causes chromosome missegregation and aneuploidy in normal breast epithelial cells

    Directory of Open Access Journals (Sweden)

    Williams Briana

    2003-10-01

    Full Text Available Abstract Background In Arabidopsis thaliana, the gene Tousled encodes a protein kinase of unknown function, but mutations in the gene lead to flowering and leaf morphology defects. We have recently cloned a mammalian Tousled-Like Kinase (TLK1B and found that it phosphorylates specifically histone H3, in vitro and in vivo. We now report the effects that overexpression of a kinase-dead mutant of TLK1B mediates in a normal diploid cell line. Results Expression of a kinase-dead mutant resulted in reduction of phosphorylated histone H3, which could have consequences in mitotic segregation of chromosomes. When analyzed by FACS and microscopy, these cells displayed high chromosome number instability and aneuploidy. This phenomenon was accompanied by less condensed chromosomes at mitosis; failure of a number of chromosomes to align properly on the metaphase plate; failure of some chromosomes to attach to microtubules; and the occasional presentation of two bipolar spindles. We also used a different method (siRNA to reduce the level of endogenous TLK1, but in this case, the main result was a strong block of cell cycle progression suggesting that TLK1 may also play a role in progression from G1. This block in S phase progression could also offer a different explanation of some of the later mitotic defects. Conclusions TLK1 has a function important for proper chromosome segregation and maintenance of diploid cells at mitosis in mammalian cells that could be mediated by reduced phosphorylation of histone H3 and condensation of chromosomes, although other explanations to the phenotype are possible.

  9. Exceptional Complex Chromosomal Rearrangements in Three Generations

    Directory of Open Access Journals (Sweden)

    Hannie Kartapradja

    2015-01-01

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

  10. Retrospective dosimetry using chromosome painting

    International Nuclear Information System (INIS)

    have performed our own dose response relationship, based on the frequency of stable chromosome aberrations detected by Chromosome Painting for Co60 γ-rays, with doses ranging from 0 Gy to 3 Gy delivered at a 0.4 Gy/min dose rate and painting chromosomes 1, 2 and 4, which represent 22% of the genome. We have scored reciprocal and non-reciprocal translocations, excess of painted acentrics, insertions, dicentrics and centric rings. After extrapolating the obtained frequencies to the full genome, the corresponding data set agree well with our previous results of dicentrics and centric rings and reciprocal and non reciprocal translocations, obtained using the same in vitro irradiation protocol. In order to collect information about the stability and the cumulative behavior of stable chromosome aberrations, we have retrospectively evaluated, using the Chromosome Painting calibration curve, a nuclear power plant worker sample with doses ranging from 500 mSv to 800 mSv. As a whole, the observed frequencies do not differ significantly from the expected frequencies obtained applying the calibration curve α coefficient. Some workers of this samples were previously evaluated using G-banding in 1995 and the present results agree well with the expected frequencies due to the accumulated during the last four years. (author)

  11. Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

    Energy Technology Data Exchange (ETDEWEB)

    Fitzgerald, Kent, E-mail: Kent.fitzgerald@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bergeron, Marcelle, E-mail: Marcelle.bergeron@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Willits, Christopher, E-mail: Chris.willits@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bowers, Simeon, E-mail: Simeon.bowers@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Aubele, Danielle L., E-mail: Danielle.aubele@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Goldbach, Erich, E-mail: Erich.goldbach@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Tonn, George, E-mail: George.tonn@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Ness, Daniel, E-mail: Dan.ness@elan.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Olaharski, Andrew, E-mail: andrew.olaharski@agios.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States)

    2013-05-15

    Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646

  12. Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

    International Nuclear Information System (INIS)

    Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646 decreased

  13. Dean flow fractionation of chromosomes

    Science.gov (United States)

    Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.

    2016-03-01

    Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.

  14. Chimpanzee chromosome 12 is homologous to human chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Most of the 46 human chromosomes find their counterparts in the 48 chimpanzee chromosomes except for chromosome 2 which has been hypothesized to have been derived from a centric fusion of two chimpanzee acrocentric chromosomes. These two chromosomes correspond to the human chromosomes 2p and 2g. This conclusion is based primarily on chromosome banding techniques, and the somatic cell hybridization technique has also been used. (HLW)

  15. CENPA overexpression promotes genome instability in pRb-depleted human cells

    Directory of Open Access Journals (Sweden)

    Lentini Laura

    2009-12-01

    Full Text Available Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was not affected by p53 loss. Quantitative real-time RT-PCR showed that pRB depletion altered expression of genes involved in centrosome duplication, kinetochore assembly and in the Spindle Assembly Checkpoint (SAC. However, despite MAD2 up-regulation pRb-depleted cells seemed to have a functional SAC since they arrested in mitosis after treatments with mitotic poisons. Moreover pRb-depleted HCT116 cells showed BRCA1 overexpression that seemed responsible for MAD2 up-regulation. Post-transcriptional silencing of CENPA by RNA interference, resulting in CENP-A protein levels similar to those present in control cells greatly reduced aneuploid cell numbers in pRb-depleted cells. Conclusion Altogether our findings indicate a novel aspect of pRb acute loss that promotes aneuploidy mainly by inducing CENPA overexpression that in turn might induce micronuclei by affecting the correct attachment of spindle microtubules to kinetochores.

  16. 不育男性Y染色体长度异常的精液质量%Effect of abnormality Y chromosome and sperm quality on the result of insisted reproductive techniques

    Institute of Scientific and Technical Information of China (English)

    谢伟; 秦雯; 莫定敢; 陈美佳; 吕福通; 覃爱平

    2016-01-01

    Objective To investigate the effect of abnormality Y chromosome and sperm quality on the clinical result of insisted reproductive technique (ART). Methods We retrospectively analyzed the effect of ab-normality Y chromosome and sperm quality on embryo quality/result of pregnancy of patients undergoing ART. In-fertile men with normality Y chromosome (n=436) and with abnormality Y chromosome (n =146) from Jan 2010 to Dec 2010 were enrolled in this study. The infertile men were divided into four groups: the normality Y chromo-some plus teratozoospermia group , the normality Y chromosome plus normal sperm quality group , the abnormality Y chromosome plus teratozoospermia group, the abnormality Y chromosome plus normal sperm quality group. Embryo quality and the results of clinic pregnancy outcome were analyzed among the four groups. Results Fertilization rate of the four groups was 73.4%, 69.0%, 70.9% and 68%, respectively (P < 0.05). No significant differences were found in thecleavage rate, optimal embryo rate and pregnancy outcome among the four groups. Conclusions Both abnormality Y chromosome length and teratozoospermia may be affect the fertility rate of the infertile men undergoing IVF/ICSI.%目的:了解在辅助生殖技术(insisted reproductive techniques,ART)中 Y 染色体长度异常患者的精液质量情况,并按不同精液质量分组,讨论其胚胎质量、临床妊娠结局及意义。方法:通过回顾性分析2010年1月1日至2010年12月31日在中心进行辅助生殖助孕的患者共2739周期,染色体检查682例,其中染色体正常436(63.93%),合并畸形精子症196例,染色体长度异常共146例(Y =22,139例;Y =18,7例),占5.33%,合并畸形精子症73例。将患者分为染色体长度正常组和染色体长度异常组,再分精子形态正常组、精子形态异常组2个亚组,共4组,即染色体长度正常且精子形态正常组(组1),染色体长度正

  17. Degeneration of the Y chromosome in evolutionary aging models

    Science.gov (United States)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  18. Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Yan [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Kwon, Yong Tae [Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261 (United States); An, Jee Young [Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Eller, Danny [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Tsai, S.-C. [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Diaz-Perez, Silvia [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Troke, Joshua J. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Teitell, Michael A. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Marahrens, York [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States)]. E-mail: ymarahrens@mednet.ucla.edu

    2006-04-11

    The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2{sup -/-} male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2{sup -/-} embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2{sup -/-} fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2{sup -/-} cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2{sup -/-} cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2{sup -/-} cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2{sup -/-} cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair.

  19. Amplification of HER2 is a marker for global genomic instability

    Directory of Open Access Journals (Sweden)

    Love Brad

    2008-10-01

    Full Text Available Abstract Background Genomic alterations of the proto-oncogene c-erbB-2 (HER-2/neu are associated with aggressive behavior and poor prognosis in patients with breast cancer. The variable clinical outcomes seen in patients with similar HER2 status, given similar treatments, suggests that the effects of amplification of HER2 can be influenced by other genetic changes. To assess the broader genomic implications of structural changes at the HER2 locus, we investigated relationships between genomic instability and HER2 status in patients with invasive breast cancer. Methods HER2 status was determined using the PathVysion® assay. DNA was extracted after laser microdissection from the 181 paraffin-embedded HER2 amplified (n = 39 or HER2 negative (n = 142 tumor specimens with sufficient tumor available to perform molecular analysis. Allelic imbalance (AI was assessed using a panel of microsatellite markers representing 26 chromosomal regions commonly altered in breast cancer. Student t-tests and partial correlations were used to investigate relationships between genomic instability and HER2 status. Results The frequency of AI was significantly higher (P P Conclusion The poor prognosis associated with HER2 amplification may be attributed to global genomic instability as cells with high frequencies of chromosomal alterations have been associated with increased cellular proliferation and aggressive behavior. In addition, high levels of DNA damage may render tumor cells refractory to treatment. In addition, specific alterations at chromosomes 11q13, 16q22-q24, and 18q21, all of which have been associated with aggressive tumor behavior, may serve as genetic modifiers to HER2 amplification. These data not only improve our understanding of HER in breast pathogenesis but may allow more accurate risk profiles and better treatment options to be developed.

  20. Mode-locking via dissipative Faraday instability

    Science.gov (United States)

    Tarasov, Nikita; Perego, Auro M.; Churkin, Dmitry V.; Staliunas, Kestutis; Turitsyn, Sergei K.

    2016-08-01

    Emergence of coherent structures and patterns at the nonlinear stage of modulation instability of a uniform state is an inherent feature of many biological, physical and engineering systems. There are several well-studied classical modulation instabilities, such as Benjamin-Feir, Turing and Faraday instability, which play a critical role in the self-organization of energy and matter in non-equilibrium physical, chemical and biological systems. Here we experimentally demonstrate the dissipative Faraday instability induced by spatially periodic zig-zag modulation of a dissipative parameter of the system--spectrally dependent losses--achieving generation of temporal patterns and high-harmonic mode-locking in a fibre laser. We demonstrate features of this instability that distinguish it from both the Benjamin-Feir and the purely dispersive Faraday instability. Our results open the possibilities for new designs of mode-locked lasers and can be extended to other fields of physics and engineering.

  1. Research for genetic instability of human genome

    International Nuclear Information System (INIS)

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author)

  2. Genome instability and aging.

    Science.gov (United States)

    Vijg, Jan; Suh, Yousin

    2013-01-01

    Genome instability has long been implicated as the main causal factor in aging. Somatic cells are continuously exposed to various sources of DNA damage, from reactive oxygen species to UV radiation to environmental mutagens. To cope with the tens of thousands of chemical lesions introduced into the genome of a typical cell each day, a complex network of genome maintenance systems acts to remove damage and restore the correct base pair sequence. Occasionally, however, repair is erroneous, and such errors, as well as the occasional failure to correctly replicate the genome during cell division, are the basis for mutations and epimutations. There is now ample evidence that mutations accumulate in various organs and tissues of higher animals, including humans, mice, and flies. What is not known, however, is whether the frequency of these random changes is sufficient to cause the phenotypic effects generally associated with aging. The exception is cancer, an age-related disease caused by the accumulation of mutations and epimutations. Here, we first review current concepts regarding the relationship between DNA damage, repair, and mutation, as well as the data regarding genome alterations as a function of age. We then describe a model for how randomly induced DNA sequence and epigenomic variants in the somatic genomes of animals can result in functional decline and disease in old age. Finally, we discuss the genetics of genome instability in relation to longevity to address the importance of alterations in the somatic genome as a causal factor in aging and to underscore the opportunities provided by genetic approaches to develop interventions that attenuate genome instability, reduce disease risk, and increase life span. PMID:23398157

  3. Potentially active copies of the gypsy retroelement are confined to the Y chromosome of some strains of Drosophila melanogaster possibly as the result of the female-specific effect of the flamenco gene.

    Science.gov (United States)

    Chalvet, F; di Franco, C; Terrinoni, A; Pelisson, A; Junakovic, N; Bucheton, A

    1998-04-01

    Gypsy is an endogenous retrovirus present in the genome of Drosophila melanogaster. This element is mobilized only in the progeny of females which contain active gypsy elements and which are homozygous for permissive alleles of a host gene called flamenco (flam). Some data strongly suggest that gypsy elements bearing a diagnostic HindIII site in the central region of the retrovirus body represent a subfamily that appears to be much more active than elements devoid of this site. We have taken advantage of this structural difference to assess by the Southern blotting technique the genomic distribution of active gypsy elements. In some of the laboratory Drosophila stocks tested, active gypsy elements were found to be restricted to the Y chromosome. Further analyses of 14 strains tested for the permissive vs. restrictive status of their flamenco alleles suggest that the presence of permissive alleles of flam in a stock tends to be associated with the confinement of active gypsy elements to the Y chromosome. This might be the result of the female-specific effect of flamenco on gypsy activity. PMID:9541538

  4. Centrosomal clustering contributes to chromosomal instability and cancer.

    Science.gov (United States)

    Milunović-Jevtić, A; Mooney, P; Sulerud, T; Bisht, J; Gatlin, J C

    2016-08-01

    Cells assemble mitotic spindles during each round of division to insure accurate segregation of their duplicated genome. In animal cells, stereotypical spindles have two poles, each containing one centrosome, from which microtubules are nucleated. By contrast, many cancer cells often contain more than two centrosomes and form transient multipolar spindle structures with more than two poles. In order to divide and produce viable progeny, the multipolar spindle intermediate must be reshaped into a pseudo-bipolar structure via a process called centrosomal clustering. Pseudo-bipolar spindles appear to function normally during mitosis, but they occasionally give rise to aneuploid and transformed daughter cells. Agents that inhibit centrosomal clustering might therefore work as a potential cancer therapy, specifically targeting mitosis in supernumerary centrosome-containing cells. PMID:27046071

  5. Fermi liquids near Pomeranchuk instabilities

    Science.gov (United States)

    Reidy, Kelly Elizabeth

    We explore features of a Fermi liquid near generalized Pomeranchuk instabilities (PIs) starting from both ordered and disordered phases. These PIs can be viewed as quantum critical points in parameter space, and thus provide an alternate viewpoint on quantum criticality. We employ the tractable crossing symmetric equation method, which is a non-perturbative diagrammatic many-particle method used to calculate the Fermi liquid interaction functions and scattering amplitudes. We consider both repulsive and attractive underlying interactions of arbitrary strength. Starting from a ferromagnetically ordered ground state, we find that upon approach to an s-wave instability in one critical channel, the system simultaneously approaches instabilities in non-critical channels. We study origins and implications of this "quantum multicriticality". We also find that a nematic (non-s-wave) instability precedes and is driven by Pomeranchuk instabilities in both the s-wave spin and density channels. Finally, we discuss potential applications of our results to physical systems, such as ferromagnetic superconductors.

  6. Dissection and cytological mapping of barley chromosome 2H in the genetic background of common wheat

    OpenAIRE

    Joshi, Giri Prasad; Nasuda, Shuhei; Endo, Takashi R.

    2011-01-01

    We used gametocidal (Gc) chromosomes 2C and 3C[SAT] to dissect barley 2H added to common wheat. The Gc chromosome induces chromosomal breakage resulting in chromosomal aberrations in the progeny of the 2H addition line of common wheat carrying the monosomic Gc chromosome. We conducted in situ hybridization to select plants carrying structurally rearranged aberrant 2H chromosomes and characterized them by sequential C-banding and in situ hybridization. We established 66 dissection lines of com...

  7. Telomerase expression is sufficient for chromosomal integrity in cells lacking p53 dependent G1 checkpoint function

    Directory of Open Access Journals (Sweden)

    Simpson Dennis

    2005-01-01

    Full Text Available Abstract Background Secondary cultures of human fibroblasts display a finite lifespan ending at senescence. Loss of p53 function by mutation or viral oncogene expression bypasses senescence, allowing cell division to continue for an additional 10 – 20 doublings. During this time chromosomal aberrations seen in mitotic cells increase while DNA damage and decatenation checkpoint functions in G2 cells decrease. Methods To explore this complex interplay between chromosomal instability and checkpoint dysfunction, human fibroblast lines were derived that expressed HPV16E6 oncoprotein or dominant-negative alleles of p53 (A143V and H179Q with or without the catalytic subunit of telomerase. Results Cells with normal p53 function displayed 86 – 93% G1 arrest after exposure to 1.5 Gy ionizing radiation (IR. Expression of HPV16E6 or p53-H179Q severely attenuated G1 checkpoint function (3 – 20% arrest while p53-A143V expression induced intermediate attenuation (55 – 57% arrest irrespective of telomerase expression. All cell lines, regardless of telomerase expression or p53 status, exhibited a normal DNA damage G2 checkpoint response following exposure to 1.5 Gy IR prior to the senescence checkpoint. As telomerase-negative cells bypassed senescence, the frequencies of chromosomal aberrations increased generally congruent with attenuation of G2 checkpoint function. Telomerase expression allowed cells with defective p53 function to grow >175 doublings without chromosomal aberrations or attenuation of G2 checkpoint function. Conclusion Thus, chromosomal instability in cells with defective p53 function appears to depend upon telomere erosion not loss of the DNA damage induced G1 checkpoint.

  8. Shoulder instability; Schulterinstabilitaeten

    Energy Technology Data Exchange (ETDEWEB)

    Kreitner, Karl-Friedrich [Mainiz Univ. (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie

    2014-06-15

    In the shoulder, the advantages of range of motion are traded for the disadvantages of vulnerability to injury and the development of instability. Shoulder instability and the lesion it produces represent one of the main causes of shoulder discomfort and pain. Shoulder instability is defined as a symptomatic abnormal motion of the humeral head relative to the glenoid during active shoulder motion. Glenohumeral instabilities are classified according to their causative factors as the pathogenesis of instability plays an important role with respect to treatment options: instabilities are classified in traumatic and atraumatic instabilities as part of a multidirectional instability syndrome, and in microtraumatic instabilities. Plain radiographs ('trauma series') are performed to document shoulder dislocation and its successful reposition. Direct MR arthrography is the most important imaging modality for delineation the different injury patterns on the labral-ligamentous complex and bony structures. Monocontrast CT-arthrography with use of multidetector CT scanners may be an alternative imaging modality, however, regarding the younger patient age, MR imaging should be preferred in the diagnostic work-up of shoulder instabilities. (orig.)

  9. Effects of electron temperature anisotropy on proton mirror instability evolution

    CERN Document Server

    Ahmadi, Narges; Raeder, Joachim

    2016-01-01

    Proton mirror modes are large amplitude nonpropagating structures frequently observed in the magnetosheath. It has been suggested that electron temperature anisotropy can enhance the proton mirror instability growth rate while leaving the proton cyclotron instability largely unaffected, therefore causing the proton mirror instability to dominate the proton cyclotron instability in Earth's magnetosheath. Here, we use particle-in-cell simulations to investigate the electron temperature anisotropy effects on proton mirror instability evolution. Contrary to the hypothesis, electron temperature anisotropy leads to excitement of the electron whistler instability. Our results show that the electron whistler instability grows much faster than the proton mirror instability and quickly consumes the electron free energy, so that there is no electron temperature anisotropy left to significantly impact the evolution of the proton mirror instability.

  10. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    Genomic instability, induced by various metabolic, genetic, and environmental factors, is the driving force of tumorigenesis. Radiation exposure from different types of radiation sources induces different types of DNA damages, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo experiments. The cell survival rates and frequency of chromosome aberrations depend on the genetic background and radiation sources. To further understand genomic instability induced by charged particles, we exposed human lymphocytes ex vivo, human fibroblast cells, human mammary epithelial cells, and bone marrow cells isolated from CBA/CaH and C57BL/6 mice to high energy protons and Fe ions, and collected chromosomes at different generations after exposure. Chromosome aberrations were analyzed with fluorescent in situ hybridization with whole chromosome specific probes.

  11. Kinetic theory of tearing instability

    International Nuclear Information System (INIS)

    The guiding-center kinetic equation with Fokker-Planck collision term is used to study, in cylindrical geometry, a class of dissipative instabilities of which the classical tearing mode is an archetype. Variational solution of the kinetic equation obviates the use of an approximate Ohm's law or adiabatic assumption, as used in previous studies, and it provides a dispersive relation which is uniformly valid for any ratio of wave frequency to collision frequency. One result of using the rigorous collision operator is the prediction of a new instability. This instability, driven by the electron temperature gradient, is predicted to occur under the long mean-free path conditions of present tokamak experiments, and has significant features in common with the kink-like oscillations observed in such experiments

  12. Interfacial Instability during Granular Erosion

    Science.gov (United States)

    Lefebvre, Gautier; Merceron, Aymeric; Jop, Pierre

    2016-02-01

    The complex interplay between the topography and the erosion and deposition phenomena is a key feature to model granular flows such as landslides. Here, we investigated the instability that develops during the erosion of a wet granular pile by a dry dense granular flow. The morphology and the propagation of the generated steps are analyzed in relation to the specific erosion mechanism. The selected flowing angle of the confined flow on a dry heap appears to play an important role both in the final state of the experiment, and for the shape of the structures. We show that the development of the instability is governed by the inertia of the flow through the Froude number. We model this instability and predict growth rates that are in agreement with the experiment results.

  13. Longitudinal instability in HIF beams

    International Nuclear Information System (INIS)

    In contrast to an electron induction accelerator, in which the particle velocity is virtually constant, the resistive and inductive components of accelerating module impedances can cause instability for an intense non-relativistic heavy ion beam accelerated in a similar structure. Since focusing requirements at the fusion pellet imply a momentum spread approx-lt 3 x 10-4 at the end of the accelerator, it is essential to understand and suppress this instability. There is also an economic issue involved for this application; selection of parameters to control the instability must not unduly affect the efficiency and cost of the accelerator. This paper will present the results of analytic and computational work on module impedances, growth rates and feed back (forward) systems. 2 refs., 3 figs

  14. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  15. Travelling-wave-induced instability of structures

    International Nuclear Information System (INIS)

    The effect of transmission time of propagating disturbances on the dynamic instability of structures is discussed in this paper. Through a parametric study it is shown that for certain values of transmission time and wave frequency parameters, the structure may become dynamically unstable. An example is worked out, and graphical results depicting the regions of instability are presented

  16. Muscle activation patterns in patients with recurrent shoulder instability

    Directory of Open Access Journals (Sweden)

    Anju Jaggi

    2012-01-01

    Conclusion: The DEMG results suggest that increased activation of LD may play a role in both anterior and posterior shoulder instability; increased activation of PM may play a role in anterior instability.

  17. Joint instability and osteoarthritis.

    Science.gov (United States)

    Blalock, Darryl; Miller, Andrew; Tilley, Michael; Wang, Jinxi

    2015-01-01

    Joint instability creates a clinical and economic burden in the health care system. Injuries and disorders that directly damage the joint structure or lead to joint instability are highly associated with osteoarthritis (OA). Thus, understanding the physiology of joint stability and the mechanisms of joint instability-induced OA is of clinical significance. The first section of this review discusses the structure and function of major joint tissues, including periarticular muscles, which play a significant role in joint stability. Because the knee, ankle, and shoulder joints demonstrate a high incidence of ligament injury and joint instability, the second section summarizes the mechanisms of ligament injury-associated joint instability of these joints. The final section highlights the recent advances in the understanding of the mechanical and biological mechanisms of joint instability-induced OA. These advances may lead to new opportunities for clinical intervention in the prevention and early treatment of OA. PMID:25741184

  18. Dynamics of explosive instability

    International Nuclear Information System (INIS)

    It was shown that in general case explosive instability dynamics should be described as four wave interaction. The main difference from three wave interaction is that this dynamics may not contain explosive instability. Besides it may by irregular. If the characteristics of one of the wave is closed to one of the interacting wave and they are connected linearly then explosive instability may be suppressed.

  19. The hierarchically organized splitting of chromosomal bands for all human chromosomes

    Directory of Open Access Journals (Sweden)

    Liehr Thomas

    2009-01-01

    Full Text Available Abstract Background Chromosome banding is widely used in cytogenetics. However, the biological nature of hierarchically organized splitting of chromosomal bands of human chromosomes is an enigma and has not been, as yet, studied. Results Here we present for the first time the hierarchically organized splitting of chromosomal bands in their sub-bands for all human chromosomes. To do this, array-proved multicolor banding (aMCB probe-sets for all human chromosomes were applied to normal metaphase spreads of three different G-band levels. We confirmed for all chromosomes to be a general principle that only Giemsa-dark bands split into dark and light sub-bands, as we demonstrated previously by chromosome stretching. Thus, the biological band splitting is in > 50% of the sub-bands different than implemented by the ISCN nomenclature suggesting also a splitting of G-light bands. Locus-specific probes exemplary confirmed the results of MCB. Conclusion Overall, the present study enables a better understanding of chromosome architecture. The observed difference of biological and ISCN band-splitting may be an explanation why mapping data from human genome project do not always fit the cytogenetic mapping.

  20. Plant sex chromosome evolution.

    Science.gov (United States)

    Charlesworth, Deborah

    2013-01-01

    It is now well established that plants have an important place in studies of sex chromosome evolution because of the repeated independent evolution of separate sexes and sex chromosomes. There has been considerable recent progress in studying plant sex chromosomes. In this review, I focus on how these recent studies have helped clarify or answer several important questions about sex chromosome evolution, and I shall also try to clarify some common misconceptions. I also outline future work that will be needed to make further progress, including testing some important ideas by genetic, molecular, and developmental approaches. Systems with different ages can clearly help show the time course of events during changes from an ancestral co-sexual state (hermaphroditism or monoecy), and I will also explain how different questions can be studied in lineages whose dioecy or sex chromosomes evolved at different times in the past. PMID:23125359

  1. Chromosome Territory Modeller and Viewer.

    Science.gov (United States)

    Tkacz, Magdalena A; Chromiński, Kornel; Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi-a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license. PMID:27505434

  2. Chromosome Territory Modeller and Viewer

    Science.gov (United States)

    Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi–a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license. PMID:27505434

  3. Results of a collaborative study of the EDNAP group regarding the reproducibility and robustness of the Y-chromosome STRs DYS19, DYS389 I and II, DYS390 and DYS393 in a PCR pentaplex format.

    Science.gov (United States)

    Carracedo, A; Beckmann, A; Bengs, A; Brinkmann, B; Caglia, A; Capelli, C; Gill, P; Gusmão, L; Hagelberg, C; Hohoff, C; Hoste, B; Kihlgren, A; Kloosterman, A; Myhre Dupuy, B; Morling, N; O'Donnell, G; Parson, W; Phillips, C; Pouwels, M; Scheithauer, R; Schmitter, H; Schneider, P M; Schumm, J; Skitsa, I; Stradmann-Bellinghausen, B; Stuart, M; Syndercombe Court, D; Vide, C

    2001-06-01

    A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in the frame work of the STADNAP program, i.e. standardization of DNA profiling in Europe, in order to evaluate the performance of a Y-chromosome STR pentaplex, which includes the loci DYS19, DYS389 I and II, DYS390 and DYS393 and to determine whether uniformity of results could be achieved among different European laboratories. Laboratories were asked to analyze the five Y-STRs using singleplex and multiplex conditions in three bloodstains and one mixed stain (95% female and 5% male). All the laboratories reported the same results even for the mixed stain included in the exercise. This demonstrates the reproducibility and robustness of Y-chromosome STR typing even with multiplex formats and proves the usefulness of Y-STR systems for analyzing mixed stains with a male component.A total of 930 male samples from 10 different populations from Europe were also analysed for all the loci included in the pentaplex. Eight of these ten populations also included haplotype data. As for single gene analysis, haplotype diversity was higher in Germany and Italy and lower in Western European countries and Finland. Pairwise haplotype analysis shows the Finnish departure from the rest of the populations and a relatively homogeneity in the other European populations with F(ST) estimates lower than 0.05.UPGMA analysis shows an association of Western European population (Ireland, UK, Portugal and Galicia) on the one hand and central European populations on the other. PMID:11348791

  4. Chromosome differentiation patterns during cichlid fish evolution

    Directory of Open Access Journals (Sweden)

    Nirchio Mauro

    2010-06-01

    Full Text Available Abstract Background Cichlid fishes have been the subject of increasing scientific interest because of their rapid adaptive radiation which has led to an extensive ecological diversity and their enormous importance to tropical and subtropical aquaculture. To increase our understanding of chromosome evolution among cichlid species, karyotypes of one Asian, 22 African, and 30 South American cichlid species were investigated, and chromosomal data of the family was reviewed. Results Although there is extensive variation in the karyotypes of cichlid fishes (from 2n = 32 to 2n = 60 chromosomes, the modal chromosome number for South American species was 2n = 48 and the modal number for the African ones was 2n = 44. The only Asian species analyzed, Etroplus maculatus, was observed to have 46 chromosomes. The presence of one or two macro B chromosomes was detected in two African species. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA gene revealed a variable number of clusters among species varying from two to six. Conclusions The karyotype diversification of cichlids seems to have occurred through several chromosomal rearrangements involving fissions, fusions and inversions. It was possible to identify karyotype markers for the subfamilies Pseudocrenilabrinae (African and Cichlinae (American. The karyotype analyses did not clarify the phylogenetic relationship among the Cichlinae tribes. On the other hand, the two major groups of Pseudocrenilabrinae (tilapiine and haplochromine were clearly discriminated based on the characteristics of their karyotypes. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA gene did not follow the chromosome diversification in the family. The dynamic evolution of the repeated units of rRNA genes generates patterns of chromosomal distribution that do not help follows the phylogenetic relationships among taxa. The presence of B chromosomes in cichlids is of particular interest because they may not be represented in

  5. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.; Rasmussen, Lene Juel

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA of...... the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  6. Combustion Instabilities Modeled

    Science.gov (United States)

    Paxson, Daniel E.

    1999-01-01

    NASA Lewis Research Center's Advanced Controls and Dynamics Technology Branch is investigating active control strategies to mitigate or eliminate the combustion instabilities prevalent in lean-burning, low-emission combustors. These instabilities result from coupling between the heat-release mechanisms of the burning process and the acoustic flow field of the combustor. Control design and implementation require a simulation capability that is both fast and accurate. It must capture the essential physics of the system, yet be as simple as possible. A quasi-one-dimensional, computational fluid dynamics (CFD) based simulation has been developed which may meet these requirements. The Euler equations of mass, momentum, and energy have been used, along with a single reactive species transport equation to simulate coupled thermoacoustic oscillations. A very simple numerical integration scheme was chosen to reduce computing time. Robust boundary condition procedures were incorporated to simulate various flow conditions (e.g., valves, open ends, and choked inflow) as well as to accommodate flow reversals that may arise during large flow-field oscillations. The accompanying figure shows a sample simulation result. A combustor with an open inlet, a choked outlet, and a large constriction approximately two thirds of the way down the length is shown. The middle plot shows normalized, time-averaged distributions of the relevant flow quantities, and the bottom plot illustrates the acoustic mode shape of the resulting thermoacoustic oscillation. For this simulation, the limit cycle peak-to-peak pressure fluctuations were 13 percent of the mean. The simulation used 100 numerical cells. The total normalized simulation time was 50 units (approximately 15 oscillations), which took 26 sec on a Sun Ultra2.

  7. Cross-species chromosome painting tracks the independent origin of multiple sex chromosomes in two cofamiliar Erythrinidae fishes

    Science.gov (United States)

    2011-01-01

    Background The Erythrinidae fish family is characterized by a large variation with respect to diploid chromosome numbers and sex-determining systems among its species, including two multiple X1X2Y sex systems in Hoplias malabaricus and Erythrinus erythrinus. At first, the occurrence of a same sex chromosome system within a family suggests that the sex chromosomes are correlated and originated from ancestral XY chromosomes that were either homomorphic or at an early stage of differentiation. To identify the origin and evolution of these X1X2Y sex chromosomes, we performed reciprocal cross-species FISH experiments with two sex-chromosome-specific probes designed from microdissected X1 and Y chromosomes of H. malabaricus and E. erythrinus, respectively. Results Our results yield valuable information regarding the origin and evolution of these sex chromosome systems. Our data indicate that these sex chromosomes evolved independently in these two closed related Erythrinidae species. Different autosomes were first converted into a poorly differentiated XY sex pair in each species, and additional chromosomal rearrangements produced both X1X2Y sex systems that are currently present. Conclusions Our data provide new insights into the origin and evolution of sex chromosomes, which increases our knowledge about fish sex chromosome evolution. PMID:21718509

  8. The subcritical baroclinic instability in local accretion disc models

    CERN Document Server

    Lesur, G

    2009-01-01

    (abridged) Aims: We present new results exhibiting a subcritical baroclinic instability (SBI) in local shearing box models. We describe the 2D and 3D behaviour of this instability using numerical simulations and we present a simple analytical model describing the underlying physical process. Results: A subcritical baroclinic instability is observed in flows stable for the Solberg-Hoiland criterion using local simulations. This instability is found to be a nonlinear (or subcritical) instability, which cannot be described by ordinary linear approaches. It requires a radial entropy gradient weakly unstable for the Schwartzchild criterion and a strong thermal diffusivity (or equivalently a short cooling time). In compressible simulations, the instability produces density waves which transport angular momentum outward with typically alpha<3e-3, the exact value depending on the background temperature profile. Finally, the instability survives in 3D, vortex cores becoming turbulent due to parametric instabilities...

  9. Analysis of the Trojan Y-Chromosome eradication strategy for an invasive species

    KAUST Repository

    Wang, Xueying

    2013-05-24

    The Trojan Y-Chromosome (TYC) strategy, an autocidal genetic biocontrol method, has been proposed to eliminate invasive alien species. In this work, we analyze the dynamical system model of the TYC strategy, with the aim of studying the viability of the TYC eradication and control strategy of an invasive species. In particular, because the constant introduction of sex-reversed trojan females for all time is not possible in practice, there arises the question: What happens if this injection is stopped after some time? Can the invasive species recover? To answer that question, we perform a rigorous bifurcation analysis and study the basin of attraction of the recovery state and the extinction state in both the full model and a certain reduced model. In particular, we find a theoretical condition for the eradication strategy to work. Additionally, the consideration of an Allee effect and the possibility of a Turing instability are also studied in this work. Our results show that: (1) with the inclusion of an Allee effect, the number of the invasive females is not required to be very low when the introduction of the sex-reversed trojan females is stopped, and the remaining Trojan Y-Chromosome population is sufficient to induce extinction of the invasive females; (2) incorporating diffusive spatial spread does not produce a Turing instability, which would have suggested that the TYC eradication strategy might be only partially effective, leaving a patchy distribution of the invasive species. © 2013 Springer-Verlag Berlin Heidelberg.

  10. DNA damage response during mitosis induces whole chromosome mis-segregation

    Science.gov (United States)

    Bakhoum, Samuel F.; Kabeche, Lilian; Murnane, John P.; Zaki, Bassem I.; Compton, Duane A.

    2014-01-01

    Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here we show that activation of the DNA damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and Plk1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or Chk2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, DDR during mitosis inappropriately stabilizes k-MTs creating a link between s-CIN and w-CIN. PMID:25107667

  11. The bar instability revisited

    CERN Document Server

    Chiodi, Filippo; Claudin, Philippe

    2012-01-01

    The river bar instability is revisited, using a hydrodynamical model based on Reynolds averaged Navier-Stokes equations. The results are contrasted with the standard analysis based on shallow water Saint-Venant equations. We first show that the stability of both transverse modes (ripples) and of small wavelength inclined modes (bars) predicted by the Saint-Venant approach are artefacts of this hydrodynamical approximation. When using a more reliable hydrodynamical model, the dispersion relation does not present any maximum of the growth rate when the sediment transport is assumed to be locally saturated. The analysis therefore reveals the fundamental importance of the relaxation of sediment transport towards equilibrium as it it is responsible for the stabilisation of small wavelength modes. This dynamical mechanism is characterised by the saturation number, defined as the ratio of the saturation length to the water depth Lsat/H. This dimensionless number controls the transition from ripples (transverse patte...

  12. Plateau Rayleigh instability simulation.

    Science.gov (United States)

    Mead-Hunter, Ryan; King, Andrew J C; Mullins, Benjamin J

    2012-05-01

    The well-known phenomena of Plateau-Rayleigh instability has been simulated using computational fluid dynamics (CFD). The breakup of a liquid film into an array of droplets on a cylindrical element was simulated using a volume-of-fluid (VOF) solver and compared to experimental observations and existing theory. It is demonstrated that the VOF method can correctly predict the breakup of thins films into an array of either axisymmetric droplets or clam-shell droplets, depending on the surface energy. The existence of unrealistically large films is precluded. Droplet spacing was found to show reasonable agreement with theory. Droplet motion and displacement under fluid flow was also examined and compared to that in previous studies. It was found that the presence of air flow around the droplet does not influence the stable film thickness; however, it reduces the time required for droplet formation. Novel relationships for droplet displacement were derived from the results. PMID:22512475

  13. Treatment of the subject of tearing instability

    International Nuclear Information System (INIS)

    A simple approach is taken to the mechanics of potential instability associated with the steady tearing portion of J-Integral R-curves. The analysis is developed from simple examples of structural component (or test specimen) configurations with cracks, examining their instability possibilities individually, in order to draw more general conclusions about elastic-plastic cracking instability as contrasted to linear-elastic behavior. Finally, an attempt is made to model a more local cleavage-like instability for material in the fracture process zone just ahead of a crack tip. Results are then presented of a testing program which clearly demonstrates the appropriateness of the tearing instability analysis and which illustrates its broad potential for future application, as well as presenting guidelines for its further development. The material selected for analysis was Ni-Cr-Mo-V rotor steel

  14. Rayleigh-Taylor instability in elastic solids.

    Science.gov (United States)

    Piriz, A R; Cela, J J López; Cortázar, O D; Tahir, N A; Hoffmann, D H H

    2005-11-01

    We present an analytical model for the Rayleigh-Taylor instability that allows for an approximate but still very accurate and appealing description of the instability physics in the linear regime. The model is based on the second law of Newton and it has been developed with the aim of dealing with the instability of accelerated elastic solids. It yields the asymptotic instability growth rate but also describes the initial transient phase determined by the initial conditions. We have applied the model to solid/solid and solid/fluid interfaces with arbitrary Atwood numbers. The results are in excellent agreement with previous models that yield exact solutions but which are of more limited validity. Our model allows for including more complex physics. In particular, the present approach is expected to lead to a more general theory of the instability that would allow for describing the transition to the plastic regime. PMID:16383751

  15. Cultural diversity, economic development and societal instability.

    Directory of Open Access Journals (Sweden)

    Daniel Nettle

    Full Text Available BACKGROUND: Social scientists have suggested that cultural diversity in a nation leads to societal instability. However, societal instability may be affected not only by within-nation or alpha diversity, but also diversity between a nation and its neighbours or beta diversity. It is also necessary to distinguish different domains of diversity, namely linguistic, ethnic and religious, and to distinguish between the direct effects of diversity on societal instability, and effects that are mediated by economic conditions. METHODOLOGY/PRINCIPAL FINDINGS: We assembled a large cross-national dataset with information on alpha and beta cultural diversity, economic conditions, and indices of societal instability. Structural equation modeling was used to evaluate the direct and indirect effects of cultural diversity on economics and societal stability. Results show that different types and domains of diversity have interacting effects. As previously documented, linguistic alpha diversity has a negative effect on economic performance, and we show that it is largely through this economic mechanism that it affects societal instability. For beta diversity, the higher the linguistic diversity among nations in a region, the less stable the nation. But, religious beta diversity has the opposite effect, reducing instability, particularly in the presence of high linguistic diversity. CONCLUSIONS: Within-nation linguistic diversity is associated with reduced economic performance, which, in turn, increases societal instability. Nations which differ linguistically from their neighbors are also less stable. However, religious diversity between neighboring nations has the opposite effect, decreasing societal instability.

  16. Cultural diversity, economic development and societal instability

    Science.gov (United States)

    Nettle, D.; Grace, J.B.; Choisy, M.; Cornell, H.V.; Guegan, J.-F.; Hochberg, M.E.

    2007-01-01

    Background. Social scientists have suggested that cultural diversity in a nation leads to societal instability. However, societal instability may be affected not only by within-nation on ?? diversity, but also diversity between a nation and its neighbours or ?? diversity. It is also necessary to distinguish different domains of diversity, namely linguistic, ethnic and religious, and to distinguish between the direct effects of diversity on societal instability, and effects that are mediated by economic conditions. Methodology/Principal Findings. We assembled a large cross-national dataset with information on ?? and ?? cultural diversity, economic conditions, and indices of societal instability. Structural equation modeling was used to evaluate the direct and indirect effects of cultural diversity on economics and societal stability. Results show that different type and domains of diversity have interacting effects. As previously documented, linguistic ?? diversity has a negative effect on economic performance, and we show that it is largely through this economic mechanism that it affects societal instability. For ?? diversity, the higher the linguistic diversity among nations in a region, the less stable the nation. But, religious ?? diversity has the opposite effect, reducing instability, particularly in the presence of high linguistic diversity. Conclusions. Within-nation linguistic diversity is associated with reduced economic performance, which, in turn, increases societal instability. Nations which differ linguistically from their neighbors are also less stable. However, religious diversity between, neighboring nations has the opposite effect, decreasing societal instability.

  17. Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells12

    OpenAIRE

    Samassekou, Oumar; Li, Huiyu; Hébert, Josée; Ntwari, Aimé; Wang, Haixia; Cliché, Catherine Grenier; Bouchard, Eric; Huang, Shiang; Yan, Ju

    2011-01-01

    Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found th...

  18. Aeroelastic instability of a flexible plate in a uniform flow

    CERN Document Server

    Eloy, Christophe; Souilliez, Claire; Schouveiler, Lionel

    2008-01-01

    The flutter instability of a flexible plate immersed in an axial flow is experimentally investigated. This instability is similar to flag flutter and results from the competition between destabilizing pressure forces and stabilizing bending stiffness. The instability threshold is measured as a function of the experimental parameters (plate size and aspect ratio) and compared to different theoretical predictions.

  19. A new chromosome was born: comparative chromosome painting in Boechera.

    Science.gov (United States)

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  20. Role of GLTSCR2 in the regulation of telomerase activity and chromosome stability.

    Science.gov (United States)

    Kim, Jee-Youn; An, Yong-Min; Park, Jae-Hoon

    2016-08-01

    Telomerase is essential for regulating telomeres, and its activation is a critical step in cellular immortalization and tumorigenesis. The transcriptional activation of human telomerase reverse transcriptase (hTERT) is critical for telomerase expression. Although several transcriptional activators have been identified, factors responsible for enhancing the hTERT promoter remain to be fully elucidated. In the present study, the role of glioma tumor-suppressor candidate region gene 2 (GLTSCR2) in telomerase regulation was analyzed. A doxycyclin-inducible green fluorescent protein (GFP)-tagged GLTSCR2-expressing adenovirus (Ad‑GLT/GFP) was used for the transduction of SK‑Hep‑1 and T98G cancer cells, and normal human umbilical vein endothelial cells. Changes in telomerase activity using telomere repeat amplification protocol assay were assessed, and the gene expression levels of hTERT were then examined. To investigate chromosome instability and senescence, Giemsa and β-galactosidase staining was performed. The results revealed that overexpression of GLTSCR2 significantly increased telomerase activity in the cancer and normal cell lines. This increase was consistent with increases in the protein and mRNA expression levels of hTERT. In luciferase assays, the hTERT promoter was activated by GLTSCR2. Knockdown of GLTSCR2 led to the downregulation of telomerase activity, abnormal nuclear morphology as a marker of chromosome instability, significant suppression of growth rate, alterations in cellular morphology and, eventually, cellular senescence. Taken together, the results of the present study suggested that GLTSCR2 is crucially involved in the positive regulation of telomerase and chromosome stability. PMID:27357325

  1. Corona-induced electrohydrodynamic instabilities in low conducting liquids

    Energy Technology Data Exchange (ETDEWEB)

    Vega, F.; Perez, A.T. [Depto. Electronica y Electromagnetismo, Facultad de Fisica, Universidad de Sevilla, Avda. Reina Mercedes, s/n. 41012, Sevilla (Spain)

    2003-06-01

    The rose-window electrohydrodynamic (EHD) instability has been observed when a perpendicular field with an additional unipolar ion injection is applied onto a low conducting liquid surface. This instability has a characteristic pattern with cells five to 10 times greater than those observed in volume instabilities caused by unipolar injection. We have used corona discharge from a metallic point to perform some measurements of the rose-window instability in low conducting liquids. The results are compared to the linear theoretical criterion for an ohmic liquid. They confirmed that the minimum voltage for this instability is much lower than that for the interfacial instability in high conducting liquids. This was predicted theoretically in the dependence of the critical voltage as a function of the non-dimensional conductivity. It is shown that in a non-ohmic liquid the rose window appears as a secondary instability after the volume instability. (orig.)

  2. Faraday instability in deformable domains

    International Nuclear Information System (INIS)

    Hydrodynamical instabilities are usually studied either in bounded regions or free to grow in space. In this article we review the experimental results of an intermediate situation, in which an instability develops in deformable domains. The Faraday instability, which consists in the formation of surface waves on a liquid experiencing a vertical forcing, is triggered in floating liquid lenses playing the role of deformable domains. Faraday waves deform the lenses from the initial circular shape and the mutual adaptation of instability patterns with the lens boundary is observed. Two archetypes of behaviour have been found. In the first archetype a stable elongated shape is reached, the wave vector being parallel to the direction of elongation. In the second archetype the waves exceed the response of the lens border and no equilibrium shape is reached. The lens stretches and eventually breaks into fragments that have a complex dynamics. The difference between the two archetypes is explained by the competition between the radiation pressure the waves exert on the lens border and its response due to surface tension.

  3. Edge instabilities of topological superconductors

    Science.gov (United States)

    Hofmann, Johannes S.; Assaad, Fakher F.; Schnyder, Andreas P.

    2016-05-01

    Nodal topological superconductors display zero-energy Majorana flat bands at generic edges. The flatness of these edge bands, which is protected by time-reversal and translation symmetry, gives rise to an extensive ground-state degeneracy. Therefore, even arbitrarily weak interactions lead to an instability of the flat-band edge states towards time-reversal and translation-symmetry-broken phases, which lift the ground-state degeneracy. We examine the instabilities of the flat-band edge states of dx y-wave superconductors by performing a mean-field analysis in the Majorana basis of the edge states. The leading instabilities are Majorana mass terms, which correspond to coherent superpositions of particle-particle and particle-hole channels in the fermionic language. We find that attractive interactions induce three different mass terms. One is a coherent superposition of imaginary s -wave pairing and current order, and another combines a charge-density-wave and finite-momentum singlet pairing. Repulsive interactions, on the other hand, lead to ferromagnetism together with spin-triplet pairing at the edge. Our quantum Monte Carlo simulations confirm these findings and demonstrate that these instabilities occur even in the presence of strong quantum fluctuations. We discuss the implications of our results for experiments on cuprate high-temperature superconductors.

  4. Weakly nonparallel and curvature effects on stationary crossflow instability: Comparison of results from multiple-scales analysis and parabolized stability equations

    Science.gov (United States)

    Singer, Bart A.; Choudhari, Meelan; Li, Fei

    1995-01-01

    A multiple-scales approach is used to approximate the effects of nonparallelism and streamwise surface curvature on the growth of stationary crossflow vortices in incompressible, three-dimesional boundary layers. The results agree with results predicted by solving the parabolized stability equations in regions where the nonparallelism is sufficiently weak. As the nonparallelism increases, the agreement between the two approaches worsens. An attempt has been made to quantify the nonparallelism on flow stability in terms of a nondimensional number that describes the rate of change of the mean flow relative to the disturbance wavelength. We find that the above nondimensional number provides useful information about the adequacy of the multiple-scales approximation for different disturbances for a given flow geometry, but the number does not collapse data for different flow geometries onto a single curve.

  5. RESULTS FROM LATARJET SURGERY FOR TREATING TRAUMATIC ANTERIOR SHOULDER INSTABILITY ASSOCIATED WITH BONE EROSION IN THE GLENOID CAVITY, AFTER MINIMUM FOLLOW-UP OF ONE YEAR

    OpenAIRE

    Ikemoto, Roberto Yukio; Murachovisky, Joel; Nascimento, Luis Gustavo Prata; Bueno, Rogério Serpone; Almeida, Luiz Henrique Oliveira; Strose, Eric; Helmer, Fábio Fernando

    2015-01-01

    Objective: Evaluate the results from the Latarjet procedure in patients with anterior recurrent dislocation of the shoulder who present bone loss of the glenoid cavity greater than 25%. Methods: Twenty six male patients underwent the Latarjet procedure, The bone loss was evaluated by means of radiography using the Bernageau view and by means of CAT scan. The patients were evaluated with regard to range of motion, using the Rowe and UCLA scales, before and after the operation, and by radiograp...

  6. Chimpanzee chromosome 13 is homologous to human chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Similarities between human and chimpanzee chromosomes are shown by chromosome banding techniques and somatic cell hybridization techniques. Cell hybrids were obtained from the chimpanzee lymphocyte LE-7, and the Chinese hamster mutant cell, Gal-2. Experiments showed that the ACPL, MDHs, and Gal-Act genes could be assigned to chimpanzee chromosome 13, and since these genes have been assigned to human chromosme 2p, it is suggested that chimpanzee chromosome 13 is homologous to human chromosome 2p. (HLW)

  7. Chromosome condensation and segmentation

    International Nuclear Information System (INIS)

    Some aspects of chromosome condensation in mammalians -humans especially- were studied by means of cytogenetic techniques of chromosome banding. Two further approaches were adopted: a study of normal condensation as early as prophase, and an analysis of chromosome segmentation induced by physical (temperature and γ-rays) or chemical agents (base analogues, antibiotics, ...) in order to show out the factors liable to affect condensation. Here 'segmentation' means an abnormal chromosome condensation appearing systematically and being reproducible. The study of normal condensation was made possible by the development of a technique based on cell synchronization by thymidine and giving prophasic and prometaphasic cells. Besides, the possibility of inducing R-banding segmentations on these cells by BrdU (5-bromodeoxyuridine) allowed a much finer analysis of karyotypes. Another technique was developed using 5-ACR (5-azacytidine), it allowed to induce a segmentation similar to the one obtained using BrdU and identify heterochromatic areas rich in G-C bases pairs

  8. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  9. Chromosomal geometry in the interface from the frequency of the radiation induced chromosome aberrations

    International Nuclear Information System (INIS)

    Ionizing radiation induces DNA double-strand breaks (DSBs) and their interaction and illegitimate recombination produces chromosomal aberrations. Stable chromosomal aberrations comprise inter-chromosomal events (translocations) and intra-chromosomal events (inversions). When DSBs induction and interaction is done at random, and the proximity effects are neglected, the expected relation between translocations and inversions is F=86, based on chromosome arm length. The number of translocations and inversions is analyzed by using G-banding in 16 lymphocytes cultures from blood samples acutely irradiated with γ-rays (dose range: 0,5 Gy - 3 Gy). The result obtained was: F=13,5, significantly smaller than F=86. Literature data show similar small F values, but strongly spread. The excess of inversions could be explained by a 'proximity effect', it means that more proximate DSBs have more interaction probability. Therefore, it is possible to postulate a special chromosome arrangement during irradiation and the subsequent interval. We propose a model where individual chromosomes show spherical confinement with some degree of overlapping and DSBs induction proportional to cross section. A DSBs interaction probability function with cut-off length= 1μ is assumed. According to our results, the confinement volume is ≅ 6.4% of the nuclear volume. Nevertheless, we presume that large spread in F data could be due to temporal variation in overlapping and spatial chromosomal confinement. (authors). 14 refs

  10. Chromosome numbers in Bromeliaceae

    OpenAIRE

    2000-01-01

    The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. u...

  11. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  12. Role of the Number of Microtubules in Chromosome Segregation during Cell Division

    CERN Document Server

    Bertalan, Zsolt; La Porta, Caterina A M; Zapperi, Stefano

    2015-01-01

    Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compa...

  13. Chromatin structure and ionizing-radiation-induced chromosome aberrations

    International Nuclear Information System (INIS)

    The possible influence of chromatic structure or activity on chromosomal radiosensitivity was studied. A cell line was isolated which contained some 105 copies of an amplified plasmid in a single large mosquito artificial chromosome (MAC). This chromosome was hypersensitive to DNase I. Its radiosensitivity was some three fold greater than normal mosquito chromosomes in the same cell. In cultured human cells irradiated during G0, the initial breakage frequency in chromosome 4, 19 and the euchromatic and heterochromatic portions of the Y chromosome were measured over a wide range of doses by inducing Premature Chromosome Condensation (PCC) immediately after irradiation with Cs-137 gamma rays. No evidence was seen that Y heterochromatin or large fragments of it remained unbroken. The only significant deviation from the expected initial breakage frequency per Gy per unit length of chromosome was that observed for the euchromatic portion of the Y chromosome, with breakage nearly twice that expected. The development of aberrations involving X and Y chromosomes at the first mitosis after irradation was also studied. Normal female cells sustained about twice the frequency of aberrations involving X chromosomes for a dose of 7.3 Gy than the corresponding male cells. Fibroblasts from individuals with supernumerary X chromosomes did not show any further increase in X aberrations for this dos. The frequency of aberrations involving the heterochromatic portion of the long arm of the Y chromosome was about what would be expected for a similar length of autosome, but the euchromatic portion of the Y was about 3 times more radiosensitive per unit length. 5-Azacytidine treatment of cultured human female fibroblasts or fibroblasts from a 49,XXXXY individual, reduced the methylation of cytosine residues in DNA, and resulted in an increased chromosomal radiosensitivity in general, but it did not increase the frequency of aberrations involving the X chromosomes

  14. Is delayed genomic instability specifically induced by high-LET particles?

    Science.gov (United States)

    Testard, Isabelle; Sabatier, Laure

    1998-12-01

    Ionizing radiation can induce a large variety of damages in the DNA. The processing or repair of this damage occurs in the first minutes up to several hours after irradiation. Afterwhile the remaining lesions are fixed in an irreparable state. However, in recent years, data have accumulated to suggest that genomic instability can manifest in the progeny of irradiated cells leading to accumulation of damage through cell generations. Different biological endpoints were described: delayed cell death, delayed mutations, de novo chromosomal instability. The question regarding the ability of sparsely ionizing X-or γ-rays to induce such phenomenon is still unclear for normal cells. In most of the reports, high linear energy transfer (LET) particles are able to induce genomic instability but not low-LET particles. The mechanisms underlying this phenomenon are still unknown. In human fibroblasts irradiated by heavy ions in a large range of LETs, we showed that the chromosomal instability is characterized by telomeric associations (TAS) involving specific chromosomes. The same instability is observed during the senescence process and during the first passages after viral transfection. The specific chromosomal instability that we observed after irradiation would not be a direct consequence of irradiation but would be a natural phenomenon occurring after many cell divisions. The effect of the irradiation would lie on the bypass of the senescence process that would permit cells with end to end fusions to survive and be transmitted through cell generations, accumulating chromosome rearrangements and chromosome imbalances. Research on molecular mechanisms of chromosomal instability is focused on the role of telomeres in end to end fusions. Such observations could contribute to understand why chromosomal instability is not a dose dependant phenomenon. Why high-LET particles would be so potent in inducing delayed instability? The answer might lie in the study of primary effects of

  15. Polygonal instabilities on interfacial vorticities

    CERN Document Server

    Labousse, Matthieu

    2015-01-01

    We report the results of a theoretical investigation of the stability of a toroidal vortex bound by an interface. Two distinct instability mechanisms are identified that rely on, respectively, surface tension and fluid inertia, either of which may prompt the transformation from a circular to a polygonal torus. Our results are discussed in the context of three experiments, a toroidal vortex ring, the hydraulic jump, and the hydraulic bump.

  16. Polygonal instabilities on interfacial vorticities.

    Science.gov (United States)

    Labousse, M; Bush, J W M

    2015-10-01

    We report the results of a theoretical investigation of the stability of a toroidal vortex bound by an interface. Two distinct instability mechanisms are identified that rely on, respectively, surface tension and fluid inertia, either of which may prompt the transformation from a circular to a polygonal torus. Our results are discussed in the context of three experiments, a toroidal vortex ring, the hydraulic jump, and the hydraulic bump. PMID:26537726

  17. Trisomy 21 and facial developmental instability.

    Science.gov (United States)

    Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

    2013-05-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. PMID:23505010

  18. Transmission Behavior of B Chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae).

    Science.gov (United States)

    Penitente, Manolo; Daniel, Sandro N; Senhorini, José A; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    The population of Prochilodus lineatus found in the Mogi-Guaçu River is karyotypically polymorphic, carrying acrocentric, metacentric, and submetacentric B chromosomes. The analysis of each B chromosome frequency in this species revealed a variation in the distribution pattern, with the metacentric type having the highest frequency (73.30%), followed by submetacentric (25.22%) and acrocentric B chromosomes (1.48%). The transmission pattern of the supernumerary chromosomes was identified by controlled crosses, and it was shown that the acro- and submetacentric B chromosomes have a transmission pattern below the Mendelian rate (kB = 0.333 and kB = 0.385, respectively), but the metacentric variant has a cumulative transmission pattern (kB = 0.587). These results indicate that the acro- and submetacentric B chromosomes are undergoing an extinction process, while the metacentric B chromosomes appear to be accumulating in frequency with each generation. PMID:26795613

  19. Deficit of mitonuclear genes on the human X chromosome predates sex chromosome formation.

    Science.gov (United States)

    Dean, Rebecca; Zimmer, Fabian; Mank, Judith E

    2015-02-01

    Two taxa studied to date, the therian mammals and Caenorhabditis elegans, display underrepresentations of mitonuclear genes (mt-N genes, nuclear genes whose products are imported to and act within the mitochondria) on their X chromosomes. This pattern has been interpreted as the result of sexual conflict driving mt-N genes off of the X chromosome. However, studies in several other species have failed to detect a convergent biased distribution of sex-linked mt-N genes, leading to questions over the generality of the role of sexual conflict in shaping the distribution of mt-N genes. Here we tested whether mt-N genes moved off of the therian X chromosome following sex chromosome formation, consistent with the role of sexual conflict, or whether the paucity of mt-N genes on the therian X is a chance result of an underrepresentation on the ancestral regions that formed the X chromosome. We used a synteny-based approach to identify the ancestral regions in the platypus and chicken genomes that later formed the therian X chromosome. We then quantified the movement of mt-N genes on and off of the X chromosome and the distribution of mt-N genes on the human X and ancestral X regions. We failed to find an excess of mt-N gene movement off of the X. The bias of mt-N genes on ancestral therian X chromosomes was also not significantly different from the biases on the human X. Together our results suggest that, rather than conflict driving mt-N genes off of the mammalian X, random biases on chromosomes that formed the X chromosome could explain the paucity of mt-N genes in the therian lineage. PMID:25637223

  20. Experimental study on low pressure flow instability

    International Nuclear Information System (INIS)

    The experiment was performed on the test loop (HRTL-5), which simulates the geometry and system design of the 5 MW reactor. The flow behavior for a wide range of inlet subcooling, in which the flow undergoes from single phase to two phase, is described in a natural circulation system at low pressure (p = 0.1, 0.24 MPa). Several kinds of flow instability, e.g. subcooled boiling instability, subcooled boiling induced flashing instability, pure flashing instability as well as flashing coupled density wave instability and high frequency flow oscillation, are investigated. The mechanism of flashing and flashing concerned flow instability, which has never been studied well in this field, is especially interpreted. The experimental results show that, firstly, for a low pressure natural circulation system the two phase flow is unstable in most of inlet subcooling conditions, the two phase stable flow can only be reached at very low inlet subcooling; secondly, at high inlet subcooling the flow instability is dominated by subcooled boiling in the heated section, and at middle inlet subcooling is dominated by void flashing in the adiabatic long riser; thirdly, in two phase stable flow region the condition for boiling out of the core, namely, single phase flow in the heated section, two phase flow in the riser due to vapor flashing, can be realized. The experimental results are very important for the design and accident analysis of the vessel and swimming pool type natural circulation nuclear heating reactor. (7 refs., 10 figs., 1 tab.)

  1. Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21

    DEFF Research Database (Denmark)

    McGinniss, M J; Kazazian, H H; Stetten, G;

    1992-01-01

    ), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another......We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage......). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy....

  2. Dielectrophoretic manipulation of human chromosomes in microfluidic channels: extracting chromosome dielectric properties

    DEFF Research Database (Denmark)

    Clausen, Casper Hyttel; Dimaki, Maria; Buckley, Sonia; Svendsen, Winnie Edith

    2011-01-01

    An investigation of the dielectric properties of polyamine buffer prepared human chromosomes is presented in this paper. Chromosomes prepared in this buffer are only a few micrometers in size and shaped roughly like spherical discs. Dielectrophoresis was therefore chosen as the method of manipula......An investigation of the dielectric properties of polyamine buffer prepared human chromosomes is presented in this paper. Chromosomes prepared in this buffer are only a few micrometers in size and shaped roughly like spherical discs. Dielectrophoresis was therefore chosen as the method of...... manipulation combined with a custom designed microfluidic system containing the required electrodes for dielectrophoresis experiments. Our results show that although this system is presently not able to distinguish between the different chromosomes, it can provide average data for the dielectric properties of...

  3. Neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes

    DEFF Research Database (Denmark)

    Zhou, Qi; Wang, Jun; Huang, Ling; Nie, Wenhui; Wang, Jinhuan; Liu, Yan; Zhao, Xiangyi; Yang, Fengtang; Wang, Wen

    2008-01-01

    BACKGROUND: The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation. RESULTS: We studied the intriguing case of black...... muntjac, in which a recent X-autosome fusion and a subsequent large autosomal inversion within just the past 0.5 million years have led to inheritance patterns identical to the traditional X-Y (neo-sex chromosomes). We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene...... SNX22 abolished a microRNA target site. Finally, expression analyses revealed complex patterns of expression divergence between neo-Y and neo-X alleles. CONCLUSION: The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals...

  4. Analysis of a valuable chromosome rearrangement induced by ionizing radiations in a cultivated chili pepper line (Capsicum baccatum var. Pendulum - solanaceae)

    International Nuclear Information System (INIS)

    Capsicum (chili peppers) is an important genus including five crop species consumed by man as spice and food. Most contributions about induced mutagenesis in Capsicum refer to gene mutations while induced changes at chromosome level are scarce. We started a program to achieve chromosome rearrangements by ionizing radiations in C. baccatum variety pendulum cultivar 'cayenne', which has a karyotype with 2n=2x=24, 11 metacentrics + 1 subtelocentric pairs, 4 pairs (1, 3, 10, 12) carrying nucleolar organizing regions (NORs) and associated satellites in short arm. Seeds were treated with different acute doses of X-rays developing M1-4 generations. A rearranged chromosome carrying NORs in both arms was found in M2 seedlings from the only surviving M1 plant after a 300 Gy treatment. The structural change was analyzed by: 1) Feulgen's staining to observe chromosome number, size and shape; 2) silver impregnation to detect active NORs; 3) fluorescent chromosome banding to reveal type and position of constitutive heterochromatic regions [triple staining with chromomycin/distamycin/4-6-diamidino-2-phenylindole (CMA/DA/DAPI)]; 4) fluorescent in situ hybridization with 18S- 25S rDNA repeated sequence as probe. A reciprocal translocation between two NOR-bearing chromosomes in the M1 plant has occurred, which gave viable progeny carrying the chromosomal interchange without any deviating phenotype after four generations, nor in heterozygous neither in homozygous condition. The lack of chromosome instability suggests a small reciprocal interchange between a member of pair 1 and of 3, both carrying active NORs in shorts arms. The results of this rearrangement were two chromosomes with little change in size, one of them easily recognized by the presence of NORs and associated CMA+/DAPI- heterochromatin in both arms. As the translocation here reported produced a conspicuous rearranged marker chromosome, the obtained plant line is considered very valuable for studies on chromosome

  5. Studies of elastic-plastic instabilities

    DEFF Research Database (Denmark)

    Tvergaard, Viggo

    1999-01-01

    Analyses of plastic instabilities are reviewed, with focus on results in structural mechanics as well as continuum mechanics. First the basic theories for bifurcation and post-bifurcation behavior are briefly presented. Then, localization of plastic flow is discussed, including shear band formation...... in solids, localized necking in biaxially stretched metal sheets, and the analogous phenomenon of buckling localization in structures. Also some recent results for cavitation instabilities in elastic-plastic solids are reviewed....

  6. Studies of elastic-plastic instabilities

    DEFF Research Database (Denmark)

    Tvergaard, Viggo

    1999-01-01

    Analyses of plastic instabilities are reviewed, with focus on results in structural mechanics as well as continuum mechanics. First the basic theories for bifurcation and post-bifurcation behavior are briefly presented. Then, localization of plastic flow is discussed, including shear band formati...... in solids, localized necking in biaxially stretched metal sheets, and the analogous phenomenon of buckling localization in structures. Also some recent results for cavitation instabilities in elastic-plastic solids are reviewed....

  7. Genomic instability and radiation risk in molecular pathways to colon cancer.

    Science.gov (United States)

    Kaiser, Jan Christian; Meckbach, Reinhard; Jacob, Peter

    2014-01-01

    Colon cancer is caused by multiple genomic alterations which lead to genomic instability (GI). GI appears in molecular pathways of microsatellite instability (MSI) and chromosomal instability (CIN) with clinically observed case shares of about 15-20% and 80-85%. Radiation enhances the colon cancer risk by inducing GI, but little is known about different outcomes for MSI and CIN. Computer-based modelling can facilitate the understanding of the phenomena named above. Comprehensive biological models, which combine the two main molecular pathways to colon cancer, are fitted to incidence data of Japanese a-bomb survivors. The preferred model is selected according to statistical criteria and biological plausibility. Imprints of cell-based processes in the succession from adenoma to carcinoma are identified by the model from age dependences and secular trends of the incidence data. Model parameters show remarkable compliance with mutation rates and growth rates for adenoma, which has been reported over the last fifteen years. Model results suggest that CIN begins during fission of intestinal crypts. Chromosomal aberrations are generated at a markedly elevated rate which favors the accelerated growth of premalignant adenoma. Possibly driven by a trend of Westernization in the Japanese diet, incidence rates for the CIN pathway increased notably in subsequent birth cohorts, whereas rates pertaining to MSI remained constant. An imbalance between number of CIN and MSI cases began to emerge in the 1980s, whereas in previous decades the number of cases was almost equal. The CIN pathway exhibits a strong radio-sensitivity, probably more intensive in men. Among young birth cohorts of both sexes the excess absolute radiation risk related to CIN is larger by an order of magnitude compared to the MSI-related risk. Observance of pathway-specific risks improves the determination of the probability of causation for radiation-induced colon cancer in individual patients, if their exposure

  8. Genomic instability and radiation risk in molecular pathways to colon cancer.

    Directory of Open Access Journals (Sweden)

    Jan Christian Kaiser

    Full Text Available Colon cancer is caused by multiple genomic alterations which lead to genomic instability (GI. GI appears in molecular pathways of microsatellite instability (MSI and chromosomal instability (CIN with clinically observed case shares of about 15-20% and 80-85%. Radiation enhances the colon cancer risk by inducing GI, but little is known about different outcomes for MSI and CIN. Computer-based modelling can facilitate the understanding of the phenomena named above. Comprehensive biological models, which combine the two main molecular pathways to colon cancer, are fitted to incidence data of Japanese a-bomb survivors. The preferred model is selected according to statistical criteria and biological plausibility. Imprints of cell-based processes in the succession from adenoma to carcinoma are identified by the model from age dependences and secular trends of the incidence data. Model parameters show remarkable compliance with mutation rates and growth rates for adenoma, which has been reported over the last fifteen years. Model results suggest that CIN begins during fission of intestinal crypts. Chromosomal aberrations are generated at a markedly elevated rate which favors the accelerated growth of premalignant adenoma. Possibly driven by a trend of Westernization in the Japanese diet, incidence rates for the CIN pathway increased notably in subsequent birth cohorts, whereas rates pertaining to MSI remained constant. An imbalance between number of CIN and MSI cases began to emerge in the 1980s, whereas in previous decades the number of cases was almost equal. The CIN pathway exhibits a strong radio-sensitivity, probably more intensive in men. Among young birth cohorts of both sexes the excess absolute radiation risk related to CIN is larger by an order of magnitude compared to the MSI-related risk. Observance of pathway-specific risks improves the determination of the probability of causation for radiation-induced colon cancer in individual patients

  9. The Collisionless Magnetothermal Instability

    CERN Document Server

    Islam, Tanim

    2013-01-01

    It is likely that nearly all central galactic massive and supermassive black holes are nonradiative: their accretion luminosities are orders of magnitude below what can be explained by efficient black hole accretion within their ambient environments. These objects, of which Sagittarius A* is the best-known example, are also dilute (mildly collisional to highly collisionless) and optically thin. In order for accretion to occur, magnetohydrodynamic instabilities must develop that not only transport angular momentum, but also gravitational energy generated through matter infall, outwards. A class of new magnetohydrodynamical fluid instabilities -- the magnetoviscous-thermal instability (MVTI) (Islam12) -- was found to transport angular momentum and energy along magnetic field lines through large (fluid) viscosities and thermal conductivities. This paper describes the collisionless and mildly collisional analogue to the MVTI, the collisional magnetothermal instability (CMTI), that similarly transports energy and ...

  10. The Curse of Instability

    OpenAIRE

    Kuehn, Christian

    2015-01-01

    High-dimensional computational challenges are frequently explained via the curse of dimensionality, i.e., increasing the number of dimensions leads to exponentially growing computational complexity. In this commentary, we argue that thinking on a different level helps to understand, why we face the curse of dimensionality. We introduce as a guiding principle the curse of instability, which triggers the classical curse of dimensionality. Furthermore, we claim that the curse of instability is a...

  11. Streaming gravity mode instability

    International Nuclear Information System (INIS)

    In this paper, we study the stability of a current sheet with a sheared flow in a gravitational field which is perpendicular to the magnetic field and plasma flow. This mixing mode caused by a combined role of the sheared flow and gravity is named the streaming gravity mode instability. The conditions of this mode instability are discussed for an ideal four-layer model in the incompressible limit. (author). 5 refs

  12. Chromosomal abnormalities in patients with sperm disorders

    Directory of Open Access Journals (Sweden)

    L. Y. Pylyp

    2013-02-01

    of sex chromosome aneuploidy and 2 cases of terminal deletion of Y chromosome. Klinefelter syndrome was detected in 67% of patients with azoospermia. A significant increase in the frequency of numerical chromosomal abnormalities was observed in a group of patients with azoospermia (P < 0.001. No differences were detected in the frequency of structural abnormalities in subgroups of patients. An increase in the frequency of chromosomal abnormalities with the decrease of sperm count was observed. Chromosomal abnormalities were detected with frequency 1.1% in a group of patients with normospermia, 1.9% in a group of patients with asthenozoospermia, 4.3% in patients with asthenoteratozoospermia, 6.5% in patients with oligoasthenozoospermia, 11.6% in patients with oligoasthenoteratozoospermia and 35% in a group of patients with azoospermia. Significant increase of the prevalence of chromosomal abnormalities was detected in subgroups of patients with azoospermia (P < 0.001 and oligozoospermia (P = 0.001 as compared to patients with normozoospermia. These results are considered to be criteria for selection of patients in need of cytogenetic studies before in vitro fertilization cycles because of the highest risk of chromosomal abnormalities detection.

  13. Mouse acute myeloid leukemia and abnormality in chromosome II

    International Nuclear Information System (INIS)

    This review described abnormality in chromosome II that is characteristic in the radiation-induced leukemia in the title (AML) in mice. The disease is reportedly increased in A-bomb survivors. AML occurs in mice of RFM, CBA and other strains 1-1.5 years after whole body irradiation. The incidence increases dependently on dose, however, it decreases over around the dose of 3 Gy of X- and γ-ray. The incidence (20-25%) is higher in males. Abnormality seen in chromosome II is classified in types I-IV and II-IV types involve terminal deletion, interstitial deletion and translocation. The deleted region common on the chromosome (marker chromosome) is about 1 cM long, which corresponds to human 11p11-12 region frequently deleted in AML patients. The AML marker chromosome is suggested to be yielded by genomic instability induced by radiation. It is also suggested that there are fragile sites in the chromosome II. Future investigations are conceivably to be concentrated for identification of the AML causing gene. (K.H.)

  14. Evaluating the Relationship between Spermatogenic Silencing of the X Chromosome and Evolution of the Y Chromosome in Chimpanzee and Human

    Science.gov (United States)

    Mulugeta Achame, Eskeatnaf; Baarends, Willy M.; Gribnau, Joost; Grootegoed, J. Anton

    2010-01-01

    Chimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY), representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural selection acting on the MSY as a unit. Positive selection might involve the performance of the MSY in spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that sperm competition is thought to provide a strong selective force acting on the Y chromosome in the chimpanzee lineage. In consequence of evolution of the heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation (MSCI) results in a transcriptionally silenced XY body in male meiotic prophase, and subsequently also in postmeiotic repression of the sex chromosomes in haploid spermatids. This has evolved to a situation where MSCI has become a prerequisite for spermatogenesis. Here, by analysis of microarray testicular expression data representing a small number of male chimpanzees and men, we obtained information indicating that meiotic and postmeiotic X chromosome silencing might be more effective in chimpanzee than in human spermatogenesis. From this, we suggest that the remarkable reorganization of the chimpanzee Y chromosome, compared to the human Y chromosome, might have an impact on its meiotic interactions with the X chromosome and thereby on X chromosome silencing in spermatogenesis. Further studies will be required to address comparative functional aspects of MSCI in chimpanzee, human, and other placental mammals. PMID:21179482

  15. Instability of refrigeration system - A review

    International Nuclear Information System (INIS)

    It is essential to ensure the stability for the normal operation of refrigeration systems. This paper reviews the researches on the theory and solutions of the instability of refrigeration systems. The instability of refrigeration systems includes two aspects: the two-phase flow instability in refrigeration system, the instability on refrigeration system control characteristics. As an inherent characteristic of two-phase evaporating flow, several separate explanations for the formation of oscillation of mixture-vapor transition point in the evaporation process by different scholars had been given but there is no general explanation till now. The investigation of instability on refrigeration system control characteristics focused on both static and dynamic researches. The minimum stable signal line theory, as a very important finding for the static instability of the evaporator and thermal expansion valve control loop, presented the different result to other researches. Dynamic researches on simulation and frequency-domain analysis provided various means for forecast and validation with considerable precision while their application range was still confined. With the development of variable capacity compressor and electronic expansion valve, further researches should be carried out to analyze the instability of the variable capacity refrigeration system with considering the influence of parameter coupling and control algorithm.

  16. Demasculinization of the Anopheles gambiae X chromosome

    Directory of Open Access Journals (Sweden)

    Magnusson Kalle

    2012-05-01

    Full Text Available Abstract Background In a number of organisms sex-biased genes are non-randomly distributed between autosomes and the shared sex chromosome X (or Z. Studies on Anopheles gambiae have produced conflicting results regarding the underrepresentation of male-biased genes on the X chromosome and it is unclear to what extent sexual antagonism, dosage compensation or X-inactivation in the male germline, the evolutionary forces that have been suggested to affect the chromosomal distribution of sex-biased genes, are operational in Anopheles. Results We performed a meta-analysis of sex-biased gene expression in Anopheles gambiae which provides evidence for a general underrepresentation of male-biased genes on the X-chromosome that increased in significance with the observed degree of sex-bias. A phylogenomic comparison between Drosophila melanogaster, Aedes aegypti and Culex quinquefasciatus also indicates that the Anopheles X chromosome strongly disfavours the evolutionary conservation of male-biased expression and that novel male-biased genes are more likely to arise on autosomes. Finally, we demonstrate experimentally that transgenes situated on the Anopheles gambiae X chromosome are transcriptionally silenced in the male germline. Conclusion The data presented here support the hypothesis that the observed demasculinization of the Anopheles X chromosome is driven by X-chromosome inactivation in the male germline and by sexual antagonism. The demasculinization appears to be the consequence of a loss of male-biased expression, rather than a failure in the establishment or the extinction of male-biased genes.

  17. Lack of sex chromosome specific meiotic silencing in platypus reveals origin of MSCI in therian mammals

    OpenAIRE

    Daish, Tasman J.; Casey, Aaron E.; Grutzner, Frank

    2015-01-01

    Background In therian mammals heteromorphic sex chromosomes are subject to meiotic sex chromosome inactivation (MSCI) during meiotic prophase I while the autosomes maintain transcriptional activity. The evolution of this sex chromosome silencing is thought to result in retroposition of genes required in spermatogenesis from the sex chromosomes to autosomes. In birds sex chromosome specific silencing appears to be absent and global transcriptional reductions occur through pachytene and sex chr...

  18. Differential genetic interactions between Sgs1, DNA-damage checkpoint components and DNA repair factors in the maintenance of chromosome stability

    Directory of Open Access Journals (Sweden)

    Doerfler Lillian

    2011-10-01

    Full Text Available Abstract Background Genome instability is associated with human cancers and chromosome breakage syndromes, including Bloom's syndrome, caused by inactivation of BLM helicase. Numerous mutations that lead to genome instability are known, yet how they interact genetically is poorly understood. Results We show that spontaneous translocations that arise by nonallelic homologous recombination in DNA-damage-checkpoint-defective yeast lacking the BLM-related Sgs1 helicase (sgs1Δ mec3Δ are inhibited if cells lack Mec1/ATR kinase. Tel1/ATM, in contrast, acts as a suppressor independently of Mec3 and Sgs1. Translocations are also inhibited in cells lacking Dun1 kinase, but not in cells defective in a parallel checkpoint branch defined by Chk1 kinase. While we had previously shown that RAD51 deletion did not inhibit translocation formation, RAD59 deletion led to inhibition comparable to the rad52Δ mutation. A candidate screen of other DNA metabolic factors identified Exo1 as a strong suppressor of chromosomal rearrangements in the sgs1Δ mutant, becoming even more important for chromosomal stability upon MEC3 deletion. We determined that the C-terminal third of Exo1, harboring mismatch repair protein binding sites and phosphorylation sites, is dispensable for Exo1's roles in chromosomal rearrangement suppression, mutation avoidance and resistance to DNA-damaging agents. Conclusions Our findings suggest that translocations between related genes can form by Rad59-dependent, Rad51-independent homologous recombination, which is independently suppressed by Sgs1, Tel1, Mec3 and Exo1 but promoted by Dun1 and the telomerase-inhibitor Mec1. We propose a model for the functional interaction between mitotic recombination and the DNA-damage checkpoint in the suppression of chromosomal rearrangements in sgs1Δ cells.

  19. Early Prevention Method for Power Systems Instability

    DEFF Research Database (Denmark)

    Dmitrova, Evgenia

    a given operational conditions and predicts the resulting stability margins for the new steady state, while avoiding time consuming time domain simulations. The method has been validated on the Western Danish power system model, containing 464 buses. The case study of aperiodic small signal angular......In the scope of this work, a method capable of fast identification of the proper countermeasure, that prevents emerging instability, has been developed. The focus is placed on the prevention of aperiodic small signal angular instability by means of manipulations applied to load nodes (nodes...... instability was created. Utilizing synthetic PMU data, the early prevention method proposed a location and an amount of the countermeasure which will prevent instability; the prediction of the resulting stability margins corresponding to application of the suggested countermeasure was carried out. The...

  20. Double contrast CT diagnosis of shoulder instability

    International Nuclear Information System (INIS)

    Purpose: To study clinical importance of double contrast CT arthrography in the diagnosis of shoulder instability. Materials and methods: Eight patients were diagnosed as having shoulder instability with double contrast CT. The technique involved injection of 4 ml, 76% urografin and 10 ml of room air through an anterior shoulder puncture. The CT images were obtained with the patients supine and prone position. Results: The results of the CT arthrography were confirmed during the surgical operation afterward. The characteristics of abnormal double contrast CT arthrograms. They included anterior labral tear: the rounded anterior glenoid labrum, detached anterior labrum and anterior labral fragment; anterior capsular stripping off the anterior scapular glenoid neck; and enlargement of anterior and posterior capsular stripping off the anterior scapular glenoid neck; and enlargement of anterior and posterior capsular cavity. Conclusion: The current CT arthrography provides important X-ray information for both diagnosis of shoulder instability and anatomical repair of shoulder instability

  1. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  2. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  3. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    OpenAIRE

    Aaraby Yoheswaran Nielsen; Morten Frier Gjerstorff

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the ...

  4. Sequence conservation on the Y chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, L.H.; Yang-Feng, L. [Yale Univ. School of Medicine, New Haven, CT (United States); Lau, C. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    The Y chromosome is present in all mammals and is considered to be essential to sex determination. Despite intense genomic research, only a few genes have been identified and mapped to this chromosome in humans. Several of them, such as SRY and ZFY, have been demonstrated to be conserved and Y-located in other mammals. In order to address the issue of sequence conservation on the Y chromosome, we performed fluorescence in situ hybridization (FISH) with DNA from a human Y cosmid library as a probe to study the Y chromosomes from other mammalian species. Total DNA from 3,000-4,500 cosmid pools were labeled with biotinylated-dUTP and hybridized to metaphase chromosomes. For human and primate preparations, human cot1 DNA was included in the hybridization mixture to suppress the hybridization from repeat sequences. FISH signals were detected on the Y chromosomes of human, gorilla, orangutan and baboon (Old World monkey) and were absent on those of squirrel monkey (New World monkey), Indian munjac, wood lemming, Chinese hamster, rat and mouse. Since sequence analysis suggested that specific genes, e.g. SRY and ZFY, are conserved between these two groups, the lack of detectable hybridization in the latter group implies either that conservation of the human Y sequences is limited to the Y chromosomes of the great apes and Old World monkeys, or that the size of the syntenic segment is too small to be detected under the resolution of FISH, or that homologeous sequences have undergone considerable divergence. Further studies with reduced hybridization stringency are currently being conducted. Our results provide some clues as to Y-sequence conservation across species and demonstrate the limitations of FISH across species with total DNA sequences from a particular chromosome.

  5. Chromosomal profile of indigenous pig (Sus scrofa

    Directory of Open Access Journals (Sweden)

    P. Guru Vishnu

    2015-02-01

    Full Text Available Aim: The objective of this study was to investigate the chromosomal profile of indigenous pigs by computing morphometric measurements. Materials and Methods: A cytogenetic study was carried out in 60 indigenous pigs to analyze the chromosomal profile by employing the short term peripheral blood lymphocyte culture technique. Results: The modal chromosome number (2n in indigenous pigs was found to be 38 and a fundamental number of 64 as in the exotic. First chromosome was the longest pair, and thirteenth pair was the second largest while Y-chromosome was the smallest in the karyotype of the pig. The mean relative length, arm ratio, centromeric indices and morphological indices of chromosomes varied from 1.99±0.01 to 11.23±0.09, 1.04±0.05 to 2.95±0.02, 0.51±0.14 to 0.75±0.09 and 2.08±0.07 to 8.08±0.15%, respectively in indigenous pigs. Sex had no significant effect (p>0.05 on all the morphometric measurements studied. Conclusion: The present study revealed that among autosomes first five pairs were sub metacentric, next two pairs were sub telocentric (6-7, subsequent five pairs were metacentric (8-12 and remaining six pairs were telocentric (13-18, while both allosomes were metacentric. The chromosomal number, morphology and various morphometric measurements of the chromosomes of the indigenous pigs were almost similar to those established breeds reported in the literature.

  6. Placing Marangoni instabilities under arrest

    CERN Document Server

    Bhamla, M Saad

    2016-01-01

    Soap bubbles occupy the rare position of delighting and fascinating both young children and scientific minds alike. Sir Isaac Newton, Joseph Plateau, Carlo Marangoni, and Pierre-Gilles de Gennes, not to mention countless others, have discovered remarkable results in optics, molecular forces and fluid dynamics from investigating this seemingly simple system. We present here a compilation of curiosity-driven experiments that systematically investigate the surface flows on a rising soap bubble. From childhood experience, we are familiar with the vibrant colors and mesmerizing display of chaotic flows on the surface of a soap bubble. These flows arise due to surface tension gradients, also known as Marangoni flows or instabilities. In Figure 1, we show the surprising effect of layering multiple instabilities on top of each other, highlighting that unexpected new phenomena are still waiting to be discovered, even in the simple soap bubble.

  7. Statistical theory of thermal instability

    CERN Document Server

    Illarionov, A F

    1997-01-01

    A new statistical approach is presented to study the thermal instability process of optically thin unmagnetized plasma. In this approach the time evolution of mass distribution function over temperature is calculated. This function characterizes the statistical properties of the multiphase medium of arbitrary spaced three-dimensional structure of arbitrary temperature perturbations. We construct our theory under the isobarical condition (P=const over space), which is satisfied in the short wavelength limit. The developed theory is illustrated in the case of thermal instability of a slowly expanding interstellar cloud. Numerical solutions of equations of the statistical theory are constucted and compared with hydrodynamical solutions. The results of both approaches are identical in the short wavelength range when the isobarity condition is satisfied. Also the limits of applicability of the statistical theory are estimated. The possible evolution of initial spectrum of perturbations is discussed. The proposed t...

  8. Instability investigation for storage mode

    International Nuclear Information System (INIS)

    The Amsterdam Pulse Stretcher (AmPS) will be used in storage mode for internal target (IT) physics. It demands the beam lifetime at least at the order of half an hour and the stored beam current of 200 mA. Bunched beam instabilities have been observed in many storage rings. The low-Q broadband impedance drives the single-bunch instability. The single bunch treshold and the equilibrium bunch length as the function of energies, RF voltages, and RF frequencies are investigated. The code ZAP has been used for investigating the stability thresholds for AmPS in storage mode. This note presents the simulation results. They gave useful information for choosing the RF parameters of AmPS. (author). 3 refs.. 6 figs.. 3 tabs

  9. Origin and evolution of X chromosome inactivation.

    Science.gov (United States)

    Gribnau, Joost; Grootegoed, J Anton

    2012-06-01

    Evolution of the mammalian sex chromosomes heavily impacts on the expression of X-encoded genes, both in marsupials and placental mammals. The loss of genes from the Y chromosome forced a two-fold upregulation of dose sensitive X-linked homologues. As a corollary, female cells would experience a lethal dose of X-linked genes, if this upregulation was not counteracted by evolution of X chromosome inactivation (XCI) that allows for only one active X chromosome per diploid genome. Marsupials rely on imprinted XCI, which inactivates always the paternally inherited X chromosome. In placental mammals, random XCI (rXCI) is the predominant form, inactivating either the maternal or paternal X. In this review, we discuss recent new insights in the regulation of XCI. Based on these findings, we propose an X inactivation center (Xic), composed of a cis-Xic and trans-Xic that encompass all elements and factors acting to control rXCI either in cis or in trans. We also highlight that XCI may have evolved from a very small nucleation site on the X chromosome in the vicinity of the Sox3 gene. Finally, we discuss the possible evolutionary road maps that resulted in imprinted XCI and rXCI as observed in present day mammals. PMID:22425180

  10. Electromechanical instability in suspended carbon nanotubes

    OpenAIRE

    Jonsson, L. M.; Gorelik, L. Y.; Shekhter, R. I.; Jonson, M.

    2005-01-01

    We have theoretically investigated electromechanical properties of freely suspended carbon nanotubes when a current is injected into the tubes using a scanning tunneling microscope. We show that a shuttle-like electromechanical instability can occur if the bias voltage exceeds a dissipation-dependent threshold value. An instability results in large amplitude vibrations of the carbon nanotube bending mode, which modify the current-voltage characteristics of the system.

  11. Instabilities and shape analyses of elastic shells

    OpenAIRE

    Knoche, Sebastian

    2014-01-01

    This thesis presents research results on the deformation of elastic shells, especially concerning buckling and wrinkling instabilities. The theoretical description of such deformations is used to develop methods of shape analysis, which serve to infer material properties from simple experimental observations of deformed shells. When an initially spherical shell is deflated, two successive instabilities can typically be observed. In a first buckling transition, an axisymmetric dimple appears....

  12. Relativistically modulational instability by strong Langmuir waves

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X. L.; Liu, S. Q. [Department of Physics, Nanchang University, Jiangxi, Nanchang 330031 (China); Li, X. Q. [Department of Physics, Nanjing Normal University, Nanjing 210097 (China)

    2012-09-15

    Based on the set of nonlinear coupling equations, which has considered the relativistic effects of electrons, modulational instability by strong Langmuir waves has been investigated in this paper. Both the characteristic scale and maximum growth rate of the Langmuir field will enhance with the increase in the electron relativistic effect. The numerical results indicate that longitudinal perturbations induce greater instability than transverse perturbations do, which will lead to collapse and formation of the pancake-like structure.

  13. Microbunching Instability Modeling in the SPARX configurations

    International Nuclear Information System (INIS)

    The modeling of the microbunching instability has been carried out for the SPARX FEL accelerator, two configurations have been considered and compared: hybrid compression scheme (velocity bunching plus magnetic compressor) and purely magnetic. The effectiveness of a lattice tuning together with the use of a laser heather has been exploited to reduce the instability drawbacks on the electron beam quality. Analytical predictions and start to end simulation results are reported in this paper.

  14. Instabilities in a Self-Gravitating Magnetized Gas Disk

    CERN Document Server

    Lee, S M; Lee, Sang Min; Hong, Seung Soo

    1999-01-01

    A linear stability analysis has been performed onto a self-gravitating magnetized gas disk bounded by external pressure. The resulting dispersion relation is fully explained by three kinds of instability: a Parker-type instability driven by self-gravity, usual Jeans gravitational instability and convection. In the direction parallel to the magnetic fields, the magnetic tension completely suppresses the convection. If the adiabatic index $\\gamma$ is less than a certain critical value, the perturbations trigger the Parker as well as the Jeans instability in the disk. Consequently, the growth rate curve has two maxima: one at small wavenumber due to a combination of the Parker and Jeans instabilities, and the other at somewhat larger wavenumber mostly due to the Parker instability. In the horizontal direction perpendicular to the fields, the convection makes the growth rate increase monotonically upto a limiting value as the perturbation wavenumber gets large. However, at small wavenumbers, the Jeans instability...

  15. Imaging findings in posterior instability of the shoulder

    International Nuclear Information System (INIS)

    Posterior shoulder instability refers to the symptoms and signs resulting from excessive posterior translation of the humerus. Magnetic resonance (MR) imaging is the radiological modality of choice in the diagnostic assessment of posterior instability. Computed tomography (CT) is useful in the evaluation of osseous abnormalities associated with posterior instability. A detailed description of the posterior osseous and labroligamentous abnormalities has evolved recently, and many variant lesions of the posteroinferior labrum and/or capsular structures have been described. As the recommended surgical management of lesions associated with posterior instability is a lesion-specific approach, awareness of the specific lesions that have been described in association with posterior instability helps in pre-surgical planning. The purpose of this article is to review the classification of, and injury mechanisms leading to, posterior shoulder instability and to describe imaging findings associated with posterior instability, with emphasis on MR imaging. (orig.)

  16. Human ESCs predisposition to karyotypic instability: Is a matter of culture adaptation or differential vulnerability among hESC lines due to inherent properties?

    Directory of Open Access Journals (Sweden)

    Bueno Clara

    2008-10-01

    , SHEF-1, which was maintained for 185 passages in feeders did not undergo any numerical or structural chromosomal change after 30 passages in feeder-free culture and over 215 passages in total. Conclusion These results support the concept that feeder-free conditions may partially contribute to hESC chromosomal changes but also confirm the hypothesis that regardless of the culture conditions, culture duration or splitting methods, some hESC lines are inherently more prone than others to karyotypic instability.

  17. Instability of the Heliopause

    International Nuclear Information System (INIS)

    The heliopause (HP) separates the tenuous hot heliosheath plasma from the relatively dense cool magnetized plasma of the local interstellar medium (LISM). Fluid acceleration in the HP region can therefore drive Rayleigh-Taylor-like and Kelvin-Helmholtz- like instabilities. Charge exchange coupling of plasma ions and primary interstellar neutral atoms provides an effective gravity, suggesting the possibility of Rayleigh Taylor-like (RT-like) instabilities. Shear flow due to the velocity difference between the heliosheath and the interstellar flows drives Kelvin Helmholtz-like (KH-like) modes on the heliopause. Magnetic fields damp the classical KH instability. However, we show that energetic neutral atoms (ENAs) destabilize KH-modes,even in the presence of interplanetary and interstellar magnetic fields. We consider a model that includes a number of effects that are important in the heliosphere such as resonant change exchange between the primary neutrals and the solar wind plasma, ENAs from the inner heliosheath, plasma flows along the heliopause and magnetic fields in the inner and outer heliosheath. We find that the nose region is unstable to RT-like modes for HP parameters, while the shoulder region is unstable to a new instability that has the characteristics of a mixed RT-KH-like mode. These instabilities are not stabilized by typical values of the magnetic fields in the inner and outer heliosheath close to the nose and shoulder regions. Whereas ENAs have a stabilizing influence on the RT instability in the vicinity of the nose region (due to counter streaming), they have a destabilizing influence on the KH instability in the vicinity of the flanks. We find that even in the presence of interplanetary and interstellar magnetic fields, ENAs can drive a new form of KH-like instability on the flanks. An analysis of the collisional and anomalous magnetic field diffusion time scales shows that ideal MHD is an appropriate model at the HP. The interstellar magnetic

  18. Amifostine Protection Against Mitomycin-induced Chromosomal Breakage in Fanconi Anaemia Lymphocytes

    Directory of Open Access Journals (Sweden)

    Miriam T. P. Lopes

    2008-08-01

    Full Text Available Fanconi anaemia (FA is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF on basal and mitomycin C (MMC-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronuclei count was higher among FA patients than healthy subjects. Pre-treatment with AMF significantly inhibited micronucleation induced by MMC in healthy subjects (23.4 ± 4.0 – MMC vs 12.3 ± 2.9 – AMF →MMC MN/1000CB, p < 0.01, one way ANOVA as well as in FA patients (80.0 ± 5.8 – MMC vs 40.1 ± 5.8 – AMF →MMC MN/1000CB, p < 0.01, ANOVA. Release of ROS by peripheral blood mononuclear cells treated with AMF →MMC and measured by chemoluminometry showed that AMF-protection was statistically higher among FA patients than in healthy individuals. Based on these results we suggest that AMF prevents chromosomal breakage induced by MMC, probably by its antioxidant effect.

  19. Plasma physics and instabilities

    International Nuclear Information System (INIS)

    These lectures procide an introduction to the theory of plasmas and their instabilities. Starting from the Bogoliubov, Born, Green, Kirkwood, and Yvon (BBGKY) hierarchy of kinetic equations, the additional concept of self-consistent fields leads to the fundamental Vlasov equation and hence to the warm two-fluid model and the one-fluid MHD, or cold, model. The properties of small-amplitude waves in magnetized (and unmagnetized) plasmas, and the instabilities to which they give rise, are described in some detail, and a complete chapter is devoted to Landau damping. The linear theory of plasma instabilities is illustrated by the current-driven electrostatic kind, with descriptions of the Penrose criterion and the energy principle of ideal MHD. There is a brief account of the application of feedback control. The non-linear theory is represented by three examples: quasi-linear velocity-space instabilities, three-wave instabilities, and the stability of an arbitrarily largeamplitude wave in a plasma. (orig.)

  20. Mackenzie's Demon with instabilities

    International Nuclear Information System (INIS)

    MacKenzie's Maxwell Demon, consisting of positively biased thin wires, heats plasma electrons without significantly affecting the plasma potential. Experiments were performed on the Maxwell Demon in a multi-dipole confined filament discharge. It is shown that given adequate bias, the Demon reduces a bi-Maxwellian electron distribution function to a single Maxwellian electron distribution function. It is shown that a small planar electrode can perform identical heating as the Demon, provided that the electrode has the area of approximately three times the Demon's conductive surface area. The instability that limits the Demon's operation is investigated. Time-resolved measurements of changes in global electron temperature, plasma density and plasma potential within a cycle of the instability are considered. It is found that the Demon's instability is a repeating pulsed anode spot. Density measurements indicate that the frequency of the instability is dependent on plasma production and loss rates. The neutral pressure dependence of the anode spot instability is measured and modeled for the first time. (paper)

  1. Molecular cytogenetics: A novel approach for measuring chromosome translocations in individuals years after exposure to low levels of ionizing radiation

    International Nuclear Information System (INIS)

    Chromosome painting was developed in our laboratory to facilitate rapid and accurate detection of chromosome translocations in human cells. Chromosome painting is the selective staining of one or more chromosomes by fluorescence in situ hybridization (FISH) using whole chromosome probes. This method permits essentially uniform hybridization and staining along the entire lengths of targeted chromosomes. Staining all other chromosomes a different color makes interchromosomal exchange aberrations readily apparent as bicolored chromosomes. Here we present a brief discussion of this methodology and recent results from studies in our laboratory

  2. Condition for convective instability of dark solitons

    International Nuclear Information System (INIS)

    Simple derivation of the condition for the transition point from absolute instability of plane dark solitons to their convective instability is suggested. It is shown that unstable wave packet expands with velocity equal to the minimal group velocity of the disturbance waves propagating along a dark soliton. The growth rate of the length of dark solitons generated by the flow of Bose-Einstein condensate past an obstacle is estimated. Analytical theory is confirmed by the results of numerical simulations. -- Highlights: → Conditions for absolute or convective instability of dark solitons are derived. → Velocity of expansion of instability front equals to the minimal group velocity. → Growth rate of length of dark solitons generated by the flow is estimated.

  3. Interfacial fluid instabilities and Kapitsa pendula

    CERN Document Server

    Krieger, Madison Ski

    2015-01-01

    The onset and development of instabilities is one of the central problems in fluid mechanics. Here we develop a connection between instabilities of free fluid interfaces and inverted pendula. When acted upon solely by the gravitational force, the inverted pendulum is unstable. This position can be stabilised by the Kapitsa phenomenon, in which high-frequency low-amplitude vertical vibrations of the base creates a fictitious force which opposes the gravitational force. By transforming the dynamical equations governing a fluid interface into an appropriate pendulum, we demonstrate how stability can be induced in fluid systems by properly tuned vibrations. We construct a "dictionary"-type relationship between various pendula and the classical Rayleigh-Taylor, Kelvin-Helmholtz, Rayleigh-Plateau and the self-gravitational instabilities. This makes several results in control theory and dynamical systems directly applicable to the study of "tunable" fluid instabilities, where the critical wavelength depends on the e...

  4. Shear instabilities in shallow-water magnetohydrodynamics

    CERN Document Server

    Mak, Julian; Hughes, D W

    2016-01-01

    Within the framework of shallow-water magnetohydrodynamics, we investigate the linear instability of horizontal shear flows, influenced by an aligned magnetic field and stratification. Various classical instability results, such as H{\\o}iland's growth rate bound and Howard's semi-circle theorem, are extended to this shallow-water system for quite general profiles. Two specific piecewise-constant velocity profiles, the vortex sheet and the rectangular jet, are studied analytically and asymptotically; it is found that the magnetic field and stratification (as measured by the Froude number) are generally both stabilising, but weak instabilities can be found at arbitrarily large Froude number. Numerical solutions are computed for corresponding smooth velocity profiles, the hyperbolic-tangent shear layer and the Bickley jet, for a uniform background field. A generalisation of the long-wave asymptotic analysis of Drazin & Howard (1962) is employed in order to understand the instability characteristics for both ...

  5. Instability in hydraulic machines demonstration rig

    Science.gov (United States)

    Muszynska, A.; Braun, M. J.

    1985-01-01

    In fluid flow machines, the working fluid involved in rotative motion due to shaft rotation significantly modifies the rotor synchronous response. This can result in the rotor maintaining the high vibration amplitude that occurs at resonance over an extended rotative speed range. The phase changes in this range are typically very small. The fluid may also create rotor instability, i.e., subsynchronous self-excited vibrations, when the rotative speed is sufficiently high. This rotor instability is often related and increases with higher rotor unbalance (Opposite to other types of instability such as oil whirl/whip, internal friction, etc.). The rotor rig demonstrates typical dynamic behavior of hydraulic machines. At lower speeds the effect of amplitude/phase mentioned above is noticeable; at higher speeds the subsynchronous instability occurs.

  6. Elliptical instability in terrestrial planets and moons

    CERN Document Server

    Cébron, David; Moutou, Claire; Gal, Patrice Le; 10.1051/0004-6361/201117741

    2012-01-01

    The presence of celestial companions means that any planet may be subject to three kinds of harmonic mechanical forcing: tides, precession/nutation, and libration. These forcings can generate flows in internal fluid layers, such as fluid cores and subsurface oceans, whose dynamics then significantly differ from solid body rotation. In particular, tides in non-synchronized bodies and libration in synchronized ones are known to be capable of exciting the so-called elliptical instability, i.e. a generic instability corresponding to the destabilization of two-dimensional flows with elliptical streamlines, leading to three-dimensional turbulence. We aim here at confirming the relevance of such an elliptical instability in terrestrial bodies by determining its growth rate, as well as its consequences on energy dissipation, on magnetic field induction, and on heat flux fluctuations on planetary scales. Previous studies and theoretical results for the elliptical instability are re-evaluated and extended to cope with ...

  7. Can dust coagulation trigger streaming instability?

    CERN Document Server

    Drazkowska, Joanna

    2014-01-01

    Streaming instability can be a very efficient way of overcoming growth and drift barriers to planetesimal formation. However, it was shown that strong clumping, which leads to planetesimal formation, requires a considerable number of large grains. State-of-the-art streaming instability models do not take into account realistic size distributions resulting from the collisional evolution of dust. We investigate whether a sufficient quantity of large aggregates can be produced by sticking and what the interplay of dust coagulation and planetesimal formation is. We develop a semi-analytical prescription of planetesimal formation by streaming instability and implement it in our dust coagulation code based on the Monte Carlo algorithm with the representative particles approach. We find that planetesimal formation by streaming instability may preferentially work outside the snow line, where sticky icy aggregates are present. The efficiency of the process depends strongly on local dust abundance and radial pressure g...

  8. 2D and 3D Chromosome Painting in Malaria Mosquitoes

    Science.gov (United States)

    George, Phillip; Sharma, Atashi; Sharakhov, Igor V

    2014-01-01

    Fluorescent in situ hybridization (FISH) of whole arm chromosome probes is a robust technique for mapping genomic regions of interest, detecting chromosomal rearrangements, and studying three-dimensional (3D) organization of chromosomes in the cell nucleus. The advent of laser capture microdissection (LCM) and whole genome amplification (WGA) allows obtaining large quantities of DNA from single cells. The increased sensitivity of WGA kits prompted us to develop chromosome paints and to use them for exploring chromosome organization and evolution in non-model organisms. Here, we present a simple method for isolating and amplifying the euchromatic segments of single polytene chromosome arms from ovarian nurse cells of the African malaria mosquito Anopheles gambiae. This procedure provides an efficient platform for obtaining chromosome paints, while reducing the overall risk of introducing foreign DNA to the sample. The use of WGA allows for several rounds of re-amplification, resulting in high quantities of DNA that can be utilized for multiple experiments, including 2D and 3D FISH. We demonstrated that the developed chromosome paints can be successfully used to establish the correspondence between euchromatic portions of polytene and mitotic chromosome arms in An. gambiae. Overall, the union of LCM and single-chromosome WGA provides an efficient tool for creating significant amounts of target DNA for future cytogenetic and genomic studies. PMID:24429496

  9. Meiotic behaviour of individual chromosomes in allotriploid Alstroemeria hybrids.

    Science.gov (United States)

    Kamstra, S A; de Jong, J H; Jacobsen, E; Ramanna, M S; Kuipers, A G J

    2004-07-01

    Chromosome association and chiasma formation were studied in pollen mother cells at metaphase I of four allotriplod BC1 plants (2n=3x=24) obtained from the backcross of the hybrid Alstroemeria aurea x A. inodora with its parent A. inodora. We distinguished the chromosomes of both parental species by genomic in situ hybridization (GISH), whereas the individual chromosomes were identified on the basis of their multicolour FISH banding patterns obtained after a second hybridization with two species-specific satellite repeats as probes. All the four BC1 plants possessed two genomes of A. inodora and one of A. aurea. Variable numbers of recombinant chromosomes, resulting from meiotic recombination in the interspecific hybrid, were present in these plants. The homologous A. inodora chromosomes generally formed bivalents, leaving the homoeologous A. aurea chromosomes unassociated. High frequencies of trivalents were observed for the chromosome sets that contained recombinant chromosomes, even when the recombinant segments were small. Chromosome associations in the trivalents were restricted to homologous segments. The implications of the absence of homoeologous chromosome pairing on gamete constitution and prospects for introgression in Alstroemeria are discussed. PMID:15100711

  10. Pathogenesis of vestibular schwannoma in ring chromosome 22

    Directory of Open Access Journals (Sweden)

    Debiec-Rychter Maria

    2009-09-01

    Full Text Available Abstract Background Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet. Methods We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and NF2 mutation analysis. Results Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the NF2 gene on the remaining chromosome 22. Conclusion We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic NF2 mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.

  11. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

    Full Text Available Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

  12. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B; Vogel, F; Noer, H; Mikkelsen, M

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation with...

  13. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  14. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  15. Chromosomes, cancer and radiosensitivity

    International Nuclear Information System (INIS)

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available

  16. Chromosome Morphology in Kniphofia.

    Directory of Open Access Journals (Sweden)

    J. M. J de Wet

    1960-12-01

    Full Text Available A number of species and varieties of the genus  Kniphofia (Liliaceae were studied cytologically. The somatic chromosome number is  2n = 12 in all the species. This is also true in  Notosceptrum natalense Baker.

  17. Neutrino beam plasma instability

    Indian Academy of Sciences (India)

    Vishnu M Bannur

    2001-10-01

    We derive relativistic fluid set of equations for neutrinos and electrons from relativistic Vlasov equations with Fermi weak interaction force. Using these fluid equations, we obtain a dispersion relation describing neutrino beam plasma instability, which is little different from normal dispersion relation of streaming instability. It contains new, nonelectromagnetic, neutrino-plasma (or electroweak) stable and unstable modes also. The growth of the instability is weak for the highly relativistic neutrino flux, but becomes stronger for weakly relativistic neutrino flux in the case of parameters appropriate to the early universe and supernova explosions. However, this mode is dominant only for the beam velocity greater than 0.25 and in the other limit electroweak unstable mode takes over.

  18. Instabilities in astrophysical jets

    International Nuclear Information System (INIS)

    Instabilities in astrophysical jets are studied in the nonlinear regime by performing 2D numerical classical gasdynamical calculations. The instabilities which arise from unsteadiness in output from the central engine feeding the jets, and those which arise from a beam in a turbulent surrounding are studied. An extra power output an order of magnitude higher than is normally delivered by the engine over a time equal to (nozzle length)/(sound velocity at centre) causes a nonlinear Kelvin-Helmholtz instability in the jet walls. Constrictions move outwards, but the jet structure is left untouched. A beam in turbulent surroundings produces internal shocks over distances of a few beam widths. If viscosity is present the throughput of material is hampered on time scales of a few beam radius sound travel times. The implications are discussed. (Auth.)

  19. Organization of the bacterial chromosome.

    OpenAIRE

    Krawiec, S.; Riley, M

    1990-01-01

    Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction ...

  20. Monitoring of chromosomal aberrations in natural populations of Pinus pallasiana

    OpenAIRE

    V. P. Koba

    2012-01-01

    This paper presents the results of monitoring research of the chromosome aberrations at the stage of anaphase-telophase. The statistical characteristics of dynamics of chromosomal aberrations in populations of Pinus pallasiana D. Don across the high-altitude zones of the Mountain Crimea is given. It is established that on the southern macroslope of the Crimean Main Ridge the frequency of chromosomal aberrations in the P. pallasiana stands is higher in the lower zone in comparison with the mid...

  1. Nonrandom involvement of chromosomal segments in human hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J. D.

    1977-01-01

    The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphenomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration of the number and/or location of genes related to nucleic acid biosynthesis. It would be expected that the proliferative advantage provided by various chromosome aberrations differs in patients with different genetic constitutions.

  2. Ringed accretion disks: instabilities

    CERN Document Server

    Pugliese, D

    2016-01-01

    We analyze the possibility that several instability points may be formed, due to the Paczy\\'nski mechanism of violation of mechanical equilibrium, in the orbiting matter around a supermassive Kerr black hole. We consider recently proposed model of ringed accretion disk, made up by several tori (rings) which can be corotating or counterrotating relative to the Kerr attractor due to the history of the accretion process. Each torus is governed by the general relativistic hydrodynamic Boyer condition of equilibrium configurations of rotating perfect fluids. We prove that the number of the instability points is generally limited and depends on the dimensionless spin of the rotating attractor.

  3. Longitudinal microwave instability

    International Nuclear Information System (INIS)

    A derivation of the relationship between growth rate and impedance is given. The only other instability considered here is the resonance effect produced by excessive tune shift due to space charge. We assume, without discussion, the (Δν)/sub max/ = .25; that is, this resonance growth is avoided (stability) by limiting the ring charge. On the other hand, the longitudinal microwave instability is assumed to be present (cannot be stabilized). Thus, the latter involves a limiting impedance to keep the growth rate low enough. The maximum allowed impedance for a maximum allowed growth rate is listed

  4. Ringed Accretion Disks: Instabilities

    Science.gov (United States)

    Pugliese, D.; Stuchlík, Z.

    2016-04-01

    We analyze the possibility that several instability points may be formed, due to the Paczyński mechanism of violation of mechanical equilibrium, in the orbiting matter around a supermassive Kerr black hole. We consider a recently proposed model of a ringed accretion disk, made up by several tori (rings) that can be corotating or counter-rotating relative to the Kerr attractor due to the history of the accretion process. Each torus is governed by the general relativistic hydrodynamic Boyer condition of equilibrium configurations of rotating perfect fluids. We prove that the number of the instability points is generally limited and depends on the dimensionless spin of the rotating attractor.

  5. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

    Science.gov (United States)

    MacKinnon, Ruth N.; Campbell, Lynda J.

    2011-01-01

    Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy. PMID:22567363

  6. A review of metaphase chromosome image selection techniques for automatic karyotype generation.

    Science.gov (United States)

    Arora, Tanvi; Dhir, Renu

    2016-08-01

    The karyotype is analyzed to detect the genetic abnormalities. It is generated by arranging the chromosomes after extracting them from the metaphase chromosome images. The chromosomes are non-rigid bodies that contain the genetic information of an individual. The metaphase chromosome image spread contains the chromosomes, but these chromosomes are not distinct bodies; they can either be individual chromosomes or be touching one another; they may be bent or even may be overlapping and thus forming a cluster of chromosomes. The extraction of chromosomes from these touching and overlapping chromosomes is a very tedious process. The segmentation of a random metaphase chromosome image may not give us correct and accurate results. Therefore, before taking up a metaphase chromosome image for analysis, it must be analyzed for the orientation of the chromosomes it contains. The various reported methods for metaphase chromosome image selection for automatic karyotype generation are compared in this paper. After analysis, it has been concluded that each metaphase chromosome image selection method has its advantages and disadvantages. PMID:26676686

  7. Results of a collaborative study of the EDNAP group regarding the reproducibility and robustness of the Y-chromosome STRs DYS19, DYS389 I and II, DYS390 and DYS393 in a PCR pentaplex format

    DEFF Research Database (Denmark)

    Carracedo, A; Beckmann, A; Bengs, A;

    2001-01-01

    A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in the frame work of the STADNAP program, i.e. standardization of DNA profiling in Europe, in order to evaluate the performance of a Y-chromosome STR pentaplex, which includes the loci DYS19, DYS389 I and II, DYS...

  8. Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor δ-chain diversity region and results in a previously unreported fusion transcript

    International Nuclear Information System (INIS)

    The authors have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which they have molecularly cloned and sequenced. Initial screening used joining (J)-segment probes from the T-cell receptor (TCR) α- and δ-chain loci. In apparent concert with the translocation, a deletion has occurred between δ-chain diversity (D)-region genes Dδ1 and Dδ2. The nature of the Dδ1-Dδ2 deletional event implicates a lymphoid recombinase in the mechanism of the translocation. As a consequence of the translocation, an unusual fusion transcript was generated. Probes from chromosome 1 detected a previously unreported transcript in RNA from both the cell line and the patient. A chromosome 14 probe identified the same transcript, thus confirming a fusion transcript derived from both chromosomes 1 and 14. This translocation may identify a gene for which they propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line

  9. Mini-chromosomes among danish Candida glabrata isolates originated through two different mechanisms

    DEFF Research Database (Denmark)

    Ahmad, K. M.; Ishchuk, O.; Hellborg, L.;

    2012-01-01

    ) through a segmental duplication which covered the centromeric region, and (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of mini-chromosomes carrying duplicated genes exhibited mitotic instability......We analyzed 201 strains of the pathogenic yeast Candida glabrata from patients, mainly suffering from systemic infection, at Danish hospitals during 1985 – 1999. Our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. Nine strains contained mini-chromosomes......, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, C. glabrata strains had independent origin and the analyzed mini-chromosomes were struc- turally not related to each other (i.e., they contained different sets o genes). We inferred two mechanisms involved in their origin: (i...

  10. B chromosomes in the species Prochilodus argenteus (Characiformes, Prochilodontidae: morphologicalidentity and dispersion

    Directory of Open Access Journals (Sweden)

    Manolo Penitente

    2015-03-01

    Full Text Available B chromosomes have attracted the attention of Neotropical fish cytogeneticists in recent years, both for their remarkable occurrence in this group and also because of the interest in studies of the genetic structure and role played in the genome of these organisms. The aim of this study was to report the first occurrence of supernumerary chromosomes in Prochilodus argenteus (Agassiz, 1829, this being the fifth carrier species among thirteen within the genus Prochilodus (Agassiz, 1829. The extra elements identified in this species are small sized heterochromatic chromosomes characterized by a low mitotic instability index, being very similar to other supernumerary chromosomes described in the species of the genus Prochilodus. Morphology, structure and dispersion of the supernumerary genomic elements which occur in species of this genus are discussed aiming to better understand aspects involved the origin of supernumerary chromosomes and the differentiation process and relationships among species of this family.

  11. B chromosomes in the species Prochilodus argenteus (Characiformes, Prochilodontidae): morphologicalidentity and dispersion

    Science.gov (United States)

    Penitente, Manolo; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    Abstract B chromosomes have attracted the attention of Neotropical fish cytogeneticists in recent years, both for their remarkable occurrence in this group and also because of the interest in studies of the genetic structure and role played in the genome of these organisms. The aim of this study was to report the first occurrence of supernumerary chromosomes in Prochilodus argenteus (Agassiz, 1829), this being the fifth carrier species among thirteen within the genus Prochilodus (Agassiz, 1829). The extra elements identified in this species are small sized heterochromatic chromosomes characterized by a low mitotic instability index, being very similar to other supernumerary chromosomes described in the species of the genus Prochilodus. Morphology, structure and dispersion of the supernumerary genomic elements which occur in species of this genus are discussed aiming to better understand aspects involved the origin of supernumerary chromosomes and the differentiation process and relationships among species of this family. PMID:25893076

  12. B chromosomes in the species Prochilodusargenteus (Characiformes, Prochilodontidae): morphologicalidentity and dispersion.

    Science.gov (United States)

    Penitente, Manolo; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    B chromosomes have attracted the attention of Neotropical fish cytogeneticists in recent years, both for their remarkable occurrence in this group and also because of the interest in studies of the genetic structure and role played in the genome of these organisms. The aim of this study was to report the first occurrence of supernumerary chromosomes in Prochilodusargenteus (Agassiz, 1829), this being the fifth carrier species among thirteen within the genus Prochilodus (Agassiz, 1829). The extra elements identified in this species are small sized heterochromatic chromosomes characterized by a low mitotic instability index, being very similar to other supernumerary chromosomes described in the species of the genus Prochilodus. Morphology, structure and dispersion of the supernumerary genomic elements which occur in species of this genus are discussed aiming to better understand aspects involved the origin of supernumerary chromosomes and the differentiation process and relationships among species of this family. PMID:25893076

  13. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  14. Cytogenetic effects of radiotherapy. Breakpoint distribution in induced chromosome aberrations

    International Nuclear Information System (INIS)

    A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo. Chromosome arms 1p, 1q, 7q, and 11p were also significantly more affected. Some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected. This band is proposed as a hot point for the clastogenic effect of ionizing radiation. A significant clustering of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpoints was also observed in bands where fragile sites, protooncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominoidea are located

  15. Cytogenetic analysis of chromosomal abnormalities in Sri Lankan children

    Institute of Scientific and Technical Information of China (English)

    Colombo; Sri Lanka

    2015-01-01

    Background: Cytogenetic analysis is a valuable investigation in the diagnostic work up of children with suspected chromosomal disorders. The objective of this study was to describe the prevalence of various types of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis. Methods: Cytogenetic reports of 1554 consecutive children with suspected chromosomal disorders who underwent karyotyping in two genetic centers in Sri Lanka from January 2006 to December 2011 were reviewed retrospectively. Results: A total of 1548 children were successfully karyotyped. Abnormal karyotypes were found in 783 (50.6%) children. Numerical and structural abnormalities accounted for 90.8% and 9.2%, respectively. Down syndrome was the commonest aneuploidy identifi ed. Other various autosomal and sex chromosomal aneuploidies as well as micro-deletion syndromes were also detected. Conclusions: The prevalence of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis for suspected chromosomal disorders was relatively higher than that in Caucasian and other Asian populations.

  16. The role of the type of pollination in the manifestation of the radiation-induced instability of a genome of plants

    International Nuclear Information System (INIS)

    The radiation-induced genome instability of plants of tobacco Nicotiana tabacum L. and onion Allium cepa L. is investigated. The increase of the amount of chromosomal aberrations in the plants of M1 and M2 is revealed. The level of chromosomal aberrations depends on the dose of irradiation and the method of plants pollination

  17. Instability of ties in compression

    DEFF Research Database (Denmark)

    Buch-Hansen, Thomas Cornelius

    2013-01-01

    Masonry cavity walls are loaded by wind pressure and vertical load from upper floors. These loads results in bending moments and compression forces in the ties connecting the outer and the inner wall in a cavity wall. Large cavity walls are furthermore loaded by differential movements from the...... temperature gradient between the outer and the inner wall, which results in critical increase of the bending moments in the ties. Since the ties are loaded by combined compression and moment forces, the loadbearing capacity is derived from instability equilibrium equations. Most of them are iterative, since...

  18. Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Jessica Hopkins

    2014-07-01

    Full Text Available Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3 proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β, two α-kleisins (RAD21L and REC8 and one STAG protein (STAG3 that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC. From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8 is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis

  19. Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner

    OpenAIRE

    Moser, Jill; Kool, Hanneke; Giakzidis, Ioannis; Caldecott, Keith; Mullenders, Leon H. F.; Fousteri, Maria I.

    2007-01-01

    Impaired gap filling and sealing of chromosomal DNA in nucleotide excision repair (NER) leads to genome instability. XRCC1-DNA ligase IIIa (XRCC1-Lig3) plays a central role in the repair of DNA single-strand breaks but has never been implicated in NER. Here we show that XRCC1-Lig3 is indispensable for ligation of NER-induced breaks and repair of UV lesions in quiescent cells. Furthermore, our results demonstrate that two distinct complexes differentially carry out gap filling in NER. XRCC1-Li...

  20. Marker chromosome 21 identified by microdissection and FISH

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Y.; Palmer, C.G. [Indiana Univ. School of Medicine, Indianapolis, IN (United States); Rubinstein, J. [Univ. Affiliated Cincinnati Center for Developmental Disorders, OH (United States)] [and others

    1995-03-27

    A child without Down`s syndrome but with developmental delay, short stature, and autistic behavior was found to be mosaic 46,XX/47,XX,+mar(21) de novo. The marker was a small ring or dot-like chromosome. Microdissection of the marker was performed. The dissected fragments were biotinylated with sequence-independent PCR as a probe pool for fluorescence in situ hybridization (FISH). FISH results suggested an acrocentric origin of the marker. Subsequent FISH with {alpha}-satellite DNA probes for acrocentric chromosomes and chromosome-specific 21 and 22 painting probes confirmed its origin from chromosome 21. 14 refs., 3 figs.

  1. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1991-01-15

    Progress toward the construction of high density genetic maps of chromosomes 17 and X has been made by isolating and characterizing a relatively large set of polymorphic probes for each chromosome and using these probes to construct genetic maps. We have mapped the same polymorphic probes against a series of chromosome breakpoints on X and 17. The probes could be assigned to over 30 physical intervals on the X chromosome and 7 intervals on 17. In many cases, this process resulted in improved characterization of the relative locations of the breakpoints with respect to each other and the definition of new physical intervals. The strategy for isolation of the polymorphic clones utilized chromosome specific libraries of 1--15 kb segments from each of the two chromosomes. From these libraries, clones were screened for those detecting restriction fragment length polymorphisms. The markers were further characterized, the chromosomal assignments confirmed and in most cases segments of the original probes were subcloned into plasmids to produce probes with improved signal to noise ratios for use in the genetic marker studies. The linkage studies utilize the CEPH reference families and other well-characterized families in our collection which have been used for genetic disease linkage work. Preliminary maps and maps of portions of specific regions of 17 and X are provided. We have nearly completed a map of the 1 megabase Mycoplasma arthritidis genome by applying these techniques to a lambda phage library of its genome. We have found bit mapping to be an efficient means to organize a contiguous set of overlapping clones from a larger genome.

  2. Elastic instabilities in rubber

    Science.gov (United States)

    Gent, Alan

    2009-03-01

    Materials that undergo large elastic deformations can exhibit novel instabilities. Several examples are described: development of an aneurysm on inflating a rubber tube; non-uniform stretching on inflating a spherical balloon; formation of internal cracks in rubber blocks at a critical level of triaxial tension or when supersaturated with a dissolved gas; surface wrinkling of a block at a critical amount of compression; debonding or fracture of constrained films on swelling, and formation of ``knots'' on twisting stretched cylindrical rods. These various deformations are analyzed in terms of a simple strain energy function, using Rivlin's theory of large elastic deformations, and the results are compared with experimental measurements of the onset of unstable states. Such comparisons provide new tests of Rivlin's theory and, at least in principle, critical tests of proposed strain energy functions for rubber. Moreover the onset of highly non-uniform deformations has serious implications for the fatigue life and fracture resistance of rubber components. [4pt] References: [0pt] R. S. Rivlin, Philos. Trans. Roy. Soc. Lond. Ser. A241 (1948) 379--397. [0pt] A. Mallock, Proc. Roy. Soc. Lond. 49 (1890--1891) 458--463. [0pt] M. A. Biot, ``Mechanics of Incremental Deformations'', Wiley, New York, 1965. [0pt] A. N. Gent and P. B. Lindley, Proc. Roy. Soc. Lond. A 249 (1958) 195--205. [0pt] A. N. Gent, W. J. Hung and M. F. Tse, Rubb. Chem. Technol. 74 (2001) 89--99. [0pt] A. N. Gent, Internatl. J. Non-Linear Mech. 40 (2005) 165--175.

  3. Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini, Primates) by classic cytogenetics and chromosome painting

    Science.gov (United States)

    2010-01-01

    Background The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature. Results Our results show that members of the Pitheciinae have conserved several chromosome forms found in the inferred ancestral Platyrrhini karyotype (associations of human homologous segments 3a/21, 5/7a, 2b/16b, 8a/18, 14/15a and 10a/16a). Further, the monophyly of this subfamily is supported by three chromosomal synapomorphies (2a/10b, an acrocentric 15/14 and an acrocentric human 19 homolog). In addition, each species presents several autapomorphies. From this data set we established a chromosomal phylogeny of Pitheciinae, resulting in a single most parsimonious tree. Conclusions In our chromosomal phylogeny, the genus Pithecia occurred in a more basal position close to the inferred ancestor of Platyrrhini, while C. c. rubicundus and C. utahicki are closely related and are linked by exclusive synapomorphies. PMID:20565908

  4. Microsatellite Instability Assay — EDRN Public Portal

    Science.gov (United States)

    Microsatellite analysis (MSA) is a promising new technique for the surveillance of bladder cancer. The technology, which permits the separation by electrophoresis of polymerase chain reaction (PCR)-amplified sequences from non-malignant and malignant sources, has been applied to the diagnosis of solid tumors arising in colon, lung, oropharynx, kidney and bladder. MSA can detect genetic changes indicative of carcinoma from urothelial cells obtained in voided urine specimens. The genetic profile of DNA purified from urine is compared to that of DNA purified from peripheral lymphocytes that are considered normal. Once the DNA from uroepithelial cells has been obtained, PCR is performed with specific oligonucleotide primers for each chromosomal locus. The PCR products are then examined for evidence of microsatellite instability (MSI) and loss of heterozygosity (LOH), which are genetic characteristics of epithelial tumors. Preliminary work shows that MSA detects 95% of cancers.

  5. Shock instability in dissipative gases

    OpenAIRE

    Radulescu, Matei I.; Sirmas, Nick

    2011-01-01

    Previous experiments have revealed that shock waves in thermally relaxing gases, such as ionizing, dissociating and vibrationally excited gases, can become unstable. To date, the mechanism controlling this instability has not been resolved. Previous accounts of the D'yakov-Kontorovich instability, and Bethe-Zel'dovich-Thompson behaviour could not predict the experimentally observed instability. To address the mechanism controlling the instability, we study the propagation of shock waves in a ...

  6. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  7. Nonaxisymmetric linear instability of cylindrical magnetohydrodynamic Taylor-Couette flow

    CERN Document Server

    Child, Adam; Hollerbach, Rainer

    2015-01-01

    We consider the nonaxisymmetric modes of instability present in Taylor-Couette flow under the application of helical magnetic fields, mainly for magnetic Prandtl numbers close to the inductionless limit, and conduct a full examination of marginal stability in the resulting parameter space. We allow for the azimuthal magnetic field to be generated by a combination of currents in the inner cylinder and fluid itself, and introduce a parameter governing the relation between the strength of these currents. A set of governing eigenvalue equations for the nonaxisymmetric modes of instability are derived and solved by spectral collocation with Chebyshev polynomials over the relevant parameter space, with the resulting instabilities examined in detail. We find that by altering the azimuthal magnetic field profiles the azimuthal magnetorotational instability, nonaxisymmetric helical magnetorotational instability, and Tayler instability yield interesting dynamics, such as different preferred mode types, and modes with a...

  8. Posterior glenoid rim deficiency in recurrent (atraumatic) posterior shoulder instability

    International Nuclear Information System (INIS)

    Objective. To assess the shape of the posterior glenoid rim in patients with recurrent (atraumatic) posterior instability.Design and patients. CT examinations of 15 shoulders with recurrent (atraumatic) posterior instability were reviewed in masked fashion with regard to abnormalities of the glenoid shape, specifically of its posterior rim. The glenoid version was also assessed. The findings were compared with the findings in 15 shoulders with recurrent anterior shoulder instability and 15 shoulders without instability. For all patients, surgical correlation was available.Results. Fourteen of the 15 (93%) shoulders with recurrent (atraumatic) posterior shoulder instability had a deficiency of the posteroinferior glenoid rim. In patients with recurrent anterior instability or stable shoulders such deficiencies were less common (60% and 73%, respectively). The craniocaudal length of the deficiencies was largest in patients with posterior instability. When a posteroinferior deficiency with a craniocaudal length of 12 mm or more was defined as abnormal, sensitivity and specificity for diagnosing recurrent (atraumatic) posterior instability were 86.7% and 83.3%, respectively. There was a statistically significant difference in glenoid version between shoulders with posterior instability and stable shoulders (P=0.01).Conclusion. Recurrent (atraumatic) posterior shoulder instability should be considered in patients with a bony deficiency of the posteroinferior glenoid rim with a craniocaudal length of more than 12 mm. (orig.)

  9. Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity.

    Directory of Open Access Journals (Sweden)

    Yuanjie Hu

    Full Text Available Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7 copy number variation (CNV in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers.

  10. Fluid elastic instability of a flexible weir: experimental observations

    International Nuclear Information System (INIS)

    A hydro-elastic instability was discovered during test operations of Super-Phenix LMFBR reactor. This instability is due to energy bringing by discharge to the fluid-structure system constituted by a flexible weir shell and adjoining fluid collectors. This paper describes the steps of the discovery and the results of the different measurements performed on site and on several mock-ups. The paper points out two typical instability mechanisms. It discusses similitude and leading parameters, for these mechanisms. And it then shows how theoretical and experimental results correlate well, allowing to find for the reactor an efficient solution to eliminate instability

  11. Nonlinear evolution of MHD instabilities

    International Nuclear Information System (INIS)

    A 3-D nonlinear MHD computer code was used to study the time evolution of internal instabilities. Velocity vortex cells are observed to persist into the nonlinear evolution. Pressure and density profiles convect around these cells for a weak localized instability, or convect into the wall for a strong instability. (U.S.)

  12. Chromosome painting defines genomic rearrangements between red howler monkey subspecies.

    Science.gov (United States)

    Consigliere, S; Stanyon, R; Koehler, U; Agoramoorthy, G; Wienberg, J

    1996-06-01

    We hybridized whole human chromosome-specific DNA libraries to chromosomes of two supposed subspecies of Alouatta seniculus: Alouatta seniculus sara and Alouatta seniculus arctoides. The number of hybridization signals per haploid set is 42 in A. s. sara and 43 in A. s. arctoidea; the two karyotypes differ by at least 16 chromosomal rearrangements, including numerous translocations. An unusual sex chromosome system is shared by both taxa. The sex chromosome system results from a Y translocation with a chromosome homologous to parts of human chromosome 3/15 and can be described as X1X2Y1Y2/X1X1X2X2 (male/female). Both red howlers also have microchromosomes, a highly unusual karyological trait not found in other higher primates. These microchromosomes are not hybridized by any human chromosome paint and therefore are probably composed of repetitive DNA. It is well known that New World monkeys have high karyological variability. It is probable that molecular cytogenetic analyses including chromosome painting will permit an accurate reconstruction of the phylogeny of these monkeys and help establish the ancestral karyotype for higher primates. PMID:8817065

  13. Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome

    Institute of Scientific and Technical Information of China (English)

    Anurag Mitra; Rima Dada; Rajeev Kumar; Narmada Prasad Gupta; Kiran Kucheria; Satish Kumar Gupta

    2006-01-01

    Aim: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). Methods: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1 Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. Results: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion:Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.

  14. Ambiguous genitalia: a clinical and chromosomal study

    Directory of Open Access Journals (Sweden)

    V. Anantha Kumari

    2015-12-01

    Methods: The study is undertaken with forty cases with ages ranging from new borne to 20 yrs. Out of these 40 cases eight cases are below one year. In these cases physical examination is correlated with ultrasonography and chromosomal analysis. Results: In chromosomal analysis three persons out of forty cases were mosaics with 45, XO/46, twenty one cases who showed the chromosomal pattern as 46, XY mostly showed with no mullarian reminents. On examination palpable gonads were found in labio-scrotal sacs in seventeen cases. One of these cases was reared as girl found cytogenetically as 46, XY with the ultrasonographic impression as small uterus with no ovaries. Nineteen cases who with ambiguous genitalia showed the chromosomal pattern as 46, XX one out of these cases showed enlargement of the breast, and on examination of external genitalia found enlarged clitoris with labiamajora and minora. The child was brought up as male. Genitogram showed the absence of uterus. Conclusions: Chromosomal studies with ultrasonography can help in rearing a child male or female in young generation by surgical and Hormonal therapy. This prevents many problems in later life. This fact should be advertised openly in the public so that illiterate people should be alert. [Int J Res Med Sci 2015; 3(12.000: 3743-3748

  15. Transverse mode coupling instability for leptons in the CERN SPS

    Energy Technology Data Exchange (ETDEWEB)

    Linnecar, T.; Shaposhnikova, E.N. [European Organization for Nuclear Research, Geneva (Switzerland)

    1996-08-01

    The intensity of leptons accelerated in the SPS machine is limited by a vertical transverse instability. The results of measurements of the thresholds for this transverse instability are compared with theoretical predictions for different broad band impedance models of the SPS. The threshold intensities found for the transverse instability and the position of the losses in the cycle enable the parameters of the broadband resonant impedance to be specified. (author)

  16. Large Eddy Simulation of thermoacoustic instabilities in annular combustion chambers

    OpenAIRE

    Wolf, Pierre

    2011-01-01

    Increasingly stringent regulations and the need to tackle rising fuel prices have placed great emphasis on the design of aeronautical gas turbines. This drive towards innovation has resulted sometimes in new concepts being prone to combustion instabilities. Combustion instabilities arise from the coupling of acoustics and combustion. In the particular field of annular combustion chambers, these instabilities often take the form of azimuthal modes. To predict these modes, one must consider the...

  17. Instability conditions for circulatory and gyroscopic conservative systems

    CERN Document Server

    Birtea, Petre; Comanescu, Dan

    2011-01-01

    We give a method which generates sufficient conditions for instability of equilibria for circulatory and gyroscopic conservative systems. The method is based on the Gramians of a set of vectors whose coordinates are powers of the roots of the characteristic polynomial for the studied systems. New instability results are obtained for general circulatory and gyroscopic conservative systems. We also apply this method for studying the instability of motion for a charged particle in a stationary electromagnetic field.

  18. Sheet Beam Klystron Instability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bane, K.L.F.; Jensen, A.; Li, Z.; Stupakov, G.; Adolphsen, C.; /SLAC

    2009-05-08

    Using the principle of energy balance we develop a 2D theory for calculating growth rates of instability in a two-cavity model of a sheet beam klystron. An important ingredient is a TE-like mode in the gap that also gives a longitudinal kick to the beam. When compared with a self-consistent particle-in-cell calculation, with sheet beam klystron-type parameters, agreement is quite good up to half the design current, 65 A; at full current, however, other, current-dependent effects come in and the results deviate significantly.

  19. Model selection emphasises the importance of non-chromosomal information in genetic studies.

    Directory of Open Access Journals (Sweden)

    Reda Rawi

    Full Text Available Ever since the case of the missing heritability was highlighted some years ago, scientists have been investigating various possible explanations for the issue. However, none of these explanations include non-chromosomal genetic information. Here we describe explicitly how chromosomal and non-chromosomal modifiers collectively influence the heritability of a trait, in this case, the growth rate of yeast. Our results show that the non-chromosomal contribution can be large, adding another dimension to the estimation of heritability. We also discovered, combining the strength of LASSO with model selection, that the interaction of chromosomal and non-chromosomal information is essential in describing phenotypes.

  20. Genomic instability. New insight into the health effects of radiation

    International Nuclear Information System (INIS)

    New research findings question the validity of some traditionally accepted theories in radiobiology. It has been discovered that new chromosome damage and gene mutations, as well as cell death, occur frequently in the descendants of cells that have survived radiation exposure. These late effects of radiation cannot be explained using the previous model, because the phenomena occur much more often than direct mutations among individual genes. It has commonly been thought that the mutagenic and carcinogenic effects of radiation result from radiation-derived damage to DNA. During the division of DNA, or as a consequence of faulty correction, the damage becomes permanent and is transferred to the next cell generations (cloning). It has been assumed that the changes occur in cell divisions that take place immediately after the exposure to radiation. The new observations concerning genomic instability force researchers to reconsider the correctness of their theories and to seek new explanations of old, sometimes even 'odd' observations. They also give reason to exercise caution when making generalizations about epidemiological data and risk estimates form one population to another, or from one type of radiation to another. (orig.)