Sample records for chromosomal instability

  1. Chromosomal instability in meningiomas. (United States)

    van Tilborg, Angela A G; Al Allak, Bushra; Velthuizen, Sandra C J M; de Vries, Annie; Kros, Johan M; Avezaat, Cees J J; de Klein, Annelies; Beverloo, H Berna; Zwarthoff, Ellen C


    Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumor suppressor gene on chromosome 22. No causative gene is known for the remaining 40%. Cytogenetic analysis shows that meningiomas caused by inactivation of the NF2 gene can be divided into tumors that show monosomy 22 as the sole abnormality and tumors with a more complex karyotype. Meningiomas not caused by the NF2 gene usually have a diploid karyotype. Here we report that, besides the clonal chromosomal aberrations, the chromosome numbers in many meningiomas varied from one metaphase spread to the other, a feature that is indicative of chromosomal instability. Unexpectedly and regardless of genotype, a subgroup of tumors was observed with an average number of 44.9 chromosomes and little variation in the number of chromosomes per metaphase spread. In addition, a second subgroup was recognized with a hyperdiploid number of chromosomes (average 48.5) and considerable variation in numbers per metaphase. However, this numerical instability resulted in a clonal karyotype with chromosomal gains and losses in addition to loss of chromosome 22 only in meningiomas caused by inactivation of the NF2 gene. In cultured cells of all tumor groups, bi- and multinucleated cells were seen, as well as anaphase bridges, residual chromatid strings, multiple spindle poles, and unseparated chromatids, suggesting defects in the mitotic apparatus or kinetochore. Thus, we conclude that even a benign and slow-growing tumor like a meningioma displays chromosomal instability.

  2. Telomere dysfunction and chromosome instability

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


    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

  3. Chromosomal instability determines taxane response

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


    -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...... 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...... 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....

  4. GSK-3 inhibitors induce chromosome instability

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    Staples Oliver D


    Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.

  5. APC and chromosome instability in colorectal cancer

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    C. M. Cabrera

    Full Text Available Colon cancer is a common disease that can be sporadic or familial. An inactivated adenomatous polyposis coli (APC suppressor gene is found in over 80% of colorectal tumors, this being an early alteration in the development of adenomatous polyps. APC function is not only critical for tumor initiation and progression, and chromosome instability (CIN is another characteristic dependent at least partly on APC mutations.

  6. Chromosomal Instability Confers Intrinsic Multidrug Resistance

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


    their diploid parental cells only with increasing chromosomal heterogeneity and isogenic cell line models of CIN+ displayed multidrug resistance relative to their CIN- parental cancer cell line derivatives. In a meta-analysis of CRC outcome following cytotoxic treatment, CIN+ predicted worse 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(5); 1858-70. (c......Aneuploidy is associated with poor prognosis in solid tumors. Spontaneous chromosome missegregation events in aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance in vitro and heighten risk for tumor relapse in animal models...

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

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    Wen Ying


    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

  8. Chromosomal instability in the lymphocytes of breast cancer patients

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    Harsimran Kaur


    Full Text Available Genomic instability in the tumor tissue has been correlated with tumor progression. In the present study, chromosomal aberrations (CAs in peripheral blood lymphocytes (PBLs of breast tumor patients were studied to assess whether chromosomal instability (CIN in PBLs correlates with aggressiveness of breast tumor (i.e., disease stage and has any prognostic utility. Cultured blood lymphocyte metaphases were scored for aberrations in 31 breast cancer patients and 20 healthy age and sex-matched controls. A variety of CAs, including aneuploidy, polyploidy, terminal deletions, acentric fragments, double minutes, chromatid separations, ring chromosome, marker chromosome, chromatid gaps, and breaks were seen in PBLs of the patients. The CAs in patients were higher than in controls. A comparison of the frequency of metaphases with aberrations by grouping the patients according to the stage of advancement of disease did not reveal any consistent pattern of variation in lymphocytic CIN. Neither was any specific chromosomal abnormality found to be associated with the stage of cancer. This might be indicative of the fact that cancer patients have constitutional CIN, which predisposes them to the disease, and this inherent difference in the level of genomic instability might play a role in disease progression and response to treatment.

  9. VHL loss causes spindle misorientation and chromosome instability. (United States)

    Thoma, Claudio R; Toso, Alberto; Gutbrodt, Katrin L; Reggi, Sabina P; Frew, Ian J; Schraml, Peter; Hergovich, Alexander; Moch, Holger; Meraldi, Patrick; Krek, Wilhelm


    Error-free mitosis depends on fidelity-monitoring checkpoint systems that ensure correct temporal and spatial coordination of chromosome segregation by the microtubule spindle apparatus. Defects in these checkpoint systems can lead to genomic instability, an important aspect of tumorigenesis. Here we show that the von Hippel-Lindau (VHL) tumour suppressor protein, pVHL, which is inactivated in hereditary and sporadic forms of renal cell carcinoma, localizes to the mitotic spindle in mammalian cells and its functional inactivation provokes spindle misorientation, spindle checkpoint weakening and chromosomal instability. Spindle misorientation is linked to unstable astral microtubules and is supressed by the restoration of wild-type pVHL in pVHL-deficient cells, but not in naturally-occurring VHL disease mutants that are defective in microtubule stabilization. Impaired spindle checkpoint function and chromosomal instability are the result of reduced Mad2 (mitotic arrest deficient 2) levels actuated by pVHL-inactivation and are rescued by re-expression of either Mad2 or pVHL in VHL-defective cells. An association between VHL inactivation, reduced Mad2 levels and increased aneuploidy was also found in human renal cancer, implying that the newly identified functions of pVHL in promoting proper spindle orientation and chromosomal stability probably contribute to tumour suppression.

  10. Mechanisms of telomere loss and their consequences for chromosome instability

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    Keiko eMuraki


    Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

  11. Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution. (United States)

    Bakhoum, Samuel F; Landau, Dan Avi


    Large-scale, massively parallel sequencing of human cancer samples has revealed tremendous genetic heterogeneity within individual tumors. Indeed, tumors are composed of an admixture of diverse subpopulations-subclones-that vary in space and time. Here, we discuss a principal driver of clonal diversification in cancer known as chromosomal instability (CIN), which complements other modes of genetic diversification creating the multilayered genomic instability often seen in human cancer. Cancer cells have evolved to fine-tune chromosome missegregation rates to balance the acquisition of heterogeneity while preserving favorable genotypes, a dependence that can be exploited for a therapeutic benefit. We discuss how whole-genome doubling events accelerate clonal evolution in a subset of tumors by providing a viable path toward favorable near-triploid karyotypes and present evidence for CIN-induced clonal speciation that can overcome the dependence on truncal initiating events.

  12. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

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    Scott F. Lindsey


    Full Text Available Melanomas demonstrate chromosomal instability (CIN. In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells “meiomitosis” could impact chromosomal instability in melanoma and other cancers.

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

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


    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......Chromosomal instability (CIN) is associated with poor prognosis in human cancer. However, in certain animal tumor models elevated CIN negatively impacts upon organism fitness, and is poorly tolerated by cancer cells. To better understand this seemingly contradictory relationship between CIN...

  14. Affected chromosome homeostasis and genomic instability of clonal yeast cultures. (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Panek, Anita; Golec, Ewelina; Lewinska, Anna; Wnuk, Maciej


    Yeast cells originating from one single colony are considered genotypically and phenotypically identical. However, taking into account the cellular heterogeneity, it seems also important to monitor cell-to-cell variations within a clone population. In the present study, a comprehensive yeast karyotype screening was conducted using single chromosome comet assay. Chromosome-dependent and mutation-dependent changes in DNA (DNA with breaks or with abnormal replication intermediates) were studied using both single-gene deletion haploid mutants (bub1, bub2, mad1, tel1, rad1 and tor1) and diploid cells lacking one active gene of interest, namely BUB1/bub1, BUB2/bub2, MAD1/mad1, TEL1/tel1, RAD1/rad1 and TOR1/tor1 involved in the control of cell cycle progression, DNA repair and the regulation of longevity. Increased chromosome fragility and replication stress-mediated chromosome abnormalities were correlated with elevated incidence of genomic instability, namely aneuploid events-disomies, monosomies and to a lesser extent trisomies as judged by in situ comparative genomic hybridization (CGH). The tor1 longevity mutant with relatively balanced chromosome homeostasis was found the most genomically stable among analyzed mutants. During clonal yeast culture, spontaneously formed abnormal chromosome structures may stimulate changes in the ploidy state and, in turn, promote genomic heterogeneity. These alterations may be more accented in selected mutated genetic backgrounds, namely in yeast cells deficient in proper cell cycle regulation and DNA repair.

  15. Non-meiotic chromosome instability in human immature oocytes. (United States)

    Daina, Gemma; Ramos, Laia; Rius, Mariona; Obradors, Albert; Del Rey, Javier; Giralt, Magda; Campillo, Mercedes; Velilla, Esther; Pujol, Aïda; Martinez-Pasarell, Olga; Benet, Jordi; Navarro, Joaquima


    Aneuploidy has been a major issue in human gametes and is closely related to fertility problems, as it is known to be present in cleavage stage embryos and gestational losses. Pre-meiotic chromosome abnormalities in women have been previously described. The aim of this study is to assess the whole-chromosome complement in immature oocytes to find those abnormalities caused by mitotic instability. For this purpose, a total of 157 oocytes at the germinal vesicle or metaphase I stage, and discarded from IVF cycles, were analysed by CGH. Fifty-six women, between 18 and 45 years old (mean 32.5 years), including 32 IVF patients (25-45 years of age) and 24 IVF oocyte donors (18-33 years of age), were included in the study. A total of 25/157 (15.9%) of the oocytes analysed, obtained from three IVF clinics, contained chromosome abnormalities, including both aneuploidy (24/157) and structural aberrations (9/157). Independently of the maternal age, the incidence of abnormal oocytes which originated before meiosis is 15.9%, and these imbalances were found in 33.9% of the females studied. This work sheds light on the relevance of mitotic instability responsible for the generation of the abnormalities present in human oocytes.

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

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    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.

  17. The TP53 dependence of radiation-induced chromosome instability in human lymphoblastoid cells (United States)

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


    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.

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

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    Bijan Fouladi


    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. Hypo-methylation mediates chromosomal instability in pancreatic NET. (United States)

    Marinoni, I; Wiederkeher, A; Wiedmer, T; Pantasis, S; Di Domenico, A; Frank, R; Vassella, E; Schmitt, A; Perren, A


    DAXX and or ATRX loss occur in 40% of pancreatic neuroendocrine tumors (PanNETs). PanNETs negative for DAXX or ATRX show an increased risk of relapse. The tumor-associated pathways activated upon DAXX or ATRX loss and how this event may induce chromosomal instability (CIN) and alternative lengthening telomeres (ALT) are still unknown. Both DAXX and ATRX are involved in DNA methylation regulation. DNA methylation of heterochromatin and of non-coding sequences is extremely important for the maintenance of genomic stability. We analyzed the association of DAXX and/or ATRX loss and CIN with global DNA methylation in human PanNET samples and the effect of DAXX knock-down on methylation and cell proliferation. We assessed LINE1 as well as global DNA methylation in 167 PanNETs, and we found that DAXX and or ATRX-negative tumors and tumors with CIN were hypomethylated. DAXX knock-down in PanNET cell lines blocked cells in G1/G0 phase and seemed to increase CIN in QGP-1 cells. However, no direct changes in DNA methylation were observed after DAXX knock-down in vitro In conclusion, our data indicate that epigenetic changes are crucial steps in the progression of PanNETs loss and suggest that DNA methylation is the mechanism via which CIN is induced, allowing clonal expansion and selection.

  20. 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: [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)


    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.

  1. 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.

  2. Chromosomal instability in near-diploid colorectal cancer: a link between numbers and structure.

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    Martine Muleris

    Full Text Available Chromosomal instability (CIN plays a crucial role in tumor development and occurs mainly as the consequence of either missegregation of normal chromosomes (MSG or structural rearrangement (SR. However, little is known about the respective chromosomal targets of MSG and SR and the way these processes combined within tumors to generate CIN. To address these questions, we karyotyped a consecutive series of 96 near-diploid colorectal cancers (CRCs and distinguished chromosomal changes generated by either MSG or SR in tumor cells. Eighty-three tumors (86% presented with chromosomal abnormalities that contained both MSGs and SRs to varying degrees whereas all 13 others (14% showed normal karyotype. Using a maximum likelihood statistical method, chromosomes affected by MSG or SR and likely to represent changes that are selected for during tumor progression were found to be different and mostly mutually exclusive. MSGs and SRs were not randomly associated within tumors, delineating two major pathways of chromosome alterations that consisted of either chromosome gains by MSG or chromosomal losses by both MSG and SR. CRCs showing microsatellite instability (MSI presented with either normal karyotype or chromosome gains whereas MSS (microsatellite stable CRCs exhibited a combination of the two pathways. Taken together, these data provide new insights into the respective involvement of MSG and SR in near-diploid colorectal cancers, showing how these processes target distinct portions of the genome and result in specific patterns of chromosomal changes according to MSI status.

  3. The evolution of chromosomal instability in Chinese hamster cells: a changing picture? (United States)

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


    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.

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

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    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.

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

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    Hong Wei Yang


    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.

  6. 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.;


    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...... 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, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows...... chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early-stage disease in two independent cohorts in multivariate analyses...

  7. The X chromosome: does it have a role in Bloom syndrome, a genomic instability disorder? (United States)

    Aslan, Deniz


    The Bloom syndrome, caused by mutations in a single gene [BLM (15q26.1)], is a rare genomic instability syndrome. Despite its autosomal recessive transmission, it shows a male dominance, suggesting the possibility of a subgroup with X-linked recessive inheritance. In view of the latest molecular developments achieved in the other genomic instability syndromes, the potential functions of the X chromosome in maintaining genomic stability, and particularly, the first clues of Bloom syndrome development by mechanisms other than the BLM, we suggest herein that the X chromosome should be investigated in Bloom syndrome.

  8. A substantial proportion of microsatellite-unstable colon tumors carry TP53 mutations while not showing chromosomal instability

    NARCIS (Netherlands)

    Westra, JL; Boven, LG; van der Wes, P; Faber, H; Sikkema, B; Schaapveld, M; Dijkhuizen, T; Hollema, H; Buys, CHCM; Plukker, JTM; Kok, K; Hofstra, RMW


    Chromosomal instability in colon tumors implies the presence of numerical and structural chromosome aberrations and is further characterized by the absence of microsatellite instability and the occurrence of KRAS and/or TP53 mutations. In a previous screening of 194 colon tumors for both microsatell

  9. Centrosome dynamics as a source of chromosomal instability

    NARCIS (Netherlands)

    Nam, H.J.; Naylor, R.M.; Deursen, J.M.A. van


    Accurate segregation of duplicated chromosomes between two daughter cells depends on bipolar spindle formation, a metaphase state in which sister kinetochores are attached to microtubules emanating from opposite spindle poles. To ensure bi-orientation, cells possess surveillance systems that safegua

  10. Chromosome instability predicts progression of premalignant lesions of the larynx

    NARCIS (Netherlands)

    Bergshoeff, Verona E.; Van der Heijden, Stijn J. A.; Haesevoets, Annick; Litjens, Sophie G. H.; Bot, Fredrik J.; Voogd, Adri C.; Chenault, Michelene N.; Hopman, Anton H. N.; Schuuring, Ed; van der Wal, Jacqueline M.; Manni, Johannes J.; Ramaekers, Frans C. S.; Kremer, Bernd; Speel, Ernst-Jan M.


    The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice.Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and

  11. Very CIN-ful: whole chromosome instability promotes tumor suppressor loss of heterozygosity. (United States)

    Sotillo, Rocio; Schvartzman, Juan-Manuel; Benezra, Robert


    Mechanisms by which whole chromosome instability lead to tumorigenesis have eluded the cancer research field. In this issue of Cancer Cell, Baker et al. show that CIN induced by a defective mitotic checkpoint, under certain genetic and tissue contexts, leads to accelerated loss of heterozygosity of a tumor suppressor gene.

  12. Centrosome dynamics as a source of chromosomal instability. (United States)

    Nam, Hyun-Ja; Naylor, Ryan M; van Deursen, Jan M


    Accurate segregation of duplicated chromosomes between two daughter cells depends on bipolar spindle formation, a metaphase state in which sister kinetochores are attached to microtubules emanating from opposite spindle poles. To ensure bi-orientation, cells possess surveillance systems that safeguard against microtubule-kinetochore attachment defects, including the spindle assembly checkpoint and the error correction machinery. However, recent developments have identified centrosome dynamics--that is, centrosome disjunction and poleward movement of duplicated centrosomes--as a central target for deregulation of bi-orientation in cancer cells. In this review, we discuss novel insights into the mechanisms that underlie centrosome dynamics and discuss how these mechanisms are perturbed in cancer cells to drive chromosome mis-segregation and advance neoplastic transformation.

  13. Loss of pRB causes centromere dysfunction and chromosomal instability. (United States)

    Manning, Amity L; Longworth, Michelle S; Dyson, Nicholas J


    Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.

  14. 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


    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.

  15. TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines (United States)

    Schwartz, J. L.; Jordan, R.; Liber, H.; Murnane, J. P.; Evans, H. H.


    Telomere shortening in telomerase-negative somatic cells leads to the activation of the TP53 protein and the elimination of potentially unstable cells. We examined the effect of TP53 gene expression on both telomere metabolism and chromosome stability in immortal, telomerase-positive cell lines. Telomere length, telomerase activity, and chromosome instability were measured in multiple clones isolated from three related human B-lymphoblast cell lines that vary in TP53 expression; TK6 cells express wild-type TP53, WTK1 cells overexpress a mutant form of TP53, and NH32 cells express no TP53 protein. Clonal variations in both telomere length and chromosome stability were observed, and shorter telomeres were associated with higher levels of chromosome instability. The shortest telomeres were found in WTK1- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability. The primary marker of instability was the presence of dicentric chromosomes. Aneuploidy and other stable chromosome alterations were also found in clones showing high levels of dicentrics. Polyploidy was found only in WTK1-derived cells. Both telomere length and chromosome instability fluctuated in the different cell populations with time in culture, presumably as unstable cells and cells with short telomeres were eliminated from the growing population. Our results suggest that transient reductions in telomere lengths may be common in immortal cell lines and that these alterations in telomere metabolism can have a profound effect on chromosome stability. Copyright 2000 Wiley-Liss, Inc.

  16. Chromosome instability and oxidative stress markers in patients with ataxia telangiectasia and their parents. (United States)

    Ludwig, Luciane Bitelo; Valiati, Victor Hugo; Palazzo, Roberta Passos; Jardim, Laura Bannach; da Rosa, Darlan Pase; Bona, Silvia; Rodrigues, Graziela; Marroni, Norma Possa; Prá, Daniel; Maluf, Sharbel Weidner


    Ataxia telangiectasia (AT) is a rare neurodegenerative disorder, inherited in an autosomal recessive manner. Total blood samples were collected from 20 patients with AT, 13 parents of patients, and 17 healthy volunteers. This study aimed at evaluating the frequency of chromosomal breaks in spontaneous cultures, induced by bleomycin and ionizing radiation, and further evaluated the rates of oxidative stress in AT patients and in their parents, compared to a control group. Three cell cultures were performed to each individual: the first culture did not receive induction to chromosomal instability, the second was exposed to bleomycin, and the last culture was exposed to ionizing radiation. To evaluate the rates of oxidative stress, the markers superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid (TBARS) were utilized. Significant differences were observed between the three kinds of culture treatments (spontaneous, bleomycin, and radiation induced) and the breaks and chromosomal aberrations in the different groups. The oxidative stress showed no significant differences between the markers. This study showed that techniques of chromosomal instability after the induction of ionizing radiation and bleomycin are efficient in the identification of syndrome patients, with the ionizing radiation being the most effective.

  17. Targeting Chromosomal Instability and Tumour Heterogeneity in HER2-Positive Breast Cancer

    DEFF Research Database (Denmark)

    Burrell, Rebecca A.; Birkbak, Nicolai Juul; Johnston, Stephen R.;


    Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population. In this article we consider evidence suggesting that CIN may be targeted and may influence...... response to distinct chemotherapy regimens, using HER2-positive breast cancer as an example. Pre-clinical models have indicated a role for HER2 signalling in initiating CIN and defective cell-cycle control, and evidence suggests that HER2-targeting may attenuate this process. Anthracyclines and platinum...... agents may target tumours with distinct patterns of karyotypic complexity, whereas taxanes may have preferential activity in tumours with relative chromosomal stability. A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel...

  18. 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


    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

  19. Chromosomal and Extrachromosomal Instability of the cyclin D2 Gene is Induced by Myc Overexpression

    Directory of Open Access Journals (Sweden)

    Sabine Mai


    Full Text Available We examined the expression of cyclins D1, D2, D3, and E in mouse B-lymphocytic tumors. Cyclin D2 mRNA was consistently elevated in plasmacytomas, which characteristically contain Myc-activating chromosome translocations and constitutive c-Myc mRNA and protein expression. We examined the nature of cyclin D2 overexpression in plasmacytomas and other tumors. Human and mouse tumor cell lines that exhibited c-Myc dysregulation displayed instability of the cyclin D2 gene, detected by Southern blot, fluorescent in situ hybridization (FISH, and in extrachromosomal preparations (Hirt extracts. Cyclin D2 instability was not seen in cells with low levels of c-Myc protein. To unequivocally demonstrate a role of c-Myc in the instability of the cyclin D2 gene, a Myc-estrogen receptor chimera was activated in two mouse cell lines. After 3 to 4 days of Myc-ERTm activation, instability at the cyclin D2 locus was seen in the form of extrachromosomal elements, determined by FISH of metaphase and interphase nuclei and of purified extrachromosomal elements. At the same time points, Northern and Western blot analyses detected increased cyclin D2 mRNA and protein levels. These data suggest that Myc-induced genomic instability may contribute to neoplasia by increasing the levels of a cell cycle—regulating protein, cyclin D2, via intrachromosomal amplification of its gene or generation of extrachromosomal copies.

  20. Role of ATRX in chromatin structure and function: implications for chromosome instability and human disease. (United States)

    De La Fuente, Rabindranath; Baumann, Claudia; Viveiros, Maria M


    Functional differentiation of chromatin structure is essential for the control of gene expression, nuclear architecture, and chromosome stability. Compelling evidence indicates that alterations in chromatin remodeling proteins play an important role in the pathogenesis of human disease. Among these, α-thalassemia mental retardation X-linked protein (ATRX) has recently emerged as a critical factor involved in heterochromatin formation at mammalian centromeres and telomeres as well as facultative heterochromatin on the murine inactive X chromosome. Mutations in human ATRX result in an X-linked neurodevelopmental condition with various degrees of gonadal dysgenesis (ATRX syndrome). Patients with ATRX syndrome may exhibit skewed X chromosome inactivation (XCI) patterns, and ATRX-deficient mice exhibit abnormal imprinted XCI in the trophoblast cell line. Non-random or skewed XCI can potentially affect both the onset and severity of X-linked disease. Notably, failure to establish epigenetic modifications associated with the inactive X chromosome (Xi) results in several conditions that exhibit genomic and chromosome instability such as fragile X syndrome as well as cancer development. Insight into the molecular mechanisms of ATRX function and its interacting partners in different tissues will no doubt contribute to our understanding of the pathogenesis of ATRX syndrome as well as the epigenetic origins of aneuploidy. In turn, this knowledge will be essential for the identification of novel drug targets and diagnostic tools for cancer progression as well as the therapeutic management of global epigenetic changes commonly associated with malignant neoplastic transformation.

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

    Directory of Open Access Journals (Sweden)

    Gilson S. Baia


    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.

  2. 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.


    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......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...

  3. Peculiarities of induction and persistence of hidden chromosome instability in peripheral blood lymphocytes of persons occupationally exposed to ionizing radiation. (United States)

    Pilinska, M A; Dybsky, S S; Dybska, O B; Shvayko, L I; Sushko, V O


    Objective - to investigate the induction of hidden chromosome instability in persons occupationally exposed to ionizing radiation and its persistence in vitro in successive mitoses. Materials and methods. Using two tests ("G2-bleomycin sensitivity assay" and two-term cultivation of human peripheral blood lymphocytes) voluntary cytogenetic examination of 15 individuals participated in the conversion of the "Shelter" ("Chornobyl NPP") into ecologically safe system had been carried out. Total 24 034 metaphase had been analyzed, of which 12 243 - without additional mutagenic exposure, 11 791 - exposed to bleomycin in vitro at concentration of 0.05 μg/ml. Results. The magnitude and dynamics of background as well as bleomycin-induced cytogenetic effects in both terms of lymphocytes' cultivation in occupational group differed significantly from the group of comparison towards increasing of chromosome instability indices with significant interindividual fluctuations. Conclusion. Interindividual differences in persistence of radiation-induced hidden chromosome instability in successive generations of human somatic cells had been found.

  4. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis (United States)

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


    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  5. Chromosomal instability in mouse embryonic fibroblasts null for the transcriptional co-repressor Ski. (United States)

    Marcelain, Katherine; Armisen, Ricardo; Aguirre, Adam; Ueki, Nobuhide; Toro, Jessica; Colmenares, Clemencia; Hayman, Michael J


    Ski is a transcriptional regulator that has been considered an oncoprotein given its ability to induce oncogenic transformation in avian model systems. However, studies in mouse and in some human tumor cells have also indicated a tumor suppressor activity for this protein. We found that Ski-/- mouse embryo fibroblasts exhibit high levels of genome instability, namely aneuploidy, consistent with a tumor suppressor function for Ski. Time-lapse microscopy revealed lagging chromosomes and chromatin/chromosome bridges as the major cause of micronuclei (MN) formation and the subsequent aneuploidy. Although these cells arrested in mitosis after treatment with spindle disrupting drugs and exhibited a delayed metaphase/anaphase transition, spindle assembly checkpoint (SAC) was not sufficient to prevent chromosome missegregation, consistent with a weakened SAC. Our in vivo analysis also showed dynamic metaphase plate rearrangements with switches in polarity in cells arrested in metaphase. Importantly, after ectopic expression of Ski the cells that displayed this metaphase arrest died directly during metaphase or after aberrant cell division, relating SAC activation and mitotic cell death. This increased susceptibility to undergo mitosis-associated cell death reduced the number of MN-containing cells. The presented data support a new role for Ski in the mitotic process and in maintenance of genetic stability, providing insights into the mechanism of tumor suppression mediated by this protein.

  6. 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:


    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

  7. Centrosome Dysfunction Contributes To Chromosome Instability, Chromoanagenesis And Genome Reprograming In Cancer.

    Directory of Open Access Journals (Sweden)

    German A Pihan


    Full Text Available The unique ability of centrosomes to nucleate and organize microtubules makes them unrivaled conductors of important interphase processes, such as intracellular payload traffic, cell polarity, cell locomotion, and organization of the immunologic synapse. But it is in mitosis that centrosomes loom large, for they orchestrate, with clockmaker’s precision, the assembly and functioning of the mitotic spindle, ensuring the equal partitioning of the replicated genome into daughter cells. Centrosome dysfunction is inextricably linked to aneuploidy and chromosome instability, both hallmarks of cancer cells. Several aspects of centrosome function in normal and cancer cells have been molecularly characterized during the last two decades, greatly enhancing our mechanistic understanding of this tiny organelle. Whether centrosome defects alone can cause cancer, remains unanswered. Until recently, the aggregate of the evidence had suggested that centrosome dysfunction, by deregulating the fidelity of chromosome segregation, promotes and accelerates the characteristic Darwinian evolution of the cancer genome enabled by increased mutational load and/or decreased DNA repair. Very recent experimental work has shown that missegreated chromosomes resulting from centrosome dysfunction may experience extensive DNA damage, suggesting additional dimensions to the role of centrosomes in cancer. Centrosome dysfunction is particularly prevalent in tumors in which the genome has undergone extensive structural rearrangements and chromosome domain reshuffling. Ongoing gene reshuffling reprograms the genome for continuous growth, survival, and evasion of the immune system. Manipulation of molecular networks controlling centrosome function may soon become a viable target for specific therapeutic intervention in cancer, particularly since normal cells, which lack centrosome alterations, may be spared the toxicity of such therapies.

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

    KAUST Repository

    Kashuba, Elena


    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.

  9. Whole chromosome instability resulting from the synergistic effects of pRB and p53 inactivation. (United States)

    Manning, A L; Benes, C; Dyson, N J


    Whole chromosome instability (CIN) is a common feature of cancer cells and has been linked to increased tumor evolution and metastasis. Several studies have shown that the loss of the pRB tumor suppressor causes mitotic defects and chromosome mis-segregation. pRB is inactivated in many types of cancer and this raises the possibility that the loss of pRB may be a general cause of CIN in tumors. Paradoxically, retinoblastoma tumor cells have a relatively stable karyotype and currently the circumstances in which pRB inactivation causes CIN in human cancers are unclear. Here we utilize a fluorescence in situ hybridization-based approach to score numerical heterogeneity in chromosome copy number as a readout of CIN. Using this technique, we show that high levels of CIN correlate with the combined inactivation of pRB and p53 and that this association is evident in two independent panels of cancer cell lines. Retinoblastoma cell lines characteristically retain a wild-type TP53 gene, providing an opportunity to test the relevance of this functional relationship. We show that retinoblastoma cell lines display mitotic defects similar to those seen when pRB is depleted from non-transformed cells, but that the presence of wild-type p53 suppresses the accumulation of aneuploid cells. A similar synergy between pRB and p53 inactivation was observed in HCT116 cells. These results suggest that the loss of pRB promotes segregation errors, whereas loss of p53 allows tolerance and continued proliferation of the resulting, genomically unstable cancer cells. Hence, it is the cooperative effect of inactivation of both pRB and p53 tumor suppressor pathways that promotes CIN.

  10. Chromosomal Instability, Aneuploidy, and Gene Mutations in Human Sporadic Colorectal Adenomas

    Directory of Open Access Journals (Sweden)

    Walter Giaretti


    Full Text Available Whether in vivo specific gene mutations lead to chromosomal instability (CIN and aneuploidy or viceversa is so far not proven. We hypothesized that aneuploidy among human sporadic colorectal adenomas and KRAS2 and APC mutations were not independent. Additionally, we investigated if 1p34–36 deletions by dual target FISH were associated with aneuploidy. Among 116 adenomas, 29 were DNA aneuploid by flow cytometry (25% and 29 were KRAS2 mutated (25%. KRAS2 mutations were associated with aneuploidy (P=0.02. However, while G–C and G–T transversions were strongly associated with DNA aneuploidy (P=0.007, G–A transitions were not. Within a second series of 61 adenomas, we found, instead, that APC mutational status and aneuploidy by flow cytometry were not associated. However, a statistically significant association was found with specific APC mutations, i.e., occurring in the mutation cluster region (MCR, codons 1200–1500 or downstream (P=0.016. Finally, the correlation of 1p34–36 deletions with flow cytometric and FISH detected aneuploidy was also significant (P=0.01. Specific KRAS2 and APC mutations and loss of genes in the 1p34–36 region appear associated with aneuploidy suggesting that these events are not independent and may cooperate in inducing human sporadic colorectal adenomas. A cause effect relationship between gene mutations and aneuploidy remains, however, to be demonstrated.

  11. Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

    Directory of Open Access Journals (Sweden)

    Federico Tommaso Bianchi


    Full Text Available Mutations in citron (CIT, leading to loss or inactivation of the citron kinase protein (CITK, cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display “spontaneous” DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development.

  12. Suppression of genome instability in pRB-deficient cells by enhancement of chromosome cohesion. (United States)

    Manning, Amity L; Yazinski, Stephanie A; Nicolay, Brandon; Bryll, Alysia; Zou, Lee; Dyson, Nicholas J


    Chromosome instability (CIN), a common feature of solid tumors, promotes tumor evolution and increases drug resistance during therapy. We previously demonstrated that loss of the retinoblastoma protein (pRB) tumor suppressor causes changes in centromere structure and generates CIN. However, the mechanism and significance of this change was unclear. Here, we show that defects in cohesion are key to the pRB loss phenotype. pRB loss alters H4K20 methylation, a prerequisite for efficient establishment of cohesion at centromeres. Changes in cohesin regulation are evident during S phase, where they compromise replication and increase DNA damage. Ultimately, such changes compromise mitotic fidelity following pRB loss. Remarkably, increasing cohesion suppressed all of these phenotypes and dramatically reduced CIN in cancer cells lacking functional pRB. These data explain how loss of pRB undermines genomic integrity. Given the frequent functional inactivation of pRB in cancer, conditions that increase cohesion may provide a general strategy to suppress CIN.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. The CIN4 chromosomal instability qPCR classifier defines tumor aneuploidy and stratifies outcome in grade 2 breast cancer

    DEFF Research Database (Denmark)

    Szász, Attila Marcell; Li, Qiyuan; Eklund, Aron Charles


    Purpose: Quantifying chromosomal instability (CIN) has both prognostic and predictive clinical utility in breast cancer. In order to establish a robust and clinically applicable gene expression-based measure of CIN, we assessed the ability of four qPCR quantified genes selected from the 70-gene...... Chromosomal Instability (CIN70) expression signature to stratify outcome in patients with grade 2 breast cancer. Methods: AURKA, FOXM1, TOP2A and TPX2 (CIN4), were selected from the CIN70 signature due to their high level of correlation with histological grade and mean CIN70 signature expression in silico. We...... assessed the ability of CIN4 to stratify outcome in an independent cohort of patients diagnosed between 1999 and 2002. 185 formalin-fixed, paraffin-embedded (FFPE) samples were included in the qPCR measurement of CIN4 expression. In parallel, ploidy status of tumors was assessed by flow cytometry. We...

  15. 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.

  16. Acquisition of high-level chromosomal instability is associated with integration of human papillomavirus type 16 in cervical keratinocytes. (United States)

    Pett, Mark R; Alazawi, William O F; Roberts, Ian; Dowen, Sally; Smith, David I; Stanley, Margaret A; Coleman, Nicholas


    Whereas two key steps in cervical carcinogenesis are integration of high-risk human papillomavirus (HR-HPV) and acquisition of an unstable host genome, the temporal association between these events is poorly understood. Chromosomal instability is induced when HR-HPV E7 oncoprotein is overexpressed from heterologous promoters in vitro. However, it is not known whether such events occur at the "physiologically" elevated levels of E7 produced by deregulation of the homologous HR-HPV promoter after integration. Indeed, an alternative possibility is that integration in vivo is favored in an already unstable host genome. We have addressed these issues using the unique human papillomavirus (HPV) 16-containing cervical keratinocyte cell line W12, which was derived from a low-grade squamous intraepithelial lesion and thus acquired HPV16 by "natural" infection. Whereas W12 at low passage contains HPV16 episomes only, long-term culture results in the emergence of cells containing integrated HPV16 only. We show that integration of HPV16 in W12 is associated with 3' deletion of the E2 transcriptional repressor, resulting in deregulation of the homologous promoter of the integrant and an increase in E7 protein levels. We further demonstrate that high-level chromosomal instability develops in W12 only after integration and that the forms of instability observed correlate with the physical state of HPV16 DNA and the level of E7 protein. Whereas intermediate E7 levels are associated with numerical chromosomal abnormalities, maximal levels are associated with both numerical and structural aberrations. HR-HPV integration is likely to be a critical event in cervical carcinogenesis, preceding the development of chromosomal abnormalities that drive malignant progression.

  17. 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


    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.

  18. 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;


    . 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...

  19. Chromosome (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  20. 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


    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 survival outcome. Results: There was increased CIN and clonal eterogeneity in ER-negative compared with ER-positive breast cancer. Consistent with a negative impact of CIN on cellular fitness, extreme CIN in ER-negative breast cancer was an independent variable associated with improved long-term survival......Background: Chromosomal instability (CIN) is thought to be associated with poor prognosis in solid tumors; however, evidence from preclinical and mouse tumor models suggest that CIN may paradoxically enhance or impair cancer cell fitness. Breast cancer prognostic expression signature sets, which...

  1. 3. Chromosomal instability in B-lymphoblasotoid cell lines from Werner's and Bloom's syndrome patients

    Institute of Scientific and Technical Information of China (English)


    @@Werner's syndrome (WS) and Bloom's syndrome (BS) are rare autosomal recessive diseases in which the feature of premature aging and the elevated risk of neoplasia may be associated with genomic instability. To cha-racterize the genomic instability of WS and BS, B-lymphoblastoid cell lines (LCLs) from WS and BS patients were cytogenetically analyzed, comparing to those from healthy donors. Although all

  2. DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat (United States)

    Blackwood, John K.; Okely, Ewa A.; Zahra, Rabaab; Eykelenboom, John K.; Leach, David R. F.


    Approximately half the human genome is composed of repetitive DNA sequences classified into microsatellites, minisatellites, tandem repeats, and dispersed repeats. These repetitive sequences have coevolved within the genome but little is known about their potential interactions. Trinucleotide repeats (TNRs) are a subclass of microsatellites that are implicated in human disease. Expansion of CAG·CTG TNRs is responsible for Huntington disease, myotonic dystrophy, and a number of spinocerebellar ataxias. In yeast DNA double-strand break (DSB) formation has been proposed to be associated with instability and chromosome fragility at these sites and replication fork reversal (RFR) to be involved either in promoting or in preventing instability. However, the molecular basis for chromosome fragility of repetitive DNA remains poorly understood. Here we show that a CAG·CTG TNR array stimulates instability at a 275-bp tandem repeat located 6.3 kb away on the Escherichia coli chromosome. Remarkably, this stimulation is independent of both DNA double-strand break repair (DSBR) and RFR but is dependent on a functional mismatch repair (MMR) system. Our results provide a demonstration, in a simple model system, that MMR at one type of repetitive DNA has the potential to influence the stability of another. Furthermore, the mechanism of this stimulation places a limit on the universality of DSBR or RFR models of instability and chromosome fragility at CAG·CTG TNR sequences. Instead, our data suggest that explanations of chromosome fragility should encompass the possibility of chromosome gaps formed during MMR. PMID:21149728

  3. 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


    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.

  4. Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, N.G.; Taalman, R.D.; Baan, C.


    Fibroblast cultures from six unrelated patients having a familial type of immunodeficiency combined with microcephaly, developmental delay, and chromosomal instability were studied with respect to their response to ionizing radiation. The cells from five of them resembled those from individuals with ataxia telangiectasia (AT) in that they were two to three times more radiosensitive on the basis of clonogenic cell survival. In addition, after exposure to either X-rays or bleomycin, they showed an inhibition of DNA replication that was less pronounced than that in normal cells and characteristic of AT fibroblasts. However, the patients are clinically very different from AT patients, not showing any signs of neurocutaneous symptoms. Genetic complementation studies in fused cells, with the radioresistant DNA synthesis used as a marker, showed that the patients' cells could complement representatives of all presently known AT complementation groups. Furthermore, they were shown to constitute a genetically heterogeneous group as well. It is concluded that these patients are similar to AT patients with respect to cytological parameters. The clinical differences between these patients and AT patients are a reflection of genetic heterogeneity. The data indicate that the patients suffer from a chromosome-instability syndrome that is distinct from AT.

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

    Directory of Open Access Journals (Sweden)

    Paraskeva Vladimirova Michailova


    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.

  6. Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth

    Directory of Open Access Journals (Sweden)

    Konstantina Rowald


    Full Text Available Chromosome instability (CIN is associated with poor survival and therapeutic outcome in a number of malignancies. Despite this correlation, CIN can also lead to growth disadvantages. Here, we show that simultaneous overexpression of the mitotic checkpoint protein Mad2 with KrasG12D or Her2 in mammary glands of adult mice results in mitotic checkpoint overactivation and a delay in tumor onset. Time-lapse imaging of organotypic cultures and pathologic analysis prior to tumor establishment reveals error-prone mitosis, mitotic arrest, and cell death. Nonetheless, Mad2 expression persists and increases karyotype complexity in Kras tumors. Faced with the selective pressure of oncogene withdrawal, Mad2-positive tumors have a higher frequency of developing persistent subclones that avoid remission and continue to grow.

  7. Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth. (United States)

    Rowald, Konstantina; Mantovan, Martina; Passos, Joana; Buccitelli, Christopher; Mardin, Balca R; Korbel, Jan O; Jechlinger, Martin; Sotillo, Rocio


    Chromosome instability (CIN) is associated with poor survival and therapeutic outcome in a number of malignancies. Despite this correlation, CIN can also lead to growth disadvantages. Here, we show that simultaneous overexpression of the mitotic checkpoint protein Mad2 with Kras(G12D) or Her2 in mammary glands of adult mice results in mitotic checkpoint overactivation and a delay in tumor onset. Time-lapse imaging of organotypic cultures and pathologic analysis prior to tumor establishment reveals error-prone mitosis, mitotic arrest, and cell death. Nonetheless, Mad2 expression persists and increases karyotype complexity in Kras tumors. Faced with the selective pressure of oncogene withdrawal, Mad2-positive tumors have a higher frequency of developing persistent subclones that avoid remission and continue to grow.

  8. Chromosomal instability and telomere shortening in long-term culture of hematopoietic stem cells: insights from a cell culture model of RPS14 haploinsufficiency. (United States)

    Thomay, K; Schienke, A; Vajen, B; Modlich, U; Schambach, A; Hofmann, W; Schlegelberger, B; Göhring, G


    The fate of cultivated primary hematopoietic stem cells (HSCs) with respect to genetic instability and telomere attrition has not yet been described in great detail. Thus, knowledge of the genetic constitution of HSCs is important when interpreting results of HSCs in culture. While establishing a cell culture model for myelodysplastic syndrome with a deletion in 5q by performing RPS14 knockdown, we found surprising data that may be of importance for any CD34+ cell culture experiments. We performed cytogenetic analyses and telomere length measurement on transduced CD34+ cells and untransduced control cells to observe the effects of long-term culturing. Initially, CD34+ cells had a normal median telomere length of about 12 kb and showed no signs of chromosomal instability. During follow-up, the median telomere length seemed to decrease and, simultaneously, increased chromosomal instability could be observed - in modified and control cells. One culture showed a clonal monosomy 7 - independent of prior RPS14 knockdown. During further culturing, it seemed that the telomeres re-elongated, and chromosomes stabilized, while TERT expression was not elevated. In summary, irrespective of our results of RPS14 knockdown in the long-term culture of CD34+ cells, it becomes clear that cell culture artefacts inducing telomere shortening and chromosomal instability have to be taken into account and regular cytogenetic analyses should always be performed.

  9. Misregulation of Scm3p/HJURP Causes Chromosome Instability in Saccharomyces cerevisiae and Human Cells


    Prashant K. Mishra; Wei-Chun Au; John S. Choy; P Henning Kuich; Baker, Richard E.; Foltz, Daniel R.; Basrai, Munira A.


    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 relevanc...

  10. Recurrent RECQL4 Imbalance and Increased Gene Expression Levels Are Associated with Structural Chromosomal Instability in Sporadic Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Georges Maire


    Full Text Available Osteosarcoma (OS is an aggressive bone tumor with complex abnormal karyotypes and a highly unstable genome, exhibiting both numerical- and structural-chromosomal instability (N- and S-CIN. Chromosomal rearrangements and genomic imbalances affecting 8q24 are frequent in OS. RECQL4 gene maps to this cytoband and encodes a putative helicase involved in the fidelity of DNA replication and repair. This protective genomic function of the protein is relevant because often patients with Rothmund-Thomson syndrome have constitutional mutations of RECQL4 and carry a very high risk of developing OS. To determine the relative level of expression of RECQL4 in OS, 18 sporadic tumors were studied by reverse transcription–polymerase chain reaction. All tumors overexpressed RECQL4 in comparison to control osteoblasts, and fluorescence in situ hybridization analysis of tumor DNA showed that expression levels were strongly copy number–dependent. Relative N- and S-CIN levels were determined by classifying copy number transitions within array comparative genomic hybridization profiles and by enumerating the frequency of break-apart fluorescence in situ hybridization within 8q24 using region-specific and control probes. Although there was no evidence that disruption of 8q24 in OS led to an elevated expression of RECQL4, there was a marked association between increased overall levels of S-CIN, determined by copy number transition frequency and higher levels of RECQL4.

  11. Mutations in MAPT gene cause chromosome instability and introduce copy number variations widely in the genome. (United States)

    Rossi, Giacomina; Conconi, Donatella; Panzeri, Elena; Redaelli, Serena; Piccoli, Elena; Paoletta, Laura; Dalprà, Leda; Tagliavini, Fabrizio


    In addition to the main function of promoting polymerization and stabilization of microtubules, other roles are being attributed to tau, now considered a multifunctional protein. In particular, previous studies suggest that tau is involved in chromosome stability and genome protection. We performed cytogenetic analysis, including molecular karyotyping, on lymphocytes and fibroblasts from patients affected by frontotemporal lobar degeneration carrying different mutations in the microtubule-associated protein tau gene, to investigate the effects of these mutations on genome stability. Furthermore, we analyzed the response of mutated lymphoblastoid cell lines to genotoxic agents to evaluate the participation of tau to DNA repair systems. We found a significantly higher level of chromosome aberrations in mutated than in control cells. Mutated lymphocytes showed higher percentages of stable lesions, clonal and total aneuploidy (medians: 2 versus 0, p $\\ll$ 0.01; 1.5 versus 0, p $\\ll$ 0.01; 16.5 versus 0, p $\\ll$ 0.01, respectively). Fibroblasts of patients showed higher percentages of stable lesions, structural aberrations and total aneuploidy (medians: 0 versus 0, p = 0.03; 5.8 versus 0, p = 0.02; 26.5 versus 12.6, p $\\ll$ 0.01, respectively). In addition, the in depth analysis of DNA copy number variations showed a higher tendency to non-allelic homologous recombination in mutated cells. Finally, while our analysis did not support an involvement of tau in DNA repair systems, it revealed its role in stabilization of chromatin. In summary, our findings indicate a role of tau in genome and chromosome stability that can be ascribed to its function as a microtubule-associated protein as well as a protein protecting chromatin integrity through interaction with DNA.

  12. 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH). (United States)

    Cortés-Gutiérrez, Elva I; Ortíz-Hernández, Brenda L; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Fernández, José Luis; López-Fernández, Carmen; Gosálvez, Jaime


    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.

  13. 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


    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.

  14. Immortalization capacity of HPV types is inversely related to chromosomal instability

    DEFF Research Database (Denmark)

    Schütze, Denise M; Krijgsman, Oscar; Snijders, Peter J F;


    High-risk human papillomavirus (hrHPV) types induce immortalization of primary human epithelial cells. Previously we demonstrated that immortalization of human foreskin keratinocytes (HFKs) is HPV type dependent, as reflected by the presence or absence of a crisis period before reaching immortality....... This study determined how the immortalization capacity of ten hrHPV types relates to DNA damage induction and overall genomic instability in HFKs.Twenty five cell cultures obtained by transduction of ten hrHPV types (i.e. HPV16/18/31/33/35/45/51/59/66/70 E6E7) in two or three HFK donors each were studied.......All hrHPV-transduced HFKs showed an increased number of double strand DNA breaks compared to controls, without exhibiting significant differences between types. However, immortal descendants of HPV-transduced HFKs that underwent a prior crisis period (HPV45/51/59/66/70-transduced HFKs) showed...

  15. Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability. (United States)

    Schalbetter, Stephanie A; Mansoubi, Sahar; Chambers, Anna L; Downs, Jessica A; Baxter, Jonathan


    Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein-DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein-DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin.

  16. Inactivation of ATM/ATR DNA damage checkpoint promotes androgen induced chromosomal instability in prostate epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yung-Tuen Chiu

    Full Text Available The ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis.

  17. Personalised pathway analysis reveals association between DNA repair pathway dysregulation and chromosomal instability in sporadic breast cancer. (United States)

    Liu, Chao; Srihari, Sriganesh; Lal, Samir; Gautier, Benoît; Simpson, Peter T; Khanna, Kum Kum; Ragan, Mark A; Lê Cao, Kim-Anh


    The Homologous Recombination (HR) pathway is crucial for the repair of DNA double-strand breaks (DSBs) generated during DNA replication. Defects in HR repair have been linked to the initiation and development of a wide variety of human malignancies, and exploited in chemical, radiological and targeted therapies. In this study, we performed a personalised pathway analysis independently for four large sporadic breast cancer cohorts to investigate the status of HR pathway dysregulation in individual sporadic breast tumours, its association with HR repair deficiency and its impact on tumour characteristics. Specifically, we first manually curated a list of HR genes according to our recent review on this pathway (Liu et al., 2014), and then applied a personalised pathway analysis method named Pathifier (Drier et al., 2013) on the expression levels of the curated genes to obtain an HR score quantifying HR pathway dysregulation in individual tumours. Based on the score, we observed a great diversity in HR dysregulation between and within gene expression-based breast cancer subtypes, and by using two published HR-defect signatures, we found HR pathway dysregulation reflects HR repair deficiency. Furthermore, we identified a novel association between HR pathway dysregulation and chromosomal instability (CIN) in sporadic breast cancer. Although CIN has long been considered as a hallmark of most solid tumours, with recent extensive studies highlighting its importance in tumour evolution and drug resistance, the molecular basis of CIN in sporadic cancers remains poorly understood. Our results imply that HR pathway dysregulation might contribute to CIN in sporadic breast cancer.

  18. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. (United States)

    Ling, Hui; Spizzo, Riccardo; Atlasi, Yaser; Nicoloso, Milena; Shimizu, Masayoshi; Redis, Roxana S; Nishida, Naohiro; Gafà, Roberta; Song, Jian; Guo, Zhiyi; Ivan, Cristina; Barbarotto, Elisa; De Vries, Ingrid; Zhang, Xinna; Ferracin, Manuela; Churchman, Mike; van Galen, Janneke F; Beverloo, Berna H; Shariati, Maryam; Haderk, Franziska; Estecio, Marcos R; Garcia-Manero, Guillermo; Patijn, Gijs A; Gotley, David C; Bhardwaj, Vikas; Shureiqi, Imad; Sen, Subrata; Multani, Asha S; Welsh, James; Yamamoto, Ken; Taniguchi, Itsuki; Song, Min-Ae; Gallinger, Steven; Casey, Graham; Thibodeau, Stephen N; Le Marchand, Loïc; Tiirikainen, Maarit; Mani, Sendurai A; Zhang, Wei; Davuluri, Ramana V; Mimori, Koshi; Mori, Masaki; Sieuwerts, Anieta M; Martens, John W M; Tomlinson, Ian; Negrini, Massimo; Berindan-Neagoe, Ioana; Foekens, John A; Hamilton, Stanley R; Lanza, Giovanni; Kopetz, Scott; Fodde, Riccardo; Calin, George A


    The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.

  19. 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


    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'.

  20. 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


    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.

  1. Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice. (United States)

    Sasada, Tatsunari; Hinoi, Takao; Saito, Yasufumi; Adachi, Tomohiro; Takakura, Yuji; Kawaguchi, Yasuo; Sotomaru, Yusuke; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Ohdan, Hideki


    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 differences

  2. 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

  3. Phenotype transformation of immortalized NCM460 colon epithelial cell line by TGF-β1 is associated with chromosome instability. (United States)

    Huang, Chao; Wen, Bin


    Transforming growth factor-β1 (TGF-β1) within tumor microenvironment has a pivotal function in cancer initiation and tumorigenesis, and hence this study was to observe the malignant transformation induced by TGF-β1 in an immortalized colon epithelial cell line NCM460 for better understanding the mechanisms of colon carcinogenesis. Immortalized colon epithelial cell line NCM460 was used as the model of this study, and was treated with different concentrations of TGF-β1 for different time. Then, immunofluorescence was performed to observe the change of phenotype hallmarks including adherent junction protein E-cadherin, cytoskeleton protein vimentin, and tight junction marker ZO-1, western blotting analysis was performed to detect the expression of the above three markers and two transcription factors (Snail and Slug) involved in the transformation by TGF-β1. In addition, chromosome instability (CHI) including analysis of DNA-ploid was detected by flow cytometry. Our results revealed significant loss or reduction of ZO-1 and E-cadherin, and robust emergence of vimentin in the cell line NCM460 after a 15-, 20-, and 25-day treatment with 10 ng/ml TGF-β1. Interestingly, 20 and 25 days after stimulation with 5 ng/ml TGF-β1, expression of E-cadherin and ZO-1 revealed a pattern roughly similar to that of 10 ng/ml TGF-β1, especially, both expressions was vanished and vimentin expression was dramatically increased at days 25 after TGF-β1 stimulation. After a stimulation with 10 ng/ml TGF-β1 for 15, 20, and 25 days, the levels of Snail and Slug expression in the cells were significantly up-regulated, compared with the cells treated with TGF-β1 inhibitor LY364947, PBS or balnk control (P TGF-β1 after its stimulation for 15, 20, and 25 days. Very few mitotic cells with treatment of PBS for 15, 20 and 25 days were non-diploid whose DNA content was greater or less than 4 N, but these cells were significantly increased after exposure to TGF-β1 for 15, 20, and

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

    Energy Technology Data Exchange (ETDEWEB)

    Fenech, Michael [CSIRO Human Nutrition, Genome Health Nutrigenomics Project, P.O. Box 10041, Adelaide BC, Adelaide, SA 5000 (Australia)]. E-mail:


    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.

  5. Analysis of the G2/M Checkpoint in fanconi anemia cells via examinating chromosomal instability during G2-phase and mitosis


    Sauer, Rica


    Fanconi anemia is a genetical and phenotypical heterogenous disease, characterized through loss of one of the 15 identified genes of the Fanconi anemia pathway what causes congenital anomalies, bone marrow failure and solid tumors. In this work the G2/M checkpoint is analysed by use of the phosphatase inhibitor Calyculin A to examine the chromosomal instability, which is typical for fanconi anemia cells, not only in mitoses but also in the G2 phase of the cell cycle. It is proved that the che...

  6. Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene

    Energy Technology Data Exchange (ETDEWEB)

    Tebbs, R.S.; Tucker, J.D.; Hwang, M. [Lawrence Livermore National Lab., CA (United States)] [and others


    The mutagen-sensitive CHO line irs1SF was previously isolated on the basis of hypersensitivity to ionizing radiation and was found to be chromosomally unstable as well as cross-sensitive to diverse kinds of DNA-damaging agents. The analysis of somatic cell hybrids formed between irs1SF and human lymphocytes implicated a human gene (defined as XRCC3; x-ray repair cross-complementing), which partially restored mitomycin C resistance to the mutant. A functional cDNA that confers mitomycin C resistance was transferred to irs1SF cells by transforming them with an expression cDNA library and obtaining primary and secondary transformants. Functional cDNA clones were recovered from a cosmid library prepared from a secondary transformant. Transformants also showed partial correction of sensitivity to displatin and {gamma}-rays, efficient correction of chromosomal instability, and substantially improved plating efficiency and growth rate. The XRCC3 cDNA insert is {approx} 2.5 kb and detects an {approx} 3.0-kb mRNA on Northern blots. The cDNA was mapped by fluorescence in situ hybridization to human chromosome 14q32.3, which was consistent with the chromosome concordance data of two independent hybrid clone panels. 30 refs., 5 figs., 2 tabs.

  7. 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


    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.

  8. Chromosomal instability associated with a novel BLM frameshift mutation (c.1980-1982delAA) in two unrelated Tunisian families with Bloom syndrome. (United States)

    Ben Salah, G; Salem, I Hadj; Masmoudi, A; Ben Rhouma, B; Turki, H; Fakhfakh, F; Ayadi, H; Kamoun, H


    The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.

  9. Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction. (United States)

    Sperka, Tobias; Song, Zhangfa; Morita, Yohei; Nalapareddy, Kodandaramireddy; Guachalla, Luis Miguel; Lechel, André; Begus-Nahrmann, Yvonne; Burkhalter, Martin D; Mach, Monika; Schlaudraff, Falk; Liss, Birgit; Ju, Zhenyu; Speicher, Michael R; Rudolph, K Lenhard


    The tumour suppressor p53 activates Puma-dependent apoptosis and p21-dependent cell-cycle arrest in response to DNA damage. Deletion of p21 improved stem-cell function and organ maintenance in progeroid mice with dysfunctional telomeres, but the function of Puma has not been investigated in this context. Here we show that deletion of Puma improves stem- and progenitor-cell function, organ maintenance and lifespan of telomere-dysfunctional mice. Puma deletion impairs the clearance of stem and progenitor cells that have accumulated DNA damage as a consequence of critically short telomeres. However, further accumulation of DNA damage in these rescued progenitor cells leads to increasing activation of p21. RNA interference experiments show that upregulation of p21 limits proliferation and evolution of chromosomal imbalances of Puma-deficient stem and progenitor cells with dysfunctional telomeres. These results provide experimental evidence that p53-dependent apoptosis and cell-cycle arrest act in cooperating checkpoints limiting tissue maintenance and evolution of chromosomal instability at stem- and progenitor-cell levels in response to telomere dysfunction. Selective inhibition of Puma-dependent apoptosis can result in temporary improvements in maintenance of telomere-dysfunctional organs.

  10. 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. (United States)

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


    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 pair of synthetically constructed inverted repeats. Fusion occurs between inverted repeats that are separated by several kilobases of DNA and share >20 base pairs of homology. Finally, we show that fusion of inverted repeats, surprisingly, does not require genes involved in double-strand break (DSB) repair or genes involved in other repeat recombination events. We therefore propose that fusion may occur by a DSB-independent, DNA replication-based mechanism (which we term "faulty template switching"). Fusion of nearby inverted repeats to form dicentrics may be a major cause of instability in yeast and in other organisms.

  11. RABL6A, a novel RAB-like protein, controls centrosome amplification and chromosome instability in primary fibroblasts.

    Directory of Open Access Journals (Sweden)

    Xuefeng Zhang

    Full Text Available RABL6A (RAB-like 6 isoform A is a novel protein that was originally identified based on its association with the Alternative Reading Frame (ARF tumor suppressor. ARF acts through multiple p53-dependent and p53-independent pathways to prevent cancer. How RABL6A functions, to what extent it depends on ARF and p53 activity, and its importance in normal cell biology are entirely unknown. We examined the biological consequences of RABL6A silencing in primary mouse embryo fibroblasts (MEFs that express or lack ARF, p53 or both proteins. We found that RABL6A depletion caused centrosome amplification, aneuploidy and multinucleation in MEFs regardless of ARF and p53 status. The centrosome amplification in RABL6A depleted p53-/- MEFs resulted from centrosome reduplication via Cdk2-mediated hyperphosphorylation of nucleophosmin (NPM at threonine-199. Thus, RABL6A prevents centrosome amplification through an ARF/p53-independent mechanism that restricts NPM-T199 phosphorylation. These findings demonstrate an essential role for RABL6A in centrosome regulation and maintenance of chromosome stability in non-transformed cells, key processes that ensure genomic integrity and prevent tumorigenesis.

  12. APC and chromosome instability in colorectal cancer APC e inestabilidad cromosómica en el cáncer de colon

    Directory of Open Access Journals (Sweden)

    C. M. Cabrera


    Full Text Available Colon cancer is a common disease that can be sporadic or familial. An inactivated adenomatous polyposis coli (APC suppressor gene is found in over 80% of colorectal tumors, this being an early alteration in the development of adenomatous polyps. APC function is not only critical for tumor initiation and progression, and chromosome instability (CIN is another characteristic dependent at least partly on APC mutations.El cáncer de colon es una enfermedad frecuente que puede ser esporádica o familiar. La inactivación del gen supresor de tumores APC (adenomatous polyposis coli se ha encontrado en más del 80% de los casos descritos de tumores colorrectales, apareciendo como una alteración temprana durante el desarrollo del pólipo adenomatoso. La inactivación del gen APC no es únicamente crítica en el proceso de iniciación y desarrollo del tumor, sino que igualmente la inestabilidad cromosómica (CIN es otra característica dependiente al menos en parte de la presencia de mutaciones en APC.

  13. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K;


    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...... chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes...

  14. 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;


    infrequently showed gains/deletions or whole-chromosome LOH, but their near-diploid karyotypes concealed mitotic recombination frequencies similar to those of MSI- lines. We analyzed p53 and chromosome 18q (SMAD4) in detail, including mutation screening. Almost all MSI- lines showed LOH and/or deletion of p53...

  15. Intergenerational Instability of the CAG Repeat of the Gene for Machado-Joseph Disease (MJD1) is Affected by the Genotype of the Normal Chromosome


    五十嵐, 修一; Igarashi, Shuichi


    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects the intergenerational instability of the CAG repeat. The [expanded (CAG) n-CGG]/[normal (CAG) n-GGG] haplotypes were found to result in significantly greater instability...

  16. Chromosome oscillations in mitosis (United States)

    Campas, Otger


    Successful cell division necessitates a tight regulation of chromosome movement via the activity of molecular motors. Many of the key players at the origin of the forces generating the motion have been identified, but their spatial and temporal organization remains elusive. In animal cells, chromosomes periodically switch between phases of movement towards and away from the pole. This characteristic oscillatory behaviour cannot be explained by the current models of chromosome positioning and congression. We perform a self-contained theoretical analysis in which the motion of mono-oriented chromosomes results from the competition between the activity of the kinetochore and chromokinesin motors on the chromosome arms. Our analysis, consistent with the available experimental data, proposes that the interplay between the aster-like morphology of the spindle and the collective kinetics of molecular motors is at the origin of chromosome oscillations, positioning and congression. It provides a natural explanation for the so-called chromosome directional instability and for the mechanism by which chromosomes sense their position in space. In addition, we estimate the in vivo velocity of chromokinesins at vanishing load and propose new experiments to assess the mechanism at the origin of chromosome movement in cell division.

  17. Causes of genome instability

    DEFF Research Database (Denmark)

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


    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...... function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make......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...

  18. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.


    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  19. Marker chromosomes. (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria


    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  20. [Oncovirus-induced permanent genetic instability in Drosophila melanogaster]. (United States)

    Mit', N V; Dzhansugurova, L B; Bersimbaev, R I


    Mutant alleles of a system of genetic instability induced by oncoviral DNAs were shown to demonstrate an unstable manifestation 500 generations after their emergence. A cytogenetic analysis of oncovirus-induced unstable lines has revealed numerous chromosome rearrangements. For the Lobe alleles of this system, a specific chromosome rearrangement, Df(2L) = 35C-36B, was found on the left arm of chromosome 2. We used recessive lethal mutations involving DNA rearrangements in a successful construction of cross systems for "explosive" instability.

  1. Studying chromosome instability in the mouse

    NARCIS (Netherlands)

    Foijer, Floris; Draviam, Viji M; Sorger, Peter K


    Aneuploidy has long been recognized as one of the hallmarks of cancer. It nonetheless remains uncertain whether aneuploidy occurring early in the development of a cancer is a primary cause of oncogenic transformation, or whether it is an epiphenomenon that arises from a general breakdown in cell cyc

  2. Mechanical instability

    CERN Document Server

    Krysinski, Tomasz


    This book presents a study of the stability of mechanical systems, i.e. their free response when they are removed from their position of equilibrium after a temporary disturbance. After reviewing the main analytical methods of the dynamical stability of systems, it highlights the fundamental difference in nature between the phenomena of forced resonance vibration of mechanical systems subjected to an imposed excitation and instabilities that characterize their free response. It specifically develops instabilities arising from the rotor-structure coupling, instability of control systems, the se

  3. Collective instabilities

    Energy Technology Data Exchange (ETDEWEB)

    K.Y. Ng


    The lecture covers mainly Sections 2.VIII and 3.VII of the book ''Accelerator Physics'' by S.Y. Lee, plus mode-coupling instabilities and chromaticity-driven head-tail instability. Besides giving more detailed derivation of many equations, simple interpretations of many collective instabilities are included with the intention that the phenomena can be understood more easily without going into too much mathematics. The notations of Lee's book as well as the e{sup jwt} convention are followed.

  4. Genetic instability in nerve sheath cell tumors

    DEFF Research Database (Denmark)

    Rogatto, Silvia Regina; Casartelli, Cacilda; Rainho, Claudia Aparecida


    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......) and chromosomes 8, 17 and 19 (two cases). Trisomy of chromosome 20 was also detected in two cases. Structural rearrangements were detected at low frequencies, with del(10)(p12) being present in two cases. In addition, we observed cell subpopulations showing a certain degree of genetic instability, reflected...

  5. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.


    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...... 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. 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


    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

  7. Modeling Chromosomes (United States)

    Robertson, Carol


    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…


    Institute of Scientific and Technical Information of China (English)

    赵旻; 伍欣星; 邱小萍; 李晖; 戴天力; 谭云


    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.

  9. Recombination instability

    DEFF Research Database (Denmark)

    D'Angelo, N.


    A recombination instability is considered which may arise in a plasma if the temperature dependence of the volume recombination coefficient, alpha, is sufficiently strong. Two cases are analyzed: (a) a steady-state plasma produced in a neutral gas by X-rays or high energy electrons; and (b) an af...

  10. [Carpal instability]. (United States)

    Redeker, J; Vogt, P M


    Carpal instability can be understood as a disturbed anatomical alignment between bones articulating in the carpus. This disturbed balance occurs either only dynamically (with movement) under the effect of physiological force or even statically at rest. The most common cause of carpal instability is wrist trauma with rupture of the stabilizing ligaments and adaptive misalignment following fractures of the radius or carpus. Carpal collapse plays a special role in this mechanism due to non-healed fracture of the scaphoid bone. In addition degenerative inflammatory alterations, such as chondrocalcinosis or gout, more rarely aseptic bone necrosis of the lunate or scaphoid bones or misalignment due to deposition (Madelung deformity) can lead to wrist instability. Under increased pressure the misaligned joint surfaces lead to bone arrosion with secondary arthritis of the wrist. In order to arrest or slow down this irreversible process, diagnosis must occur as early as possible. Many surgical methods have been thought out to regain stability ranging from direct reconstruction of the damaged ligaments, through ligament replacement to partial stiffening of the wrist joint.

  11. One-hit wonders of genomic instability

    Directory of Open Access Journals (Sweden)

    Strunnikov Alexander V


    Full Text Available Abstract Recent data show that cells from many cancers exhibit massive chromosome instability. The traditional view is that the gradual accumulation of mutations in genes involved in transcriptional regulation and cell cycle controls results in tumor development. This, however, does not exclude the possibility that some mutations could be more potent than others in destabilizing the genome by targeting both chromosomal integrity and corresponding checkpoint mechanisms simultaneously. Three such examples of "single-hit" lesions potentially leading to heritable genome destabilization are discussed. They include: failure to release sister chromatid cohesion due to the incomplete proteolytic cleavage of cohesin; massive merotelic kinetochore misattachments upon condensin depletion; and chromosome under-replication. In all three cases, cells fail to detect potential chromosomal bridges before anaphase entry, indicating that there is a basic cell cycle requirement to maintain a degree of sister chromatid bridging that is not recognizable as chromosomal damage.

  12. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes. (United States)

    Thayer, Mathew J


    Recent studies indicate that mammalian chromosomes contain discrete cis-acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non-coding RNA gene ASAR6 results in late replication, an under-condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono-allelic expression and asynchronous replication timing. Additional "chromosome engineering" studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain "inactivation/stability centers" that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types of cis-acting elements, origins, telomeres, centromeres, and "inactivation/stability centers", all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes.

  13. ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15.

    Directory of Open Access Journals (Sweden)

    Nathan Donley


    Full Text Available DNA replication initiates at multiple sites along each mammalian chromosome at different times during each S phase, following a temporal replication program. We have used a Cre/loxP-based strategy to identify cis-acting elements that control this replication-timing program on individual human chromosomes. In this report, we show that rearrangements at a complex locus at chromosome 15q24.3 result in delayed replication and structural instability of human chromosome 15. Characterization of this locus identified long, RNA transcripts that are retained in the nucleus and form a "cloud" on one homolog of chromosome 15. We also found that this locus displays asynchronous replication that is coordinated with other random monoallelic genes on chromosome 15. We have named this locus ASynchronous replication and Autosomal RNA on chromosome 15, or ASAR15. Previously, we found that disruption of the ASAR6 lincRNA gene results in delayed replication, delayed mitotic condensation and structural instability of human chromosome 6. Previous studies in the mouse found that deletion of the Xist gene, from the X chromosome in adult somatic cells, results in a delayed replication and instability phenotype that is indistinguishable from the phenotype caused by disruption of either ASAR6 or ASAR15. In addition, delayed replication and chromosome instability were detected following structural rearrangement of many different human or mouse chromosomes. These observations suggest that all mammalian chromosomes contain similar cis-acting loci. Thus, under this scenario, all mammalian chromosomes contain four distinct types of essential cis-acting elements: origins, telomeres, centromeres and "inactivation/stability centers", all functioning to promote proper replication, segregation and structural stability of each chromosome.

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

    Directory of Open Access Journals (Sweden)

    Senthil Kumar Pazhanisamy


    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.


    Directory of Open Access Journals (Sweden)

    Ionescu Cristian


    Full Text Available There is an important link between the following two variables: financial instability and political instability. Often, the link is bidirectional, so both may influence each other. This is way the lately crisis are becoming larger and increasingly complex. Therefore, the academic environment is simultaneously talking about economic crises, financial crises, political crises, social crises, highlighting the correlation and causality between variables belonging to the economic, financial, political and social areas, with repercussions and spillover effects that extend from one area to another. Given the importance, relevance and the actuality of the ones described above, I consider that at least a theoretical analysis between economic, financial and political factors is needed in order to understand the reality. Thus, this paper aims to find links and connections to complete the picture of the economic reality.

  16. Synthetic chromosomes. (United States)

    Schindler, Daniel; Waldminghaus, Torsten


    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.

  17. Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies

    Energy Technology Data Exchange (ETDEWEB)

    Pampalona, J.; Soler, D.; Genesca, A. [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra E-08193 (Spain); Tusell, L., E-mail: [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra E-08193 (Spain)


    The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16{sup INK4a} protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and

  18. [Y chromosome structural abnormalities and Turner's syndrome]. (United States)

    Ravel, C; Siffroi, J-P


    Although specifically male, the human Y chromosome may be observed in female karyotypes, mostly in women with Turner syndrome stigmata. In women with isolated gonadal dysgenesis but otherwise normal stature, the testis determining factor or SRY gene may have been removed from the Y chromosome or may be mutated. In other women with Turner syndrome, the karyotype is usually abnormal and shows a frequent 45,X/46,XY mosaicism. In these cases, the phenotype depends on the ratio between Y positive and 45,X cell lines in the body. When in mosaicism, Y chromosomes are likely to carry structural abnormalities which explain mitotic instability, such as the existence of two centromeres. Dicentric Y isochromosomes for the short arm (idic[Yp]) or ring Y chromosomes (r[Y]) are the most frequent abnormal Y chromosomes found in infertile patients and in Turner syndrome in mosaic with 45,X cells. Although monocentric, deleted Y chromosomes for the long arm and those carrying microdeletions in the AZF region are also instable and are frequently associated with a 45,X cell line. Management of infertile patients carrying such abnormal Y chromosomes must take into account the risk and the consequences of a mosaicism in the offspring.

  19. Unusual maternal uniparental isodisomic x chromosome mosaicism with asymmetric y chromosomal rearrangement. (United States)

    Lee, B Y; Kim, S Y; Park, J Y; Choi, E Y; Kim, D J; Kim, J W; Ryu, H M; Cho, Y H; Park, S Y; Seo, J T


    Infertile men with azoospermia commonly have associated microdeletions in the azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or sex chromosome rearrangements. In this study, we describe an unusual 46,XX and 45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pter→q11.222::p11.2→pter)[25]. The derivative Y chromosome had a deletion at Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed by fluorescence in situ hybridization analysis, and complete deletion of the AZFb and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and derived from the maternal gamete, as determined by examination of short tandem repeat markers. We postulate that the derivative Y chromosome might have been generated during paternal meiosis or early embryogenesis. Also, we suggest that the very rare mosaicism of isodisomic X chromosomes might be formed during maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/ 45,X lineage because of the instability of the derivative Y chromosome. To our knowledge, this is the first confirmatory study to verify the origin of a sex chromosome mosaicism with a Y chromosome rearrangement.

  20. Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis. (United States)

    Gascoigne, Karen E; Cheeseman, Iain M


    Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a "dicentric" chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cells. Here, we tested the ability of a single dicentric chromosome to contribute to genomic instability and neoplastic conversion in vertebrate cells. We developed a system to transiently and reversibly induce dicentric chromosome formation on a single chromosome with high temporal control. We find that induced dicentric chromosomes are frequently damaged and mis-segregated during mitosis, and that this leads to extensive chromosomal rearrangements including translocations with other chromosomes. Populations of pre-neoplastic cells in which a single dicentric chromosome is induced acquire extensive genomic instability and display hallmarks of cellular transformation including anchorage-independent growth in soft agar. Our results suggest that a single dicentric chromosome could contribute to tumor initiation.

  1. Chromosome Analysis (United States)


    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  2. Induction of genomic instability and activation of autophagy in artificial human aneuploid cells

    Energy Technology Data Exchange (ETDEWEB)

    Ariyoshi, Kentaro [Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564 (Japan); Miura, Tomisato; Kasai, Kosuke; Fujishima, Yohei [Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564 (Japan); Oshimura, Mitsuo [Chromosome Engineering Research Center (CERC), Tottori University, Nishicho 86, Yonago, Tottori 683-8503 (Japan); Yoshida, Mitsuaki A., E-mail: [Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564 (Japan)


    Highlights: • Clones with artificial aneuploidy of chromosome 8 or chromosome 22 both show inhibited proliferation and genomic instability. • Increased autophagy was observed in the artificially aneuploid clones. • Inhibition of autophagy resulted in increased genomic instability and DNA damage. • Intracellular levels of reactive oxygen species were up-regulated in the artificially aneuploid clones. - Abstract: Chromosome missegregation can lead to a change in chromosome number known as aneuploidy. Although aneuploidy is a known hallmark of cancer cells, the various mechanisms by which altered gene and/or DNA copy number facilitate tumorigenesis remain unclear. To understand the effect of aneuploidy occurring in non-tumorigenic human breast epithelial cells, we generated clones harboring artificial aneuploidy using microcell-mediated chromosome transfer. Our results demonstrate that clones with artificial aneuploidy of chromosome 8 or chromosome 22 both show inhibited proliferation and genomic instability. Also, the increased autophagy was observed in the artificially aneuploidy clones, and inhibition of autophagy resulted in increased genomic instability and DNA damage. In addition, the intracellular levels of reactive oxygen species were up-regulated in the artificially aneuploid clones, and inhibition of autophagy further increased the production of reactive oxygen species. Together, these results suggest that even a single extraneous chromosome can induce genomic instability, and that autophagy triggered by aneuploidy-induced stress is a mechanism to protect cells bearing abnormal chromosome number.

  3. Unrepaired DNA damage facilitates elimination of uniparental chromosomes in interspecific hybrid cells. (United States)

    Wang, Zheng; Yin, Hao; Lv, Lei; Feng, Yingying; Chen, Shaopeng; Liang, Junting; Huang, Yun; Jiang, Xiaohua; Jiang, Hanwei; Bukhari, Ihtisham; Wu, Lijun; Cooke, Howard J; Shi, Qinghua


    Elimination of uniparental chromosomes occurs frequently in interspecific hybrid cells. For example, human chromosomes are always eliminated during clone formation when human cells are fused with mouse cells. However, the underlying mechanisms are still elusive. Here, we show that the elimination of human chromosomes in human-mouse hybrid cells is accompanied by continued cell division at the presence of DNA damage on human chromosomes. Deficiency in DNA damage repair on human chromosomes occurs after cell fusion. Furthermore, increasing the level of DNA damage on human chromosomes by irradiation accelerates human chromosome loss in hybrid cells. Our results indicate that the elimination of human chromosomes in human-mouse hybrid cells results from unrepaired DNA damage on human chromosomes. We therefore provide a novel mechanism underlying chromosome instability which may facilitate the understanding of carcinogenesis.

  4. Microsatellite instability and cytogenetic survey in myeloid leukemias

    Directory of Open Access Journals (Sweden)

    E.M.S.F. Ribeiro


    Full Text Available Microsatellites are short tandem repeat sequences dispersed throughout the genome. Their instability at multiple genetic loci may result from mismatch repair errors and it occurs in hereditary nonpolyposis colorectal cancer. This instability is also found in many sporadic cancers. In order to evaluate the importance of this process in myeloid leukemias, we studied five loci in different chromosomes of 43 patients, 22 with chronic myelocytic leukemia (CML in the chronic phase, 7 with CML in blast crisis, and 14 with acute myeloid leukemia (AML, by comparing leukemic DNA extracted from bone marrow and constitutional DNA obtained from buccal epithelial cells. Only one of the 43 patients (2.1%, with relapsed AML, showed an alteration in the allele length at a single locus. Cytogenetic analysis was performed in order to improve the characterization of leukemic subtypes and to determine if specific chromosome aberrations were associated with the presence of microsatellite instability. Several chromosome aberrations were observed, most of them detected at diagnosis and during follow-up of the patients, according to current literature. These findings suggest that microsatellite instability is an infrequent genetic event in myeloid leukemias, adding support to the current view that the mechanisms of genomic instability in solid tumors differ from those observed in leukemias, where specific chromosome aberrations seem to play a major role.

  5. Chromosomal Instability of Human Tracheal Epithelia Cells BEAS-2B Induced by Extract of Coal Tar Pitch Fume%煤焦沥青烟提取物致人支气管上皮细胞BEAS-2B染色体不稳定性研究

    Institute of Scientific and Technical Information of China (English)

    李智涛; 冯艳铭; 王威; 王丽霞; 赵勇; 祝寒松; 吴卫东; 吴逸明


    目的 建立煤焦沥青烟提取物诱导的人支气管上皮细胞BEAS-2B株的恶化模型;观察不同时期细胞的染色体不稳定性与细胞恶性转化之间的关系.方法用四唑蓝(MTT)法测定煤焦沥青烟提取物的细胞毒性,以煤焦沥青烟提取物诱导并观察BEAS-2B细胞传代转化过程中的形态学改变;软琼脂克隆形成实验检测细胞恶性转化能力,流式细胞术检测细胞增殖周期变化,核型分析观察细胞染色体不稳定性.结果 煤焦沥青烟提取物的半数致死浓度(LC50)为8.64 mg/L.以诱导剂量(2.0 mg/L)诱导细胞转化,经过30代传代培养,细胞形态发生恶性变化.第30代时,诱导组细胞即能在软琼脂上形成阳性克隆,细胞克隆形成率为21.50‰,明显高于正常对照组和溶剂对照组.流式细胞术检测诱导组G1期细胞比例明显减少,G2/M期细胞比例明显增加.煤焦沥青诱导组从第10代开始细胞二倍体核型的比例明显下降,非整倍体细胞的比例明显增加.随着传代次数增加,染色体不稳定性更明显.细胞克隆形成率和染色体变异的细胞百分比两者呈正相关.结论 煤焦沥青烟提取物可以在体外诱导BEAS-2B细胞产生染色体不稳定性并发生恶化.%Objective To establish a cell model of malignant transformation with human bronchial epithelial cells BEAS-2B induced by extract of coal tar pitch fume and to observe the relationship between chromosome instability and the cell malignant transformation in different cell generations. Methods MTT assay was used to determine the cytotoxicity of the extract of coal tar pitch fume. After induced by coal tar pitch fume extract at 2.0 mg/L, the morphological changes of BEAS-2B cells were observed in their passage and transformation. In every 10 generations the soft agar cell colony formation rate was used to detect the malignant transformation capability, and traditional methods were used to observe the chromosome karyotype

  6. Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).

    NARCIS (Netherlands)

    Hagleitner, M.M.; Lankester, A.; Maraschio, P.; Hulten, M.; Fryns, J.P.; Schuetz, C.; Gimelli, G.; Davies, E.G.; Gennery, A.; Belohradsky, B.H.; Groot, R. de; Gerritsen, E.J.; Mattina, T.; Howard, P.J.; Fasth, A.; Reisli, I.; Furthner, D.; Slatter, M.A.; Cant, A.J.; Cazzola, G.; Dijken, P.J. van; Deuren, M. van; Greef, J.C. de; Maarel, S.M. van der; Weemaes, C.M.R.


    BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a

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

    Energy Technology Data Exchange (ETDEWEB)

    Howard L. Liber; Jeffrey L. Schwartz


    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. Electron heat flux instability (United States)

    Saeed, Sundas; Sarfraz, M.; Yoon, P. H.; Lazar, M.; Qureshi, M. N. S.


    The heat flux instability is an electromagnetic mode excited by a relative drift between the protons and two-component core-halo electrons. The most prominent application may be in association with the solar wind where drifting electron velocity distributions are observed. The heat flux instability is somewhat analogous to the electrostatic Buneman or ion-acoustic instability driven by the net drift between the protons and bulk electrons, except that the heat flux instability operates in magnetized plasmas and possesses transverse electromagnetic polarization. The heat flux instability is also distinct from the electrostatic counterpart in that it requires two electron species with relative drifts with each other. In the literature, the heat flux instability is often called the 'whistler' heat flux instability, but it is actually polarized in the opposite sense to the whistler wave. This paper elucidates all of these fundamental plasma physical properties associated with the heat flux instability starting from a simple model, and gradually building up more complexity towards a solar wind-like distribution functions. It is found that the essential properties of the instability are already present in the cold counter-streaming electron model, and that the instability is absent if the protons are ignored. These instability characteristics are highly reminiscent of the electron firehose instability driven by excessive parallel temperature anisotropy, propagating in parallel direction with respect to the ambient magnetic field, except that the free energy source for the heat flux instability resides in the effective parallel pressure provided by the counter-streaming electrons.

  9. Evaluating shoulder instability treatment

    NARCIS (Netherlands)

    van der Linde, J.A.


    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

  10. [The dependence of the level of chromosome aberrations in human lymphocytes on the duration of their cultivation under ultraviolet irradiation]. (United States)

    Rushkovskiĭ, S R; Bezrukov, V F; Bariliak, I R


    The effect of duration of cultivation of lymphocytes of human UV-irradiated peripheral blood on the chromosomal aberration rate was studied. Under prolonged cultivation the more irradiated blood samples revealed higher level of chromosomal aberrations. The existence of UV-induced delayed chromosomal instability is supposed that may be found under prolonged cultivation. The mechanisms of this phenomenon are discussed.

  11. Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. (United States)

    Holubcová, Zuzana; Blayney, Martyn; Elder, Kay; Schuh, Melina


    Aneuploidy in human eggs is the leading cause of pregnancy loss and several genetic disorders such as Down syndrome. Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg's progenitor cell. The basis for particularly error-prone chromosome segregation in human oocytes is not known. We analyzed meiosis in more than 100 live human oocytes and identified an error-prone chromosome-mediated spindle assembly mechanism as a major contributor to chromosome segregation defects. Human oocytes assembled a meiotic spindle independently of either centrosomes or other microtubule organizing centers. Instead, spindle assembly was mediated by chromosomes and the small guanosine triphosphatase Ran in a process requiring ~16 hours. This unusually long spindle assembly period was marked by intrinsic spindle instability and abnormal kinetochore-microtubule attachments, which favor chromosome segregation errors and provide a possible explanation for high rates of aneuploidy in human eggs.

  12. Effects of hepatitis B virus infection on human sperm chromosomes

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Huang; Tian-Hua Huang; Huan-Ying Qiu; Xiao-Wu Fang; Tian-Gang Zhuang; Hong-Xi Liu; Yong-Hua Wang; Li-Zhi Deng; Jie-Wen Qiu


    AIM: To evaluate the level of sperm chromosome aberrations in male patients with hepatitis B, and to directly detect whether there are HBV DNA integrations in sperm chromosomes of hepatitis B patients.METHODS: Sperm chromosomes of 14 tested subjects (5healthy controls, 9 patients with HBV infection, including 1with acute hepatitis B, 2 with chronic active hepatitis B, 4with chronic persistent hepatitis B, 2 chronic HBsAg carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free golden hamster ova and human spermatozoa, and the frequencies of aberration spermatozoa were compared between subjects of HBV infection and controls. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes.RESULTS: The total frequency of sperm chromosome aberrations in HBV infection group (14.8%, 33/223) was significantly higher than that in the control group (4.3%,5/116). Moreover, the sperm chromosomes in HBV infection patients commonly presented stickiness, clumping, failure to staining, etc, which would affect the analysis of sperm chromosomes. Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis. In 9 (9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots, others presented 2 to 4signals. There was significant difference of fluorescence intensity among the signal spots. The distribution of signal sites among chromosomes was random.CONCLUSION: HBV infection can bring about mutagenic effects on sperm chromosomes. Integrations of viral DNA into sperm chromosomes which are multisites and nonspecific, can further increase the instability of sperm chromosomes. This study suggested that HBV infection can create extensively hereditary effects by alteration genetic constituent and

  13. Evolutionary interaction between W/Y chromosome and transposable elements. (United States)

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


    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.

  14. Shoulder instability; Schulterinstabilitaeten

    Energy Technology Data Exchange (ETDEWEB)

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


    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.)

  15. Undetected sex chromosome aneuploidy by chromosomal microarray. (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay


    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  16. Widespread telomere instability in prostatic lesions. (United States)

    Tu, LiRen; Huda, Nazmul; Grimes, Brenda R; Slee, Roger B; Bates, Alison M; Cheng, Liang; Gilley, David


    A critical function of the telomere is to disguise chromosome ends from cellular recognition as double strand breaks, thereby preventing aberrant chromosome fusion events. Such chromosome end-to-end fusions are known to initiate genomic instability via breakage-fusion-bridge cycles. Telomere dysfunction and other forms of genomic assault likely result in misregulation of genes involved in growth control, cell death, and senescence pathways, lowering the threshold to malignancy and likely drive disease progression. Shortened telomeres and anaphase bridges have been reported in a wide variety of early precursor and malignant cancer lesions including those of the prostate. These findings are being extended using methods for the analysis of telomere fusions (decisive genetic markers for telomere dysfunction) specifically within human tissue DNA. Here we report that benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) prostate lesions all contain similarly high frequencies of telomere fusions and anaphase bridges. Tumor-adjacent, histologically normal prostate tissue generally did not contain telomere fusions or anaphase bridges as compared to matched PCa tissues. However, we found relatively high levels of telomerase activity in this histologically normal tumor-adjacent tissue that was reduced but closely correlated with telomerase levels in corresponding PCa samples. Thus, we present evidence of high levels of telomere dysfunction in BPH, an established early precursor (PIN) and prostate cancer lesions but not generally in tumor adjacent normal tissue. Our results suggest that telomere dysfunction may be a common gateway event leading to genomic instability in prostate tumorigenesis. .

  17. Microsatellite instability in cancer of the proximal colon

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, S.N.; Bren, G.; Schaid, D. (Mayo Clinic and Foundation, Rochester, MN (United States))


    Colorectal tumor DNA was examined for somatic instability at (CA)[sub n] repeats on human chromosomes 5q, 15q, 17p, and 18q. Differences between tumor and normal DNA were detected in 25 of the 90 (28 percent) tumors examined. This instability appeared as either a substantial change in repeat length (often heterogeneous in nature) or a minor change (typically two base pairs). Microsatellite instability was significantly correlated with the tumor's location in the proximal colon (P = 0.003), with increased patient survival (P = 0.02), and, inversely, with loss of heterozygosity for chromosomes 5q, 17p, and 18q. These data suggest that some colorectal cancers may arise through a mechanism that does not necessarily involve loss of heterozygosity. 23 refs., 2 figs., 3 tabs.

  18. Identification and Investigation of Native Chromosomal Fragile Sites in the Avian Cell Line DT40

    DEFF Research Database (Denmark)

    Pentzold, Constanze

    Chromosomal fragile sites are a cytogenetic phenomenon of genome instability that manifests in gaps or breaks on metaphase chromosomes. Diverse mechanisms are involved in their expression but all of them originate from the idea of replication impairment as the main driver for fragility. Cellular ...... kingdom....

  19. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li


    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.

  20. Chromosome Disorder Outreach (United States)

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  1. Chromosome painting in plants.

    NARCIS (Netherlands)

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


    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


    NARCIS (Netherlands)



    Banding techniques were carried out on metaphase chromosomes of zebrafish (Danio rerio) embryos. The karyotypes with the longest chromosomes consist of 12 metacentrics, 26 submetacentrics, and 12 subtelocentrics (2n = 50). All centromeres are C-band positive. Eight chromosomes have a pericentric C-b

  3. 直结肠癌BUBR1的过度表达与TP53突变及微卫星状态关系提示其过度表达与染色体不稳定表型有关%Correlation between over expression of BUBR1 and chromosomal instability in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    赵岩; 张涛; 郑志超; 张剑军; 赵宜良; 前原喜彦


    Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P<0.01) and TP53 mutation (P<0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.%在有丝分裂过程中BUBR1监视微管与着丝点的结合,是保证染色体均等分离的重要分子机制之一.BUBIB变异家谱研究及其敲除模型的研究表明,BUBR1缺陷与染色体不稳定性及肿瘤的发生直接相关.近来在数种人类肿瘤,对BUBR1蛋白过度表达有所报道.但在直结肠癌,BUBR1的过度表达是否与染色体不稳定性的发生有关目前仍无定论.在人类结直肠癌的遗传不稳定性主要表现为两种类型,染色体不稳定性及微卫星不稳定性,它们提示了两条独立的肿瘤发生路径.一般认为不存在高频度微卫星不稳定性表型的肿瘤通过染

  4. 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.

  5. Cavitation Instabilities in Inducers (United States)


    gas handling turbomachines . The fluctuation of the cavity length is plotted in Fig.8 under the surge mode oscillation vi . The major differences...Cavitation Instabilities of Turbomachines .” AIAA Journal of Propulsion and Power, Vol.17, No.3, 636-643. [5] Tsujimoto, Y., (2006), “Flow Instabilities in

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

    NARCIS (Netherlands)

    Hamada, M.; Malureanu, L.A.; Wijshake, T.; Zhou, W.; Deursen, J.M.A. van


    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

  7. Nitric Oxide: Genomic Instability And Synthetic Lethality

    Directory of Open Access Journals (Sweden)

    Vasily A. Yakovlev


    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.

  8. Acentric chromosome ends are prone to fusion with functional chromosome ends through a homology-directed rearrangement. (United States)

    Ohno, Yuko; Ogiyama, Yuki; Kubota, Yoshino; Kubo, Takuya; Ishii, Kojiro


    The centromeres of many eukaryotic chromosomes are established epigenetically on potentially variable tandem repeats; hence, these chromosomes are at risk of being acentric. We reported previously that artificially created acentric chromosomes in the fission yeast Schizosaccharomyces pombe can be rescued by end-to-end fusion with functional chromosomes. Here, we show that most acentric/functional chromosome fusion events in S. pombe cells harbouring an acentric chromosome I differed from the non-homologous end-joining-mediated rearrangements that result in deleterious dicentric fusions in normal cells, and were elicited by a previously unidentified homologous recombination (HR) event between chromosome end-associated sequences. The subtelomere repeats associated with the non-fusogenic ends were also destabilized in the surviving cells, suggesting a causal link between general subtelomere destabilization and acentric/functional chromosome fusion. A mutational analysis indicated that a non-canonical HR pathway was involved in the rearrangement. These findings are indicative of a latent mechanism that conditionally induces general subtelomere instability, presumably in the face of accidental centromere loss events, resulting in rescue of the fatal acentric chromosomes by interchromosomal HR.

  9. Sex chromosome mosaicism in males carrying Y chromosome long arm deletions. (United States)

    Siffroi, J P; Le Bourhis, C; Krausz, C; Barbaux, S; Quintana-Murci, L; Kanafani, S; Rouba, H; Bujan, L; Bourrouillou, G; Seifer, I; Boucher, D; Fellous, M; McElreavey, K; Dadoune, J P


    Microdeletions of the long arm of the Y chromosome (Yq) are a common cause of male infertility. Since large structural rearrangements of the Y chromosome are commonly associated with a 45,XO/46,XY chromosomal mosaicism, we studied whether submicroscopic Yq deletions could also be associated with the development of 45,XO cell lines. We studied blood samples from 14 infertile men carrying a Yq microdeletion as revealed by polymerase chain reaction (PCR). Patients were divided into two groups: group 1 (n = 6), in which karyotype analysis demonstrated a 45,X/46,XY mosaicism, and group 2 (n = 8) with apparently a normal 46,XY karyotype. 45,XO cells were identified by fluorescence in-situ hybridization (FISH) using X and Y centromeric probes. Lymphocytes from 11 fertile men were studied as controls. In addition, sperm cells were studied in three oligozoospermic patients in group 2. Our results showed that large and submicroscopic Yq deletions were associated with significantly increased percentages of 45,XO cells in lymphocytes and of sperm cells nullisomic for gonosomes, especially for the Y chromosome. Moreover, two isodicentric Y chromosomes, classified as normal by cytogenetic methods, were detected. Therefore, Yq microdeletions may be associated with Y chromosomal instability leading to the formation of 45,XO cell lines.

  10. 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


    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.

  11. Nonlinear helical MHD instability

    Energy Technology Data Exchange (ETDEWEB)

    Zueva, N.M.; Solov' ev, L.S.


    An examination is made of the boundary problem on the development of MHD instability in a toroidal plasma. Two types of local helical instability are noted - Alfven and thermal, and the corresponding criteria of instability are cited. An evaluation is made of the maximum attainable kinetic energy, limited by the degree to which the law of conservation is fulfilled. An examination is made of a precise solution to a kinematic problem on the helical evolution of a cylindrical magnetic configuration at a given velocity distribution in a plasma. A numerical computation of the development of MHD instability in a plasma cylinder by a computerized solution of MHD equations is made where the process's helical symmetry is conserved. The development of instability is of a resonance nature. The instability involves the entire cross section of the plasma and leads to an inside-out reversal of the magnetic surfaces when there is a maximum unstable equilibrium configuration in the nonlinear stage. The examined instability in the tore is apparently stabilized by a magnetic hole when certain limitations are placed on the distribution of flows in the plasma. 29 references, 8 figures.

  12. Causes of genome instability: the effect of low dose chemical exposures in modern society (United States)

    Langie, Sabine A.S.; Koppen, Gudrun; Desaulniers, Daniel; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Azqueta, Amaya; Bisson, William H.; Brown, Dustin; Brunborg, Gunnar; Charles, Amelia K.; Chen, Tao; Colacci, Annamaria; Darroudi, Firouz; Forte, Stefano; Gonzalez, Laetitia; Hamid, Roslida A.; Knudsen, Lisbeth E.; Leyns, Luc; Lopez de Cerain Salsamendi, Adela; Memeo, Lorenzo; Mondello, Chiara; Mothersill, Carmel; Olsen, Ann-Karin; Pavanello, Sofia; Raju, Jayadev; Rojas, Emilio; Roy, Rabindra; Ryan, Elizabeth; Ostrosky-Wegman, Patricia; Salem, Hosni K.; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Van Schooten, Frederik J.; Valverde, Mahara; Woodrick, Jordan; Zhang, Luoping; van Larebeke, Nik; Kirsch-Volders, Micheline; Collins, Andrew R.


    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, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis. PMID:26106144

  13. Spondylolisthesis and Posterior Instability

    Energy Technology Data Exchange (ETDEWEB)

    Niggemann, P.; Beyer, H.K.; Frey, H.; Grosskurth, D. (Privatpraxis fuer Upright MRT, Koeln (Germany)); Simons, P.; Kuchta, J. (Media Park Klinik, Koeln (Germany))


    We present the case of a patient with a spondylolisthesis of L5 on S1 due to spondylolysis at the level L5/S1. The vertebral slip was fixed and no anterior instability was found. Using functional magnetic resonance imaging (MRI) in an upright MRI scanner, posterior instability at the level of the spondylolytic defect of L5 was demonstrated. A structure, probably the hypertrophic ligament flava, arising from the spondylolytic defect was displaced toward the L5 nerve root, and a bilateral contact of the displaced structure with the L5 nerve root was shown in extension of the spine. To our knowledge, this is the first case described of posterior instability in patients with spondylolisthesis. The clinical implications of posterior instability are unknown; however, it is thought that this disorder is common and that it can only be diagnosed using upright MRI.

  14. Analysis of plant meiotic chromosomes by chromosome painting. (United States)

    Lysak, Martin A; Mandáková, Terezie


    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  15. Instabilities in nuclei

    CERN Document Server

    Csernai, László P; Papp, G


    The evolution of dynamical perturbations is examined in nuclear multifragmentation in the frame of Vlasov equation. Both plane wave and bubble type of perturbations are investigated in the presence of surface (Yukawa) forces. An energy condition is given for the allowed type of instabilities and the time scale of the exponential growth of the instabilities is calculated. The results are compared to the mechanical spinodal region predictions. PACS: 25.70 Mn

  16. Prediction of Algebraic Instabilities (United States)

    Zaretzky, Paula; King, Kristina; Hill, Nicole; Keithley, Kimberlee; Barlow, Nathaniel; Weinstein, Steven; Cromer, Michael


    A widely unexplored type of hydrodynamic instability is examined - large-time algebraic growth. Such growth occurs on the threshold of (exponentially) neutral stability. A new methodology is provided for predicting the algebraic growth rate of an initial disturbance, when applied to the governing differential equation (or dispersion relation) describing wave propagation in dispersive media. Several types of algebraic instabilities are explored in the context of both linear and nonlinear waves.

  17. Identifying Instability Pockets (United States)


    TYPE SAMS Monograph 3. DATES COVERED (From - To) FEB 2014 – DEC 2014 4. TITLE AND SUBTITLE IDENTIFYING INSTABILITY POCKETS 5a. CONTRACT...century, and if the first few years of the new century are indicative of the future, Central Asia is surely destined to be a focus of the world...reasons. First, there is a possibility of the collapse and instability of Afghanistan once all the U.S troops vacate .107 This stability will most

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

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


    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.

  19. The Precarious Prokaryotic Chromosome


    Kuzminov, Andrei


    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the t...

  20. Mechanisms for chromosome segregation. (United States)

    Bouet, Jean-Yves; Stouf, Mathieu; Lebailly, Elise; Cornet, François


    Bacteria face the problem of segregating their gigantic chromosomes without a segregation period restricted in time and space, as Eukaryotes do. Segregation thus involves multiple activities, general or specific of a chromosome region and differentially controlled. Recent advances show that these various mechanisms conform to a “pair and release” rule, which appears as a general rule in DNA segregation. We describe the latest advances in segregation of bacterial chromosomes with emphasis on the different pair and release mechanisms.

  1. Bacterial chromosome segregation. (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier


    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  2. Propagating Instabilities in Solids (United States)

    Kyriakides, Stelios


    Instability is one of the factors which limit the extent to which solids can be loaded or deformed and plays a pivotal role in the design of many structures. Such instabilities often result in localized deformation which precipitates catastrophic failure. Some materials have the capacity to recover their stiffness following a certain amount of localized deformation. This local recovery in stiffness arrests further local deformation and spreading of the instability to neighboring material becomes preferred. Under displacement controlled loading the propagation of the transition fronts can be achieved in a steady-state manner at a constant stress level known as the propagation stress. The stresses in the transition fronts joining the highly deformed zone to the intact material overcome the instability nucleation stresses and, as a result, the propagation stress is usually much lower than the stress required to nucleate the instability. The classical example of this class of material instabilities is L/"uders bands which tend to affect mild steels and other metals. Recent work has demonstrated that propagating instabilities occur in several other materials. Experimental and analytical results from four examples will be used to illustrate this point: First the evolution of L=FCders bands in mild steel strips will be revisited. The second example involves the evolution of stress induced phase transformations (austenite to martensite phases and the reverse) in a shape memory alloy under displacement controlled stretching. The third example is the crushing behavior of cellular materials such as honeycombs and foams made from metals and polymers. The fourth example involves the axial broadening/propagation of kink bands in aligned fiber/matrix composites under compression. The microstructure and, as a result, the micromechanisms governing the onset, localization, local arrest and propagation of instabilities in each of the four materials are vastly different. Despite this

  3. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J


    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...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...... with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications...

  4. Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background (United States)

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


    Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

  5. XYY chromosome anomaly and schizophrenia. (United States)

    Rajagopalan, M; MacBeth, R; Varma, S L


    Sex chromosome anomalies have been associated with psychoses, and most of the evidence is linked to the presence of an additional X chromosome. We report a patient with XYY chromosome anomaly who developed schizophrenia.

  6. Formation of complex and unstable chromosomal translocations in yeast.

    Directory of Open Access Journals (Sweden)

    Kristina H Schmidt

    Full Text Available Genome instability, associated with chromosome breakage syndromes and most human cancers, is still poorly understood. In the yeast Saccharomyces cerevisiae, numerous genes with roles in the preservation of genome integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that lack Sgs1, a RecQ-like DNA helicase related to the human Bloom's-syndrome-associated helicase BLM, show an increased rate of genome instability, and we have previously shown that they accumulate recurring chromosomal translocations between three similar genes, CAN1, LYP1 and ALP1. Here, the chromosomal location, copy number and sequence similarity of the translocation targets ALP1 and LYP1 were altered to gain insight into the formation of complex translocations. Among 844 clones with chromosomal rearrangements, 93 with various types of simple and complex translocations involving CAN1, LYP1 and ALP1 were identified. Breakpoint sequencing and mapping showed that the formation of complex translocation types is strictly dependent on the location of the initiating DNA break and revealed that complex translocations arise via a combination of interchromosomal translocation and template-switching, as well as from unstable dicentric intermediates. Template-switching occurred between sequences on the same chromosome, but was inhibited if the genes were transferred to different chromosomes. Unstable dicentric translocations continuously gave rise to clones with multiple translocations in various combinations, reminiscent of intratumor heterogeneity in human cancers. Base substitutions and evidence of DNA slippage near rearrangement breakpoints revealed that translocation formation can be accompanied by point mutations, and their presence in different translocation types within the same clone provides evidence that some of the different translocation types are derived from each other rather than being formed de novo. These findings provide insight into eukaryotic

  7. Neutrino beam plasma instability

    Indian Academy of Sciences (India)

    Vishnu M Bannur


    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.

  8. Mixing through shear instabilities

    CERN Document Server

    Brüggen, M


    In this paper we present the results of numerical simulations of the Kelvin-Helmholtz instability in a stratified shear layer. This shear instability is believed to be responsible for extra mixing in differentially rotating stellar interiors and is the prime candidate to explain the abundance anomalies observed in many rotating stars. All mixing prescriptions currently in use are based on phenomenological and heuristic estimates whose validity is often unclear. Using three-dimensional numerical simulations, we study the mixing efficiency as a function of the Richardson number and compare our results with some semi-analytical formalisms of mixing.

  9. Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast (United States)

    Weinert, Ted


    DNA replication errors at certain sites in the genome initiate chromosome instability that ultimately leads to stable genomic rearrangements. Where instability begins is often unclear. And, early instability may form unstable chromosome intermediates whose transient nature also hinders mechanistic understanding. We report here a budding yeast model that reveals the genetic ontogeny of genome rearrangements, from initial replication error to unstable chromosome formation to their resolution. Remarkably, the initial error often arises in or near the telomere, and frequently forms unstable chromosomes. Early unstable chromosomes may then resolve to an internal "collection site" where a dicentric forms and resolves to an isochromosome (other outcomes are possible at each step). The initial telomere-proximal unstable chromosome is increased in mutants in telomerase subunits, Tel1, and even Rad9, with no known telomere-specific function. Defects in Tel1 and in Rrm3, a checkpoint protein kinase with a role in telomere maintenance and a DNA helicase, respectively, synergize dramatically to generate unstable chromosomes, further illustrating the consequence of replication error in the telomere. Collectively, our results suggest telomeric replication errors may be a common cause of seemingly unrelated genomic rearrangements located hundreds of kilobases away. PMID:27716774

  10. Critically short telomeres in acute myeloid leukemia with loss or gain of parts of chromosomes. (United States)

    Swiggers, Susan J J; Kuijpers, Marianne A; de Cort, Maartje J M; Beverloo, H Berna; Zijlmans, J Mark J M


    Telomeres, nucleoprotein complexes at chromosome ends, protect chromosomes against end-to-end fusion. Previous in vitro studies in human fibroblast models indicated that telomere dysfunction results in chromosome instability. Loss of telomere function can result either from critical shortening of telomeric DNA or from loss of distinct telomere-capping proteins. It is less clear whether telomere dysfunction has an important role in human cancer development in vivo. Acute myeloid leukemia (AML) is a good model to study mechanisms that generate chromosome instability in human cancer development because distinct groups of AML are characterized either by aberrations that theoretically could result from telomere dysfunction (terminal deletions, gains/losses of chromosome parts, nonreciprocal translocations), or aberrations that are unlikely to result from telomere dysfunction (e.g., reciprocal translocations or inversions). Here we demonstrate that AML with multiple chromosome aberrations that theoretically could result from telomere dysfunction is invariably characterized by critically short telomeres. Short telomeres in this group are not associated with low telomerase activity or decreased expression of essential telomeric capping proteins TRF2 and POT1. In contrast, telomerase activity levels are significantly higher in AML with short telomeres. Notably, short telomeres in the presence of high telomerase may relate to significantly higher expression of TRF1, a negative regulator of telomere length. Our observations suggest that, consistent with previous in vitro fibroblast models, age-related critical telomere shortening may have a role in generating chromosome instability in human AML development.

  11. Ontogeny of Unstable Chromosomes Generated by Telomere Error in Budding Yeast. (United States)

    Beyer, Tracey; Weinert, Ted


    DNA replication errors at certain sites in the genome initiate chromosome instability that ultimately leads to stable genomic rearrangements. Where instability begins is often unclear. And, early instability may form unstable chromosome intermediates whose transient nature also hinders mechanistic understanding. We report here a budding yeast model that reveals the genetic ontogeny of genome rearrangements, from initial replication error to unstable chromosome formation to their resolution. Remarkably, the initial error often arises in or near the telomere, and frequently forms unstable chromosomes. Early unstable chromosomes may then resolve to an internal "collection site" where a dicentric forms and resolves to an isochromosome (other outcomes are possible at each step). The initial telomere-proximal unstable chromosome is increased in mutants in telomerase subunits, Tel1, and even Rad9, with no known telomere-specific function. Defects in Tel1 and in Rrm3, a checkpoint protein kinase with a role in telomere maintenance and a DNA helicase, respectively, synergize dramatically to generate unstable chromosomes, further illustrating the consequence of replication error in the telomere. Collectively, our results suggest telomeric replication errors may be a common cause of seemingly unrelated genomic rearrangements located hundreds of kilobases away.

  12. Sequential cloning of chromosomes (United States)

    Lacks, S.A.


    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. 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 (class IIS) 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. 9 figs.

  13. Chromosomal mosaicism goes global

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B


    Full Text Available Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy. It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.




    Studies of the chromosomes of four American marsupials demonstrated that Caluromys derbianus and Marmosa mexicana have a diploid number of 14 chromosomes, and that Philander opossum and Didelphis marsupialis have a diploid number of 22. The karyotypes of C. derbianus and M. mexicana are similar, whereas those of P. opossum and D. marsupialis are dissimilar. If the 14-chromosome karyotype represents a reduction from a primitive number of 22, these observations suggest that the change has occurred independently in the American and Australasian forms.

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


    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.

  16. c-Myc—Dependent Formation of Robertsonian Translocation Chromosomes in Mouse Cells

    Directory of Open Access Journals (Sweden)

    Amanda Guffei


    Full Text Available Robertsonian (Rb translocation chromosomes occur in human and murine cancers and involve the aberrant joining of two acrocentric chromosomes in humans and two telocentric chromosomes in mice. Mechanisms leading to their generation remain elusive, but models for their formation have been proposed. They include breakage of centromeric sequences and their subsequent fusions, centric misdivision, misparing between highly repetitive sequences of p-tel or p-arm repeats, and recombinational joining of centromeres and/or centromeric fusions. Here, we have investigated the role of the oncoprotein c-Myc in the formation of Rb chromosomes in mouse cells harboring exclusively telocentric chromosomes. In mouse plasmacytoma cells with constitutive c-Myc deregulation and in immortalized mouse lymphocytes with conditional c-Myc expression, we show that positional remodeling of centromeres in interphase nuclei coincides with the formation of Rb chromosomes. Furthermore, we demonstrate that c-Myc deregulation in a myc box II-dependent manner is sufficient to induce Rb translocation chromosomes. Because telomeric signals are present at all joined centromeres of Rb chromosomes, we conclude that c-Myc mediates Rb chromosome formation in mouse cells by telomere fusions at centromeric termini of telocentric chromosomes. Our findings are relevant to the understanding of nuclear chromosome remodeling during the initiation of genomic instability and tumorigenesis.

  17. Role of the Number of Microtubules in Chromosome Segregation during Cell Division

    CERN Document Server

    Bertalan, Zsolt; La Porta, Caterina A M; Zapperi, Stefano


    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...

  18. Shock instability in dissipative gases


    Radulescu, Matei I.; Sirmas, Nick


    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 ...

  19. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz


    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.

  20. [Sex chromosomes and meiosis]. (United States)

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C


    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  1. Chromosome doubling method (United States)

    Kato, Akio


    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  2. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)


    markdownabstractIn mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution.

  3. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk


    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.

  4. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy


    MacKinnon, Ruth N.; Campbell, Lynda J.


    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 centrom...

  5. Microsatellite Instability Assay — EDRN Public Portal (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.

  6. Genetic instability in Gynecological Cancer

    Institute of Scientific and Technical Information of China (English)

    ZHAO Qing-hua; ZHOU Hong-lin


    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.

  7. Modulation instability: The beginning (United States)

    Noskov, Roman; Belov, Pavel; Kivshar, Yuri


    The study of metal nanoparticles plays a central role in the emerging novel technologies employing optics beyond the diffraction limit. Combining strong surface plasmon resonances, high intrinsic nonlinearities and deeply subwavelength scales, arrays of metal nanoparticles offer a unique playground to develop novel concepts for light manipulation at the nanoscale. Here we suggest a novel principle to control localized optical energy in chains of nonlinear subwavelength metal nanoparticles based on the fundamental nonlinear phenomenon of modulation instability. In particular, we demonstrate that modulation instability can lead to the formation of long-lived standing and moving nonlinear localized modes of several distinct types such as bright and dark solitons, oscillons, and domain walls. We analyze the properties of these nonlinear localized modes and reveal different scenarios of their dynamics including transformation of one type of mode to another. We believe this work paves a way towards the development of nonlinear nanophotonics circuitry.

  8. Instabilities in sensory processes (United States)

    Balakrishnan, J.


    In any organism there are different kinds of sensory receptors for detecting the various, distinct stimuli through which its external environment may impinge upon it. These receptors convey these stimuli in different ways to an organism's information processing region enabling it to distinctly perceive the varied sensations and to respond to them. The behavior of cells and their response to stimuli may be captured through simple mathematical models employing regulatory feedback mechanisms. We argue that the sensory processes such as olfaction function optimally by operating in the close proximity of dynamical instabilities. In the case of coupled neurons, we point out that random disturbances and fluctuations can move their operating point close to certain dynamical instabilities triggering synchronous activity.

  9. Instability and internet design

    Directory of Open Access Journals (Sweden)

    Sandra Braman


    Full Text Available Instability - unpredictable but constant change in one’s environment and the means with which one deals with it - has replaced convergence as the focal problem for telecommunications policy in general and internet policy in particular. Those who designed what we now call the internet during the first decade of the effort (1969-1979, who in essence served simultaneously as its policy-makers, developed techniques for coping with instability of value for network designers today and for those involved with any kind of large-scale sociotechnical infrastructure. Analysis of the technical document series that was medium for and record of that design process reveals coping techniques that began with defining the problem and went on to include conceptual labour, social practices, and technical approaches.

  10. Modulation instability: The beginning (United States)

    Zakharov, V. E.; Ostrovsky, L. A.


    We discuss the early history of an important field of “sturm and drang” in modern theory of nonlinear waves. It is demonstrated how scientific demand resulted in independent and almost simultaneous publications by many different authors on modulation instability, a phenomenon resulting in a variety of nonlinear processes such as envelope solitons, envelope shocks, freak waves, etc. Examples from water wave hydrodynamics, electrodynamics, nonlinear optics, and convection theory are given.

  11. The instability of markets

    CERN Document Server

    Huberman, B A; Huberman, Bernardo A; Youssefmir, Michael


    Recent developments in the global liberalization of equity and currency markets, coupled to advances in trading technologies, are making markets increasingly interdependent. This increased fluidity raises questions about the stability of the international financial system. In this paper, we show that as couplings between stable markets grow, the likelihood of instabilities is increased, leading to a loss of general equilibrium as the system becomes increasingly large and diverse.

  12. Carpal instability nondissociative. (United States)

    Wolfe, Scott W; Garcia-Elias, Marc; Kitay, Alison


    Carpal instability nondissociative (CIND) represents a spectrum of conditions characterized by kinematic dysfunction of the proximal carpal row, often associated with a clinical "clunk." CIND is manifested at the midcarpal and/or radiocarpal joints, and it is distinguished from carpal instability dissociative (CID) by the lack of disruption between bones within the same carpal row. There are four major subcategories of CIND: palmar, dorsal, combined, and adaptive. In palmar CIND, instability occurs across the entire proximal carpal row. When nonsurgical management fails, surgical options include arthroscopic thermal capsulorrhaphy, soft-tissue reconstruction, or limited radiocarpal or intercarpal fusions. In dorsal CIND, the capitate subluxates dorsally from its reduced resting position. Dorsal CIND usually responds to nonsurgical management; refractory cases respond to palmar ligament reefing and/or dorsal intercarpal capsulodesis. Combined CIND demonstrates signs of both palmar and dorsal CIND and can be treated with soft-tissue or bony procedures. In adaptive CIND, the volar carpal ligaments are slackened and are less capable of inducing the physiologic shift of the proximal carpal row from flexion into extension as the wrist ulnarly deviates. Treatment of choice is a corrective osteotomy to restore the normal volar tilt of the distal radius.

  13. Unique genomic structure and distinct mitotic behavior of ring chromosome 21 in two unrelated cases. (United States)

    Zhang, H Z; Xu, F; Seashore, M; Li, P


    A ring chromosome replacing a normal chromosome could involve variable structural rearrangements and mitotic instability. However, most previously reported cases lacked further genomic characterization. High-resolution oligonucleotide array comparative genomic hybridization with single-nucleotide polymorphism typing (aCGH+SNP) was used to study 2 unrelated cases with a ring chromosome 21. Case 1 had severe myopia, hypotonia, joint hypermobility, speech delay, and dysmorphic features. aCGH detected a 1.275-Mb duplication of 21q22.12-q22.13 and a 6.731-Mb distal deletion at 21q22.2. Case 2 showed severe growth and developmental retardations, intractable seizures, and dysmorphic features. aCGH revealed a contiguous pattern of a 3.612- Mb deletion of 21q22.12-q22.2, a 4.568-Mb duplication of 21q22.2-q22.3, and a 2.243-Mb distal deletion at 21q22.3. Mitotic instability was noted in 13, 30, and 76% of in vitro cultured metaphase cells, interphase cells, and leukocyte DNA, respectively. The different phenotypes of these 2 cases are likely associated with the unique genomic structure and distinct mitotic behavior of their ring chromosome 21. These 2 cases represent a subtype of ring chromosome 21 probably involving somatic dicentric ring breakage and reunion. A cytogenomic approach is proposed for characterizing the genomic structure and mitotic instability of ring chromosome abnormalities.

  14. "Chromosome": a knowledge-based system for the chromosome classification. (United States)

    Ramstein, G; Bernadet, M


    Chromosome, a knowledge-based analysis system has been designed for the classification of human chromosomes. Its aim is to perform an optimal classification by driving a tool box containing the procedures of image processing, pattern recognition and classification. This paper presents the general architecture of Chromosome, based on a multiagent system generator. The image processing tool box is described from the met aphasic enhancement to the fine classification. Emphasis is then put on the knowledge base intended for the chromosome recognition. The global classification process is also presented, showing how Chromosome proceeds to classify a given chromosome. Finally, we discuss further extensions of the system for the karyotype building.

  15. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires


    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.

  16. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)



    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.

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

    Directory of Open Access Journals (Sweden)

    Yerle Martine


    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.

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

  19. Chromosomal rearrangement interferes with meiotic X chromosome inactivation


    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri


    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X–autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencin...

  20. Modulational instability of nematic phase

    Indian Academy of Sciences (India)

    T Mithun; K Porsezian


    We numerically observe the effect of homogeneous magnetic field on the modulationally stable case of polar phase in = 2 spinor Bose–Einstein condensates (BECs). Also we investigate the modulational instability of uniaxial and biaxial (BN) states of polar phase. Our observations show that the magnetic field triggers the modulational instability and demonstrate that irrespective of the magnetic field effect the uniaxial and biaxial nematic phases show modulational instability.

  1. Weibel instability with nonextensive distribution

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Hui-Bin; Liu, Shi-Bing [Strong-field and Ultrafast Photonics Lab, Institute of Laser Engineering, Beijing University of Technology, Beijing 100124 (China)


    Weibel instability in plasma, where the ion distribution is isotropic and the electron component of the plasma possesses the anisotropic temperature distribution, is investigated based on the kinetic theory in context of nonextensive statistics mechanics. The instability growth rate is shown to be dependent on the nonextensive parameters of both electron and ion, and in the extensive limit, the result in Maxwellian distribution plasma is recovered. The instability growth rate is found to be enhanced as the nonextensive parameter of electron increases.

  2. Political Instability and Economic Growth


    Swagel, Phillip; Roubini, Nouriel; Ozler, Sule; Alesina, Alberto


    This paper investigates the relationship between political instability and per capita GDP growth in a sample of 113 countries for the period 1950-1982. We define ?political instability? as the propensity of a government collapse, and we estimate a model in which political instability and economic growth are jointly determined. The main result of this paper is that in countries and time periods with a high propensity of government collapse, growth is significantly lower than otherwise. This ef...

  3. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

    Directory of Open Access Journals (Sweden)

    Ruth N. MacKinnon


    Full Text Available 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.

  4. The role of dicentric chromosome formation and secondary centromere deletion in the evolution of myeloid malignancy. (United States)

    Mackinnon, Ruth N; Campbell, Lynda J


    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.

  5. B chromosomes in the species Prochilodus argenteus (Characiformes, Prochilodontidae: morphologicalidentity and dispersion

    Directory of Open Access Journals (Sweden)

    Manolo Penitente


    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.

  6. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;


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

  7. Chromosome Variations And Human Behavior (United States)

    Soudek, D.


    Article focused on the science of cytogenetics, which studied the transmission of the units of heredity called chromosomes, and considered the advantage of proper diagnosis of genetic diseases, treated on the chromosomal level. (Author/RK)

  8. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B;


    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...

  9. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.


    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.

  10. The Y Chromosome (United States)

    Offner, Susan


    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…

  11. Why Chromosome Palindromes?

    Directory of Open Access Journals (Sweden)

    Esther Betrán


    Full Text Available We look at sex-limited chromosome (Y or W evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the “palindromes as protectors” view: (1 genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2 under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes.

  12. Libration driven multipolar instabilities

    CERN Document Server

    Cébron, David; Herreman, Wietze


    We consider rotating flows in non-axisymmetric enclosures that are driven by libration, i.e. by a small periodic modulation of the rotation rate. Thanks to its simplicity, this model is relevant to various contexts, from industrial containers (with small oscillations of the rotation rate) to fluid layers of terrestial planets (with length-of-day variations). Assuming a multipolar $n$-fold boundary deformation, we first obtain the two-dimensional basic flow. We then perform a short-wavelength local stability analysis of the basic flow, showing that an instability may occur in three dimensions. We christen it the Libration Driven Multipolar Instability (LDMI). The growth rates of the LDMI are computed by a Floquet analysis in a systematic way, and compared to analytical expressions obtained by perturbation methods. We then focus on the simplest geometry allowing the LDMI, a librating deformed cylinder. To take into account viscous and confinement effects, we perform a global stability analysis, which shows that...

  13. Instability of enclosed horizons

    CERN Document Server

    Kay, Bernard S


    We study the classical massless scalar wave equation on the region of 1+1-dimensional Minkowski space between the two branches of the hyperbola $x^2-t^2=1$ with vanishing boundary conditions on it. We point out that there are initially finite-energy initially, say, right-going waves for which the stress-energy tensor becomes singular on the null-line $t+x=0$. We also construct the quantum theory of this system and show that, while there is a regular Hartle-Hawking-Israel-like state, there are coherent states built on this for which there is a similar singularity in the expectation value of the renormalized stress-energy tensor. We conjecture that in 1+3-dimensional situations with 'enclosed horizons' such as a (maximally extended) Schwarzschild black hole in equilibrium in a stationary box or the (maximally extended) Schwarzschild-AdS spacetime, there will be a similar singularity at the horizon and that would signal an instability when matter perturbations and/or gravity are switched on. Such an instability ...

  14. [Aspirin suppresses microsatellite instability]. (United States)

    Wallinger, S; Dietmaier, W; Beyser, K; Bocker, T; Hofstädter, F; Fishel, R; Rüschoff, J


    Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit cancer preventive effects and have been shown to induce regression of adenomas in FAP patients. In order to elucidate the probable underlying mechanism, the effect of NSAIDs on mismatch repair related microsatellite instability was investigated. Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. For rapid in vitro analysis of MSI a microcloning assay was developed by combining Laser microdissection and random (PEP-) PCR prior to specific MSI-PCR. Effects of NSAIDs on cell cycle and apoptosis were systematically investigated by using flow cytometry and cell-sorting. MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment. This effect was reversible, time- and concentration dependent. However, in the hPMS2 deficient endometrial cancer cell line (HEC-1-A) the MSI phenotype kept unchanged. According to cell sorting, non-apoptotic cells were stable and apoptotic cells were unstable. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may thus provide an effective prophylactic therapy for HNPCC related colorectal carcinomas.

  15. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation (United States)

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


    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.

  16. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation (United States)

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


    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.

  17. [Dicentric Y chromosome]. (United States)

    Abdelmoula, N Bouayed; Amouri, A


    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  18. Dynamics of X Chromosome Inactivation

    NARCIS (Netherlands)

    F. Loos (Friedemann)


    markdownabstract__Abstract__ Dosage compensation evolved to account for the difference in expression of sex chromosome-linked genes. In mammals dosage compensation is achieved by inactivation of one X chromosome during early female embryogenesis in a process called X chromosome inactivation (XCI).

  19. Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20. (United States)

    Guediche, N; Brisset, S; Benichou, J-J; Guérin, N; Mabboux, P; Maurin, M-L; Bas, C; Laroudie, M; Picone, O; Goldszmidt, D; Prévot, S; Labrune, P; Tachdjian, G


    The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.

  20. Familial complex chromosomal rearrangement resulting in a recombinant chromosome. (United States)

    Berend, Sue Ann; Bodamer, Olaf A F; Shapira, Stuart K; Shaffer, Lisa G; Bacino, Carlos A


    Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We report on a CCR identified in a child with congenital heart disease and dysmorphic features. Initially, the child's karyotype was thought to involve a straightforward three-way translocation between chromosomes 3, 8, and 16. However, after analyzing the mother's chromosomes, the mother was found to have a more complex rearrangement that resulted in a recombinant chromosome in the child. The mother's karyotype included an inverted chromosome 2 and multiple translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or duplication that could account for the clinical findings in the child was identified.

  1. 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.

  2. Bony instability of the shoulder. (United States)

    Bushnell, Brandon D; Creighton, R Alexander; Herring, Marion M


    Instability of the shoulder is a common problem treated by many orthopaedists. Instability can result from baseline intrinsic ligamentous laxity or a traumatic event-often a dislocation that injures the stabilizing structures of the glenohumeral joint. Many cases involve soft-tissue injury only and can be treated successfully with repair of the labrum and ligamentous tissues. Both open and arthroscopic approaches have been well described, with recent studies of arthroscopic soft-tissue techniques reporting results equal to those of the more traditional open techniques. Over the last decade, attention has focused on the concept of instability of the shoulder mediated by bony pathology such as a large bony Bankart lesion or an engaging Hill-Sachs lesion. Recent literature has identified unrecognized large bony lesions as a primary cause of failure of arthroscopic reconstruction for instability, a major cause of recurrent instability, and a difficult diagnosis to make. Thus, although such bony lesions may be relatively rare compared with soft-tissue pathology, they constitute a critically important entity in the management of shoulder instability. Smaller bony lesions may be amenable to arthroscopic treatment, but larger lesions often require open surgery to prevent recurrent instability. This article reviews recent developments in the diagnosis and treatment of bony instability.

  3. Cinerama sickness and postural instability

    NARCIS (Netherlands)

    Bos, J.E.; Ledegang, W.D.; Lubeck, A.J.A.; Stins, J.F.


    Motion sickness symptoms and increased postural instability induced by motion pictures have been reported in a laboratory, but not in a real cinema. We, therefore, carried out an observational study recording sickness severity and postural instability in 19 subjects before, immediately and 45 min af

  4. Marital instability after midlife. (United States)

    Wu, Z; Penning, M J


    "Divorce in later life has been shown to produce dramatic declines in the economic, psychological, and physical well-being of marital partners. This study examines the prevalence and determinants of marital disruption after midlife using Becker's theory of marital instability. Using recent Canadian national data, the marital outcomes of women and men who were married as of age 40 are tracked across the remaining years of the marriage. Cox proportional hazard regression models indicate stabilizing effects of the duration of the marriage, the age at first marriage, the presence of young children, as well as of remarriage for middle-aged and older persons. Other significant risk factors include education, heterogamous marital status, premarital cohabitation, number of siblings, and region."

  5. Structural and Material Instability

    DEFF Research Database (Denmark)

    Cifuentes, Gustavo Cifuentes

    This work is a small contribution to the general problem of structural and material instability. In this work, the main subject is the analysis of cracking and failure of structural elements made from quasi-brittle materials like concrete. The analysis is made using the finite element method. Three...... use of interface elements) is used successfully to model cases where the path of the discontinuity is known in advance, as is the case of the analysis of pull-out of fibers embedded in a concrete matrix. This method is applied to the case of non-straight fibers and fibers with forces that have....... Numerical problems associated with the use of elements with embedded cracks based on the extended finite element method are presented in the next part of this work. And an alternative procedure is used in order to successfully remove these numerical problems. In the final part of this work, a computer...

  6. The bar instability revisited

    CERN Document Server

    Chiodi, Filippo; Claudin, Philippe


    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...

  7. Instability and Information

    CERN Document Server

    Patzelt, Felix


    Many complex systems exhibit extreme events far more often than expected for a normal distribution. This work examines how self-similar bursts of activity across several orders of magnitude can emerge from first principles in systems that adapt to information. Surprising connections are found between two apparently unrelated research topics: hand-eye coordination in balancing tasks and speculative trading in financial markets. Seemingly paradoxically, locally minimising fluctuations can increase a dynamical system's sensitivity to unpredictable perturbations and thereby facilitate global catastrophes. This general principle is studied in several domain-specific models and in behavioural experiments. It explains many findings in both fields and resolves an apparent antinomy: the coexistence of stabilising control or market efficiency and perpetual instabilities resembling critical phenomena in physical systems.

  8. Gravitational Instabilities in Circumstellar Disks

    CERN Document Server

    Kratter, Kaitlin M


    [Abridged] Star and planet formation are the complex outcomes of gravitational collapse and angular momentum transport mediated by protostellar and protoplanetary disks. In this review we focus on the role of gravitational instability in this process. We begin with a brief overview of the observational evidence for massive disks that might be subject to gravitational instability, and then highlight the diverse ways in which the instability manifests itself in protostellar and protoplanetary disks: the generation of spiral arms, small scale turbulence-like density fluctuations, and fragmentation of the disk itself. We present the analytic theory that describes the linear growth phase of the instability, supplemented with a survey of numerical simulations that aim to capture the non-linear evolution. We emphasize the role of thermodynamics and large scale infall in controlling the outcome of the instability. Despite apparent controversies in the literature, we show a remarkable level of agreement between analyt...

  9. Beam instability Workshop - plenary sessions

    Energy Technology Data Exchange (ETDEWEB)



    The purpose of this workshop was to provide a review of the mechanisms of limiting beam instabilities, their cures, including feedback, and beam measurement for synchrotron radiation light sources. 12 plenary sessions took place whose titles are: 1) challenging brilliance and lifetime issues with increasing currents; 2) limiting instabilities in multibunch; 3) experience from high currents in B factories; 4) longitudinal dynamics in high intensity/bunch; 5) Transverse instabilities for high intensity/bunch; 6) working group introduction from ESRF experience; 7) impedance modelling: simulations, minimization; 8) report on the broadband impedance measurements and modelling workshop; 9) feedback systems for synchrotron light sources; 10) beam instabilities diagnostics; 11) harmonic cavities: the pros and cons; and 12) experimental study of fast beam-ion instabilities at PLS. This document gathers the 12 articles that were presented during these sessions.

  10. Equilibrium Electro-osmotic Instability

    CERN Document Server

    Rubinstein, Isaak


    Since its prediction fifteen years ago, electro-osmotic instability has been attributed to non-equilibrium electro-osmosis related to the extended space charge which develops at the limiting current in the course of concentration polarization at a charge-selective interface. This attribution had a double basis. Firstly, it has been recognized that equilibrium electro-osmosis cannot yield instability for a perfectly charge-selective solid. Secondly, it has been shown that non-equilibrium electro-osmosis can. First theoretical studies in which electro-osmotic instability was predicted and analyzed employed the assumption of perfect charge-selectivity for the sake of simplicity and so did the subsequent numerical studies of various time-dependent and nonlinear features of electro-osmotic instability. In this letter, we show that relaxing the assumption of perfect charge-selectivity (tantamount to fixing the electrochemical potential in the solid) allows for equilibrium electro-osmotic instability. Moreover, we s...

  11. Instability in Shocked Granular Gases

    CERN Document Server

    Sirmas, Nick; Radulescu, Matei


    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.

  12. Instability in shocked granular gases (United States)

    Sirmas, Nick; Falle, Sam; Radulescu, Matei


    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.

  13. Gravitational Instabilities in Circumstellar Disks (United States)

    Kratter, Kaitlin; Lodato, Giuseppe


    Star and planet formation are the complex outcomes of gravitational collapse and angular momentum transport mediated by protostellar and protoplanetary disks. In this review, we focus on the role of gravitational instability in this process. We begin with a brief overview of the observational evidence for massive disks that might be subject to gravitational instability and then highlight the diverse ways in which the instability manifests itself in protostellar and protoplanetary disks: the generation of spiral arms, small-scale turbulence-like density fluctuations, and fragmentation of the disk itself. We present the analytic theory that describes the linear growth phase of the instability supplemented with a survey of numerical simulations that aim to capture the nonlinear evolution. We emphasize the role of thermodynamics and large-scale infall in controlling the outcome of the instability. Despite apparent controversies in the literature, we show a remarkable level of agreement between analytic predictions and numerical results. In the next part of our review, we focus on the astrophysical consequences of the instability. We show that the disks most likely to be gravitationally unstable are young and relatively massive compared with their host star, Md/M*≥0.1. They will develop quasi-stable spiral arms that process infall from the background cloud. Although instability is less likely at later times, once infall becomes less important, the manifestations of the instability are more varied. In this regime, the disk thermodynamics, often regulated by stellar irradiation, dictates the development and evolution of the instability. In some cases the instability may lead to fragmentation into bound companions. These companions are more likely to be brown dwarfs or stars than planetary mass objects. Finally, we highlight open questions related to the development of a turbulent cascade in thin disks and the role of mode-mode coupling in setting the maximum angular

  14. 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))


    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.

  15. Contributions of microtubule dynamic instability and rotational diffusion to kinetochore capture

    CERN Document Server

    Blackwell, Robert; Edelmaier, Christopher; Gergely, Zachary R; Flynn, Patrick J; Montes, Salvador; Crapo, Ammon; Doostan, Alireza; McIntosh, J Richard; Glaser, Matthew A; Betterton, Meredith D


    Microtubule dynamic instability allows search and capture of kinetochores during spindle formation, an important process for accurate chromosome segregation during cell division. Recent work has found that microtubule rotational diffusion about minus-end attachment points contributes to kinetochore capture in fission yeast, but the relative contributions of dynamic instability and rotational diffusion are not well understood. We have developed a biophysical model of kinetochore capture in small fission-yeast nuclei using hybrid Brownian dynamics/kinetic Monte Carlo simulation techniques. With this model, we have studied the importance of dynamic instability and microtubule rotational diffusion for kinetochore capture, both to the lateral surface of a microtubule and at or near its end. Over a range of biologically relevant parameters, microtubule rotational diffusion decreased capture time, but made a relatively small contribution compared to dynamic instability. At most, rotational diffusion reduced capture ...

  16. Genomic instability caused by hepatitis B virus: into the hepatoma inferno. (United States)

    Hsieh, Yi-Hsuan; Hsu, Jye-Lin; Su, Ih-Jen; Huang, Wenya


    Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide, especially in Asia. HBV induces HCC through multiple oncogenic pathways. Hepatitis-induced hepatocyte inflammation and regeneration stimulates cell proliferation. The interplay between the viral and host factors activates oncogenic signaling pathways and triggers cell transformation. In this review, we summarize previous studies, which reported that HBV induces host genomic instability and that HBV-induced genomic instability is a significant factor that accelerates carcinogenesis. The various types of genomic changes in HBV-induced HCC--chromosomal instability, telomere attrition, and gene-level mutations--are reviewed. In addition, the two viral factors, HBx and the pre-S2 mutant large surface antigen, are discussed for their roles in promoting genomic instability as their main features as viral oncoproteins.

  17. Embryos of robertsonian translocation carriers exhibit a mitotic interchromosomal effect that enhances genetic instability during early development.

    Directory of Open Access Journals (Sweden)

    Samer Alfarawati

    genetic fidelity are relaxed and chromosome rearrangements are present (e.g. in tumors displaying chromosomal instability.

  18. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ørntoft Torben


    Full Text Available Abstract Background Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1 or high grade of dysplasia are at "high risk" of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI is associated with high tumor stage and grade, and possibly with the risk of progression. Methods To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with "high-risk" non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical resections and full prospective clinical follow-up (> 5 years. We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays. Results Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a "high-risk" tumor. However, about 25% of the "high-risk" tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Conclusion Chromosomal instability (CI was associated with "high risk

  19. Abelianization of QCD plasma instabilities (United States)

    Arnold, Peter; Lenaghan, Jonathan


    QCD plasma instabilities appear to play an important role in the equilibration of quark-gluon plasmas in heavy-ion collisions in the theoretical limit of weak coupling (i.e. asymptotically high energy). It is important to understand what nonlinear physics eventually stops the exponential growth of unstable modes. It is already known that the initial growth of plasma instabilities in QCD closely parallels that in QED. However, once the unstable modes of the gauge fields grow large enough for non-Abelian interactions between them to become important, one might guess that the dynamics of QCD plasma instabilities and QED plasma instabilities become very different. In this paper, we give suggestive arguments that non-Abelian self-interactions between the unstable modes are ineffective at stopping instability growth, and that the growing non-Abelian gauge fields become approximately Abelian after a certain stage in their growth. This in turn suggests that understanding the development of QCD plasma instabilities in the nonlinear regime may have close parallels to similar processes in traditional plasma physics. We conjecture that the physics of collisionless plasma instabilities in SU(2) and SU(3) gauge theory becomes equivalent, respectively, to (i) traditional plasma physics, which is U(1) gauge theory, and (ii) plasma physics of U(1)×U(1) gauge theory.

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

    Directory of Open Access Journals (Sweden)

    Payne CM


    Full Text Available 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 with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  1. Instability of ties in compression

    DEFF Research Database (Denmark)

    Buch-Hansen, Thomas Cornelius


    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...... exact instability solutions are complex to derive, not to mention the extra complexity introducing dimensional instability from the temperature gradients. Using an inverse variable substitution and comparing an exact theory with an analytical instability solution a method to design tie...

  2. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    Directory of Open Access Journals (Sweden)

    Aaraby Yoheswaran Nielsen


    Full Text Available 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 similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.

  3. Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients. (United States)

    George, Alex; Dey, Rupraj; Bhuria, Vikas; Banerjee, Shouvik; Ethirajan, Sivakumar; Siluvaimuthu, Ashok; Saraswathy, Radha


    Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANEUP) in patients (CSAs, 0.0294±0.0038; CTAs, 0.0925±0.0060; DICs, 0.0213±0.0028; and CANEUPs, 0.0308±0.0035) compared to controls (CSAs, 0.0005±0.0003; CTAs, 0.0058±0.0015; DICs, 0.0005±0.0003; and CANEUPs, 0.0052±0.0013) where pnuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, 0.01867±0.00108; NPBs, 0.01561±0.00234; NBUDs, 0.00658±0.00068) compared with controls (MNi, 0.00027±0.00009; NPBs, 0.00002±0.00002; NBUDs, 0.00011±0.00007).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients (1.525±0.005552) compared to healthy subjects (1.686±0.009520 ) (pproliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

  4. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin


    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  5. Chromosome assortment in Saccharum. (United States)

    Al-Janabi, S M; Honeycutt, R J; Sobral, B W


    Recent work has revealed random chromosome pairing and assortment in Saccharum spontaneum L., the most widely distributed, and morphologically and cytologically variable of the species of Saccharum. This conclusion was based on the analysis of a segregating population from across between S. spontaneum 'SES 208' and a spontaneously-doubled haploid of itself, derived from anther culture. To determine whether polysomic inheritance is common in Saccharum and whether it is observed in a typical biparental cross, we studied chromosome pairing and assortment in 44 progeny of a cross between euploid, meiotically regular, 2n=80 forms of Saccharum officinarum 'LA Purple' and Saccharum robustum ' Mol 5829'. Papuan 2n=80 forms of S. robustum have been suggested as the immediate progenitor species for cultivated sugarcane (S. officinarum). A total of 738 loci in LA Purple and 720 loci in Mol 5829 were amplified and typed in the progeny by arbitrarily primed PCR using 45 primers. Fifty and 33 single-dose polymorphisms were identified in the S. officinarum and S. robustum genomes, respectively (χ 2 at 98%). Linkage analysis of single-dose polymorphisms in both genomes revealed linkages in repulsion and coupling phases. In the S. officinarum genome, a map hypothesis gave 7 linkage groups with 17 linked and 33 unlinked markers. Four of 13 pairwise linkages were in repulsion phase and 9 were in coupling phase. In the S. robustum genome, a map hypothesis gave 5 linkage groups, defined by 12 markers, with 21 markers unlinked, and 2 of 9 pairwise linkages were in repulsion phase. Therefore, complete polysomic inheritance was not observed in either species, suggesting that chromosomal behavior is different from that observed by linkage analysis of over 500 markers in the S. spontaneum map. Implications of this finding for evolution and breeding are discussed.

  6. Evaporative instabilities in climbing films (United States)

    Hosoi, A. E.; Bush, John W. M.


    We consider flow in a thin film generated by partially submerging an inclined rigid plate in a reservoir of ethanol or methanol water solution and wetting its surface. Evaporation leads to concentration and surface tension gradients that drive flow up the plate. An experimental study indicates that the climbing film is subject to two distinct instabilities. The first is a convective instability characterized by flattened convection rolls aligned in the direction of flow and accompanied by free-surface deformations; in the meniscus region, this instability gives rise to pronounced ridge structures aligned with the mean flow. The second instability, evident when the plate is nearly vertical, takes the form of transverse surface waves propagating up the plate.

  7. 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


    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...

  8. Atlantoaxial instability in Down's syndrome


    J Gordon Millichap


    The radiographs and clinical evaluations of 90 children with Down’s syndrome were reassessed after an interval of 5 years in a study of atlantoaxial instability (AAI) at the Derbyshire Children’s Hospital and Infirmary, Derby, UK.

  9. Midcarpal instability: a radiological perspective

    Energy Technology Data Exchange (ETDEWEB)

    Toms, Andoni Paul [Norfolk and Norwich University Hospital NHS Trust, Department of Radiology, Norwich, Norfolk (United Kingdom); Radiology Academy, Cotman Centre, Norwich, Norfolk (United Kingdom); Chojnowski, Adrian [Norfolk and Norwich University Hospital NHS Trust, Department of Orthopaedic Surgery, Norwich, Norfolk (United Kingdom); Cahir, John G. [Norfolk and Norwich University Hospital NHS Trust, Department of Radiology, Norwich, Norfolk (United Kingdom)


    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.)

  10. Material Instabilities in Particulate Systems (United States)

    Goddard, J. D.


    Following is a brief summary of a theoretical investigation of material (or constitutive) instability associated with shear induced particle migration in dense particulate suspensions or granular media. It is shown that one can obtain a fairly general linear-stability analysis, including the effects of shear-induced anisotropy in the base flow as well as Reynolds dilatancy. A criterion is presented here for simple shearing instability in the absence of inertia and dilatancy.

  11. Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells. (United States)

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


    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.

  12. Instability of enclosed horizons (United States)

    Kay, Bernard S.


    We point out that there are solutions to the scalar wave equation on dimensional Minkowski space with finite energy tails which, if they reflect off a uniformly accelerated mirror due to (say) Dirichlet boundary conditions on it, develop an infinite stress-energy tensor on the mirror's Rindler horizon. We also show that, in the presence of an image mirror in the opposite Rindler wedge, suitable compactly supported arbitrarily small initial data on a suitable initial surface will develop an arbitrarily large stress-energy scalar near where the two horizons cross. Also, while there is a regular Hartle-Hawking-Israel-like state for the quantum theory between these two mirrors, there are coherent states built on it for which there are similar singularities in the expectation value of the renormalized stress-energy tensor. We conjecture that in other situations with analogous enclosed horizons such as a (maximally extended) Schwarzschild black hole in equilibrium in a (stationary spherical) box or the (maximally extended) Schwarzschild-AdS spacetime, there will be similar stress-energy singularities and almost-singularities—leading to instability of the horizons when gravity is switched on and matter and gravity perturbations are allowed for. All this suggests it is incorrect to picture a black hole in equilibrium in a box or a Schwarzschild-AdS black hole as extending beyond the past and future horizons of a single Schwarzschild (/Schwarzschild-AdS) wedge. It would thus provide new evidence for 't Hooft's brick wall model while seeming to invalidate the picture in Maldacena's ` Eternal black holes in AdS'. It would thereby also support the validity of the author's matter-gravity entanglement hypothesis and of the paper ` Brick walls and AdS/CFT' by the author and Ortíz.

  13. Vector-Resonance-Multimode Instability (United States)

    Sergeyev, S. V.; Kbashi, H.; Tarasov, N.; Loiko, Yu.; Kolpakov, S. A.


    The modulation and multimode instabilities are the main mechanisms which drive spontaneous spatial and temporal pattern formation in a vast number of nonlinear systems ranging from biology to laser physics. Using an Er-doped fiber laser as a test bed, here for the first time we demonstrate both experimentally and theoretically a new type of a low-threshold vector-resonance-multimode instability which inherits features of multimode and modulation instabilities. The same as for the multimode instability, a large number of longitudinal modes can be excited without mode synchronization. To enable modulation instability, we modulate the state of polarization of the lasing signal with the period of the beat length by an adjustment of the in-cavity birefringence and the state of polarization of the pump wave. As a result, we show the regime's tunability from complex oscillatory to periodic with longitudinal mode synchronization in the case of resonance matching between the beat and cavity lengths. Apart from the interest in laser physics for unlocking the tunability and stability of dynamic regimes, the proposed mechanism of the vector-resonance-multimode instability can be of fundamental interest for the nonlinear dynamics of various distributed systems.

  14. Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia. (United States)

    Sarova, Iveta; Brezinova, Jana; Zemanova, Zuzana; Ransdorfova, Sarka; Izakova, Silvia; Svobodova, Karla; Pavlistova, Lenka; Berkova, Adela; Cermak, Jaroslav; Jonasova, Anna; Siskova, Magda; Michalova, Kyra


    Dicentric chromosomes (DCs) have been described in many hematological diseases, including acute myeloid leukemia (AML). They are markers of cancer and induce chromosomal instability, leading to the formation of other chromosomal aberrations and the clonal evolution of pathological cells. Our knowledge of the roles and behavior of human DCs is often derived from studies of induced DCs and cell lines. It is difficult to identify all the DCs in the karyotypes of patients because of the limitations of metaphase cytogenetic methods. The aim of this study was to revise the karyotypes of 20 AML patients in whom DCs were found with conventional G-banding or multicolor fluorescence in situ hybridization (mFISH) with (multi)centromeric probes and to characterize the DCs at the molecular cytogenetic level. FISH analyses confirmed 23 of the 29 expected DCs in 18 of 20 patients and identified 13 others that had not been detected cytogenetically. Fourteen DCs were altered by other chromosomal changes. In conclusion, karyotypes with DCs are usually very complex, and we have shown that they often contain more than one DC, which can be missed with conventional or mFISH methods. Our study indicates an association between number of DCs in karyotype and very short survival of patients.

  15. Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes (United States)

    Liehr, Thomas; Karamysheva, Tatyana; Merkas, Martina; Brecevic, Lukrecija; Hamid, Ahmed B.; Ewers, Elisabeth; Mrasek, Kristin; Kosyakova, Nadezda; Weise, Anja


    Somatic mosaicism is something that is observed in everyday lives of cytogeneticists. Chromosome instability is one of the leading causes of large-scale genome variation analyzable since the correct human chromosome number was established in 1956. Somatic mosaicism is also a well-known fact to be present in cases with small supernumerary marker chromosomes (sSMC), i.e. karyotypes of 47,+mar/46. In this study, the data available in the literature were collected concerning the frequency mosaicism in different subgroups of patients with sSMC. Of 3124 cases with sSMC 1626 (52%) present with somatic mosaicism. Some groups like patients with Emanuel-, cat-eye- or i(18p)- syndrome only tend rarely to develop mosaicism, while in Pallister-Killian syndrome every patient is mosaic. In general, acrocentric and non-acrocentric derived sSMCs are differently susceptible to mosaicism; non-acrocentric derived ones are hereby the less stable ones. Even though, in the overwhelming majority of the cases, somatic mosaicism does not have any detectable clinical effects, there are rare cases with altered clinical outcomes due to mosaicism. This is extremely important for prenatal genetic counseling. Overall, as mosaicism is something to be considered in at least every second sSMC case, array-CGH studies cannot be offered as a screening test to reliably detect this kind of chromosomal aberration, as low level mosaic cases and cryptic mosaics are missed by that. PMID:21358988

  16. The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes Genomic Instability in Diploid Cells of Saccharomyces cerevisiae (United States)

    Quevedo, Oliver; Ramos-Pérez, Cristina; Petes, Thomas D.; Machín, Félix


    Genomic instability is a common feature found in cancer cells . Accordingly, many tumor suppressor genes identified in familiar cancer syndromes are involved in the maintenance of the stability of the genome during every cell division and are commonly referred to as caretakers. Inactivating mutations and epigenetic silencing of caretakers are thought to be the most important mechanisms that explain cancer-related genome instability. However, little is known of whether transient inactivation of caretaker proteins could trigger genome instability and, if so, what types of instability would occur. In this work, we show that a brief and reversible inactivation, during just one cell cycle, of the key phosphatase Cdc14 in the model organism Saccharomyces cerevisiae is enough to result in diploid cells with multiple gross chromosomal rearrangements and changes in ploidy. Interestingly, we observed that such transient loss yields a characteristic fingerprint whereby trisomies are often found in small-sized chromosomes, and gross chromosome rearrangements, often associated with concomitant loss of heterozygosity, are detected mainly on the ribosomal DNA-bearing chromosome XII. Taking into account the key role of Cdc14 in preventing anaphase bridges, resetting replication origins, and controlling spindle dynamics in a well-defined window within anaphase, we speculate that the transient loss of Cdc14 activity causes cells to go through a single mitotic catastrophe with irreversible consequences for the genome stability of the progeny. PMID:25971663

  17. Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisong [ORNL; Liu, Yie [ORNL


    Msh2 is a key mammalian DNA mismatch repair (MMR) gene and mutations or deficiencies in mammalian Msh2 gene result in microsatellite instability (MSI+) and the development of cancer. Here, we report that primary mouse embryonic fibroblasts (MEFs) deficient in the murine MMR gene Msh2 (Msh2-/-) showed a significant increase in chromosome aneuploidy, centrosome amplification, and defective mitotic spindle organization and unequal chromosome segregation. Although Msh2-/- mouse tissues or primary MEFs had no apparent change in telomerase activity, telomere length, or recombination at telomeres, Msh2-/- MEFs showed an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA. These data suggest that MSH2 helps to maintain genomic stability through the regulation of the centrosome and normal telomere capping in vivo and that defects in MMR can contribute to oncogenesis through multiple pathways.

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

    Energy Technology Data Exchange (ETDEWEB)

    Taalman, R.D.F.M.; Scheres, J.M.J.C.; Hustinx, T.W.J. (Katholieke Univ. Nijmegen (Netherlands). Dept. of Human Genetics); Jaspers, N.G.J.; de Wit, J. (Erasmus Universiteit, Rotterdam (Netherlands). Lab. of Cell Biology and Genetics)


    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 G/sub 2/. 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.

  19. Chromosome Connections: Compelling Clues to Common Ancestry (United States)

    Flammer, Larry


    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…

  20. Chromosomal rearrangement interferes with meiotic X chromosome inactivation. (United States)

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri


    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  1. Elliptic and magneto-elliptic instabilities

    Directory of Open Access Journals (Sweden)

    Lyra Wladimir


    Full Text Available Vortices are the fundamental units of turbulent flow. Understanding their stability properties therefore provides fundamental insights on the nature of turbulence itself. In this contribution I briely review the phenomenological aspects of the instability of elliptic streamlines, in the hydro (elliptic instability and hydromagnetic (magneto-elliptic instability regimes. Vortex survival in disks is a balance between vortex destruction by these mechanisms, and vortex production by others, namely, the Rossby wave instability and the baroclinic instability.

  2. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)


    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  3. Microsatellite instability confounds engraftment analysis of hematopoietic stem-cell transplantation. (United States)

    Tseng, Li-Hui; Tang, Jih-Luh; Haley, Lisa; Beierl, Katie; Gocke, Christopher D; Eshleman, James R; Lin, Ming-Tseh


    Polymorphic short tandem-repeat, or microsatellite, loci have been widely used to analyze chimerism status after allogeneic hematopoietic stem-cell transplantation. In molecular diagnostic laboratories, it is recommended to calculate mixed chimerism for at least 2 informative loci and to avoid microsatellite loci on chromosomes with copy number changes. In this report, we show that microsatellite instability observed in 2 patients with acute leukemia may confound chimerism analysis. Interpretation errors may occur even if 2 to 3 loci are analyzed because of length variation in multiple microsatellite loci. Although microsatellite loci with length variation should not be selected for chimerism analysis, the presence of microsatellite instability, like copy number alteration because of aberrant chromosomes, provides evidence of recurrent or residual cancer cells after hematopoietic stem-cell transplantation.

  4. Genetics Home Reference: Y chromosome infertility (United States)

    ... Home Health Conditions Y chromosome infertility Y chromosome infertility Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Y chromosome infertility is a condition that affects the production of ...

  5. Higher order structure of chromosomes. (United States)

    Okada, T A; Comings, D E


    Isolated Chinese hamster metaphase chromosomes were resuspended in 4 M ammonium acetate and spread on a surface of distilled water or 0.15 to 0.5 M ammonium acetate. The DNA was released in the form of a regular series of rosettes connected by interrossette DNA. The mean length of the rosette DNA was 14 micron, similar to the mean length of 10 micron for chromomere DNA of Drosophila polytene chromosomes. The mean interrosette DNA was 4.2 micron. SDS gel electrophoresis of the chromosomal nonhistone proteins showed them to be very similar to nuclear nonhistone proteins except for the presence of more actin and tubulin. Nuclear matrix proteins were present in the chromosomes and may play a role in forming the rosettes. Evidence that the rosette pattern is artifactual versus the possibility that it represents a real organizational substructure of the chromosomes is reviewed.

  6. Bacterial chromosome organization and segregation. (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T


    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation.

  7. Chromosome choreography: the meiotic ballet. (United States)

    Page, Scott L; Hawley, R Scott


    The separation of homologous chromosomes during meiosis in eukaryotes is the physical basis of Mendelian inheritance. The core of the meiotic process is a specialized nuclear division (meiosis I) in which homologs pair with each other, recombine, and then segregate from each other. The processes of chromosome alignment and pairing allow for homolog recognition. Reciprocal meiotic recombination ensures meiotic chromosome segregation by converting sister chromatid cohesion into mechanisms that hold homologous chromosomes together. Finally, the ability of sister kinetochores to orient to a single pole at metaphase I allows the separation of homologs to two different daughter cells. Failures to properly accomplish this elegant chromosome dance result in aneuploidy, a major cause of miscarriage and birth defects in human beings.

  8. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others


    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  9. Kinesin 5B (KIF5B is required for progression through female meiosis and proper chromosomal segregation in mitotic cells.

    Directory of Open Access Journals (Sweden)

    Dawit Kidane

    Full Text Available The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD and failure in extrusion of the first polar body (PBE. In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

  10. Kinesin 5B (KIF5B) is required for progression through female meiosis and proper chromosomal segregation in mitotic cells. (United States)

    Kidane, Dawit; Sakkas, Denny; Nottoli, Timothy; McGrath, James; Sweasy, Joann B


    The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b) during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi)-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD) and failure in extrusion of the first polar body (PBE). In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

  11. Chromosome number evolution in Hymenophyllum (Hymenophyllaceae), with special reference to the subgenus Hymenophyllum. (United States)

    Hennequin, Sabine; Ebihara, Atsushi; Dubuisson, Jean-Yves; Schneider, Harald


    With about 100 species distributed worldwide, Hymenophyllum subg. Hymenophyllum is the largest subgenus of filmy ferns. It also displays morphological disparity and extreme chromosome numbers variation, with n=11, 12, 13, 14, 18, 21, 22, 26, 28, and 34. We use DNA sequences from the genes rbcL, part of accD, rps4, and the intergenic spacers rbcL-accD, rps4-trnS, and trnG-trnR to infer relationships within Hymenophyllum, with a focus on this subgenus. In the subgenus Hymenophyllum, two main clades are retrieved together with several minor clades whose placement within the subgenus remains ambiguous. We then investigate the evolution of chromosome numbers in the genus and the subgenus, using a maximum likelihood approach taking into account phylogenetic uncertainty. We provide evidence that Hymenophyllum experienced descending aneuploidy during its evolutionary history, especially within the subgenus Hymenophyllum. Reduction in chromosome numbers is particularly extreme in one clade of the subgenus, with the lowest number reported for homosporous ferns. In addition, this group of species displays a high instability in its chromosome number. Both the reduction and the instability in chromosome number may coincide with the distribution of these species in either temperate areas or at high elevations.

  12. 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


    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.

  13. Structural Chromosomal Alterations Induced by Dietary Bioflavonoids in Fanconi Anemia Lymphocytes

    Directory of Open Access Journals (Sweden)

    Gonzalo Guevara


    Full Text Available IntroductionFanconi anemia is an autosomal recessive diseasecharacterized by a variety of congenital abnormalities,progressive bone marrow failure,increased chromosomal instability and higherrisk to acute myeloid leukemia, solid tumors. Thisentity can be considered an appropriate biologicalmodel to analyze natural substances with possiblegenotoxic effect. The aims of this study wereto describe and quantify structural chromosomalaberrations induced by 5 flavones, 2 isoflavonesand a topoisomerase II chemotherapeutic inhibitorin Fanconi anemia lymphocytes in order todetermine chromosomal numbers changes and/or type of chromosomal damage.Materials and methodsChromosomes stimulated by phytohaemagglutininM, from Fanconi anemia lymphocytes,were analysed by conventional cytogenetic culture.For each chemical substance and controls,one hundred metaphases were evaluated. Chromosomalalterations were documented by photographyand imaging analyzer. To statisticalanalysis was used chi square test to identify significantdifferences between frequencies of chromosomaldamage of basal and exposed cellcultured a P value less than 0.05.ResultsThere were 431 chromosomal alterations in1000 metaphases analysed; genistein was themore genotoxic bioflavonoid, followed in descendentorder by genistin, fisetin, kaempferol,quercetin, baicalein and miricetin. Chromosomalaberrations observed were: chromatidbreaks, chromosomal breaks, cromatid andchromosomal gaps, quadriratials exchanges,dicentrics chromosome and complex rearrangements.ConclusionBioflavonoids as genistein, genistin and fisetin,which are commonly present in the human diet,showed statistical significance in the number ofchromosomal aberrations in Fanconi anemialymphocytes, regarding the basal damage.


    Institute of Scientific and Technical Information of China (English)

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君


    Objective: To investigate whether deletion of chromosome 17 is involved in the carcinogenesis of primary glioblastoma multiforme and to localize the possible common deletion region in the aforementioned chromosome. Methods: Polymerase chain reaction-based microsatellite analysis was used to assess loss of heterozygosity (LOH) on chromosome 17 in 20 primary glioblastoma multiforme (GBM). Fifteen fluorescent dye-labeled polymorphic markers were used. Results: Thirteen of twenty (65%) GBM displayed LOH on at least one marker of chromosome 17p. Two tumors showed either LOH or non-informativeness on all markers tested. The most frequent LOH was observed at loci including D17s799 (53.3%), Dl7s1852 (53.8%), Dl7s938 (63.20/o), Dl7s831 (55.6%). The loci D17s831 (on 17pl3) and D17s799(Dl7sl852 (17p11.2(pl2) are distal and proximal to p53 respectively. The frequencies of LOH at all loci examined on chromosome 17q were relatively low (<30%). None of informative loci exhibited microsatellite instability in this study. Conclusion: Loss of genetic material on chromosome 17p may play an important role in the pathogenesis of GBM. Besides the well-known TSG p53 on 17p, other unknown TSCs associated with GBM may be present on the chromosomal regions 17pl3 and 17p11.2(pl2, which are distal and proximal to p53 respectively.

  15. Chromatid Painting for Chromosomal Inversion Detection Project (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...



  17. Chromatid Painting for Chromosomal Inversion Detection Project (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  18. Ring Chromosome 9 and Chromosome 9p Deletion Syndrome in a Patient Associated with Developmental Delay: A Case Report and Review of the Literature. (United States)

    Sivasankaran, Aswini; Kanakavalli, Murthy K; Anuradha, Deenadayalu; Samuel, Chandra R; Kandukuri, Lakshmi R


    Ring chromosomes have been described for all human chromosomes and are typically associated with physical and/or mental abnormalities resulting from a deletion of the terminal ends of both chromosome arms. This report describes the presence of a ring chromosome 9 in a 2-year-old male child associated with developmental delay. The proband manifested a severe phenotype comprising facial dysmorphism, congenital heart defects, and seizures. The child also exhibited multiple cell lines with mosaic patterns of double rings, a dicentric ring and loss of the ring associated with mitotic instability and dynamic tissue-specific mosaicism. His karyotype was 46,XY,r(9)(p22q34)[89]/46,XY,dic r(9; 9)(p22q34;p22q34)[6]/45, XY,-9[4]/47,XY,r(9),+r(9)[1]. However, the karyotypes of his parents and elder brother were normal. FISH using mBAND probe and subtelomeric probes specific for p and q arms for chromosome 9 showed no deletion in any of the regions. Chromosomal microarray analysis led to the identification of a heterozygous deletion of 15.7 Mb from 9p22.3 to 9p24.3. The probable role of the deleted genes in the manifestation of the phenotype of the proband is discussed.

  19. Chromosome aberrations and micronucleus in continuously irradiated mice for a low dose rate of {sup 137}Cs {gamma}-rays

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Jun; Yanai, Takanori; Shirata, Katsutoshi; Tanaka, Kimio; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)


    Delayed chromosomal instability is developed by radiation after several cell divisions in cultured rodent and human cells. The genetic instability might be related to cancer development and it has been mainly found in cultured rodent and human cells irradiated at high dose rate. It has not been well studied whether the genetic instability is induced by prolonged irradiation with low dose rate in vivo or not. Mice irradiated with 20 mGy/day for 5-8 Gy were analyzed by FISH to estimate the chromosome aberration rate and micronucleus incidence in spleen and bone marrow cells. Spleen cells in mice exposed to 8 Gy have higher incidence of monosomy and trisomy than non-exposed mice. The number of cells with 2-4 micronuclei in 10,000 scored spleen cells is also higher in 5-8 Gy exposed mice. These numerical chromosome aberrations are not induced directly by radiation exposure. These results indicate that prolonged {sup 137}Cs {gamma} ray-irradiation with low dose rates of 20 mGy/day induces delayed chromosome instability in mice. (author)

  20. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail:


    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  1. Initiation of genome instability and preneoplastic processes through loss of Fhit expression.

    Directory of Open Access Journals (Sweden)

    Joshua C Saldivar

    Full Text Available Genomic instability drives tumorigenesis, but how it is initiated in sporadic neoplasias is unknown. In early preneoplasias, alterations at chromosome fragile sites arise due to DNA replication stress. A frequent, perhaps earliest, genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus, leading to loss of Fhit protein expression. Because common chromosome fragile sites are exquisitely sensitive to replication stress, it has been proposed that their clonal alterations in cancer cells are due to stress sensitivity rather than to a selective advantage imparted by loss of expression of fragile gene products. Here, we show in normal, transformed, and cancer-derived cell lines that Fhit-depletion causes replication stress-induced DNA double-strand breaks. Using DNA combing, we observed a defect in replication fork progression in Fhit-deficient cells that stemmed primarily from fork stalling and collapse. The likely mechanism for the role of Fhit in replication fork progression is through regulation of Thymidine kinase 1 expression and thymidine triphosphate pool levels; notably, restoration of nucleotide balance rescued DNA replication defects and suppressed DNA breakage in Fhit-deficient cells. Depletion of Fhit did not activate the DNA damage response nor cause cell cycle arrest, allowing continued cell proliferation and ongoing chromosomal instability. This finding was in accord with in vivo studies, as Fhit knockout mouse tissue showed no evidence of cell cycle arrest or senescence yet exhibited numerous somatic DNA copy number aberrations at replication stress-sensitive loci. Furthermore, cells established from Fhit knockout tissue showed rapid immortalization and selection of DNA deletions and amplifications, including amplification of the Mdm2 gene, suggesting that Fhit loss-induced genome instability facilitates transformation. We propose that loss of Fhit expression in precancerous lesions is the first step in the

  2. Interfacial instabilities and Kapitsa pendula (United States)

    Krieger, Madison


    Determining the critera for onset and amplitude growth of instabilities is one of the central problems of fluid mechanics. We develop a parallel between the Kapitsa effect, in which a pendulum subject to high-frequency low-amplitude vibrations becomes stable in the inverted position, and interfaces separating fluids of different density. It has long been known that such interfaces can be stabilized by vibrations, even when the denser fluid is on top. We demonstrate that the stability diagram for these fluid interfaces is identical to the stability diagram for an appopriate Kapitsa pendulum. We expand the robust, ``dictionary''-type relationship between Kapitsa pendula and interfacial instabilities by considering the classical Rayleigh-Taylor, Kelvin-Helmholtz and Plateau instabilities, as well as less-canonical examples ranging in scale from the micron to the width of a galaxy.

  3. Evaporative Instability in Binary Mixtures (United States)

    Narayanan, Ranga; Uguz, Erdem


    In this talk we depict the physics of evaporative convection for binary systems in the presence of surface tension gradient effects. Two results are of importance. The first is that a binary system, in the absence of gravity, can generate an instability only when heated from the vapor side. This is to be contrasted with the case of a single component where instability can occur only when heated from the liquid side. The second result is that a binary system, in the presence of gravity, will generate an instability when heated from either the vapor or the liquid side provided the heating is strong enough. In addition to these results we show the conditions at which interfacial patterns can occur. Support from NSF OISE 0968313, Partner Univ. Fund and a Chateaubriand Fellowship is acknowledged.

  4. Laboratory blast wave driven instabilities (United States)

    Kuranz, Carolyn


    This presentation discusses experiments involving the evolution of hydrodynamic instabilities in the laboratory under high-energy-density (HED) conditions. These instabilities are driven by blast waves, which occur following a sudden, finite release of energy, and consist of a shock front followed by a rarefaction wave. When a blast wave crosses an interface with a decrease in density, hydrodynamic instabilities will develop. Instabilities evolving under HED conditions are relevant to astrophysics. These experiments include target materials scaled in density to the He/H layer in SN1987A. About 5 kJ of laser energy from the Omega Laser facility irradiates a 150 μm plastic layer that is followed by a low-density foam layer. A blast wave structure similar to those in supernovae is created in the plastic layer. The blast wave crosses an interface having a 2D or 3D sinusoidal structure that serves as a seed perturbation for hydrodynamic instabilities. This produces unstable growth dominated by the Rayleigh-Taylor (RT) instability in the nonlinear regime. We have detected the interface structure under these conditions using x-ray backlighting. Recent advances in our diagnostic techniques have greatly improved the resolution of our x-ray radiographic images. Under certain conditions, the improved images show some mass extending beyond the RT spike and penetrating further than previously observed or predicted by current simulations. The observed effect is potentially of great importance as a source of mass transport to places not anticipated by current theory and simulation. I will discuss the amount of mass in these spike extensions, the associated uncertainties, and hypotheses regarding their origin We also plan to show comparisons of experiments using single mode and multimode as well as 2D and 3D initial conditions. This work is sponsored by DOE/NNSA Research Grants DE-FG52-07NA28058 (Stewardship Sciences Academic Alliances) and DE-FG52-04NA00064 (National Laser User

  5. Hydromagnetic Instabilities in Neutron Stars

    CERN Document Server

    Lasky, Paul D; Kokkotas, Kostas D; Glampedakis, Kostas


    We model the non-linear ideal magnetohydrodynamics of poloidal magnetic fields in neutron stars in general relativity assuming a polytropic equation of state. We identify familiar hydromagnetic modes, in particular the 'sausage/varicose' mode and 'kink' instability inherent to poloidal magnetic fields. The evolution is dominated by the kink instability, which causes a cataclysmic reconfiguration of the magnetic field. The system subsequently evolves to new, non-axisymmetric, quasi-equilibrium end-states. The existence of this branch of stable quasi-equilibria may have consequences for magnetar physics, including flare generation mechanisms and interpretations of quasi-periodic oscillations.

  6. Mechanical Instabilities of Biological Tubes (United States)

    Hannezo, Edouard; Prost, Jacques; Joanny, Jean-François


    We study theoretically the morphologies of biological tubes affected by various pathologies. When epithelial cells grow, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated: varicose, dilated, sinuous, or sausagelike. They are all found in pathologies of tracheal, renal tubes, or arteries. The final shape depends crucially on the mechanical parameters of the tissues: Young’s modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation.

  7. Political instability and illegal immigration. (United States)

    Campos, J E; Lien, D


    "Economic theory suggests that transnational migration results from the push-pull effect of wage differentials between host and source countries. In this paper, we argue that political instability exacerbates the migration flow, with greater instability leading to relatively larger flows. We conclude then that an optimal solution to the illegal immigration problem requires proper coordination of immigration and foreign policies by the host country. A narrow preoccupation with tougher immigration laws is wasteful and may be marginally effective." Emphasis is on the United States as a host country.

  8. Stringy bounces and gradient instabilities

    CERN Document Server

    Giovannini, Massimo


    Bouncing solutions are obtained from a generally covariant action characterized by a potential which is a nonlocal functional of the dilaton field at two separated space-time points. Gradient instabilities are shown to arise in this context but they are argued to be nongeneric. After performing a gauge-invariant and frame-invariant derivation of the evolution equations of the fluctuations, a heuristic criterium for the avoidance of pathological instabilities is proposed and corroborated by a number of explicit examples that turn out to be compatible with a quasi-flat spectrum of curvature inhomogeneities for typical wavelengths larger than the Hubble radius.

  9. Research on aviation fuel instability (United States)

    Baker, C. E.; Bittker, D. A.; Cohen, S. M.; Seng, G. T.


    The problems associated with aircraft fuel instability are discussed. What is currently known about the problem is reviewed and a research program to identify those areas where more research is needed is discussed. The term fuel instability generally refers to the gums, sediments, or deposits which can form as a result of a set of complex chemical reactions when a fuel is stored for a long period at ambient conditions or when the fuel is thermally stressed inside the fuel system of an aircraft.

  10. Undulation Instability of Epithelial Tissues

    CERN Document Server

    Basan, Markus; Prost, Jacques; Risler, Thomas; 10.1103/PhysRevLett.106.158101


    Treating the epithelium as an incompressible fluid adjacent to a viscoelastic stroma, we find a novel hydrodynamic instability that leads to the formation of protrusions of the epithelium into the stroma. This instability is a candidate for epithelial fingering observed in vivo. It occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Our work provides physical insight into a potential mechanism by which interfaces between epithelia and stromas undulate, and potentially by which tissue dysplasia leads to cancerous invasion.

  11. Chromosome substitution strain assessment of a Huntington's disease modifier locus. (United States)

    Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R; St Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S; Sequeiros, Jorge; Wheeler, Vanessa C; Alonso, Isabel; MacDonald, Marcy E


    Huntington's disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human-mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23-24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) Hdh(Q111) knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr10(A/J)/NaJ chromosome substitution strain (CSS10), in which only chromosome 10 (chr10), in synteny with the human 6q23-24 region, is derived from the A/J (AJ) strain. Crosses were performed to assess the possibility of dominantly acting chr10 AJ-B6J variants of strong effect that may modulate CAG-dependent Hdh(Q111/+) phenotypes. Testing of F1 progeny confirmed that a single AJ chromosome had a significant effect on the rate of body weight gain and in Hdh(Q111) mice the AJ chromosome was associated subtle alterations in somatic CAG instability in the liver and the formation of intra-nuclear inclusions, as well as DARPP-32 levels, in the striatum. These findings in relatively small cohorts are suggestive of dominant chr10 AJ-B6 variants that may modify effects of the CAG expansion, and encourage a larger study with CSS10 and sub-strains. This cross-species approach may therefore be suited to functional in vivo prioritisation of genomic regions harbouring genes that can modify the early effects of the HD mutation.

  12. Secondary instabilities of linearly heated falling films

    Institute of Scientific and Technical Information of China (English)

    HU Jun; SUN Dejun; HU Guohui; YIN Xieyuan


    Secondary instabilities of linearly heated failing films are studied through three steps. Firstly, the analysis of the primary linear instability on Miladinova's long wave equation of the linearly heated film is performed. Secondly, the similar Landau equation is derived through weak nonlinear theory, and a two-dimensional nonlinear saturation solution of primary instability is obtained within the weak nonlinear domain. Thirdly, the secondary (three-dimensional) instability of the two-dimensional wave is studied by the Floquet theorem.Our secondary instability analysis shows that the Marangoni number has destabilization effect on the secondary instability.

  13. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine. (United States)

    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H


    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

  14. Chromosome segregation in Vibrio cholerae. (United States)

    Ramachandran, Revathy; Jha, Jyoti; Chattoraj, Dhruba K


    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae compare with those in other bacteria, and highlight some of the remaining questions regarding the process of bacterial chromosome segregation.

  15. Numerous transitions of sex chromosomes in Diptera. (United States)

    Vicoso, Beatriz; Bachtrog, Doris


    Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot), but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes). Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.

  16. Genomic instability and telomere fusion of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Junko Maeda

    Full Text Available Canine osteosarcoma (OSA is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of γ-H2AX and telomere signals in interphase cells was observed. Each cell line was characterized by a combination of data representing cellular doubling time, DNA content, chromosome number, metacentric chromosome frequency, telomere signal level, cellular radiosensitivity, and DNA-PKcs protein expression level. We have also studied primary cultures from 10 spontaneous canine OSAs. Based on the observation of telomere aberrations in those primary cell cultures, we are reasonably certain that our observations in cell lines are not an artifact of prolonged culture. A correlation between telomere fusions and the other characteristics analyzed in our study could not be identified. However, it is important to note that all of the canine OSA samples exhibiting telomere fusion utilized in our study were telomerase positive. Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA.

  17. Waves and instabilities in plasmas

    CERN Document Server

    Chen Liu


    The topics covered in these notes are selective and tend to emphasize more on kinetic-theory approaches to waves and instabilities in both uniform and non-uniform plasmas, students are assumed to have some basic knowledge of plasma dynamics in terms of single-particle and fluid descriptions.

  18. Lending sociodynamics and economic instability (United States)

    Hawkins, Raymond J.


    We show how the dynamics of economic instability and financial crises articulated by Keynes in the General Theory and developed by Minsky as the Financial Instability Hypothesis can be formalized using Weidlich’s sociodynamics of opinion formation. The model addresses both the lending sentiment of a lender in isolation as well as the impact on that lending sentiment of the behavior of other lenders. The risk associated with lending is incorporated through a stochastic treatment of loan dynamics that treats prepayment and default as competing risks. With this model we are able to generate endogenously the rapid changes in lending opinion that attend slow changes in lending profitability and find these dynamics to be consistent with the rise and collapse of the non-Agency mortgage-backed securities market in 2007/2008. As the parameters of this model correspond to well-known phenomena in cognitive and social psychology, we can both explain why economic instability has proved robust to advances in risk measurement and suggest how policy for reducing economic instability might be formulated in an experimentally sound manner.

  19. The Chemistry of Beer Instability (United States)

    Stewart, Graham G.


    Brewing of beer, one of the oldest biotechnology industries was one of the earliest processes to be undertaken on commercial basis. Biological instability involves contamination of bacteria, yeast, or mycelia fungi and there is always a risk in brewing that beer can become contaminated by micro-organisms.

  20. Edge instabilities of topological superconductors (United States)

    Hofmann, Johannes S.; Assaad, Fakher F.; Schnyder, Andreas P.


    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.

  1. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri


    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  2. Chromosome Segregation in Vibrio cholerae


    Ramachandran, R.; Jha, J.; Chattoraj, DK


    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae com...

  3. B chromosomes and sex in animals. (United States)

    Camacho, J P M; Schmid, M; Cabrero, J


    Supernumerary (B) chromosomes are dispensable elements found in many eukaryote genomes in addition to standard (A) chromosomes. In many respects, B chromosomes resemble sex chromosomes, so that a common ancestry for them has frequently been suggested. For instance, B chromosomes in grasshoppers, and other insects, show a pycnotic cycle of condensation-decondensation during meiosis remarkably similar to that of the X chromosome. In some cases, B chromosome size is even very similar to that of the X chromosome. These resemblances have led to suggest the X as the B ancestor in many cases. In addition, sex chromosome origin from B chromosomes has also been suggested. In this article, we review the existing evidence for both evolutionary pathways, as well as sex differences for B frequency at adult and embryo progeny levels, B chromosome effects or B chromosome transmission. In addition, we review cases found in the literature showing sex-ratio distortion associated with B chromosome presence, the most extreme case being the paternal sex ratio (PSR) chromosomes in some Hymenoptera. We finally analyse the possibility of B chromosome regularisation within the host genome and, as a consequence of it, whether B chromosomes can become regular members of the host genome.

  4. Origin and domestication of papaya Yh chromosome (United States)

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previo...

  5. Prognostic values of chromosome 18q microsatellite alterations in stage Ⅱ colonic carcinoma

    Institute of Scientific and Technical Information of China (English)


    AIM: To investigate the prognostic value of chromosome 18q microsatellite alterations (MA) in stage Ⅱ colon cancer. METHODS: One hundred and six patients with sporadic stage Ⅱ colon cancer were enrolled in this study. DNA was extracted from formalin-fixed, paraffin-embedded tumor and adjacent normal mucosal tissue samples. MA, including loss of heterozygosity (LOH) and microsatellite instability (MSI), was analyzed by polymerase chain reaction, polyacrylamide gel-electrophoresis and DNA sequencing at 5 micr...

  6. Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction


    Reyes, Céline; Serrurier, Céline; Gauthier, Tiphaine; Gachet, Yannick; Tournier, Sylvie


    The segregation of centromeres and telomeres at mitosis is coordinated at multiple levels to prevent the formation of aneuploid cells, a phenotype frequently observed in cancer. Mitotic instability arises from chromosome segregation defects, giving rise to chromatin bridges at anaphase. Most of these defects are corrected before anaphase onset by a mechanism involving Aurora B kinase, a key regulator of mitosis in a wide range of organisms. Here, we describe a new role for Aurora B in telomer...

  7. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)



    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  8. 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


    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.

  9. 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.

  10. Flow karyotyping and sorting of human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Peters, D.; Pinkel, D.; Trask, B.; van den Engh, G.; Van Dilla, M.A.


    Flow cytometry and sorting are becoming increasingly useful as tools for chromosome classfication and for the detection of numerical and structural chromosome aberrations. Chromosomes of a single type can be purified with these tools to facilitate gene mapping or production of chromosome specific recombinant DNA libraries. For analysis of chromosomes with flow cytometry, the chromosomes are extracted from mitotic cells, stained with one or more fluorescent dyes and classified one-by-one according to their dye content(s). Thus, the flow approach is fundamentally different than conventional karyotyping where chromosomes are classified within the context of a metaphase spread. Flow sorting allows purification of chromosomes that can be distinguished flow cytometrically. The authors describe the basic principles of flow cytometric chromosome classification i.e. flow karyotyping, and chromosome sorting and describe several applications. 30 refs., 8 figs.

  11. Observation of Parametric Instability in Advanced LIGO

    CERN Document Server

    Evans, Matthew; Fritschel, Peter; Miller, John; Barsotti, Lisa; Martynov, Denis; Brooks, Aidan; Coyne, Dennis; Abbott, Rich; Adhikari, Rana; Arai, Koji; Bork, Rolf; Kells, Bill; Rollins, Jameson; Smith-Lefebvre, Nicolas; Vajente, Gabriele; Yamamoto, Hiroaki; Derosa, Ryan; Effler, Anamaria; Kokeyama, Keiko; Betzweiser, Joseph; Frolov, Valera; Mullavey, Adam; O`Reilly, Brian; Dwyer, Sheila; Izumi, Kiwamu; Kawabe, Keita; Landry, Michael; Sigg, Daniel; Ballmer, Stefan; Massinger, Thomas J; Staley, Alexa; Mueller, Chris; Grote, Hartmut; Ward, Robert; King, Eleanor; Blair, David; Ju, Li; Zhao, Chunnong


    Parametric instabilities have long been studied as a potentially limiting effect in high-power interferometric gravitational wave detectors. Until now, however, these instabilities have never been observed in a kilometer-scale interferometer. In this work we describe the first observation of parametric instability in an Advanced LIGO detector, and the means by which it has been removed as a barrier to progress.

  12. Analogy between thermal convective and magnetohydrodynamic instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Valdmanis, Ya.Ya.; Kukainis, O.A.


    An examination is made of the analogy between thermo-convective instability and instability produced by various electromagnetic forces both in steady and alternating thermal and electromagnetic fields. An example is given for calculating an assumed bubble instability which could occur in an alternating magnetic field. 17 references.

  13. Amplitude Equation for Instabilities Driven at Deformable Surfaces - Rosensweig Instability (United States)

    Pleiner, Harald; Bohlius, Stefan; Brand, Helmut R.


    The derivation of amplitude equations from basic hydro-, magneto-, or electrodynamic equations requires the knowledge of the set of adjoint linear eigenvectors. This poses a particular problem for the case of a free and deformable surface, where the adjoint boundary conditions are generally non-trivial. In addition, when the driving force acts on the system via the deformable surface, not only Fredholm's alternative in the bulk, but also the proper boundary conditions are required to get amplitude equations. This is explained and demonstrated for the normal field (or Rosensweig) instability in ferrofluids as well as in ferrogels. An important aspect of the problem is its intrinsic dynamic nature, although at the end the instability is stationary. The resulting amplitude equation contains cubic and quadratic nonlinearities as well as first and (in the gel case) second order time derivatives. Spatial variations of the amplitudes cannot be obtained by using simply Newell's method in the bulk.

  14. Chromosome mis-segregation and cytokinesis failure in trisomic human cells. (United States)

    Nicholson, Joshua M; Macedo, Joana C; Mattingly, Aaron J; Wangsa, Darawalee; Camps, Jordi; Lima, Vera; Gomes, Ana M; Dória, Sofia; Ried, Thomas; Logarinho, Elsa; Cimini, Daniela


    Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome.

  15. Induction of small-segment-translocation between wheat and rye chromosomes

    Institute of Scientific and Technical Information of China (English)

    任正隆; 张怀琼


    A new approach to produce wheat-rye translocation, based on the genetic instability caused by monosomic addition of rye chromosome in wheat, is described. 1 283 plants from the selfed progenies of monosomic addition lines with single chromosome of inbred rye line R12 and complete chromosome complement of wheat cultivar Mianyang 11 were cytologically analyzed on a plant-by-plant basis by the improved C-banding technique. 63 of the plants, with 2n = 42, were found containing wheat-rye translocation or substitution, with a frequency of 4. 91% . Compared with the wheat parent, other 32 plants with 2n = 42 exhibited obvious phenotypic variation, but their com-ponent of rye chromosome could not be detected using the C-banding technique. In situ hybridization with a biotin-la-beled DNA probe was used to detect rye chromatin and to determine the insertion sites of rye segments in the wheat chromosomes. In 20 out of the 32 variant wheat plants, small segments of rye chromosomes were found being inserted into dif

  16. Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs). (United States)

    Kim, Taehyun; Bershteyn, Marina; Wynshaw-Boris, Anthony


    The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations.


    Institute of Scientific and Technical Information of China (English)

    GUO; Xue-jun


    [1]Froudarakis ME, Bouros D, Spandidos DA, et al. Microsatellite instability and loss of heterozygosity at chromosomes 17 in non-small cell lung cancer [J]. Chest 1998; 113:1091.[2]Fong KM, Zimmerman PV, Smith PJ. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer [J]. Cancer Res 1994; 54:2098.[3]Mountain CF. A new international staging system for lung cancer [J]. Chest 1986; 89(suppl):225.[4]Shridhar V, Siegfried J, Hunt J, et al. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas [J]. Cancer Res 1994; 54:2084.[5]Loeb LA. Microsatellite instability: Marker of a mutator phenotype in cancer [J]. Cancer Res 1994; 54:5059.[6]Sanchez CM, Monzo M, Rosell R, et al. Detection of chromosome 3p alterations in serum DNA of non-small cell lung cancer patients [J]. Ann Oncol 1989; 113.

  18. Competing structural instabilities in cubic perovskites

    CERN Document Server

    Vanderbilt, D


    We study the antiferrodistortive instability and its interaction with ferroelectricity in cubic perovskite compounds. Our first-principles calculations show that coexistence of both instabilities is very common. We develop a first-principles scheme to study the thermodynamics of these compounds when both instabilities are present, and apply it to SrTiO$_3$. We find that increased pressure enhances the antiferrodistortive instability while suppressing the ferroelectric one. Moreover, the presence of one instability tends to suppress the other. A very rich $P$--$T$ phase diagram results.

  19. An update on the mechanisms and pathophysiological consequences of genomic instability with a focus on ionizing radiation

    Directory of Open Access Journals (Sweden)

    Streffer C


    Full Text Available Christian Streffer Institute for Medical Radiobiology, University Clinics Essen, Essen, Germany Abstract: The genome of eukaryotic cells is generally instable. DNA damage occurs by endogenous processes and exogenous toxic agents. The efficient DNA repair pathways conserve the genetic information to a large extent throughout the life. However, exposure to genotoxic agents can increase the genomic instability. This phenomenon develops in a delayed manner after approximately 20 and more cell generations. It is comparatively thoroughly investigated after the exposure to ionizing radiation. The increase of genomic instability has been observed after exposures to ionizing radiation in vitro and in vivo as well as with many different types of radiation. The effect is induced over a wide dose range, and it has been found with cell death, chromosomal damage, cell transformations, mutations, double-strand breaks, malformations, and cancers. No specific chromosomes or genomic sites have been observed for such events. The increased genomic instability can be transmitted to the next generation. Possible mechanisms such as oxidative stress (mitochondria may be involved, reduced DNA repair, changes in telomeres, epigenetic effects are discussed. A second wave of oxidative stress has been observed after radiation exposures with considerably high doses as well as with cytotoxic agents at time periods when an increased genomic instability was seen. However, the increase of genomic instability also happens to much lower radiation doses. Hypoxia induces an increase of genomic instability. This effect is apparently connected with a reduction of DNA repair. Changes of telomeres appear as the most probable mechanisms for the increase of genomic instability. Syndromes have been described with a genetic predisposition for high radiosensitivity. These individuals show an increase of cancer, a deficient DNA repair, a disturbed regulation of the cell cycle, and an

  20. On dynamical (black hole) instabilities

    CERN Document Server

    Coutant, Antonin; Parentani, Renaud


    Black hole dynamical instabilities have been mostly studied in specific models. To display their common features, we study the general properties of the complex frequency modes which are responsible for such instabilities. We show that they are square integrable, have a vanishing conserved norm, and appear in mode doublets or quartets. We also study how they appear in the spectrum and how their complex frequencies subsequently evolve when varying some external parameter. When working on an infinite domain, they appear from the reservoir of quasi-normal modes obeying outgoing boundary conditions. This is illustrated by generalizing, in a non-positive definite Krein space, a solvable model (Friedrichs model) which originally describes the appearance of a resonance when coupling an isolated system to a mode continuum. In a finite spatial domain instead, they arise from the fusion of two real frequency modes with opposite norms, through a process that closely resembles avoided crossing.

  1. Stretching Folding Instability and Nanoemulsions

    CERN Document Server

    Chan, Chon U


    Here we show a folding-stretching instability in a microfluidic flow focusing device using silicon oil (100cSt) and water. The fluid dynamics video demonstrates an oscillating thread of oil focused by two co-flowing streams of water. We show several high-speed sequences of these oscillations with 30,000 frames/s. Once the thread is decelerated in a slower moving pool downstream an instability sets in and water-in-oil droplets are formed. We reveal the details of the pinch-off with 500,000 frames/s. The pinch-off is so repeatable that complex droplet patterns emerge. Some of droplets are below the resolution limit, thus smaller than 1 micrometer in diameter.

  2. Modern management of patellar instability. (United States)

    Rhee, Shin-Jae; Pavlou, George; Oakley, Jeremy; Barlow, David; Haddad, Farres


    Recurrent patellofemoral instability is a disabling condition, attributed to a variety of anatomical aetiologies. Trochlear dysplasia, patella alta, an increased tibial tubercle trochlear groove distance of greater than 20 mm and soft tissue abnormalities such as a torn medial patellofemoral ligament and inadequate vastus medialis obliquus are all factors to be considered. Management of this condition remains difficult and controversial and knowledge of the functional anatomy and biomechanics of the patellofemoral joint, a detailed history and clinical examination, and an accurate patient assessment are all imperative to formulate an appropriate management plan. Surgical treatment is based on the underlying anatomical pathology with an aim to restore normal patellofemoral kinematics. We summarise aspects of assessment, treatment and outcome of patellofemoral instability and propose an algorithm of treatment.

  3. Buckling instability of squeezed droplets

    CERN Document Server

    Elfring, Gwynn J


    Motivated by recent experiments, we consider theoretically the compression of droplets pinned at the bottom on a surface of finite area. We show that if the droplet is sufficiently compressed at the top by a surface, it will always develop a shape instability at a critical compression. When the top surface is flat, the shape instability occurs precisely when the apparent contact angle of the droplet at the pinned surface is pi, regardless of the contact angle of the upper surface, reminiscent of past work on liquid bridges and sessile droplets as first observed by Plateau. After the critical compression, the droplet transitions from a symmetric to an asymmetric shape. The force required to deform the droplet peaks at the critical point then progressively decreases indicative of catastrophic buckling. We characterize the transition in droplet shape using illustrative examples in two dimensions followed by perturbative analysis as well as numerical simulation in three dimensions. When the upper surface is not f...

  4. Streaming Instabilities in Protoplanetary Disks

    CERN Document Server

    Youdin, A N; Youdin, Andrew N.; Goodman, Jeremy


    Interpenetrating streams of solids and gas in a Keplerian disk produce a local, linear instability. The two components mutually interact via aerodynamic drag, which generates radial drift and triggers unstable modes. The secular instability does not require self-gravity, yet it generates growing particle density perturbations that could seed planetesimal formation. Growth rates are slower than dynamical, but faster than radial drift, timescales. Growth rates, like streaming velocities, are maximized for marginal coupling (stopping times comparable dynamical times). Fastest growth occurs when the solid to gas density ratio is order unity and feedback is strongest. Curiously, growth is strongly suppressed when the densities are too nearly equal. The relation between background drift and wave properties is explained by analogy with Howard's semicircle theorem. The three-dimensional, two-fluid equations describe a sixth order (in the complex frequency) dispersion relation. A terminal velocity approximation allows...

  5. Nonlinear evolution of drift instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, W.W.; Krommes, J.A.; Oberman, C.R.; Smith, R.A.


    The nonlinear evolution of collisionless drift instabilities in a shear-free magnetic field has been studied by means of gyrokinetic particle simulation as well as numerical integration of model mode-coupling equations. The purpose of the investigation is to identify relevant nonlinear mechanisms responsible for the steady-state drift wave fluctuations. It is found that the saturation of the instability is mainly caused by the nonlinear E x B convection of the resonant electrons and their associated velocity space nonlinearity. The latter also induces energy exchange between the competing modes, which, in turn, gives rise to enhanced diffusion. The nonlinear E x B convection of the ions, which contributes to the nonlinear frequency shift, is also an important ingredient for the saturation.

  6. Circulation in blast driven instabilities (United States)

    Henry de Frahan, Marc; Johnsen, Eric


    Mixing in many natural phenomena (e.g. supernova collapse) and engineering applications (e.g. inertial confinement fusion) is often initiated through hydrodynamic instabilities. Explosions in these systems give rise to blast waves which can interact with perturbations at interfaces between different fluids. Blast waves are formed by a shock followed by a rarefaction. This wave profile leads to complex time histories of interface acceleration. In addition to the instabilities induced by the acceleration field, the rarefaction from the blast wave decompresses the material at the interface, further increasing the perturbation growth. After the passage of the wave, circulation circulation generated by the blast wave through baroclinic vorticity continues to act upon the interface. In this talk, we provide scaling laws for the circulation and amplitude growth induced by the blast wave. Numerical simulations of the multifluid Euler equations solved using a high-order accurate Discontinuous Galerkin method are used to validate the theoretical results.

  7. Instability of supersymmetric microstate geometries

    CERN Document Server

    Eperon, Felicity C; Santos, Jorge E


    We investigate the classical stability of supersymmetric, asymptotically flat, microstate geometries with five non-compact dimensions. Such geometries admit an "evanescent ergosurface": a timelike hypersurface of infinite redshift. On such a surface, there are null geodesics with zero energy relative to infinity. These geodesics are stably trapped in the potential well near the ergosurface. We present a heuristic argument indicating that this feature is likely to lead to a nonlinear instability of these solutions. We argue that the precursor of such an instability can be seen in the behaviour of linear perturbations: nonlinear stability would require that all linear perturbations decay sufficiently rapidly but the stable trapping implies that some linear perturbation decay very slowly. We study this in detail for the most symmetric microstate geometries. By constructing quasinormal modes of these geometries we show that generic linear perturbations decay slower than any inverse power of time.

  8. Mechanical Instabilities of Biological Tubes

    CERN Document Server

    Hannezo, Edouard; Prost, Jacques; 10.1103/PhysRevLett.109.018101


    We study theoretically the shapes of biological tubes affected by various pathologies. When epithelial cells grow at an uncontrolled rate, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated : varicose, enlarged, sinusoidal or sausage-like, all of which are found in pathologies of tracheal, renal tubes or arteries. The final shape depends crucially on the mechanical parameters of the tissues : Young modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation.

  9. Fluctuations and Instability in Sedimentation

    KAUST Repository

    Guazzelli, Élisabeth


    This review concentrates on the fluctuations of the velocities of sedimenting spheres, and on the structural instability of a suspension of settling fibers. For many years, theoretical estimates and numerical simulations predicted the fluctuations of the velocities of spheres to increase with the size of the container, whereas experiments found no such variation. Two ideas have increased our understanding. First, the correlation length of the velocity fluctuations was found experimentally to be 20 interparticle separations. Second, in dilute suspensions, a vertical variation in the concentration due to the spreading of the front with the clear fluid can inhibit the velocity fluctuations. In a very dilute regime, a homogeneous suspension of fibers suffers a spontaneous instability in which fast descending fiber-rich columns are separated by rising fiber-sparse columns. In a semidilute regime, the settling is hindered, more so than for spheres. © 2011 by Annual Reviews. All rights reserved.

  10. Placing Marangoni instabilities under arrest

    CERN Document Server

    Bhamla, M Saad


    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.

  11. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types (United States)

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


    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.

  12. In the shadow of phylogenetic uncertainty: the recent diversification of Lysandra butterflies through chromosomal change. (United States)

    Talavera, Gerard; Lukhtanov, Vladimir A; Rieppel, Lukas; Pierce, Naomi E; Vila, Roger


    The phylogeny of the butterfly genus Lysandra (Lycaenidae, Polyommatinae) has been intractable using both molecular and morphological characters, which could be a result of speciation due to karyotype instability. Here we reconstruct the phylogeny of the group using multi-locus coalescent-based methods on seven independent genetic markers. While the genus is ca. 4.9 Mya old, the diversification of the extant lineages was extremely recent (ca. 1.5 Mya) and involved multiple chromosomal rearrangements. We find that relationships are uncertain due to both incomplete lineage sorting and hybridization. Minimizing the impact of reticulation in inferring the species tree by testing for mitochondrial introgression events yields a partially resolved tree with three main supported clades: L. punctifera+L. bellargus, the corydonius taxa, and L. coridon+the Iberian taxa, plus three independent lineages without apparently close relatives (L. ossmar, L. syriaca and L. dezina). Based on these results and new karyotypic data, we propose a rearrangement recognizing ten species within the genus. Finally, we hypothesize that chromosomal instability may have played a crucial role in the Lysandra recent diversification. New chromosome rearrangements might be fixed in populations after severe bottlenecks, which at the same time might promote rapid sorting of neutral molecular markers. We argue that population bottlenecks might be a prerequisite for chromosomal speciation in this group.

  13. Fragile X gene instability: Anchoring AGGs and linked microsatellites

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Nan; Yang, Weihong; Dobkin, C. [Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)] [and others


    Interspersed AGGs within the FMR1 gene CGG repeat region may anchor the sequence and prevent slippage during replication. In order to detect the AGG position variations, we developed a method employing partial MnlI restriction analysis and analyzed X chromosomes from 187 males, including 133 normal controls (17 with 20-34 and 16 with 35-52 repeats), plus 54 fragile X premutations with 56-180 repeats. Among controls, the interspersed AGG positions were highly polymorphic, with heterozygosity of 91%. Among the control samples, 1.5% had no AGG positions, 25% had one, 71% had two, and 3% had three. Among the fragile X premutation samples, 63% had no AGG, while 37% had only one AGG. Analysis of premutation samples within fragile X families showed that variation occurred only within the 3{prime} end of the region. Thus, the instability was polar. Controls with {ge}15 pure CGG repeats were associated with the longest alleles of two nearby microsatellites, FRAXAC1 with 20-21 repeats and DXS548 with 202-206 bp and with increased microsatellite heterzygosity. The association of long pure CGG regions, as with fragile X chromosomes, with the longer and more heterozygous microsatellite alleles suggests they may be related mechanistically. Further, our results do not support a recent suggestion that the frequency of fragile X alleles may be increasing. Finally, analysis of a set of nonhuman primate samples showed that long pure CGG tracks are variable in size and are located within the 3{prime} region, which suggests that polar instability within FMR1 is evolutionarily quite old. 55 refs., 3 figs., 4 tabs.

  14. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.


    Objective To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. Methods From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome abnorma

  15. MD 751: Train Instability Threshold

    CERN Document Server

    Carver, Lee Robert; Metral, Elias; Salvant, Benoit; Levens, Tom; Nisbet, David; Zobov, M; CERN. Geneva. ATS Department


    The purpose of this MD is to measure the octupole current thresholds for stability for a single bunch, and then make an immediate comparison (with the same operational settings) for a train of 72 bunches separated by 25ns. From theory, the expected thresholds should be similar. Any discrepancy between the two cases will be of great interest as it could indicate the presence of additional mechanisms that contribute to the instability threshold, for example electron cloud.

  16. Polygonal instabilities on interfacial vorticities

    CERN Document Server

    Labousse, Matthieu


    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.

  17. Instability of colliding metastable strings

    Energy Technology Data Exchange (ETDEWEB)

    Hiramatsu, Takashi [Kyoto Univ. (Japan). Yukawa Inst. for Theoretical Physics; Eto, Minoru [Yamagata Univ. (Japan). Dept. of Physics; Kamada, Kohei [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kobayashi, Tatsuo [Kyoto Univ. (Japan). Dept. of Physics; Ookouchi, Yutaka [Kyoto Univ. (Japan). Dept. of Physics; Kyoto Univ. (Japan). The Hakubi Center for Advanced Research


    We investigate the collision dynamics of two metastable strings which can be viewed as tube-like domain walls with winding numbers interpolating a false vacuum and a true vacuum. We find that depending on the relative angle and speed of two strings, instability of strings increases and the false vacuum is filled out by rapid expansion of the strings or of a remnant of the collision.

  18. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. (United States)

    Mlecnik, Bernhard; Bindea, Gabriela; Angell, Helen K; Maby, Pauline; Angelova, Mihaela; Tougeron, David; Church, Sarah E; Lafontaine, Lucie; Fischer, Maria; Fredriksen, Tessa; Sasso, Maristella; Bilocq, Amélie M; Kirilovsky, Amos; Obenauf, Anna C; Hamieh, Mohamad; Berger, Anne; Bruneval, Patrick; Tuech, Jean-Jacques; Sabourin, Jean-Christophe; Le Pessot, Florence; Mauillon, Jacques; Rafii, Arash; Laurent-Puig, Pierre; Speicher, Michael R; Trajanoski, Zlatko; Michel, Pierre; Sesboüe, Richard; Frebourg, Thierry; Pagès, Franck; Valge-Archer, Viia; Latouche, Jean-Baptiste; Galon, Jérôme


    Microsatellite instability in colorectal cancer predicts favorable outcomes. However, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune cells, Immunoscore, and their impact on patient survival remains to be elucidated. We found significant differences in mutational patterns, chromosomal instability, and gene expression that correlated with patient microsatellite instability status. A prominent immune gene expression was observed in microsatellite-instable (MSI) tumors, as well as in a subgroup of microsatellite-stable (MSS) tumors. MSI tumors had increased frameshift mutations, showed genetic evidence of immunoediting, had higher densities of Th1, effector-memory T cells, in situ proliferating T cells, and inhibitory PD1-PDL1 cells, had high Immunoscores, and were infiltrated with mutation-specific cytotoxic T cells. Multivariate analysis revealed that Immunoscore was superior to microsatellite instability in predicting patients' disease-specific recurrence and survival. These findings indicate that assessment of the immune status via Immunoscore provides a potent indicator of tumor recurrence beyond microsatellite-instability staging that could be an important guide for immunotherapy strategies.

  19. Microphysics of cosmic ray driven plasma instabilities

    CERN Document Server

    Bykov, A M; Malkov, M A; Osipov, S M


    Energetic nonthermal particles (cosmic rays, CRs) are accelerated in supernova remnants, relativistic jets and other astrophysical objects. The CR energy density is typically comparable with that of the thermal components and magnetic fields. In this review we discuss mechanisms of magnetic field amplification due to instabilities induced by CRs. We derive CR kinetic and magnetohydrodynamic equations that govern cosmic plasma systems comprising the thermal background plasma, comic rays and fluctuating magnetic fields to study CR-driven instabilities. Both resonant and non-resonant instabilities are reviewed, including the Bell short-wavelength instability, and the firehose instability. Special attention is paid to the longwavelength instabilities driven by the CR current and pressure gradient. The helicity production by the CR current-driven instabilities is discussed in connection with the dynamo mechanisms of cosmic magnetic field amplification.

  20. Gravitational instabilities in astrophysical fluids (United States)

    Tohline, Joel E.


    Over the past decade, the significant advancements that have been made in the development of computational tools and numerical techniques have allowed astrophysicists to begin to model accurately the nonlinear growth of gravitational instabilities in a variety of physical systems. The fragmentation or rotationally driven fission of dynamically evolving, self-gravitating ``drops and bubbles'' is now routinely modeled in full three-dimensional generality as we attempt to understand the behavior of protostellar clouds, rotating stars, galaxies, and even the primordial soup that defined the birth of the universe. A brief review is presented here of the general insights that have been gained from studies of this type, followed by a somewhat more detailed description of work, currently underway, that is designed to explain the process of binary star formation. A short video animation sequence, developed in conjunction with some of the research being reviewed, illustrates the basic-nature of the fission instability in rotating stars and of an instability that can arise in a massive disk that forms in a protostellar cloud.

  1. Dean flow fractionation of chromosomes (United States)

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


    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.

  2. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola


    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

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

    Directory of Open Access Journals (Sweden)

    Mulder Chris JJ


    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.

  4. The Reduction of Chromosome Number in Meiosis Is Determined by Properties Built into the Chromosomes


    Paliulis, Leocadia V.; Nicklas, R. Bruce


    In meiosis I, two chromatids move to each spindle pole. Then, in meiosis II, the two are distributed, one to each future gamete. This requires that meiosis I chromosomes attach to the spindle differently than meiosis II chromosomes and that they regulate chromosome cohesion differently. We investigated whether the information that dictates the division type of the chromosome comes from the whole cell, the spindle, or the chromosome itself. Also, we determined when chromosomes can switch from ...

  5. Early and Late Chromosome Damages in Human Lymphocytes Induced by Gamma Rays and Fe Ions (United States)

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


    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.

  6. 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.

  7. Modes of storage ring coherent instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.M.


    Longitudinal impedance in a beam and various modes of longitudinal coherent instabilities are discussed. The coasting beam coherent instability, microwave instability, and single-bunch longitudinal coherent instabilities are considered. The Vlasov equation is formulated, and a method of solving it is developed. The synchrotron modes are treated, which take the possible bunch shape distortion fully into consideration. A method of treating the synchrotron mode coupling in the case of a small bunch is discussed which takes advantage of the fact that only a few of the synchrotron modes can contribute in such a case. The effect of many bunches on the coherent motion of the beam and the longitudinal symmetric coupled bunch modes are discussed. The transverse impedance is then introduced, and the transverse coasting beam instability is discussed. Various bunched beam instabilities are discussed, including both single bunch instabilities and coupled bunch instabilities. The Vlasov equation for transverse as well as longitudinal motion of particles is introduced as well as a method of solving it within a linear approximation. Head-tail modes and short bunch instabilities and strong coupling instabilities in the long bunch case are covered. (LEW)

  8. Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1) at Serine 284 and Serine 292 during Mitosis. (United States)

    Xu, Chang; Wang, Yan; Wang, Lu; Wang, Qin; Du, Li-Qing; Fan, Saijun; Liu, Qiang; Li, Lei


    Chromosome instability usually leads to tumorigenesis. Bloom syndrome (BS) is a genetic disease associated with chromosome instability. The BS gene product, BLM, has been reported to function in the spindle assembly checkpoint (SAC) to prevent chromosome instability. BTR complex, composed of BLM, topoisomerase IIIα (Topo IIIα), RMI1 (RecQ-mediated genome instability protein 1, BLAP75) and RMI2 (RecQ-mediated genome instability protein 2, BLAP18), is crucial for maintaining genome stability. Recent work has demonstrated that RMI2 also plays critical role in SAC. However, little is know about RMI1 regulation during the cell cycle. Here we present that RMI1 protein level does not change through G1, S and G2 phases, but significantly increases in M phase. Moreover, phosphorylation of RMI1 occurs in mitosis. Upon microtubule-disturbing agent, RMI1 is phosphorylated primarily at the sites of Serine 284 and Serine 292, which does not interfere with the formation of BTR complex. Additionally, this phosphorylation is partially reversed by roscovitine treatment, implying cycling-dependent kinase 1 (CDK1) might be one of the upstream kinases.

  9. Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1 at Serine 284 and Serine 292 during Mitosis

    Directory of Open Access Journals (Sweden)

    Chang Xu


    Full Text Available Chromosome instability usually leads to tumorigenesis. Bloom syndrome (BS is a genetic disease associated with chromosome instability. The BS gene product, BLM, has been reported to function in the spindle assembly checkpoint (SAC to prevent chromosome instability. BTR complex, composed of BLM, topoisomerase IIIα (Topo IIIα, RMI1 (RecQ-mediated genome instability protein 1, BLAP75 and RMI2 (RecQ-mediated genome instability protein 2, BLAP18, is crucial for maintaining genome stability. Recent work has demonstrated that RMI2 also plays critical role in SAC. However, little is know about RMI1 regulation during the cell cycle. Here we present that RMI1 protein level does not change through G1, S and G2 phases, but significantly increases in M phase. Moreover, phosphorylation of RMI1 occurs in mitosis. Upon microtubule-disturbing agent, RMI1 is phosphorylated primarily at the sites of Serine 284 and Serine 292, which does not interfere with the formation of BTR complex. Additionally, this phosphorylation is partially reversed by roscovitine treatment, implying cycling-dependent kinase 1 (CDK1 might be one of the upstream kinases.

  10. Chromosome-specific families in Vibrio genomes

    Directory of Open Access Journals (Sweden)

    Oksana eLukjancenko


    Full Text Available We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown. Of the chromosome specific core protein families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different `Molecular Function` GO categories were found for chromosome 1 specific protein families, and these include several broad activities: pyridoxine 5' phosphate synthetase, glucosylceramidase, heme transport, DNA ligase, amino acid binding, and ribosomal components; in contrast, chromosome 2 specific protein families have only 66 Molecular Function GO terms and include many membrane-associated activities, such as ion channels, transmembrane transporters, and electron transport chain proteins. Thus, it appears that whilst there are many 'housekeeping systems' encoded in chromosome 1, there are far fewer core functions found in chromosome 2. However, the presence of many membrane-associated encoded proteins in chromosome 2 is surprising.

  11. Autophagy-independent senescence and genome instability driven by targeted telomere dysfunction. (United States)

    Mar, Florie A; Debnath, Jayanta; Stohr, Bradley A


    Telomere dysfunction plays a complex role in tumorigenesis. While dysfunctional telomeres can block the proliferation of incipient cancer clones by inducing replicative senescence, fusion of dysfunctional telomeres can drive genome instability and oncogenic genomic rearrangements. Therefore, it is important to define the regulatory pathways that guide these opposing effects. Recent work has shown that the autophagy pathway regulates both senescence and genome instability in various contexts. Here, we apply models of acute telomere dysfunction to determine whether autophagy modulates the resulting genome instability and senescence responses. While telomere dysfunction rapidly induces autophagic flux in human fibroblast cell lines, inhibition of the autophagy pathway does not have a significant impact upon the transition to senescence, in contrast to what has previously been reported for oncogene-induced senescence. Our results suggest that this difference may be explained by disparities in the development of the senescence-associated secretory phenotype. We also show that chromosome fusions induced by telomere dysfunction are comparable in autophagy-proficient and autophagy-deficient cells. Altogether, our results highlight the complexity of the senescence-autophagy interface and indicate that autophagy induction is unlikely to play a significant role in telomere dysfunction-driven senescence and chromosome fusions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Aghajanyan, Anna, E-mail: [Cytogenetics Laboratory, FSI Russian Scientific Center of Roentgenology and Radiology, Profsoyuznaya 86, GSP-7, Moscow, 117997 (Russian Federation); Suskov, Igor [Laboratory of Ecological Genetics, N.I. Vavilov Institute of General Genetics Russian Academy of Sciences, Gybkin st. 3, Moscow 119991 (Russian Federation)


    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 < 0.01), but also in their children born after the accident (n = 159, p < 0.05). This is an indicative of the phenomenon of transgenerational genomic instability. To elucidate this phenomenon, experiments were undertaken to model genomic instability by using single and fractional in vitro {gamma}-irradiation ({sup 137}Cs) 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.

  13. Compressor instability with integral methods

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Y.K. Eddie [Nanyang Technological Univ., Singapore (Singapore). School of Mechanical and Aerospace Engineering; Liu, Ningyu [Singapore National Univ. (Singapore). Dept. of Mechanical Engineering


    ''Compressor Instability with Integral Methods'' is a book, to bring together the quick integral approaches and advances in the field for the prediction of stall and surge problem in compressor. This book is useful for people involved in the flow analysis, design and testing of rotating machinery. For students, it can be used as a specialized topic of senior undergraduate or graduate study. The book can also be served as a self-study material to those who keen to acquire this knowledge. In brief, this book focuses on the numerical/computational analysis for the effect of distorted inlet flow propagation on the rotating stall and surge in axial compressors. It gains insight into the basic phenomena controlling these flow instabilities, and reveals the influence of inlet parameters on rotating stall and surge. The book starts from the confirmation and application of Kim et al's integral method and then follows by a development to this method through the proposing and applying a critical distortion line. This line is applied successfully on the stall prediction of in-flight compressor due to flaming of refueling leakage near inlet, a typical real and interesting example of compressor stall and surge operation. Further, after a parametric study on the integral method and the distorted flow field of compressor using Taguchi method, a novel integral method is formulated using more appropriate and practical airfoil characteristics, with a less assumptions needed for derivation. Finally, as an extended work, the famous Greitzer's instability flow model, the well-known B-parameter model applied for analyzing the stall and surge characteristics, is studied parametrically using Taguchi method. (orig.)

  14. Genetic Instability in Gastric Epithelial Neoplasias Categorized by the Revised Vienna Classification (United States)

    Chung, Woo Chul; Jung, Sung Hoon; Lee, Kang Moon; Paik, Chang Nyol; Kwak, Jae Wuk; Jung, Ji Han; Yoo, Jin Young; Lee, Min Kyoung


    Background/Aims The aim of this study was to determine the structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), at multiple tumor suppressor gene loci in gastric epithelial neoplasia categorized by the revised Vienna classification. Methods All tissue samples were excised by endoscopic mucosal resection. Sixty category 3 (low-grade adenoma) tissue samples and 51 category 4 samples (high-grade adenoma and intramucosal carcinoma with adenoma) were examined at the 7 sets of microsatellite loci linked to the tumor suppressor gene locus. Results For category 3 and 4 tissue samples, there were no differences in the frequencies of LOH-positive chromosomes or the extent of chromosomal loss. The Helicobacter-pylori (H. pylori)-positive rate was significantly higher in MSI-positive category 4 samples than in category 3 samples (p=0.04). The frequency of MSI positivity was significantly higher in category 4 samples than in category 3 samples (p=0.003). Conclusions H. pylori infection is associated with genetic instability of the premalignant lesion. MSI occurs in the early stages of gastric carcinogenesis and its occurrence increases during malignant transformation. Detection of MSI in premalignant gastric lesions may be a surveillant of risk of malignant transformation. PMID:20559519

  15. Genomic instability in rat: Breakpoints induced by ionising radiation and interstitial telomeric-like sequences

    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); Ruiz-Herrera, Aurora [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Acien, Maribel [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Paya, Pilar [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Giulotto, Elena [Dipartimento di Genetica e Microbiologia Adriano Buzzati Traverso, Universita degli Studi di Pavia, 27100 Pavia (Italy); Egozcue, Josep [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); Garcia, Montserrat [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain) and Departament de Biologia Cellular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)]. E-mail:


    The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs.

  16. Spatiotemporal chaos involving wave instability (United States)

    Berenstein, Igal; Carballido-Landeira, Jorge


    In this paper, we investigate pattern formation in a model of a reaction confined in a microemulsion, in a regime where both Turing and wave instability occur. In one-dimensional systems, the pattern corresponds to spatiotemporal intermittency where the behavior of the systems alternates in both time and space between stationary Turing patterns and traveling waves. In two-dimensional systems, the behavior initially may correspond to Turing patterns, which then turn into wave patterns. The resulting pattern also corresponds to a chaotic state, where the system alternates in both space and time between standing wave patterns and traveling waves, and the local dynamics may show vanishing amplitude of the variables.

  17. Nonlinear Instability of Liquid Layers. (United States)

    Newhouse, Lori Ann

    The nonlinear instability of two superposed viscous liquid layers in planar and axisymmetric configurations is investigated. In the planar configuration, the light layer fluid is bounded below by a wall and above by a heavy semiinfinite fluid. Gravity drives the instability. In the first axisymmetric configuration, the layer is confined between a cylindrical wall and a core of another fluid. In the second, a thread is suspended in an infinite fluid. Surface tension forces drive the instability in the axisymmetric configurations. The nonlinear evolution of the fluid-fluid interface is computed for layers of arbitrary thickness when their dynamics are fully coupled to those of the second fluid. Under the assumption of creeping flow, the flow field is represented by an interfacial distribution of Green's functions. A Fredholm integral equation of the second kind for the strength of the distribution is derived and then solved using an iterative technique. The Green's functions produce flow fields which are periodic in the direction parallel to the wall and have zero velocity on the wall. For small and moderate surface tension, planar layers evolve into a periodic array of viscous plumes which penetrate into the overlying fluid. The morphology of the plumes depends on the surface tension and the ratio of the fluid viscosities. As the viscosity of the layer increases, the plumes change from a well defined drop on top of a narrow stem to a compact column of rising fluid. The capillary instability of cylindrical interfaces and interfaces in which the core thickness varies in the axial direction are investigated. In both the unbounded and wall bounded configurations, the core evolves into a periodic array of elongated fluid drops connected by thin, almost cylindrical fluid links. The characteristics of the drop-link structure depend on the core thickness, the ratio of the core radius to the wall radius, and the ratio of the fluid viscosities. The factors controlling the

  18. Bathtub vortex induced by instability (United States)

    Mizushima, Jiro; Abe, Kazuki; Yokoyama, Naoto


    The driving mechanism and the swirl direction of the bathtub vortex are investigated by the linear stability analysis of the no-vortex flow as well as numerical simulations. We find that only systems having plane symmetries with respect to vertical planes deserve research for the swirl direction. The bathtub vortex appearing in a vessel with a rectangular cross section having a drain hole at the center of the bottom is proved to be induced by instability when the flow rate exceeds a threshold. The Coriolis force is capable of determining the swirl direction to be cyclonic.

  19. Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Gericke, G.S.; Simonic, I.; Cloete, E.; Buckle, C. [Univ. of Pretoria (South Africa)] [and others


    Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites. 32 refs., 1 tab.

  20. Transverse Instabilities in the Fermilab Recycler

    Energy Technology Data Exchange (ETDEWEB)

    Prost, L.R.; Burov, A.; Shemyakin, A.; Bhat, C.M.; Crisp, J.; Eddy, N.; /Fermilab


    Transverse instabilities of the antiproton beam have been observed in the Recycler ring soon after its commissioning. After installation of transverse dampers, the threshold for the instability limit increased significantly but the instability is still found to limit the brightness of the antiprotons extracted from the Recycler for Tevatron shots. In this paper, we describe observations of the instabilities during the extraction process as well as during dedicated studies. The measured instability threshold phase density agrees with the prediction of the rigid beam model within a factor of 2. Also, we conclude that the instability threshold can be significantly lowered for a bunch contained in a narrow and shallow potential well due to effective exclusion of the longitudinal tails from Landau damping.

  1. Optimal excitation of two dimensional Holmboe instabilities

    CERN Document Server

    Constantinou, Navid C


    Highly stratified shear layers are rendered unstable even at high stratifications by Holmboe instabilities when the density stratification is concentrated in a small region of the shear layer. These instabilities may cause mixing in highly stratified environments. However these instabilities occur in tongues for a limited range of parameters. We perform Generalized Stability analysis of the two dimensional perturbation dynamics of an inviscid Boussinesq stratified shear layer and show that Holmboe instabilities at high Richardson numbers can be excited by their adjoints at amplitudes that are orders of magnitude larger than by introducing initially the unstable mode itself. We also determine the optimal growth that obtains for parameters for which there is no instability. We find that there is potential for large transient growth regardless of whether the background flow is exponentially stable or not and that the characteristic structure of the Holmboe instability asymptotically emerges for parameter values ...

  2. Mode-locking via dissipative Faraday instability (United States)

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


    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.

  3. Mode-locking via dissipative Faraday instability. (United States)

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


    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.

  4. Sex chromosome rearrangements in Polyphaga beetles. (United States)

    Dutrillaux, A M; Dutrillaux, B


    The presence of a parachute sex chromosome bivalent (Xyp) at metaphase I of male meiosis is a well-known characteristic of Coleoptera, present in almost all families of this order and assumed to represent their ancestral sex chromosome formula. Sex chromosomes appear to be manifold more frequently involved in inter-chromosomal rearrangements than the average of the nine autosomal pairs usually forming their karyotype. This leads to various formulae such as neo-sex, multiple sex and perhaps unique sex chromosomes. These rearrangements alter the intimate association between sex chromosomes and nucleolar proteins, which are usual components of the Xyp. Different situations, selected in a series of 125 mitotic and meiotic cytogenetic studies of Polyphaga beetle species, are reported and discussed, with the aim to improve our knowledge on the mechanisms of sex chromosome rearrangements, the relationships with nucleoli and the consequences on dosage compensation and chromosome segregation.

  5. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David


    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...

  6. Chromosome Territory Modeller and Viewer. (United States)

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


    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.


    We have used CHEF gel electrophoresis to screen preparations of large DNA from different Burkholderia cepacia isolates for the presence of DNA species corresponding to the linearized forms of the three chromosomes of 3.4,2.5, and 0.9 Mb identified in B. cepacia strain 17616. DNA ...

  8. Chromosome synteny in cucumis species (United States)

    Cucumber, Cucumis sativus L. (2n = 2x = 14) and melon, C. melo L. (2n = 2x = 24) are two important vegetable species in the genus Cucumis (family Cucurbitaceae). Two inter-fertile botanical varieties with 14 chromosomes, the cultivated C. sativus var. sativus L. and the wild C. sativus var. hardwick...

  9. Chromosomal disorders and male infertility

    Institute of Scientific and Technical Information of China (English)

    Gary L Harton; Helen G Tempest


    infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family.Despite this,the molecular and genetic factors underlying the cause of infertility remain largely undiscovered.Nevertheless,more and more genetic factors associated with infertility are being identified.This review will focus on our current understanding of the chromosomal basis of male infertility specifically:chromosomal aneuploidy,structural and numerical karyotype abnormalities and Y chromosomal microdeletions.Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans.Aneuploidy is predominantly maternal in origin,but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts.Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm.Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed,as well as the application of preimplantation genetic diagnosis (PGD) in such cases.Clinical recommendations where possible will be made,as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

  10. Fishbone Instability Excited by Barely Trapped Electrons

    Institute of Scientific and Technical Information of China (English)

    WANG Zhong-Tian; LONG Yong-Xing; DONG Jia-Qi; WANG Long; Fulvio Zonca


    Fishbone instability excited by barely trapped suprathermal electrons (BTSEs) in tokamaks is investigated theoretically. The frequency of the mode is found to close to procession frequency of BTSEs. The growth rate of the mode is much smaller than that of the ideal magnetohytrodynamic (MHD) internal kink mode that is in contrast to the case of trapped ion driven fishbone instability. The analyses also show that spatial density gradient reversal is necessary for the instability. The correlation of the results with experiments is discussed.

  11. Electron proton instability in the CSNS ring

    Institute of Scientific and Technical Information of China (English)

    WANG Na; QIN Qing; LIU Yu-Dong


    The electron proton(e-p)instability has been observed in many proton accelerators.It will induce transverse beam size blow-up,cause beam loss and restrict the machine performance.Much research work has been done on the causes,dynamics and cures of this instability.A simulation code is developed to study the e-p instability in the ring of the China Spallation Neutron Source(CSNS).

  12. Beam Instabilities in the Scale Free Regime

    CERN Document Server

    Folli, Viola; Conti, Claudio; 10.1103/PhysRevLett.108.033901


    The instabilities arising in a one-dimensional beam sustained by the diffusive photorefractive nonlinearity in out-of-equilibrium ferroelectrics are theoretically and numerically investigated. In the "scale-free model", in striking contrast with the well-known spatial modulational instability, two different beam instabilities dominate: a defocusing and a fragmenting process. Both are independent of the beam power and are not associated to any specific periodic pattern.

  13. Instabilities and transition in boundary layers

    Indian Academy of Sciences (India)

    N Vinod; Rama Govindarajan


    Some recent developments in boundary layer instabilities and transition are reviewed. Background disturbance levels determine the instability mechanism that ultimately leads to turbulence. At low noise levels, the traditional Tollmien–Schlichting route is followed, while at high levels, a `by-pass' route is more likely. Our recent work shows that spot birth is related to the pattern of secondary instability in either route.

  14. [Cervical spine instability in the surgical patient]. (United States)

    Barbeito, A; Guerri-Guttenberg, R A


    Many congenital and acquired diseases, including trauma, may result in cervical spine instability. Given that airway management is closely related to the movement of the cervical spine, it is important that the anesthesiologist has detailed knowledge of the anatomy, the mechanisms of cervical spine instability, and of the effects that the different airway maneuvers have on the cervical spine. We first review the normal anatomy and biomechanics of the cervical spine in the context of airway management and the concept of cervical spine instability. In the second part, we review the protocols for the management of cervical spine instability in trauma victims and some of the airway management options for these patients.

  15. Systems and methods for controlling flame instability

    KAUST Repository

    Cha, Min Suk


    A system (62) for controlling flame instability comprising: a nozzle (66) coupled to a fuel supply line (70), an insulation housing (74) coupled to the nozzle, a combustor (78) coupled to the nozzle via the insulation housing, where the combustor is grounded (80), a pressure sensor (82) coupled to the combustor and configured to detect pressure in the combustor, and an instability controlling assembly coupled to the pressure sensor and to an alternating current power supply (86), where, the instability controlling assembly can control flame instability of a flame in the system based on pressure detected by the pressure sensor.

  16. Review of two-phase instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Han Ok; Seo, Han Ok; Kang, Hyung Suk; Cho, Bong Hyun; Lee, Doo Jeong


    KAERI is carrying out a development of the design for a new type of integral reactors. The once-through helical steam generator is important design features. The study on designs and operating conditions which prevent flow instability should precede the introduction of one-through steam generator. Experiments are currently scheduled to understand two-phase instability, evaluate the effect of each design parameter on the critical point, and determine proper inlet throttling for the prevention of instability. This report covers general two-phase instability with review of existing studies on this topics. The general classification of two phase flow instability and the characteristics of each type of instability are first described. Special attention is paid to BWR core flow instability and once-through steam generator instability. The reactivity feedback and the effect of system parameters are treated mainly for BWR. With relation to once-through steam generators, the characteristics of convective heating and dryout point oscillation are first investigated and then the existing experimental studies are summarized. Finally chapter summarized the proposed correlations for instability boundary conditions. (author). 231 refs., 5 tabs., 47 figs

  17. Aeroelastic instability problems for wind turbines

    DEFF Research Database (Denmark)

    Hansen, Morten Hartvig


    This paper deals with the aeroelostic instabilities that have occurred and may still occur for modem commercial wind turbines: stall-induced vibrations for stall-turbines, and classical flutter for pitch-regulated turbines. A review of previous works is combined with derivations of analytical...... stiffness and chordwise position of the center of gravity along the blades are the main parameters for flutter. These instability characteristics are exemplified by aeroelastic stability analyses of different wind turbines. The review of each aeroelastic instability ends with a list of current research...... issues that represent unsolved aeroelostic instability problems for wind turbines. Copyright (c) 2007 John Wiley & Sons, Ltd....

  18. Two-Fluid Interface Instability Being Studied (United States)

    Niederhaus, Charles E.


    The interface between two fluids of different density can experience instability when gravity acts normal to the surface. The relatively well known Rayleigh-Taylor (RT) instability results when the gravity is constant with a heavy fluid over a light fluid. An impulsive acceleration applied to the fluids results in the Richtmyer-Meshkov (RM) instability. The RM instability occurs regardless of the relative orientation of the heavy and light fluids. In many systems, the passing of a shock wave through the interface provides the impulsive acceleration. Both the RT and RM instabilities result in mixing at the interface. These instabilities arise in a diverse array of circumstances, including supernovas, oceans, supersonic combustion, and inertial confinement fusion (ICF). The area with the greatest current interest in RT and RM instabilities is ICF, which is an attempt to produce fusion energy for nuclear reactors from BB-sized pellets of deuterium and tritium. In the ICF experiments conducted so far, RM and RT instabilities have prevented the generation of net-positive energy. The $4 billion National Ignition Facility at Lawrence Livermore National Laboratory is being constructed to study these instabilities and to attempt to achieve net-positive yield in an ICF experiment.

  19. Instabilities of flows and transition to turbulence

    CERN Document Server

    Sengupta, Tapan K


    Introduction to Instability and TransitionIntroductionWhat Is Instability?Temporal and Spatial InstabilitySome Instability MechanismsComputing Transitional and Turbulent FlowsFluid Dynamical EquationsSome Equilibrium Solutions of the Basic EquationBoundary Layer TheoryControl Volume Analysis of Boundary LayersNumerical Solution of the Thin Shear Layer (TSL) EquationLaminar Mixing LayerPlane Laminar JetIssues of Computing Space-Time Dependent FlowsWave Interaction: Group Velocity and Energy FluxIssues of Space-Time Scale Resolution of FlowsTemporal Scales in Turbulent FlowsComputing Time-Averag

  20. Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner

    NARCIS (Netherlands)

    Moser, Jill; Kool, Hanneke; Giakzidis, Ioannis; Caldecott, Keith; Mullenders, Leon H. F.; Fousteri, Maria I.


    Impaired gap filling and sealing of chromosomal DNA in nucleotide excision repair (NER) leads to genome instability. XRCC1-DNA ligase III alpha (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 indispensa

  1. A Plain English Map of the Human Chromosomes. (United States)

    Offner, Susan


    Presents a chromosome map for 19 known chromosomes in human genetics. Describes the characteristics attributed to the genetic codes for each of the chromosomes and discusses the teaching applications of the chromosome map. (MDH)

  2. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael


    A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented...... and discussed, and the previously reported cases of familially transmitted G-group ring chromosomes are reviewed....

  3. Female meiotic sex chromosome inactivation in chicken

    NARCIS (Netherlands)

    S. Schoenmakers (Sam); E. Wassenaar (Evelyne); J.W. Hoogerbrugge (Jos); J.S.E. Laven (Joop); J.A. Grootegoed (Anton); W.M. Baarends (Willy)


    textabstractDuring meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI) leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (Z

  4. Cosmic Rays and Radiative Instabilities

    CERN Document Server

    Hartquist, T W; Falle, S A E G; Pittard, J M; Van Loo, S


    In the absence of magnetic fields and cosmic rays, radiative cooling laws with a range of dependences on temperature affect the stability of interstellar gas. For about four and a half decades, astrophysicists have recognised the importance of the thermal instablity for the formation of clouds in the interstellar medium. Even in the past several years, many papers have concerned the role of the thermal instability in the production of molecular clouds. About three and a half decades ago, astrophysicists investigating radiative shocks noticed that for many cooling laws such shocks are unstable. Attempts to address the effects of cosmic rays on the stablity of radiative media that are initially uniform or that have just passed through shocks have been made. The simplest approach to such studies involves the assumption that the cosmic rays behave as a fluid. Work based on such an approach is described. Cosmic rays have no effect on the stability of initially uniform, static media with respect to isobaric perturb...

  5. Visco-Resistive Plasmoid Instability

    CERN Document Server

    Comisso, Luca


    The plasmoid instability in visco-resistive current sheets is analyzed in both the linear and nonlinear regimes. The linear growth rate and the wavenumber are found to scale as $S^{1/4} {\\left( {1 + {P_m}} \\right)}^{-5/8}$ and $S^{3/8} {\\left( {1 + {P_m}} \\right)}^{-3/16}$ with respect to the Lundquist number $S$ and the magnetic Prandtl number $P_m$. Furthermore, the linear layer width is shown to scale as $S^{-1/8} {(1+P_m)}^{1/16}$. The growth of the plasmoids slows down from an exponential growth to an algebraic growth when they enter into the nonlinear regime. In particular, the time-scale of the nonlinear growth of the plasmoids is found to be $\\tau_{NL} \\sim S^{-3/16} {(1 + P_m)^{19/32}}{\\tau _{A,L}}$. The nonlinear growth of the plasmoids is radically different from the linear one and it is shown to be essential to understand the global current sheet disruption. It is also discussed how the plasmoid instability enables fast magnetic reconnection in visco-resistive plasmas. In particular, it is shown t...

  6. Combustion instability modeling and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Santoro, R.J.; Yang, V.; Santavicca, D.A. [Pennsylvania State Univ., University Park, PA (United States)] [and others


    It is well known that the two key elements for achieving low emissions and high performance in a gas turbine combustor are to simultaneously establish (1) a lean combustion zone for maintaining low NO{sub x} emissions and (2) rapid mixing for good ignition and flame stability. However, these requirements, when coupled with the short combustor lengths used to limit the residence time for NO formation typical of advanced gas turbine combustors, can lead to problems regarding unburned hydrocarbons (UHC) and carbon monoxide (CO) emissions, as well as the occurrence of combustion instabilities. Clearly, the key to successful gas turbine development is based on understanding the effects of geometry and operating conditions on combustion instability, emissions (including UHC, CO and NO{sub x}) and performance. The concurrent development of suitable analytical and numerical models that are validated with experimental studies is important for achieving this objective. A major benefit of the present research will be to provide for the first time an experimentally verified model of emissions and performance of gas turbine combustors.

  7. The Chemistry of Beer Instability (United States)

    Stewart, Graham G.


    Compared to most other alcoholic beverages, beer is unique because it is unstable when in the final package. This instability can be divided into biological and nonbiological instability. Nonbiological stability of beer involves a wide range of chemical processes and can be considered in a number of categories: physical, flavor, light, foam, and gushing. It is the balance between flavanoid polyphenols (tannoids) and sensitive proteins that specifically combine with polyphenols to form haze that largely dictates physical stability. The flavor stability of beer primarily depends on the oxygen concentration of packaged beer but is influenced by all stages of the brewing process. Foam stability in a glass of beer reflects the quality of the beverage. The backbone of foam is hydrophobic polypeptides. Novel brewing processes such as high-gravity brewing result in a disproportionate loss of these polypeptides and have a negative effect on the foam stability of the resulting beer. Beer is light sensitive, especially in the 350 500 nm range. Beer exposed to this wavelength range in clear or green glass containers quickly develop nauseous skunky-like off-flavors resulting from the formation of 3-methyl-2-butene-1-thiol. Methods of enhancing all of these types of beer stability are discussed.

  8. Chromosomal Engineering of Escherichia coli for Efficient Production of Coenzyme Q10

    Institute of Scientific and Technical Information of China (English)

    黄明涛; 陈韵妍; 刘建忠


    The plasmid-expression system is routinely plagued by potential plasmid instability. Chromosomal in-tegration is one powerful approach to overcome the problem. Herein we report a plasmid-free hyper-producer E. coli strain for coenzyme Q10 production. A series of integration expression vectors, pxKC3T5b and pxKT5b, were constructed for chemically inducible chromosomal evolution (multiple copy integration) and replicon-free and markerless chromosomal integration (single copy integration), respectively. A coenzyme Q10 hyper-producer Es-cherichia coli TBW20134 was constructed by applying chemically inducible chromosomal evolution, replicon-free and markerless chromosomal integration as well as deletion of menaquinone biosynthetic pathway. The engineered E. coli TBW20134 produced 10.7 mg per gram of dry cell mass (DCM) of coenzyme Q10 when supplemented with 0.075 g·L-1 of 4-hydroxy benzoic acid;this yield is unprecedented in E. coli and close to that of the commercial producer Agrobacterium tumefaciens. With this strain, the coenzyme Q10 production capacity was very stable after 30 sequential transfers and no antibiotics were required during the fermentation process. The strategy presented may be useful as a general approach for construction of stable production strains synthesizing natural products where various copy numbers for different genes are concerned.

  9. Karyotyping of Chromosomes in Human Bronchial Epithelial Cells Transformed by High Energy Fe Ions (United States)

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


    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.

  10. Differentiation and evolutionary relationships in Erythrinus erythrinus (Characiformes, Erythrinidae): occurrence and distribution of B chromosomes. (United States)

    Martins, N F; Cioffi, M B; Troy, W P; Martinez, J F; Moreira-Filho, O; Bertollo, L A C


    Erythrinus erythrinus, a Neotropical fish species of the Erythrinidae family, has a wide distribution in South America. Previous cytogenetic analysis showed that this species presents extensive karyotype diversity, with 4 karyomorphs (A-D) described herein. This study investigated the karyotypic structure of 2 new populations of E. erythrinus from the Brazilian Pantanal region, in order to improve the knowledge of the chromosomal diversity in this species. Both populations showed typical characteristics of karyomorph A, with 2n=54 chromosomes (6m+2st+46a), without differentiation between males and females. In addition, identical supernumerary B chromosomes, appearing as double-minute chromosomes, were also found in both populations. These findings suggest the presence of mitotic instability in view of their high intra- and inter-individual numerical variation. The presence of these chromosomes is likely a basal characteristic for this group, since the same kind of Bs also occurs in some other populations and karyomorphs of E. erythrinus. As such, they are important markers of biodiversity found in this nominal species, which probably corresponds to a species complex.

  11. Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment.

    Directory of Open Access Journals (Sweden)

    Miyako Kondoh

    Full Text Available There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, >30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment.

  12. High rates of chromosome missegregation suppress tumor progression but do not inhibit tumor initiation (United States)

    Zasadil, Lauren M.; Britigan, Eric M. C.; Ryan, Sean D.; Kaur, Charanjeet; Guckenberger, David J.; Beebe, David J.; Moser, Amy R.; Weaver, Beth A.


    Aneuploidy, an abnormal chromosome number that deviates from a multiple of the haploid, has been recognized as a common feature of cancers for >100 yr. Previously, we showed that the rate of chromosome missegregation/chromosomal instability (CIN) determines the effect of aneuploidy on tumors; whereas low rates of CIN are weakly tumor promoting, higher rates of CIN cause cell death and tumor suppression. However, whether high CIN inhibits tumor initiation or suppresses the growth and progression of already initiated tumors remained unclear. We tested this using the ApcMin/+ mouse intestinal tumor model, in which effects on tumor initiation versus progression can be discriminated. ApcMin/+ cells exhibit low CIN, and we generated high CIN by reducing expression of the kinesin-like mitotic motor protein CENP-E. CENP-E+/−;ApcMin/+ doubly heterozygous cells had higher rates of chromosome missegregation than singly heterozygous cells, resulting in increased cell death and a substantial reduction in tumor progression compared with ApcMin/+ animals. Intestinal organoid studies confirmed that high CIN does not inhibit tumor cell initiation but does inhibit subsequent cell growth. These findings support the conclusion that increasing the rate of chromosome missegregation could serve as a successful chemotherapeutic strategy. PMID:27146113

  13. Partial Hepatectomy in Acetylation-Deficient Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yoo-Kyung Lee


    Full Text Available BackgroundAneuploidy has been suggested as one of the major causes of cancer from the time of Boveri. In support of this notion, many studies have shown that cancer cells exhibit aneuploidy. However, there are evidences that do not support the aneuploidy hypothesis. We have previously reported that the spindle assembly checkpoint protein BubR1 is acetylated in mitosis and that the acetylation of BubR1 is crucial for checkpoint maintenance and chromosome-spindle attachment. Mice heterozygous for acetylation-deficient BubR1 (K243R/+ spontaneously develop cancer with chromosome instability. As K243R/+ mice develop hepatocellular carcinoma, we set out to test if chromosome mis-segregation was the cause of their liver cancer.MethodsPrimary hepatocytes in the regenerating liver after partial hepatectomy (PH were analyzed and compared for various mitotic parameters.ResultsPrimary hepatocytes isolated from K243R/+ mice after PH displayed a marked increase of chromosome misalignment, accompanied by an increase of micronuclei. In comparison, the number of nuclei per cell and the centrosome numbers were not different between wild-type and K243R/+ mice. Taken together, chromosome mis-segregation provokes tumorigenesis in mouse liver.ConclusionOur results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice.

  14. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure (United States)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu


    Tumor formation in humans or animals is a multi-step process. 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. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  15. Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment (United States)

    Hida, Yasuhiro; Maishi, Nako; Towfik, Alam Mohammad; Inoue, Nobuo; Shindoh, Masanobu; Hida, Kyoko


    There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, >30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment. PMID:24260373

  16. The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary


    Wienberg, Johannes; Jauch, Anna; Lüdecke, H J; Senger, G.; Horsthemke, B; Claussen, U.; Cremer, Thomas; Arnold, N; Lengauer, Christoph


    Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of ...

  17. Y-chromosome polymorphism: Possible largest Y chromosome in man?

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, D.S.K.; Al-Awadi, S.A.; Bastaki, L. [Kuwait Medical Genetics Centre, Sulaibikat (Kuwait)] [and others


    The role of variations (inversions/deletion or duplication) in the heterochromatin in gonadal development and function, reproductive fitness, and malignant disease has been extensively studied. However, the causal-relationship of large Y (Yqh+) and repeated fetal loss has not been established unequivocally. An Arab couple (?Bedouin origin) with a history of repeated abortions were investigated. Karyotype analysis of the husband showed a very large Y chromosome, confirmed by GTG-, QFQ- and CBG-banding techniques. C-banding showed discontinuous distribution of the heterochromatin blocks separated by pale bands. The origin of the large heterochromatin segment could be due to tandem duplication of the Yq region or translocation (Yq:Yq). No other relatives (males) of the propositus have been available for investigation. Polymorphism of the Y chromosome could be attributed to evolutionary changes from an ancestral type, either by deletion or duplication of the heterochromatin segment. More detailed studies on isolated, aboriginal/tribal human populations will enable us to better understand the significance of the Y chromosome polymorphism.

  18. 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.

  19. Chromosome congression explained by nanoscale electrostatics. (United States)

    Gagliardi, L John; Shain, Daniel H


    Nanoscale electrostatic microtubule disassembly forces between positively charged molecules in kinetochores and negative charges on plus ends of microtubules have been implicated in poleward chromosome motions and may also contribute to antipoleward chromosome movements. We propose that chromosome congression can be understood in terms of antipoleward nanoscale electrostatic microtubule assembly forces between negatively charged microtubule plus ends and like-charged chromosome arms, acting in conjunction with poleward microtubule disassembly forces. Several other aspects of post-attachment prometaphase chromosome motions, as well as metaphase oscillations, are consistently explained within this framework.

  20. The Chromosomes of Birds during Meiosis. (United States)

    Pigozzi, María I


    The cytological analysis of meiotic chromosomes is an exceptional tool to approach complex processes such as synapsis and recombination during the division. Chromosome studies of meiosis have been especially valuable in birds, where naturally occurring mutants or experimental knock-out animals are not available to fully investigate the basic mechanisms of major meiotic events. This review highlights the main contributions of synaptonemal complex and lampbrush chromosome research to the current knowledge of avian meiosis, with special emphasis on the organization of chromosomes during prophase I, the impact of chromosome rearrangements during meiosis, and distinctive features of the ZW pair.

  1. Polymer models of chromosome (re)organization (United States)

    Mirny, Leonid

    Chromosome Conformation Capture technique (Hi-C) provides comprehensive information about frequencies of spatial interactions between genomic loci. Inferring 3D organization of chromosomes from these data is a challenging biophysical problem. We develop a top-down approach to biophysical modeling of chromosomes. Starting with a minimal set of biologically motivated interactions we build ensembles of polymer conformations that can reproduce major features observed in Hi-C experiments. I will present our work on modeling organization of human metaphase and interphase chromosomes. Our works suggests that active processes of loop extrusion can be a universal mechanism responsible for formation of domains in interphase and chromosome compaction in metaphase.

  2. Chromosome painting of Z and W sex chromosomes in Characidium (Characiformes, Crenuchidae). (United States)

    Pazian, Marlon F; Shimabukuro-Dias, Cristiane Kioko; Pansonato-Alves, José Carlos; Oliveira, Claudio; Foresti, Fausto


    Some species of the genus Characidium have heteromorphic ZZ/ZW sex chromosomes with a totally heterochromatic W chromosome. Methods for chromosome microdissection associated with chromosome painting have become important tools for cytogenetic studies in Neotropical fish. In Characidium cf. fasciatum, the Z chromosome contains a pericentromeric heterochromatin block, whereas the W chromosome is completely heterochromatic. Therefore, a probe was produced from the W chromosome through microdissection and degenerate oligonucleotide-primed polymerase chain reaction amplification. FISH was performed using the W probe on the chromosomes of specimens of this species. This revealed expressive marks in the pericentromeric region of the Z chromosome as well as a completely painted W chromosome. When applying the same probe on chromosome preparations of C. cf. gomesi and Characidium sp., a pattern similar to C. cf. fasciatum was found, while C. cf. zebra, C. cf. lagosantense and Crenuchus spilurus species showed no hybridization signals. Structural changes in the chromosomes of an ancestral sexual system in the group that includes the species C. cf. gomesi, C. cf. fasciatum and Characidium sp., could have contributed to the process of speciation and could represent a causal mechanism of chromosomal diversification in this group. The heterochromatinization process possibly began in homomorphic and homologous chromosomes of an ancestral form, and this process could have given rise to the current patterns found in the species with sex chromosome heteromorphism.

  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. Interfacial instabilities in vibrated fluids (United States)

    Porter, Jeff; Laverón-Simavilla, Ana; Tinao Perez-Miravete, Ignacio; Fernandez Fraile, Jose Javier


    Vibrations induce a range of different interfacial phenomena in fluid systems depending on the frequency and orientation of the forcing. With gravity, (large) interfaces are approximately flat and there is a qualitative difference between vertical and horizontal forcing. Sufficient vertical forcing produces subharmonic standing waves (Faraday waves) that extend over the whole interface. Horizontal forcing can excite both localized and extended interfacial phenomena. The vibrating solid boundaries act as wavemakers to excite traveling waves (or sloshing modes at low frequencies) but they also drive evanescent bulk modes whose oscillatory pressure gradient can parametrically excite subharmonic surface waves like cross-waves. Depending on the magnitude of the damping and the aspect ratio of the container, these locally generated surfaces waves may interact in the interior resulting in temporal modulation and other complex dynamics. In the case where the interface separates two fluids of different density in, for example, a rectangular container, the mass transfer due to vertical motion near the endwalls requires a counterflow in the interior region that can lead to a Kelvin-Helmholtz type instability and a ``frozen wave" pattern. In microgravity, the dominance of surface forces favors non-flat equilibrium configurations and the distinction between vertical and horizontal applied forcing can be lost. Hysteresis and multiplicity of solutions are more common, especially in non-wetting systems where disconnected (partial) volumes of fluid can be established. Furthermore, the vibrational field contributes a dynamic pressure term that competes with surface tension to select the (time averaged) shape of the surface. These new (quasi-static) surface configurations, known as vibroequilibria, can differ substantially from the hydrostatic state. There is a tendency for the interface to orient perpendicular to the vibrational axis and, in some cases, a bulge or cavity is induced

  5. TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability

    DEFF Research Database (Denmark)

    Germann, Susanne M; Schramke, Vera; Pedersen, Rune Troelsgaard


    DNA anaphase bridges are a potential source of genome instability that may lead to chromosome breakage or nondisjunction during mitosis. Two classes of anaphase bridges can be distinguished: DAPI-positive chromatin bridges and DAPI-negative ultrafine DNA bridges (UFBs). Here, we establish budding...... yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion...... instability. In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination....

  6. Chromosomal patterns in human malignant astrocytomas. (United States)

    Rey, J A; Bello, M J; de Campos, J M; Kusak, M E; Ramos, C; Benitez, J


    Cytogenetic analysis by direct and/or in vitro preparations was performed on 34 malignant astrocytomas. Thirty tumors showed near-diploid chromosome numbers, whereas, tritetraploid chromosome complements were present in four tumors. The most frequent chromosomal changes implied numerical deviations by a gain of chromosomes #7, #19, and #20, and by losses of #10, #22, and Y. Structural rearrangements were present in stem- or side lines of 24 tumors. Although no common chromosomal rearrangement seems to exist among those tumors, chromosomes #1, #6, #7, and #9 were predominantly involved. Polysomy and structural rearrangements of chromosome #7 could be related to the overexpression of epidermal growth factor gene, previously observed in some malignant gliomas.

  7. Entropy as the driver of chromosome segregation. (United States)

    Jun, Suckjoon; Wright, Andrew


    We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in the regulation of chromosome structure and segregation may in fact function primarily in supporting such an entropy-driven segregation mechanism by regulating the physical state of chromosomes. We conclude that bacterial chromosome segregation is best understood in terms of spontaneous demixing of daughter strands. Our concept may also have important implications for chromosome segregation in eukaryotes, in which spindle-dependent chromosome movement follows an extended period of sister chromatid demixing and compaction.

  8. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.


    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  9. Chromosome X aneuploidy in Brazilian schizophrenic patients. (United States)

    de Moraes, Leopoldo Silva; Khayat, André Salim; de Lima, Patrícia Danielle Lima; Lima, Eleonidas Moura; Pinto, Giovanny Rebouças; Leal, Mariana Ferreira; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez


    The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

  10. On the descriptions of beam instabilities

    CERN Document Server

    Maillard, Antoine


    We investigate two interesting features of beam instabilities in accelerators : First, we provide the equivalence between two models to describe transverse instabilities, the circulant matrix model (based on a longitudinal phase space discretization) and the Vlasov formalism. Secondly, we show how to derive dispersion integrals for transverse detuning effects in the Vlasov formalism, thus allowing for Landau damping mechanism.

  11. The short circuit instability in protoplanetary disks

    DEFF Research Database (Denmark)

    Hubbard, A.; McNally, C.P.; Mac Low, M.M.;


    We introduce a magneto-hydrodynamic instability which occurs, among other locations, in the inner, hot regions of protoplanetary disks, and which alters the way in which resistive dissipation of magnetic energy into heat proceeds. This instability can be likened to both an electrical short circuit...

  12. Energetic particle instabilities in fusion plasmas

    NARCIS (Netherlands)

    Sharapov, S. E.; Alper, B.; Berk, H. L.; Borba, D. N.; Breizman, B. N.; Challis, C. D.; Classen, I.G.J.; Edlund, E. M.; Eriksson, J.; Fasoli, A.; Fredrickson, E. D.; Fu, G. Y.; Garcia-Munoz, M.; Gassner, T.; Ghantous, K.; Goloborodko, V.; Gorelenkov, N. N.; Gryaznevich, M. P.; Hacquin, S.; Heidbrink, W. W.; Hellesen, C.; Kiptily, V. G.; Kramer, G. J.; Lauber, P.; Lilley, M. K.; Lisak, M.; Nabais, F.; Nazikian, R.; Nyqvist, R.; Osakabe, M.; C. Perez von Thun,; Pinches, S. D.; Podesta, M.; Porkolab, M.; Shinohara, K.; Schoepf, K.; Todo, Y.; Toi, K.; VanZeeland, M. A.; Voitsekhovich, I.; White, R. B.; Yavorskij, V.; ITPA EP TG Contributors,; JET-EFDA Contributors,


    Remarkable progress has been made in diagnosing energetic particle instabilities on present-day machines and in establishing a theoretical framework for describing them. This overview describes the much improved diagnostics of Alfvén instabilities and modelling tools developed world-wide, and discus

  13. Cultural diversity, economic development and societal instability (United States)

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


    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.

  14. Mapping Instabilities in Polymer Friction (United States)

    Rand, Charles; Crosby, Alfred


    Schallamach waves are instabilities that occur as interfaces between a soft elastomer and rigid surface slide past each other.(1) The presence of Schallamach waves can lead to drastic changes in frictional properties. Although the occurrence of Schallamach waves has been studied for the past several decades, a general map relating fundamental material properties, geometry, and operating conditions (i.e. speed and temperature) has not been established. Using a combinatorial approach, we illustrate the role of modulus, testing velocity and surface energetics of crosslinked poly(dimethyl siloxane) on the generation Schallamach waves. This knowledge will be used with polymer patterning processes to fabricate responsive coatings for applications such as anti-fouling coatings. (1)Schallamach, A.;Wear 1971,17, 301-312.

  15. Transient spirals as superposed instabilities

    CERN Document Server

    Sellwood, J A


    We present evidence that recurrent spiral activity, long manifested in simulations of disk galaxies, results from the super-position of a few transient spiral modes. Each mode lasts between five and ten rotations at its corotation radius where its amplitude is greatest. The scattering of stars as each wave decays takes place over narrow ranges of angular momentum, causing abrupt changes to the impedance of the disk to subsequent traveling waves. Partial reflections of waves at these newly created features, allows new standing-wave instabilities to appear that saturate and decay in their turn, scattering particles at new locations, creating a recurring cycle. The spiral activity causes the general level of random motion to rise, gradually decreasing the ability of the disk to support further activity unless the disk contains a dissipative gas component from which stars form on near-circular orbits. We also show that this interpretation is consistent with the behavior reported in other recent simulations with l...

  16. Gravitational Instability of a Kink

    CERN Document Server

    Barreto, W; Lehner, L; Winicour, J


    We study the equilibria of a self-gravitating scalar field in the region outside a reflecting barrier. By introducing a potential difference between the barrier and infinity, we create a kink which cannot decay to a zero energy state. In the realm of small amplitude, the kink decays to a known static solution of the Einstein-Klein-Gordon equation. However, for larger kinks the static equilibria are degenerate, forming a system with two energy levels. The upper level is unstable and, under small perturbations, decays to the lower energy stable equilibrium. Under large perturbations, the unstable upper level undergoes collapse to a black hole. The equilibrium of the system provides a remarkably simple and beautiful illustration of a turning point instability.

  17. Hydrodynamic Instabilities in Rotating Fluids

    Institute of Scientific and Technical Information of China (English)



    Rotating flow systems are often used to study stability phenomena and structure developments.The closed spherical gap prblem is generalized into an open flow system by superimposing a mass flux in meridional direction.The basic solutions at low Reynolds numbers are described by analytical methods.The nonlinear supercritical solutions are simulated numerically and realized in experiments.Novel steady and time-dependent modes of flows are obtained.The extensive results concern the stability behaviour.non-uniqueness of supercritical solutions,symmetry behaviour and transitions between steady and time-dependent solutions.The experimental investigations concern the visualization of the various instabilities and the quatitative description of the flow structures including the laminar-turbulent transition.A Comparison between theoretical and experimental results shows good agreement within the limit of rotational symmetric solutions from the theory.

  18. The role of APC/C(Cdh1) in replication stress and origin of genomic instability. (United States)

    Greil, C; Krohs, J; Schnerch, D; Follo, M; Felthaus, J; Engelhardt, M; Wäsch, R


    It has been proposed that the APC/C(Cdh1) functions as a tumor suppressor by maintaining genomic stability. However, the exact nature of genomic instability following loss of Cdh1 is unclear. Using biochemistry and live cell imaging of single cells we found that Cdh1 knockdown (kd) leads to strong nuclear stabilization of the substrates cyclin A and B and deregulated kinetics of DNA replication. Restoration of the Cdh1-dependent G2 DNA damage checkpoint did not result in G2 arrest but blocked cells in prometaphase, suggesting that these cells enter mitosis despite incomplete replication. This results in DNA double-strand breaks, anaphase bridges, cytokinesis defects and tetraploidization. Tetraploid cells are the source of supernumerary centrosomes following Cdh1-kd, leading to multipolar mitosis or centrosome clustering, in turn resulting in merotelic attachment and lagging chromosomes. Whereas some of these events cause apoptosis during mitosis, surviving cells may accumulate chromosomal aberrations.

  19. Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium (United States)

    The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...

  20. Bacterial Chromosome Organization and Segregation


    Toro, Esteban; Shapiro, Lucy


    Bacterial chromosomes are generally ∼1000 times longer than the cells in which they reside, and concurrent replication, segregation, and transcription/translation of this crowded mass of DNA poses a challenging organizational problem. Recent advances in cell-imaging technology with subdiffraction resolution have revealed that the bacterial nucleoid is reliably oriented and highly organized within the cell. Such organization is transmitted from one generation to the next by progressive segrega...

  1. Environmental pollution, chromosomes, and health (United States)

    Bell, Peter M.

    In mid-May, 1980, President Carter declared a state of emergency at the Love Canal area, near Niagara Falls, New York. The reason for this was for the U.S. to underwrite the relocation costs ($3-5 million) of some 2500 residents who, according to a report by the EPA (Environmental Protection Agency) may have suffered damaged chromosomes. These injuries were apparently caused by contact with toxic wastes that had been dumped in the area in the years prior to development for housing.That the toxic compounds exist in the Love Canal and Niagara Falls subsurface zones, including public water supplies, appears to be established fact. That the residents of the Love Canal area suffered chromosomal damage may be established fact as well. Whether or not these two findings can be linked to ill health of the residents is another matter. Recently, the EPA report has been described as having ‘close to zero scientific significance,’ and has been ‘discredited’(Science, 208, 123a, 1980). The reasons for this disparity go beyond differences of opinion, beyond possible inadequacies of the EPA study, and even beyond problems that probably will arise from future studies, including those now in the planning stages. The problem is that even if victims have easily recognizable injuries from toxic substances (injury that apparently has not occurred to Love Canal residents), medical science usually cannot show a causal relationship. Even chromosomal damage is, at best, difficult to interpret. In ideal studies of significant populations and control groups, the association of toxic chemical to chromosome damage and to cancer and birth defects is indirect and, up to now, has been shown to have little or no significance to an individual member of the exposed population.

  2. Hypomethylation and Genetic Instability in Monosomy Blastocysts May Contribute to Decreased Implantation Potential.

    Directory of Open Access Journals (Sweden)

    Blair R McCallie

    Full Text Available DNA methylation is a key epigenetic mechanism responsible for gene regulation, chromatin remodeling, and genome stability, playing a fundamental role during embryonic development. The aim of this study was to determine if these epigenetic marks are associated with chromosomal aneuploidy in human blastocysts. Surplus, cryopreserved blastocysts that were donated to research with IRB consent were chosen with varying chromosomal aneuploidies and respective implantation potential: monosomies and trisomies 7, 11, 15, 21, and 22. DNA methylation analysis was performed using the Illumina Infinium HumanMethylation450 BeadChip (~485,000 CpG sites. The methylation profiles of these human blastocysts were found to be similar across all samples, independent of chromosome constitution; however, more detailed examination identified significant hypomethylation in the chromosome involved in the monosomy. Real-time PCR was also performed to determine if downstream messenger RNA (mRNA was affected for genes on the monosomy chromosome. Gene dysregulation was observed for monosomy blastocysts within significant regions of hypo-methylation (AVEN, CYFIP1, FAM189A1, MYO9A, ADM2, PACSIN2, PARVB, and PIWIL3 (P < 0.05. Additional analysis was performed to examine the gene expression profiles of associated methylation regulators including: DNA methyltransferases (DNMT1, DNMT3A, DNMT3B, DNMT3L, chromatin modifying regulators (CSNK1E, KDM1, PRKCA, and a post-translational modifier (PRMT5. Decreased RNA transcription was confirmed for each DNMT, and the regulators that impact DNMT activity, for only monosomy blastocysts (P < 0.05. In summary, monosomy blastocysts displayed hypomethylation for the chromosome involved in the error, as well as transcription alterations of associated developmental genes. Together, these modifications may be contributing to genetic instability and therefore be responsible for the limited implantation potential observed for full monosomy

  3. Dependence of Early and Late Chromosomal Aberrations on Radiation Quality and Cell Types (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Rohde, Larry; Wu, Honglu


    Exposure to radiation induces different types of DNA damage, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo. The susceptibility of cells to radiation depends on genetic background and growth condition of cells, as well as types of radiation. Mammalian cells of different tissue types and with different genetic background are known to have different survival rate and different mutation rate after cytogenetic insults. Genomic instability, induced by various genetic, metabolic, and environmental factors including radiation, is the driving force of tumorigenesis. Accurate measurements of the relative biological effectiveness (RBE) is important for estimating radiation-related risks. To further understand genomic instability induced by charged particles and their RBE, we exposed human lymphocytes ex vivo, human fibroblast AG1522, human mammary epithelial cells (CH184B5F5/M10), and bone marrow cells isolated from CBA/CaH(CBA) and C57BL/6 (C57) mice to high energy protons and Fe ions. Normal human fibroblasts AG1522 have apparently normal DNA damage response and repair mechanisms, while mammary epithelial cells (M10) are deficient in the repair of DNA DSBs. Mouse strain CBA is radio-sensitive while C57 is radio-resistant. Metaphase chromosomes at different cell divisions after radiation exposure were collected and chromosome aberrations were analyzed as RBE for different cell lines exposed to different radiations at various time points up to one month post irradiation.

  4. 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.


    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

  5. Mechanisms of Chromosome Congression during Mitosis (United States)

    Maiato, Helder; Gomes, Ana Margarida; Sousa, Filipe; Barisic, Marin


    Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E) that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle microtubule

  6. Mechanisms of Chromosome Congression during Mitosis

    Directory of Open Access Journals (Sweden)

    Helder Maiato


    Full Text Available Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle

  7. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.


    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  8. Secondary instability in boundary-layer flows (United States)

    Nayfeh, A. H.; Bozatli, A. N.


    The stability of a secondary Tollmien-Schlichting wave, whose wavenumber and frequency are nearly one half those of a fundamental Tollmien-Schlichting instability wave is analyzed using the method of multiple scales. Under these conditions, the fundamental wave acts as a parametric exciter for the secondary wave. The results show that the amplitude of the fundamental wave must exceed a critical value to trigger this parametric instability. This value is proportional to a detuning parameter which is the real part of k - 2K, where k and K are the wavenumbers of the fundamental and its subharmonic, respectively. For Blasius flow, the critical amplitude is approximately 29% of the mean flow, and hence many other secondary instabilities take place before this parametric instability becomes significant. For other flows where the detuning parameter is small, such as free-shear layer flows, the critical amplitude can be small, thus the parametric instability might play a greater role.

  9. Tensile Instability in a Thick Elastic Body (United States)

    Overvelde, Johannes T. B.; Dykstra, David M. J.; de Rooij, Rijk; Weaver, James; Bertoldi, Katia


    A range of instabilities can occur in soft bodies that undergo large deformation. While most of them arise under compressive forces, it has previously been shown analytically that a tensile instability can occur in an elastic block subjected to equitriaxial tension. Guided by this result, we conducted centimeter-scale experiments on thick elastomeric samples under generalized plane strain conditions and observed for the first time this elastic tensile instability. We found that equibiaxial stretching leads to the formation of a wavy pattern, as regions of the sample alternatively flatten and extend in the out-of-plane direction. Our work uncovers a new type of instability that can be triggered in elastic bodies, enlarging the design space for smart structures that harness instabilities to enhance their functionality.

  10. Taylor instability in rhyolite lava flows (United States)

    Baum, B. A.; Krantz, W. B.; Fink, J. H.; Dickinson, R. E.


    A refined Taylor instability model is developed to describe the surface morphology of rhyolite lava flows. The effect of the downslope flow of the lava on the structures resulting from the Taylor instability mechanism is considered. Squire's (1933) transformation is developed for this flow in order to extend the results to three-dimensional modes. This permits assessing why ridges thought to arise from the Taylor instability mechanism are preferentially oriented transverse to the direction of lava flow. Measured diapir and ridge spacings for the Little and Big Glass Mountain rhyolite flows in northern California are used in conjunction with the model in order to explore the implications of the Taylor instability for flow emplacement. The model suggests additional lava flow features that can be measured in order to test whether the Taylor instability mechanism has influenced the flows surface morphology.

  11. 3-D nonlinear evolution of MHD instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, G.; Hicks, H. R.; Wooten, J. W.


    The nonlinear evolution of ideal MHD internal instabilities is investigated in straight cylindrical geometry by means of a 3-D initial-value computer code. These instabilities are characterized by pairs of velocity vortex cells rolling off each other and helically twisted down the plasma column. The cells persist until the poloidal velocity saturates at a few tenths of the Alfven velocity. The nonlinear phase is characterized by convection around these essentially fixed vortex cells. For example, the initially centrally peaked temperature profile is convected out and around to form an annulus of high temperature surrounding a small region of lower temperature. Weak, centrally localized instabilities do not alter the edge of the plasma. Strong, large-scale instabilities, resulting from a stronger longitudinal equilibrium current, drive the plasma against the wall. After three examples of instability are analyzed in detail, the numerical methods and their verification are discussed.

  12. Whipping Instabilities in Electrified Liquid Jets

    CERN Document Server

    Marin, Alvaro G; Loscertales, Ignacio G; Barrero, Antonio


    A liquid jet may develop different types of instabilities, like the so-called Rayleigh-Plateau instability, which breaks the jet into droplets. However, another type of instabilities may appear when we electrify a liquid jet and induce some charge at his surface. Among them, the most common is the so-called Whipping Instability, which is characterized by violent and fast lashes of the jet. In the submitted fluid dynamic video(see, we will show an unstable charged glycerine jet in a dielectric liquid bath, which permits an enhanced visualization of the instability. For this reason, it is probably the first time that these phenomena are visualized with enough clarity to analyze features as the effect of the feeding liquid flow rate through the jet or as the surprising spontaneous stabilization at some critical distance to the ground electrode.

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

    Directory of Open Access Journals (Sweden)

    Sebastian Pita


    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.

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

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


    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.

  15. Cytogenetic characterization and B chromosome diversity in direct-developing frogs of the genus Oreobates (Brachycephaloidea, Craugastoridae) (United States)

    Ferro, Juan Martín; Taffarel, Alberto; Cardozo, Darío; Grosso, Jimena; Puig, María Pía; Suárez, Pablo; Akmentins, Mauricio Sebastián; Baldo, Diego


    Abstract Oreobates Jiménez de la Espada, 1872 is a large group of South American frogs with terrestrial reproduction and direct development, located in the superfamily Brachycephaloidea. About 260 brachycephaloidean species have been cytogenetically studied so far, at least with standard techniques. However, this information represents fewer than 17% species of the family Craugastoridae Hedges, Duellman & Heinicke, 2008, where the genus Oreobates is included. In the present work, using a diversity of standard and molecular techniques, we describe the karyotype of Oreobates barituensis Vaira & Ferrari, 2008, Oreobates berdemenos Pereyra, Cardozo, Baldo & Baldo, 2014 and Oreobates discoidalis (Peracca, 1895), from northwestern Argentina. The three species analyzed showed a diploid karyotype with 2n = 22 biarmed chromosomes, fundamental number (FN) = 44, nucleolus organizer regions (NORs) located pericentromerically on pair 7, and a centromeric and pericentromeric C-banding pattern. We observed variations in the chromosome number in Oreobates barituensis due the presence of two morphs of B chromosomes, one medium-sized telocentric (BT) and another subtelocentric and smaller (Bst). Both B chromosomes are mitotically stable and were recorded in all somatic and germinal cells analyzed. The BT chromosome occurred at a maximum of one per individual (2n = 22+BT), and the other one was observed single (2n = 22 + Bst) or as a pair in two doses (2n = 22 + 2BT). We additionally observed other supernumerary chromosomes in the three species analyzed, all of them euchromatic, small, dot-shaped and with instability during mitoses, showing a frequency of occurrence below 50% in studied specimens. The occurrence of polymorphic and spontaneous chromosomal rearrangements and supernumerary chromosomes is a recurrent feature reported in frogs with terrestrial habits (Brachycephaloidea and Hemiphractidae Peters, 1862), which suggests that Brachycephaloidea may be a promising group for

  16. Dicentric chromosomes and 20q11.2 amplification in MDS/AML with apparent monosomy 20. (United States)

    Mackinnon, R N; Campbell, L J


    FISH analysis of 41 previously karyotyped cases of MDS and AML with apparent monosomy of chromosome 20 revealed a variety of dicentric abnormalities involving chromosome 20. These usually, but not always, involved a breakpoint in the long arm of chromosome 20 and loss of the common deleted region at 20q12. Not one case of true monosomy 20 was confirmed. We found evidence for dicentric chromosome formation in 21 of 24 unbalanced translocations containing chromosome 20 and that were studied in more detail. Subsequent loss of one of the centromeres had occurred in eight of these 24 cases, and was more frequent than centromere inactivation as a means of resolving the inherent instability of a dicentric chromosome. In the three cases with dicentric chromosomes from which proximal 20q had been excised along with the 20 centromere, the excised segment was retained, and in two of these it was amplified. Proximal 20q was clearly retained in all but three cases, and present in three or more copies in 17 of 41 cases. The retention and amplification of proximal 20q provides support for the hypothesis that there is an oncogene located in this region of 20q that is activated in cases of MDS/AML with del(20q). Apparent monosomy 20 in MDS/AML should be treated as evidence of unidentified chromosome 20 abnormalities, and familiarity with the typical G-banded morphology of these derivatives can help with their identification. The reported incidence of dicentric chromosomes is clearly an under-estimate but is increasing in myeloid disorders as more cases are studied with methods allowing their detection.

  17. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells.

    Directory of Open Access Journals (Sweden)

    William T Silkworth

    Full Text Available Many cancer cells display a CIN (Chromosome Instability phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed gamma-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells.

  18. Chromosome aberrations induced by zebularine in triticale. (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun


    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  19. The importance of having two X chromosomes. (United States)

    Arnold, Arthur P; Reue, Karen; Eghbali, Mansoureh; Vilain, Eric; Chen, Xuqi; Ghahramani, Negar; Itoh, Yuichiro; Li, Jingyuan; Link, Jenny C; Ngun, Tuck; Williams-Burris, Shayna M


    Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes.

  20. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar


    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.

  1. Deciphering evolutionary strata on plant sex chromosomes and fungal mating-type chromosomes through compositional segmentation. (United States)

    Pandey, Ravi S; Azad, Rajeev K


    Sex chromosomes have evolved from a pair of homologous autosomes which differentiated into sex determination systems, such as XY or ZW system, as a consequence of successive recombination suppression between the gametologous chromosomes. Identifying the regions of recombination suppression, namely, the "evolutionary strata", is central to understanding the history and dynamics of sex chromosome evolution. Evolution of sex chromosomes as a consequence of serial recombination suppressions is well-studied for mammals and birds, but not for plants, although 48 dioecious plants have already been reported. Only two plants Silene latifolia and papaya have been studied until now for the presence of evolutionary strata on their X chromosomes, made possible by the sequencing of sex-linked genes on both the X and Y chromosomes, which is a requirement of all current methods that determine stratum structure based on the comparison of gametologous sex chromosomes. To circumvent this limitation and detect strata even if only the sequence of sex chromosome in the homogametic sex (i.e. X or Z chromosome) is available, we have developed an integrated segmentation and clustering method. In application to gene sequences on the papaya X chromosome and protein-coding sequences on the S. latifolia X chromosome, our method could decipher all known evolutionary strata, as reported by previous studies. Our method, after validating on known strata on the papaya and S. latifolia X chromosome, was applied to the chromosome 19 of Populus trichocarpa, an incipient sex chromosome, deciphering two, yet unknown, evolutionary strata. In addition, we applied this approach to the recently sequenced sex chromosome V of the brown alga Ectocarpus sp. that has a haploid sex determination system (UV system) recovering the sex determining and pseudoautosomal regions, and then to the mating-type chromosomes of an anther-smut fungus Microbotryum lychnidis-dioicae predicting five strata in the non

  2. Scaling Chromosomes for an Evolutionary Karyotype: A Chromosomal Tradeoff between Size and Number across Woody Species. (United States)

    Liang, Guolu; Chen, Hong


    This study aims to examine the expected scaling relationships between chromosome size and number across woody species and to clarify the importance of the scaling for the maintenance of chromosome diversity by analyzing the scaling at the inter- & intra-chromosomal level. To achieve for the goals, chromosome trait data were extracted for 191 woody species (including 56 evergreen species and 135 deciduous species) from the available literature. Cross-species analyses revealed a tradeoff among chromosomes between chromosome size and number, demonstrating there is selective mechanism crossing chromosomes among woody species. And the explanations for the result were presented from intra- to inter-chromosome contexts that the scaling may be compromises among scale symmetry, mechanical requirements, and resource allocation across chromosomes. Therein, a 3/4 scaling pattern was observed between total chromosomes and m-chromosomes within nucleus which may imply total chromosomes may evolve from more to less. In addition, the primary evolutionary trend of karyotype and the role of m-chromosomes in the process of karyotype evolution were also discussed.

  3. Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria. (United States)

    Teruel, María; Cabrero, Josefa; Montiel, Eugenia E; Acosta, Manuel J; Sánchez, Antonio; Camacho, Juan Pedro M


    Acquisition of knowledge of the nature and DNA content of B chromosomes has been triggered by a collection of molecular techniques, one of which, microdissection, has provided interesting results in a number of B chromosome systems. Here we provide the first data on the molecular composition of B chromosomes in Locusta migratoria, after microdissection of the B and X chromosomes, DNA amplification by one (B) or two (X) different methods, and chromosome painting. The results showed that B chromosomes share at least two types of repetitive DNA sequences with the A chromosomes, suggesting that Bs in this species most likely arose intraspecifically. One of these repetitive DNAs is located on the heterochromatic distal half of the B chromosome and in the pericentromeric regions of about half of the A chromosomes, including the X. The other type of repetitive DNA is located interspersedly over the non-centromeric euchromatic regions of all A chromosomes and in an interstitial part of the proximal euchromatic half of the B chromosome. Chromosome painting, however, did not provide results sufficiently reliable to determine, in this species, which A chromosome gave rise to the B; this might be done by detailed analysis of the microdissected DNA sequences.

  4. Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes. (United States)

    Kitada, Kunio; Taima, Akira; Ogasawara, Kiyomoto; Metsugi, Shouichi; Aikawa, Satoko


    Analysis of structural rearrangements at the individual chromosomal level is still technologically challenging. Here we optimized a chromosome isolation method using fluorescent marker-assisted laser-capture and laser-beam microdissection and applied it to structural analysis of two aberrant chromosomes found in a lung cancer cell line. A high-density array-comparative genomic hybridization (array-CGH) analysis of DNA samples prepared from each of the chromosomes revealed that these two chromosomes contained 296 and 263 segments, respectively, ranging from 1.5 kb to 784.3 kb in size, derived from different portions of chromosome 8. Among these segments, 242 were common in both aberrant chromosomes, but 75 were found to be chromosome-specific. Sequences of 263 junction sites connecting the ends of segments were determined using a PCR/Sanger-sequencing procedure. Overlapping microhomologies were found at 169 junction sites. Junction partners came from various portions of chromosome 8 and no biased pattern in the positional distribution of junction partners was detected. These structural characteristics suggested the occurrence of random fragmentation of the entire chromosome 8 followed by random rejoining of these fragments. Based on that, we proposed a model to explain how these aberrant chromosomes are formed. Through these structural analyses, it was demonstrated that the optimized chromosome isolation method described here can provide high-quality chromosomal DNA for high resolution array-CGH analysis and probably for massively parallel sequencing analysis.

  5. Quantum effects in beam-plasma instabilities

    CERN Document Server

    Bret, A


    Among the numerous works on quantum effects that have been published in recent years, streaming instabilities in plasma have also been revisited. Both the fluid quantum and the kinetic Wigner-Maxwell models have been used to explore quantum effects on the Weibel, Filamentation and Two-Stream instabilities. While quantum effects usually tend to reduce the instabilities, they can also spur new unstable branches. A number of theoretical results will be reviewed together with the implications to one physical setting, namely the electron driven fast ignition scenario.

  6. Fingering instability in combustion: an extended view. (United States)

    Zik, O; Moses, E


    We detail the experimental situation concerning the fingering instability that occurs when a solid fuel is forced to burn against a horizontal oxidizing wind. The instability appears when the Rayleigh number for convection is below criticality. The focus is on the developed fingering state. We present direct measurements of the depletion of oxygen by the front as well as new results that connect heat losses to the characteristic scale of the instability. In addition, we detail the experimental system, elaborate (qualitatively and quantitatively) on the results that were previously presented, and discuss new observations. We also show that the same phenomenological model applies to electrochemical deposition.

  7. More on core instabilities of magnetic monopoles

    CERN Document Server

    Striet, J


    In this paper we present new results on the core instability of the 't Hooft Polyakov monopoles we reported on before. This instability, where the spherical core decays in a toroidal one, typically occurs in models in which charge conjugation is gauged. In this paper we also discuss a third conceivable configuration denoted as ``split core'', which brings us to some details of the numerical methods we employed. We argue that a core instability of 't Hooft Polyakov type monopoles is quite a generic feature of models with charged Higgs particles.

  8. Building bridges within the bacterial chromosome. (United States)

    Song, Dan; Loparo, Joseph J


    All organisms must dramatically compact their genomes to accommodate DNA within the cell. Bacteria use a set of DNA-binding proteins with low sequence specificity called nucleoid-associated proteins (NAPs) to assist in chromosome condensation and organization. By bending or bridging DNA, NAPs also facilitate chromosome segregation and regulate gene expression. Over the past decade, emerging single-molecule and chromosome conformation capture techniques have investigated the molecular mechanisms by which NAPs remodel and organize the bacterial chromosome. In this review we describe how such approaches reveal the biochemical mechanisms of three NAPs that are believed to facilitate DNA bridging: histone-like nucleoid structuring protein (H-NS), ParB, and structural maintenance of chromosomes (SMC). These three proteins form qualitatively different DNA bridges, leading to varied effects on transcription and chromosome segregation.

  9. Sexual maldevelopment and sex reversal, chromosomal causes. (United States)

    Magenis, R Ellen


    The SRY gene on the Y chromosome is the testis determining factor (TDF). It is therefore the initial male determining factor. However, phenotypic sex determination includes a cascade of genes located on autosomes as well as sex chromosomes. Aberrations of these genes may cause sexual maldevelopment or sex reversal. Abnormalities may include single gene mutations and gene loss or gain-changes may involve only sex organs or may be part of syndromes. These changes may also arise as chromosome abnormalities involving contiguous genes. Eight cases with chromosomal abnormalities involving different causative mechanisms are described herein. The most common cause is nondisjunction, including loss or gain of sex chromosomes. Less common causes are mispairing and crossing over in meiosis, chromosome breaks with repair, nonhomologous pairing due to low copy repeats and crossing over, and translocation (familial or de novo) with segregation. Cases include: [see: text].

  10. Careers in conditions of instability

    Directory of Open Access Journals (Sweden)

    Hohlova Valentina Vasil'evna


    Full Text Available The purpose of this work is the research of the social-economic phenomenon of a career as a result of conscious human position and behaviour in the field of employment, which is connected with job and professional growth, as a chain of events which are components of life, the sequence of professional activities and other biographical roles, which all together express the commitment of a person’s activity according to his generalized model of self-development. On the basis of the theoretical analysis the dependence of making a career in the condition of instability and indefiniteness on job market flexibility, erosion and even the destruction of the usual way of life and labor relations. The career concepts under the conditions of flexible capitalism and of career policy as the typology of empiric differences of job biographic models are considered. The peculiarity of the proposed career policy concept is that its individual alternatives of career making oppose to organization management and personal demands: the difference between a professional’s wishes and a specific strategy of the development phases are quite noticeable. According to the results of empiric research carried out through the methods of interview, polling, expert assessment, the analysis of the received results, the mathematical data processing the basic types of the career policy and its connection with the organization’s personal development are revealed.

  11. Boyle's law and gravitational instability

    CERN Document Server

    Lombardi, M; Lombardi, Marco; Bertin, Giuseppe


    We have re-examined the classical problem of the macroscopic equation of state for a hydrostatic isothermal self-gravitating gas cloud bounded by an external medium at constant pressure. We have obtained analytical conditions for its equilibrium and stability without imposing any specific shape and symmetry to the cloud density distribution. The equilibrium condition can be stated in the form of an upper limit to the cloud mass; this is found to be inversely proportional to the power 3/2 of a form factor \\mu characterizing the shape of the cloud. In this respect, the spherical solution, associated with the maximum value of the form factor, \\mu = 1, turns out to correspond to the shape that is most difficult to realize. Surprisingly, the condition that defines the onset of the Bonnor instability (or gravothermal catastrophe) can be cast in the form of an upper limit to the density contrast within the cloud that is independent of the cloud shape. We have then carried out a similar analysis in the two-dimensiona...

  12. Magnetorotational instability in protoplanetary discs

    CERN Document Server

    Salmeron, Roberto Aureliano; Salmeron, Raquel; Wardle, Mark


    We investigate the linear growth and vertical structure of the magnetorotational instability (MRI) in weakly ionised, stratified accretion discs. The magnetic field is initially vertical and dust grains are assumed to have settled towards the midplane, so charges are carried by electrons and ions only. Solutions are obtained at representative radial locations from the central protostar for different choices of the initial magnetic field strength, sources of ionisation, and disc surface density. The MRI is active over a wide range of magnetic field strengths and fluid conditions in low conductivity discs. For the minimum-mass solar nebula model, incorporating cosmic ray ionisation, perturbations grow at 1 AU for B < 8 G. For a significant subset of these strengths (0.2 - 5 G), the growth rate is of order the ideal MHD rate (0.75 Omega). Similarly, when cosmic rays are assumed to be excluded from the disc by the winds emitted by the magnetically active protostar, unstable modes grow at this radius for B less...

  13. The azimuthal magnetorotational instability (AMRI)

    CERN Document Server

    Ruediger, G; Schultz, M; Hollerbach, R; Stefani, F


    We consider the interaction of differential rotation and toroidal fields that are current-free in the gap between two corotating axially unbounded cylinders. It is shown that nonaxisymmetric perturbations are unstable if the rotation rate and Alfven frequency of the field are of the same order almost independent of the magnetic Prandtl number Pm. For the very steep rotation law \\Omega\\propto R^{-2} (the Rayleigh limit) this Azimuthal MagnetoRotational Instability (AMRI) scales with the ordinary Reynolds number and the Hartmann number, which allows a laboratory experiment with liquid metals like sodium or gallium in a Taylor-Couette container. The growth rate of AMRI scales with \\Omega^2 in the low-conductivity limit and with \\Omega in the high-conductivity limit. For the weakly nonlinear system the numerical values of the kinetic energy and the magnetic energy are derived for magnetic Prandtl numbers between 0.05 and unity. We find that the magnetic energy scales with the magnetic Reynolds number Rm, while th...

  14. Thermal instability of cell nuclei (United States)

    Warmt, Enrico; Kießling, Tobias R.; Stange, Roland; Fritsch, Anatol W.; Zink, Mareike; Käs, Josef A.


    DNA is known to be a mechanically and thermally stable structure. In its double stranded form it is densely packed within the cell nucleus and is thermo-resistant up to 70\\:^\\circ {\\rm{C}}. In contrast, we found a sudden loss of cell nuclei integrity at relatively moderate temperatures ranging from 45 to 55\\:^\\circ {\\rm{C}}. In our study, suspended cells held in an optical double beam trap were heated under controlled conditions while monitoring the nuclear shape. At specific critical temperatures, an irreversible sudden shape transition of the nuclei was observed. These temperature induced transitions differ in abundance and intensity for various normal and cancerous epithelial breast cells, which clearly characterizes different cell types. Our results show that temperatures slightly higher than physiological conditions are able to induce instabilities of nuclear structures, eventually leading to cell death. This is a surprising finding since recent thermorheological cell studies have shown that cells have a lower viscosity and are thus more deformable upon temperature increase. Since the nucleus is tightly coupled to the outer cell shape via the cytoskeleton, the force propagation of nuclear reshaping to the cell membrane was investigated in combination with the application of cytoskeletal drugs.

  15. Transient spirals as superposed instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Sellwood, J. A. [Department of Physics and Astronomy, Rutgers University, 136 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Carlberg, R. G., E-mail:, E-mail: [Department of Astronomy and Astrophysics, University of Toronto, Toronto, ON M5S 3H4 (Canada)


    We present evidence that recurrent spiral activity, long manifested in simulations of disk galaxies, results from the superposition of a few transient spiral modes. Each mode lasts between 5 and 10 rotations at its corotation radius where its amplitude is greatest. The scattering of stars as each wave decays takes place over narrow ranges of angular momentum, causing abrupt changes to the impedance of the disk to subsequent traveling waves. Partial reflections of waves at these newly created features allows new standing-wave instabilities to appear that saturate and decay in their turn, scattering particles at new locations, creating a recurring cycle. The spiral activity causes the general level of random motion to rise, gradually decreasing the ability of the disk to support further activity unless the disk contains a dissipative gas component from which stars form on near-circular orbits. We also show that this interpretation is consistent with the behavior reported in other recent simulations with low-mass disks.

  16. Pulsational-Pair Instability Supernovae

    CERN Document Server

    Woosley, S E


    The final evolution of stars in the mass range 60 - 150 solar masses is explored. Depending upon their mass loss and rotation rates, many of these stars will end their lives as pulsational pair-instability supernovae. Even a non-rotating 70 solar mass star is pulsationally unstable during oxygen shell burning and can power a sub-luminous supernova. Rotation decreases the limit further. For more massive stars, the pulsations are less frequent, span a longer time, and are more powerful. Violent pulsations eject not only any residual low density envelope, but also that fraction of the helium core mass outside about 35 - 50 solar masses. The remaining core of helium and heavy elements continues to evolve, ultimately forming an iron core of about 2.5 solar masses that probably collapses to a black hole. A variety of observational transients result with total durations ranging from days to 10,000 years, and luminosities from 10$^{41}$ to 10$^{44}$ erg s$^{-1}$. Many transients resemble ordinary Type IIp supernovae,...

  17. Taylor Instability of Incompressible Liquids (United States)

    Fermi, E.; von Neumann, J.


    A discussion is presented in simplified form of the problem of the growth of an initial ripple on the surface of an incompressible liquid in the presence of an acceleration, g, directed from the outside into the liquid. The model is that of a heavy liquid occupying at t = 0 the half space above the plane z = 0, and a rectangular wave profile is assumed. The theory is found to represent correctly one feature of experimental results, namely the fact that the half wave of the heavy liquid into the vacuum becomes rapidly narrower while the half wave pushing into the heavy liquid becomes more and more blunt. The theory fails to account for the experimental results according to which the front of the wave pushing into the heavy liquid moves with constant velocity. The case of instability at the boundary of 2 fluids of different densities is also explored. Similar results are obtained except that the acceleration of the heavy liquid into the light liquid is reduced.

  18. Chromosomal rearrangements in Tourette syndrome

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Debes, Nanette Mol; Hjermind, Lena E


    Tourette syndrome (TS) is a childhood-onset complex neurobiological disorder characterized by a combination of persistent motor and vocal tics and frequent presence of other neuropsychiatric comorbidities. TS shares the fate of other complex disorders, where the genetic etiology is largely unknown......, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has...

  19. Meiosis I: When Chromosomes Undergo Extreme Makeover


    Miller, Matthew P; Amon, Angelika; Ünal, Elçin


    The ultimate success of cell division relies on the accurate partitioning of the genetic material. Errors in this process occur in nearly all tumors and are the leading cause of miscarriages and congenital birth defects in humans. Two cell divisions, mitosis and meiosis, use common as well as unique mechanisms to ensure faithful chromosome segregation. In mitosis, alternating rounds of DNA replication and chromosome segregation preserves the chromosome complement of the progenitor cell. In co...

  20. Movement of chromosomes with severed kinetochore microtubules. (United States)

    Forer, Arthur; Johansen, Kristen M; Johansen, Jørgen


    Experiments dating from 1966 and thereafter showed that anaphase chromosomes continued to move poleward after their kinetochore microtubules were severed by ultraviolet microbeam irradiation. These observations were initially met with scepticism as they contradicted the prevailing view that kinetochore fibre microtubules pulled chromosomes to the pole. However, recent experiments using visible light laser microbeam irradiations have corroborated these earlier experiments as anaphase chromosomes again were shown to move poleward after their kinetochore microtubules were severed. Thus, multiple independent studies using different techniques have shown that chromosomes can indeed move poleward without direct microtubule connections to the pole, with only a kinetochore 'stub' of microtubules. An issue not yet settled is: what propels the disconnected chromosome? There are two not necessarily mutually exclusive proposals in the literature: (1) chromosome movement is propelled by the kinetochore stub interacting with non-kinetochore microtubules and (2) chromosome movement is propelled by a spindle matrix acting on the stub. In this review, we summarise the data indicating that chromosomes can move with severed kinetochore microtubules and we discuss proposed mechanisms for chromosome movement with severed kinetochore microtubules.

  1. Genome architecture: domain organization of interphase chromosomes. (United States)

    Bickmore, Wendy A; van Steensel, Bas


    The architecture of interphase chromosomes is important for the regulation of gene expression and genome maintenance. Chromosomes are linearly segmented into hundreds of domains with different protein compositions. Furthermore, the spatial organization of chromosomes is nonrandom and is characterized by many local and long-range contacts among genes and other sequence elements. A variety of genome-wide mapping techniques have made it possible to chart these properties at high resolution. Combined with microscopy and computational modeling, the results begin to yield a more coherent picture that integrates linear and three-dimensional (3D) views of chromosome organization in relation to gene regulation and other nuclear functions.

  2. Cognitive and medical features of chromosomal aneuploidy. (United States)

    Hutaff-Lee, Christa; Cordeiro, Lisa; Tartaglia, Nicole


    This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed.

  3. Research on automatic human chromosome image analysis (United States)

    Ming, Delie; Tian, Jinwen; Liu, Jian


    Human chromosome karyotyping is one of the essential tasks in cytogenetics, especially in genetic syndrome diagnoses. In this thesis, an automatic procedure is introduced for human chromosome image analysis. According to different status of touching and overlapping chromosomes, several segmentation methods are proposed to achieve the best results. Medial axis is extracted by the middle point algorithm. Chromosome band is enhanced by the algorithm based on multiscale B-spline wavelets, extracted by average gray profile, gradient profile and shape profile, and calculated by the WDD (Weighted Density Distribution) descriptors. The multilayer classifier is used in classification. Experiment results demonstrate that the algorithms perform well.

  4. Meiotic chromosome abnormalities in human spermatogenesis. (United States)

    Martin, Renée H


    The last few years have witnessed an explosion in the information about chromosome abnormalities in human sperm and the meiotic events that predispose to these abnormalities. We have determined that all chromosomes are susceptible to nondisjunction, but chromosomes 21 and 22 and, especially, the sex chromosomes have an increased frequency of aneuploidy. Studies are just beginning on the effects of potential mutagens on the chromosomal constitution of human sperm. The effects of pesticides and cancer therapeutic agents have been reviewed. In the last decade, there has been a great impetus to study chromosome abnormalities in sperm from infertile men because the advent of intracytoplasmic sperm injection (ICSI) made it possible for these men to father pregnancies. A large number of studies have demonstrated that infertile men have an increased frequency of chromosomally abnormal sperm and children, even when they have a normal somatic karyotype. Meiotic studies on the pachytene stage of spermatogenesis have demonstrated that infertile men have impaired chromosome synapsis, a significantly decreased frequency of recombination, and an increased frequency of chromosomes completely lacking a recombination site. Such errors make these cells susceptible to meiotic arrest and the production of aneuploid gametes.

  5. The DNA-instability test as a specific marker of malignancy and its application to detect cancer clones in borderline malignancy

    Directory of Open Access Journals (Sweden)

    M Fukuda


    Full Text Available Recent progress in cytogenetic and biochemical mutator assay technologies has enabled us to detect single gene alterations and gross chromosomal rearrangements, and it became clear that all cancer cells are genetically unstable. In order to detect the genome-wide instability of cancer cells, a new simple method, the DNA-instability test, was developed. The methods to detect genomic instability so far reported have only demonstrated the presence of qualitative and quantitative alterations in certain specific genomic loci. In contrast to these commonly used methods to reveal the genomic instability at certain specific DNA regions, the newly introduced DNA-instability test revealed the presence of physical DNA-instability in the entire DNA molecule of a cancer cell nucleus as revealed by increased liability to denature upon HCl hydrolysis or formamide exposure. When this test was applied to borderline malignancies, cancer clones were detected in all cases at an early-stage of cancer progression. We proposed a new concept of “procancer” clones to define those cancer clones with “functional atypia” showing positivities for various cancer markers, as well as DNA-instability testing, but showing no remarkable ordinary “morphological atypia” which is commonly used as the basis of histopathological diagnosis of malignancy.

  6. Biophysical modelling of early and delayed radiation damage at chromosome level (United States)

    Andreev, S.; Eidelman, Y.

    Exposure by ionising radiation increases cancer risk in human population Cancer is thought to originate from an altered expression of certain number of specific genes It is now widely recognised that chromosome aberrations CA are involved in stable change in expression of genes by gain or loss of their functions Thus CA can contribute to initiation or progression of cancer Therefore understanding mechanisms of CA formation in the course of cancer development might be valuable tool for quantification and prognosis of different stages of radiation carcinogenesis Early CA are defined as aberrations induced in first post-irradiation mitotic cycle The present work describes the original biophysical technique for early CA modelling It includes the following simulation steps the ionising particle track structure the structural organisation of all chromosomes in G 0 G 1 cell nucleus spatial distribution of radiation induced DNA double-strand breaks dsb within chromosomes dsb rejoining and misrejoining modelling cell cycle taking into account mitotic delay which results in complex time dependence of aberrant cells in first mitosis The results on prediction of dose-response curves for simple and complex CA measured in cells undergoing first division cycle are presented in comparison with recent experimental data There is increasing evidence that CA are also observed in descendents of irradiated cells many generations after direct DNA damage These delayed CA or chromosome instability CI are thought to be a manifestation of genome

  7. Nuclear actin-related protein is required for chromosome segregation in Toxoplasma gondii. (United States)

    Suvorova, Elena S; Lehmann, Margaret M; Kratzer, Stella; White, Michael W


    Apicomplexa parasites use complex cell cycles to replicate that are not well understood mechanistically. We have established a robust forward genetic strategy to identify the essential components of parasite cell division. Here we describe a novel temperature sensitive Toxoplasma strain, mutant 13-20C2, which growth arrests due to a defect in mitosis. The primary phenotype is the mis-segregation of duplicated chromosomes with chromosome loss during nuclear division. This defect is conditional-lethal with respect to temperature, although relatively mild in regard to the preservation of the major microtubule organizing centers. Despite severe DNA loss many of the physical structures associated with daughter budding and the assembly of invasion structures formed and operated normally at the non-permissive temperature before completely arresting. These results suggest there are coordinating mechanisms that govern the timing of these events in the parasite cell cycle. The defect in mutant 13-20C2 was mapped by genetic complementation to Toxoplasma chromosome III and to a specific mutation in the gene encoding an ortholog of nuclear actin-related protein 4. A change in a conserved isoleucine to threonine in the helical structure of this nuclear actin related protein leads to protein instability and cellular mis-localization at the higher temperature. Given the age of this protist family, the results indicate a key role for nuclear actin-related proteins in chromosome segregation was established very early in the evolution of eukaryotes.

  8. Chromosomal polymorphism in two species of Hypancistrus (Siluriformes: Loricariidae): an integrative approach for understanding their biodiversity. (United States)

    da Silva, Maelin; Ribeiro, Emanuell D; Matoso, Daniele A; Sousa, Leandro M; Hrbek, Tomas; Py-Daniel, Lucia Rapp; Feldberg, Eliana


    Structural chromosome changes are widely described in different vertebrate groups and generate genetic, phenotypic and behavioral diversity. During the evolution of loricariids, several rearrangements (fissions, fusions, inversions) seem to have occurred. Hypancistrus, tribe Ancistrini, are highly demanded for fishkeeping around the world. In this tribe, the diploid chromosome number 2n = 52 is considered a synapomorphy, and paracentric-type inversions appear to be involved in the chromosomal evolution of the tribe. The present study investigated the karyotypes of H. zebra and H. cf. debilittera using cytogenetic, classical and molecular tools, as well as DNA barcoding. Data reveal that, although diploid number in both species corroborates the proposed synapomorphy for the tribe, there is a complex karyotype dynamics, reflected in the intense chromosomal polymorphism, resulting from rearrangements involving ribosomal regions (5S and 18S rDNA), which are suggested to be paracentric inversions. Besides, DNA barcode confirms reciprocal monophyletism between the species, validating the existence of two species, only. This scenario, coupled with genomic instability caused by exogenous sequences such as Rex-3 retrotransposons and the species' sedentary lifestyle, which helps the fast polymorphism fixation, may reflect different phenotypic color patterns in natural populations, as observed in H. cf. debilittera.

  9. Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies (United States)

    Lombardi, Sara; Fuoco, Ilenia; di Fluri, Giorgia; Costa, Francesco; Ricchiuti, Angelo; Biondi, Graziano; Nardini, Vincenzo; Scarpato, Roberto


    Inflammatory bowel disease (IBD) and polyps, are common colorectal pathologies in western society and are risk factors for development of colorectal cancer (CRC). Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy. Cellular stress, may contribute to genomic instability. In colorectal biopsies and peripheral blood lymphocytes of patients with IBD, polyps and CRC, we evaluated 1) genomic instability using the γH2AX assay as marker of DSB and micronuclei in mononuclear lymphocytes kept under cytodieresis inhibition, and 2) cellular stress through expression and cellular localization of glutathione-S-transferase omega 1 (GSTO1). Colon biopsies showed γH2AX increase starting from polyps, while lymphocytes already from IBD. Micronuclei frequency began to rise in lymphocytes of subjects with polyps, suggesting a systemic genomic instability condition. Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression. Lymphocytes did not change GSTO1 expression and localization until CRC formation, where enzyme expression was increased. We propose that the growing genomic instability found in our patients is connected with the alteration of cellular environment. Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC. PMID:26046795

  10. Nonlinear electrostatic drift Kelvin-Helmholtz instability (United States)

    Sharma, Avadhesh C.; Srivastava, Krishna M.


    Nonlinear analysis of electrostatic drift Kelvin-Helmholtz instability is performed. It is shown that the analysis leads to the propagation of the weakly nonlinear dispersive waves, and the nonlinear behavior is governed by the nonlinear Burger's equation.

  11. Can dust coagulation trigger streaming instability?

    CERN Document Server

    Drazkowska, Joanna


    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...

  12. Electrocapillary instability of magnetic fluid peak

    CERN Document Server

    Mkrtchyan, Levon; Dikansky, Yuri


    The paper presents an experimental study of the capillary electrostatic instability occurring under effect of a constant electric field on a magnetic fluid individual peak. The peaks under study occur at disintegration of a magnetic fluid layer applied on a flat electrode surface under effect of a perpendicular magnetic field. The electrocapillary instability shows itself as an emission of charged drops jets from the peak point in direction of the opposing electrode. The charged drops emission repeats periodically and results in the peak shape pulsations. It is shown that a magnetic field affects the electrocapillary instability occurrence regularities and can stimulate its development. The critical electric and magnetic field strengths at which the instability occurs have been measured; their dependence on the peak size is shown. The hysteresis in the system has been studied; it consists in that the charged drops emission stops at a lesser electric (or magnetic) field strength than that of the initial occurr...

  13. Interfacial fluid instabilities and Kapitsa pendula

    CERN Document Server

    Krieger, Madison Ski


    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...

  14. Fluid description for the resonant Weibel instability

    CERN Document Server

    Sarrat, M; Ghizzo, A


    We discuss a fluid model with inclusion of the complete pressure tensor dynamics for the description of Weibel type instabilities in a counterstreaming beams configuration. Differently from the case recently studied in Sarrat et al. 2016, where perturbations perpendicular to the beams were considered, here we focus only on modes propagating along the beams. Such a configuration is responsible for the growth of two kind of instabilities, the Two-Stream Instability and the Weibel instability, which in this geometry becomes "time-resonant", i.e. propagative. This fluid description agrees with the kinetic one and makes it possible e.g. to identify the transition between non-propagative and propagative Weibel modes, already evidenced by Lazar et al. 2009 as a "slope-breaking" of the growth rate, in terms of a merger of two non propagative Weibel modes.

  15. Experimental Replication of an Aeroengine Combustion Instability (United States)

    Cohen, J. M.; Hibshman, J. R.; Proscia, W.; Rosfjord, T. J.; Wake, B. E.; McVey, J. B.; Lovett, J.; Ondas, M.; DeLaat, J.; Breisacher, K.


    Combustion instabilities in gas turbine engines are most frequently encountered during the late phases of engine development, at which point they are difficult and expensive to fix. The ability to replicate an engine-traceable combustion instability in a laboratory-scale experiment offers the opportunity to economically diagnose the problem (to determine the root cause), and to investigate solutions to the problem, such as active control. The development and validation of active combustion instability control requires that the causal dynamic processes be reproduced in experimental test facilities which can be used as a test bed for control system evaluation. This paper discusses the process through which a laboratory-scale experiment was designed to replicate an instability observed in a developmental engine. The scaling process used physically-based analyses to preserve the relevant geometric, acoustic and thermo-fluid features. The process increases the probability that results achieved in the single-nozzle experiment will be scalable to the engine.

  16. The Growth Effects of Institutional Instability

    DEFF Research Database (Denmark)

    Berggren, Niclas; Bergh, Andreas; Bjørnskov, Christian

    the growth effects of institutional quality and instability, using the political risk index from the ICRG in a cross-country study of 132 countries, measuring instability as the coefficient of variation. Using the aggregate index, we find evidence that institutional quality is positively linked to growth...... Both institutional quality and institutional stability have been argued to stimulate economic growth. But to improve institutional quality, a country must endure a period of institutional change, which implies at least a little and possibly a lot of institutional instability. We investigate....... While institutional instability is negatively related to growth in the baseline case, there are indications that the effect can be positive in rich countries, suggesting that institutional reform is not necessarily costly even during a transition period. Sensitivity analysis, e.g., decomposing...

  17. Elliptical instability in terrestrial planets and moons

    CERN Document Server

    Cébron, David; Moutou, Claire; Gal, Patrice Le; 10.1051/0004-6361/201117741


    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 ...

  18. Zonostrophic instability driven by discrete particle noise

    CERN Document Server

    St-Onge, D A


    The consequences of discrete particle noise for a system possessing a possibly unstable collective mode are discussed. It is argued that a zonostrophic instability (of homogeneous turbulence to the formation of zonal flows) occurs just below the threshold for linear instability. The scenario provides a new interpretation of the random forcing that is ubiquitously invoked in stochastic models such as the second-order cumulant expansion (CE2) or stochastic structural instability theory (SSST); neither intrinsic turbulence nor coupling to extrinsic turbulence is required. A representative calculation of the zonostrophic neutral curve is made for a simple two-field model of toroidal ion-temperature-gradient-driven modes. To the extent that the damping of zonal flows is controlled by the ion--ion collision rate, the point of zonostrophic instability is independent of that rate.

  19. Magnetorotational Explosive Instability in Keplerian Disks

    CERN Document Server

    Shtemler, Yuri; Mond, Michael


    In this paper it is shown that deferentially rotating disks that are in the presence of weak axial magnetic field are prone to a new nonlinear explosive instability. The latter occurs due to the near-resonance three-wave interactions of a magnetorotational instability with stable Alfven-Coriolis and magnetosonic modes. The dynamical equations that govern the temporal evolution of the amplitudes of the three interacting modes are derived. Numerical solutions of the dynamical equations indicate that small frequency mismatch gives rise to two types of behavior: 1. explosive instability which leads to infinite values of the three amplitudes within a finite time, and 2. bounded irregular oscillations of all three amplitudes. Asymptotic solutions of the dynamical equations are obtained for the explosive instability regimes and are shown to match the numerical solutions near the explosion time.

  20. Shear instabilities in shallow-water magnetohydrodynamics

    CERN Document Server

    Mak, Julian; Hughes, D W


    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 ...

  1. Overview of Rayleigh-Taylor instability

    Energy Technology Data Exchange (ETDEWEB)

    Sharp, D.H.


    The aim of this talk is to survey Rayleigh-Taylor instability, describing the phenomenology that occurs at a Taylor unstable interface, and reviewing attempts to understand these phenomena quantitatively.

  2. Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

    Directory of Open Access Journals (Sweden)

    Eilers Paul HC


    Full Text Available Abstract Background Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes. Methods We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry. Results Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF. The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss. Conclusion On basis of integrative analysis this study identified one well known CRC gene (SMAD2 and several other genes (EFNA1, BOP1, TGIF2 and STMN3 that possibly could be used for rectal cancer characterization.

  3. Increased chromosome radiosensitivity during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard [Commissariat a l`Energie Atomique, Laboratoire de Radiobiologie et Oncologie, DRR, DSV, Fontenay aux roses (France)


    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions.

  4. The Philadelphia chromosome in leukemogenesis

    Institute of Scientific and Technical Information of China (English)

    ZhiJieKang; JinSongYan; QuentinLiu; YuFeiLiu; LingZhiXu; ZiJieLong; DanHuang; YaYang; BingLiu; JiuXingFeng; YuJiaPan


    The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Phila‑delphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region‑proto‑oncogene tyrosine‑protein kinase (BCR‑ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentia‑tion, and conferring resistance to cell death. During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase, the expression patterns of different BCR‑ABL1 transcripts vary. Each BCR‑ABL1 transcript is present in a distinct leukemia phenotype, which predicts both response to therapy and clinical outcome. Besides CML, the Ph is found in acute lymphoblastic leukemia, acute myeloid leukemia, and mixed‑phenotype acute leukemia. Here, we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph‑positive leukemia and highlight key ifndings regarding leukemogenesis.

  5. Chromosomal replicons of higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Van' t Hof, J.


    This brief discussion of replicons of higher plants offers a glimpse into the properties of chromosomal DNA replication. It gives evidence that the S phase of unrelated plant species is comprised of temporally ordered replicon families that increase in number with genome size. This orderly process, which assures a normal inheritance of genetic material to recipient daughter cells, is maintained at the level of replicon clusters by two mutually exclusive mechanisms, one involving the rate at which single replicons replicate their allotment of DNA, and another by means of the tempo-pause. The same two mechanisms are used by cells to alter the pattern of chromosomal DNA replication just prior to and during normal development. Both mechanisms are genetically determined and produce genetic effects when disturbed of disrupted by additional non-conforming DNAs. Further insight into how these two mechanisms operate requires more molecular information about the nature of replicons and the factors that govern when a replicon family replicates. Plant material is a rich and ideal source for this information just awaiting exploitation. 63 refs.

  6. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen


    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  7. DNA double-strand breaks coupled with PARP1 and HNRNPA2B1 binding sites flank coordinately expressed domains in human chromosomes.

    Directory of Open Access Journals (Sweden)

    Nickolai A Tchurikov


    Full Text Available Genome instability plays a key role in multiple biological processes and diseases, including cancer. Genome-wide mapping of DNA double-strand breaks (DSBs is important for understanding both chromosomal architecture and specific chromosomal regions at DSBs. We developed a method for precise genome-wide mapping of blunt-ended DSBs in human chromosomes, and observed non-random fragmentation and DSB hot spots. These hot spots are scattered along chromosomes and delimit protected 50-250 kb DNA domains. We found that about 30% of the domains (denoted forum domains possess coordinately expressed genes and that PARP1 and HNRNPA2B1 specifically bind DNA sequences at the forum domain termini. Thus, our data suggest a novel type of gene regulation: a coordinated transcription or silencing of gene clusters delimited by DSB hot spots as well as PARP1 and HNRNPa2B1 binding sites.

  8. Radiation induced genome instability: multiscale modelling and data analysis (United States)

    Andreev, Sergey; Eidelman, Yuri


    Genome instability (GI) is thought to be an important step in cancer induction and progression. Radiation induced GI is usually defined as genome alterations in the progeny of irradiated cells. The aim of this report is to demonstrate an opportunity for integrative analysis of radiation induced GI on the basis of multiscale modelling. Integrative, systems level modelling is necessary to assess different pathways resulting in GI in which a variety of genetic and epigenetic processes are involved. The multilevel modelling includes the Monte Carlo based simulation of several key processes involved in GI: DNA double strand breaks (DSBs) generation in cells initially irradiated as well as in descendants of irradiated cells, damage transmission through mitosis. Taking the cell-cycle-dependent generation of DNA/chromosome breakage into account ensures an advantage in estimating the contribution of different DNA damage response pathways to GI, as to nonhomologous vs homologous recombination repair mechanisms, the role of DSBs at telomeres or interstitial chromosomal sites, etc. The preliminary estimates show that both telomeric and non-telomeric DSB interactions are involved in delayed effects of radiation although differentially for different cell types. The computational experiments provide the data on the wide spectrum of GI endpoints (dicentrics, micronuclei, nonclonal translocations, chromatid exchanges, chromosome fragments) similar to those obtained experimentally for various cell lines under various experimental conditions. The modelling based analysis of experimental data demonstrates that radiation induced GI may be viewed as processes of delayed DSB induction/interaction/transmission being a key for quantification of GI. On the other hand, this conclusion is not sufficient to understand GI as a whole because factors of DNA non-damaging origin can also induce GI. Additionally, new data on induced pluripotent stem cells reveal that GI is acquired in normal mature


    Directory of Open Access Journals (Sweden)

    Traian MAZILU


    Full Text Available The railway vehicles have two sources of instability. The most common is the hunting induced by the reversed conic shape of the rolling surfaces of the wheels. The other one is related by the anomalous Doppler effect that can occurs when the train velocity exceeds the phase velocity of the waves induced in the track structure. Some aspects regarding the two sources of instability are presented.

  10. Systematics of shoulder instability; Systematik der Schulterinstabilitaet

    Energy Technology Data Exchange (ETDEWEB)

    Kreitner, K.F.; Maehringer-Kunz, A. [Johannes-Gutenberg-Universitaet Mainz, Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Mainz (Germany)


    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.) [German] Unter einer Schulterinstabilitaet versteht man jede zu Beschwerden fuehrende Translation des Humeruskopfs in Relation zur Gelenkpfanne waehrend einer aktiven Bewegung der Schulter. Glenohumerale Instabilitaeten werden heute nach ihrer Aetiologie eingeteilt, da bei der Wahl der Therapie der Entstehungsmechanismus der Instabilitaet eine wichtige Rolle spielt. Danach unterscheidet man primaer traumatisch von atraumatisch entstandenen Instabilitaeten sowie Mikroinstabilitaeten. Bei der Diagnostik dienen konventionelle Roentgenuebersichtsaufnahmen nur noch zur Dokumentation einer Luxation und zur Beurteilung der Reposition. Die durch eine Instabilitaet hervorgerufenen Verletzungsfolgen am labroligamentaeren Komplex und den knoechernen Strukturen werden heute bevorzugt mit der direkten MR-Arthrographie dargestellt. Hierbei koennen unterschiedliche Verletzungsmuster dargestellt werden. Nach

  11. Resonant Triad Instability in Stratified Fluids

    CERN Document Server

    Joubaud, Sylvain; Odier, Philippe; Dauxois, Thierry


    Internal gravity waves contribute to fluid mixing and energy transport, not only in oceans but also in the atmosphere and in astrophysical bodies. We provide here the first experimental measurement of the growth rate of a resonant triad instability (also called parametric subharmonic instability) transferring energy to smaller scales where it is dissipated. We make careful and quantitative comparisons with theoretical predictions for propagating vertical modes in laboratory experiments.

  12. Weibel instability in relativistic quantum plasmas (United States)

    Mendonça, J. T.; Brodin, G.


    Generation of quasi-static magnetic fields, due to the Weibel instability is studied in a relativistic quantum plasma. This instability is induced by a temperature anisotropy. The dispersion relation and growth rates for low frequency electromagnetic perturbations are derived using a wave-kinetic equation which describes the evolution of the electron Wigner quasi-distribution. The influence of parallel kinetic effects is discussed in detail.

  13. A hydrodynamic approach to QGP instabilities

    CERN Document Server

    Calzetta, E


    We show that the usual linear analysis of QGP Weibel instabilities based on the Maxwell-Boltzmann equation may be reproduced in a purely hydrodynamic model. The latter is derived by the Entropy Production Variational Method from a transport equation including collisions, and can describe highly nonequilibrium flow. We find that, as expected, collisions slow down the growth of Weibel instabilities. Finally, we discuss the strong momentum anisotropy limit.

  14. Jeans instability in the linearized Burnett regime

    CERN Document Server

    García-Colin, L S


    Jeans instability is derived for the case of a low density self-gravitating gas beyond the Navier-Stokes equations. The Jeans instability criterium is shown to depend on a Burnett coefficient if the formalism is taken up to fourth order in the wave number. It is also shown that previously known viscosity corrections to the Jeans wave-number are enhanced if the full fourth order formalism is applied to the stability analysis.

  15. Energetic particle instabilities in fusion plasmas

    CERN Document Server

    Sharapov, S E; Berk, H L; Borba, D N; Breizman, B N; Challis, C D; Classen, I G J; Edlund, E M; Eriksson, J; Fasoli, A; Fredrickson, E D; Fu, G Y; Garcia-Munoz, M; Gassner, T; Ghantous, K; Goloborodko, V; Gorelenkov, N N; Gryaznevich, M P; Hacquin, S; Heidbrink, W W; Hellesen, C; Kiptily, V G; Kramer, G J; Lauber, P; Lilley, M K; Lisak, M; Nabais, F; Nazikian, R; Nyqvist, R; Osakabe, M; von Thun, C Perez; Pinches, S D; Podesta, M; Porkolab, M; Shinohara, K; Schoepf, K; Todo, Y; Toi, K; Van Zeeland, M A; Voitsekhovich, I; White, R B; Yavorskij, V; TG, ITPA EP; Contributors, JET-EFDA


    Remarkable progress has been made in diagnosing energetic particle instabilities on present-day machines and in establishing a theoretical framework for describing them. This overview describes the much improved diagnostics of Alfven instabilities and modelling tools developed world-wide, and discusses progress in interpreting the observed phenomena. A multi-machine comparison is presented giving information on the performance of both diagnostics and modelling tools for different plasma conditions outlining expectations for ITER based on our present knowledge.

  16. Summary of impedance issues and beam instabilities

    CERN Document Server

    Zimmermann, Frank


    This paper summarizes the session on impedance issues and beam instabilities at the ICFA workshop on future circular electron-positron factories “eeFACT2016” [1] held at the Cockcroft Institute, Daresbury, from 24 to 27 October 2016. This session also covered active beam stabilization by feedback systems. Beam-beam effects and coherent beambeam instabilities were addressed separately and, therefore, are not included here.

  17. Plasma wave instabilities in nonequilibrium graphene

    DEFF Research Database (Denmark)

    Aryal, Chinta M.; Hu, Ben Yu-Kuang; Jauho, Antti-Pekka


    We study two-stream instabilities in a nonequilibrium system in which a stream of electrons is injected into doped graphene. As with equivalent nonequilibrium parabolic band systems, we find that the graphene systems can support unstable charge-density waves whose amplitudes grow with time. We...... of the injected electrons that maximizes the growth rate increases with increasing | q |. We compare the range and strength of the instability in graphene to that of two- and three-dimensional parabolic band systems....

  18. Conservation of chromosomes syntenic with avian autosomes in squamate reptiles revealed by comparative chromosome painting. (United States)

    Pokorná, Martina; Giovannotti, Massimo; Kratochvíl, Lukáš; Caputo, Vincenzo; Olmo, Ettore; Ferguson-Smith, Malcolm A; Rens, Willem


    In contrast to mammals, birds exhibit a slow rate of chromosomal evolution. It is not clear whether high chromosome conservation is an evolutionary novelty of birds or was inherited from an earlier avian ancestor. The evolutionary conservatism of macrochromosomes between birds and turtles supports the latter possibility; however, the rate of chromosomal evolution is largely unknown in other sauropsids. In squamates, we previously reported strong conservatism of the chromosomes syntenic with the avian Z, which could reflect a peculiarity of this part of the genome. The chromosome 1 of iguanians and snakes is largely syntenic with chromosomes 3, 5 and 7 of the avian ancestral karyotype. In this project, we used comparative chromosome painting to determine how widely this synteny is conserved across nine families covering most of the main lineages of Squamata. The results suggest that the association of the avian ancestral chromosomes 3, 5 and 7 can be dated back to at least the early Jurassic and could be an ancestral characteristic for Unidentata (Serpentes, Iguania, Anguimorpha, Laterata and Scinciformata). In Squamata chromosome conservatism therefore also holds for the parts of the genome which are homologous to bird autosomes, and following on from this, a slow rate of chromosomal evolution could be a common characteristic of all sauropsids. The large evolutionary stasis in chromosome organization in birds therefore seems to be inherited from their ancestors, and it is particularly striking in comparison with mammals, probably the only major tetrapod lineage with an increased rate of chromosomal rearrangements as a whole.

  19. Spinal instability in ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Badve Siddharth


    Full Text Available Background: Unstable spinal lesions in patients with ankylosing spondylitis are common and have a high incidence of associated neurological deficit. The evolution and presentation of these lesions is unclear and the management strategies can be confusing. We present retrospective analysis of the cases of ankylosing spondylitis developing spinal instability either due to spondylodiscitis or fractures for mechanisms of injury, presentations, management strategies and outcome. Materials and Methods: In a retrospective analysis of 16 cases of ankylosing spondylitis, treated surgically for unstable spinal lesions over a period of 12 years (1995-2007; 87.5% (n=14 patients had low energy (no obvious/trivial trauma while 12.5% (n=2 patients sustained high energy trauma. The most common presentation was pain associated with neurological deficit. The surgical indications included neurological deficit, chronic pain due to instability and progressive deformity. All patients were treated surgically with anterior surgery in 18.8% (n=3 patients, posterior in 56.2% (n=9 patients and combined approach in 25% (n=4 patients. Instrumented fusion was carried out in 87.5% (n=14 patients. Average surgical duration was 3.84 (Range 2-7.5 hours, blood loss 765.6 (± 472.5 ml and follow-up 54.5 (Range 18-54 months. The patients were evaluated for pain score, Frankel neurological grading, deformity progression and radiological fusion. One patient died of medical complications a week following surgery. Results: Intra-operative adverse events like dural tears and inadequate deformity correction occurred in 18.7% (n=3 patients (Cases 6, 7 and 8 which could be managed conservatively. There was a significant improvement in the Visual analogue score for pain from a pre-surgical median of 8 to post-surgical median of 2 (P=0.001, while the neurological status improved in 90% (n=9 patients among those with preoperative neurological deficit who could be followed-up (n =10. Frankel

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

    Directory of Open Access Journals (Sweden)

    Soumini Vasan


    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.