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Sample records for affects chromosome stability

  1. Chromosome analysis of arsenic affected cattle

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    S. Shekhar

    2014-10-01

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

  2. Evolutionary stability of sex chromosomes in snakes.

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    Rovatsos, Michail; Vukić, Jasna; Lymberakis, Petros; Kratochvíl, Lukáš

    2015-12-22

    Amniote vertebrates possess various mechanisms of sex determination, but their variability is not equally distributed. The large evolutionary stability of sex chromosomes in viviparous mammals and birds was believed to be connected with their endothermy. However, some ectotherm lineages seem to be comparably conserved in sex determination, but previously there was a lack of molecular evidence to confirm this. Here, we document a stability of sex chromosomes in advanced snakes based on the testing of Z-specificity of genes using quantitative PCR (qPCR) across 37 snake species (our qPCR technique is suitable for molecular sexing in potentially all advanced snakes). We discovered that at least part of sex chromosomes is homologous across all families of caenophidian snakes (Acrochordidae, Xenodermatidae, Pareatidae, Viperidae, Homalopsidae, Colubridae, Elapidae and Lamprophiidae). The emergence of differentiated sex chromosomes can be dated back to about 60 Ma and preceded the extensive diversification of advanced snakes, the group with more than 3000 species. The Z-specific genes of caenophidian snakes are (pseudo)autosomal in the members of the snake families Pythonidae, Xenopeltidae, Boidae, Erycidae and Sanziniidae, as well as in outgroups with differentiated sex chromosomes such as monitor lizards, iguanas and chameleons. Along with iguanas, advanced snakes are therefore another example of ectothermic amniotes with a long-term stability of sex chromosomes comparable with endotherms.

  3. Evolutionary stability of sex chromosomes in snakes

    Science.gov (United States)

    Rovatsos, Michail; Vukić, Jasna; Lymberakis, Petros; Kratochvíl, Lukáš

    2015-01-01

    Amniote vertebrates possess various mechanisms of sex determination, but their variability is not equally distributed. The large evolutionary stability of sex chromosomes in viviparous mammals and birds was believed to be connected with their endothermy. However, some ectotherm lineages seem to be comparably conserved in sex determination, but previously there was a lack of molecular evidence to confirm this. Here, we document a stability of sex chromosomes in advanced snakes based on the testing of Z-specificity of genes using quantitative PCR (qPCR) across 37 snake species (our qPCR technique is suitable for molecular sexing in potentially all advanced snakes). We discovered that at least part of sex chromosomes is homologous across all families of caenophidian snakes (Acrochordidae, Xenodermatidae, Pareatidae, Viperidae, Homalopsidae, Colubridae, Elapidae and Lamprophiidae). The emergence of differentiated sex chromosomes can be dated back to about 60 Ma and preceded the extensive diversification of advanced snakes, the group with more than 3000 species. The Z-specific genes of caenophidian snakes are (pseudo)autosomal in the members of the snake families Pythonidae, Xenopeltidae, Boidae, Erycidae and Sanziniidae, as well as in outgroups with differentiated sex chromosomes such as monitor lizards, iguanas and chameleons. Along with iguanas, advanced snakes are therefore another example of ectothermic amniotes with a long-term stability of sex chromosomes comparable with endotherms. PMID:26702042

  4. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes.

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    Thayer, Mathew J

    2012-09-01

    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.

  5. The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.

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    Huang, Chun-Jie; Yuan, Yi-Feng; Wu, Di; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Huo, Li-Jun

    2017-03-01

    Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.

  6. Acrocentric Chromosomes in Cultured Leukocytes from Mothers of Children Affected With the G1- Trisomy Syndrome

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    And Others; Cotton, James E.

    1973-01-01

    Analysis of venous blood samples from 24 mothers of G1-trisomy-affected (Down's Syndrome) children and 23 mothers of chromosomally normal children indicated that mothers of G1-trisomy-affected children had a greater than expected involvement of the G-chromosomes in associations of acrocentric satellited (chromosome configuration) chromosomes.…

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

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    Nathan Donley

    2015-01-01

    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.

  8. Affected chromosome homeostasis and genomic instability of clonal yeast cultures.

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

    2016-05-01

    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.

  9. Y-chromosomal genes affecting male fertility: A review

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    Dhanoa, Jasdeep Kaur; Mukhopadhyay, Chandra Sekhar; Arora, Jaspreet Singh

    2016-01-01

    The mammalian sex-chromosomes (X and Y) have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion) of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility. PMID:27536043

  10. Y-chromosomal genes affecting male fertility: A review

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    Jasdeep Kaur Dhanoa

    2016-07-01

    Full Text Available The mammalian sex-chromosomes (X and Y have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility.

  11. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

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    Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Brinton, Louise A.; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Canzian, Federico; Carreón, Tania; Chaffee, Kari G.; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C.; Cook, Linda S.; Crous Bou, Marta; Cullen, Michael; Davis, Faith G.; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Friedenreich, Christine M.; Fuchs, Charles S.; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hsiung, Chao A.; Hu, Nan; Hu, Wei; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P.; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M.; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Moore, Lee; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A.; Rodriguez-Santiago, Benjamin; Ruder, Avima M.; Savage, Sharon A.; Schumacher, Fredrick; Schwartz, Ann G.; Schwartz, Kendra L.; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G.; Perez-Jurado, Luis A.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.

    2016-01-01

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. PMID:27291797

  12. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

    DEFF Research Database (Denmark)

    Machiela, Mitchell J; Zhou, Weiyin; Karlins, Eric

    2016-01-01

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chrom...

  13. Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere.

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    Falk, Samantha J; Guo, Lucie Y; Sekulic, Nikolina; Smoak, Evan M; Mani, Tomoyasu; Logsdon, Glennis A; Gupta, Kushol; Jansen, Lars E T; Van Duyne, Gregory D; Vinogradov, Sergei A; Lampson, Michael A; Black, Ben E

    2015-05-01

    Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.

  14. Chromosome

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    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 ...

  15. Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.

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    Murdoch, Brenda; Owen, Nichole; Stevense, Michelle; Smith, Helen; Nagaoka, So; Hassold, Terry; McKay, Michael; Xu, Huiling; Fu, Jun; Revenkova, Ekaterina; Jessberger, Rolf; Hunt, Patricia

    2013-01-01

    Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC) and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

  16. Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.

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    Brenda Murdoch

    Full Text Available Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

  17. Parameters affect foaming and foam stability during foam drilling

    Institute of Scientific and Technical Information of China (English)

    Hazaea Mohammed; Youhong SUN; Ould El Houssein Yarbana

    2007-01-01

    The authors presented indoor practice experiments of parameters affect on foaming and foam stability. Experiments were carried out and special equipments were used to determine foaming and foam stability; tests were tabulated and charted. The effects of chemical and physical parameters on foaming and foam stability have been conducted.

  18. Stability of Facial Affective Expressions in Schizophrenia

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    H. Fatouros-Bergman

    2012-01-01

    Full Text Available Thirty-two videorecorded interviews were conducted by two interviewers with eight patients diagnosed with schizophrenia. Each patient was interviewed four times: three weekly interviews by the first interviewer and one additional interview by the second interviewer. 64 selected sequences where the patients were speaking about psychotic experiences were scored for facial affective behaviour with Emotion Facial Action Coding System (EMFACS. In accordance with previous research, the results show that patients diagnosed with schizophrenia express negative facial affectivity. Facial affective behaviour seems not to be dependent on temporality, since within-subjects ANOVA revealed no substantial changes in the amount of affects displayed across the weekly interview occasions. Whereas previous findings found contempt to be the most frequent affect in patients, in the present material disgust was as common, but depended on the interviewer. The results suggest that facial affectivity in these patients is primarily dominated by the negative emotions of disgust and, to a lesser extent, contempt and implies that this seems to be a fairly stable feature.

  19. FoxM1 is required for execution of the mitotic programme and chromosome stability

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Brás, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, H.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  20. FoxM1 is required for execution of the mitotic programme and chromosome stability.

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Bras, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, J.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  1. A new function of microtubule-associated protein tau: involvement in chromosome stability.

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    Rossi, Giacomina; Dalprà, Leda; Crosti, Francesca; Lissoni, Sara; Sciacca, Francesca L; Catania, Marcella; Di Fede, Giuseppe; Mangieri, Michela; Giaccone, Giorgio; Croci, Danilo; Tagliavini, Fabrizio

    2008-06-15

    Tau is a microtubule-associated protein that promotes assembly and stabilization of cytoskeleton microtubules. It is mostly expressed in neuronal and glial cells but it is also present in non-neural cells such as fibroblasts and lymphocytes. An altered tau produces cytoskeleton pathology resulting in neurodegenerative diseases such as Alzheimer's disease and tauopathies. Tau has been suggested to be a multifunctional protein, due to its localization in different cellular compartments. However its further functions are still unclear. We analyzed the distribution of tau in human skin fibroblasts showing its localization in the nucleus and along mitotic chromosomes. Then, we investigated if an altered tau, such as the P301L mutated protein associated with frontotemporal dementia, could produce nuclear pathology. We found that patients carrying the mutation consistently had several chromosome aberrations in their fibroblasts and lymphocytes: chromosome and chromatid breakages or gaps, aneuploidies, translocations, in addition to chromatin bridges and decondensed chromosomes. Our findings argue for a role of tau in chromosome stability by means of its interaction with both microtubules and chromatin.

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

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    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.

  3. Mouthrinses affect color stability of composite

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    Baig, Arshia Rashid; Shori, Deepa Deepak; Shenoi, Pratima Ramakrishna; Ali, Syed Navid; Shetti, Sanjay; Godhane, Alkesh

    2016-01-01

    Aim: The aim of this study is to evaluate the effect of alcohol and nonalcohol containing mouth rinses on the color stability of a nanofilled resin composite restorative material. Materials and Methods: A total of 120 samples of a nanofilled resin composite material (Tetric N-Ceram, Ivoclar Vivadent AG, FL-9494 Schaan/Liechtenstein) were prepared and immersed in distilled water for 24 h. Baseline color values were recorded using Color Spectrophotometer 3600d (Konica Minolta, Japan). Samples were then randomly distributed into six groups: Group I - distilled water (control group), Group II - Listerine, Group III - Eludril, Group IV - Phosflur, Group V - Amflor, and Group VI - Rexidin. The postimmersion color values of the samples were then recorded, respectively. Results: Significant reduction in the mean color value (before and after immersion) was observed in nonalcohol containing mouth rinses (P resin composite restorative material, but the color shift was dependent on the material and the mouthrinse used. Group VI (Rexidin) showed maximum color change. PMID:27563186

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

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    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.

  5. Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

    Directory of Open Access Journals (Sweden)

    Akira Shimamoto

    Full Text Available Werner syndrome (WS is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

  6. Plant ecology. Anthropogenic environmental changes affect ecosystem stability via biodiversity.

    Science.gov (United States)

    Hautier, Yann; Tilman, David; Isbell, Forest; Seabloom, Eric W; Borer, Elizabeth T; Reich, Peter B

    2015-04-17

    Human-driven environmental changes may simultaneously affect the biodiversity, productivity, and stability of Earth's ecosystems, but there is no consensus on the causal relationships linking these variables. Data from 12 multiyear experiments that manipulate important anthropogenic drivers, including plant diversity, nitrogen, carbon dioxide, fire, herbivory, and water, show that each driver influences ecosystem productivity. However, the stability of ecosystem productivity is only changed by those drivers that alter biodiversity, with a given decrease in plant species numbers leading to a quantitatively similar decrease in ecosystem stability regardless of which driver caused the biodiversity loss. These results suggest that changes in biodiversity caused by drivers of environmental change may be a major factor determining how global environmental changes affect ecosystem stability.

  7. ATM is required for telomere maintenance and chromosome stability during Drosophila development.

    Science.gov (United States)

    Silva, Elizabeth; Tiong, Stanley; Pedersen, Michael; Homola, Ellen; Royou, Anne; Fasulo, Barbara; Siriaco, Giorgia; Campbell, Shelagh D

    2004-08-10

    ATM is a large, multifunctional protein kinase that regulates responses required for surviving DNA damage: including DNA repair, apoptosis, and cell cycle checkpoints. Here, we show that Drosophila ATM function is essential for normal adult development. Extensive, inappropriate apoptosis occurs in proliferating atm mutant tissues, and in clonally derived atm mutant embryos, frequent mitotic defects were seen. At a cellular level, spontaneous telomere fusions and other chromosomal abnormalities are common in atm larval neuroblasts, suggesting a conserved and essential role for dATM in the maintenance of normal telomeres and chromosome stability. Evidence from other systems supports the idea that DNA double-strand break (DSB) repair functions of ATM kinases promote telomere maintenance by inhibition of illegitimate recombination or fusion events between the legitimate ends of chromosomes and spontaneous DSBs. Drosophila will be an excellent model system for investigating how these ATM-dependent chromosome structural maintenance functions are deployed during development. Because neurons appear to be particularly sensitive to loss of ATM in both flies and humans, this system should be particularly useful for identifying cell-specific factors that influence sensitivity to loss of dATM and are relevant for understanding the human disease, ataxia-telangiectasia.

  8. High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Evert van den Broek

    Full Text Available Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA and structural variants (SVs. Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on carcinogenesis and patient outcome remains poorly understood. This study aimed to perform a systematic analysis of genes that are affected by CNA-associated chromosomal breaks in colorectal cancer (CRC and to determine the clinical relevance of recurrent breakpoint genes.Primary CRC samples of patients with metastatic disease from CAIRO and CAIRO2 clinical trials were previously characterized by array-comparative genomic hybridization. These data were now used to determine the prevalence of CNA-associated chromosomal breaks within genes across 352 CRC samples. In addition, mutation status of the commonly affected APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS genes was determined for 204 CRC samples by targeted massive parallel sequencing. Clinical relevance was assessed upon stratification of patients based on gene mutations and gene breakpoints that were observed in >3% of CRC cases.In total, 748 genes were identified that were recurrently affected by chromosomal breaks (FDR 3% of cases, indicating that prevalence of gene breakpoints is comparable to the prevalence of well-known gene point mutations. Patient stratification based on gene breakpoints and point mutations revealed one CRC subtype with very poor prognosis.We conclude that CNA-associated chromosomal breaks within genes represent a highly prevalent and clinically relevant subset of SVs in CRC.

  9. Centromere binding and a conserved role in chromosome stability for SUMO-dependent ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Loes A L van de Pasch

    Full Text Available The Saccharomyces cerevisiae Slx5/8 complex is the founding member of a recently defined class of SUMO-targeted ubiquitin ligases (STUbLs. Slx5/8 has been implicated in genome stability and transcription, but the precise contribution is unclear. To characterise Slx5/8 function, we determined genome-wide changes in gene expression upon loss of either subunit. The majority of mRNA changes are part of a general stress response, also exhibited by mutants of other genome integrity pathways and therefore indicative of an indirect effect on transcription. Genome-wide binding analysis reveals a uniquely centromeric location for Slx5. Detailed phenotype analyses of slx5Δ and slx8Δ mutants show severe mitotic defects that include aneuploidy, spindle mispositioning, fish hooks and aberrant spindle kinetics. This is associated with accumulation of the PP2A regulatory subunit Rts1 at centromeres prior to entry into anaphase. Knockdown of the human STUbL orthologue RNF4 also results in chromosome segregation errors due to chromosome bridges. The study shows that STUbLs have a conserved role in maintenance of chromosome stability and links SUMO-dependent ubiquitination to a centromere-specific function during mitosis.

  10. Identification of susceptibility genes for bipolar affective disorder and schizophrenia on chromosome 22q13

    DEFF Research Database (Denmark)

    Severinsen, Jacob Eg

    2006-01-01

    Linkage analyses suggest that chromosome 22q12-13 may harbor one or more shared susceptibility loci for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of distantly related cases and control individuals from the Faeroe Islands our group has previously reported that chromosome 22......q13 may harbor two shared susceptibility loci for BPD and SZ. The aim of the Ph.D. project was to identify and characterize susceptibility genes for BPD and SZ located in these two loci on 22q13, primarily by association analyses of selected positional candidate genes in a number of population...... samples (total of 1,751 individuals), and by bioinformatic and expression analyses of a subset of disease associated genes and gene variants. In total 67 single nucleotide polymorphisms (SNPs) located in 18 positional candidate genes, and 4 microsattelite markers were investigated, using a Scottish case...

  11. Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs

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    Jiao Yang

    2016-05-01

    Full Text Available Ten-eleven translocation (Tet family proteins convert 5-methylcytosine to 5-hydroxymethylcytosine. We show that mouse embryonic stem cells (ESCs depleted of Tet1 and/or Tet2 by RNAi exhibit short telomeres and chromosomal instability, concomitant with reduced telomere recombination. Tet1 and Tet2 double-knockout ESCs also display short telomeres but to a lesser extent. Notably, Tet1/2/3 triple-knockout ESCs show heterogeneous telomere lengths and increased frequency of telomere loss and chromosomal fusion. Mechanistically, Tets depletion or deficiency increases Dnmt3b and decreases 5hmC levels, resulting in elevated methylation levels at sub-telomeres. Consistently, knockdown of Dnmt3b or addition of 2i (MAPK and GSK3β inhibitors, which also inhibits Dnmt3b, reduces telomere shortening, partially rescuing Tet1/2 deficiency. Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening. Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels.

  12. Stability in chromosome number and DNA content in synthetic tetraploids of Lolium multiflorum after two generations of selection

    Directory of Open Access Journals (Sweden)

    Roselaine Cristina Pereira

    Full Text Available ABSTRACT: Chromosome doubling of Italian ryegrass genotypes ( Lolium multiflorum Lam. adapted to the brazilian edaphoclimatic conditions is an important strategy used by breeders and aims to obtain more vigorous genotypes with better forage quality and disease resistance. The effectiveness of chromosome doubling can be measured by genetic stability and fertility rates of plants over generations. However, a common problem in the polyploidization process is the regeneration of mixoploid plants that have impaired fertility and genetic stability. The objective of this study was to verify if progenies of recently tetraploidized plants remain stable regarding DNA content and chromosome number, over two generations. Progenies of L. multiflorum plants artificially tetraploidized with colchicine treatment were evaluated. Chromosome counting and estimates of the DNA content were used to evaluate the genetic stability. The percentage of tetraploid plants (4X increased over generations (18%, 34% and 91% in cycle 0, 1 and 2, respectively. All progenies identified as tetraploid by flow citometry showed variation in chromosome number (mixoploidy, but produced viable seeds. Results showed that stabilization in chromosome number and DNA content in tetraploidized plant progenies requires time and that the success of this procedure depends on a continuous and accurate screening and selection.

  13. Switching the centromeres on and off: epigenetic chromatin alterations provide plasticity in centromere activity stabilizing aberrant dicentric chromosomes.

    Science.gov (United States)

    Sato, Hiroshi; Saitoh, Shigeaki

    2013-12-01

    The kinetochore, which forms on a specific chromosomal locus called the centromere, mediates interactions between the chromosome and the spindle during mitosis and meiosis. Abnormal chromosome rearrangements and/or neocentromere formation can cause the presence of multiple centromeres on a single chromosome, which results in chromosome breakage or cell cycle arrest. Analyses of artificial dicentric chromosomes suggested that the activity of the centromere is regulated epigenetically; on some stably maintained dicentric chromosomes, one of the centromeres no longer functions as a platform for kinetochore formation, although the DNA sequence remains intact. Such epigenetic centromere inactivation occurs in cells of various eukaryotes harbouring 'regional centromeres', such as those of maize, fission yeast and humans, suggesting that the position of the active centromere is determined by epigenetic markers on a chromosome rather than the nucleotide sequence. Our recent findings in fission yeast revealed that epigenetic centromere inactivation consists of two steps: disassembly of the kinetochore initiates inactivation and subsequent heterochromatinization prevents revival of the inactivated centromere. Kinetochore disassembly followed by heterochromatinization is also observed in normal senescent human cells. Thus epigenetic centromere inactivation may not only stabilize abnormally generated dicentric chromosomes, but also be part of an intrinsic mechanism regulating cell proliferation.

  14. Stage structure alters how complexity affects stability of ecological networks

    Science.gov (United States)

    Rudolf, V.H.W.; Lafferty, Kevin D.

    2011-01-01

    Resolving how complexity affects stability of natural communities is of key importance for predicting the consequences of biodiversity loss. Central to previous stability analysis has been the assumption that the resources of a consumer are substitutable. However, during their development, most species change diets; for instance, adults often use different resources than larvae or juveniles. Here, we show that such ontogenetic niche shifts are common in real ecological networks and that consideration of these shifts can alter which species are predicted to be at risk of extinction. Furthermore, niche shifts reduce and can even reverse the otherwise stabilizing effect of complexity. This pattern arises because species with several specialized life stages appear to be generalists at the species level but act as sequential specialists that are hypersensitive to resource loss. These results suggest that natural communities are more vulnerable to biodiversity loss than indicated by previous analyses.

  15. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy.

    Science.gov (United States)

    Ottesen, Anne Marie; Aksglaede, Lise; Garn, Inger; Tartaglia, Nicole; Tassone, Flora; Gravholt, Claus H; Bojesen, Anders; Sørensen, Kaspar; Jørgensen, Niels; Rajpert-De Meyts, Ewa; Gerdes, Tommy; Lind, Anne-Marie; Kjaergaard, Susanne; Juul, Anders

    2010-05-01

    Tall stature and eunuchoid body proportions characterize patients with 47,XXY Klinefelter syndrome, whereas patients with 45,X Turner syndrome are characterized by impaired growth. Growth is relatively well characterized in these two syndromes, while few studies describe the growth of patients with higher grade sex chromosome aneuploidies. It has been proposed that tall stature in sex chromosome aneuploidy is related to an overexpression of SHOX, although the copy number of SHOX has not been evaluated in previous studies. Our aims were therefore: (1) to assess stature in 305 patients with sex chromosome aneuploidy and (2) to determine the number of SHOX copies in a subgroup of these patients (n = 255) these patients and 74 healthy controls. Median height standard deviation scores in 46,XX males (n = 6) were -1.2 (-2.8 to 0.3), +0.9 (-2.2 to +4.6) in 47,XXY (n = 129), +1.3 (-1.8 to +4.9) in 47,XYY (n = 44), +1.1 (-1.9 to +3.4) in 48,XXYY (n = 45), +1.8 (-2.0 to +3.2) in 48,XXXY (n = 9), and -1.8 (-4.2 to -0.1) in 49,XXXXY (n = 10). Median height standard deviation scores in patients with 45,X (n = 6) were -2.6 (-4.1 to -1.6), +0.7 (-0.9 to +3.2) in 47,XXX (n = 40), -0.6 (-1.9 to +2.1) in 48,XXXX (n = 13), and -1.0 (-3.5 to -0.8) in 49,XXXXX (n = 3). Height increased with an increasing number of extra X or Y chromosomes, except in males with five, and in females with four or five sex chromosomes, consistent with a nonlinear effect on height.

  16. Genetic stability of murine pluripotent and somatic hybrid cells may be affected by conditions of their cultivation.

    Science.gov (United States)

    Ivanovna, Shramova Elena; Alekseevich, Larionov Oleg; Mikhailovich, Khodarovich Yurii; Vladimirovna, Zatsepina Olga

    2011-01-01

    Using mouse pluripotent teratocarcinoma PCC4azal cells and proliferating spleen lymphocytes we obtained a new type of hybrids, in which marker lymphocyte genes were suppressed, but expression the Oct-4 gene was not effected; the hybrid cells were able to differentiate to cardiomyocytes. In order to specify the environmental factors which may affect the genetic stability and other hybrid properties, we analyzed the total chromosome number and differentiation potencies of hybrids respectively to conditions of their cultivation. Particular attention was paid to the number and transcription activity of chromosomal nucleolus organizing regions (NORs), which harbor the most actively transcribed - ribosomal - genes. The results showed that the hybrids obtained are characterized by a relatively stable chromosome number which diminished less than in 5% during 27 passages. However, a long-term cultivation of hybrid cells in non-selective conditions resulted in preferential elimination of some NO- chromosomes, whereas the number of active NORs per cell was increased due to activation of latent NORs. On the contrary, in selective conditions, i.e. in the presence of hypoxantine, aminopterin and thymidine, the total number of NOR-bearing chromosomes was not changed, but a partial inactivation of remaining NORs was observed. The higher number of active NORs directly correlated with the capability of hybrid cells for differentiation to cardiomyocytes.

  17. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy

    DEFF Research Database (Denmark)

    Ottesen, Anne-Marie; Aksglaede, Lise; Garn, Inger

    2010-01-01

    chromosome aneuploidy and (2) to determine the number of SHOX copies in a subgroup of these patients (n = 255) these patients and 74 healthy controls. Median height standard deviation scores in 46,XX males (n = 6) were -1.2 (-2.8 to 0.3), +0.9 (-2.2 to +4.6) in 47,XXY (n = 129), +1.3 (-1.8 to +4.9) in 47,XYY...

  18. Low-level infrared laser modulates muscle repair and chromosome stabilization genes in myoblasts.

    Science.gov (United States)

    da Silva Neto Trajano, Larissa Alexsandra; Stumbo, Ana Carolina; da Silva, Camila Luna; Mencalha, Andre Luiz; Fonseca, Adenilson S

    2016-08-01

    Infrared laser therapy is used for skeletal muscle repair based on its biostimulative effect on satellite cells. However, shortening of telomere length limits regenerative potential in satellite cells, which occurs after each cell division cycle. Also, laser therapy could be more effective on non-physiologic tissues. This study evaluated low-level infrared laser exposure effects on mRNA expression from muscle injury repair and telomere stabilization genes in myoblasts in normal and stressful conditions. Laser fluences were those used in clinical protocols. C2C12 myoblast cultures were exposed to low-level infrared laser (10, 35, and 70 J/cm(2)) in standard or normal (10 %) and reduced (2 %) fetal bovine serum concentrations; total RNA was extracted for mRNA expression evaluation from muscle injury repair (MyoD and Pax7) and chromosome stabilization (TRF1 and TRF2) genes by real time quantitative polymerization chain reaction. Data show that low-level infrared laser increases the expression of MyoD and Pax7 in 10 J/cm(2) fluence, TRF1 expression in all fluences, and TRF2 expression in 70 J/cm(2) fluence in both 10 and 2 % fetal bovine serum. Low-level infrared laser increases mRNA expression from genes related to muscle repair and telomere stabilization in myoblasts in standard or normal and stressful conditions.

  19. Reduced rDNA Copy Number Does Not Affect “Competitive” Chromosome Pairing in XYY Males of Drosophila melanogaster

    OpenAIRE

    Keith A. Maggert

    2014-01-01

    The ribosomal DNA (rDNA) arrays are causal agents in X-Y chromosome pairing in meiosis I of Drosophila males. Despite broad variation in X-linked and Y-linked rDNA copy number, polymorphisms in regulatory/spacer sequences between rRNA genes, and variance in copy number of interrupting R1 and R2 retrotransposable elements, there is little evidence that different rDNA arrays affect pairing efficacy. I investigated whether induced rDNA copy number polymorphisms affect chromosome pairing in a “co...

  20. Genetic investigations on 8 patients affected by ring 20 chromosome syndrome

    Directory of Open Access Journals (Sweden)

    Giordano Lucio

    2010-10-01

    Full Text Available Abstract Background Mosaic Chromosome 20 ring [r(20] is a chromosomal disorder associated with a rare syndrome characterized by a typical seizure phenotype, a particular electroclinical pattern, cognitive impairment, behavioural problems and absence of a consistent pattern of dysmorphology. The pathogenic mechanism underlying seizures disorders in r(20 syndrome is still unknown. We performed a detailed clinical and genetic study on 8 patients with r(20 chromosome, aimed at detecting the genetic mechanism underlying r(20 syndrome. Methods We submitted 8 subjects with a previous diagnosis of ring 20 chromosome mosaicism to a clinical re-evaluation, followed by cytogenetic, FISH, array-CGH and molecular analyses. The genetic study was also extended to their available parents. Results FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20 chromosome associated disease. Moreover, no evidence of chromosome 20 uniparental disomy was found. Analysis of FISH signals given by variant in size alphoid tandem repeats probes on the normal chromosome 20 and the r(20 chromosome in the mosaic carriers suggests that the r(20 chromosome is the same chromosome not circularized in the "normal" cell line. Conclusions Higher percentages of r(20 chromosome cells were observed to be related with precocious age at seizure onset and with resistance to antiepileptic drug treatment. Behavioural problems also seem to be associated with higher percentages of r(20 chromosome cells. Our results suggest that an epigenetic mechanism perturbing the expression of genes close to the telomeric regions, rather than deletion of genes located at the distal 20p and/or 20q regions, may underlie the manifestation of r(20 syndrome.

  1. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.

    Science.gov (United States)

    Rodriguez, Marisela R; Lundgren, Alyssa; Sabastian, Pearl; Li, Qian; Churchill, Gary; Brown, Michael G

    2009-07-01

    NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

  2. Mechanism of chromosomal DNA replication initiation and replication fork stabilization in eukaryotes.

    Science.gov (United States)

    Wu, LiHong; Liu, Yang; Kong, DaoChun

    2014-05-01

    Chromosomal DNA replication is one of the central biological events occurring inside cells. Due to its large size, the replication of genomic DNA in eukaryotes initiates at hundreds to tens of thousands of sites called DNA origins so that the replication could be completed in a limited time. Further, eukaryotic DNA replication is sophisticatedly regulated, and this regulation guarantees that each origin fires once per S phase and each segment of DNA gets duplication also once per cell cycle. The first step of replication initiation is the assembly of pre-replication complex (pre-RC). Since 1973, four proteins, Cdc6/Cdc18, MCM, ORC and Cdt1, have been extensively studied and proved to be pre-RC components. Recently, a novel pre-RC component called Sap1/Girdin was identified. Sap1/Girdin is required for loading Cdc18/Cdc6 to origins for pre-RC assembly in the fission yeast and human cells, respectively. At the transition of G1 to S phase, pre-RC is activated by the two kinases, cyclindependent kinase (CDK) and Dbf4-dependent kinase (DDK), and subsequently, RPA, primase-polα, PCNA, topoisomerase, Cdc45, polδ, and polɛ are recruited to DNA origins for creating two bi-directional replication forks and initiating DNA replication. As replication forks move along chromatin DNA, they frequently stall due to the presence of a great number of replication barriers on chromatin DNA, such as secondary DNA structures, protein/DNA complexes, DNA lesions, gene transcription. Stalled forks must require checkpoint regulation for their stabilization. Otherwise, stalled forks will collapse, which results in incomplete DNA replication and genomic instability. This short review gives a concise introduction regarding the current understanding of replication initiation and replication fork stabilization.

  3. Identification of a short region on chromosome 6 affecting direct calving ease in Piedmontese cattle breed.

    Directory of Open Access Journals (Sweden)

    Silvia Bongiorni

    Full Text Available Calving in cattle is affected by calf morphology and by dam characteristics. It is described by two different traits: maternal calving ease, which is the ability to generate dams with good physiological predisposition to calving, and direct calving ease, which is the ability to generate calves that are easily born. The aim of this study was to identify regions of cattle genome harboring genes possibly affecting direct calving ease in the Piedmontese cattle breed. A population of 323 bulls scored for direct calving ease (EBV was analyzed by a medium-density SNP marker panel (54,001 SNPs to perform a genome-wide scan. The strongest signal was detected on chromosome 6 between 37.8 and 38.7 Mb where 13 SNPs associated to direct calving ease were found. Three genes are located in this region: LAP3, encoding for a leucine aminopeptidase involved in the oxytocin hydrolysis; NCAPG, encoding for a non-SMC condensin I complex, which has been associated in cattle with fetal growth and carcass size; and LCORL, which has been associated to height in humans and cattle. To further confirm the results of the genome-wide scan we genotyped additional SNPs within these genes and analyzed their association with direct calving ease. The results of this additional analysis fully confirmed the findings of the GWAS and particularly indicated LAP3 as the most probable gene involved. Linkage Disequilibrium (LD analysis showed high correlation between SNPs located within LAP3 and LCORL indicating a possible selection signature due either to increased fitness or breeders' selection for the trait.

  4. The role of BUBR1 in the maintenance of chromosomal stability

    NARCIS (Netherlands)

    Suijkerbuijk, S.J.E.

    2012-01-01

    The majority of solid tumours contain an incorrect number of chromosomes. This state, called aneuploidy, can be caused by defects in chromosome segregation during the division of cells. Prevention against aneuploidy is dependent on BUBR1. This protein is an essential component of a surveillance mech

  5. Genetic isolation of a chromosome 1 region affecting susceptibility to hypertension-induced renal damage in the spontaneously hypertensive rat.

    Science.gov (United States)

    St Lezin, E; Griffin, K A; Picken, M; Churchill, M C; Churchill, P C; Kurtz, T W; Liu, W; Wang, N; Kren, V; Zidek, V; Pravenec, M; Bidani, A K

    1999-08-01

    Linkage studies in the fawn-hooded hypertensive rat have suggested that genes influencing susceptibility to hypertension-associated renal failure may exist on rat chromosome 1q. To investigate this possibility in a widely used model of hypertension, the spontaneously hypertensive rat (SHR), we compared susceptibility to hypertension-induced renal damage between an SHR progenitor strain and an SHR congenic strain that is genetically identical except for a defined region of chromosome 1q. Backcross breeding with selection for the markers D1Mit3 and Igf2 on chromosome 1 was used to create the congenic strain (designated SHR.BN-D1Mit3/Igf2) that carries a 22 cM segment of chromosome 1 transferred from the normotensive Brown Norway rat onto the SHR background. Systolic blood pressure (by radiotelemetry) and urine protein excretion were measured in the SHR progenitor and congenic strains before and after the induction of accelerated hypertension by administration of DOCA-salt. At the same level of DOCA-salt hypertension, the SHR.BN-D1Mit3/Igf2 congenic strain showed significantly greater proteinuria and histologically assessed renal vascular and glomerular injury than the SHR progenitor strain. These findings demonstrate that a gene or genes that influence susceptibility to hypertension-induced renal damage have been trapped in the differential chromosome segment of the SHR.BN-D1Mit3/Igf2 congenic strain. This congenic strain represents an important new model for the fine mapping of gene(s) on chromosome 1 that affect susceptibility to hypertension-induced renal injury in the rat.

  6. Tumor suppressor protein DAB2IP participates in chromosomal stability maintenance through activating spindle assembly checkpoint and stabilizing kinetochore-microtubule attachments

    Science.gov (United States)

    Yu, Lan; Shang, Zeng-Fu; Abdisalaam, Salim; Lee, Kyung-Jong; Gupta, Arun; Hsieh, Jer-Tsong; Asaithamby, Aroumougame; Chen, Benjamin P.C.; Saha, Debabrata

    2016-01-01

    Defects in kinetochore-microtubule (KT-MT) attachment and the spindle assembly checkpoint (SAC) during cell division are strongly associated with chromosomal instability (CIN). CIN has been linked to carcinogenesis, metastasis, poor prognosis and resistance to cancer therapy. We previously reported that the DAB2IP is a tumor suppressor, and that loss of DAB2IP is often detected in advanced prostate cancer (PCa) and is indicative of poor prognosis. Here, we report that the loss of DAB2IP results in impaired KT-MT attachment, compromised SAC and aberrant chromosomal segregation. We discovered that DAB2IP directly interacts with Plk1 and its loss inhibits Plk1 kinase activity, thereby impairing Plk1-mediated BubR1 phosphorylation. Loss of DAB2IP decreases the localization of BubR1 at the kinetochore during mitosis progression. In addition, the reconstitution of DAB2IP enhances the sensitivity of PCa cells to microtubule stabilizing drugs (paclitaxel, docetaxel) and Plk1 inhibitor (BI2536). Our findings demonstrate a novel function of DAB2IP in the maintenance of KT-MT structure and SAC regulation during mitosis which is essential for chromosomal stability. PMID:27568005

  7. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Directory of Open Access Journals (Sweden)

    Tejasvi S Niranjan

    Full Text Available X-linked Intellectual Disability (XLID is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  8. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Science.gov (United States)

    Niranjan, Tejasvi S; Skinner, Cindy; May, Melanie; Turner, Tychele; Rose, Rebecca; Stevenson, Roger; Schwartz, Charles E; Wang, Tao

    2015-01-01

    X-linked Intellectual Disability (XLID) is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome) in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families) using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  9. CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs.

    Science.gov (United States)

    van Wolfswinkel, Josien C; Claycomb, Julie M; Batista, Pedro J; Mello, Craig C; Berezikov, Eugene; Ketting, René F

    2009-10-02

    We have studied the function of a conserved germline-specific nucleotidyltransferase protein, CDE-1, in RNAi and chromosome segregation in C. elegans. CDE-1 localizes specifically to mitotic chromosomes in embryos. This localization requires the RdRP EGO-1, which physically interacts with CDE-1, and the Argonaute protein CSR-1. We found that CDE-1 is required for the uridylation of CSR-1 bound siRNAs, and that in the absence of CDE-1 these siRNAs accumulate to inappropriate levels, accompanied by defects in both meiotic and mitotic chromosome segregation. Elevated siRNA levels are associated with erroneous gene silencing, most likely through the inappropriate loading of CSR-1 siRNAs into other Argonaute proteins. We propose a model in which CDE-1 restricts specific EGO-1-generated siRNAs to the CSR-1 mediated, chromosome associated RNAi pathway, thus separating it from other endogenous RNAi pathways. The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals.

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

    Directory of Open Access Journals (Sweden)

    Wen Ying

    2010-07-01

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

  11. Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies

    Science.gov (United States)

    Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L.; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N.

    2015-01-01

    The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry. PMID:25568109

  12. Mapping the stability of human brain asymmetry across five sex-chromosome aneuploidies.

    Science.gov (United States)

    Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N; Raznahan, Armin

    2015-01-07

    The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.

  13. Search for a shared segment on chromosome 10q26 in patients with bipolar affective disorder or schizophrenia from the Faroe Islands

    DEFF Research Database (Denmark)

    Ewald, Henrik; Flint, Tracey J; Jorgensen, Tove H;

    2002-01-01

    Previous linkage studies have suggested a new locus for bipolar affective disorder and possibly also for schizophrenia on chromosome 10q26. We searched for allelic association and chromosome segment and haplotype sharing on chromosome 10q26 among distantly related patients with bipolar affective ...... in patients with bipolar affective disorder was supported by Fisher's exact test, tests based on genealogy and by haplotype data mining. Our findings yield some support for a risk gene for bipolar affective disorder and possibly also for schizophrenia.......Previous linkage studies have suggested a new locus for bipolar affective disorder and possibly also for schizophrenia on chromosome 10q26. We searched for allelic association and chromosome segment and haplotype sharing on chromosome 10q26 among distantly related patients with bipolar affective...... and D10S2322, which has been implied in previous linkage analyses, received some support. A search for segment sharing yielded empirical P-values around 0.02 among patients with bipolar affective disorder and around 0.03 for patients with schizophrenia. For both disorders combined allelic association...

  14. Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus

    Energy Technology Data Exchange (ETDEWEB)

    Nikali, K.; Suomalainen, A.; Koskinen, T.; Peltonen, L. [Univ. of Helsinki (Finland); Terwilliger, J. [Univ. of Oxford (United Kingdom); Weissenbach, J. [Genethon, Evry (France)

    1995-05-01

    Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials. 30 refs., 3 figs., 2 tabs.

  15. Arabidopsis PTD is required for type I crossover formation and affects recombination frequency in two different chromosomal regions.

    Science.gov (United States)

    Lu, Pingli; Wijeratne, Asela J; Wang, Zhengjia; Copenhaver, Gregory P; Ma, Hong

    2014-03-20

    In eukaryotes, crossovers together with sister chromatid cohesion maintain physical association between homologous chromosomes, ensuring accurate chromosome segregation during meiosis I and resulting in exchange of genetic information between homologues. The Arabidopsis PTD (Parting Dancers) gene affects the level of meiotic crossover formation, but its functional relationships with other core meiotic genes, such as AtSPO11-1, AtRAD51, and AtMSH4, are unclear; whether PTD has other functions in meiosis is also unknown. To further analyze PTD function and to test for epistatic relationships, we compared the meiotic chromosome behaviors of Atspo11-1 ptd and Atrad51 ptd double mutants with the relevant single mutants. The results suggest that PTD functions downstream of AtSPO11-1 and AtRAD51 in the meiotic recombination pathway. Furthermore, we found that meiotic defects in rck ptd and Atmsh4 ptd double mutants showed similar meiotic phenotypes to those of the relevant single mutants, providing genetic evidences for roles of PTD and RCK in the type I crossovers pathway. Moreover, we employed a pollen tetrad-based fluorescence method and found that the meiotic crossover frequencies in two genetic intervals were significantly reduced from 6.63% and 22.26% in wild-type to 1.14% and 6.36%, respectively, in the ptd-2 mutant. These results revealed new aspects of PTD function in meiotic crossover formation.

  16. Sugar and chromosome stability: clastogenic effects of sugars in vitamin B6-deficient cells.

    Directory of Open Access Journals (Sweden)

    Antonio Marzio

    2014-03-01

    Full Text Available Pyridoxal 5'-phosphate (PLP, the active form of vitamin B6, has been implicated in preventing human pathologies, such as diabetes and cancer. However, the mechanisms underlying the beneficial effects of PLP are still unclear. Using Drosophila as a model system, we show that PLP deficiency, caused either by mutations in the pyridoxal kinase-coding gene (dPdxk or by vitamin B6 antagonists, results in chromosome aberrations (CABs. The CAB frequency in PLP-depleted cells was strongly enhanced by sucrose, glucose or fructose treatments, and dPdxk mutant cells consistently displayed higher glucose contents than their wild type counterparts, an effect that is at least in part a consequence of an acquired insulin resistance. Together, our results indicate that a high intracellular level of glucose has a dramatic clastogenic effect if combined with PLP deficiency. This is likely due to an elevated level of Advanced Glycation End-products (AGE formation. Treatment of dPdxk mutant cells with α-lipoic acid (ALA lowered both AGE formation and CAB frequency, suggesting a possible AGE-CAB cause-effect relationship. The clastogenic effect of glucose in PLP-depleted cells is evolutionarily conserved. RNAi-mediated silencing of PDXK in human cells or treatments with PLP inhibitors resulted in chromosome breakage, which was potentiated by glucose and reduced by ALA. These results suggest that patients with concomitant hyperglycemia and vitamin B6 deficiency may suffer chromosome damage. This might impact cancer risk, as CABs are a well-known tumorigenic factor.

  17. Lamb meat colour stability as affected by dietary tannins

    Directory of Open Access Journals (Sweden)

    Pietro Pennisi

    2010-01-01

    Full Text Available Twenty-one male Comisana lambs were divided into three groups at 45 days of age and were individually penned for 60 days. Seven lambs were fed a concentrate-based diet (C, seven lambs received the same concentrate with the addiction of tannins from quebracho (Schinopsis lorentzii; T, whereas the remaining animals were fed exclusively fresh vetch (Vicia sativa; H. Colour descriptors (a*, b* and H* and metmyoglobin (MMb percentages were measured on minced semimembranosus muscle over 14 days of refrigerated storage in a high oxygen atmosphere. Regardless of dietary treatment, meat redness decreased, while yellowness and hue angle increased (P < 0.001 over storage duration. However, higher a* values, lower b* values and lower H* values were observed in meat from both H- and T-fed animals as compared to meat from C-fed lambs (P = 0.012; P = 0.02; P = 0.003, respectively. Metmyoglobin formation increased over time (P < 0.001, but H diet resulted in lower metmyoglobin percentages than C diet (P = 0.007. We conclude that the inclusion of tannins into the concentrate improved meat colour stability compared to a tannin-free concentrate. Moreover, the protective effect of tannins against meat discolouration was comparable to that obtained by feeding lambs fresh herbage.

  18. Mitotic phosphorylation of Bloom helicase at Thr182 is required for its proteasomal degradation and maintenance of chromosomal stability.

    Science.gov (United States)

    Kharat, S S; Tripathi, V; Damodaran, A P; Priyadarshini, R; Chandra, S; Tikoo, S; Nandhakumar, R; Srivastava, V; Priya, S; Hussain, M; Kaur, S; Fishman, J B; Sengupta, S

    2016-02-25

    Mutations in Bloom helicase (BLM) lead to Bloom Syndrome (BS). BS is characterized by multiple clinical manifestations including predisposition to a wide spectrum of cancers. Studies have revealed the mechanism of BLM recruitment after stalled replication and its role during the repair of DNA damage. We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates. Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges. Consequently lack of Thr182 phosphorylation leads to multiple manifestations of chromosomal instability including increased levels of DNA damage, lagging chromatin, micronuclei formation, breaks and quadriradials. Hence Thr182 phosphorylation on BLM has two functions-it regulates BLM turnover during mitosis and also helps to maintain the chromosomal stability.

  19. Essential functions of Sds22p in chromosome stability and nuclear localization of PP1.

    Science.gov (United States)

    Peggie, Mark W; MacKelvie, Sarah H; Bloecher, Andrew; Knatko, Elena V; Tatchell, Kelly; Stark, Michael J R

    2002-01-01

    Sds22p is a conserved, leucine-rich repeat protein that interacts with the catalytic subunit of protein phosphatase 1 (PP1(C)) and which has been proposed to regulate one or more functions of PP1(C) during mitosis. Here we show that Saccharomyces cerevisiae Sds22p is a largely nuclear protein, most of which is present as a sTable 1:1 complex with yeast PP1(C) (Glc7p). Temperature-sensitive (Ts(-)) S. cerevisiae sds22 mutants show profound chromosome instability at elevated growth temperatures but do not confer a cell cycle stage-specific arrest. In the sds22-6 Ts(-) mutant, nuclear Glc7p is both reduced in level and aberrantly localized at 37 degrees C and the interaction between Glc7p and Sds22p in vitro is reduced at higher temperatures, consistent with the in vivo Ts(-) growth defect. Like some glc7 mutations, sds22-6 can suppress the Ts(-) growth defect associated with ipl1-2, a loss of function mutation in a protein kinase that is known to work in opposition to PP1 on at least two nuclear substrates. This, together with reciprocal genetic interactions between GLC7 and SDS22, suggests that Sds22p functions positively with Glc7p to promote dephosphorylation of nuclear substrates required for faithful transmission of chromosomes during mitosis, and this role is at least partly mediated by effects of Sds22p on the nuclear distribution of Glc7p

  20. Search for a shared segment on chromosome 10q26 in patients with bipolar affective disorder or schizophrenia from the Faroe Islands

    DEFF Research Database (Denmark)

    Ewald, H.; Flint, T.J.; Jorgensen, T.H.

    2002-01-01

    and D10S2322, which has been implied in previous linkage analyses, received some support. A search for segment sharing yielded empirical P-values around 0.02 among patients with bipolar affective disorder and around 0.03 for patients with schizophrenia. For both disorders combined allelic association...... yielded empirical P-values around 0.003 at marker D10S1723. A haplotype data mining approach supported haplotype sharing in this region. In another, more distal, 11.5 cM region between markers D10S214 and D10S505, which has received support in previous linkage studies, increased haplotype sharing......Previous linkage studies have suggested a new locus for bipolar affective disorder and possibly also for schizophrenia on chromosome 10q26. We searched for allelic association and chromosome segment and haplotype sharing on chromosome 10q26 among distantly related patients with bipolar affective...

  1. Dermal nanocrystals from medium soluble actives - physical stability and stability affecting parameters.

    Science.gov (United States)

    Zhai, Xuezhen; Lademann, Jürgen; Keck, Cornelia M; Müller, Rainer H

    2014-09-01

    Nanocrystals are meanwhile applied to increase the dermal penetration of drugs, but were applied by now only to poorly soluble drugs (e.g. 1-10 μg/ml). As a new concept nanocrystals from medium soluble actives were produced, using caffeine as model compound (solubility 16 mg/ml at 20 °C). Penetration should be increased by (a) further increase in solubility and (b) mainly by increased hair follicle targeting of nanocrystals compared to pure solution. Caffeine nanocrystal production in water lead to pronounced crystal growth. Therefore the stability of nanocrystals in water-ethanol (1:9) and ethanol-propylene glycol (3:7) mixtures with lower dielectric constant D was investigated, using various stabilizers. Both mixtures in combination with Carbopol 981 (non-neutralized) yielded stable nanosuspensions over 2 months at 4 °C and room temperature. Storage at 40 °C lead to crystal growth, attributed to too strong solubility increase, supersaturation and Ostwald ripening effects. Stability of caffeine nanocrystals at lower temperatures could not only be attributed to lower solubility, because the solubilities of caffeine in mixtures and in water are not that much different. Other effects such as quantified by reduced dielectric constant D, and specific interactions between dispersion medium and crystal surface seem to play a role. With the 2 mixtures and Carbopol 981, a basic formulation composition for this type of nanocrystals has been established, to be used in the in vivo proof of principle of the new concept.

  2. Hypersensitivity of Drosophila mei-41 mutants to hydroxyurea is associated with reduced mitotic chromosome stability.

    Science.gov (United States)

    Banga, S S; Shenkar, R; Boyd, J B

    1986-11-01

    6 mutant alleles of the mei-41 locus in Drosophila melanogaster are shown to cause hypersensitivity to hydroxyurea in larvae. The strength of that sensitivity is directly correlated with the influence of the mutant alleles on meiosis in that: alleles exhibiting a strong meiotic effect (mei-41D2, mei-41D5, mei-41D7) are highly sensitive; alleles with negligible meiotic effects (mei-41(104)D1, mei-41(104)D2) are moderately sensitive and an allele which expresses meiotic effects only under restricted conditions (mei-41D9) has an intermediate sensitivity. This sensitivity is not a general feature of strong postreplication repair-deficient mutants, because mutants with that phenotype from other loci do not exhibit sensitivity (mus(2)205A1, mus(3)302D1, mus(3)310D1). The observed lethality is not due to hypersensitivity of DNA synthesis in mei-41 larvae to hydroxyurea as assayed by tritiated thymidine incorporation. Lethality is, however, potentially attributable to an abnormal enhancement of chromosomal aberrations by hydroxyurea in mutant mei-41 larvae. Both in vivo and in vitro exposure of neuroblast cells to hydroxyurea results in an increase in 3 types of aberrations which is several fold higher in mei-41 tissue. Since hydroxyurea disrupts DNA synthesis, these results further implicate the mei-41 locus in DNA metabolism and provide an additional tool for an elucidation of its function. The possible existence of additional genes of this nature is suggested by a more modest sensitivity to hydroxyurea which has been detected in two stocks carrying mutagen-sensitive alleles of alternate genes.

  3. The use of "stabilization exercises" to affect neuromuscular control in the lumbopelvic region: a narrative review.

    Science.gov (United States)

    Bruno, Paul

    2014-06-01

    It is well-established that the coordination of muscular activity in the lumbopelvic region is vital to the generation of mechanical spinal stability. Several models illustrating mechanisms by which dysfunctional neuromuscular control strategies may serve as a cause and/or effect of low back pain have been described in the literature. The term "core stability" is variously used by clinicians and researchers, and this variety has led to several rehabilitative approaches suggested to affect the neuromuscular control strategies of the lumbopelvic region (e.g. "stabilization exercise", "motor control exercise"). This narrative review will highlight: 1) the ongoing debate in the clinical and research communities regarding the terms "core stability" and "stabilization exercise", 2) the importance of sub-grouping in identifying those patients most likely to benefit from such therapeutic interventions, and 3) two protocols that can assist clinicians in this process.

  4. Karyotype stability and predictors of chromosome number variation in sedges: a study in Carex section Spirostachyae (Cyperaceae).

    Science.gov (United States)

    Escudero, Marcial; Hipp, Andrew L; Luceño, Modesto

    2010-10-01

    Previous work on holocentric chromosomes in the angiosperm genus Carex demonstrates that many of the traditional sections are marked by different ranges of chromosome number, suggesting phylogenetic autocorrelation. It has been hypothesized that shifting constraints on chromosome rearrangements may limit the potential for hybridization among lineages, promoting speciation. In this study, we evaluated alternative evolutionary models to test for such transitions in Carex section Spirostachyae as well as the relative effects of several plausible drivers of intraspecific chromosome diversity. Chromosome number variation in section Spirostachyae shows significant phylogenetic signal, but no evidence of clade-specific shifts in chromosome number distribution. This gradual model of chromosome evolution contrasts with the shifting equilibrium model previously identified in a younger section of the same genus, suggesting that section Spirostachyae may have a more slowly evolving karyotype. Chromosome number variance, on the other hand, exhibits low phylogenetic signal. Average time of coalescence rather than geographic range or chromosome number itself predicts chromosome number variance, demonstrating a previously unreported relationship between population history and cytogenetic variation.

  5. Asexual Reproduction Does Not Apparently Increase the Rate of Chromosomal Evolution: Karyotype Stability in Diploid and Triploid Clonal Hybrid Fish (Cobitis, Cypriniformes, Teleostei).

    Science.gov (United States)

    Majtánová, Zuzana; Choleva, Lukáš; Symonová, Radka; Ráb, Petr; Kotusz, Jan; Pekárik, Ladislav; Janko, Karel

    2016-01-01

    Interspecific hybridization, polyploidization and transitions from sexuality to asexuality considerably affect organismal genomes. Especially the last mentioned process has been assumed to play a significant role in the initiation of chromosomal rearrangements, causing increased rates of karyotype evolution. We used cytogenetic analysis and molecular dating of cladogenetic events to compare the rate of changes of chromosome morphology and karyotype in asexually and sexually reproducing counterparts in European spined loach fish (Cobitis). We studied metaphases of three sexually reproducing species and their diploid and polyploid hybrid clones of different age of origin. The material includes artificial F1 hybrid strains, representatives of lineage originated in Holocene epoch, and also individuals of an oldest known age to date (roughly 0.37 MYA). Thereafter we applied GISH technique as a marker to differentiate parental chromosomal sets in hybrids. Although the sexual species accumulated remarkable chromosomal rearrangements after their speciation, we observed no differences in chromosome numbers and/or morphology among karyotypes of asexual hybrids. These hybrids possess chromosome sets originating from respective parental species with no cytogenetically detectable recombinations, suggesting their integrity even in a long term. The switch to asexual reproduction thus did not provoke any significant acceleration of the rate of chromosomal evolution in Cobitis. Asexual animals described in other case studies reproduce ameiotically, while Cobitis hybrids described here produce eggs likely through modified meiosis. Therefore, our findings indicate that the effect of asexuality on the rate of chromosomal change may be context-dependent rather than universal and related to particular type of asexual reproduction.

  6. Asexual Reproduction Does Not Apparently Increase the Rate of Chromosomal Evolution: Karyotype Stability in Diploid and Triploid Clonal Hybrid Fish (Cobitis, Cypriniformes, Teleostei.

    Directory of Open Access Journals (Sweden)

    Zuzana Majtánová

    Full Text Available Interspecific hybridization, polyploidization and transitions from sexuality to asexuality considerably affect organismal genomes. Especially the last mentioned process has been assumed to play a significant role in the initiation of chromosomal rearrangements, causing increased rates of karyotype evolution. We used cytogenetic analysis and molecular dating of cladogenetic events to compare the rate of changes of chromosome morphology and karyotype in asexually and sexually reproducing counterparts in European spined loach fish (Cobitis. We studied metaphases of three sexually reproducing species and their diploid and polyploid hybrid clones of different age of origin. The material includes artificial F1 hybrid strains, representatives of lineage originated in Holocene epoch, and also individuals of an oldest known age to date (roughly 0.37 MYA. Thereafter we applied GISH technique as a marker to differentiate parental chromosomal sets in hybrids. Although the sexual species accumulated remarkable chromosomal rearrangements after their speciation, we observed no differences in chromosome numbers and/or morphology among karyotypes of asexual hybrids. These hybrids possess chromosome sets originating from respective parental species with no cytogenetically detectable recombinations, suggesting their integrity even in a long term. The switch to asexual reproduction thus did not provoke any significant acceleration of the rate of chromosomal evolution in Cobitis. Asexual animals described in other case studies reproduce ameiotically, while Cobitis hybrids described here produce eggs likely through modified meiosis. Therefore, our findings indicate that the effect of asexuality on the rate of chromosomal change may be context-dependent rather than universal and related to particular type of asexual reproduction.

  7. The karyotypes of five species of the Scinax perpusillus group (Amphibia, Anura, Hylidae) of southeastern Brazil show high levels of chromosomal stabilization in this taxon.

    Science.gov (United States)

    Peixoto, Marco Antônio Amorim; Lacerda, João Victor Andrade; Coelho-Augusto, Carolina; Feio, Renato Neves; Dergam, Jorge Abdala

    2015-12-01

    Based on morphological, bioacoustics, and morphological traits, the genus Scinax has been subdivided into two major clades: S. catharinae and S. ruber. The first clade includes S. catharinae and S. perpusillus groups, whereas the second clade includes S. rostratus and S. uruguayus groups. Chromosome morphology, NOR and C-banding patterns of variation support these clades. This study aims the cytogenetic characterization of five species currently included in the S. perpusillus group: Scinax sp. (gr. perpusillus), S. arduous, S. belloni, S. cosenzai, and S. v-signatus, including standard cytogenetic techniques and repetitive DNA FISH probes. All species had 2n = 24 chromosomes. Nucleolar organizing regions occurred in chromosome pair 6 in all species, but differed in their locations among some species, suggesting a putative synaponomastic character for the clade. In S. belloni, the first chromosome pair was a metacentric, contrasting with the submetacentric first pair reported in all other species of the genus. Scinax sp. (gr. perpusillus) and S. v-signatus had similar karyotypic formulae, suggesting they are related species. Scinax cosenzai had a divergent C-banding pattern. Repetitive DNA probes hybridized more frequently in chromosomal subtelomeric regions in all species indicating recent cladogenesis in these species. Karyotypic evidence indicates unreported high levels of stabilization within S. perpusillus and in S. catharinae clade, resulting in a wealth of characters potentially informative for higher phylogenetic analyses.

  8. Emulsifier type, metal chelation and pH affect oxidative stability of n-3-enriched emulsions

    DEFF Research Database (Denmark)

    Haahr, Anne-Mette; Jacobsen, Charlotte

    2008-01-01

    Recent research has shown that the oxidative stability of oil-in-water emulsions is affected by the type of surfactant used as emulsifier. The aim of this study was to evaluate the effect of real food emulsifiers as well as metal chelation by EDTA and pH on the oxidative stability of a 10% n-3...... to their ability to chelate iron, scavenge free radicals, interfere with interactions between the lipid hydroperoxides and iron as well as to form a physical harrier around the oil droplets....

  9. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders

    Science.gov (United States)

    Ji, Baohu; Higa, Kerin K.; Kelsoe, John R.; Zhou, Xianjin

    2015-01-01

    Background Psychiatric disorders are common mental disorders without a pathological biomarker. Classic genetic studies found that an extra X chromosome frequently causes psychiatric symptoms in patients with either Klinefelter syndrome (XXY) or Triple X syndrome (XXX). Over-dosage of some X-linked escapee genes was suggested to cause psychiatric disorders. However, relevance of these rare genetic diseases to the pathogenesis of psychiatric disorders in the general population of psychiatric patients is unknown. Methods XIST and several X-linked genes were studied in 36 lymphoblastoid cell lines from healthy females and 60 lymphoblastoid cell lines from female patients with either bipolar disorder or recurrent major depression. XIST and KDM5C expression was also quantified in 48 RNA samples from postmortem human brains of healthy female controls and female psychiatric patients. Findings We found that the XIST gene, a master in control of X chromosome inactivation (XCI), is significantly over-expressed (p = 1 × 10− 7, corrected after multiple comparisons) in the lymphoblastoid cells of female patients with either bipolar disorder or major depression. The X-linked escapee gene KDM5C also displays significant up-regulation (p = 5.3 × 10− 7, corrected after multiple comparisons) in the patients' cells. Expression of XIST and KDM5C is highly correlated (Pearson's coefficient, r = 0.78, p = 1.3 × 10− 13). Studies on human postmortem brains supported over-expression of the XIST gene in female psychiatric patients. Interpretations We propose that over-expression of XIST may cause or result from subtle alteration of XCI, which up-regulates the expression of some X-linked escapee genes including KDM5C. Over-expression of X-linked genes could be a common mechanism for the development of psychiatric disorders between patients with those rare genetic diseases and the general population of female psychiatric patients with XIST over-expression. Our studies

  10. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

    Directory of Open Access Journals (Sweden)

    Lucie Šedová

    Full Text Available Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16 and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx into the genomic background of the spontaneously hypertensive rat (SHR strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference and diastolic (10-15 mmHg difference blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001. The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1. Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic

  11. The Parent-of-Origin of the Extra X Chromosome May Differentially Affect Psychopathology in Klinefelter Syndrome

    NARCIS (Netherlands)

    Bruining, Hilgo; van Rijn, Sophie; Swaab, Hanna; Giltay, Jacques; Kates, Wendy; Kas, Martien J. H.; van Engeland, Herman; de Sonneville, Leo

    2010-01-01

    Background: Several genetic mechanisms have been proposed for the variability of the Klinefelter syndrome (KS) phenotype such as the parent-of-origin of the extra X chromosome. Parent-of-origin effects on behavior in KS can possibly provide insights into X-linked imprinting effects on psychopatholog

  12. The parent-of-origin of the extra X chromosome may differentially affect psychopathology in Klinefelter syndrome

    NARCIS (Netherlands)

    Bruining, Hilgo; van Rijn, Sophie; Swaab, Hanna; Giltay, Jacques; Kates, Wendy; Kas, Martien J H; van Engeland, Herman; de Sonneville, Leo

    2010-01-01

    BACKGROUND: Several genetic mechanisms have been proposed for the variability of the Klinefelter syndrome (KS) phenotype such as the parent-of-origin of the extra X chromosome. Parent-of-origin effects on behavior in KS can possibly provide insights into X-linked imprinting effects on psychopatholog

  13. Stability Limits of Capillary Bridges: How Contact Angle Hysteresis Affects Morphology Transitions of Liquid Microstructures.

    Science.gov (United States)

    de Ruiter, Riëlle; Semprebon, Ciro; van Gorcum, Mathijs; Duits, Michèl H G; Brinkmann, Martin; Mugele, Frieder

    2015-06-12

    The equilibrium shape of a drop in contact with solid surfaces can undergo continuous or discontinuous transitions upon changes in either drop volume or surface energies. In many instances, such transitions involve the motion of the three-phase contact line and are thus sensitive to contact angle hysteresis. Using a combination of electrowetting-based experiments and numerical calculations, we demonstrate for a generic sphere-plate confinement geometry how contact angle hysteresis affects the mechanical stability of competing axisymmetric and nonaxisymmetric drop conformations and qualitatively changes the character of transitions between them.

  14. HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore microtubules in the vicinity of chromosomes

    NARCIS (Netherlands)

    Silljé, Herman H W; Nagel, Susanna; Körner, Roman; Nigg, Erich A

    2006-01-01

    BACKGROUND: Formation of a bipolar mitotic spindle in somatic cells requires the cooperation of two assembly pathways, one based on kinetochore capture by centrosomal microtubules, the other on RanGTP-mediated microtubule organization in the vicinity of chromosomes. How RanGTP regulates kinetochore-

  15. Inherited Mendelian defects of nuclear-mitochondrial communication affecting the stability of mitochondrial DNA.

    Science.gov (United States)

    Limongelli, Anna; Tiranti, Valeria

    2002-11-01

    The presence of mtDNA abnormalities inherited as Mendelian traits indicates the existence of mutations in nuclear genes affecting the integrity of the mitochondrial genome. Two groups of nucleus-driven abnormalities have been described: qualitative alterations of mtDNA, i.e. multiple large-scale deletions of mtDNA, and quantitative decrease of the mtDNA copy number, i.e. tissue-specific depletion of mtDNA. Autosomal dominant or recessive (adPEO), progressive ophthalmoplegia and autosomal-recessive mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), are three neurodegenerative disorders associated with the coexistence of wild-type mtDNA with several deletion-containing mtDNA species. Heterozygous mutations of the genes encoding the muscle-heart isoform of the adenosine diphosphate/adenosine triphosphate mitochondrial translocator (ANT1), the main subunit of polymerase gamma (POLG1), and of the putative mtDNA helicase (Twinkle) have been found in adPEO families linked to three different loci, on chromosomes 4q34-35, 10q24, and 15q25, respectively. Mutations in the gene encoding thymidine phosphorylase have been identified in several MNGIE patients. Severe, tissue-specific depletion of mtDNA is the molecular hallmark of rapidly progressive hepatopathies or myopathies of infancy and childhood. Two genes, deoxyguanosine kinase and thymidine kinase type 2, both involved in the mitochondrion-specific salvage pathways of deoxynucleotide pools, have been associated with depletion syndromes in selected families.

  16. Milk protein composition and stability changes affected by iron in water sources.

    Science.gov (United States)

    Wang, Aili; Duncan, Susan E; Knowlton, Katharine F; Ray, William K; Dietrich, Andrea M

    2016-06-01

    Water makes up more than 80% of the total weight of milk. However, the influence of water chemistry on the milk proteome has not been extensively studied. The objective was to evaluate interaction of water-sourced iron (low, medium, and high levels) on milk proteome and implications on milk oxidative state and mineral content. Protein composition, oxidative stability, and mineral composition of milk were investigated under conditions of iron ingestion through bovine drinking water (infused) as well as direct iron addition to commercial milk in 2 studies. Four ruminally cannulated cows each received aqueous infusions (based on water consumption of 100L) of 0, 2, 5, and 12.5mg/L Fe(2+) as ferrous lactate, resulting in doses of 0, 200, 500 or 1,250mg of Fe/d, in a 4×4Latin square design for a 14-d period. For comparison, ferrous sulfate solution was directly added into commercial retail milk at the same concentrations: control (0mg of Fe/L), low (2mg of Fe/L), medium (5mg of Fe/L), and high (12.5mg of Fe/L). Two-dimensional electrophoresis coupled with matrix-assisted laser desorption/ionization-tandem time-of-flight (MALDI-TOF/TOF) high-resolution tandem mass spectrometry analysis was applied to characterize milk protein composition. Oxidative stability of milk was evaluated by the thiobarbituric acid reactive substances (TBARS) assay for malondialdehyde, and mineral content was measured by inductively coupled plasma mass spectrometry. For milk from both abomasal infusion of ferrous lactate and direct addition of ferrous sulfate, an iron concentration as low as 2mg of Fe/L was able to cause oxidative stress in dairy cattle and infused milk, respectively. Abomasal infusion affected both caseins and whey proteins in the milk, whereas direct addition mainly influenced caseins. Although abomasal iron infusion did not significantly affect oxidation state and mineral balance (except iron), it induced oxidized off-flavor and partial degradation of whey proteins. Direct

  17. Factors affecting the fatty acid composition and fat oxidative stability in pigs

    Directory of Open Access Journals (Sweden)

    Karel Vehovsky

    2015-03-01

    Full Text Available The aim of the study was to evaluate the effect of selected factors affecting fatty acids (FA composition in pig fat. In the experiment, the influence of nutrition, gender, carcass weight, lean meat proportion (LMP and intramuscular fat (IMF were monitored. The effect of diet, specifically the influence of added linseed or corn on the fatty acids composition in the backfat was studied in pigs. From the perspective of the required increase of polyunsaturated fatty acids (PUFA only the addition of the linseed proved to have a significant effect. Another evaluated aspect concerning the FA spectrum was the gender. While the backfat in barrows showed higher (P≤0.05 amount of monounsaturated fatty acids (MUFA, the backfat in gilts displayed a significantly higher proportion (P≤0.01 of the PUFA and total unsaturated fatty acids (UFA. A significant effect on the PUFA proportion has also been demonstrated for the lean meat proportion (LMP parameter, which therefore represents not only a qualitative carcass meat parameter but also plays an important role in relation to the FA composition in the fat in pigs. In connection to the FA proportion changes the study also monitored the fat oxidative stability with the use of the TBARS method. Concerning the oxidative stability the effects of nutrition, FA groups, gender, carcass weight and LMP were studied. The relationship between the above mentioned factors and oxidative stability was found to be insignificant.

  18. Genetics Home Reference: Y chromosome infertility

    Science.gov (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 ...

  19. Quantitative trait locus affecting birth weight on bovine chromosome 5 in a F2 Gyr x Holstein population

    Directory of Open Access Journals (Sweden)

    Gustavo Gasparin

    2005-12-01

    Full Text Available Segregation between a genetic marker and a locus influencing a quantitative trait in a well delineated population is the basis for success in mapping quantitative trait loci (QTL. To detect bovine chromosome 5 (BTA5 birth weight QTL we genotyped 294 F2 Gyr (Bos indicus x Holstein (Bos taurus crossbreed cattle for five microsatellite markers. A linkage map was constructed for the markers and an interval analysis for the presence of QTL was performed. The linkage map indicated differences in the order of two markers relative to the reference map (http://www.marc.usda.gov. Interval analysis detected a QTL controlling birth weight (p < 0.01 at 69 centimorgans (cM from the most centromeric marker with an effect of 0.32 phenotypic standard-error. These results support other studies with crossbred Bos taurus x Bos indicus populations.

  20. Harvest date affects aronia juice polyphenols, sugars, and antioxidant activity, but not anthocyanin stability.

    Science.gov (United States)

    Bolling, Bradley W; Taheri, Rod; Pei, Ruisong; Kranz, Sarah; Yu, Mo; Durocher, Shelley N; Brand, Mark H

    2015-11-15

    The goal of this work was to characterize how the date of harvest of 'Viking' aronia berry impacts juice pigmentation, sugars, and antioxidant activity. Aronia juice anthocyanins doubled at the fifth week of the harvest, and then decreased. Juice hydroxycinnamic acids decreased 33% from the first week, while proanthocyanidins increased 64%. Juice fructose and glucose plateaued at the fourth week, but sorbitol increased 40% to the seventh harvest week. Aronia juice pigment density increased due to anthocyanin concentration, and polyphenol copigmentation did not significantly affect juice pigmentation. Anthocyanin stability at pH 4.5 was similar between weeks. However, addition of quercetin, sorbitol, and chlorogenic acid to aronia anthocyanins inhibited pH-induced loss of color. Sorbitol and citric acid may be partially responsible for weekly variation in antioxidant activity, as addition of these agents inhibited DPPH scavenging 13-30%. Thus, aronia polyphenol and non-polyphenol components contribute to its colorant and antioxidant functionality.

  1. Factors that Affect Social Stability of Rural Areas in Ganzi District

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Through the sample investigation of Kangding County, Daofu County, Luhuo County and Xiangcheng County in Sichuan Province in 2010 and by combining the quantitative and qualitative methods, various kinds of indexes from the aspects of society, politics, economy and values in Ganzi District are analyzed, as well as the factors that affect the rural social stability of current Ganzi District area. The results show that rural areas of Ganzi District are stable on the whole, but the economic development level is backward; the social security measures are imperfect; disputes among rural residents still exist and most of them are economic disputes; the disputes among ethnics are mainly caused by religious belief; the autonomous situation of partial rural residents are bad and rural residents’ evaluation on social justice is low. Therefore, it should establish and perfect relevant prevention and control mechanism.

  2. Homogenization conditions affect the oxidative stability of fish oil enriched milk emulsions: lipid oxidation.

    Science.gov (United States)

    Let, Mette B; Jacobsen, Charlotte; Sørensen, Ann-Dorit M; Meyer, Anne S

    2007-03-07

    In this study fish oil was incorporated into commercial homogenized milk using different homogenization temperatures and pressures. The main aim was to understand the significance of homogenization temperature and pressure on the oxidative stability of the resulting milks. Increasing homogenization temperature from 50 to 72 degrees C decreased droplet size only slightly, whereas a pressure increase from 5 to 22.5 MPa decreased droplet size significantly. Surprisingly, emulsions having small droplets, and therefore large interfacial area, were less oxidized than emulsions having bigger droplets. Emulsions with similar droplet size distributions, but resulting from different homogenization conditions, had significantly different oxidative stabilities, indicating that properties of significance to oxidation other than droplet size itself were affected by the different treatments. In general, homogenization at 72 degrees C appeared to induce protective effects against oxidation as compared to homogenization at 50 degrees C. The results thus indicated that the actual composition of the oil-water interface is more important than total surface area itself.

  3. Plant species richness and functional traits affect community stability after a flood event.

    Science.gov (United States)

    Fischer, Felícia M; Wright, Alexandra J; Eisenhauer, Nico; Ebeling, Anne; Roscher, Christiane; Wagg, Cameron; Weigelt, Alexandra; Weisser, Wolfgang W; Pillar, Valério D

    2016-05-19

    Climate change is expected to increase the frequency and magnitude of extreme weather events. It is therefore of major importance to identify the community attributes that confer stability in ecological communities during such events. In June 2013, a flood event affected a plant diversity experiment in Central Europe (Jena, Germany). We assessed the effects of plant species richness, functional diversity, flooding intensity and community means of functional traits on different measures of stability (resistance, resilience and raw biomass changes from pre-flood conditions). Surprisingly, plant species richness reduced community resistance in response to the flood. This was mostly because more diverse communities grew more immediately following the flood. Raw biomass increased over the previous year; this resulted in decreased absolute value measures of resistance. There was no clear response pattern for resilience. We found that functional traits drove these changes in raw biomass: communities with a high proportion of late-season, short-statured plants with dense, shallow roots and small leaves grew more following the flood. Late-growing species probably avoided the flood, whereas greater root length density might have allowed species to better access soil resources brought from the flood, thus growing more in the aftermath. We conclude that resource inputs following mild floods may favour the importance of traits related to resource acquisition and be less associated with flooding tolerance.

  4. Periodic Tail Motion Linked to Wing Motion Affects the Longitudinal Stability of Ornithopter Flight

    Institute of Scientific and Technical Information of China (English)

    Jun-seong Lee; Joong-kwan Kim; Jae-hung Han; Charles P. Ellington

    2012-01-01

    During slow level flight of a pigeon,a caudal muscle involved in tail movement,the levator caudae pars vertebralis,is activated at a particular phase with the pectoralis wing muscle.Inspired by mechanisms for the control of stability in flying animals,especially the role of the tail in avian flight,we investigated how periodic tail motion linked to motion of the wings affects the longitudinal stability of omithopter flight.This was achieved by using an integrative ornithopter flight simulator that included aeroelastic behaviour of the flexible wings and tail.Trim flight trajectories of the simulated ornithopter model were calculated by time integration of the nonlinear equations of a flexible multi-body dynamics coupled with a semi-empirical flapping-wing and tail aerodynamic models.The unique trim flight characteristics of ornithopter,Limit-Cycle Oscillation,were found under the sets of wingbeat frequency and tail elevation angle,and the appropriate phase angle of tail motion was determined by parameter studies minimizing the amplitude of the oscillations.The numerical simulation results show that tail actuation synchronized with wing motion suppresses the oscillation of body pitch angle over a wide range of wingbeat frequencies.

  5. Phosphorylation of Sli15 by Ipl1 is important for proper CPC localization and chromosome stability in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Vasso Makrantoni

    Full Text Available The chromosomal passenger complex (CPC is a key regulator of eukaryotic cell division, consisting of the protein kinase Aurora B/Ipl1 in association with its activator (INCENP/Sli15 and two additional proteins (Survivin/Bir1 and Borealin/Nbl1. Here we have identified multiple sites of CPC autophosphorylation on yeast Sli15 that are located within its central microtubule-binding domain and examined the functional significance of their phosphorylation by Ipl1 through mutation of these sites, either to non-phosphorylatable alanine (sli15-20A or to acidic residues to mimic constitutive phosphorylation (sli15-20D. Both mutant sli15 alleles confer chromosome instability, but this is mediated neither by changes in the capacity of Sli15 to activate Ipl1 kinase nor by decreased efficiency of chromosome biorientation, a key process in cell division that requires CPC function. Instead, we find that mimicking constitutive phosphorylation of Sli15 on the Ipl1 phosphorylation sites causes delocalization of the CPC in metaphase, whereas blocking phosphorylation of Sli15 on the Ipl1 sites drives excessive localization of Sli15 to the mitotic spindle in pre-anaphase cells. Consistent with these results, direct interaction of Sli15 with microtubules in vitro is greatly reduced either following phosphorylation by Ipl1 or when constitutive phosphorylation at the Ipl1-dependent phosphorylation sites is mimicked by aspartate or glutamate substitutions. Furthermore, we find that mimicking Ipl1 phosphorylation of Sli15 interferes with the 'tension checkpoint'--the CPC-dependent mechanism through which cells activate the spindle assembly checkpoint to delay anaphase in the absence of tension on kinetochore-microtubule attachments. Ipl1-dependent phosphorylation of Sli15 therefore inhibits its association with microtubules both in vivo and in vitro and may negatively regulate the tension checkpoint mechanism.

  6. Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis.

    Directory of Open Access Journals (Sweden)

    Laetitia Martinerie

    2014-02-01

    Full Text Available Loss of function of cyclin E1 or E2, important regulators of the mitotic cell cycle, yields viable mice, but E2-deficient males display reduced fertility. To elucidate the role of E-type cyclins during spermatogenesis, we characterized their expression patterns and produced additional deletions of Ccne1 and Ccne2 alleles in the germline, revealing unexpected meiotic functions. While Ccne2 mRNA and protein are abundantly expressed in spermatocytes, Ccne1 mRNA is present but its protein is detected only at low levels. However, abundant levels of cyclin E1 protein are detected in spermatocytes deficient in cyclin E2 protein. Additional depletion of E-type cyclins in the germline resulted in increasingly enhanced spermatogenic abnormalities and corresponding decreased fertility and loss of germ cells by apoptosis. Profound meiotic defects were observed in spermatocytes, including abnormal pairing and synapsis of homologous chromosomes, heterologous chromosome associations, unrepaired double-strand DNA breaks, disruptions in telomeric structure and defects in cyclin-dependent-kinase 2 localization. These results highlight a new role for E-type cyclins as important regulators of male meiosis.

  7. Over-expression of a human chromosome 22q11.2 segment including TXNRD2, COMT and ARVCF developmentally affects incentive learning and working memory in mice.

    Science.gov (United States)

    Suzuki, Go; Harper, Kathryn M; Hiramoto, Takeshi; Funke, Birgit; Lee, MoonSook; Kang, Gina; Buell, Mahalah; Geyer, Mark A; Kucherlapati, Raju; Morrow, Bernice; Männistö, Pekka T; Agatsuma, Soh; Hiroi, Noboru

    2009-10-15

    Duplication of human chromosome 22q11.2 is associated with elevated rates of mental retardation, autism and many other behavioral phenotypes. However, because duplications cover 1.5-6 Mb, the precise manner in which segments of 22q11.2 causally affect behavior is not known in humans. We have now determined the developmental impact of over-expression of an approximately 190 kb segment of human 22q11.2, which includes the genes TXNRD2, COMT and ARVCF, on behaviors in bacterial artificial chromosome (BAC) transgenic (TG) mice. BAC TG mice and wild-type (WT) mice were tested for their cognitive capacities, affect- and stress-related behaviors and motor activity at 1 and 2 months of age. An enzymatic assay determined the impact of BAC over-expression on the activity level of COMT. BAC TG mice approached a rewarded goal faster (i.e. incentive learning), but were impaired in delayed rewarded alternation during development. In contrast, BAC TG and WT mice were indistinguishable in rewarded alternation without delays, spontaneous alternation, prepulse inhibition, social interaction, anxiety-, stress- and fear-related behaviors and motor activity. Compared with WT mice, BAC TG mice had an approximately 2-fold higher level of COMT activity in the prefrontal cortex, striatum and hippocampus. These data suggest that over-expression of this 22q11.2 segment enhances incentive learning and impairs the prolonged maintenance of working memory, but has no apparent effect on working memory per se, affect- and stress-related behaviors or motor capacity. High copy numbers of this 22q11.2 segment might contribute to a highly selective set of phenotypes in learning and cognition during development.

  8. A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

    Directory of Open Access Journals (Sweden)

    Cigudosa Juan C

    2011-05-01

    Full Text Available Abstract Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs, will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents. With the extension of this analysis to an Array-CGH dataset (glioblastomas from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.

  9. The Stability of G6PD Is Affected by Mutations with Different Clinical Phenotypes

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2014-11-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzyme deficiency worldwide, causing a wide spectrum of conditions with severity classified from the mildest (Class IV to the most severe (Class I. To correlate mutation sites in the G6PD with the resulting phenotypes, we studied four naturally occurring G6PD variants: Yucatan, Nashville, Valladolid and Mexico City. For this purpose, we developed a successful over-expression method that constitutes an easier and more precise method for obtaining and characterizing these enzymes. The kcat (catalytic constant of all the studied variants was lower than in the wild-type. The structural rigidity might be the cause and the most evident consequence of the mutations is their impact on protein stability and folding, as can be observed from the protein yield, the T50 (temperature where 50% of its original activity is retained values, and differences on hydrophobic regions. The mutations corresponding to more severe phenotypes are related to the structural NADP+ region. This was clearly observed for the Classes III and II variants, which became more thermostable with increasing NADP+, whereas the Class I variants remained thermolabile. The mutations produce repulsive electric charges that, in the case of the Yucatan variant, promote increased disorder of the C-terminus and consequently affect the binding of NADP+, leading to enzyme instability.

  10. Stability of Anthocyanins from Rubus glaucus and Solanum betaceum as affected by Temperature and Water Activity

    Directory of Open Access Journals (Sweden)

    Garzon Monroy Gloria Astrid

    2009-12-01

    Full Text Available The stability of sprayed-dried microencapsulated anthocyanins from Andes berry (Rubus glaucus and Tamarillo (Solanum betaceum, as affected by storage time, water activity (Aw and temperature was compared. The fruits were osmotically dehydrated with ethanol and the anthocyanin extract was microencapsulated with maltodextrin DE 20 by spray drying. Half life of the anthocyanins; changes in color, total phenolics, and antioxidant activity of the powders, were analyzed during storage at two different temperatures (25 °C and 40 °C and two Aw levels (0.20 and 0.35. A decrease in monomeric anthocyanin was observed in both samples. The half life of the Andes berry pigments ranged between 11 and 32 days while the half life of the tamarillo pigments ranged between 9 and 21 days. A darkening effect occurred in both samples as a result of storage time.  The antioxidant activity decreased while the phenolic content increased with time. Antioxidant activity of Andes berry samples was highly correlated with anthocyanin content and total phenolic content while the antioxidant activity of tamarillo samples was highly correlated with total phenolic content. These results would be useful in developing applications for spray-dried anthocyanin as powdered food-grade colorants.

  11. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    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.

  12. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders

    Directory of Open Access Journals (Sweden)

    Baohu Ji

    2015-08-01

    Research in context: Due to lack of biological markers, diagnosis and treatment of psychiatric disorders are subjective. There is utmost urgency to identify biomarkers for clinics, research, and drug development. We found that XIST and KDM5C gene expression may be used as a biological marker for diagnosis of major affective disorders in a significantly large subset of female patients from the general population. Our studies show that over-expression of XIST and some X-linked escapee genes may be a common mechanism for development of psychiatric disorders between the patients with rare genetic diseases (XXY or XXX and the general population of female psychiatric patients.

  13. A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

    Energy Technology Data Exchange (ETDEWEB)

    Gill, M.; Vallada, H.; Collier, D. [Institute of Psychiatry, London (United Kingdom)] [and others

    1996-02-16

    Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not shared (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that there may be a susceptibility locus for schizophrenia at 22q12. 27 refs., 3 tabs.

  14. 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.;

    2014-01-01

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

  15. A new powerful method for site-specific transgene stabilization based on chromosomal double-strand break repair.

    Directory of Open Access Journals (Sweden)

    Artem Tkachuk

    Full Text Available Transgenic insects are a promising tool in sterile insect techniques and population replacement strategies. Such transgenic insects can be created using nonautonomous transposons, which cannot be transferred without a transposase source. In biocontrol procedures where large numbers of insects are released, there is increased risk of transgene remobilization caused by external transposase sources that can alter the characteristics of the transgenic organisms lead horizontal transgene transfer to other species. Here we describe a novel, effective method for transgene stabilization based on the introduction of directed double-strand breaks (DSB into a genome-integrated sequence and their subsequent repair by the single-strand annealing (SSA pathway. Due to the construct's organization, the repair pathway is predictable, such that all transposon and marker sequences can be deleted, while preserving integration of exogenous DNA in the genome. The exceptional conservation of DNA repair pathways makes this method suitable for a broad range of organisms.

  16. A New Powerful Method for Site-Specific Transgene Stabilization Based on Chromosomal Double-Strand Break Repair

    Science.gov (United States)

    Kravchuk, Oksana; Savitsky, Mikhail

    2011-01-01

    Transgenic insects are a promising tool in sterile insect techniques and population replacement strategies. Such transgenic insects can be created using nonautonomous transposons, which cannot be transferred without a transposase source. In biocontrol procedures where large numbers of insects are released, there is increased risk of transgene remobilization caused by external transposase sources that can alter the characteristics of the transgenic organisms lead horizontal transgene transfer to other species. Here we describe a novel, effective method for transgene stabilization based on the introduction of directed double-strand breaks (DSB) into a genome-integrated sequence and their subsequent repair by the single-strand annealing (SSA) pathway. Due to the construct's organization, the repair pathway is predictable, such that all transposon and marker sequences can be deleted, while preserving integration of exogenous DNA in the genome. The exceptional conservation of DNA repair pathways makes this method suitable for a broad range of organisms. PMID:22022613

  17. Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations.

    Directory of Open Access Journals (Sweden)

    Miguel R Branco

    2006-05-01

    Full Text Available After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.

  18. Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers.

    Science.gov (United States)

    Dopp, E; Schuler, M; Schiffmann, D; Eastmond, D A

    1997-06-09

    This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chrysotile and crocidolite asbestos, and ceramic fibers. The response of human (amniotic fluid cells) and rodent (Syrian hamster embryo fibroblasts, SHE) cells to fiber treatment was compared using the micronucleus assay. The data of the rodent studies were taken from a previous investigation (Dopp, E. et al. (1995) Environ. Health Perspect., 103, 268-271). All types of mineral fibers caused a significant increase of micronucleated cells. The kinetochore analysis revealed that all three types of asbestos and ceramic fibers yielded similar effects. Approximately 50% of the induced micronuclei were kinetochore-negative indicating formation through clastogenic events. Human amniotic cells were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. This again demonstrates that SHE cells are more susceptible to chromosomal changes than human amniotic fluid cells. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed information about specific structural chromosome aberrations in the 1 (cen-q12) and 9 (cen-q12) regions and about abnormal numbers of chromosomes in interphase human amniotic fluid cells. Using this FISH approach we found a statistically significant increase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in interphase human amniotic cells after exposure to asbestos and ceramic fibers compared to control cells. The number of hyperdiploid cells was also significantly increased. Our results show that asbestos fibers as well as ceramic fibers are inducers of structural and numerical chromosomal aberrations in human amniotic fluid cells.

  19. Denaturation and Oxidative Stability of Hemp Seed (Cannabis sativa L.) Protein Isolate as Affected by Heat Treatment.

    Science.gov (United States)

    Raikos, Vassilios; Duthie, Garry; Ranawana, Viren

    2015-09-01

    The present study investigated the impact of heat treatments on the denaturation and oxidative stability of hemp seed protein during simulated gastrointestinal digestion (GID). Heat-denatured hemp protein isolate (HPI) solutions were prepared by heating HPI (2 mg/ml, pH 6.8) to 40, 60, 80 and 100 °C for 10 min. Heat-induced denaturation of the protein isolates was monitored by polyacrylamide gel electrophoresis. Heating HPI at temperatures above 80 °C significantly reduced solubility and led to the formation of large protein aggregates. The isolates were then subjected to in vitro GID and the oxidative stability of the generated peptides was investigated. Heating did not significantly affect the formation of oxidation products during GID. The results suggest that heat treatments should ideally remain below 80 °C if heat stability and solubility of HPI are to be preserved.

  20. The use of “stabilization exercises” to affect neuromuscular control in the lumbopelvic region: a narrative review

    Science.gov (United States)

    Bruno, Paul

    2014-01-01

    It is well-established that the coordination of muscular activity in the lumbopelvic region is vital to the generation of mechanical spinal stability. Several models illustrating mechanisms by which dysfunctional neuromuscular control strategies may serve as a cause and/or effect of low back pain have been described in the literature. The term “core stability” is variously used by clinicians and researchers, and this variety has led to several rehabilitative approaches suggested to affect the neuromuscular control strategies of the lumbopelvic region (e.g. “stabilization exercise”, “motor control exercise”). This narrative review will highlight: 1) the ongoing debate in the clinical and research communities regarding the terms “core stability” and “stabilization exercise”, 2) the importance of sub-grouping in identifying those patients most likely to benefit from such therapeutic interventions, and 3) two protocols that can assist clinicians in this process. PMID:24932016

  1. Chemical expansion affected oxygen vacancy stability in different oxide structures from first principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Aidhy, Dilpuneet S.; Liu, Bin; Zhang, Yanwen; Weber, William J.

    2015-03-01

    We study the chemical expansion for neutral and charged oxygen vacancies in fluorite, rocksalt, perovskite and pyrochlores materials using first principles calculations. We show that the neutral oxygen vacancy leads to lattice expansion whereas the charged vacancy leads to lattice contraction. In addition, we show that there is a window of strain within which an oxygen vacancy is stable; beyond that range, the vacancy can become unstable. Using CeO2|ZrO2 interface structure as an example, we show that the concentration of oxygen vacancies can be manipulated via strain, and the vacancies can be preferentially stabilized. These results could serve as guiding principles in predicting oxygen vacancy stability in strained systems and in the design of vacancy stabilized materials.

  2. Homogenization Pressure and Temperature Affect Protein Partitioning and Oxidative Stability of Emulsions

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Barouh, Nathalie; Nielsen, Nina Skall;

    2013-01-01

    The oxidative stability of 10 % fish oil-in-water emulsions was investigated for emulsions prepared under different homogenization conditions. Homogenization was conducted at two different pressures (5 or 22.5 MPa), and at two different temperatures (22 and 72 °C). Milk proteins were used...... it decreased the oxidative stability of emulsions with α-lactalbumin and β-lactoglobulin. For both types of emulsions the partitioning of proteins between the interface and the aqueous phase appeared to be important for the oxidative stability. The effect of pre-heating the aqueous phase with the milk proteins...... prior to homogenization did not have any clear effect on lipid oxidation in either of the two types of emulsions....

  3. Formation and Water Stability of Aggregates in Red Soils as Affected by Organic Matter

    Institute of Scientific and Technical Information of China (English)

    ZHANGMINGKUI等; M.J.WILSON; 等

    1996-01-01

    The water stability of aggregates in various size classes separated from 18 samples of red soils under different managements,and the mechanisms responsible for the formation of waer-stable soil aggregates were studied.The results showed that the water stbility of soil aggregates declined with increasing size,especially for the low organic matter soils.Organic matter plays a key role in the formation of water-stable soil aggregates.The larger the soil aggregate size.the greater the impact of organic matter on the water stability of soil aggregates.Removal of organic matter markedly disintegrated the large water-stable aggregates(>2.0mm)and increased the small ones(2.0mm)were mainly glued up by organic mater,Both free oxides and organic matter contribute to the formation and water stability of aggregates in red soils.

  4. Stability and heavy metal distribution of soil aggregates affected by application of apatite, lime, and charcoal.

    Science.gov (United States)

    Cui, Hongbiao; Ma, Kaiqiang; Fan, Yuchao; Peng, Xinhua; Mao, Jingdong; Zhou, Dongmei; Zhang, Zhongbin; Zhou, Jing

    2016-06-01

    Only a few studies have been reported on the stability and heavy metal distribution of soil aggregates after soil treatments to reduce the availability of heavy metals. In this study, apatite (22.3 t ha(-1)), lime (4.45 t ha(-1)), and charcoal (66.8 t ha(-1)) were applied to a heavy metal-contaminated soil for 4 years. The stability and heavy metal distribution of soil aggregates were investigated by dry and wet sieving. No significant change in the dry mean weight diameter was observed in any treatments. Compared with the control, three-amendment treatments significantly increased the wet mean weight diameter, but only charcoal treatment significantly increased the wet aggregate stability. The soil treatments increased the content of soil organic carbon, and the fraction 0.25-2 mm contained the highest content of soil organic carbon. Amendments' application slightly increased soil total Cu and Cd, but decreased the concentrations of CaCl2 -extractable Cu and Cd except for the fraction 2 and 0.25-2 mm contained the highest concentrations of CaCl2-extractable Cu and Cd, accounted for about 74.5-86.8 % of CaCl2-extractable Cu and Cd in soil. The results indicated that amendments' application increased the wet soil aggregate stability and decreased the available Cu and Cd. The distribution of available heavy metals in wet soil aggregates was not controlled by soil aggregate stability, but possibly by soil organic carbon.

  5. Sublethal concentrations of silver nanoparticles affect the mechanical stability of biofilms.

    Science.gov (United States)

    Grün, Alexandra Y; Meier, Jutta; Metreveli, George; Schaumann, Gabriele E; Manz, Werner

    2016-12-01

    Bacterial biofilms are most likely confronted with silver nanoparticles (Ag NPs) as a pollutant stressor in aquatic systems. In this study, biofilms of Aquabacterium citratiphilum were exposed for 20 h to 30 and 70 nm citrate stabilized Ag NPs in low-dose concentrations ranging from 600 to 2400 μg l(-1), and the Ag NP-mediated effects on descriptive, structural, and functional biofilm characteristics, including viability, protein content, architecture, and mechanical stability, were investigated. Viability, based on the bacterial cell membrane integrity of A. citratiphilum, as determined by epifluorescence microscopy, remained unaffected after Ag NP exposure. Moreover, in contrast to information in the current literature, protein contents of cells and extracellular polymeric substances (EPS) and biofilm architecture, including dry mass, thickness, and density, were not significantly impacted by exposure to Ag NPs. However, the biofilms themselves served as effective sinks for Ag NPs, exhibiting enrichment factors from 5 to 8. Biofilms showed a greater capacity to accumulate 30 nm sized Ag NPs than 70 nm Ag NPs. Furthermore, Ag NPs significantly threatened the mechanical stability of biofilms, as determined by a newly developed assay. For 30 nm Ag NPs, the mechanical stability of biofilms decreased as the Ag NP concentrations applied to them increased. In contrast, 70 nm Ag NPs produced a similar decrease in mechanical stability for each applied concentration. Overall, this finding demonstrates that exposure to Ag NPs triggers remarkable changes in biofilm adhesion and/or cohesiveness. Because of biofilm-mediated ecological services, this response raises environmental concerns regarding Ag NP release into freshwater systems, even in sublethal concentrations.

  6. Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

    2013-01-01

    Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

  7. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

    Science.gov (United States)

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli; Liu, Jianping

    2016-09-01

    Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10-100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer-polymer and polymer-cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.

  8. Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase.

    Directory of Open Access Journals (Sweden)

    Amanda J Cork

    Full Text Available Group A Streptococcus (GAS is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen. Streptococcal surface enolase (SEN is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SENK312A and SENK362A is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen to its binding sites, leading to more efficient plasmin(ogen binding and activation.

  9. Stabilization/solidification of heavy metals in sludge ceramsite and leachability affected by oxide substances.

    Science.gov (United States)

    Xu, Guoren; Zou, Jinlong; Li, Guibai

    2009-08-01

    To investigate stabilization of heavy metals in ceramsite made from wastewater treatment sludge (WWTS) and drinking water treatment sludge (DWTS), leaching tests were conducted to find out the effect of SiO2:Al2O3, acidic oxides (SiO2 and Al2O3), Fe2O3: CaO:MgO, and basic oxides (Fe2O3, CaO, and MgO) on the binding ability of heavy metals. Results show that as ratios of SiO2: Al2O3 decrease, leaching contents of Cu and Pb increase, while leaching contents of Cd and Cr first decrease and then increase; under the variation of Fe2O3:CaO:MgO (Fe2O3 contents decrease), leaching contents of Cd, Cu, and Pb increase, while leaching contents of Cr decrease. Acidic and basic oxide leaching results show that higher contents of Al2O3, Fe2O3, and MgO are advantageous to improve the stability of heavy metals, while the binding capacity for Cd, Cu, and Pb is significantly reduced at higher contents of SiO2 and CaO. The solidifying efficiencies of heavy metals are improved by crystallization, and the main compounds in ceramsite are crocoite, chrome oxide, cadmium silicate, and copper oxide. These results can be considered as a basic understanding for new technologies of stabilization of heavy metals in heavily polluted WWTS.

  10. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.

    Science.gov (United States)

    Ogata, Tsutomu; Kagami, Masayo

    2016-02-01

    Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications.

  11. Stability of the Stevia-Derived Sweetener Rebaudioside A in Solution as Affected by Ultraviolet Light Exposure.

    Science.gov (United States)

    Zhang, Jiewen; Bell, Leonard N

    2017-02-20

    Rebaudioside A is a natural noncaloric high-potency sweetener extracted from the leaves of Stevia rebaudiana. With rebaudioside A use increasing in foods, understanding the factors affecting its stability is necessary. This project evaluated the degradation rate constants of rebaudioside A in water, 0.1 M phosphate buffer, and 0.1 M citrate buffer at pH 3 and 7 as a function of ultraviolet (UV) light intensity (365 nm, 0 μW/cm(2) for dark conditions, 27 μW/cm(2) for low intensity, and 190 μW/cm(2) for high intensity) at 32.5 °C. Rebaudioside A stability was adversely affected by light exposure. The pseudo-1st-order degradation rate constants increased significantly (P exposure to UV light resulted in rebaudioside A degradation occurring approximately 10 times faster in citrate than in phosphate buffers at both pH levels. The sensitivity of rebaudioside A to UV light was greater in citrate buffers than in water or phosphate buffers. The use of light-protective packaging for beverages containing rebaudioside A will improve its stability.

  12. Phytochemical stability in dried tomato pulp and peel as affected by moisture properties.

    Science.gov (United States)

    Lavelli, Vera; Kerr, William; Sri Harsha, P S C

    2013-01-23

    Phytochemical stability was studied in dried tomato pulp and dried tomato peel stored at 30 °C with various water activity (a(w)) levels and related to glass transition temperature (T(g)) and water mobility. At a(w) 30 °C for both the pulp and peel, indicating that they were in the glassy state, with little molecular mobility. At a(w) = 0.56, T(g) was lycopene and α-tocopherol were mostly unstable for samples in the glassy state. These results could be used to optimize phytochemical contents in tomato products that must be dried prior to further processing.

  13. Factors affecting the thermal shock behavior of yttria stabilized hafnia based graphite and tungsten composites.

    Science.gov (United States)

    Lineback, L. D.; Manning, C. R.

    1971-01-01

    Hafnia-based composites containing either graphite or tungsten were investigated as rocket nozzle throat inserts in solid propellant rocket engines. The thermal shock resistance of these materials is considered in terms of macroscopic thermal conductivity, thermal expansion, modulus of elasticity, and compressive fracture stress. The effect of degree of hafnia stabilization, density, and graphite or tungsten content upon these parameters is discussed. The variation of the ratio of elastic modulus to compressive fracture stress with density and its effect upon thermal shock resistance of these materials are discussed in detail.

  14. Modeling Chromosomes

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    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…

  15. Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity

    Science.gov (United States)

    DeFeo, Christopher J.; Alvarado-Facundo, Esmeralda; Vassell, Russell

    2015-01-01

    ABSTRACT Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well

  16. Redefining a Bizarre Situation: Relative Concept Stability in Affect Control Theory

    Science.gov (United States)

    Nelson, Steven M.

    2006-01-01

    I analyze the process by which we react cognitively to information that contradicts our culturally held sentiments in the context of affect control theory. When bizarre, unanticipated events come to our attention and we have no opportunity to act so as to alter them, we must reidentify at least one event component: the actor, the behavior, or the…

  17. Dissecting the Factors Affecting the Fluorescence Stability of Quantum Dots in Live Cells.

    Science.gov (United States)

    Wang, Zhi-Gang; Liu, Shu-Lin; Hu, Yuan-Jun; Tian, Zhi-Quan; Hu, Bin; Zhang, Zhi-Ling; Pang, Dai-Wen

    2016-04-06

    Labeling and imaging of live cells with quantum dots (QDs) has attracted great attention in the biomedical field over the past two decades. Maintenance of the fluorescence of QDs in a biological environment is crucial for performing long-term cell tracking to investigate the proliferation and functional evolution of cells. The cell-penetrating peptide transactivator of transcription (TAT) is a well-studied peptide to efficiently enhance the transmembrane delivery. Here, we used TAT peptide-conjugated QDs (TAT-QDs) as a model system to examine the fluorescence stability of QDs in live cells. By confocal microscopy, we found that TAT-QDs were internalized into cells by endocytosis, and transported into the cytoplasm via the mitochondria, Golgi apparatus, and lysosomes. More importantly, the fluorescence of TAT-QDs in live cells was decreased mainly by cell proliferation, and the low pH value in the lysosomes could also lower the fluorescence intensity of intracellular QDs. Quantitative analysis of the amount of QDs in the extracellular region and whole cells indicated that the exocytosis was not the primary cause of fluorescence decay of intracellular QDs. This work facilitates a better understanding of the fluorescence stability of QDs for cell imaging and long-term tracking in live cells. Also, it provides insights into the utility of TAT for transmembrane transportation, and the preparation and modification of QDs for cell imaging and tracking.

  18. Heat stability and acid gelation properties of calcium-enriched reconstituted skim milk affected by ultrasonication.

    Science.gov (United States)

    Chandrapala, Jayani; Bui, Don; Kentish, Sandra; Ashokkumar, Muthupandian

    2014-05-01

    The aggregation of proteins after heating of calcium-fortified milks has been an ongoing problem in the dairy industry. This undesirable effect restricts the manufacture of calcium rich dairy products. To overcome this problem, a completely new approach in controlling the heat stability of dairy protein solutions, developed in our lab, has been employed. In this approach, high intensity, low frequency ultrasound is applied for a very short duration after a pre-heating step at ⩾70 °C. The ultrasound breaks apart whey/whey and whey/casein aggregates through the process of acoustic cavitation. Protein aggregates do not reform on subsequent post-heating, thereby making the systems heat stable. In this paper, the acid gelation properties of ultrasonicated calcium-enriched skim milks have also been investigated. It is shown that ultrasonication alone does not change the gelation properties significantly whereas a sequence of preheating (72 °C/1 min) followed by ultrasonication leads to decreased gelation times, decreased gel syneresis and increased skim milk viscosity in comparison to heating alone. Overall, ultrasonication has the potential to provide calcium-fortified dairy products with increased heat stability. However, enhanced gelation properties can only be achieved when ultrasonication is completed in conjunction with heating.

  19. Oxidative stability of soybean oil in oleosomes as affected by pH and iron.

    Science.gov (United States)

    Kapchie, Virginie N; Yao, Linxing; Hauck, Catherine C; Wang, Tong; Murphy, Patricia A

    2013-12-01

    The oxidative stability of oil in soybean oleosomes, isolated using the Enzyme-Assisted Aqueous Extraction Process (EAEP), was evaluated. The effects of ferric chloride, at two concentration levels (100 and 500 μM), on lipid oxidation, was examined under pH 2 and 7. The peroxide value (PV) and thiobarbituric acid-reactive substance (TBARS) value of oil, in oleosome suspensions stored at 60 °C, were measured over a 12 day period. The presence of ferric chloride significantly (Poil in the isolated oleosome, as measured by the PV and TBARS. Greater lipid oxidation occurred under an acidic pH. In the pH 7 samples, the positively charged transition metals were strongly attracted to the negatively charged droplets. However, the low ζ-potential and the high creaming rate at this pH, may have limited the oxidation. Freezing, freeze-drying or heating of oleosomes have an insignificant impact on the oxidative stability of oil in isolated soybean oleosomes. Manufacturers should be cautious when adding oleosomes as ingredients in food systems containing transition metal ions.

  20. Stability of micronutrients and phytochemicals of grapefruit jam as affected by the obtention process.

    Science.gov (United States)

    Igual, M; García-Martínez, E; Camacho, M M; Martínez-Navarrete, N

    2016-04-01

    Fruits are widely revered for their micronutrient properties. They serve as a primary source of vitamins and minerals as well as of natural phytonutrients with antioxidant properties. Jam constitutes an interesting way to preserve fruit. Traditionally, this product is obtained by intense heat treatment that may cause irreversible loss of these bioactive compounds responsible for the health-related properties of fruits. In this work, different grapefruit jams obtained by conventional, osmotic dehydration (OD) without thermal treatment and/or microwave (MW) techniques were compared in terms of their vitamin, organic acid and phytochemical content and their stability through three months of storage. If compared with heating, osmotic treatments lead to a greater loss of organic acids and vitamin C during both processing and storage. MW treatments permit jam to be obtained which has a similar nutritional and functional value than that obtained when using a conventional heating method, but in a much shorter time.

  1. Factors Affecting the Stability of Crude and Transmission Oil Emulsion Swith Surfactant Solutions

    Directory of Open Access Journals (Sweden)

    Erich Martínez Martín

    2016-04-01

    Full Text Available Crude oil emulsions with surfactant solutions are used to transport this for piping systems. The applicationof this technique requires that the emulsions remain stable during the pumping period and haveseparated after transporting the crude. In this paper, experimental assays were performed using differentconcentrations of surfactant, and mixing types settling conditions. They were employed as the continuousphase two substances: oil transmission and Cuban crude oil. The strong infl uence of the concentrationand type of mixing on the stability of the emulsions was observed. The results demonstrate the similaritiesin thermalhydraulic fl uid parameters objects of study. Allowing infer the approximate behavior of theCuban crude oil from experimental work with transmission oil.

  2. The actinobacterial signature protein ParJ (SCO1662) regulates ParA polymerization and affects chromosome segregation and cell division during Streptomyces sporulation.

    Science.gov (United States)

    Ditkowski, Bartosz; Troć, Paulina; Ginda, Katarzyna; Donczew, Magdalena; Chater, Keith F; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara

    2010-12-01

    Bacterial chromosome segregation usually involves cytoskeletal ParA proteins, ATPases which can form dynamic filaments. In aerial hyphae of the mycelial bacterium Streptomyces coelicolor, ParA filaments extend over tens of microns and are responsible for segregation of dozens of chromosomes. We have identified a novel interaction partner of S. coelicolor ParA, ParJ. ParJ negatively regulates ParA polymerization in vitro and is important for efficient chromosome segregation in sporulating aerial hyphae. ParJ-EGFP formed foci along aerial hyphae even in the absence of ParA. ParJ, which is encoded by sco1662, turned out to be one of the five actinobacterial signature proteins, and another of the five is a ParJ paralogue. We hypothesize that polar growth, which is characteristic not only of streptomycetes, but even of simple Actinobacteria, may be interlinked with ParA polymer assembly and its specific regulation by ParJ.

  3. A CSTR-hollow-fiber system for continuous hydrolysis of proteins. Factors affecting long-term stability of the reactor.

    Science.gov (United States)

    Deeslie, W D; Cheryan, M

    1982-01-01

    Factors affecting the long-term operational stability of a CSTR-hollow-fiber reactor for continuous hydrolysis of proteins were studied. The activity declined in a stepwise manner during a run. Declining from 92% conversion to 60% conversion in about ten hours at a space time of four minutes. Initial decay appears to be due to leakage of small active fragments of the enzyme mixture (Pronase) through the membrane, and later decay due to thermal degradation and loss of activators such as calcium through the membrane. The rate of buildup of unconverted substrate in the reaction vessel was controlled by operational variables, but did not appear to affect the reactor output or the operation of the reactor. The decay of the reactor could be partially compensated for by appropriate manipulation of the space-time variables.

  4. To what extent clay mineralogy affects soil aggregation? Consequences for soil organic matter stabilization

    Science.gov (United States)

    Fernandez-Ugalde, O.; Barré, P.; Hubert, F.; Virto, I.; Chenu, C.; Ferrage, E.; Caner, L.

    2012-12-01

    Aggregation is a key process for soil functioning as it influences C storage, vulnerability to erosion and water holding capacity. While the influence of soil organic C on aggregation has been documented, much less is known about the role of soil mineralogy. Soils usually contain a mixture of clay minerals with contrasted surface properties, which should result on different abilities of clay minerals to aggregation. We took advantage of the intrinsic mineral heterogeneity of a temperate Luvisol to compare the role of clay minerals (illite, smectite, kaolinite, and mixed-layer illite-smectite) in aggregation. In a first step, grassland and tilled soil samples were fractionated in water in aggregate-size classes according to the hierarchical model of aggregation (Tisdall and Oades, 1982). Clay mineralogy and organic C in the aggregate-size classes were analyzed. The results showed that interstratified minerals containing swelling phases accumulated in aggregated fractions (>2 μm) compared to free clay fractions (500 μm) to micro-aggregates (50-250 μm). C concentration and C/N ratio followed the opposite trend. These results constitute a clay mineral-based evidence for the hierarchical model of aggregation, which postulates an increasing importance of the reactivity of clay minerals in the formation of micro-aggregates compared to larger aggregates. In the latter aggregates, formation relies on the physical enmeshment of particles by fungal hyphae, and root and microbial exudates. In a second step, micro-aggregates from the tilled soil samples were submitted to increasingly disaggregating treatments by sonication to evaluate the link between their water stability and clay mineralogy. Micro-aggregates with increasing stability showed an increase of interstratified minerals containing swelling phases and C concentration for low intensities of disaggregation (from 0 to 5 J mL-1). This suggests that swelling phases promote their stability. Swelling phases and organic C

  5. Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

    Directory of Open Access Journals (Sweden)

    Nancy L Saccone

    2010-08-01

    Full Text Available Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking, lung cancer, and chronic obstructive pulmonary disease (COPD. We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers, and 2,614 COPD cases and 3,568 COPD-free controls (all smokers. We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35 and <10(-8 respectively. Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6. In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20 and observe a nominally significant association with COPD (p = 0.01; the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765

  6. Stabilization

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    Muhammad H. Al-Malack

    2016-07-01

    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  7. Negative energy balance affects imprint stability in oocytes recovered from postpartum dairy cows.

    Science.gov (United States)

    O'Doherty, Alan M; O'Gorman, Aoife; al Naib, Abdullah; Brennan, Lorraine; Daly, Edward; Duffy, Pat; Fair, Trudee

    2014-09-01

    Ovarian follicle development in post-partum, high-producing dairy cows, occurs in a compromised endogenous metabolic environment (referred to as negative energy balance, NEB). Key events that occur during oocyte/follicle growth, such as the vital process of genomic imprinting, may be detrimentally affected by this altered ovarian environment. Imprinting is crucial for placental function and regulation of fetal growth, therefore failure to establish and maintain imprints during oocyte growth may contribute to early embryonic loss. Using ovum pick-up (OPU), oocytes and follicular fluid samples were recovered from cows between days 20 and 115 post-calving, encompassing the NEB period. In a complimentary study, cumulus oocyte complexes were in vitro matured under high non-esterified fatty acid (NEFA) concentrations and in the presence of the methyl-donor S-adenosylmethionine (SAM). Pyrosequencing revealed the loss of methylation at several imprinted loci in the OPU derived oocytes. The loss of DNA methylation was observed at the PLAGL1 locus in oocytes, following in vitro maturation (IVM) in the presence of elevated NEFAs and SAM. Finally, metabolomic analysis of postpartum follicular fluid samples revealed significant differences in several branched chain amino acids, with fatty acid profiles bearing similarities to those characteristic of lactating dairy cows. These results provide the first evidence that (1) the postpartum ovarian environment may affect maternal imprint acquisition and (2) elevated NEFAs during IVM can lead to the loss of imprinted gene methylation in bovine oocytes.

  8. Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans

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    Dolf Segers

    2011-01-01

    Full Text Available Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE-/- mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P=0.002, smooth muscle cell content increased 2-fold (P=0.03, while macrophage MHC class II expression decreased by 50% (P=0.005. Also, the size of necrotic cores decreased by 41% (P=0.01. In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P=0.003, with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.

  9. Screening of mutations affecting protein stability and dynamics of FGFR1—A simulation analysis

    Directory of Open Access Journals (Sweden)

    C. George Priya Doss

    2012-12-01

    Full Text Available Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 (FGFR1 destabilize protein and have been implicated in several genetic disorders like various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss syndrome, etc. In order to gain functional insight into mutation caused by amino acid substitution to protein function and expression, special emphasis was laid on molecular dynamics simulation techniques in combination with in silico tools such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68% nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT (37%, PolyPhen 2.0 (61% and SNAP (58%. From the observed results, P722S mutation was found to be most deleterious by comparing results of all in silico tools. By molecular dynamics approach, we have shown that P722S mutation leads to increase in flexibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. In addition, biophysical analysis revealed a clear insight of stability loss due to P722S mutation in FGFR1 protein. Majority of mutations predicted by these in silico tools were in good concordance with the experimental results.

  10. Biochar affects carbon composition and stability in soil: a combined spectroscopy-microscopy study

    Science.gov (United States)

    Hernandez-Soriano, Maria C.; Kerré, Bart; Kopittke, Peter M.; Horemans, Benjamin; Smolders, Erik

    2016-04-01

    The use of biochar can contribute to carbon (C) storage in soil. Upon addition of biochar, there is a spatial reorganization of C within soil particles, but the mechanisms remain unclear. Here, we used Fourier transformed infrared-microscopy and confocal laser scanning microscopy to examine this reorganization. A silty-loam soil was amended with three different organic residues and with the biochar produced from these residues and incubated for 237 d. Soil respiration was lower in biochar-amended soils than in residue-amended soils. Fluorescence analysis of the dissolved organic matter revealed that biochar application increased a humic-like fluorescent component, likely associated with biochar-C in solution. The combined spectroscopy-microscopy approach revealed the accumulation of aromatic-C in discrete spots in the solid-phase of microaggregates and its co-localization with clay minerals for soil amended with raw residue or biochar.The co-localization of aromatic-C:polysaccharides-C was consistently reduced upon biochar application. We conclude that reduced C metabolism is an important mechanism for C stabilization in biochar-amended soils.

  11. Factors affecting the microstructural stability and durability of thermal barrier coatings fabricated by air plasma spraying

    Energy Technology Data Exchange (ETDEWEB)

    Helminiak, M.A.; Yanar, N.M.; Pettit, F.S.; Meier, G.H. [National Energy Technology Laboratory, Pittsburgh, PA 15236 (United States); Department of Mechanical Engineering and Materials Science, University of Pittsburgh, 636 Benedum Hall, 3700 O& #x27; Hara Street, Pittsburgh, PA 15261 (United States); Taylor, T.A. [Praxair Surface Technologies, Inc., 1400 Polco Street, Indianapolis, IN 46224 (United States)

    2012-10-15

    The high-temperature behavior of high-purity, low-density (HP-LD) air plasma sprayed (APS) thermal barrier coatings (TBCs) with NiCoCrAlY bond coats deposited by argon-shrouded plasma spraying is described. The high purity yttria-stabilized zirconia resulted in top coats which are highly resistant to sintering and transformation from the metastable tetragonal phase to the equilibrium mixture of monoclinic and cubic phases. The thermal conductivity of the as-processed TBC is low but increases during high temperature exposure even before densification occurs. The porous topcoat microstructure also resulted in good spallation resistance during thermal cycling. The actual failure mechanisms of the APS coatings were found to depend on topcoat thickness, topcoat density, and the thermal cycle frequency. The failure mechanisms are described and the durability of the HP-LD coatings is compared with that of state-of-the-art electron beam physical vapor deposition TBCs. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Dispersal, environmental forcing, and parasites combine to affect metapopulation synehrony and stability.

    Science.gov (United States)

    Duncan, Alison B; Gonzalez, Andrew; Kaltz, Oliver

    2015-01-01

    Dispersal can have positive and negative effects on metapopulation stability and persistence. One prediction is that high levels of dispersal synchronize density fluctuations between subpopulations. However, little is still known about how biotic and abiotic factors combine to modify the effects of dispersal rate on synchrony and metapopulation dynamics. In a fully factorial experimental design, we investigated the combined effects of (1) dispersal, (2) parasite infection, and (3) synchrony in temperature fluctuations on subpopulation synchrony, metapopulation instability, and minimum population size, in laboratory metapopulations of the ciliate Paramecium caudatum. Metapopulations, comprising two subpopulations linked by high or low levels of dispersal, were exposed to daily fluctuations in temperature between permissive (23 degrees C) and restrictive (5 degrees C) conditions. Infected metapopulations started the experiment with one subpopulation uninfected, while the other was infected at a prevalence of 5% with the bacterial parasite Holospora undulata. The temperature synchrony treatment involved subpopulations within a metapopulation following the same (synchronous temperatures) or different (asynchronous temperatures) temporal sequences. Population size was tracked over the 56-day experiment. We found that subpopulation density fluctuations were synchronized by high dispersal in infected metapopulations, and by synchronous temperatures in all metapopulations. Subpopulation synchrony was positively correlated with metapopulation instability and minimum metapopulation size, highlighting the multiple consequences of our treatments for metapopulation dynamics. Our results illustrate how parasites can generate dispersal-driven synchrony in non-cycling, declining populations. This "biotic forcing" via a natural enemy added to the temperature-dependent environmental forcing. We therefore conclude that predictions of metapopulation persistence in natural populations

  13. Chromatin dynamics during cell cycle mediate conversion of DNA damage into chromatid breaks and affect formation of chromosomal aberrations: Biological and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Terzoudi, Georgia I.; Hatzi, Vasiliki I. [Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' Demokritos' , 15310 Ag. Paraskevi Attikis, Athens (Greece); Donta-Bakoyianni, Catherine [Oral Diagnosis and Radiology, University of Athens Dental School, Athens (Greece); Pantelias, Gabriel E., E-mail: gabriel@ipta.demokritos.gr [Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' Demokritos' , 15310 Ag. Paraskevi Attikis, Athens (Greece)

    2011-06-03

    The formation of diverse chromosomal aberrations following irradiation and the variability in radiosensitivity at different cell-cycle stages remain a long standing controversy, probably because most of the studies have focused on elucidating the enzymatic mechanisms involved using simple DNA substrates. Yet, recognition, processing and repair of DNA damage occur within the nucleoprotein complex of chromatin which is dynamic in nature, capable of rapid unfolding, disassembling, assembling and refolding. The present work reviews experimental work designed to investigate the impact of chromatin dynamics and chromosome conformation changes during cell-cycle in the formation of chromosomal aberrations. Using conventional cytogenetics and premature chromosome condensation to visualize interphase chromatin, the data presented support the hypothesis that chromatin dynamic changes during cell-cycle are important determinants in the conversion of sub-microscopic DNA lesions into chromatid breaks. Consequently, the type and yield of radiation-induced chromosomal aberrations at a given cell-cycle-stage depends on the combined effect of DNA repair processes and chromatin dynamics, which is cell-cycle-regulated and subject to up- or down-regulation following radiation exposure or genetic alterations. This new hypothesis is used to explain the variability in radiosensitivity observed at various cell-cycle-stages, among mutant cells and cells of different origin, or among different individuals, and to revisit unresolved issues and unanswered questions. In addition, it is used to better understand hypersensitivity of AT cells and to provide an improved predictive G2-assay for evaluating radiosensitivity at individual level. Finally, experimental data at single cell level obtained using hybrid cells suggest that the proposed hypothesis applies only to the irradiated component of the hybrid.

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

    Science.gov (United States)

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

    2014-01-01

    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.

  15. Feeding dried distillers grains with solubles affects composition but not oxidative stability of milk.

    Science.gov (United States)

    Testroet, E D; Li, G; Beitz, D C; Clark, S

    2015-05-01

    detected off-flavor scores were less than 1.5cm on a 15-cm line scale, indicating that the differences are not practically significant. Peroxide values support the findings by the sensory panel that both feeding DDGS at 10 and 25% and vitamin E and C fortification did not practically change the oxidative stability of milk. These results, taken together, indicate that feeding DDGS under our experimental conditions modified milk composition, but did not contribute to the development of off-flavors in milk.

  16. The Conditions of the Environment as Factors Affecting the Social and Political Stability of Populations

    Directory of Open Access Journals (Sweden)

    Fausto Pedrazzini

    2010-10-01

    Full Text Available In this review article, the different conditions of the environment which could affect the well-being of the populations living on it are taken into consideration and analysed. A specific attention is paid to the phenomenon of water reduction, land degradation and consequent desertification. Such a phenomenon is particularly worrying in selected regions of the world (the Mediterranean Region and Central Asia in which a combination of several factors including climate variations, pressure of populations and increased competition for the available resources have a direct consequence on the economical, social and political conditions of the population. In addition, migrations could also take place, increasing the instability of entire regions. A proper management of water resources and the preservation of land and soil resources are essential requisites to counteract the mentioned adverse effects. Such a management is frequently a transboundary concern since it might involve different regions and countries; this is an additional reason for debating the environment degradation issues at the international level and for increasing the awareness of the civil society, the policy makers and governments.

  17. Dynamics of aggregate stability and soil organic C distribution as affected by climatic aggressiveness: a mesocosm approach

    Science.gov (United States)

    Pellegrini, Sergio; Elio Agnelli, Alessandro; Costanza Andrenelli, Maria; Barbetti, Roberto; Castelli, Fabio; Costantini, Edoardo A. C.; Lagomarsino, Alessandra; Pasqui, Massimiliano; Tomozeiu, Rodica; Razzaghi, Somayyeh; Vignozzi, Nadia

    2014-05-01

    In the framework of a research project aimed at evaluating the adaptation scenarios of the Italian agriculture to the current climate change, a mesocosm experiment under controlled conditions was set up for studying the dynamics of soil aggregate stability and organic C in different size fractions. Three alluvial loamy soils (BOV - Typic Haplustalfs coarse-loamy; CAS - Typic Haplustalfs fine-loamy; MED - Typic Hapludalfs fine-loamy) along a climatic gradient (from dryer to moister pedoclimatic conditions) in the river Po valley (northern Italy), under crop rotation for animal husbandry from more than 40 years, were selected. The Ap horizons (0-30cm) were taken and placed in 9 climatic chambers under controlled temperature and rainfall. Each soil was subjected to three different climate scenarios in terms of erosivity index obtained by combining Modified Fournier and Bagnouls-Gaussen indexes: i) typical (TYP), the median year of each site related to the 1961-1990 reference period; ii) maximum aggressive year (MAX) observed in the same period, and iii) the simulated climate (SIM), obtained by projections of climate change precipitation and temperature for the period 2021-2050 as provided by the IPCC-A1B emission scenario. In the climatic chambers the year climate was reduced to six months. The soils were analyzed for particle size distribution, aggregate stability by wet and dry sieving, and organic C content at the beginning and at the end of the trial. The soils showed different behaviour in terms of aggregate stability and dynamics of organic C in the diverse size fractions. The soils significantly differed in terms of initial mean weight diameter (MWD) (CAS>MED>BOV). A general reduction of MWD in all sites was observed at the end of the experiment, with the increase of the smallest aggregate fractions (0.250-0.05 mm). In particular, BOV showed the maximum decrease of the aggregate stability and MED the lowest. C distribution in aggregate fractions significantly

  18. How can climate, soil, and monitoring schedule affect temporal stability of soil water contents?

    Science.gov (United States)

    Martinez, G.; Pachepsky, Y. A.; Vereecken, H.

    2012-12-01

    Temporal stability (TS) of soil water content (SWC) reflects the spatio-temporal organization of soil water. The TS SWC was originally recognized as a phenomenon that can be used to provide temporal average SWC of an area of interest from observations at a representative location(s). Currently application fields of TS SWC are numerous, e.g. up- and downscaling SWC, SWC monitoring and data assimilation, precision farming, and sensor network design and optimization. However, the factors that control the SWC organization and TS SWC are not completely understood. Among these factors are soil hydraulic properties that are considered as local controls, weather patterns, and the monitoring schedule. The objective of this work was to use modeling to assess the effect of these factors on the spatio-temporal patterns of SWC. We ran the HYDRUS6 code to simulate four years of SWC in 4-m long soil columns. The columns were assumed homogeneous, soil hydraulic conductivity was drawn from lognormal distributions. Sets of columns were generated separately for sandy loam and loamy soils, soil water retention was set to typical values for those soil textures. Simulations were carried out for four climates present at the continental US. The climate-specific weather patterns were obtained with the CLIGEN code using climate-specific weather observation locations that were humid subtropical from College Station (TX), humid continental from Indianapolis (IN), cold semiarid from Moscow (ID) and hot semiarid from Tucson (AZ). We evaluated the TS and representative location (RL) selections by comparing i) different climates; ii) for the same climates different years; iii) different time intervals between samplings; iv) one year duration surveys vs. one month summer campaigns; and v) different seasons of the same year. Spatial variability of the mean relative differences (MRD) differed among climates for both soils, as the probability of observing the same variance in the MRD was lower than

  19. Cognitive vulnerability to depression during middle childhood: Stability and associations with maternal affective styles and parental depression.

    Science.gov (United States)

    Hayden, Elizabeth P; Olino, Thomas M; Mackrell, Sarah V M; Jordan, Patricia L; Desjardins, Jasmine; Katsiroumbas, Patrice

    2013-11-01

    Theories of cognitive vulnerability to depression (CVD) imply that CVD is early-emerging and trait-like; however, little longitudinal work has tested this premise in middle childhood, or examined theoretically relevant predictors of child CVD. We examined test-retest correlations of self-referent encoding task performance and self-reported attributional styles and their associations with parental characteristics in 205 seven-year-olds. At baseline, child CVD was assessed, structured clinical interviews were conducted with parents, and ratings of observed maternal affective styles were made. Children's CVD was re-assessed approximately one and two years later. Both measures of children's CVD were prospectively and concurrently associated with children's depressive symptoms and showed modest stability. Multilevel modeling indicated that maternal criticism and paternal depression were related to children's CVD. Findings indicate that even early-emerging CVD is a valid marker of children's depression risk.

  20. The oxidation of methionine-54 of epoetinum alfa does not affect molecular structure or stability, but does decrease biological activity.

    Science.gov (United States)

    Labrenz, Steven R; Calmann, Melissa A; Heavner, George A; Tolman, Glen

    2008-01-01

    Erythropoietin therapy is used to treat severe anemia in renal failure and chemotherapy patients. One of these therapies based on recombinant human erythropoietin is marketed under the trade name of EPREX and utilizes epoetinum alfa as the active pharmaceutical ingredient. The effect of oxidation of methionine-54 on the structure and stability of the erythropoietin molecule has not been directly tested. We have observed partial and full chemical oxidation of methionine-54 to methionine-54 sulfoxide, accomplished using tert-Butylhydroperoxide and hydrogen peroxide, respectively. A blue shift in the fluorescence center of spectral mass wavelength was observed as a linear response to the level of methionine sulfoxide in the epoetinum alfa molecule, presumably arising from a local change in the environment near tryptophan-51, as supported by potassium iodide quenching studies. Circular dichroism studies demonstrated no change in the folded structure of the molecule with methionine oxidation. The thermal unfolding profiles of partial and completely oxidized epoetinum alfa overlap, with a T(m) of 49.5 degrees C across all levels of methionine sulfoxide content. When the protein was tested for activity, a decrease in biological activity was observed, correlating with methionine sulfoxide levels. An allosteric effect between Met54, Trp51, and residues involved in receptor binding is proposed. These results indicate that methionine oxidation has no effect on the folded structure and global thermodynamic stability of the recombinant human erythropoietin molecule. Oxidation can affect potency, but only at levels significantly in excess of those seen in EPREX.

  1. 京枣试管苗染色体稳定性观察%Observation on Chromosomal Stability of Test-tube Seedlings of Jujube Cultivar ‘Jingzao'

    Institute of Scientific and Technical Information of China (English)

    权燕敏; 肖海峰; 陈宗礼

    2013-01-01

    以继代培养20代后经生根培养基生根的京枣试管苗为试验材料,用常规染色体压片和显微观察相结合的方法对根尖进行染色体数目观察,结果显示,京枣试管苗的染色体数目2n=24条的占85%,说明经继代培养的京枣试管苗仍保持遗传稳定性.%The test-tube seedlings of Jujube ‘ Jingzao' after rooting culture and 20 generations of subcultures were used as experiment materials.The methods of traditional chromosome tabletting and microscopic observation were adopted to observe the chromosomal number of root tip cell.The results showed that 85% of the chromosomal number of ‘ Jingzao' was found as 2n =24,which indicated that the test-tube seedlings of ‘ Jingzao' still kept the genetic stability after subculture.

  2. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

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

  3. UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells.

    Directory of Open Access Journals (Sweden)

    Jee Young An

    Full Text Available The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa, conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known

  4. Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae.

    Science.gov (United States)

    Ayyadevara, Srinivas; Tazearslan, Cagdas; Alla, Ramani; Jiang, James C; Jazwinski, S Michal; Shmookler Reis, Robert J

    2014-01-01

    A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently implicated by mapping longevity genes. QTLs for lifespan and three stress-resistance traits coincided within a span of thermal stresses, and lower male frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741) by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy (opposing effects on lifespan vs. reproduction), and/or balancing selection wherein genomic disruption increases genetic variation under harsh conditions.

  5. An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions.

    Directory of Open Access Journals (Sweden)

    Bum Jun Kim

    Full Text Available Individuals with terminal and interstitial deletions of chromosome 1p36 have a spectrum of defects that includes eye anomalies, postnatal growth deficiency, structural brain anomalies, seizures, cognitive impairment, delayed motor development, behavior problems, hearing loss, cardiovascular malformations, cardiomyopathy, and renal anomalies. The proximal 1p36 genes that contribute to these defects have not been clearly delineated. The arginine-glutamic acid dipeptide (RE repeats gene (RERE is located in this region and encodes a nuclear receptor coregulator that plays a critical role in embryonic development as a positive regulator of retinoic acid signaling. Rere-null mice die of cardiac failure between E9.5 and E11.5. This limits their usefulness in studying the role of RERE in the latter stages of development and into adulthood. To overcome this limitation, we created an allelic series of RERE-deficient mice using an Rere-null allele, om, and a novel hypomorphic Rere allele, eyes3 (c.578T>C, p.Val193Ala, which we identified in an N-ethyl-N-nitrosourea (ENU-based screen for autosomal recessive phenotypes. Analyses of these mice revealed microphthalmia, postnatal growth deficiency, brain hypoplasia, decreased numbers of neuronal nuclear antigen (NeuN-positive hippocampal neurons, hearing loss, cardiovascular malformations-aortic arch anomalies, double outlet right ventricle, and transposition of the great arteries, and perimembranous ventricular septal defects-spontaneous development of cardiac fibrosis and renal agenesis. These findings suggest that RERE plays a critical role in the development and function of multiple organs including the eye, brain, inner ear, heart and kidney. It follows that haploinsufficiency of RERE may contribute-alone or in conjunction with other genetic, environmental, or stochastic factors-to the development of many of the phenotypes seen in individuals with terminal and interstitial deletions that include the

  6. Detection of quantitative trait loci affecting the milk fatty acid profile on sheep chromosome 22: role of the stearoyl-CoA desaturase gene in Spanish Churra sheep.

    Science.gov (United States)

    García-Fernández, M; Gutiérrez-Gil, B; García-Gámez, E; Sánchez, J P; Arranz, J J

    2010-01-01

    Sheep milk fat contains several components that may provide human health benefits, such as monounsaturated fatty acids and conjugated linoleic acid (CLA). Most of the CLA in ruminant milk is synthesized in the mammary gland by the action of the enzyme stearoyl-CoA desaturase (SCD) on circulating vaccenic acid (trans-11 C18:2; VA). Previous studies have found significant associations between polymorphisms in the SCD gene and the fatty acid composition of ruminant products, including sheep milk. Based on this, we performed a quantitative trait loci (QTL) analysis of an ovine chromosome (22) that harbors the SCD gene for effects on milk fatty acid composition traits and classical milk production traits. We identified a suggestive QTL influencing the CLA/VA ratio with the maximum statistic at position 26 cM of the studied chromosome, whereas the SCD gene has been mapped to position 41.6 cM. The individual introduction of 4 SCD single nucleotide polymorphisms in the QTL model did not cause a reduction of the variance explained by the QTL, which suggests that the SCD gene is not directly responsible for the detected effect in the Churra population studied herein. This conclusion was supported by the lack of any significant association identified between the 4 SCD single nucleotide polymorphisms and the CLA/VA ratio. This association analysis suggested a possible effect of the SCD gene on milk fat percentage in Churra sheep. An independent confirmation of these primary results will be required before attempting its practical implementation in selection programs.

  7. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    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.

  8. Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions.

    Science.gov (United States)

    Krupková, Michaela; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Kren, Vladimír; Seda, Ondrej

    2010-04-16

    Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control (standard diet) and DEX-treated 7-month-old males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4). These two inbred strains differ in a defined segment of chromosome 4, originally transferred from the spontaneously hypertensive rat (SHR) including the mutant Cd36 gene, a known target of DEX. Compared to BN, the standard-diet-fed BN.SHR4 showed higher cholesterol and triacylglycerol concentrations across many lipoprotein fractions, particularly in small VLDL and LDL particles. Total cholesterol was decreased by DEX by more than 21% in BN.SHR4 contrasting with the tendency to increase in BN (strain*DEX interaction p = 0.0017). Similar pattern was observed for triacylglycerol concentrations in LDL. The LDL particle size was significantly reduced by DEX in both strains. Also, while control BN and BN.SHR4 displayed comparable glycaemic profiles during oral glucose tolerance test, we observed a markedly blunted DEX induction of glucose intolerance in BN.SHR4 compared to BN. In summary, we report a pharmacogenetic interaction between limited genomic segment with mutated Cd36 gene and dexamethasone-induced glucose intolerance and triacylglycerol and cholesterol redistribution into lipoprotein fractions.

  9. Similar frequency of paternal uniparental disomy involving chromosome 20q (patUPD20q) in Japanese and Caucasian patients affected by sporadic pseudohypoparathyroidism type Ib (sporPHP1B).

    Science.gov (United States)

    Takatani, Rieko; Minagawa, Masanori; Molinaro, Angelo; Reyes, Monica; Kinoshita, Kaori; Takatani, Tomozumi; Kazukawa, Itsuro; Nagatsuma, Misako; Kashimada, Kenichi; Sato, Kenichi; Matsushita, Kazuyuki; Nomura, Fumio; Shimojo, Naoki; Jüppner, Harald

    2015-10-01

    Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance to parathyroid hormone that occurs in most cases in the absence of Albright's Hereditary Osteodystrophy (AHO). Familial forms of PHP1B are caused by maternally inherited microdeletions within STX16, the gene encoding syntaxin 16, or within GNAS, a complex genetic locus on chromosome 20q13.3 encoding Gsα and several splice variants thereof. These deletions lead either to a loss-of-methylation affecting GNAS exon A/B alone or to epigenetic changes involving multiple differentially methylated regions (DMRs) within GNAS. Broad GNAS methylation abnormalities are also observed in most sporadic PHP1B (sporPHP1B) cases. However, with the exception of paternal uniparental disomy involving chromosome 20q (patUPD20q), the molecular mechanism leading to this disease variant remains unknown. We now investigated 23 Japanese sporPHP1B cases, who presented with hypocalcemia, hyperphosphatemia, elevated PTH levels, and occasionally with TSH elevations and mild AHO features. Age at diagnosis was 10.6 ± 1.45 years. Calcium, phosphate, and PTH were 6.3 ± 0.23 mg/dL, 7.7 ± 0.33 mg/dL, and 305 ± 34.5 pg/mL, respectively, i.e. laboratory findings that are indistinguishable from those previously observed for Caucasian sporPHP1B cases. All investigated patients showed broad GNAS methylation changes. Eleven individuals were homozygous for SNPs within exon NESP and a pentanucleotide repeat in exon A/B. Two of these patients furthermore revealed homozygosity for numerous microsatellite markers on chromosome 20q raising the possibility of patUPD20q, which was confirmed through the analysis of parental DNA. Based on this and our previous reports, paternal duplication of the chromosomal region comprising the GNAS locus appears to be a fairly common cause of sporPHP1B that is likely to occur with equal frequency in Caucasians and Asians.

  10. Some Numerical Investigations of the Stability of Electrochemical Digital Simulation, Particularly as affected by First-Order Homogeneous Reactions

    DEFF Research Database (Denmark)

    Britz, Dieter; Østerby, Ole

    1994-01-01

    A reported analysis of the stability of some digital simulation methods is investigated by numerical experiments and the results are consistent with the analysis. Traditional stability conditions need to be modified slightly in the presence of homogeneous reactions, though not to a degree that ha...

  11. How do how internal and external processes affect the behaviors of coupled marsh mudflat systems; infill, stabilize, retreat, or drown?

    Science.gov (United States)

    Carr, J. A.; Mariotti, G.; Wiberg, P.; Fagherazzi, S.; McGlathery, K.

    2013-12-01

    an eventual lateral equilibrium are possible only with large allochthonous sediment supply. Once marshes expanded, marsh retreat can be prevented by a sediment supply smaller than the one that filled the basin. At the GCE, the Altamaha River allows for enhanced allochthonous supply directly to the salt marsh platform, reducing the importance of waves on the tidal flat. As a result, infilling or retreat become the prevalent behaviors. For the VCR, the presence of seagrass decreases near bed shear stresses and sediment flux to the salt marsh platform, however, seagrass also reduces the wave energy acting on the boundary of the marsh reducing boundary erosion. Results indicate that the reduction in wave power allows for seagrass to provide a strong stabilizing affect on the coupled salt marsh tidal flat system, but as external sediment supply increases and light conditions decline the system reverts to that of a bare tidal flat. Across all systems and with current rates of sea level rise, retreat is a more likely marsh loss modality than drowning.

  12. Chromosome I duplications in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    McKim, K.S.; Rose, A.M. (Univ. of British Columbia, Vancouver (Canada))

    1990-01-01

    We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.

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

    OpenAIRE

    五十嵐, 修一; Igarashi, Shuichi

    1997-01-01

    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...

  14. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle.

    Science.gov (United States)

    Darroudi, Firouz; Wiegant, Wouter; Meijers, Matty; Friedl, Anna A; van der Burg, Mirjam; Fomina, Janna; van Dongen, Jacques J M; van Gent, Dik C; Zdzienicka, Małgorzata Z

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and gammaH2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G(1)/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G(2) resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G(1) cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G(1)-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4> or =AT>Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when cells are devoid of

  15. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Darroudi, Firouz [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands)]. E-mail: F.Darroudi@LUMC.NL; Wiegant, Wouter [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Meijers, Matty [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Friedl, Anna A. [Radiobiological Institute, University of Munich, Munich (Germany); Institute of Radiobiology, GSF National Research Center for Environment and Health, Neuherberg (Germany); Burg, Mirjam van der [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Fomina, Janna [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Dongen, Jacques J.M. van [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Gent, Dik C. van [Department of Cell Biology and Genetics, Erasmus Medical Centre, Rotterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Department of Molecular Cell Genetics, Collegium Medicum, N. Corpernicus University, Bydgoszcz (Poland)

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and {gamma}H2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G{sub 1}/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G{sub 2} resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G{sub 1} cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G{sub 1}-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4 {>=} AT > Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when

  16. Amino Acid Substitutions That Affect Receptor Binding and Stability of the Hemagglutinin of Influenza A/H7N9 Virus

    Science.gov (United States)

    Schrauwen, Eefje J. A.; Burke, David F.; Rimmelzwaan, Guus F.; Herfst, Sander; Fouchier, Ron A. M.

    2016-01-01

    Receptor-binding preference and stability of hemagglutinin have been implicated as crucial determinants of airborne transmission of influenza viruses. Here, amino acid substitutions previously identified to affect these traits were tested in the context of an A/H7N9 virus. Some combinations of substitutions, most notably G219S and K58I, resulted in relatively high affinity for α2,6-linked sialic acid receptor and acid and temperature stability. Thus, the hemagglutinin of the A/H7N9 virus may adopt traits associated with airborne transmission. PMID:26792744

  17. Dicentric chromosomes: unique models to study centromere function and inactivation

    OpenAIRE

    Kaitlin M Stimpson; Matheny, Justyne E.; Sullivan, Beth A.

    2012-01-01

    Dicentric chromosomes are products of genome rearrangement that place two centromeres on the same chromosome. Depending on the organism, dicentric stability varies after formation. In humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell divisi...

  18. Does the Implant Surgical Technique Affect the Primary and/or Secondary Stability of Dental Implants? A Systematic Review

    Directory of Open Access Journals (Sweden)

    Rola Muhammed Shadid

    2014-01-01

    Full Text Available Background. A number of surgical techniques for implant site preparation have been advocated to enhance the implant of primary and secondary stability. However, there is insufficient scientific evidence to support the association between the surgical technique and implant stability. Purpose. This review aimed to investigate the influence of different surgical techniques including the undersized drilling, the osteotome, the piezosurgery, the flapless procedure, and the bone stimulation by low-level laser therapy on the primary and/or secondary stability of dental implants. Materials and methods. A search of PubMed, Cochrane Library, and grey literature was performed. The inclusion criteria comprised observational clinical studies and randomized controlled trials (RCTs conducted in patients who received dental implants for rehabilitation, studies that evaluated the association between the surgical technique and the implant primary and/or secondary stability. The articles selected were carefully read and classified as low, moderate, and high methodological quality and data of interest were tabulated. Results. Eight clinical studies were included then they were classified as moderate or high methodological quality and control of bias. Conclusions. There is a weak evidence suggesting that any of previously mentioned surgical techniques could influence the primary and/or secondary implant stability.

  19. How hydrophobicity and the glycosylation site of glycans affect protein folding and stability: a molecular dynamics simulation.

    Science.gov (United States)

    Lu, Diannan; Yang, Cheng; Liu, Zheng

    2012-01-12

    Glycosylation is one of the most common post-translational modifications in the biosynthesis of protein, but its effect on the protein conformational transitions underpinning folding and stabilization is poorly understood. In this study, we present a coarse-grained off-lattice 46-β barrel model protein glycosylated by glycans with different hydrophobicity and glycosylation sites to examine the effect of glycans on protein folding and stabilization using a Langevin dynamics simulation, in which an H term was proposed as the index of the hydrophobicity of glycan. Compared with its native counterpart, introducing glycans of suitable hydrophobicity (0.1 enthalpy effect. The simulations have shown both the stabilization and the destabilization effects of glycosylation, as experimentally reported in the literature, and provided molecular insight into glycosylated proteins. The understanding of the effects of glycans with different hydrophobicities on the folding and stability of protein, as attempted by the present work, is helpful not only to explain the stabilization and destabilization effect of real glycoproteins but also to design protein-polymer conjugates for biotechnological purposes.

  20. Stability of single copy transgene expression in CHOK1 cells is affected by histone modifications but not by DNA methylation.

    Science.gov (United States)

    Spencer, Shawal; Gugliotta, Agustina; Koenitzer, Jennifer; Hauser, Hansjörg; Wirth, Dagmar

    2015-02-10

    Intraclonal heterogeneity of genetically modified mammalian cells has been observed as a phenomenon that has a strong impact on overall transgene expression levels and that limits the predictability of transgene expression in genetically modified cells, thereby hampering single cell based screening approaches. The underlying mechanism(s) leading to this variance are poorly understood. To study the dynamics and mechanisms of heterogeneity of early stage silencing we analyzed the expression in more than 100 independent clones of CHOK1 cells that harbour genetically stable integrates of single copy reporter cassettes driven by EF1α and CMV promoters. Single cell analysis showed intraclonal variability with heterogeneity in expression in genetically uniform populations. DNA methylation is a well known mechanism responsible for silencing of gene expression. Interestingly, loss of expression was not associated with DNA methylation of the CMV promoter. However, in most of the clonal populations expression could be increased by inhibitors of the histone deacetylases (HDACi) suggesting that heterogeneity of transgene expression is crucially governed by histone modifications. Further, to determine if the epigenetic status of transgene expression is governed by the chromosomal integration locus we targeted heterologous expression cassettes into two chromosomal sites using recombinase mediated cassette exchange (RMCE). The expression status of a particular clone was faithfully re-established when the same promoter used. In this way the problem of early stage cell clone instability can be bypassed. However, upon introduction of an unrelated promoter methylation-independent silencing was observed. Together, these results suggest that histone modifications are the relevant mechanisms by which epigenetic modulation of transgene expression cassettes is governed in the early phase of clone generation.

  1. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation.

    Science.gov (United States)

    Pérez-Pérez, Rafael; Lobo-Jarne, Teresa; Milenkovic, Dusanka; Mourier, Arnaud; Bratic, Ana; García-Bartolomé, Alberto; Fernández-Vizarra, Erika; Cadenas, Susana; Delmiro, Aitor; García-Consuegra, Inés; Arenas, Joaquín; Martín, Miguel A; Larsson, Nils-Göran; Ugalde, Cristina

    2016-08-30

    Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.

  2. Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability.

    Science.gov (United States)

    Karimi, Maryam; Ignasiak, Marta T; Chan, Bun; Croft, Anna K; Radom, Leo; Schiesser, Carl H; Pattison, David I; Davies, Michael J

    2016-12-12

    Disulfide bonds play a key role in stabilizing protein structures, with disruption strongly associated with loss of protein function and activity. Previous data have suggested that disulfides show only modest reactivity with oxidants. In the current study, we report kinetic data indicating that selected disulfides react extremely rapidly, with a variation of 10(4) in rate constants. Five-membered ring disulfides are particularly reactive compared with acyclic (linear) disulfides or six-membered rings. Particular disulfides in proteins also show enhanced reactivity. This variation occurs with multiple oxidants and is shown to arise from favorable electrostatic stabilization of the incipient positive charge on the sulfur reaction center by remote groups, or by the neighboring sulfur for conformations in which the orbitals are suitably aligned. Controlling these factors should allow the design of efficient scavengers and high-stability proteins. These data are consistent with selective oxidative damage to particular disulfides, including those in some proteins.

  3. Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability

    Science.gov (United States)

    Karimi, Maryam; Ignasiak, Marta T.; Chan, Bun; Croft, Anna K.; Radom, Leo; Schiesser, Carl H.; Pattison, David I.; Davies, Michael J.

    2016-12-01

    Disulfide bonds play a key role in stabilizing protein structures, with disruption strongly associated with loss of protein function and activity. Previous data have suggested that disulfides show only modest reactivity with oxidants. In the current study, we report kinetic data indicating that selected disulfides react extremely rapidly, with a variation of 104 in rate constants. Five-membered ring disulfides are particularly reactive compared with acyclic (linear) disulfides or six-membered rings. Particular disulfides in proteins also show enhanced reactivity. This variation occurs with multiple oxidants and is shown to arise from favorable electrostatic stabilization of the incipient positive charge on the sulfur reaction center by remote groups, or by the neighboring sulfur for conformations in which the orbitals are suitably aligned. Controlling these factors should allow the design of efficient scavengers and high-stability proteins. These data are consistent with selective oxidative damage to particular disulfides, including those in some proteins.

  4. Restricted Arm Swing Affects Gait Stability and Increased Walking Speed Alters Trunk Movements in Children with Cerebral Palsy

    Science.gov (United States)

    Delabastita, Tijs; Desloovere, Kaat; Meyns, Pieter

    2016-01-01

    Observational research suggests that in children with cerebral palsy, the altered arm swing is linked to instability during walking. Therefore, the current study investigates whether children with cerebral palsy use their arms more than typically developing children, to enhance gait stability. Evidence also suggests an influence of walking speed on gait stability. Moreover, previous research highlighted a link between walking speed and arm swing. Hence, the experiment aimed to explore differences between typically developing children and children with cerebral palsy taking into account the combined influence of restricting arm swing and increasing walking speed on gait stability. Spatiotemporal gait characteristics, trunk movement parameters and margins of stability were obtained using three dimensional gait analysis to assess gait stability of 26 children with cerebral palsy and 24 typically developing children. Four walking conditions were evaluated: (i) free arm swing and preferred walking speed; (ii) restricted arm swing and preferred walking speed; (iii) free arm swing and high walking speed; and (iv) restricted arm swing and high walking speed. Double support time and trunk acceleration variability increased more when arm swing was restricted in children with bilateral cerebral palsy compared to typically developing children and children with unilateral cerebral palsy. Trunk sway velocity increased more when walking speed was increased in children with unilateral cerebral palsy compared to children with bilateral cerebral palsy and typically developing children and in children with bilateral cerebral palsy compared to typically developing children. Trunk sway velocity increased more when both arm swing was restricted and walking speed was increased in children with bilateral cerebral palsy compared to typically developing children. It is proposed that facilitating arm swing during gait rehabilitation can improve gait stability and decrease trunk movements in

  5. Experimental and molecular dynamics studies showed that CBP KIX mutation affects the stability of CBP:c-Myb complex.

    Science.gov (United States)

    Odoux, Anne; Jindal, Darren; Tamas, Tamara C; Lim, Benjamin W H; Pollard, Drake; Xu, Wu

    2016-06-01

    The coactivators CBP (CREBBP) and its paralog p300 (EP300), two conserved multi-domain proteins in eukaryotic organisms, regulate gene expression in part by binding DNA-binding transcription factors. It was previously reported that the CBP/p300 KIX domain mutant (Y650A, A654Q, and Y658A) altered both c-Myb-dependent gene activation and repression, and that mice with these three point mutations had reduced numbers of platelets, B cells, T cells, and red blood cells. Here, our transient transfection assays demonstrated that mouse embryonic fibroblast cells containing the same mutations in the KIX domain and without a wild-type allele of either CBP or p300, showed decreased c-Myb-mediated transcription. Dr. Wright's group solved a 3-D structure of the mouse CBP:c-Myb complex using NMR. To take advantage of the experimental structure and function data and improved theoretical calculation methods, we performed MD simulations of CBP KIX, CBP KIX with the mutations, and c-Myb, as well as binding energy analysis for both the wild-type and mutant complexes. The binding between CBP and c-Myb is mainly mediated by a shallow hydrophobic groove in the center where the side-chain of Leu302 of c-Myb plays an essential role and two salt bridges at the two ends. We found that the KIX mutations slightly decreased stability of the CBP:c-Myb complex as demonstrated by higher binding energy calculated using either MM/PBSA or MM/GBSA methods. More specifically, the KIX mutations affected the two salt bridges between CBP and c-Myb (CBP-R646 and c-Myb-E306; CBP-E665 and c-Myb-R294). Our studies also revealed differing dynamics of the hydrogen bonds between CBP-R646 and c-Myb-E306 and between CBP-E665 and c-Myb-R294 caused by the CBP KIX mutations. In the wild-type CBP:c-Myb complex, both of the hydrogen bonds stayed relatively stable. In contrast, in the mutant CBP:c-Myb complex, hydrogen bonds between R646 and E306 showed an increasing trend followed by a decreasing trend, and hydrogen

  6. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    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.

  7. The importance of having two X chromosomes.

    Science.gov (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

    2016-02-19

    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.

  8. Does Implant Design Affect Implant Primary Stability? A Resonance Frequency Analysis-Based Randomized Split-Mouth Clinical Trial.

    Science.gov (United States)

    Gehrke, Sergio Alexandre; da Silva, Ulisses Tavares; Del Fabbro, Massimo

    2015-12-01

    The purpose of this study was to assess implant stability in relation to implant design (conical vs. semiconical and wide-pitch vs narrow-pitch) using resonance frequency analysis. Twenty patients with bilateral edentulous maxillary premolar region were selected. In one hemiarch, conical implants with wide pitch (group 1) were installed; in the other hemiarch, semiconical implants with narrow pitch were installed (group 2). The implant allocation was randomized. The implant stability quotient (ISQ) was measured by resonance frequency analysis immediately following implant placement to assess primary stability (time 1) and at 90 days after placement (time 2). In group 1, the mean and standard deviation ISQ for time 1 was 65.8 ± 6.22 (95% confidence interval [CI], 55 to 80), and for time 2, it was 68.0 ± 5.52 (95% CI, 57 to 77). In group 2, the mean and standard deviation ISQ was 63.6 ± 5.95 (95% CI, 52 to 78) for time 1 and 67.0 ± 5.71 (95% CI, 58 to 78) for time 2. The statistical analysis demonstrated significant difference in the ISQ values between groups at time 1 (P = .007) and no statistical difference at time 2 (P = .54). The greater primary stability of conical implants with wide pitch compared with semiconical implants with narrow pitch might suggest a preference for the former in case of the adoption of immediate or early loading protocols.

  9. Disruption of a hydrogen bond network in human versus spider monkey cytochrome c affects heme crevice stability.

    Science.gov (United States)

    Goldes, Matthew E; Jeakins-Cooley, Margaret E; McClelland, Levi J; Mou, Tung-Chung; Bowler, Bruce E

    2016-05-01

    The hypothesis that the recent rapid evolution of primate cytochromes c, which primarily involves residues in the least stable Ω-loop (Ω-loop C, residues 40-57), stabilizes the heme crevice of cytochrome c relative to other mammals, is tested. To accomplish this goal, we have compared the properties of human and spider monkey cytochrome c and a set of four variants produced in the process of converting human cytochrome c into spider monkey cytochrome c. The global stability of all variants has been measured by guanidine hydrochloride denaturation. The stability of the heme crevice has been assessed with the alkaline conformational transition. Structural insight into the effects of the five amino acid substitutions needed to convert human cytochrome c into spider monkey cytochrome c is provided by a 1.15Å resolution structure of spider monkey cytochrome c. The global stability for all variants is near 9.0kcal/mol at 25°C and pH7, which is higher than that observed for other mammalian cytochromes c. The heme crevice stability is more sensitive to the substitutions required to produce spider monkey cytochrome c with decreases of up to 0.5 units in the apparent pKa of the alkaline conformational transition relative to human cytochrome c. The structure of spider monkey cytochrome c indicates that the Y46F substitution destabilizes the heme crevice by disrupting an extensive hydrogen bond network that connects three surface loops including Ω-loop D (residues 70-85), which contains the Met80 heme ligand.

  10. Cloning, Expression, and Chromosomal Stabilization of the Propionibacterium shermanii Proline Iminopeptidase Gene (pip) for Food-Grade Application in Lactococcus lactis

    Science.gov (United States)

    Leenhouts, Kees; Bolhuis, Albert; Boot, Johan; Deutz, Inge; Toonen, Marjolein; Venema, Gerard; Kok, Jan; Ledeboer, Aat

    1998-01-01

    Proline iminopeptidase produced by Propionibacterium shermanii plays an essential role in the flavor development of Swiss-type cheeses. The enzyme (Pip) was purified and characterized, and the gene (pip) was cloned and expressed in Escherichia coli and Lactococcus lactis, the latter species being an extensively studied, primary cheese starter culture that is less fastidious in its growth condition requirements than P. shermanii. The levels of expression of the pip gene could be enhanced with a factor 3 to 5 by using a strong constitutive promoter in L. lactis or the inducible tac promoter in E. coli. Stable replication of the rolling-circle replicating (rcr) plasmid, used to express pip in L. lactis, could only be obtained by providing the repA gene in trans. Upon the integration of pip, clear gene dosage effects were observed and stable multicopy integrants could be maintained upon growth under the selective pressure of sucrose. The multicopy integrants demonstrated a high degree of stability in the presence of glucose. This study examines the possibilities to overexpress genes that play an important role in food fermentation processes and shows a variety of options to obtain stable food-grade expression of such genes in L. lactis. PMID:9835556

  11. The influence of somatosensory and muscular deficits on postural stabilization: Insights from an instrumented analysis of subjects affected by different types of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Lencioni, Tiziana; Piscosquito, Giuseppe; Rabuffetti, Marco; Bovi, Gabriele; Calabrese, Daniela; Aiello, Alessia; Di Sipio, Enrica; Padua, Luca; Diverio, Manuela; Pareyson, Davide; Ferrarin, Maurizio

    2015-08-01

    Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder. CMT1 is primarily demyelinating, CMT2 is primarily axonal, and CMTX1 is characterized by both axonal and demyelinating abnormalities. We investigated the role of somatosensory and muscular deficits on quiet standing and postural stabilization in patients affected by different forms of CMT, comparing their performances with those of healthy subjects. Seventy-six CMT subjects (CMT1A, CMT2 and CMTX1) and 41 healthy controls were evaluated during a sit-to-stand transition and the subsequent quiet upright posture by means of a dynamometric platform. All CMT patients showed altered balance and postural stabilization compared to controls. Multivariate analysis showed that in CMT patients worsening of postural stabilization was related to vibration sense deficit and to dorsi-flexor's weakness, while quiet standing instability was related to the reduction of pinprick sensibility and to plantar-flexor's weakness. Our results show that specific sensory and muscular deficits play different roles in balance impairment of CMT patients, both during postural stabilization and in static posture. An accurate evaluation of residual sensory and muscular functions is therefore necessary to plan for the appropriate balance rehabilitation treatment for each patient, besides the CMT type.

  12. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

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

    2012-11-01

    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.

  13. How Does Functional Soccer Training on Uneven Ground Affect Dynamic Stability of Lower Limbs in Young Soccer Players

    OpenAIRE

    Plenzler, Marcin; Mrozińska, Natalia; Mierzwińska, Anna; Korbolewska, Olga; Mejnartowicz, Daria; Popieluch, Marcin; Śmigielski, Robert

    2014-01-01

    Objectives: The aim of the study was to assess the level of lower limbs’ stability under dynamic conditions in soccer players before and after the preparatory period. The results of young players were compared with the control group’s records. The analysis included, both, the dominant (the one kicking the ball) and the non-dominant (supporting) limb. Methods: 13 players from AGAPE Soccer Academy in Białołęka (year 2002), participated in this study. The control group were 18 young, healthy, an...

  14. Longevity and developmental stability in the dung fly Sepsis cynipsea, as affected by the ectoparasitic mite, Pediculoides mesembrinae

    Directory of Open Access Journals (Sweden)

    Oliver Y. Martin

    2009-12-01

    Full Text Available Fluctuating asymmetry (FA is a widely employed measure of developmental stability. It has been found to increase with many stressors including parasite infection. Associations between parasites and FA may exist for several reasons in addition to parasites being the direct cause of increased FA. Developmentally stable individuals may have superior immune systems, and be less susceptible to parasite infection, and/or may be less exposed to parasites than developmentally unstable ones. Mites negatively impact host fitness in a number of insects, and if FA is a reflection of general genetic quality, as has been proposed, associations between mite number and FA are predicted. Potential relationships were investigated between an ectoparasitic mite, Pediculoides mesembrinae (Canestrini (Phthiraptera: Menoponidae and FA in the common dung fly Sepsis cynipsea (L. (Diptera: Sepsidae. While it was found that mite infested flies died much faster than flies without mites, indicating that mites indeed stress their hosts, counter to expectations, no associations between mites and FA were found in any analyses. Additionally, FA in mite-infected flies generally did not differ from previously published FA data from uninfected S. cynipsea. Nevertheless, parasitized males tended to be somewhat less asymmetrical than non-parasitized males, but based on our data, it does not appear that mite infestation is generally associated with developmental stability in S. cynipsea.

  15. The cellular energization state affects peripheral stalk stability of plant vacuolar H+-ATPase and impairs vacuolar acidification.

    Science.gov (United States)

    Schnitzer, Daniel; Seidel, Thorsten; Sander, Tim; Golldack, Dortje; Dietz, Karl-Josef

    2011-05-01

    The plant vacuolar H(+)-ATPase takes part in acidifying compartments of the endomembrane system including the secretory pathway and the vacuoles. The structural variability of the V-ATPase complex as well as its presence in different compartments and tissues involves multiple isoforms of V-ATPase subunits. Furthermore, a versatile regulation is essential to allow for organelle- and tissue-specific fine tuning. In this study, results from V-ATPase complex disassembly with a chaotropic reagent, immunodetection and in vivo fluorescence resonance energy transfer (FRET) analyses point to a regulatory mechanism in plants, which depends on energization and involves the stability of the peripheral stalks as well. Lowering of cellular ATP by feeding 2-deoxyglucose resulted in structural alterations within the V-ATPase, as monitored by changes in FRET efficiency between subunits VHA-E and VHA-C. Potassium iodide-mediated disassembly revealed a reduced stability of V-ATPase after 2-deoxyglucose treatment of the cells, but neither the complete V(1)-sector nor VHA-C was released from the membrane in response to 2-deoxyglucose treatment, precluding a reversible dissociation mechanism like in yeast. These data suggest the existence of a regulatory mechanism of plant V-ATPase by modification of the peripheral stator structure that is linked to the cellular energization state. This mechanism is distinct from reversible dissociation as reported for the yeast V-ATPase, but might represent an evolutionary precursor of reversible dissociation.

  16. Isolation and characterization of bovine herpesvirus 4 (BoHV-4 from a cow affected by post partum metritis and cloning of the genome as a bacterial artificial chromosome

    Directory of Open Access Journals (Sweden)

    Cavirani Sandro

    2009-08-01

    Full Text Available Abstract Background Bovine herpesvirus 4 (BoHV-4 is a gammaherpesvirus with a Worldwide distribution in cattle and is often isolated from the uterus of animals with postpartum metritis or pelvic inflammatory disease. Virus strain adaptation to an organ, tissue or cell type is an important issue for the pathogenesis of disease. To explore the mechanistic role of viral strain variation for uterine disease, the present study aimed to develop a tool enabling precise genetic discrimination between strains of BoHV-4 and to easily manipulate the viral genome. Methods A strain of BoHV-4 was isolated from the uterus of a persistently infected cow and designated BoHV-4-U. The authenticity of the isolate was confirmed by RFLP-PCR and sequencing using the TK and IE2 loci as genetic marker regions for the BoHV-4 genome. The isolated genome was cloned as a Bacterial Artificial Chromosome (BAC and manipulated through recombineering technology Results The BoHV-4-U genome was successfully cloned as a BAC, and the stability of the pBAC-BoHV-4-U clone was confirmed over twenty passages, with viral growth similar to the wild type virus. The feasibility of using BoHV-4-U for mutagenesis was demonstrated using the BAC recombineering system. Conclusion The analysis of genome strain variation is a key method for investigating genes associated with disease. A resource for dissection of the interactions between BoHV-4 and host endometrial cells was generated by cloning the genome of BoHV-4 as a BAC.

  17. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    Science.gov (United States)

    Sharma, Reetu; Sastry, G Narahari

    2015-01-01

    Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

  18. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Reetu Sharma

    Full Text Available Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

  19. The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity.

    Directory of Open Access Journals (Sweden)

    Mara Marongiu

    Full Text Available The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.

  20. Does the personal lift-assist device affect the local dynamic stability of the spine during lifting?

    Science.gov (United States)

    Graham, Ryan B; Sadler, Erin M; Stevenson, Joan M

    2011-02-03

    The personal lift-assist device (PLAD) is an on-body ergonomic aid that reduces low back physical demands through the restorative moment of an external spring element, which possesses a mechanical advantage over the erector spinae. Although the PLAD has proven effective at reducing low back muscular demand, spinal moments, and localized muscular fatigue during laboratory and industrial tasks, the effects of the device on the neuromuscular control of spinal stability during lifting have yet to be assessed. Thirty healthy subjects (15M, 15F) performed repetitive lifting for three minutes, at a rate of 10 lifts per minute, with and without the PLAD. Maximum finite-time Lyapunov exponents, representing short-term (λ(max-s)) and long-term (λ(max-l)) divergence were calculated from the measured trunk kinematics to estimate the local dynamic stability of the lumbar spine. Using a mixed-design repeated-measures ANOVA, it was determined that wearing the PLAD did not significantly change λ(max-s) (μ(NP)=0.335, μ(P)=0.321, p=0.225), but did significantly reduce λ(max-l) (μ(NP)=0.0024, μ(P)=-0.0011, p=0.014, η(2)=0.197). There were no between-subject effects of sex, or significant interactions (p>0.720). The present results indicated that λ(max-s) was not statistically different between the device conditions, but that the PLAD significantly reduced λ(max-l) to a negative (stable) value. This shows that subjects' neuromuscular systems were able to respond to local perturbations more effectively when wearing the device, reflecting a more stable control of spinal movements. These findings are important when recommending the PLAD for long-term industrial or clinical use.

  1. Chromosome Disorder Outreach

    Science.gov (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 ...

  2. Cell division control by the Chromosomal Passenger Complex

    Energy Technology Data Exchange (ETDEWEB)

    Waal, Maike S. van der; Hengeveld, Rutger C.C.; Horst, Armando van der; Lens, Susanne M.A., E-mail: s.m.a.lens@umcutrecht.nl

    2012-07-15

    The Chromosomal Passenger Complex (CPC) consisting of Aurora B kinase, INCENP, Survivin and Borealin, is essential for genomic stability by controlling multiple processes during both nuclear and cytoplasmic division. In mitosis it ensures accurate segregation of the duplicated chromosomes by regulating the mitotic checkpoint, destabilizing incorrectly attached spindle microtubules and by promoting the axial shortening of chromosomal arms in anaphase. During cytokinesis the CPC most likely prevents chromosome damage by imposing an abscission delay when a chromosome bridge connects the two daughter cells. Moreover, by controlling proper cytoplasmic division, the CPC averts tetraploidization. This review describes recent insights on how the CPC is capable of conducting its various functions in the dividing cell to ensure chromosomal stability.

  3. Aggregate stability and associated C and N in a silty loam soil as affected by organic material inputs

    Institute of Scientific and Technical Information of China (English)

    LONG Pan; SUI Peng; GAO Wang-sheng; WANG Bin-bin; HUANG Jian-xiong; YAN Peng; ZOU Juan-xiu; YAN Ling-ling; CHEN Yuan-quan

    2015-01-01

    To make recycling utilization of organic materials produced in various agricultural systems, ifve kinds of organic materials were applied in a ifeld test, including crop straw (CS), biogas residue (BR), mushroom residue (MR), wine residue (WR), pig manure (PM), with a mineral fertilizer (CF) and a no-fertilizer (CK) treatment as a control. Our objectives were:i) to quantify the effects of organic materials on soil C and N accumulation;i ) to evaluate the effects of organic materials on soil aggregate stability, along with the total organic carbon (TOC), and N in different aggregate fractions;and i i) to assess the relationships among the organic material components, soil C and N, and C, N in aggregate fractions. The trial was conducted in Wuqiao County, Hebei Province, China. The organic materials were incorporated at an equal rate of C, and combined with a mineral fertilizer in amounts of 150 kg N ha-1, 26 kg P ha-1 and 124 kg K ha-1 respectively during each crop season of a wheat-maize rotation system. The inputted C quantity of each organic material treatment was equivalent to the total amount of C contained in the crop straw harvested in CS treatement in the previous season. TOC, N, water-stable aggregates, and aggregate-associated TOC and N were investigated. The results showed that organic material incorpora-tion increased soil aggregation and stabilization. On average, the soil macroaggregate proportion increased by 14%, the microaggregate proportion increased by 3%, and mean-weight diameter (MWD) increased by 20%. TOC content fol owed the order of PM>WR>MR>BR>CS>CK>CF;N content fol owed the order WR>PM>MR>BR>CS>CF>CK. No signiifcant correlation was found between TOC, N, and the quality of organic material. Soil silt and clay particles contained the largest part of TOC, whereas the smal macroaggregate fraction was the most sensitive to organic materials. Our results indicate that PM and WR exerted better effects on soil C and N accumulation, fol owed by MR

  4. Permeability models affecting nonlinear stability in the asymptotic suction boundary layer: the Forchheimer versus the Darcy model

    Science.gov (United States)

    Wedin, Håkan; Cherubini, Stefania

    2016-12-01

    The asymptotic suction boundary layer (ASBL) is used for studying two permeability models, namely the Darcy and the Forchheimer model, the latter being more physically correct according to the literature. The term that defines the two apart is a function of the non-Darcian wall permeability {\\hat{K}}2 and of the wall suction {\\hat{V}}0, whereas the Darcian wall permeability {\\hat{K}}1 is common to the two models. The underlying interest of the study lies in the field of transition to turbulence where focus is put on two-dimensional nonlinear traveling waves (TWs) and their three-dimensional linear stability. Following a previous study by Wedin et al (2015 Phys. Rev. E 92 013022), where only the Darcy model was considered, the present work aims at comparing the two models, assessing where in the parameter space they cease to produce the same results. For low values of {\\hat{K}}1 both models produce almost identical TW solutions. However, when both increasing the suction {\\hat{V}}0 to sufficiently high amplitudes (i.e. lowering the Reynolds number Re, based on the displacement thickness) and using large values of the wall porosity, differences are observed. In terms of the non-dimensional Darcian wall permeability parameter, a, strong differences in the overall shape of the bifurcation curves are observed for a≳ 0.70, with the emergence of a new family of solutions at Re lower than 100. For these large values of a, a Forchheimer number {{Fo}}\\max ≳ 0.5 is found, where Fo expresses the ratio between the kinetic and viscous forces acting on the porous wall. Moreover, the minimum Reynolds number, {{Re}}g, for which the Navier-Stokes equations allow for nonlinear solutions, decreases for increasing values of a. Fixing the streamwise wavenumber to α = 0.154, as used in the study by Wedin et al referenced above, we find that {{Re}}g is lowered from Re ≈ 3000 for zero permeability, to below 50 for a = 0.80 for both permeability models. Finally, the stability of

  5. 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

    1995-06-01

    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.

  6. Hepatitis B Virus Core Protein Phosphorylation Sites Affect Capsid Stability and Transient Exposure of the C-terminal Domain.

    Science.gov (United States)

    Selzer, Lisa; Kant, Ravi; Wang, Joseph C-Y; Bothner, Brian; Zlotnick, Adam

    2015-11-20

    Hepatitis B virus core protein has 183 amino acids divided into an assembly domain and an arginine-rich C-terminal domain (CTD) that regulates essential functions including genome packaging, reverse transcription, and intracellular trafficking. Here, we investigated the CTD in empty hepatitis B virus (HBV) T=4 capsids. We examined wild-type core protein (Cp183-WT) and a mutant core protein (Cp183-EEE), in which three CTD serines are replaced with glutamate to mimic phosphorylated protein. We found that Cp183-WT capsids were less stable than Cp183-EEE capsids. When we tested CTD sensitivity to trypsin, we detected two different populations of CTDs differentiated by their rate of trypsin cleavage. Interestingly, CTDs from Cp183-EEE capsids exhibited a much slower rate of proteolytic cleavage when compared with CTDs of Cp183-WT capsids. Cryo-electron microscopy studies of trypsin-digested capsids show that CTDs at five-fold symmetry vertices are most protected. We hypothesize that electrostatic interactions between glutamates and arginines in Cp183-EEE, particularly at five-fold, increase capsid stability and reduce CTD exposure. Our studies show that quasi-equivalent CTDs exhibit different rates of exposure and thus might perform distinct functions during the hepatitis B virus lifecycle. Our results demonstrate a structural role for CTD phosphorylation and indicate crosstalk between CTDs within a capsid particle.

  7. Storage Stability of Kinnow Fruit (Citrus reticulata as Affected by CMC and Guar Gum-Based Silver Nanoparticle Coatings

    Directory of Open Access Journals (Sweden)

    Syed Wasim Ahmad Shah

    2015-12-01

    Full Text Available The influence of carboxy methyl cellulose (CMC and guargum-based coatings containing silver nanoparticles was studied on the postharvest storage stability of the kinnow mandarin (Citrus reticulata cv. Blanco for a period of 120 days (85%–90% relative humidity at 4 °C and 10 °C. Physicochemical and microbiological qualities were monitored after every 15 days of storage. Overall results revealed an increase in total soluble solid (TSS, total sugars, reducing sugars and weight loss but this increase was comparatively less significant in coated fruits stored at 4 °C. Ascorbic acid, total phenolics, and antioxidant activity was significantly enhanced in coated fruits stored at 4 °C. Titratable acidity significantly decreased during storage except for coated kinnow stored at 4 °C. In control samples stored at 10 °C, high intensity of fruit rotting and no chilling injury was observed. Total aerobic psychrotrophic bacteria and yeast and molds were noticed in all treatments during storage but the growth was not significant in coated fruits at 4 °C. Kinnow fruit can be kept in good quality after coating for four months at 4 °C and for 2 months at 10 °C.

  8. Chromosome painting in plants.

    NARCIS (Netherlands)

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

    2001-01-01

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

  9. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

    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

  10. A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells.

    Science.gov (United States)

    Partanen, Sanna; Storch, Stephan; Löffler, Hans-Gerhard; Hasilik, Andrej; Tyynelä, Jaana; Braulke, Thomas

    2003-01-01

    The substitution of an active-site aspartic acid residue by asparagine in the lysosomal protease cathepsin D (CTSD) results in a loss of enzyme activity and severe cerebrocortical atrophy in a novel form of neuronal ceroid lipofuscinosis in sheep [Tyynelä, Sohar, Sleat, Gin, Donnelly, Baumann, Haltia and Lobel (2000) EMBO J. 19, 2786-2792]. In the present study we have introduced the corresponding mutation by replacing aspartic acid residue 293 with asparagine (D293N) into the mouse CTSD cDNA to analyse its effect on synthesis, transport and stability in transfected HEK-293 cells. The complete inactivation of mutant D293N mouse CTSD was confirmed by a newly developed fluorimetric quantification system. Moreover, in the heterologous overexpression systems used, mutant D293N mouse CTSD was apparently unstable and proteolytically modified during early steps of the secretory pathway, resulting in a loss of mass by about 1 kDa. In the affected sheep, the endogenous mutant enzyme was stable but also showed the shift in its molecular mass. In HEK-293 cells, the transport of the mutant D293N mouse CTSD to the lysosome was delayed and associated with a low secretion rate compared with wild-type CTSD. These data suggest that the mutation may result in a conformational change which affects stability, processing and transport of the enzyme. PMID:12350228

  11. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation

    Directory of Open Access Journals (Sweden)

    Rafael Pérez-Pérez

    2016-08-01

    Full Text Available Mitochondrial respiratory chain (MRC complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.

  12. Role of ATRX in chromatin structure and function: implications for chromosome instability and human disease.

    Science.gov (United States)

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

    2011-08-01

    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.

  13. 会计稳健性影响因素实证研究%An Empirical Research on Accounting Factors Affecting the Stability

    Institute of Scientific and Technical Information of China (English)

    赵小玉

    2011-01-01

    以2009年沪深两市的上市公司数据作为研究样本,在Basu模型的基础上,增加了新的变量,以影响因素的替代变量为解释变量,对影响会计稳健性的因素进行了实证研究。结果表明:会计信息对"坏消息"的敏感程度比对"好消息"敏感程度更强公司规模与会计稳健性存在负相关关系,市价账面比与会计稳健性存在正相关关系,财务杠杆与会计稳健性的关系与国外研究结果不一致。该研究结果与国外的研究结果基本一致。%With the data of the public company in Shanghai and Shenzhen markets in 2009 as the research sample,an empirical study is made for the elements of affecting the accounting stability,which is on the base of Basu model,adding the new variable and making the substitution variables of the influence factors as explanatory variable.The result shows that the degree of sensitivity for the accounting information facing the bad news is much higher than that facing the good news.There exists the negative correlation between the scale of the company and accounting stability,while the positive correlation exists between the ratios of market price and accounting stability,the study result for the relationship between the financial leverage and the accounting stability is different from the result abroad.This research result is almost the same with the one oversea.

  14. Evaluating factors affecting the permeability of emulsions used to stabilize radioactive contamination from a radiological dispersal device.

    Science.gov (United States)

    Fox, Garey A; Medina, Victor F

    2005-05-15

    Present strategies for alleviating radioactive contamination from a radiological dispersal device (RDD) or dirty bomb involve either demolishing and removing radioactive surfaces or abandoning portions of the area near the release point. In both cases, it is imperative to eliminate or reduce migration of the radioisotopes until the cleanup is complete or until the radiation has decayed back to acceptable levels. This research investigated an alternative strategy of using emulsions to stabilize radioactive particulate contamination. Emergency response personnel would coat surfaces with emulsions consisting of asphalt or tall oil pitch to prevent migration of contamination. The site can then be evaluated and cleaned up as needed. In order for this approach to be effective, the treatment must eliminate migration of the radioactive agents in the terror device. Water application is an environmental condition that could promote migration into the external environment. This research investigated the potential for water, and correspondingly contaminant, migration through two emulsions consisting of Topein, a resinous byproduct during paper manufacture. Topein C is an asphaltic-based emulsion and Topein S is a tall oil pitch, nonionic emulsion. Experiments included water adsorption/ mobilization studies, filtration tests, and image analysis of photomicrographs from an environmental scanning electron microscope (ESEM) and a stereomicroscope. Both emulsions were effective at reducing water migration. Conductivity estimates were on the order of 10(-80) cm s(-1) for Topein C and 10(-7) cm s(-1) for Topein S. Water mobility depended on emulsion flocculation and coalescence time. Photomicrographs indicate that Topein S consisted of greater and more interconnected porosity. Dilute foams of isolated spherical gas cells formed when emulsions were applied to basic surfaces. Gas cells rose to the surface and ruptured, leaving void spaces that penetrated throughout the emulsion. These

  15. Experimentally increased temperature and hypoxia affect stability of social hierarchy and metabolism of the Amazonian cichlid Apistogramma agassizii.

    Science.gov (United States)

    Kochhann, Daiani; Campos, Derek Felipe; Val, Adalberto Luis

    2015-12-01

    The primary goal of this study was to understand how changes in temperature and oxygen could influence social behaviour and aerobic metabolism of the Amazonian dwarf cichlid Apistogramma agassizii. Social hierarchies were established over a period of 96h by observing the social interactions, feeding behaviour and shelter use in groups of four males. In the experimental environment, temperature was increased to 29°C in the high-temperature treatment, and oxygen lowered to 1.0mg·L(-1)O2 in the hypoxia treatment. Fish were maintained at this condition for 96h. The control was maintained at 26°C and 6.6mg·L(-1)O2. After the experimental exposure, metabolism was measured as routine metabolic rate (RMR) and electron transport system (ETS) activity. There was a reduction in hierarchy stability at high-temperature. Aggression changed after environmental changes. Dominant and subdominant fish at high temperatures increased their biting, compared with control-dominant. In contrast, hypoxia-dominant fish decreased their aggressive acts compared with all other fish. Shelter use decreased in control and hypoxic dominant fish. Dominant fish from undisturbed environments eat more than their subordinates. There was a decrease of RMR in fish exposed to the hypoxic environment when compared with control or high-temperature fish, independent of social position. Control-dominant fish had higher RMR than their subordinates. ETS activity increased in fish exposed to high temperatures; however, there was no effect on social rank. Our study reinforces the importance of environmental changes for the maintenance of hierarchies and their characteristics and highlights that most of the changes occur in the dominant position.

  16. Factors affecting individual foraging specialization and temporal diet stability across the range of a large “generalist” apex predator

    Science.gov (United States)

    Rosenblatt, Adam E.; Nifong, James C.; Heithaus, Michael R.; Mazzotti, Frank J.; Cherkiss, Michael S.; Jeffery, Brian M.; Elsey, Ruth M.; Decker, Rachel A.; Silliman, Brian R.; Guillette, Louis J.; Lowers, Russell H.; Larson, Justin C.

    2015-01-01

    Individual niche specialization (INS) is increasingly recognized as an important component of ecological and evolutionary dynamics. However, most studies that have investigated INS have focused on the effects of niche width and inter- and intraspecific competition on INS in small-bodied species for short time periods, with less attention paid to INS in large-bodied reptilian predators and the effects of available prey types on INS. We investigated the prevalence, causes, and consequences of INS in foraging behaviors across different populations of American alligators (Alligator mississippiensis), the dominant aquatic apex predator across the southeast US, using stomach contents and stable isotopes. Gut contents revealed that, over the short term, although alligator populations occupied wide ranges of the INS spectrum, general patterns were apparent. Alligator populations inhabiting lakes exhibited lower INS than coastal populations, likely driven by variation in habitat type and available prey types. Stable isotopes revealed that over longer time spans alligators exhibited remarkably consistent use of variable mixtures of carbon pools (e.g., marine and freshwater food webs). We conclude that INS in large-bodied reptilian predator populations is likely affected by variation in available prey types and habitat heterogeneity, and that INS should be incorporated into management strategies to efficiently meet intended goals. Also, ecological models, which typically do not consider behavioral variability, should include INS to increase model realism and applicability.

  17. The X chromosome and immune associated genes.

    Science.gov (United States)

    Bianchi, Ilaria; Lleo, Ana; Gershwin, M Eric; Invernizzi, Pietro

    2012-05-01

    The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. Again, the plethora of autoimmune stigmata observed in patients with Turner syndrome, a disease due to the lack of one X chromosome or the presence of major X chromosome deletions, indicate that X-linked genes play a unique and major role in autoimmunity. There have been several reports on a role of X chromosome gene dosage through inactivation or duplication in women with autoimmune diseases, for example through a higher rate of circulating cells with a single X chromosome (i.e. with X monosomy). Finally, a challenge for researchers in the coming years will be to dissect the role for the large number of X-linked microRNAs from the perspective of autoimmune disease development. Taken together, X chromosome might well constitute the common trait of the susceptibility to autoimmune diseases, other than to explain the female preponderance of these conditions. This review will focus on the available evidence on X chromosome changes and discuss their potential implications and limitations.

  18. Chromosomal instability in meningiomas.

    Science.gov (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

    2005-04-01

    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.

  19. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    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.

  20. The Precarious Prokaryotic Chromosome

    OpenAIRE

    Kuzminov, Andrei

    2014-01-01

    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...

  1. Mechanisms for chromosome segregation.

    Science.gov (United States)

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

    2014-12-01

    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.

  2. Spatial organization of chromatin domains and compartments in single chromosomes.

    Science.gov (United States)

    Wang, Siyuan; Su, Jun-Han; Beliveau, Brian J; Bintu, Bogdan; Moffitt, Jeffrey R; Wu, Chao-ting; Zhuang, Xiaowei

    2016-08-05

    The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.

  3. Conserved sex chromosomes across adaptively radiated Anolis lizards.

    Science.gov (United States)

    Rovatsos, Michail; Altmanová, Marie; Pokorná, Martina; Kratochvíl, Lukáš

    2014-07-01

    Vertebrates possess diverse sex-determining systems, which differ in evolutionary stability among particular groups. It has been suggested that poikilotherms possess more frequent turnovers of sex chromosomes than homoiotherms, whose effective thermoregulation can prevent the emergence of the sex reversals induced by environmental temperature. Squamate reptiles used to be regarded as a group with an extensive variability in sex determination; however, we document how the rather old radiation of lizards from the genus Anolis, known for exceptional ecomorphological variability, was connected with stability in sex chromosomes. We found that 18 tested species, representing most of the phylogenetic diversity of the genus, share the gene content of their X chromosomes. Furthermore, we discovered homologous sex chromosomes in species of two genera (Sceloporus and Petrosaurus) from the family Phrynosomatidae, serving here as an outgroup to Anolis. We can conclude that the origin of sex chromosomes within iguanas largely predates the Anolis radiation and that the sex chromosomes of iguanas remained conserved for a significant part of their evolutionary history. Next to therian mammals and birds, Anolis lizards therefore represent another adaptively radiated amniote clade with conserved sex chromosomes. We argue that the evolutionary stability of sex-determining systems may reflect an advanced stage of differentiation of sex chromosomes rather than thermoregulation strategy.

  4. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    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.

  5. Chromosome oscillations in mitosis

    Science.gov (United States)

    Campas, Otger

    2008-03-01

    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.

  6. The thermodynamic stability of insulin disulfides is not affected by the C-domain of insulin-like growth factor 1

    Institute of Scientific and Technical Information of China (English)

    郭占云; 冯佑民

    2002-01-01

    Both Insulin and insulin-like growth factor 1 are members of insulin superfamily. They share homologous primary and tertiary structure as well as weakly overlapping biological activity. However, their folding behavior is different: insulin and its recombinant precursor (PIP) fold into one unique tertiary structure, while IGF-1 folds into two disulfides isomers with similar thermodynamic stability. To elucidate the molecular mechanism of their different folding behavior, we prepared a single-chain hybrid of insulin and IGF-1, [B10Glu]Ins/IGF-1(C), and studied its folding behavior compared with that of PIP and IGF-1. We also separated a major non-native disulfides isomer of the hybrid and studied its refolding. The data showed that the C-domain of IGF-1 did not affect the folding thermodynamics of insulin, that is, the primary structure of the hybrid encoded only one thermodynamically stable disulfides linkage. However, the folding kinetics of insulin was affected by the C-domain of IGF-1.

  7. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J

    1983-01-01

    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...

  8. 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

    2003-01-01

    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

  9. Increased sex chromosome expression and epigenetic abnormalities in spermatids from male mice with Y chromosome deletions.

    Science.gov (United States)

    Reynard, Louise N; Turner, James M A

    2009-11-15

    During male meiosis, the X and Y chromosomes are transcriptionally silenced, a process termed meiotic sex chromosome inactivation (MSCI). Recent studies have shown that the sex chromosomes remain substantially transcriptionally repressed after meiosis in round spermatids, but the mechanisms involved in this later repression are poorly understood. Mice with deletions of the Y chromosome long arm (MSYq-) have increased spermatid expression of multicopy X and Y genes, and so represent a model for studying post-meiotic sex chromosome repression. Here, we show that the increase in sex chromosome transcription in spermatids from MSYq- mice affects not only multicopy but also single-copy XY genes, as well as an X-linked reporter gene. This increase in transcription is accompanied by specific changes in the sex chromosome histone code, including almost complete loss of H4K8Ac and reduction of H3K9me3 and CBX1. Together, these data show that an MSYq gene regulates sex chromosome gene expression as well as chromatin remodelling in spermatids.

  10. Tracking of chromosome dynamics in live Streptococcus pneumoniae reveals that transcription promotes chromosome segregation.

    Science.gov (United States)

    Kjos, Morten; Veening, Jan-Willem

    2014-03-01

    Chromosome segregation is an essential part of the bacterial cell cycle but is poorly characterized in oval-shaped streptococci. Using time-lapse fluorescence microscopy and total internal reflection fluorescence microscopy, we have tracked the dynamics of chromosome segregation in live cells of the human pathogen Streptococcus pneumoniae. Our observations show that the chromosome segregation process last for two-thirds of the total cell cycle; the origin region segregates rapidly in the early stages of the cell cycle while nucleoid segregation finishes just before cell division. Previously we have demonstrated that the DNA-binding protein ParB and the condensin SMC promote efficient chromosome segregation, likely by an active mechanism. We now show that in the absence of SMC, cell division can occur over the unsegregated chromosomes. However, neither smc nor parB are essential in S. pneumoniae, suggesting the importance of additional mechanisms. Here we have identified the process of transcription as one of these mechanisms important for chromosome segregation in S. pneumoniae. Transcription inhibitors rifampicin and streptolydigin as well as mutants affected in transcription elongation cause chromosome segregation defects. Together, our results highlight the importance of passive (or indirect) processes such as transcription for chromosome segregation in oval-shaped bacteria.

  11. Climate, soil texture, and soil types affect the contributions of fine-fraction-stabilized carbon to total soil organic carbon in different land uses across China.

    Science.gov (United States)

    Cai, Andong; Feng, Wenting; Zhang, Wenju; Xu, Minggang

    2016-05-01

    Mineral-associated organic carbon (MOC), that is stabilized by fine soil particles (i.e., silt plus clay, soil organic carbon (SOC) persistence and sequestration, due to its large contribution to total SOC (TSOC) and long turnover time. Our objectives were to investigate how climate, soil type, soil texture, and agricultural managements affect MOC contributions to TSOC in China. We created a dataset from 103 published papers, including 1106 data points pairing MOC and TSOC across three major land use types: cropland, grassland, and forest. Overall, the MOC/TSOC ratio ranged from 0.27 to 0.80 and varied significantly among soil groups in cropland, grassland, and forest. Croplands and forest exhibited significantly higher median MOC/TSOC ratios than in grassland. Moreover, forest and grassland soils in temperate regions had higher MOC/TSOC ratios than in subtropical regions. Furthermore, the MOC/TSOC ratio was much higher in ultisol, compared with the other soil types. Both the MOC content and MOC/TSOC ratio were positively correlated with the amount of fine fraction (silt plus clay) in soil, highlighting the importance of soil texture in stabilizing organic carbon across various climate zones. In cropland, different fertilization practices and land uses (e.g., upland, paddy, and upland-paddy rotation) significantly altered MOC/TSOC ratios, but not in cropping systems (e.g., mono- and double-cropping) characterized by climatic differences. This study demonstrates that the MOC/TSOC ratio is mainly driven by soil texture, soil types, and related climate and land uses, and thus the variations in MOC/TSOC ratios should be taken into account when quantitatively estimating soil C sequestration potential of silt plus clay particles on a large scale.

  12. Major Bio-Factors Affecting Beef Color Stability%影响牛肉肉色稳定性的主要生化因子

    Institute of Scientific and Technical Information of China (English)

    陈景宜; 牛力; 黄明; 周光宏

    2012-01-01

    [Objective] The experiment was designed to investigate the major bio-factors affecting color stability from different bovine muscles, [Method] Three representative bovine muscles- M. longissimus lumborum (LL), M. semimembranosus (SM), and M. psoas major (PM) were obtained from 8 beef carcasses. Instrumental color, pigment content, pH value, MDA content, NADH concentration, LDH and metmyoglobin reductase activity were measured every two days over a period of 7d retail display at 0-4℃. [Result] The order of color stability of the three muscles was: LL>SM>PM. The a* value, NADH concentration, LDH and metmyoglobin reductase activity was the highest in LL and the MDA content was the least. While the a* value, NADH concentration, LDH and metmyoglobin reductase activity of PM was the lowest and MDA content was the highest. I Conclusion] NADH concentration, LDH and metmyoglobin reductase activity in beef muscle have a significant correlation with color stability (P<0.05) .%[目的]探讨影响不同部位的牛肉肉色稳定性差异的主要生化因素.[方法]从8头牛胴体上分别取背最长肌、半膜肌和腰大肌,在0-4℃冷藏7d,每隔1d分别测定肉色、色素含量、pH、MDA含量、NADH浓度、乳酸脱氢酶和高铁肌红蛋白还原酶活性等指标.[结果]背最长肌在整个冷藏期间的a*值最高且变化最小,MDA含量最少,NADH浓度、乳酸脱氢酶和高铁肌红蛋白还原酶活性最高,肉色最稳定;半膜肌居中,而腰大肌的a*值最小,变化最显著,MDA含量最高,NADH浓度、乳酸脱氢酶和高铁肌红蛋白还原酶活性最低,肉色最不稳定.[结论]牛肉肉色稳定性与其NADH浓度、乳酸脱氢酶和高铁肌红蛋白还原酶活性显著相关(P<0.05).

  13. XYY chromosome anomaly and schizophrenia.

    Science.gov (United States)

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

    1998-02-07

    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.

  14. Mutations in MAPT gene cause chromosome instability and introduce copy number variations widely in the genome.

    Science.gov (United States)

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

    2013-01-01

    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.

  15. The genetic background affects composition, oxidative stability and quality traits of Iberian dry-cured hams: purebred Iberian versus reciprocal Iberian × Duroc crossbred pigs.

    Science.gov (United States)

    Fuentes, Verónica; Ventanas, Sonia; Ventanas, Jesús; Estévez, Mario

    2014-02-01

    This study examined the physico-chemical characteristics, oxidative stability and sensory properties of Iberian cry-cured hams as affected by the genetic background of the pigs: purebred Iberian (PBI) pigs vs reciprocal cross-bred Iberian × Duroc pigs (IB × D pigs: Iberian dams × Duroc sires; D × IB pigs: Duroc dams × Iberian sires). Samples from PBI pigs contained significantly higher amounts of IMF, monounsaturated fatty acids, heme pigments and iron than those from crossbred pigs. The extent of lipid and protein oxidation was significantly larger in dry-cured hams of crossbred pigs than in those from PBI pigs. Dry-cured hams from PBI pigs were defined by positive sensory properties (i.e. redness, brightness and juiciness) while hams from crossbred pigs were ascribed to negative ones (i.e. hardness, bitterness and sourness). Hams from PBI pigs displayed a superior quality than those from crossbred pigs. The position of the dam or the sire in reciprocal Iberian × Duroc crosses had no effect on the quality of Iberian hams.

  16. Psychotic disorder and its characteristics in sex chromosome aneuploidies

    Directory of Open Access Journals (Sweden)

    Annapia Verri

    2009-09-01

    Full Text Available Sex chromosome anomalies have been associated with psychoses. We report a patient with XYY chromosome anomaly who developed a paranoid psychosis. The second case deal with a 51-year-old woman affected by Turner Syndrome and Psychotic Disorder, with a prevalent somatic and sexual focus.

  17. Never settling down: frequent changes in sex chromosomes.

    Directory of Open Access Journals (Sweden)

    Kevin H-C Wei

    2015-04-01

    Full Text Available A new study reveals multiple dramatic changes in sex chromosome structure and identity in flies; such transitions are accompanied by a series of genomic events that affect chromosome biology, gene regulation, and sex determination. See the accompanying Research Article.

  18. Sequential cloning of chromosomes

    Science.gov (United States)

    Lacks, S.A.

    1995-07-18

    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.

  19. Chromosomal mosaicism goes global

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    Yurov Yuri B

    2008-11-01

    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.

  20. Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes.

    Science.gov (United States)

    Kinney, Nicholas Allen; Onufriev, Alexey V; Sharakhov, Igor V

    2015-01-01

    We use a combined experimental and computational approach to study the effects of chromosome-nuclear envelope (Chr-NE) attachments on the 3D genome organization of Drosophila melanogaster (fruit fly) salivary gland nuclei. We consider 3 distinct models: a Null model - without specific Chr-NE attachments, a 15-attachment model - with 15 previously known Chr-NE attachments, and a 48-attachment model - with 15 original and 33 recently identified Chr-NE attachments. The radial densities of chromosomes in the models are compared to the densities observed in 100 experimental images of optically sectioned salivary gland nuclei forming "z-stacks." Most of the experimental z-stacks support the Chr-NE 48-attachment model suggesting that as many as 48 chromosome loci with appreciable affinity for the NE are necessary to reproduce the experimentally observed distribution of chromosome density in fruit fly nuclei. Next, we investigate if and how the presence and the number of Chr-NE attachments affect several key characteristics of 3D genome organization: chromosome territories and gene-gene contacts. This analysis leads to novel insight about the possible role of Chr-NE attachments in regulating the genome architecture. Specifically, we find that model nuclei with more numerous Chr-NE attachments form more distinct chromosome territories and their chromosomes intertwine less frequently. Intra-chromosome and intra-arm contacts are more common in model nuclei with Chr-NE attachments compared to the Null model (no specific attachments), while inter-chromosome and inter-arm contacts are less common in nuclei with Chr-NE attachments. We demonstrate that Chr-NE attachments increase the specificity of long-range inter-chromosome and inter-arm contacts. The predicted effects of Chr-NE attachments are rationalized by intuitive volume vs. surface accessibility arguments.

  1. CHROMOSOMES OF AMERICAN MARSUPIALS.

    Science.gov (United States)

    BIGGERS, J D; FRITZ, H I; HARE, W C; MCFEELY, R A

    1965-06-18

    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.

  2. Synthetic secondary chromosomes in Escherichia coli based on the replication origin of chromosome II in Vibrio cholerae.

    Science.gov (United States)

    Messerschmidt, Sonja J; Kemter, Franziska S; Schindler, Daniel; Waldminghaus, Torsten

    2015-02-01

    Recent developments in DNA-assembly methods make the synthesis of synthetic chromosomes a reachable goal. However, the redesign of primary chromosomes bears high risks and still requires enormous resources. An alternative approach is the addition of synthetic chromosomes to the cell. The natural secondary chromosome of Vibrio cholerae could potentially serve as template for a synthetic secondary chromosome in Escherichia coli. To test this assumption we constructed a replicon named synVicII based on the replication module of V. cholerae chromosome II (oriII). A new assay for the assessment of replicon stability was developed based on flow-cytometric analysis of unstable GFP variants. Application of this assay to cells carrying synVicII revealed an improved stability compared to a secondary replicon based on E. coli oriC. Cell cycle analysis and determination of cellular copy numbers of synVicII indicate that replication timing of the synthetic replicon in E. coli is comparable to the natural chromosome II (ChrII) in V. cholerae. The presented synthetic biology work provides the basis to use secondary chromosomes in E. coli to answer basic research questions as well as for several biotechnological applications.

  3. Chromosome analysis and sorting using flow cytometry.

    Science.gov (United States)

    Doležel, Jaroslav; Kubaláková, Marie; Cíhalíková, Jarmila; Suchánková, Pavla; Simková, Hana

    2011-01-01

    Chromosome analysis and sorting using flow cytometry (flow cytogenetics) is an attractive tool for fractionating plant genomes to small parts. The reduction of complexity greatly simplifies genetics and genomics in plant species with large genomes. However, as flow cytometry requires liquid suspensions of particles, the lack of suitable protocols for preparation of solutions of intact chromosomes delayed the application of flow cytogenetics in plants. This chapter outlines a high-yielding procedure for preparation of solutions of intact mitotic chromosomes from root tips of young seedlings and for their analysis using flow cytometry and sorting. Root tips accumulated at metaphase are mildly fixed with formaldehyde, and solutions of intact chromosomes are prepared by mechanical homogenization. The advantages of the present approach include the use of seedlings, which are easy to handle, and the karyological stability of root meristems, which can be induced to high degree of metaphase synchrony. Chromosomes isolated according to this protocol have well-preserved morphology, withstand shearing forces during sorting, and their DNA is intact and suitable for a range of applications.

  4. The chromosome 9q subtelomere deletion syndrome

    NARCIS (Netherlands)

    Stewart, D.R.; Kleefstra, T.

    2007-01-01

    The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invar

  5. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  6. [Sex chromosomes and meiosis].

    Science.gov (United States)

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

    2009-01-01

    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.

  7. Chromosome doubling method

    Science.gov (United States)

    Kato, Akio

    2006-11-14

    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.

  8. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)

    2016-01-01

    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.

  9. Chromosome painting reveals asynaptic full alignment of homologs and HIM-8-dependent remodeling of X chromosome territories during Caenorhabditis elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Kentaro Nabeshima

    2011-08-01

    Full Text Available During early meiotic prophase, a nucleus-wide reorganization leads to sorting of chromosomes into homologous pairs and to establishing associations between homologous chromosomes along their entire lengths. Here, we investigate global features of chromosome organization during this process, using a chromosome painting method in whole-mount Caenorhabditis elegans gonads that enables visualization of whole chromosomes along their entire lengths in the context of preserved 3D nuclear architecture. First, we show that neither spatial proximity of premeiotic chromosome territories nor chromosome-specific timing is a major factor driving homolog pairing. Second, we show that synaptonemal complex-independent associations can support full lengthwise juxtaposition of homologous chromosomes. Third, we reveal a prominent elongation of chromosome territories during meiotic prophase that initiates prior to homolog association and alignment. Mutant analysis indicates that chromosome movement mediated by association of chromosome pairing centers (PCs with mobile patches of the nuclear envelope (NE-spanning SUN-1/ZYG-12 protein complexes is not the primary driver of territory elongation. Moreover, we identify new roles for the X chromosome PC (X-PC and X-PC binding protein HIM-8 in promoting elongation of X chromosome territories, separable from their role(s in mediating local stabilization of pairing and association of X chromosomes with mobile SUN-1/ZYG-12 patches. Further, we present evidence that HIM-8 functions both at and outside of PCs to mediate chromosome territory elongation. These and other data support a model in which synapsis-independent elongation of chromosome territories, driven by PC binding proteins, enables lengthwise juxtaposition of chromosomes, thereby facilitating assessment of their suitability as potential pairing partners.

  10. Human ring chromosomes and small supernumerary marker chromosomes-do they have telomeres?

    Science.gov (United States)

    Guilherme, Roberta Santos; Klein, Elisabeth; Venner, Claudia; Hamid, Ahmed B; Bhatt, Samarth; Melaragno, Maria Isabel; Volleth, Marianne; Polityko, Anna; Kulpanovich, Anna; Kosyakova, Nadezda; Liehr, Thomas

    2012-10-01

    Ring chromosomes and small supernumerary marker chromosomes (sSMC) are enigmatic types of derivative chromosomes, in which the telomeres are thought to play a crucial role in their formation and stabilization. Considering that there are only a few studies that evaluate the presence of telomeric sequences in ring chromosomes and on sSMC, here, we analyzed 14 ring chromosomes and 29 sSMC for the presence of telomeric sequences through fluorescence in situ hybridization (FISH). The results showed that ring chromosomes can actually fall into two groups: the ones with or without telomeres. Additionally, telomeric signals were detectable at both ends of centric and neocentric sSMC with inverted duplication shape, as well as in complex sSMC. Apart from that, generally both ring- and centric minute-shaped sSMC did not present telomeric sequences neither detectable by FISH nor by a second protein-directed immunohistochemical approach. However, the fact that telomeres are absent does not automatically mean that the sSMC has a ring shape, as often deduced in the previous literature. Overall, the results obtained by FISH studies directed against telomeres need to be checked carefully by other approaches.

  11. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

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

  12. 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

    2016-01-01

    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.

  13. Recovery and Visualization of 3D Structure of Chromosomes from Tomographic Reconstruction Images

    Directory of Open Access Journals (Sweden)

    Tsap Leonid V

    2006-01-01

    Full Text Available The objectives of this work include automatic recovery and visualization of a 3D chromosome structure from a sequence of 2D tomographic reconstruction images taken through the nucleus of a cell. Structure is very important for biologists as it affects chromosome functions, behavior of the cell, and its state. Analysis of chromosome structure is significant in the detection of diseases, identification of chromosomal abnormalities, study of DNA structural conformation, in-depth study of chromosomal surface morphology, observation of in vivo behavior of the chromosomes over time, and in monitoring environmental gene mutations. The methodology incorporates thresholding based on a histogram analysis with a polyline splitting algorithm, contour extraction via active contours, and detection of the 3D chromosome structure by establishing corresponding regions throughout the slices. Visualization using point cloud meshing generates a 3D surface. The 3D triangular mesh of the chromosomes provides surface detail and allows a user to interactively analyze chromosomes using visualization software.

  14. Release of chromosomes from the nuclear envelope: a universal mechanism for eukaryotic mitosis?

    Science.gov (United States)

    Kanoh, Junko

    2013-01-01

    Multiple domains of chromosomes are associated with the nuclear envelope (NE) in interphase. The association between chromosomes and the NE is involved in a variety of chromosomal reactions, such as gene expression and DNA repair. However, efficient chromosome movements are required for the fidelity of chromosome segregation in mitosis. Most higher eukaryotes perform open mitosis, in which the NE is broken down, enabling chromosomes to be released from the NE as well as spindle microtubules to access to kinetochores. By contrast, lower eukaryotes, such as Schizosaccharomyces pombe, perform closed mitosis, during which NE breakdown does not occur. In S. pombe, telomeres are tethered to the NE in interphase. Phosphorylation of the telomere-binding protein Rap1 at M phase promotes transient dissociation of telomeres from the NE, facilitating the faithful chromosome segregation. These findings imply a common mechanism for genome stability via the dissociation of chromosomes from the NE in eukaryotic mitosis.

  15. Klinefelter syndrome and other sex chromosomal aneuploidies

    Directory of Open Access Journals (Sweden)

    Graham John M

    2006-10-01

    Full Text Available Abstract The term Klinefelter syndrome (KS describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH, and luteinizing hormone (LH. The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ decrease of approximately 15–16 points, with language most affected

  16. Are chromosomal imbalances important in cancer?

    Science.gov (United States)

    Stallings, Raymond L

    2007-06-01

    Tumor-specific patterns of large-scale chromosomal imbalances characterize most forms of cancer. Based on evidence primarily from neuroblastomas, it can be argued that large-scale chromosomal imbalances are crucial for tumor pathogenesis and have an impact on the global transcriptional profile of cancer cells, and that some imbalances even initiate cancer. The genes and genetic pathways that have been dysregulated by such imbalances remain surprisingly elusive. Many genes are affected by the regions of gain and loss, and there are complex interactions and relationships that occur between these genes, hindering their identification. The study of untranslated RNA sequences, such as microRNAs, is in its infancy, and it is likely that such sequences are also dysregulated by chromosomal imbalance, contributing to pathogenesis.

  17. "Chromosome": a knowledge-based system for the chromosome classification.

    Science.gov (United States)

    Ramstein, G; Bernadet, M

    1993-01-01

    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.

  18. Liquid marbles stabilized by charged polymer latexes: how does the drying of the latex particles affect the properties of liquid marbles?

    Science.gov (United States)

    Sun, Guanqing; Sheng, Yifeng; Wu, Jie; Ma, Guanghui; Ngai, To

    2014-10-28

    The coating of solid particles on the surface of liquid in air makes liquid marbles a promising approach in the transportation of a small amount of liquid. The stabilization of liquid marbles by polymeric latex particles imparts extra triggers such as pH and temperature, leading to the remote manipulation of droplets for many potential applications. Because the functionalized polymeric latexes can exist either as colloidally stable latex or as flocculated latex in a dispersion, the drying of latex dispersions under different conditions may play a significant role in the stabilization of subsequent liquid marbles. This article presents the investigation of liquid marbles stabilized by poly(styrene-co-methacrylic acid) (PS-co-MAA) particles drying under varied conditions. Protonation of the particles before freeze drying makes the particles excellent liquid marble stabilizers, but it is hard to stabilize liquid marbles for particles dried in their deprotonated states. The static properties of liquid marbles with increasing concentrations of protonating reagent revealed that the liquid marbles are gradually undermined by protonating the stabilizers. Furthermore, the liquid marbles stabilized by different particles showed distinct behaviors in separation and merging manipulated by tweezers. This study shows that the initial state of the particles should be carefully taken into account in formulating liquid marbles.

  19. The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

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    Tamara Potapova

    2017-02-01

    Full Text Available Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.

  20. The chromosome sets stability of hybrid progeny in different ploidy loach%不同倍性泥鳅杂交后代染色体数目组成的研究

    Institute of Scientific and Technical Information of China (English)

    李雅娟; 钱聪; 印杰; 高敏; 高养春; 刘博; 王玉生

    2012-01-01

    The early embryo, and 6-month old and 12-month old reciprocal crossed triploid progenies were obtained through the cross of diploid loach and natural tetraploid loach (original crossed 2n×4n, reciprocal crossed 4n ×2n) , and these six hybrid groups were studied in this article. According to the method of chromosome counting, the chromosome amounts of these hybrid triploid progenies were counted and analysed. Consequently, the chromosome number of early embryonic cells of original crossed and reciprocal crossed progenies ranged from 67 to 81, 67 to 82. The percentages of the number of triploid's chromosome (3n=75) were 22% and 20% in one hundred well metaphases of the early embryonic cells. And this was the highest percent compared with other chromosome number in the same group. In addition, the hypo-triploid (3n75) (41% , 29%) were found largely. The chromosome number of 6-month original crossed and reciprocal crossed progenies were in the range of 68 to 79, 66 to 80. It was also the maximal percentage (26% , 41% ) in their respective group when the number of triploid's chromosome was 75. Moreover, massive hypo-triploid (34% , 49% ) and hyper-triploid (40% , 10%) were discovered. The chromosome quantities of 12-month original crossed and reciprocal crossed progenies varied from 68 to 82, 69 to 83. Similarly, the percentage of the chromosome number (3n = 75) was also higher than others in each group (28% , 54%). There were also findings many hypo-triploids (48% , 20% ) and hyper-triploids (24% , 26% ). The findings showed that the reciprocal crossed triploid progenies were obtained through the hybridization of diploid loach (female and male) and natural tetraploid loach ( male and female) were found lots of non integral triploid survived, the percentage of non integral triploids were downtrend with the prolonging cultural period and the percentage of original crossed non integral triploid was more than the percentage of reciprocal crossed non integral triploid

  1. The two-component system CpxR/A represses the expression of Salmonella virulence genes by affecting the stability of the transcriptional regulator HilD

    Science.gov (United States)

    De la Cruz, Miguel A.; Pérez-Morales, Deyanira; Palacios, Irene J.; Fernández-Mora, Marcos; Calva, Edmundo; Bustamante, Víctor H.

    2015-01-01

    Salmonella enterica can cause intestinal or systemic infections in humans and animals mainly by the presence of pathogenicity islands SPI-1 and SPI-2, containing 39 and 44 genes, respectively. The AraC-like regulator HilD positively controls the expression of the SPI-1 genes, as well as many other Salmonella virulence genes including those located in SPI-2. A previous report indicates that the two-component system CpxR/A regulates the SPI-1 genes: the absence of the sensor kinase CpxA, but not the absence of its cognate response regulator CpxR, reduces their expression. The presence and absence of cell envelope stress activates kinase and phosphatase activities of CpxA, respectively, which in turn controls the level of phosphorylated CpxR (CpxR-P). In this work, we further define the mechanism for the CpxR/A-mediated regulation of SPI-1 genes. The negative effect exerted by the absence of CpxA on the expression of SPI-1 genes was counteracted by the absence of CpxR or by the absence of the two enzymes, AckA and Pta, which render acetyl-phosphate that phosphorylates CpxR. Furthermore, overexpression of the lipoprotein NlpE, which activates CpxA kinase activity on CpxR, or overexpression of CpxR, repressed the expression of SPI-1 genes. Thus, our results provide several lines of evidence strongly supporting that the absence of CpxA leads to the phosphorylation of CpxR via the AckA/Pta enzymes, which represses both the SPI-1 and SPI-2 genes. Additionally, we show that in the absence of the Lon protease, which degrades HilD, the CpxR-P-mediated repression of the SPI-1 genes is mostly lost; moreover, we demonstrate that CpxR-P negatively affects the stability of HilD and thus decreases the expression of HilD-target genes, such as hilD itself and hilA, located in SPI-1. Our data further expand the insight on the different regulatory pathways for gene expression involving CpxR/A and on the complex regulatory network governing virulence in Salmonella. PMID:26300871

  2. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  3. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  4. Factors Affecting the Oxidative Stability of Foods-Interesterified Soybean Oil with High Intensity Ultrasound Treatment and Trona Mineral in Packaged Fresh Meats

    OpenAIRE

    Lee, Jiwon

    2013-01-01

    Oxidation in oils and muscle foods has been studied for many years to understand its mechanism and furthermore to control and manage it. A series of different processing steps or different packaging techniques can alter oxidative stability. The objective of the current study was to examine oxidative stability of processed oil and to evaluate the effect of carbon dioxide generating mineral on quality of beef and chicken under different storage conditions. In Study 1 (Chapter 3), the effect of ...

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

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

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

  6. Agronomic performance, chromosomal stability and resistance to velvetbean caterpillar of transgenic soybean expressing cry1Ac gene Performance agronômica, estabilidade cromossômica e resistência à lagarta-da-soja em soja transgênica que expressa o gene cry1Ac

    Directory of Open Access Journals (Sweden)

    Milena Schenkel Homrich

    2008-07-01

    Full Text Available The objective of this work was to analyze the agronomic performance and chromosomal stability of transgenic homozygous progenies of soybean [Glycine max (L. Merrill.], and to confirm the resistance of these plants against Anticarsia gemmatalis. Eleven progenies expressing cry1Ac, hpt and gusA genes were evaluated for agronomic characteristics in relation to the nontransformed parent IAS 5 cultivar. Cytogenetical analysis was carried out on transgenic and nontransgenic plants. Two out of the 11 transgenic progenies were also evaluated, in vitro and in vivo, for resistance to A. gemmatalis. Two negative controls were used in resistance bioassays: a transgenic homozygous line, containing only the gusA reporter gene, and nontransgenic 'IAS 5' plants. The presence of cry1Ac transgene affected neither the development nor the yield of plants. Cytogenetical analysis showed that transgenic plants presented normal karyotype. In detached-leaf bioassay, cry1Ac plants exhibited complete efficacy against A. gemmatalis, whereas negative controls were significantly damaged. Whole-plant feeding assay confirmed a very high protection of cry1Ac against velvetbean caterpillar, while nontransgenic 'IAS 5' plants and homozygous gusA line exhibited 56.5 and 71.5% defoliation, respectively. The presence of cry1Ac transgene doesn't affect the majority of agronomic traits (including yield of soybean and grants high protection against A. gemmatalis.O objetivo deste trabalho foi analisar a performance agronômica e a estabilidade cromossômica de progênies transgênicas homozigotas de soja [Glycine max (L. Merrill.], e confirmar a resistência dessas plantas a Anticarsia gemmatalis. Onze progênies com expressão dos genes cry1Ac, hpt e gusA foram avaliadas quanto às características agronômicas, em relação à cultivar parental IAS 5 não transformada. Análises citogenéticas foram realizadas em plantas transgênicas e não transgênicas. Duas das 11 prog

  7. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    OpenAIRE

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

    2007-01-01

    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...

  8. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  9. Chromosome Variations And Human Behavior

    Science.gov (United States)

    Soudek, D.

    1974-01-01

    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)

  10. Ring chromosome 13

    DEFF Research Database (Denmark)

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

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...

  11. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  12. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  13. Why Chromosome Palindromes?

    Directory of Open Access Journals (Sweden)

    Esther Betrán

    2012-01-01

    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.

  14. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-01

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

  15. [Dicentric Y chromosome].

    Science.gov (United States)

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    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.

  16. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study.

    Science.gov (United States)

    Baccarani, Michele; Druker, Brian J; Branford, Susan; Kim, Dong-Wook; Pane, Fabrizio; Mongay, Lidia; Mone, Manisha; Ortmann, Christine-Elke; Kantarjian, Hagop M; Radich, Jerald P; Hughes, Timothy P; Cortes, Jorge E; Guilhot, François

    2014-01-01

    The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival(PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR.Adverse events were more frequent with high-dose imatinib. Patients with B1 treatment interruption (vs [1) and those able to maintain imatinib C600 mg/day (vs\\600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with longterm clinical outcomes.

  17. Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation.

    Directory of Open Access Journals (Sweden)

    Georgina Gómez-Saldivar

    2016-06-01

    Full Text Available Nucleoporins are the constituents of nuclear pore complexes (NPCs and are essential regulators of nucleocytoplasmic transport, gene expression and genome stability. The nucleoporin MEL-28/ELYS plays a critical role in post-mitotic NPC reassembly through recruitment of the NUP107-160 subcomplex, and is required for correct segregation of mitotic chromosomes. Here we present a systematic functional and structural analysis of MEL-28 in C. elegans early development and human ELYS in cultured cells. We have identified functional domains responsible for nuclear envelope and kinetochore localization, chromatin binding, mitotic spindle matrix association and chromosome segregation. Surprisingly, we found that perturbations to MEL-28's conserved AT-hook domain do not affect MEL-28 localization although they disrupt MEL-28 function and delay cell cycle progression in a DNA damage checkpoint-dependent manner. Our analyses also uncover a novel meiotic role of MEL-28. Together, these results show that MEL-28 has conserved structural domains that are essential for its fundamental roles in NPC assembly and chromosome segregation.

  18. Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes.

    Science.gov (United States)

    Schvarzstein, Mara; Wignall, Sarah M; Villeneuve, Anne M

    2010-02-01

    Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms must devise strategies to couple sister chromatids so that they stay together during the first meiotic division (when homologous chromosomes separate) and then segregate away from one another during the second division. Here we review recent findings that shed light on how Caenorhabditis elegans, an organism with holocentric chromosomes, deals with these challenges of meiosis by differentiating distinct chromosomal subdomains and remodeling chromosome structure during prophase. Furthermore, we discuss how features of chromosome organization established during prophase affect later chromosome behavior during the meiotic divisions. Finally, we illustrate how analysis of holocentric meiosis can inform our thinking about mechanisms that operate on monocentric chromosomes.

  19. Dynamics of X Chromosome Inactivation

    NARCIS (Netherlands)

    F. Loos (Friedemann)

    2015-01-01

    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).

  20. 中国汉人 X染色体上情感障碍易感性基因的遗传学研究及关联分析%Susceptible gene for affection disorder of chromosome X in Han people of Chinese:genetical study and relative analysis

    Institute of Scientific and Technical Information of China (English)

    吴怀安; 闫小华; 邓小敏; 沈其杰

    2002-01-01

    Objective In order to detect the Susceptible gene on X chromosome for Han nationality of Chinese who suffer from affective disorder(AD),to explore the association between DXS1114 polymorphism and AD and the feature of genetics.Method We used the technique of the amplified fragment length polymorphism(Amp FLP)to detect the polymorphism distribution of DXS1114 for 40 patients with AD and 40 normal controls.Results We found that there were 4 polymorphism fragments of DXS1114 on the γ -chromosome in AD and normal controls.The result of statistics showed that four polymorphism fragments(117bp.113bp.111bp 109bp)had not significant difference(P>0.05)between patients and normal controls.Conclusion We report that the DXS1114 is not associated with Chinese who suffer from AD.The results indicate that there maybe no a susceptible gene of AD on xq26.1 in our research simples.

  1. Origin and domestication of papaya Yh chromosome.

    Science.gov (United States)

    VanBuren, Robert; Zeng, Fanchang; Chen, Cuixia; Zhang, Jisen; Wai, Ching Man; Han, Jennifer; Aryal, Rishi; Gschwend, Andrea R; Wang, Jianping; Na, Jong-Kuk; Huang, Lixian; Zhang, Lingmao; Miao, Wenjing; Gou, Jiqing; Arro, Jie; Guyot, Romain; Moore, Richard C; Wang, Ming-Li; Zee, Francis; Charlesworth, Deborah; Moore, Paul H; Yu, Qingyi; Ming, Ray

    2015-04-01

    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 (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations' geographic locations, but gene flow is detected for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Y(h) arose only ∼ 4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h) chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males.

  2. Genome-wide detection of chromosomal rearrangements, indels, and mutations in circular chromosomes by short read sequencing

    DEFF Research Database (Denmark)

    Skovgaard, Ole; Bak, Mads; Løbner-Olesen, Anders;

    2011-01-01

    a combination of WGS and genome copy number analysis, for the identification of mutations that suppress the growth deficiency imposed by excessive initiations from the Escherichia coli origin of replication, oriC. The E. coli chromosome, like the majority of bacterial chromosomes, is circular, and DNA...... replication is initiated by assembling two replication complexes at the origin, oriC. These complexes then replicate the chromosome bidirectionally toward the terminus, ter. In a population of growing cells, this results in a copy number gradient, so that origin-proximal sequences are more frequent than...... origin-distal sequences. Major rearrangements in the chromosome are, therefore, readily identified by changes in copy number, i.e., certain sequences become over- or under-represented. Of the eight mutations analyzed in detail here, six were found to affect a single gene only, one was a large chromosomal...

  3. Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20.

    Science.gov (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

    2010-02-01

    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.

  4. Dicentric chromosomes: unique models to study centromere function and inactivation.

    Science.gov (United States)

    Stimpson, Kaitlin M; Matheny, Justyne E; Sullivan, Beth A

    2012-07-01

    Dicentric chromosomes are products of genome rearrangement that place two centromeres on the same chromosome. Depending on the organism, dicentric stability varies after formation. In humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell division. The molecular basis for centromere inactivation is not well understood, although studies in model organisms and in humans suggest that genomic and epigenetic mechanisms can be involved. Furthermore, constitutional dicentric chromosomes ascertained in patients presumably represent the most stable chromosomes, so the spectrum of dicentric fates, if it exists, is not entirely clear. Studies of engineered or induced dicentrics in budding yeast and plants have provided significant insight into the fate of dicentric chromosomes. And, more recently, studies have shown that dicentrics in humans can also undergo multiple fates after formation. Here, we discuss current experimental evidence from various organisms that has deepened our understanding of dicentric behavior and the intriguingly complex process of centromere inactivation.

  5. Familial complex chromosomal rearrangement resulting in a recombinant chromosome.

    Science.gov (United States)

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

    2002-05-15

    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.

  6. Homogenization conditions affect the oxidative stability of fish oil enriched milk emulsions: oxidation linked to changes in protein composition at the oil-water interface

    DEFF Research Database (Denmark)

    Sørensen, Ann-Dorit M.; Baron, Caroline P.; Let, Mette B.;

    2007-01-01

    Fish oil was incorporated into milk under different homogenization temperatures (50 and 72 °C) and pressures (5, 15, and 22.5 MPa). Subsequently, the oxidative stability of the milk and changes in the protein composition of the milk fat globule membrane (MFGM) were examined. Results showed...

  7. [Dicentric Y chromosomes. First part: cytogenetic and molecular aspects].

    Science.gov (United States)

    Bouayed Abdelmoula, N; Amouri, A

    2005-01-01

    Dicentric Y chromosomes have been reviewed twice in 1994 by Hsu et al. and in 1995 by Tuck-Muller et al. who showed that dic(Y) are the most common Y structural abnormalities and that their influence on gonadal and somatic development is extremely variable. The prediction of their phenotypic consequences is often difficult because of the variety of genomic sequences concerned by duplications and deletions, because of the variable degrees of mosaicism (cell line 45,X in particular) and at the end, because of identification and analysis technical difficulties of the structure of the rearranged Y chromosome. The clinical specter of this cytogenetic abnormality is rather wide going from almost-normal or infertile males, to females with or without stigmas of Turner syndrome. Middle phenotypes consist of various degrees of genital ambiguities. However, clinical expression seems to be related to the genomic capital of the Y chromosome, mainly the Y genes involved in the control of the process of the determination of gonads (Yp) and spermatogenesis (Yq) as well as control of the growth and the skeletal development (Yp). Here, we report a third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. In the light of previous reviews as well as the recent data of the genetic cartography of the Y chromosome, we try, in this first part, to determine characteristics of reported dicentric Y chromosomes as well as their chromosomal mechanics, their mitotic stability and finally their cytogenetic and molecular investigations.

  8. Effects of Sex Chromosome Aneuploidies on Brain Development: Evidence from Neuroimaging Studies

    Science.gov (United States)

    Lenroot, Rhoshel K.; Lee, Nancy Raitano; Giedd, Jay N.

    2009-01-01

    Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the…

  9. Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

    OpenAIRE

    Smith, Owen K.; Aladjem, Mirit I.

    2014-01-01

    The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes ...

  10. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  11. Meiotic sex chromosome inactivation in Drosophila.

    Science.gov (United States)

    Vibranovski, Maria D

    2014-01-01

    In several different taxa, there is indubitable evidence of transcriptional silencing of the X and Y chromosomes in male meiotic cells of spermatogenesis. However, the so called meiotic sex chromosome inactivation (MSCI) has been recently a hot bed for debate in Drosophila melanogaster. This review covers cytological and genetic observations, data from transgenic constructs with testis-specific promoters, global expression profiles obtained from mutant, wild-type, larvae and adult testes as well as from cells of different stages of spermatogenesis. There is no dispute on that D. melanogaster spermatogenesis presents a down-regulation of X chromosome that does not result from the lack of dosage compensation. However, the issue is currently focused on the level of reduction of X-linked expression, the precise time it occurs and how many genes are affected. The deep examination of data and experiments in this review exposes the limitations intrinsic to the methods of studying MSCI in D. melanogaster. The current methods do not allow us to affirm anything else than the X chromosome down-regulation in meiosis (MSCI). Therefore, conclusion about level, degree or precise timing is inadequate until new approaches are implemented to know the details of MSCI or other processes involved for D. melanogaster model.

  12. Analysis of SAT type foot-and-mouth disease virus capsid proteins and the identification of putative amino acid residues affecting virus stability.

    Science.gov (United States)

    Maree, Francois F; Blignaut, Belinda; de Beer, Tjaart A P; Rieder, Elizabeth

    2013-01-01

    Foot-and-mouth disease virus (FMDV) initiates infection by adhering to integrin receptors on target cells, followed by cell entry and disassembly of the virion through acidification within endosomes. Mild heating of the virions also leads to irreversible dissociation into pentamers, a characteristic linked to reduced vaccine efficacy. In this study, the structural stability of intra- and inter-serotype chimeric SAT2 and SAT3 virus particles to various conditions including low pH, mild temperatures or high ionic strength, was compared. Our results demonstrated that while both the SAT2 and SAT3 infectious capsids displayed different sensitivities in a series of low pH buffers, their stability profiles were comparable at high temperatures or high ionic strength conditions. Recombinant vSAT2 and intra-serotype chimeric viruses were used to map the amino acid differences in the capsid proteins of viruses with disparate low pH stabilities. Four His residues at the inter-pentamer interface were identified that change protonation states at pH 6.0. Of these, the H145 of VP3 appears to be involved in interactions with A141 in VP3 and K63 in VP2, and may be involved in orientating H142 of VP3 for interaction at the inter-pentamer interfaces.

  13. Paddy Soil Stability and Mechanical Properties as Affected by Long-Term Application of Chemical Fertilizer and Animal Manure in Subtropical China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Wet stability, penetration resistance (PR), and tensile strength (TS) of paddy soils under a fertilization experiment for 22 years were determined to elucidate the function of soil organic matter in paddy soil stabilization. The treatments included no fertilization (CK), normal chemical fertilization (NPK), double the NPK application rates (2NPK), and NPK mixed with organic manure (NPK+OM). Compared with CK, fertilization increased soil organic carbon (SOC) and soil porosity. The results of soil aggregate fragmentation degree (SAFD) showed that fast wetting by water was the key fragmentation mechanism. Among the treatments, the NPK+OM treatment had the largest size of water-stable aggregates and greatest normal mean weight diameter (NMWD) (P ≤ 0.05), but the lowest PR and TS in both cultivated horizon (Ap) and plow pan. The CK and 2NPK treatments were measured with PR > 2.0 MPa and friability index < 0.20,respectively, in the Ap horizon, suggesting that the soils was mechanically unfavourable to root growth and tillage. In the plow pan, the fertilization treatments had greater TS and PR than in CK. TS and PR of the tested soil aggregates were negatively correlated to SOC content and soil porosity. This study suggested that chemical fertilization could cause deterioration of mechanical properties while application of organic manure could improve soil stability and mechanical properties.

  14. Analysis of SAT Type Foot-And-Mouth Disease Virus Capsid Proteins and the Identification of Putative Amino Acid Residues Affecting Virus Stability

    Science.gov (United States)

    Maree, Francois F.; Blignaut, Belinda; de Beer, Tjaart A. P.; Rieder, Elizabeth

    2013-01-01

    Foot-and-mouth disease virus (FMDV) initiates infection by adhering to integrin receptors on target cells, followed by cell entry and disassembly of the virion through acidification within endosomes. Mild heating of the virions also leads to irreversible dissociation into pentamers, a characteristic linked to reduced vaccine efficacy. In this study, the structural stability of intra- and inter-serotype chimeric SAT2 and SAT3 virus particles to various conditions including low pH, mild temperatures or high ionic strength, was compared. Our results demonstrated that while both the SAT2 and SAT3 infectious capsids displayed different sensitivities in a series of low pH buffers, their stability profiles were comparable at high temperatures or high ionic strength conditions. Recombinant vSAT2 and intra-serotype chimeric viruses were used to map the amino acid differences in the capsid proteins of viruses with disparate low pH stabilities. Four His residues at the inter-pentamer interface were identified that change protonation states at pH 6.0. Of these, the H145 of VP3 appears to be involved in interactions with A141 in VP3 and K63 in VP2, and may be involved in orientating H142 of VP3 for interaction at the inter-pentamer interfaces. PMID:23717387

  15. Analysis of SAT type foot-and-mouth disease virus capsid proteins and the identification of putative amino acid residues affecting virus stability.

    Directory of Open Access Journals (Sweden)

    Francois F Maree

    Full Text Available Foot-and-mouth disease virus (FMDV initiates infection by adhering to integrin receptors on target cells, followed by cell entry and disassembly of the virion through acidification within endosomes. Mild heating of the virions also leads to irreversible dissociation into pentamers, a characteristic linked to reduced vaccine efficacy. In this study, the structural stability of intra- and inter-serotype chimeric SAT2 and SAT3 virus particles to various conditions including low pH, mild temperatures or high ionic strength, was compared. Our results demonstrated that while both the SAT2 and SAT3 infectious capsids displayed different sensitivities in a series of low pH buffers, their stability profiles were comparable at high temperatures or high ionic strength conditions. Recombinant vSAT2 and intra-serotype chimeric viruses were used to map the amino acid differences in the capsid proteins of viruses with disparate low pH stabilities. Four His residues at the inter-pentamer interface were identified that change protonation states at pH 6.0. Of these, the H145 of VP3 appears to be involved in interactions with A141 in VP3 and K63 in VP2, and may be involved in orientating H142 of VP3 for interaction at the inter-pentamer interfaces.

  16. Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

    Directory of Open Access Journals (Sweden)

    Judit Pampalona

    Full Text Available Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

  17. Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

    Science.gov (United States)

    Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

    2016-01-01

    Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

  18. Centromere inactivation on a neo-Y fusion chromosome in threespine stickleback fish.

    Science.gov (United States)

    Cech, Jennifer N; Peichel, Catherine L

    2016-12-01

    Having one and only one centromere per chromosome is essential for proper chromosome segregation during both mitosis and meiosis. Chromosomes containing two centromeres are known as dicentric and often mis-segregate during cell division, resulting in aneuploidy or chromosome breakage. Dicentric chromosome can be stabilized by centromere inactivation, a process which reestablishes monocentric chromosomes. However, little is known about this process in naturally occurring dicentric chromosomes. Using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence combined with FISH (IF-FISH) on metaphase chromosome spreads, we demonstrate that centromere inactivation has evolved on a neo-Y chromosome fusion in the Japan Sea threespine stickleback fish (Gasterosteus nipponicus). We found that the centromere derived from the ancestral Y chromosome has been inactivated. Our data further suggest that there have been genetic changes to this centromere in the two million years since the formation of the neo-Y chromosome, but it remains unclear whether these genetic changes are a cause or consequence of centromere inactivation.

  19. Social cognition and underlying cognitive mechanisms in children with an extra X chromosome : a comparison with autism spectrum disorder

    NARCIS (Netherlands)

    van Rijn, S.; Stockmann, L.; van Buggenhout, G.; van Ravenswaaij-Arts, C.; Swaab, H.

    2014-01-01

    Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess theory of mind and facial affect labeling in children with an extra X chromosome. Forty-six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with Tri

  20. The occurrence of different Bs in Cestrum intermedium and C. strigilatum (Solanaceae) evidenced by chromosome banding.

    Science.gov (United States)

    Fregonezi, J N; Rocha, C; Torezan, J M D; Vanzela, A L L

    2004-01-01

    In this study, we examine the morphology, mitotic stability, meiotic behavior and the composition of heterochromatin of B chromosomes in Cestrum intermedium and C. strigilatum. The results showed that B chromosome number shows intraindividual variation in the root meristem, which seems to lead to a slight rate of B elimination in this somatic tissue. B chromosomes in both species were similar in size and shape, but differed with regard to the type, size and distribution of heterochromatin. Possible evolutionary pathways for B chromosome origin in Cestrum are discussed.

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

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

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

  2. Cohesin Is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Shay Covo

    2010-07-01

    Full Text Available Double-strand break (DSB repair through homologous recombination (HR is an evolutionarily conserved process that is generally error-free. The risk to genome stability posed by nonallelic recombination or loss-of-heterozygosity could be reduced by confining HR to sister chromatids, thereby preventing recombination between homologous chromosomes. Here we show that the sister chromatid cohesion complex (cohesin is a limiting factor in the control of DSB repair and genome stability and that it suppresses DNA damage-induced interactions between homologues. We developed a gene dosage system in tetraploid yeast to address limitations on various essential components in DSB repair and HR. Unlike RAD50 and RAD51, which play a direct role in HR, a 4-fold reduction in the number of essential MCD1 sister chromatid cohesion subunit genes affected survival of gamma-irradiated G(2/M cells. The decreased survival reflected a reduction in DSB repair. Importantly, HR between homologous chromosomes was strongly increased by ionizing radiation in G(2/M cells with a single copy of MCD1 or SMC3 even at radiation doses where survival was high and DSB repair was efficient. The increased recombination also extended to nonlethal doses of UV, which did not induce DSBs. The DNA damage-induced recombinants in G(2/M cells included crossovers. Thus, the cohesin complex has a dual role in protecting chromosome integrity: it promotes DSB repair and recombination between sister chromatids, and it suppresses damage-induced recombination between homologues. The effects of limited amounts of Mcd1and Smc3 indicate that small changes in cohesin levels may increase the risk of genome instability, which may lead to genetic diseases and cancer.

  3. Chromosome length scaling in haploid, asexual reproduction

    Science.gov (United States)

    de Oliveira, P. M. C.

    2007-02-01

    We study the genetic behaviour of a population formed by haploid individuals which reproduce asexually. The genetic information for each individual is stored along a bit-string (or chromosome) with L bits, where 0-bits represent the wild allele and 1-bits correspond to harmful mutations. Each newborn inherits this chromosome from its parent with a few random mutations: on average a fixed number m of bits are flipped. Selection is implemented according to the number N of 1-bits counted along the individual's chromosome: the smaller N the higher the probability an individual has to survive a new time step. Such a population evolves, with births and deaths, and its genetic distribution becomes stabilized after sufficiently many generations have passed. The question we pose concerns the procedure of increasing L. The aim is to get the same distribution of genetic loads N/L among the equilibrated population, in spite of a larger L. Should we keep the same mutation rate m/L for different values of L? The answer is yes, which intuitively seems to be plausible. However, this conclusion is not trivial, according to our simulation results: the question also involves the population size.

  4. Chromosome length scaling in haploid, asexual reproduction

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, P M C de [Instituto de Fisica, Universidade Federal Fluminense, avenida Litoranea s/n, Boa Viagem, Niteroi 24210-340 (Brazil)

    2007-02-14

    We study the genetic behaviour of a population formed by haploid individuals which reproduce asexually. The genetic information for each individual is stored along a bit-string (or chromosome) with L bits, where 0-bits represent the wild allele and 1-bits correspond to harmful mutations. Each newborn inherits this chromosome from its parent with a few random mutations: on average a fixed number m of bits are flipped. Selection is implemented according to the number N of 1-bits counted along the individual's chromosome: the smaller N the higher the probability an individual has to survive a new time step. Such a population evolves, with births and deaths, and its genetic distribution becomes stabilized after sufficiently many generations have passed. The question we pose concerns the procedure of increasing L. The aim is to get the same distribution of genetic loads N/L among the equilibrated population, in spite of a larger L. Should we keep the same mutation rate m/L for different values of L? The answer is yes, which intuitively seems to be plausible. However, this conclusion is not trivial, according to our simulation results: the question also involves the population size.

  5. Associated chromosomal DNA changes in polyploids.

    Science.gov (United States)

    Raina, S N; Parida, A; Koul, K K; Salimath, S S; Bisht, M S; Raja, V; Khoshoo, T N

    1994-08-01

    The 2C and 4C nuclear DNA amounts were estimated in eight diploid species, belonging to three diverse genera (Vicia, Tephrosia, and Phlox) and their corresponding colchitetraploids. In P. drummondii, T. purpurea, and T. oxygona tetraploids the deviation from the expectation was highly significant. The DNA in P. drummondii was further discarded in subsequent (C1, C2) generations, thus attaining an overall reduction of about 25%. The DNA content in the subsequent generations was the same as that of C2. It is concluded that rapid DNA loss in the first and subsequent generations was not only associated with the substantial increase (30-66%) in the seed set, but it also helped in the establishment and stabilization of the tetraploid. The possible relationship between such a nucleotypic change and success of polyploids is discussed. The DNA change from the expected value in the P. drummondii tetraploid was achieved by equal decrement to each chromosome independent of size, i.e., small chromosomes loose the same amount of DNA as the large chromosomes.

  6. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    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.

  7. Chromosome assortment in Saccharum.

    Science.gov (United States)

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

    1994-12-01

    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.

  8. Chromosome structuring limits genome plasticity in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Emilie Esnault

    2007-12-01

    Full Text Available Chromosome organizations of related bacterial genera are well conserved despite a very long divergence period. We have assessed the forces limiting bacterial genome plasticity in Escherichia coli by measuring the respective effect of altering different parameters, including DNA replication, compositional skew of replichores, coordination of gene expression with DNA replication, replication-associated gene dosage, and chromosome organization into macrodomains. Chromosomes were rearranged by large inversions. Changes in the compositional skew of replichores, in the coordination of gene expression with DNA replication or in the replication-associated gene dosage have only a moderate effect on cell physiology because large rearrangements inverting the orientation of several hundred genes inside a replichore are only slightly detrimental. By contrast, changing the balance between the two replication arms has a more drastic effect, and the recombinational rescue of replication forks is required for cell viability when one of the chromosome arms is less than half than the other one. Macrodomain organization also appears to be a major factor restricting chromosome plasticity, and two types of inverted configurations severely affect the cell cycle. First, the disruption of the Ter macrodomain with replication forks merging far from the normal replichore junction provoked chromosome segregation defects. The second major problematic configurations resulted from inversions between Ori and Right macrodomains, which perturb nucleoid distribution and early steps of cytokinesis. Consequences for the control of the bacterial cell cycle and for the evolution of bacterial chromosome configuration are discussed.

  9. Clinical Expression of an Inherited Unbalanced Translocation in Chromosome 6

    Directory of Open Access Journals (Sweden)

    Bani Bandana Ganguly

    2011-01-01

    Full Text Available Unbalanced chromosomal rearrangements are not common; however, they have a significant clinical expression. The parental balanced translocation produces unbalanced chromosome, which is transmitted to next generation through fertilization of gametes carrying the derivative chromosome. The carriers of balanced rearrangements mostly do not have recognizable phenotypic expression. We report a family comprising of healthy and non-consanguineous young parents and their preemie newborn severely affected with congenital anomalies and systemic disorders. Conventional Gbanding analysis of somatic chromosomes identified a balanced translocation, t(6;10(p23;q24, in mother and an unbalanced rearrangement, der(6t(6:10(p23;q24mat, in the child. The child has inherited a derivative chromosome 6 with partial deletion of 6(p23-pter and partial trisomy 10(q24-qter, which has resulted in fusion of genes of two different chromosomes. The prominent phenotypic features of del(6p, including high forehead, flat nasal bridge, agenesis of left ear, atrial septal defect (ASD, craniosynostosis, and growth retardation, are overlapping with specific Axenfeld-Reiger-, Larsen-, and Ritscher-Sinzel/3-C syndromes, however, lacking in ocular anomalies, skeletal laxity, or cerebellar malformation. Therefore, this paper rules out the isolated effect of del(6p23 or trisomy 10(q24 on distinct previously reported syndromes and proposes the combined effect of unbalanced chromosomal alteration.

  10. Formulation factors affecting the isomerization rate of betamethasone-17-valerate in a developmental hydrophilic cream - a HPLC and microscopy based stability study.

    Science.gov (United States)

    Byrne, Jonathan; Wyraz, Anke; Velasco-Torrijos, Trinidad; Reinhardt, Robert

    2016-02-19

    The formulation of betamethasone-17-valerate (BV) into topical medicines presents a significant challenge for the formulation chemist. The substance is susceptible to acid and base catalyzed isomerization in aqueous environments, which results in valerate transesterification from carbon 17 to carbon 21 of the steroid ring system. This acyl migration process is of significant clinical importance since the 21-valerate ester possesses only a fraction of the potency of the 17-valerate parent compound. Isomerization of BV should therefore be reduced to a minimum through design of a suitable drug vehicle. In this study, the effect of varying the concentration of several excipient components on the isomerization rate of betamethasone valerate in a model hydrophilic cream has been investigated. These excipients include the emulsifier macrogolstearylether-20/21, the co-emulsifier cetylstearyl alcohol and the thickening agent hydroxyl propyl methylcellulose. Additionally, the influence of pH, the presence of the antioxidant, alpha-tocopherol, as well as the chelating agent, disodium edetate, on the stability of the formulation have been investigated. Trial drug product formulations, which were designed to investigate the influence of the above-mentioned components/parameters were manufactured and their stability was tested according to current ICH Guidelines. The content, purity and crystalline structure of the active substance in these formulations was analyzed by a combination of HPLC and microscopy techniques. The study demonstrates that the rate of isomerization of betamethasone valerate depends significantly on the concentration of emulsifier used in the cream formulation. At higher concentrations of emulsifier the isomerization proceeds rapidly with significant degradation over a period of weeks, whereas at lower concentrations significant degradation may not be observed, even after several years' storage. The influence of the emulsifier has been shown to be

  11. Dengue type 4 live-attenuated vaccine viruses passaged in vero cells affect genetic stability and dengue-induced hemorrhaging in mice.

    Directory of Open Access Journals (Sweden)

    Hsiang-Chi Lee

    Full Text Available Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4 virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3' NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q(438H, E-V(463L, NS2B-Q(78H, and NS2B-A(113T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine

  12. Long-term culture and cryopreservation does not affect the stability and functionality of human embryonic stem cell-derived hepatocyte-like cells.

    Science.gov (United States)

    Mandal, Arundhati; Raju, Sheena; Viswanathan, Chandra

    2016-02-01

    Human embryonic stem cells (hESCs) are predicted to be an unlimited source of hepatocytes which can pave the way for applications such as cell replacement therapies or as a model of human development or even to predict the hepatotoxicity of drug compounds. We have optimized a 23-d differentiation protocol to generate hepatocyte-like cells (HLCs) from hESCs, obtaining a relatively pure population which expresses the major hepatic markers and is functional and mature. The stability of the HLCs in terms of hepato-specific marker expression and functionality was found to be intact even after an extended period of in vitro culture and cryopreservation. The hESC-derived HLCs have shown the capability to display sensitivity and an alteration in the level of CYP enzyme upon drug induction. This illustrates the potential of such assays in predicting the hepatotoxicity of a drug compound leading to advancement of pharmacology.

  13. Micromechanical study of protein-DNA interactions and chromosomes

    Science.gov (United States)

    Marko, John

    I will discuss micromechanics experiments that our group has used to analyze protein-DNA interactions and chromosome organization. In single-DNA experiments we have found that a feature of protein-DNA complexes is that their dissociation rates can depend strikingly on bulk solution concentrations of other proteins and DNA segments; I will describe experiments which demonstrate this effect, which can involve tens-fold changes in off-rates with submicromolar changes in solution concentrations. Second, I will discuss experiments aimed at analyzing large-scale human chromosome structure; we isolate metaphase chromosomes, which in their native form behave as remarkably elastic networks of chromatin. Exposure to DNA-cutting restriction enzymes completely eliminates this elasticity, indicating that there is not a mechanically contiguous protein ''scaffold'' from which the chromosome gains its stability. I will show results of siRNA experiments indicating that depletion of condensin proteins leads to destabilization of chromosome mechanics, indicating condensin's role as the major chromatin ''cross-linker'' in metaphase chromosomes. Finally I will discuss similar experiments on human G1 nuclei, where we use genetic and chemical modifications to separate the contributions of the nuclear lamina and chromatin to the mechanical stiffness of the nucleus as a whole. Supported by the NSF (DMR-1206868, MCB-1022117) and the NIH (GM105847, CA193419).

  14. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

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

  15. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    Science.gov (United States)

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

    2007-10-01

    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.

  16. Strong purifying selection at genes escaping X chromosome inactivation.

    Science.gov (United States)

    Park, Chungoo; Carrel, Laura; Makova, Kateryna D

    2010-11-01

    To achieve dosage balance of X-linked genes between mammalian males and females, one female X chromosome becomes inactivated. However, approximately 15% of genes on this inactivated chromosome escape X chromosome inactivation (XCI). Here, using a chromosome-wide analysis of primate X-linked orthologs, we test a hypothesis that such genes evolve under a unique selective pressure. We find that escape genes are subject to stronger purifying selection than inactivated genes and that positive selection does not significantly affect the evolution of these genes. The strength of selection does not differ between escape genes with similar versus different expression levels in males versus females. Intriguingly, escape genes possessing Y homologs evolve under the strongest purifying selection. We also found evidence of stronger conservation in gene expression levels in escape than inactivated genes. We hypothesize that divergence in function and expression between X and Y gametologs is driving such strong purifying selection for escape genes.

  17. Genome stability in Caenorhabditis elegans

    NARCIS (Netherlands)

    Haaften, G.W. van

    2006-01-01

    Genome stability is closely linked to cancer. Most, if not all tumor cells show some form of genome instability, mutations can range from single point mutations to gross chromosomal rearrangements and aneuploidy. Genome instability is believed to be the driving force behind tumorigenesis. In order t

  18. Sister chromatid exchange assessment by chromosome orientation-fluorescence in situ hybridization on the bovine sex chromosomes and autosomes 16 and 26.

    Science.gov (United States)

    Revay, T; King, W A

    2012-01-01

    Mammalian genome replication and maintenance are intimately coupled with the mechanisms that ensure cohesion between the resultant sister chromatids and the repair of DNA breaks. Although a sister chromatid exchange (SCE) is an error-free swapping of precisely matched and identical DNA strands, repetitive elements adjacent to the break site can act as alternative template sites and an unequal sister chromatid exchange can result, leading to structural variations and copy number change. Here we test the vulnerability for SCEs of the repeat-rich bovine Y chromosome in comparison with X, 16 and 26 chromosomes, using chromosome orientation-fluorescence in situ hybridization. The mean SCE rate of the Y chromosome (0.065 ± 0.029) was similar to that of BTA16 and BTA26 (0.065, 0.055), but was only approximately half of that of the X chromosome (0.142). As the chromosomal length affects the number of SCE events, we adjusted the SCE rates of the Y, 16, and 26 chromosomes to the length of the largest chromosome X resulting in very similar adjusted SCE (SCE(adj)) rates in all categories. Our results - based on 3 independent bulls - show that, although the cattle Y chromosome is a chest full of repeated elements, their presence and the documented activity of repeats in SCE formation does not manifest in significantly higher SCE(adj) rates and suggest the importance of the structural organization of the Y chromosome and the role of alternative mitotic DNA repair mechanisms.

  19. Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats

    Directory of Open Access Journals (Sweden)

    Benedito Vagner A

    2011-10-01

    Full Text Available Abstract Background Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Methods Female Sprague-Dawley rats (age 28 d were randomly assigned (n = 10/group to be fed a high fat 12% (wt diet consisting of either corn oil (CO or n-3 PUFA rich flaxseed (FO, krill (KO, menhaden (MO, salmon (SO or tuna (TO oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs and thromoboxanes (TXBs using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS and total antioxidant capacity (TAC using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR. Results Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. Conclusions On the basis that the optimal n-3 PUFA sources should

  20. Chromosomal mosaicism in mouse two-cell embryos after paternal exposure to acrylamide

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Bishop, Jack; Lowe, Xiu; Wyrobek, Andrew J

    2008-10-14

    Chromosomal mosaicism in human preimplantation embryos is a common cause ofspontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization (FISH) painting to investigate whether paternally-transmitted chromosomal aberrations result in mosaicism in mouse 2-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective 2-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and 2-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected 2-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and 2-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division ofembryogenesis, while both dicentrics and translocations apparently underwent propersegregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic 2-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally-transmitted chromosomal abnromalities increase the risk of missegregation leading to embryonic mosaicism.

  1. Homogenization conditions affect the oxidative stability of fish oil enriched milk emulsions: oxidation linked to changes in protein composition at the oil-water interface.

    Science.gov (United States)

    Sørensen, Ann-Dorit M; Baron, Caroline P; Let, Mette B; Brüggemann, Dagmar A; Pedersen, Lise R L; Jacobsen, Charlotte

    2007-03-07

    Fish oil was incorporated into milk under different homogenization temperatures (50 and 72 degrees C) and pressures (5, 15, and 22.5 MPa). Subsequently, the oxidative stability of the milk and changes in the protein composition of the milk fat globule membrane (MFGM) were examined. Results showed that high pressure and high temperature (72 degrees C and 22.5 MPa) resulted in less lipid oxidation, whereas low pressure and low temperature (50 degrees C and 5 MPa) resulted in faster lipid oxidation. Analysis of protein oxidation indicated that especially casein was prone to oxidation. The level of free thiol groups was increased by high temperature (72 degrees C) and with increasing pressure. Furthermore, SDS-PAGE and confocal laser scanning microscopy (CLSM) indicated that high temperature resulted in an increase in beta-lactoglobulin adsorbed at the oil-water interface. This was even more pronounced with higher pressure. Less casein seemed to be present at the oil-water interface with increasing pressure. Overall, the results indicated that a combination of more beta-lactoglobulin and less casein at the oil-water interface gave the most stable emulsions with respect to lipid oxidation.

  2. A new stable human dicentric chromosome, tdic(4;21)(p16;q22), in a woman with first trimester abortion.

    OpenAIRE

    Wang, F.; Li, Y.

    1993-01-01

    A woman with first trimester abortion and a dicentric chromosome formed from a 4 and a 21 is described. The dicentric chromosome was stable and in the majority of cells the 21 centromere was active, while in a minority the chromosome 4 centromere was active. This shows that both centromeres were functional, but that only one functioned in any given cell. Suppression of the activity of one centromere might be the mechanism by which this dicentric chromosome achieved its stability. A dicentric ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-03-01

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

  5. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    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.

  6. Higher order structure of chromosomes.

    Science.gov (United States)

    Okada, T A; Comings, D E

    1979-04-01

    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.

  7. Bacterial chromosome organization and segregation.

    Science.gov (United States)

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

    2015-01-01

    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.

  8. Chromosome choreography: the meiotic ballet.

    Science.gov (United States)

    Page, Scott L; Hawley, R Scott

    2003-08-08

    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.

  9. Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability.

    Science.gov (United States)

    Fontanesi, Flavia; Palmieri, Luigi; Scarcia, Pasquale; Lodi, Tiziana; Donnini, Claudia; Limongelli, Anna; Tiranti, Valeria; Zeviani, Massimo; Ferrero, Iliana; Viola, Anna Maria

    2004-05-01

    Autosomal dominant and recessive forms of progressive external ophthalmoplegia (adPEO and arPEO) are mitochondrial disorders characterized by the presence of multiple deletions of mitochondrial DNA in affected tissues. Four adPEO-associated missense mutations have been identified in the ANT1 gene. In order to investigate their functional consequences on cellular physiology, we introduced three of them at equivalent positions in AAC2, the yeast orthologue of human ANT1. We demonstrate here that expression of the equivalent mutations in aac2-defective haploid strains of Saccharomyces cerevisiae results in (a) a marked growth defect on non-fermentable carbon sources, and (b) a concurrent reduction of the amount of mitochondrial cytochromes, cytochrome c oxidase activity and cellular respiration. The efficiency of ATP and ADP transport was variably affected by the different AAC2 mutations. However, irrespective of the absolute level of activity, the AAC2 pathogenic mutants showed a significant defect in ADP versus ATP transport compared with wild-type AAC2. In order to study whether a dominant phenotype, as in humans, could be observed, the aac2 mutant alleles were also inserted in combination with the endogenous wild-type AAC2 gene. The heteroallelic strains behaved as recessive for oxidative growth and petite-negative phenotype. In contrast, reduction in cytochrome content and increased mtDNA instability appeared to behave as dominant traits in heteroallelic strains. Our results indicate that S. cerevisiae is a suitable in vivo model to study the pathogenicity of the human ANT1 mutations and the pathophysiology leading to impairment of oxidative phosphorylation and damage of mtDNA integrity, as found in adPEO.

  10. Breakage-fusion-bridge cycles and large insertions contribute to the rapid evolution of accessory chromosomes in a fungal pathogen.

    Science.gov (United States)

    Croll, Daniel; Zala, Marcello; McDonald, Bruce A

    2013-06-01

    Chromosomal rearrangements are a major driver of eukaryotic genome evolution, affecting speciation, pathogenicity and cancer progression. Changes in chromosome structure are often initiated by mis-repair of double-strand breaks in the DNA. Mis-repair is particularly likely when telomeres are lost or when dispersed repeats misalign during crossing-over. Fungi carry highly polymorphic chromosomal complements showing substantial variation in chromosome length and number. The mechanisms driving chromosome polymorphism in fungi are poorly understood. We aimed to identify mechanisms of chromosomal rearrangements in the fungal wheat pathogen Zymoseptoria tritici. We combined population genomic resequencing and chromosomal segment PCR assays with electrophoretic karyotyping and resequencing of parents and offspring from experimental crosses to show that this pathogen harbors a highly diverse complement of accessory chromosomes that exhibits strong global geographic differentiation in numbers and lengths of chromosomes. Homologous chromosomes carried highly differentiated gene contents due to numerous insertions and deletions. The largest accessory chromosome recently doubled in length through insertions totaling 380 kb. Based on comparative genomics, we identified the precise breakpoint locations of these insertions. Nondisjunction during meiosis led to chromosome losses in progeny of three different crosses. We showed that a new accessory chromosome emerged in two viable offspring through a fusion between sister chromatids. Such chromosome fusion is likely to initiate a breakage-fusion-bridge (BFB) cycle that can rapidly degenerate chromosomal structure. We suggest that the accessory chromosomes of Z. tritici originated mainly from ancient core chromosomes through a degeneration process that included BFB cycles, nondisjunction and mutational decay of duplicated sequences. The rapidly evolving accessory chromosome complement may serve as a cradle for adaptive evolution in

  11. Breakage-fusion-bridge cycles and large insertions contribute to the rapid evolution of accessory chromosomes in a fungal pathogen.

    Directory of Open Access Journals (Sweden)

    Daniel Croll

    2013-06-01

    Full Text Available Chromosomal rearrangements are a major driver of eukaryotic genome evolution, affecting speciation, pathogenicity and cancer progression. Changes in chromosome structure are often initiated by mis-repair of double-strand breaks in the DNA. Mis-repair is particularly likely when telomeres are lost or when dispersed repeats misalign during crossing-over. Fungi carry highly polymorphic chromosomal complements showing substantial variation in chromosome length and number. The mechanisms driving chromosome polymorphism in fungi are poorly understood. We aimed to identify mechanisms of chromosomal rearrangements in the fungal wheat pathogen Zymoseptoria tritici. We combined population genomic resequencing and chromosomal segment PCR assays with electrophoretic karyotyping and resequencing of parents and offspring from experimental crosses to show that this pathogen harbors a highly diverse complement of accessory chromosomes that exhibits strong global geographic differentiation in numbers and lengths of chromosomes. Homologous chromosomes carried highly differentiated gene contents due to numerous insertions and deletions. The largest accessory chromosome recently doubled in length through insertions totaling 380 kb. Based on comparative genomics, we identified the precise breakpoint locations of these insertions. Nondisjunction during meiosis led to chromosome losses in progeny of three different crosses. We showed that a new accessory chromosome emerged in two viable offspring through a fusion between sister chromatids. Such chromosome fusion is likely to initiate a breakage-fusion-bridge (BFB cycle that can rapidly degenerate chromosomal structure. We suggest that the accessory chromosomes of Z. tritici originated mainly from ancient core chromosomes through a degeneration process that included BFB cycles, nondisjunction and mutational decay of duplicated sequences. The rapidly evolving accessory chromosome complement may serve as a cradle for

  12. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (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...

  13. CHROMOSOMAL MAPPING IN STRAINS OF STAPHYLOCOCCUS AUREUS,

    Science.gov (United States)

    STAPHYLOCOCCUS AUREUS , CHROMOSOMES), (*CHROMOSOMES, MAPPING), NITROSO COMPOUNDS, GUANIDINES, GENETICS, MUTATIONS, DRUGS, TOLERANCES(PHYSIOLOGY), TEST METHODS, DEOXYRIBONUCLEIC ACIDS, INHIBITION, RESISTANCE(BIOLOGY).

  14. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (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...

  15. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    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

  16. The Chromosomal Courtship Dance-homolog pairing in early meiosis.

    Science.gov (United States)

    Klutstein, Michael; Cooper, Julia Promisel

    2014-02-01

    The intermingling of genomes that characterizes sexual reproduction requires haploid gametes in which parental homologs have recombined. For this, homologs must pair during meiosis. In a crowded nucleus where sequence homology is obscured by the enormous scale and packaging of the genome, partner alignment is no small task. Here we review the early stages of this process. Chromosomes first establish an initial docking site, usually at telomeres or centromeres. The acquisition of chromosome-specific patterns of binding factors facilitates homolog recognition. Chromosomes are then tethered to the nuclear envelope (NE) and subjected to nuclear movements that 'shake off' inappropriate contacts while consolidating homolog associations. Thereafter, homolog connections are stabilized by building the synaptonemal complex or its equivalent and creating genetic crossovers. Recent perspectives on the roles of these stages will be discussed.

  17. Construction of a consistent YAC contig for human chromosome region 3p14.1

    NARCIS (Netherlands)

    Bardenheuer, W; Michaelis, S; Lux, A; Vieten, L; Brocker, F; Julicher, K; Willers, C; Siebert, R; Smith, DI; vanderHout, AH; Buys, C; Schutte, J; Opalka, B

    1996-01-01

    Chromosomal deletions and translocations of human chromosome region 3p14 are observed in various human malignancies and suggest the existence of a tumor suppressor gene locus within this region. Tumors most frequently affected by these aberrations are small-cell lung cancer and renal-cell carcinoma.

  18. Occurrence of differential meiotic associations and additional chromosomes in the embryo-sac mother cells of Allium roylei Stearn

    Indian Academy of Sciences (India)

    Geeta Sharma; Ravinder N. Gohil

    2011-04-01

    A small population of complex translocation heterozygote plants of Allium roylei from the Bani region of Jammu Province was studied for meiosis in the female track. This study resulted in identification of two variants, having embryo-sac mother cells (EMCs) with more than 16 chromosomes. EMCs of the remaining plants invariably had diploid $(2n = 16)$ chromosome complement. Female meiosis, in general, was found to be abnormal, with nearly 23% and 11% chromosomes associating as quadrivalents or trivalents at prophase I and at metaphase I, respectively. This was followed by irregular segregation of chromosomes at anaphase I. Amongst the variants; one had 38% EMCs with eight bivalents plus two small sized chromosomes. Their small size, dispensable nature and tendency to affect the pairing behaviour of normal complement are some of the features that latter chromosomes share with the B chromosomes. Seventeen to nineteen chromosomes were observed in 35% EMCs of other variant; the remaining cells had 16 chromosomes. Chromosomal behaviour in both kind of cells (euploid and aneuploid) was more or less similar. Unlike female meiocytes, male meiocytes analysed earlier of this strain always had 16 chromosomes which paired to form extremely complex associations involving 3–16 chromosomes. The most likely cause of this asynchrony with regards to number of chromosomes involved in multivalent formation seems to be interaction of genes controlling chiasma formation with the different physiological conditions of male and female meiocytes.

  19. Affection of the rotor-flux error on the induction motor full-order observer stability%转子磁链误差对感应电机观测器稳定性影响

    Institute of Scientific and Technical Information of China (English)

    许思猛; 陈冲

    2012-01-01

    The rotor flux error affection on the stability of the induction motor full-order speed adaptive rotor flux observer was studied using the voltage model. The positive-real property of the forward path transfer function of the observer equivalent error system was analyzed. Stability domain border equations in ω1 -ωs plane were derived. A modified rotor flux error model excluding a pure integrator was suggested. Affection of the modified model on open-loop zeros plots of the linearized equivalent speed control system was investigated, and the stability region distribution in all motor operation modes was studied. Research results indicate the stability region is enlarged by amplifying the rotor flux error. The observer with the modified model is stable in the low-speed region with regenerative loads but unstable in low-speed motoring mode. Simulation results illustrate the adaptive observer with combined speed adaptive laws is stable in all motor operation modes.%利用转子磁链电压模型研究转子磁链误差对感应电动机全阶转速自适应转子磁链观测器稳定性影响.通过研究观测器等效误差系统前向通道传递函数正实性,得到观测器在ω1-ωs平面中稳定区域边界方程.提出不舍纯积分器的新型转子磁链误差模型,通过分析该模型对线性化等效转速控制系统开环零点分布影响,研究不同工况下观测器稳定区域分布.研究结果表明增大转子磁链误差能够扩大稳定区域,所提出的模型解决了低速再生发电工况时观测器稳定问题,但在低速电动工况时观测器不稳定.仿真结果表明组合应用不同转速自适应律观测器在所有工况下均能稳定.

  20. Substitutions at the opening of the Rubisco central solvent channel affect holoenzyme stability and CO2/O 2 specificity but not activation by Rubisco activase.

    Science.gov (United States)

    Esquivel, M Gloria; Genkov, Todor; Nogueira, Ana S; Salvucci, Michael E; Spreitzer, Robert J

    2013-12-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the initial step of carbon metabolism in photosynthesis. The holoenzyme comprises eight large subunits, arranged as a tetramer of dimers around a central solvent channel that defines a fourfold axis of symmetry, and eight small subunits, arranged as two tetramers at the poles of the axis. The phylogenetically divergent small-subunit loops between β-strands A and B form the entrance to the solvent channel. In the green alga Chlamydomonas reinhardtii, Ile-58 from each of the four small-subunit βA-βB loops defines the minimal diameter of the channel opening. To understand the role of the central solvent channel in Rubisco function, directed mutagenesis and transformation of Chlamydomonas were employed to replace Ile-58 with Ala, Lys, Glu, Trp, or three Trp residues (I58W3) to close the entrance to the channel. The I58E, I58K, and I58W substitutions caused only small decreases in photosynthetic growth at 25 and 35 °C, whereas I58W3 had a substantial effect at both temperatures. The mutant enzymes had decreased carboxylation rates, but the I58W3 enzyme had decreases in both carboxylation and CO2/O2 specificity. The I58E, I58W, and I58W3 enzymes were inactivated at lower temperatures than wild-type Rubisco, and were degraded at slower rates under oxidative stress. However, these mutant enzymes were activated by Rubisco activase at normal rates, indicating that the structural transition required for carboxylation is not affected by altering the solvent channel opening. Structural dynamics alone may not be responsible for these distant effects on the Rubisco active site.

  1. Dynamic conformations of nucleophosmin (NPM1 at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

    Directory of Open Access Journals (Sweden)

    Wei D Duan-Porter

    Full Text Available Nucleophosmin (NPM1 is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM that shared all these properties. We used deuterium exchange mass spectrometry (DXMS to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We tested the importance of interactions at the β-hairpin "latch" by replacing a conserved tyrosine in the middle of the β-hairpin loop with glutamic acid, generating Y67E-NPM. Y67E-NPM did not form stable oligomers and further, prevented wild-type NPM1 oligomerization in a dominant-negative fashion, supporting the critical role of the β-hairpin "latch" in monomer-monomer interactions. Also, we show preferential cleavage by granzyme B at one of two available aspartates (either D161 or D122 in M7-NPM and Y67E-NPM, whereas wild-type NPM1 was cleaved at both sites. Thus, we observed a correlation between the propensity to form oligomers and granzyme B cleavage site selection in nucleophosmin proteins, suggesting that a small change at an important monomer-monomer interface can affect conformational shifts and impact protein-protein interactions.

  2. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

    Science.gov (United States)

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

    2013-07-08

    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.

  3. Chromosome segregation in Vibrio cholerae.

    Science.gov (United States)

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

    2014-01-01

    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.

  4. Numerous transitions of sex chromosomes in Diptera.

    Science.gov (United States)

    Vicoso, Beatriz; Bachtrog, Doris

    2015-04-01

    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.

  5. TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines

    Science.gov (United States)

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

    2001-01-01

    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.

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

    Science.gov (United States)

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

    1992-11-01

    We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in affected individuals, although dissimilar, were sufficient to encourage a search for a deletion of chromosome 4p. By Southern blot analysis and fluorescence in situ hybridization, a deletion of material mapping approximately 150 kb from chromosome 4pter was discovered. This deletion is notable because it does not result in the Wolf-Hirschhorn syndrome and can result in an apparently normal phenotype. We speculate that homology between subterminal repeat sequences on 4p and sequences on the acrocentric short arms may explain the origin of the rearrangement and that position effect may play a role in the expression of the abnormal phenotype.

  7. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.

    Science.gov (United States)

    Brooks, Wesley H; Renaudineau, Yves

    2015-01-01

    Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune

  8. Chromosome 14 translocations in non-Burkitt lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Fukuhara, S.; Rowley, J.D.

    1978-01-01

    Chromosome studies were performed on malignant cells obtained from 27 patients with non-Burkitt lymphomas. A marker chromosome affecting the long arm of No. 14 (14q+) was the single most frequent abnormality and was noted in 17 of these patients. The frequency of the 14q+ marker varied with the type of lymphoma. For patients with malignant lymphoma, histiocytic, the frequency was 5 or 8; for mixed-cell type, 1 of 3; for poorly differentiated lymphocytic, 8 of 8; for well-differentiated lymphocytic, 0.3; for lymphoblastic, 0 of 1; for Hodgkin's disease, 2 of 3; and for mycosis fungoides, 1 of 1. The donor chromosome involved in the 14q translocation was identified in 12 cases; certain chromosomes appeared to be affected more frequently than others. Although the break point was band 14q32 in most cases, the exact location of the receptor site on 14q was not always consistent. The distal part of 14q24 was also involved as a receptor site in at least one translocation. These findings suggest that, in some types of lymphoid malignancy, cells with a 14q translocation have a proliferative advantage over cells with other chromosome rearrangements. The presence of the 14q translocation may be important in the future for the distinction among morphologically different, but functionally comparable, subgroups of lymphoid malignancies.

  9. VHL loss causes spindle misorientation and chromosome instability.

    Science.gov (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

    2009-08-01

    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. Tubulin tyrosine ligase like 12 links to prostate cancer through tubulin posttranslational modification and chromosome ploidy.

    Science.gov (United States)

    Wasylyk, Christine; Zambrano, Alberto; Zhao, Chunhua; Brants, Jan; Abecassis, Joseph; Schalken, Jack A; Rogatsch, Hermann; Schaefer, Georg; Pycha, Armin; Klocker, Helmut; Wasylyk, Bohdan

    2010-12-01

    Prostate cancer is a common cause of death, and an important goal is to establish the pathways and functions of causative genes. We isolated RNAs that are differentially expressed in macrodissected prostate cancer samples. This study focused on 1 identified gene, TTLL12, which was predicted to modify tubulins, an established target for tumor therapy. TTLL12 is the most poorly characterized member of a recently discovered 14-member family of proteins that catalyze posttranslational modification of tubulins. We show that human TTLL12 is expressed in the proliferating layer of benign prostate. Expression increases during cancer progression to metastasis. It is highly expressed in many metastatic prostate cancer cell lines. It partially colocalizes with vimentin intermediate filaments and cellular structures containing tubulin, including midbodies, centrosomes, intercellular bridges and the mitotic spindle. Downregulation of TTLL12 affects several posttranslational modifications of tubulin (detyrosination and subsequent deglutamylation and polyglutamylation). Overexpression alters chromosomal ploidy. These results raise the possibility that TTLL12 could contribute to tumorigenesis through effects on the cytoskeleton, tubulin modification and chromosome number stability. This study contributes a step toward developing more selective agents targeting microtubules, an already successful target for tumor therapy.

  11. Chromosomal aberrations induced by Glycidol in Allium cepa L root meristem cells

    Directory of Open Access Journals (Sweden)

    N.Panneerselvam

    2012-02-01

    Full Text Available Glycidol is used as a stabilizer in the manufacture of vinyl polymers and natural oils and as an intermediate in the synthesis of glycerol, glycidyl ethers, and amines. It is also used as an alkylating agent,demulsifier, and dye-leveling agent and for sterilizing milk of magnesia. Glycidol is an alkylating agent which reacts readily with glutathione; it causes a decrease in glutathione content in rat liver, probably reflecting its binding to glutathione. It is a suspected reproductive toxicant and exposure to it has the potential to negatively affect the human reproductive system. The study investigated the cytotoxic effects of glycidol in Allium cepa L root meristem cells. Different concentrations of glycidol ranging 10, 20, 40 and 50μg/ml for 1, 2, 3 and 5h were treated with root meristem cells of Allium cepa L. Fuelgen squash technique was used to determine the aberrations in root tip cells. For each concentration 3000 well-spread cells were scored and cytological abnormalities such as break, gap, exchange, multiple breaks and chromosome fragments were observed. One way analysis of variance was used the study the significant different control and treatment exposed root tip cells.Significant difference between control and glycidol exposed cells were observed. Increasing concentrations increased the number of chromosomal aberrations.

  12. Recovery and Visualization of 3D Structure of Chromosomes from Tomographic Reconstruction Images

    Energy Technology Data Exchange (ETDEWEB)

    Babu, S; Liao, P; Shin, M C; Tsap, L V

    2004-04-28

    The objectives of this work include automatic recovery and visualization of a 3D chromosome structure from a sequence of 2D tomographic reconstruction images taken through the nucleus of a cell. Structure is very important for biologists as it affects chromosome functions, behavior of the cell and its state. Chromosome analysis is significant in the detection of deceases and in monitoring environmental gene mutations. The algorithm incorporates thresholding based on a histogram analysis with a polyline splitting algorithm, contour extraction via active contours, and detection of the 3D chromosome structure by establishing corresponding regions throughout the slices. Visualization using point cloud meshing generates a 3D surface. The 3D triangular mesh of the chromosomes provides surface detail and allows a user to interactively analyze chromosomes using visualization software.

  13. Production and stability of chlorine dioxide in organic acid solutions as affected by pH, type of acid, and concentration of sodium chlorite, and its effectiveness in inactivating Bacillus cereus spores.

    Science.gov (United States)

    Kim, Hoikyung; Kang, Youngjee; Beuchat, Larry R; Ryu, Jee-Hoon

    2008-12-01

    We studied the production and stability of chlorine dioxide (ClO(2)) in organic acid solutions and its effectiveness in killing Bacillus cereus spores. Sodium chlorite (5000, 10,000, or 50,000 microg/ml) was added to 5% acetic, citric, or lactic acid solution, adjusted to pH 3.0, 4.0, 5.0, or 6.0, and held at 21 degrees C for up to 14 days. The amount of ClO(2) produced was higher as the concentration of sodium chlorite was increased and as the pH of the acid solutions was decreased. However, the stability in production of ClO(2) was enhanced by increasing the pH of the organic acid solutions. To evaluate the lethal activity of ClO(2) produced in various acid solutions as affected by acidulant and pH, suspensions of B. cereus spores were treated at 21 degrees C for 1, 3, 5, or 10 min in hydrochloric acid or organic acid solutions (pH 3.0, 4.0, 5.0, or 6.0) containing ClO(2) at concentrations of 100, 50, or 25 microg/ml. Populations of viable spores treated with ClO(2) at concentrations of 100 or 50 microg/ml in organic acid solutions decreased more rapidly than populations treated with the same concentrations of ClO(2) in HCl. Rates of inactivation tended to increase with higher pH of ClO(2) solutions. Results show that ClO(2) formed in organic acid solutions has higher stability and is more lethal to B. cereus spores than ClO(2) formed at the same concentration in HCl solution. This finding emphasizes the benefits of using organic acid solutions to prepare ClO(2) intended for use as an antimicrobial.

  14. Farnesyltransferase inhibitor treatment restores chromosome territory positions and active chromosome dynamics in Hutchinson-Gilford progeria syndrome cells

    Science.gov (United States)

    2011-01-01

    Background Hutchinson-Gilford progeria syndrome (HGPS) is a premature ageing syndrome that affects children leading to premature death, usually from heart infarction or strokes, making this syndrome similar to normative ageing. HGPS is commonly caused by a mutation in the A-type lamin gene, LMNA (G608G). This leads to the expression of an aberrant truncated lamin A protein, progerin. Progerin cannot be processed as wild-type pre-lamin A and remains farnesylated, leading to its aberrant behavior during interphase and mitosis. Farnesyltransferase inhibitors prevent the accumulation of farnesylated progerin, producing a less toxic protein. Results We have found that in proliferating fibroblasts derived from HGPS patients the nuclear location of interphase chromosomes differs from control proliferating cells and mimics that of control quiescent fibroblasts, with smaller chromosomes toward the nuclear interior and larger chromosomes toward the nuclear periphery. For this study we have treated HGPS fibroblasts with farnesyltransferase inhibitors and analyzed the nuclear location of individual chromosome territories. We have found that after exposure to farnesyltransferase inhibitors mis-localized chromosome territories were restored to a nuclear position akin to chromosomes in proliferating control cells. Furthermore, not only has this treatment afforded chromosomes to be repositioned but has also restored the machinery that controls their rapid movement upon serum removal. This machinery contains nuclear myosin 1β, whose distribution is also restored after farnesyltransferase inhibitor treatment of HGPS cells. Conclusions This study not only progresses the understanding of genome behavior in HGPS cells but demonstrates that interphase chromosome movement requires processed lamin A. PMID:21838864

  15. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    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.

  16. Chromosome Segregation in Vibrio cholerae

    OpenAIRE

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

    2014-01-01

    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...

  17. B chromosomes and sex in animals.

    Science.gov (United States)

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

    2011-01-01

    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.

  18. Origin and domestication of papaya Yh chromosome

    Science.gov (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...

  19. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    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.

  20. 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.

    1986-07-16

    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.

  1. Chromosome numbers and meiotic analysis in the pre-breeding of Brachiaria decumbens (Poaceae)

    Indian Academy of Sciences (India)

    Gléia Cristina Laverde Ricci; Alice Maria De Souza-Kaneshima; Mariana Ferrari Felismino; Andrea Beatriz Mendes-Bonato; Maria Suely Pagliarini; Cacilda Borges Do Valle

    2011-08-01

    A total of 44 accessions of Brachiaria decumbens were analysed for chromosome count and meiotic behaviour in order to identify potential progenitors for crosses. Among them, 15 accessions presented $2n = 18$; 27 accessions, $2n = 36$; and 2 accessions, $2n = 45$ chromosomes. Among the diploid accessions, the rate of meiotic abnormalities was low, ranging from 0.82% to 7.93%. In the 27 tetraploid accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The most common meiotic abnormalities were related to irregular chromosome segregation, but chromosome stickiness and abnormal cytokinesis were observed in low frequency. All abnormalities can compromise pollen viability by generating unbalanced gametes. Based on the chromosome number and meiotic stability, the present study indicates the apomictic tetraploid accessions that can act as male genitor to produce interspecific hybrids with B. ruziziensis or intraspecific hybrids with recently artificially tetraploidized accessions.

  2. Chromosome numbers and meiotic analysis in the pre-breeding of Brachiaria decumbens (Poaceae).

    Science.gov (United States)

    Ricci, Gléia Cristina Laverde; De Souza-Kaneshima, Alice Maria; Felismino, Mariana Ferrari; Mendes-Bonato, Andrea Beatriz; Pagliarini, Maria Suely; Do Valle, Cacilda Borges

    2011-08-01

    A total of 44 accessions of Brachiaria decumbens were analysed for chromosome count and meiotic behaviour in order to identify potential progenitors for crosses. Among them, 15 accessions presented 2n = 18; 27 accessions, 2n = 36; and 2 accessions, 2n = 45 chromosomes. Among the diploid accessions, the rate of meiotic abnormalities was low, ranging from 0.82% to 7.93%. In the 27 tetraploid accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The most common meiotic abnormalities were related to irregular chromosome segregation, but chromosome stickiness and abnormal cytokinesis were observed in low frequency. All abnormalities can compromise pollen viability by generating unbalanced gametes. Based on the chromosome number and meiotic stability, the present study indicates the apomictic tetraploid accessions that can act as male genitor to produce interspecific hybrids with B. ruziziensis or intraspecific hybrids with recently artificially tetraploidized accessions.

  3. Tissue-specific features of the X chromosome and nucleolus spatial dynamics in a malaria mosquito, Anopheles atroparvus

    Science.gov (United States)

    Bondarenko, Semen M.; Artemov, Gleb N.; Stegniy, Vladimir N.

    2017-01-01

    Spatial organization of chromosome territories is important for maintenance of genomic stability and regulation of gene expression. Recent studies have shown tissue-specific features of chromosome attachments to the nuclear envelope in various organisms including malaria mosquitoes. However, other spatial characteristics of nucleus organization, like volume and shape of chromosome territories, have not been studied in Anopheles. We conducted a thorough analysis of tissue-specific features of the X chromosome and nucleolus volume and shape in follicular epithelium and nurse cells of the Anopheles atroparvus ovaries using a modern open-source software. DNA of the polytene X chromosome from ovarian nurse cells was obtained by microdissection and was used as a template for amplification with degenerate oligo primers. A fluorescently labeled X chromosome painting probe was hybridized with formaldehyde-fixed ovaries of mosquitoes using a 3D-FISH method. The nucleolus was stained by immunostaining with an anti-fibrillarin antibody. The analysis was conducted with TANGO—a software for a chromosome spatial organization analysis. We show that the volume and position of the X chromosome have tissue-specific characteristics. Unlike nurse cell nuclei, the growth of follicular epithelium nuclei is not accompanied with the proportional growth of the X chromosome. However, the shape of the X chromosome does not differ between the tissues. The dynamics of the X chromosome attachment regions location is tissue-specific and it is correlated with the process of nucleus growth in follicular epithelium and nurse cells. PMID:28158219

  4. Chromosome sites play dual roles to establish homologous synapsisduring meiosis in C. elegans

    Energy Technology Data Exchange (ETDEWEB)

    MacQueen, Amy J.; Phillips, Carolyn M.; Bhalla, Needhi; Weiser,Pinky; Villeneuve, Anne M.; Dernburg, Abby F.

    2005-06-05

    required for accurate segregation of homologous chromosomesduring meiosisin C. elegans. We find that these sites play two distinctroles that contribute to proper segregation. Chromosomes lacking PCsusually fail to synapse and also lack a synapsis-independentstabilization activity. The presence of a PC on justone copy of achromosome pair promotes synapsis but does not supportsynapsis-independent pairing stabilization, indicating that thesefunctions are separable. Once initiated, synapsis is highly processive,even between non homologous chromosomes of disparate lengths, elucidatinghow translocations suppress meiotic recombination in C. elegans. Thesefindings suggest a multistep pathway for chromosome synapsis in which PCsimpart selectivity and efficiency through a kinetic proofreadingmechanism. We speculate that concentration of these activities at oneregion per chromosome may have co-evolved with the loss of a pointcentromere to safeguard karyotype stability.

  5. A high-resolution comparative map between pig chromosome 17 and human chromosomes 4, 8, and 20: Identification of synteny breakpoints

    DEFF Research Database (Denmark)

    Lahbib-Mansais, Yvette; Karlskov-Mortensen, Peter; Mompart, Florence;

    2005-01-01

    We report on the construction of a high-resolution comparative map of porcine chromosome 17 (SSC17) focusing on evolutionary breakpoints with human chromosomes. The comparative map shows high homology with human chromosome 20 but suggests more limited homologies with other human chromosomes. SSC17...... is of particular interest in studies of chromosomal organization due to the presence of QTLs that affect meat quality and carcass composition. A total of 158 pig ESTs available in databases or developed by the Sino-Danish Pig Genome Sequencing Consortium were mapped using the INRA-University of Minnesota porcine...... radiation hydrid panel. The high-resolution map was further anchored by fluorescence in situ hybridization. This study confirmed the extensive conservation between SSC17 and HSA20 and enabled the gene order to be determined. The homology of the SSC17 pericentromeric region was extended to other human...

  6. What is regressive autism and why does it occur? Is it the consequence of multi-systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature?

    OpenAIRE

    Graham W. Ewing

    2009-01-01

    There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the ex...

  7. Chromosome identification in the Andean common bean accession G19833 (Phaseolus vulgaris L., Fabaceae

    Directory of Open Access Journals (Sweden)

    Sarah Altrock

    2011-01-01

    Full Text Available Characterization of all chromosomes of the Andean G19833 bean genotype was carried out by fluorescent in situ hybridization. Eleven single-copy genomic sequences, one for each chromosome, two BACs containing subtelomeric and pericentromeric repeats and the 5S and 45S ribosomal DNA (rDNA were used as probes. Comparison to the Mesoamerican accession BAT93 showed little divergence, except for additional 45S rDNA sites in four chromosome pairs. Altogether, the results indicated a relative karyotypic stability during the evolution of the Andean and Mesoamerican gene pools of P. vulgaris.

  8. 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.

    2008-01-01

    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

  9. Masculinization of the x chromosome in the pea aphid.

    Directory of Open Access Journals (Sweden)

    Julie Jaquiéry

    Full Text Available Evolutionary theory predicts that sexually antagonistic mutations accumulate differentially on the X chromosome and autosomes in species with an XY sex-determination system, with effects (masculinization or feminization of the X depending on the dominance of mutations. Organisms with alternative modes of inheritance of sex chromosomes offer interesting opportunities for studying sexual conflicts and their resolution, because expectations for the preferred genomic location of sexually antagonistic alleles may differ from standard systems. Aphids display an XX/X0 system and combine an unusual inheritance of the X chromosome with the alternation of sexual and asexual reproduction. In this study, we first investigated theoretically the accumulation of sexually antagonistic mutations on the aphid X chromosome. Our results show that i the X is always more favourable to the spread of male-beneficial alleles than autosomes, and should thus be enriched in sexually antagonistic alleles beneficial for males, ii sexually antagonistic mutations beneficial for asexual females accumulate preferentially on autosomes, iii in contrast to predictions for standard systems, these qualitative results are not affected by the dominance of mutations. Under the assumption that sex-biased gene expression evolves to solve conflicts raised by the spread of sexually antagonistic alleles, one expects that male-biased genes should be enriched on the X while asexual female-biased genes should be enriched on autosomes. Using gene expression data (RNA-Seq in males, sexual females and asexual females of the pea aphid, we confirm these theoretical predictions. Although other mechanisms than the resolution of sexual antagonism may lead to sex-biased gene expression, we argue that they could hardly explain the observed difference between X and autosomes. On top of reporting a strong masculinization of the aphid X chromosome, our study highlights the relevance of organisms displaying

  10. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  11. Activation of proto-oncogenes by disruption of chromosome neighborhoods.

    Science.gov (United States)

    Hnisz, Denes; Weintraub, Abraham S; Day, Daniel S; Valton, Anne-Laure; Bak, Rasmus O; Li, Charles H; Goldmann, Johanna; Lajoie, Bryan R; Fan, Zi Peng; Sigova, Alla A; Reddy, Jessica; Borges-Rivera, Diego; Lee, Tong Ihn; Jaenisch, Rudolf; Porteus, Matthew H; Dekker, Job; Young, Richard A

    2016-03-25

    Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells.

  12. Dean flow fractionation of chromosomes

    Science.gov (United States)

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

    2016-03-01

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

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

    OpenAIRE

    Paliulis, Leocadia V.; Nicklas, R. Bruce

    2000-01-01

    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 ...

  14. Fosfato e micorriza na estabilidade de agregados em amostras de latossolos cultivados e não-cultivados Aggregate stability in two cropped and no-cropped Oxisols as affected by phosphate addition and mycorrhiza

    Directory of Open Access Journals (Sweden)

    Júlio César Azevedo Nóbrega

    2001-11-01

    Full Text Available Nos trópicos, existe escassez de informação quanto à contribuição de espécies fúngicas do solo na formação e estabilização de agregados. Este estudo teve como objetivo avaliar o efeito do histórico de uso, níveis de P, de inoculação micorrízica e cultivo com braquiária e soja em casa de vegetação, sobre o diâmetro médio geométrico dos agregados (DMG, o índice de floculação das partículas, a matéria seca das raízes, a colonização micorrízica e o comprimento total de hifas, em amostras de Latossolo Vermelho distrófico e Latossolo Vermelho distroférrico. Amostras dos dois solos, previamente cultivados por longos períodos, e de solos não-cultivados, foram trazidas para casa de vegetação, submetidas a inoculação, e a dois níveis de P, e então cultivadas com braquiária e soja, em dois cultivos sucessivos. Os resultados mostraram que o solo previamente cultivado apresentou menor comprimento total de hifas, menor estabilidade de agregados (menor diâmetro médio de agregados e menor índice de floculação. A inoculação propiciou maior estabilidade dos agregados, e este efeito é condicionado ao nível de P do solo e ao histórico de uso. A presença de P promoveu, indiretamente, maior agregação, por propiciar maior comprimento total das hifas e matéria seca de raízes.In the tropics there is little information on the contribution of soil microorganisms on aggregate stability in the soils. Soil management, crop and fertilization can affect the fungi specie in soil, and also affect aggregate stability. This study attempted to evaluate the effect of earlier cropping, phosphate, inoculation with AMF, and brachiaria and soybean on the geometric mean diameter (GMD, particle flocculation index, root dry matter, and total hyphal length, in dystrophic Red Latosol and dystroferric Red Latosol (both Oxisols. Samples of both soils under natural condition and previously cultivated were brought to the green house and

  15. The chromosomal passenger complex activates Polo kinase at centromeres.

    Directory of Open Access Journals (Sweden)

    Mar Carmena

    2012-01-01

    Full Text Available The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC, which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

  16. The chromosomal passenger complex activates Polo kinase at centromeres.

    Science.gov (United States)

    Carmena, Mar; Pinson, Xavier; Platani, Melpi; Salloum, Zeina; Xu, Zhenjie; Clark, Anthony; Macisaac, Fiona; Ogawa, Hiromi; Eggert, Ulrike; Glover, David M; Archambault, Vincent; Earnshaw, William C

    2012-01-01

    The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

  17. Oxidative DNA damage in mouse sperm chromosomes: Size matters.

    Science.gov (United States)

    Kocer, Ayhan; Henry-Berger, Joelle; Noblanc, Anais; Champroux, Alexandre; Pogorelcnik, Romain; Guiton, Rachel; Janny, Laurent; Pons-Rejraji, Hanae; Saez, Fabrice; Johnson, Graham D; Krawetz, Stephen A; Alvarez, Juan G; Aitken, R John; Drevet, Joël R

    2015-12-01

    Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models that display high levels of sperm oxidative DNA damage, a common alteration encountered both in in vivo and in vitro reproduction. Immunoprecipitation of oxidized sperm DNA coupled to deep sequencing showed that mouse chromosomes may be largely affected by oxidative alterations. We show that the vulnerability of chromosomes to oxidative attack inversely correlated with their size and was not linked to their GC richness. It was neither correlated with the chromosome content in persisting nucleosomes nor associated with methylated sequences. A strong correlation was found between oxidized sequences and sequences rich in short interspersed repeat elements (SINEs). Chromosome position in the sperm nucleus as revealed by fluorescent in situ hybridization appears to be a confounder. These data map for the first time fragile mouse sperm chromosomal regions when facing oxidative damage that may challenge the repair mechanisms of the oocyte post-fertilization.

  18. History of chromosome rearrangements reflects the spatial organization of yeast chromosomes.

    Science.gov (United States)

    Khrameeva, Ekaterina E; Fudenberg, Geoffrey; Gelfand, Mikhail S; Mirny, Leonid A

    2016-04-01

    Three-dimensional (3D) organization of genomes affects critical cellular processes such as transcription, replication, and deoxyribo nucleic acid (DNA) repair. While previous studies have investigated the natural role, the 3D organization plays in limiting a possible set of genomic rearrangements following DNA repair, the influence of specific organizational principles on this process, particularly over longer evolutionary time scales, remains relatively unexplored. In budding yeast S.cerevisiae, chromosomes are organized into a Rabl-like configuration, with clustered centromeres and telomeres tethered to the nuclear periphery. Hi-C data for S.cerevisiae show that a consequence of this Rabl-like organization is that regions equally distant from centromeres are more frequently in contact with each other, between arms of both the same and different chromosomes. Here, we detect rearrangement events in Saccharomyces species using an automatic approach, and observe increased rearrangement frequency between regions with higher contact frequencies. Together, our results underscore how specific principles of 3D chromosomal organization can influence evolutionary events.

  19. In vivo effect on pig chromosomes of high dosage vaccine against classic swine fever.

    Science.gov (United States)

    Genghini, R; Tiranti, I; Segade, G; Amado, J; Wittouck, P; Mian, L

    1998-12-03

    Hog cholera virus (HCV) can induce chromosome abnormalities in diseased pigs as well as in those vaccinated with attenuated virus vaccine against classic swine fever. An experiment was made using animals from potency and safety control tests of commercial vaccines in Argentina. The different types of chromosomal alterations observed were chromatid and chromosome breaks, chromatid exchanges, polyploid, multiple aberrations cells, and chromosome pulverization. In this study the occurrence of chromosome alterations in pigs receiving either 1 or 10 vaccine doses was evaluated by means of blood sampling at different periods after vaccination. An essay comparing prolificity between treated and non-treated sows was also made. Significant differences in the amount of damaged chromosomes as well as differences in the type of predominant alterations between the two treatments were observed. Aberration frequencies increased from the 5-day postvaccination period reaching the highest value of 4.14% at the 10th, for the one-dose treatment; and highest value of 42.7% including 33.96% of cell with chromosome pulverization which was found in the 7th day interval when applying 10 doses. From then on, the proportion of affected cells dropped until the 20th day interval, which was the last recorded. The prolificity trial did not show any difference between treated and control sows, indicating that chromosome alteration might be limited to lymphocytes. It is concluded that HCV maintains its mutagenic potentiality in the attenuated vaccine, being able to induce chromosomal damage as it does in classic swine fever diseased animals.

  20. pain2: A neuropathic pain QTL identified on rat chromosome 2.

    Science.gov (United States)

    Nissenbaum, Jonathan; Shpigler, Hagai; Pisanté, Anne; DelCanho, Sonia; Minert, Anne; Seltzer, Ze'ev; Devor, Marshall; Darvasi, Ariel

    2008-03-01

    We aimed to locate a chronic pain-associated QTL in the rat (Rattus norvegicus) based on previous findings of a QTL (pain1) on chromosome 15 of the mouse (Mus musculus). The work was based on rat selection lines HA (high autotomy) and LA (low autotomy) which show a contrasting pain phenotype in response to nerve injury in the neuroma model of neuropathic pain. An F(2) segregating population was generated from HA and LA animals. Phenotyped F(2) rats were genotyped on chromosome 7 and chromosome 2, regions that share a partial homology with mouse chromosome 15. Our interval mapping analysis revealed a LOD score value of 3.63 (corresponding to p=0.005 after correcting for multiple testing using permutations) on rat chromosome 2, which is suggestive of the presence of a QTL affecting the predisposition to neuropathic pain. This QTL was mapped to the 14-26cM interval of chromosome 2. Interestingly, this region is syntenic to mouse chromosome 13, rather than to the region of mouse chromosome 15 that contains pain1. This chromosomal position indicates that it is possibly a new QTL, and hence we name it pain2. Further work is needed to replicate and to uncover the underlying gene(s) in both species.

  1. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice.

    Science.gov (United States)

    Cox, Kimberly H; Quinnies, Kayla M; Eschendroeder, Alex; Didrick, Paula M; Eugster, Erica A; Rissman, Emilie F

    2015-01-01

    Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders.

  2. Sex ratio in normal and disomic sperm: Evidence that the extra chromosome 21 preferentially segregates with the Y chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, D.K.; Millie, E.A.; Hassold, T.J. [Case Western Univ., Cleveland, OH (United States)]|[Univ. Hospitals of Cleveland, OH (United States)] [and others

    1996-11-01

    In humans, deviations from a 1:1 male:female ratio have been identified in both chromosomally normal and trisomic live births: among normal newborns there is a slight excess of males, among trisomy 18 live borns a large excess of females, and among trisomy 21 live borns an excess of males. These differences could arise from differential production of or fertilization by Y- or X-bearing sperm or from selection against male or female conceptions. To examine the proportion of Y- and X- bearing sperm in normal sperm and in sperm disomic for chromosomes 18 or 21, we used three-color FISH (to the X and Y and either chromosome 18 or chromosome 21) to analyze > 300,000 sperm from 24 men. In apparently normal sperm, the sex ratio was nearly 1:1 (148,074 Y-bearing to 148,657 X-bearing sperm), and the value was not affected by the age of the donor. Certain of the donors, however, had significant excesses of Y- or X-bearing sperm. In disomy 18 sperm, there were virtually identical numbers of Y- and X-bearing sperm; thus, the excess of females in trisomy 18 presumably is due to selection against male trisomic conceptions. In contrast, we observed 69 Y-bearing and 44 X-bearing sperm disomic for chromosome 21. This is consistent with previous molecular studies, which have identified an excess of males among paternally derived cases of trisomy 21, and suggests that some of the excess of males among Down syndrome individuals is attributable to a nondisjunctional mechanism in which the extra chromosome 21 preferentially segregates with the Y chromosome. 17 refs., 2 tabs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-14

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

  4. M-BAND Study of Radiation-Induced Chromosome Aberrations in Human Epithelial Cells: Radiation Quality and Dose Rate Effects

    Science.gov (United States)

    Hada, Megumi; Cucinotta, Francis; Wu, Honglu

    2009-01-01

    The advantage of the multicolor banding in situ hybridization (mBAND) technique is its ability to identify both inter- (translocation to unpainted chromosomes) and intra- (inversions and deletions within a single painted chromosome) chromosome aberrations simultaneously. To study the detailed rearrangement of low- and high-LET radiation induced chromosome aberrations in human epithelial cells (CH184B5F5/M10) in vitro, we performed a series of experiments with Cs-137 gamma rays of both low and high dose rates, neutrons of low dose rate and 600 MeV/u Fe ions of high dose rate, with chromosome 3 painted with multi-binding colors. We also compared the chromosome aberrations in both 2- and 3-dimensional cell cultures. Results of these experiments revealed the highest chromosome aberration frequencies after low dose rate neutron exposures. However, detailed analysis of the radiation induced inversions revealed that all three radiation types induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intra-chromosomal aberrations but few inversions were accompanied by inter-chromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosomal exchanges. The location of the breaks involved in chromosome exchanges was analyzed along the painted chromosome. The breakpoint distribution was found to be randomly localized on chromosome 3 after neutron or Fe ion exposure, whereas non-random distribution with clustering breakpoints was observed after -ray exposure. Our comparison of chromosome aberration yields between 2- and 3-dimensional cell cultures indicated a significant difference for gamma exposures, but not for Fe ion exposures. These experimental results indicated that the track structure of the radiation and the cellular/chromosome structure can both affect radiation-induced chromosome

  5. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Science.gov (United States)

    Mengoli, Valentina; Bucciarelli, Elisabetta; Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-10-01

    Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences

  6. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Directory of Open Access Journals (Sweden)

    Valentina Mengoli

    2014-10-01

    Full Text Available Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on

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

    Science.gov (United States)

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

    2016-08-01

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

  8. Chromosome-specific families in Vibrio genomes

    Directory of Open Access Journals (Sweden)

    Oksana eLukjancenko

    2014-03-01

    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.

  9. [Developing a physical map of human chromosome 22]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Simon, M.I.

    1991-12-31

    We have developed bacterial F-factor based systems for cloning large fragments of human DNA in E. coli. In addition to large size, these systems are capable of maintaining human DNA with a high degree of stability. The cosmid size clones are called Fosmids and the clones containing larger inserts (100--200 kb) are called bacterial artificial chromosomes (BACs). The ultimate test of the effectiveness of cloning and mapping technology is the degree to which it can be efficiently applied to solve complex mapping problems. We, therefore, plan to use the large fragment cloning procedure as well as a variety of other approaches to generate a complete map of overlapping clones corresponding to human chromosome 22. We have thus far prepared two human chromosome 22 specific Fosmid libraries and we are in the process of constructing a chromosome 22 specific BAC library composed of fragments larger than 100 kb. We will further optimize the technology so that libraries of fragments larger than 200 kb can be readily prepared.

  10. (Developing a physical map of human chromosome 22)

    Energy Technology Data Exchange (ETDEWEB)

    Simon, M.I.

    1991-01-01

    We have developed bacterial F-factor based systems for cloning large fragments of human DNA in E. coli. In addition to large size, these systems are capable of maintaining human DNA with a high degree of stability. The cosmid size clones are called Fosmids and the clones containing larger inserts (100--200 kb) are called bacterial artificial chromosomes (BACs). The ultimate test of the effectiveness of cloning and mapping technology is the degree to which it can be efficiently applied to solve complex mapping problems. We, therefore, plan to use the large fragment cloning procedure as well as a variety of other approaches to generate a complete map of overlapping clones corresponding to human chromosome 22. We have thus far prepared two human chromosome 22 specific Fosmid libraries and we are in the process of constructing a chromosome 22 specific BAC library composed of fragments larger than 100 kb. We will further optimize the technology so that libraries of fragments larger than 200 kb can be readily prepared.

  11. The chromosomes of the Didelphidae (Marsupialia) and their evolutionary significance

    Science.gov (United States)

    Reig, O.; Gardner, A.L.; Bianchi, N.O.; Patton, J.L.

    1977-01-01

    One hundred and seventy-seven specimens of American didelphids, representing 9 genera and 22 species have been studied for their chromosomal constitution. Didelphids are very conservative in chromosomal complements. All of the studied species can be sorted into one of three kinds of karyotypes: 2n= 14 (three species of Didelphis, one of Lutreolina, two of Philander, and one of Chironectes), 2n = 14 (eight species of Marmosa, one of Metachirus, three of Caluromys, and one of Dromiciops), and 2n= 18 (three species of Monodelphis). These karyotypes are stable, showing only minor variations within each basic pattern. It is concluded that chromosomals evolution in the Didelphidae proceededs from low numbers to higher numbers by a process of centromeric fissioning complemented by some pericentric inversions and/or translocations. The pattern of karyotypic stability is consistent with bradytely at the organismic level of evolution. This is explained by a low rate of regulatory genetic evolution promoted by epistatic selection favouring the retention of chromosomal arrangements highly advantageous for overall adaptation.

  12. Sex chromosome rearrangements in Polyphaga beetles.

    Science.gov (United States)

    Dutrillaux, A M; Dutrillaux, B

    2009-01-01

    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.

  13. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    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...

  14. Chromosome Territory Modeller and Viewer.

    Science.gov (United States)

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

    2016-01-01

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

  15. CHROMOSOMAL MULTIPLICITY IN BURKHOLDERIA CEPACIA

    Science.gov (United States)

    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 ...

  16. Chromosome synteny in cucumis species

    Science.gov (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...

  17. Chromosomal disorders and male infertility

    Institute of Scientific and Technical Information of China (English)

    Gary L Harton; Helen G Tempest

    2012-01-01

    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.

  18. A Plain English Map of the Human Chromosomes.

    Science.gov (United States)

    Offner, Susan

    1992-01-01

    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)

  19. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

    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....

  20. 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)

    2009-01-01

    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

  1. Chromosomal assignment of canine THADA gene to CFA 10q25

    Directory of Open Access Journals (Sweden)

    Dolf Gaudenz

    2008-06-01

    Full Text Available Abstract Background Chromosomal translocations affecting the chromosome 2p21 cluster in a 450 kb breakpoint region are frequently observed in human benign thyroid adenomas. THADA (thyroid adenoma associated was identified as the affected gene within this breakpoint region. In contrast to man tumours of the thyroid gland of dogs (Canis lupus familiaris constitute mainly as follicular cell carcinomas, with malignant thyroid tumours being more frequent than benign thyroid adenomas. In order to elucidate if the THADA gene is also a target of chromosomal rearrangements in thyroid adenomas of the dog we have physically mapped the canine THADA gene to canine chromosome 10. A PCR was established to screen a canine genome library for a BAC clone containing the gene sequence of canine THADA. Further PCR reactions were done using the identified BAC clone as a template in order to verify the corresponding PCR product by sequencing. Canine whole blood was incubated with colcemid in order to arrest the cultured cells in metaphases. The verified BAC DNA was digoxigenin labeled and used as a probe in fluorescence in situ hybridization (FISH. Ten well spread metaphases were examined indicating a signal on canine chromosome 10 on both chromatids. A detailed fine mapping was performed indicating the canine THADA gene locus on the q-arm of chromosome 10. Results The canine THADA gene locus was mapped on chromosome 10q25. Our mapping results obtained in this study following the previously described nomenclature for the canine karyotype. Conclusion We analysed whether the THADA gene locus is a hotspot of canine chromosomal rearrangements in canine neoplastic lesions of the thyroid and in addition might play a role as a candidate gene for a possible malignant transformation of canine thyroid adenomas. Although the available cytogenetic data of canine thyroid adenomas are still insufficient the chromosomal region to which the canine THADA has been mapped seems to be no

  2. Shearing stability of lubricants

    Science.gov (United States)

    Shiba, Y.; Gijyutsu, G.

    1984-01-01

    Shearing stabilities of lubricating oils containing a high mol. wt. polymer as a viscosity index improver were studied by use of ultrasound. The oils were degraded by cavitation and the degradation generally followed first order kinetics with the rate of degradation increasing with the intensity of the ultrasonic irradiation and the cumulative energy applied. The shear stability was mainly affected by the mol. wt. of the polymer additive and could be determined in a short time by mechanical shearing with ultrasound.

  3. Shearing stability of lubricants

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Y.; Gijyutsu, G.

    1984-03-01

    Shearing stabilities of lubricating oils containing a high mol. wt. polymer as a viscosity index improver were studied by use of ultrasound. The oils were degraded by cavitation and the degradation generally followed first order kinetics with the rate of degradation increasing with the intensity of the ultrasonic irradiation and the cumulative energy applied. The shear stability was mainly affected by the mol. wt. of the polymer additive and could be determined in a short time by mechanical shearing with ultrasound.

  4. Food Fortification Stability Study

    Science.gov (United States)

    Sirmons, T. A.; Cooper, M. R.; Douglas, G. L.

    2017-01-01

    This study aimed to assess the stability of vitamin content, sensory acceptability and color variation in fortified spaceflight foods over a period of two years. Findings will help to identify optimal formulation, processing, and storage conditions to maintain stability and acceptability of commercially available fortification nutrients. Changes in food quality were monitored to indicate whether fortification affects quality over time (compared to the unfortified control), thus indicating their potential for use on long-duration missions.

  5. Food Fortification Stability Study

    Science.gov (United States)

    Sirmons, T. A.; Cooper, M. R.; Douglas, G. L.

    2016-01-01

    This study aims to assess the stability of vitamin content, sensory acceptability and color variation in fortified spaceflight foods over a period of 2 years. Findings will identify optimal formulation, processing, and storage conditions to maintain stability and acceptability of commercially available fortification nutrients. Changes in food quality are being monitored to indicate whether fortification affects quality over time (compared to the unfortified control), thus indicating their potential for use on long-duration missions.

  6. Replisome Assembly at Bacterial Chromosomes and Iteron Plasmids

    Directory of Open Access Journals (Sweden)

    Katarzyna Ewa Wegrzyn

    2016-08-01

    Full Text Available The proper initiation and occurrence of DNA synthesis depends on the formation and rearrangements of nucleoprotein complexes within the origin of DNA replication. In this review article, we present the current knowledge on the molecular mechanism of replication complex assembly at the origin of bacterial chromosome and plasmid replicon containing direct repeats (iterons within the origin sequence. We describe recent findings on chromosomal and plasmid replication initiators, DnaA and Rep proteins, respectively, and their sequence-specific interactions with double and single stranded DNA. Also, we discuss the current understanding of the activities of DnaA and Rep proteins required for replisome assembly that is fundamental to the duplication and stability of genetic information in bacterial cells.

  7. The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

    Directory of Open Access Journals (Sweden)

    Noonan James P

    2001-07-01

    Full Text Available Abstract Background Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10 or PML (promyelocytic leukemia nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. Results This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies.

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

    OpenAIRE

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

    1994-01-01

    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 ...

  9. Computer simulations predict that chromosome movements and rotations accelerate mitotic spindle assembly without compromising accuracy.

    Science.gov (United States)

    Paul, Raja; Wollman, Roy; Silkworth, William T; Nardi, Isaac K; Cimini, Daniela; Mogilner, Alex

    2009-09-15

    The mitotic spindle self-assembles in prometaphase by a combination of centrosomal pathway, in which dynamically unstable microtubules search in space until chromosomes are captured, and a chromosomal pathway, in which microtubules grow from chromosomes and focus to the spindle poles. Quantitative mechanistic understanding of how spindle assembly can be both fast and accurate is lacking. Specifically, it is unclear how, if at all, chromosome movements and combining the centrosomal and chromosomal pathways affect the assembly speed and accuracy. We used computer simulations and high-resolution microscopy to test plausible pathways of spindle assembly in realistic geometry. Our results suggest that an optimal combination of centrosomal and chromosomal pathways, spatially biased microtubule growth, and chromosome movements and rotations is needed to complete prometaphase in 10-20 min while keeping erroneous merotelic attachments down to a few percent. The simulations also provide kinetic constraints for alternative error correction mechanisms, shed light on the dual role of chromosome arm volume, and compare well with experimental data for bipolar and multipolar HT-29 colorectal cancer cells.

  10. 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

    1994-09-01

    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.

  11. Ideal Stabilization

    CERN Document Server

    Nesterenko, Mikhail

    2009-01-01

    We define and explore the concept of ideal stabilization. The program is ideally stabilizing if its every state is legitimate. Ideal stabilization allows the specification designer to prescribe with arbitrary degree of precision not only the fault-free program behavior but also its recovery operation. Specifications may or may not mention all possible states. We identify approaches to designing ideal stabilization to both kinds of specifications. For the first kind, we state the necessary condition for an ideally stabilizing solution. On the basis of this condition we prove that there is no ideally stabilizing solution to the leader election problem. We illustrate the utility of the concept by providing examples of well-known programs and proving them ideally stabilizing. Specifically, we prove ideal stabilization of the conflict manager, the alternator, the propagation of information with feedback and the alternating bit protocol.

  12. Immunodeficiency in Patients With 49,XXXXY Chromosomal Variation

    OpenAIRE

    Keller, Michael D; Sadeghin, Teresa; Samango-Sprouse, Carole; Orange, Jordan S.

    2013-01-01

    Boys affected with 49,XXXXY sex chromosomal variation have been described to have high incidence of recurrent otitis media and asthma, the cause of which is unknown. We hypothesized that primary immunodeficiency occurs in patients with XXXXY aneuploidy. To investigate this, 31 boys with known 49,XXXXY were evaluated through a multidisciplinary clinic. Screening history was performed using the “10 Warning Signs of primary immunodeficiency” (Jeffrey Modell Foundation), as well as by history of ...

  13. Chromosome congression explained by nanoscale electrostatics.

    Science.gov (United States)

    Gagliardi, L John; Shain, Daniel H

    2014-02-24

    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.

  14. The Chromosomes of Birds during Meiosis.

    Science.gov (United States)

    Pigozzi, María I

    2016-01-01

    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.

  15. Polymer models of chromosome (re)organization

    Science.gov (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.

  16. 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

    2011-01-01

    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.

  17. Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe

    Indian Academy of Sciences (India)

    Aditya S Pratihar; Vishnu P Tripathi; Mukesh P Yadav; Dharani D Dubey

    2015-12-01

    Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2OO4, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2OO4 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727-associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2OO4 or ars727 remains unaltered by the extended chromosomal context.

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

    Science.gov (United States)

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

    1998-01-01

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

  19. The role of dicentric chromosome formation and secondary centromere deletion in the evolution of myeloid malignancy.

    Science.gov (United States)

    Mackinnon, Ruth N; Campbell, Lynda J

    2011-01-01

    Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy.

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

    Science.gov (United States)

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

    2013-03-01

    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.

  1. Polymorphic haplotypes on R408BW PKU and normal PAH chromosomes in Quebec and European populations

    Energy Technology Data Exchange (ETDEWEB)

    Byck, S.; Morgan, K.; Scriver, C.R. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    The R408W mutation in the phenylalanine hydroxylase gene (PAH) is associated with haplotype 2.3 (RFLP haplotype 2, VNTR 3 of the HindIII system) in most European populations. Another chromosome, first observed in Quebec and then in northwest Europe, carries R408W on haplotype 1.8. The occurrence of the R408W mutation on two different PKU chromosomes could be the result of intragenic recombination, recurrent mutation or gene conversion. In this study, we analyzed both normal and R408W chromosomes carrying 1.8 and 2.3 haplotypes in Quebec and European populations; we used the TCTA{sub (n)} short tandem repeat sequence (STR) at the 5{prime} end of the PAH gene and the HindIII VNTR system at the 3{prime} end of the PAH gene to characterize chromosomes. Fourteen of sixteen R408W chromosomes from {open_quotes}Celtic{close_quotes} families in Quebec and the United Kingdom (UK) harbor a 244 bp STR allele; the remaining two chromosomes, carry a 240 bp or 248bp STR allele. Normal chromosomes (n=18) carry the 240 bp STR allele. R408W chromosomes are different from mutant H1.8 chromosomes; mutant H2.3 carries the 240 bp STR allele (14 of 16 chromosomes) or the 236 allele (2 of 16 chromosomes). The HindIII VNTR comprises variable numbers of 30 bp repeats (cassettes); the repeats also vary in nucleotide sequence. Variation clusters toward the 3{prime} end of cassettes and VNTRs. VNTR 3 alleles on normal H2 (n=9) and mutant R408W H2 (n=19) chromosomes were identical. VNTR 8 alleles on normal H1 chromosomes (n=9) and on R408W H1 chromosomes (n=15) differ by 1 bp substitution near the 3{prime} end of the 6th cassette. In summary, the mutant H1.8 chromosome harboring the R408W mutation has unique features at both the 5{prime} and 3{prime} end of the gene that distinguish it from the mutant H2.3 and normal H1.8 and H2.3 counterparts. The explanation for the occurrence of R408W on two different PAH haplotypes is recurrent mutation affecting the CpG dinucleotide in PAH codon 408.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisong [ORNL; Liu, Yie [ORNL

    2006-01-01

    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.

  3. Factors affecting stability of activated sludge process for sorbitol wastewater treatment%山梨醇废水生物处理工程稳定运行的影响因素分析

    Institute of Scientific and Technical Information of China (English)

    赵印; 吴育津; 顾向阳; 沈标

    2009-01-01

    In the present paper factors affecting the stability of activated sludge process for sorbitol wastewater treatment were analyzed. Results showed that organic shock loads, excessive input of siliceous marl or Ni~(2+) ion constituted major factors affecting sorbitol wastewater treatment efficiency and effluent quality. Intermittent and continuous shock loading had been observed during the 5-month operation of sorbitol wastewater treatment system using activated sludge process. Intermittent shock loading showed no adverse effects on effluent quality whereas continuous shock loading led to lower chemical oxygen demand ( COD) removal rate with effluent COD concentration higher than discharge standards. Inferior effluent quality could also result from input of excessive amounts of siliceous marl or Ni~(2+) to the process wastewater. In order to achieve long-term stable operation of sorbitol wastewater treatment system, leakage of siliceous marl or Ni~(2+) into process wastewater has to be prevented through strengthening facility operation and management.%根据工程运行数据对影响山梨醇废水生物处理工程稳定运行的因素进行了系统分析.结果发现:影响废水处理效率和出水水质的因素主要有有机负荷冲击、高浓度硅藻土和Ni~(2+)毒性负荷冲击.有机负荷冲击有间歇性冲击和连续性冲击两种形式,间歇性负荷冲击对系统处理效能没有不利影响,但连续性负荷冲击时化学需氧量(COD)去除率明显下降,出水水质严重超标.高浓度硅藻土和Ni~(2+)冲击对出水水质也有较大影响,且持续时间较长.因此,加强生产设备的操作和管理,杜绝硅藻土和Ni~(2+)泄漏进入工艺废水,是山梨醇废水工程长期稳定运行的必要条件.

  4. Detection of Embryo Sex Chromosome by Dual Color Fluorescent In-Situ Hybridization

    Institute of Scientific and Technical Information of China (English)

    刘群; 朱桂金

    2003-01-01

    Summary: In order to evaluate the effects of sex chromosomal mosaicism on the accuracy of single-cell gender diagnosis, sex chromosomes of 21 normal fertilized embryos were detected by dual colorfluorescent in-situ hybridization (FISH). The results showed that 4 embryos had sex chromosomalmosaicism (19%) and the remaining 17 showed uniformly XX or XY signals in all blastomeres. Inconclusion, identification of sex by dual color FISH analysis of a single cell was accurate and efficient,and sex chromosomal mosaicism would not affect preimplantation gender diagnosis.

  5. Chromosomal patterns in human malignant astrocytomas.

    Science.gov (United States)

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

    1987-12-01

    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.

  6. Entropy as the driver of chromosome segregation.

    Science.gov (United States)

    Jun, Suckjoon; Wright, Andrew

    2010-08-01

    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.

  7. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-05-11

    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.

  8. Chromosome X aneuploidy in Brazilian schizophrenic patients.

    Science.gov (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

    2010-01-01

    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.

  9. Cytogenetics of Premature Ovarian Failure: An Investigation on 269 Affected Women

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    Simona Baronchelli

    2011-01-01

    Full Text Available The importance of X chromosome in the aetiology of premature ovarian failure (POF is well-known but in many cases POF still remains idiopathic. Chromosome aneuploidy increase is a physiological phenomenon related to aging, but the role of low-level sex chromosome mosaicism in ovarian function is still undiscovered. Standard cytogenetic analysis was carried out in a total of 269 patients affected by POF: 27 chromosomal abnormalities were identified, including X chromosome and autosomal structural and numerical abnormalities. In 47 patients with 46,XX karyotype we performed interphase FISH using X alpha-satellite probe in order to identify X chromosome mosaicism rate. Aneuploidy rate in the patient group was significantly higher than the general population group. These findings underline the importance of X chromosome in the aetiology of POF and highlight the potential role of low-level sex chromosome mosaicism in ovarian aging that may lead to a premature onset of menopause.

  10. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

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

    2009-01-01

    -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....

  11. A case of acute lymphoblastic leukemia with additional chromosomes X and 5 associated with a Philadelphia chromosome in the bone marrow

    Directory of Open Access Journals (Sweden)

    Burak Durmaz

    2010-12-01

    Full Text Available We report herein a very rare case of acute lymphoblastic leukemia having a chromosomal constitution of 48,XY,+X,+5,t(9;22(q34;q11 in the bone marrow. A patient with additional chromosomes X and 5 with a Philadelphia chromosome has not been reported previously. However, no abnormal karyotype was obtained from the lymphocytes in our patient, and he did not have the characteristics of Klinefelter syndrome. He achieved a complete remission with IDA-FLAG and dasatinib therapy. The mechanism of trisomy 5 or any other chromosomal aneuploidy in the pathogenesis of leukemogenesis remains unclear. Further studies involving the genes affected by this karyotype and their products may lead to strategies to further increase the understanding of drug-resistant acute lymphoblastic leukemia and may represent the next frontier in the targeted therapy of those patients.

  12. Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium

    Science.gov (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...

  13. Bacterial Chromosome Organization and Segregation

    OpenAIRE

    Toro, Esteban; Shapiro, Lucy

    2010-01-01

    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...

  14. Environmental pollution, chromosomes, and health

    Science.gov (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.

  15. GSK-3 inhibitors induce chromosome instability

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    Staples Oliver D

    2007-08-01

    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.

  16. Mechanisms of Chromosome Congression during Mitosis

    Science.gov (United States)

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

    2017-01-01

    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

  17. Mechanisms of Chromosome Congression during Mitosis

    Directory of Open Access Journals (Sweden)

    Helder Maiato

    2017-02-01

    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

  18. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

    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.

  19. Chromosomal basis of viability differences in Tigriopus californicus interpopulation hybrids.

    Science.gov (United States)

    Harrison, J S; Edmands, S

    2006-11-01

    Crosses between populations of Tigriopus californicus result in backcross and F2 hybrid breakdown for a variety of fitness related measures. The magnitude of this hybrid breakdown is correlated with evolutionary divergence. We assessed the chromosomal basis of viability differences in nonrecombinant backcross hybrids using markers mapped to individual chromosomes. To assess effects of evolutionary divergence we crossed one population to three different populations: two distantly related (approximately 18% mitochondrial COI sequence divergence) and one closely related (approximately 1% mitochondrial COI sequence divergence). We found that all three interpopulation crosses resulted in significant deviations from expected Mendelian ratios at a majority of the loci studied. In all but one case, deviations were due to a deficit of parental homozygotes. This pattern implies that populations of T. californicus carry a significant genetic load, and that a combination of beneficial dominance and deleterious homozygote-heterozygote interactions significantly affects hybrid viability. Pairwise tests of linkage disequilibrium detected relatively few significant interactions. For the two divergent crosses, effects of individual chromosomes were highly concordant. These two crosses also showed higher heterozygote excess in females than males across the vast majority of chromosomes.

  20. ETOPOSIDE INDUCES CHROMOSOMAL ABNORMALITIES IN SPERMATOCYTES AND SPERMATOGONIAL STEM CELLS

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Pearson, F S; Bishop, J B; Wyrobek, A J

    2005-07-15

    Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukemia, lymphomas and many solid tumors, such as testicular and ovarian cancers, that affect patients in their reproductive years. The purpose of the study was to use sperm FISH analyses to characterize the long-term effects of ET on male germ cells. We used a mouse model to characterize the induction of chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. ET treatment resulted in major increases in the frequencies of sperm carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. These results demonstrate that male meiotic germ cells are considerably more sensitive to ET than spermatogonial stem-cell and that increased frequencies of sperm with structural aberrations persist after spermatogonial stem-cell treatment. These findings predict that patients who undergo chemotherapy with ET may have transient elevations in the frequencies of aneuploid sperm, but more importantly, may have persistent elevations in the frequencies of sperm with chromosomal aberrations, placing them at higher risk for abnormal reproductive outcomes long after the end of their chemotherapy.

  1. A Case of Autism with Ring Chromosome 14.

    Directory of Open Access Journals (Sweden)

    Massoumeh Tajeran

    2013-11-01

    Full Text Available Autism is a complex neuropsychiatric disorder that manifests in early childhood. Although the etiology is unknown yet but, new hypothesis focused on identifying the key genes related to autism may elucidate its etiology. The main objective of the present study was to verify the value of karyotyping in autistic children and identifying association between chromosome abnormalities and autism.We examined the peripheral blood lymphocytes cell culture for cytogenetic alterations by GTG-banding technique. The investigation was carried out on 50 autistic patients referred by Pediatric neurologist to Cytogenetic Laboratory in Khorasan-e-razavi Province, Iran.Using GTG-banding technique, the chromosome analysis of patients identified an unbalanced male karyotype with a r (14 in all 50 metaphaseswere examined.Since structural abnormalities may have a critical role in the etiology of autism, according to the region where is affected and number of related genes, therefore an outcome with wide spectrum of clinical manifestations could be expected. Furthermore by considering of recent study, the results indicated that there is an association between chromosome 14 with brain development and neurological disorders, but, in conclusion, it could not be suggested that in order to postulate cytogenetic testing in idiopathic autism patients, specifically screening for chromosome 14 which might has diagnostic value.

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

    Directory of Open Access Journals (Sweden)

    Sebastian Pita

    2013-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

    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.

  4. Neocentric X-chromosome in a girl with Turner-like syndrome

    Directory of Open Access Journals (Sweden)

    Hemmat Morteza

    2012-06-01

    Full Text Available Abstract Background Neocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. We report the finding of a structurally abnormal X chromosome with a neocentromere in a 15-year-old girl with clinical features suggestive of Turner syndrome, including short stature and primary amenorrhea. Result G-banded chromosome analysis revealed a mosaic female karyotype involving two abnormal cell lines. One cell line (84% of analyzed metaphases had a structurally abnormal X chromosome (duplication of the long arm and deletion of the short arm and a normal X chromosome. The other cell line (16% of cells exhibited monosomy X. C-banding studies were negative for the abnormal X chromosome. FISH analysis revealed lack of hybridization of the abnormal X chromosome with both the X centromere-specific probe and the “all human centromeres” probe, a pattern consistent with lack of the X chromosome endogenous centromere. A FISH study using an XIST gene probe revealed the presence of two XIST genes, one on each long arm of the iso(Xq, required for inactivation of the abnormal X chromosome. R-banding also demonstrated inactivation of the abnormal X chromosome. An assay for centromeric protein C (CENP-C was positive on both the normal and the abnormal X chromosomes. The position of CENP-C in the abnormal X chromosome defined a neocentromere, which explains its mitotic stability. The karyotype is thus designated as 46,X,neo(X(qter- > q12::q12- > q21.2- > neo- > q21.2- > qter[42]/45,X[8], which is consistent with stigmata of Turner syndrome. The mother of this patient has a normal karyotype; however, the father was not available for study. Conclusion To our knowledge, this is the first case of mosaic Turner syndrome involving an analphoid iso(Xq chromosome with a proven neocentromere among 90 previously described cases with a proven neocentromere.

  5. X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

    Directory of Open Access Journals (Sweden)

    Martínez F

    2007-11-01

    Full Text Available Abstract Background Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH, may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb, all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%. Conclusion This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.

  6. Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata

    DEFF Research Database (Denmark)

    Poláková, S.; Blume, C.; Zárate, J. A.

    2009-01-01

    , Candida glabrata, for their genome structure and stability. This organism has recently become the second most prevalent yeast pathogen in humans. Although the gene sequences were well conserved among different strains, their chromosome structures differed drastically. The most frequent events reshaping...

  7. A CHROMOSOMAL KARYOTYPING STUDY IN MALE WITH PRIMARY INFERTILITY IN A WESTERN WEST BENGAL POPULATION

    Directory of Open Access Journals (Sweden)

    Abhijit

    2016-03-01

    Full Text Available CONTEXT It is interesting that the primary infertility is a major problem in a society like ours where the population is going to be exploded. It is because that infertility severely affects the family or couples psychological harmony, sexual life & social status. Of the many factors responsible for primary male infertility which may be manifested as azoospermia or oligozoospermia, one of the important etiological factors is genetic abnormality affecting the Y chromosome. Among the different parameters known to be responsible for normal spermatogenesis, a small region in the long arm of Y chromosome, containing genes or gene cluster, defined as ‘Azoospermia Factor’ (AZF is definitely maintains the normal spermatogenesis to occur. Any abnormality in that part of the Y chromosome in the form of deletion or deviation of normal gene arrangement produces azoospermia or oligozoospermia and subsequently produces primary male infertility. SETTINGS Bankura Sammilani Medical College and Hospitals, Bankura, West Bengal. DESIGN Simple random sampling method. DURATION OF STUDY November 2013 to march 2015 (One and a half year. METHOD 80 males suffering from primary infertility with azoospermia or oligozoospermia were selected attending the antenatal outpatient department. STATISTICAL ANALYSIS 2.5% patients showed numerical chromosomal abnormality i.e. Klinefelter syndrome (47XXY. Structural abnormalities were detected in 3.75% patients in the form of deletion in the long arm of Y chromosome and ring chromosome. RESULT Out of 80 patients 5 patients showed chromosomal abnormalities in the form of both numerical as Klinefelter syndrome (2 patients & qualitative as deletions (2 patients & ring chromosome (1 patient. CONCLUSION Y chromosomal abnormalities either numerical or structural, is an important factor of male infertility as oligospermia or azoospermia. These abnormalities can be easily detected by simple aids like karyotyping and does not require high

  8. Chromosome numbers in three species groups of freshwater flatworms increase with increasing latitude.

    Science.gov (United States)

    Lorch, Sven; Zeuss, Dirk; Brandl, Roland; Brändle, Martin

    2016-03-01

    Polyploidy in combination with parthenogenesis offers advantages for plasticity and the evolution of a broad ecological tolerance of species. Therefore, a positive correlation between the level of ploidy and increasing latitude as a surrogate for environmental harshness has been suggested. Such a positive correlation is well documented for plants, but examples for animals are still rare. Species of flatworms (Platyhelminthes) are widely distributed, show a remarkably wide range of chromosome numbers, and offer therefore good model systems to study the geographical distribution of chromosome numbers. We analyzed published data on counts of chromosome numbers and geographical information of three flatworm "species" (Phagocata vitta, Polycelis felina and Crenobia alpina) sampled across Europe (220 populations). We used the mean chromosome number across individuals of a population as a proxy for the level of ploidy within populations, and we tested for relationships of this variable with latitude, mode of reproduction (sexual, asexual or both) and environmental variables (annual mean temperature, mean diurnal temperature range, mean precipitation and net primary production). The mean chromosome numbers of all three species increased with latitude and decreased with mean annual temperature. For two species, chromosome number also decreased with mean precipitation and net primary production. Furthermore, high chromosome numbers within species were accompanied with a loss of sexual reproduction. The variation of chromosome numbers within individuals of two of the three species increased with latitude. Our results support the hypothesis that polyploid lineages are able to cope with harsh climatic conditions at high latitudes. Furthermore, we propose that asexual reproduction in populations with high levels of polyploidization stabilizes hybridization events. Chromosomal irregularities within individuals tend to become more frequent at the extreme environments of high

  9. Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes.

    Science.gov (United States)

    Wolstenholme, J T; Rissman, E F; Bekiranov, S

    2013-03-01

    Neural sexual differentiation begins during embryogenesis and continues after birth for a variable amount of time depending on the species and brain region. Because gonadal hormones were the first factors identified in neural sexual differentiation, their role in this process has eclipsed investigation of other factors. Here, we use a mouse with a spontaneous translocation that produces four different unique sets of sex chromosomes. Each genotype has one normal X-chromosome and a unique second sex chromosome creating the following genotypes: XY(*x) , XX, XY(*) , XX(Y) (*) . This Y(*) mouse line is used by several laboratories to study two human aneuploid conditions: Turner and Klinefelter syndromes. As sex chromosome number affects behavior and brain morphology, we surveyed brain gene expression at embryonic days 11.5 and 18.5 to isolate X-chromosome dose effects in the developing brain as possible mechanistic changes underlying the phenotypes. We compared gene expression differences between gonadal males and females as well as individuals with one vs. two X-chromosomes. We present data showing, in addition to genes reported to escape X-inactivation, a number of autosomal genes are differentially expressed between the sexes and in mice with different numbers of X-chromosomes. Based on our results, we can now identify the genes present in the region around the chromosomal break point that produces the Y(*) model. Our results also indicate an interaction between gonadal development and sex chromosome number that could further elucidate the role of sex chromosome genes and hormones in the sexual differentiation of behavior.

  10. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (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

    2016-07-01

    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.

  11. 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.

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

    Science.gov (United States)

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

    2013-01-01

    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.

  13. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Xiangdong Bu; Rotter, J.I. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  14. Moral Hazard and Stability

    DEFF Research Database (Denmark)

    Tumennasan, Norovsambuu

    2014-01-01

    not form. Formally, we study the team formation problem in which the agents’ efforts are not verifiable and the size of teams does not exceed quota r . We show that if the team members cannot make transfers, then moral hazard affects stability positively in a large class of games. For example, a stable...

  15. Deciphering evolutionary strata on plant sex chromosomes and fungal mating-type chromosomes through compositional segmentation.

    Science.gov (United States)

    Pandey, Ravi S; Azad, Rajeev K

    2016-03-01

    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

  16. Scaling Chromosomes for an Evolutionary Karyotype: A Chromosomal Tradeoff between Size and Number across Woody Species.

    Science.gov (United States)

    Liang, Guolu; Chen, Hong

    2015-01-01

    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.

  17. Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria.

    Science.gov (United States)

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

    2009-01-01

    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.

  18. Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes.

    Science.gov (United States)

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

    2011-04-01

    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.

  19. Clinical utility of the X-chromosome array.

    Science.gov (United States)

    Zarate, Yuri A; Dwivedi, Alka; Bartel, Frank O; Bellomo, M Allison; Cathey, Sara S; Champaigne, Neena L; Clarkson, L Kate; Dupont, Barbara R; Everman, David B; Geer, Joseph S; Gordon, Barbara C; Lichty, Angie W; Lyons, Michael J; Rogers, R Curtis; Saul, Robert A; Schroer, Richard J; Skinner, Steven A; Stevenson, Roger E

    2013-01-01

    Previous studies have limited the use of specific X-chromosome array designed platforms to the evaluation of patients with intellectual disability. In this retrospective analysis, we reviewed the clinical utility of an X-chromosome array in a variety of scenarios. We divided patients according to the indication for the test into four defined categories: (1) autism spectrum disorders and/or developmental delay and/or intellectual disability (ASDs/DD/ID) with known family history of neurocognitive disorders; (2) ASDs/DD/ID without known family history of neurocognitive disorders; (3) breakpoint definition of an abnormality detected by a different cytogenetic test; and (4) evaluation of suspected or known X-linked conditions. A total of 59 studies were ordered with 27 copy number variants detected in 25 patients (25/59 = 42%). The findings were deemed pathogenic/likely pathogenic (16/59 = 27%), benign (4/59 = 7%) or uncertain (7/59 = 12%). We place particular emphasis on the utility of this test for the diagnostic evaluation of families affected with X-linked conditions and how it compares to whole genome arrays in this setting. In conclusion, the X-chromosome array frequently detects genomic alterations of the X chromosome and it has advantages when evaluating some specific X-linked conditions. However, careful interpretation and correlation with clinical findings is needed to determine the significance of such changes. When the X-chromosome array was used to confirm a suspected X-linked condition, it had a yield of 63% (12/19) and was useful in the evaluation and risk assessment of patients and families.

  20. Building bridges within the bacterial chromosome.

    Science.gov (United States)

    Song, Dan; Loparo, Joseph J

    2015-03-01

    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.

  1. Sexual maldevelopment and sex reversal, chromosomal causes.

    Science.gov (United States)

    Magenis, R Ellen

    2006-01-01

    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].

  2. Occupational risk factors and frequency of sex chromosome disomy.

    Science.gov (United States)

    Radwan, Michał; Jurewicz, Joanna; Radwan, Paweł; Ulańska, Anna; Jakubowski, Lucjusz; Hanke, Wojciech

    2015-09-01

    Possible reproductive toxicants such as occupational factors may affect the normal disjunction of chromosomes during meiosis, thereby altering the number of chromosomes in sperm nuclei. The purpose of the present analysis was to determine whether exposure to occupational factors existing in a contemporary work setting affected sperm aneuploidy. The study population consisted of 212 men who attended the infertility clinic for diagnostic purposes. The men either had a normal semen concentration of 20-300 million/ml or slight oligozoospermia (semen concentration of 15-20 million/ml) ( WHO 1999 ). All participants were interviewed and provided a semen sample. Sperm aneuploidy was assessed using multicolor FISH. After adjustment for potential confounders, positive associations were found between disomy XY18, 18, and sex chromosome disomy and exposure to mechanical vibrations (p = 0.03, p = 0.04, p = 0.03, respectively). In addition, sitting for more than 6 h at work increased X and Y disomy (p = 0.03, p = 0.04, respectively). To the best of our knowledge, this is the first study to show a significant effect of occupational factors on sperm aneuploidy. As such, the results need to be confirmed in larger studies.

  3. Chromosomal rearrangements in Tourette syndrome

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  4. Meiosis I: When Chromosomes Undergo Extreme Makeover

    OpenAIRE

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

    2013-01-01

    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...

  5. Association testing to detect gene-gene interactions on sex chromosomes in trio data

    Directory of Open Access Journals (Sweden)

    Yeonok eLee

    2013-11-01

    Full Text Available Autism Spectrum Disorder (ASD occurs more often among males than females in a 4:1 ratio. Among theories used to explain the causes of ASD, the X chromosome and the Y chromosome theories attribute ASD to X-linked mutation and the male-limited gene expressions on the Y chromosome, respectively. Despite the rationale of the theory, studies have failed to attribute the sex-biased ratio to the significant linkage or association on the regions of interest on X chromosome. We further study the gender biased ratio by examining the possible interaction effects between two genes in the sex chromosomes. We propose a logistic regression model with mixed effects to detect gene-gene interactions on sex chromosomes. We investigated the power and type I error rates of the approach for a range of minor allele frequencies and varying linkage disequilibrium between markers and QTLs. We also evaluated the robustness of the model to population stratification. We applied the model to a trio-family data set with an ASD affected male child to study gene-gene interactions on sex chromosomes.

  6. Chromosome territories, X;Y translocation and Premature Ovarian Failure: is there a relationship?

    Directory of Open Access Journals (Sweden)

    Betri Enrico

    2009-09-01

    Full Text Available Abstract Background Premature ovarian failure (POF is a secondary hypergonadotrophic amenorrhea occurring before the age of 40 and affecting 1-3% of females. Chromosome anomalies account for 6-8% of POF cases, but only few cases are associated with translocations involving X and Y chromosomes. This study shows the cytogenetic and molecular analysis of a POF patient came to our attention as she developed a left ovary choriocarcinoma at the age of 10 and at 14 years of age she presented secondary amenorrhea with elevated levels of gonadotropins. Results Breakpoint position on X and Y chromosomes was investigated using Fluorescent In Situ Hybridisation (FISH with a panel of specific BAC probes, microsatellite analysis and evaluation of copy number changes and loss of heterozigosity by Affymetrix® GeneChip platform (Santa Clara, CA, USA. Patient's karyotype resulted 46, X, der(Yt(X;Y(q13.1;q11.223. X inactivation study was assessed by RBA banding and showed preferential inactivation of derivative chromosome. The reciprocal spatial disposition of sexual chromosome territories was investigated using whole chromosome painting and centromeres probes: patient's results didn't show a significant difference in comparison to normal controls. Conclusion The peculiar clinical case come to our attention highlighted the complexity of POF aetiology and of the translocation event, even if our results seem to exclude any effect on nuclear organisation. POF phenotype could be partially explained by skewed X chromosome inactivation that influences gene expression.

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

    Science.gov (United States)

    Khedkar, Supriya; Seshasayee, Aswin Sai Narain

    2016-06-01

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

  8. Atomic force microscopic examination of chromosomes treated with trypsin or ethidium bromide.

    Science.gov (United States)

    Wu, Yangzhe; Cai, Jiye; Cheng, Longqiu; Yun, Keyu; Wang, Chenxi; Chen, Yong

    2006-04-01

    Trypsin treatment is frequently used during chromosome preparation for removal of cellular contaminants, and ethidium bromide (EB) staining of bands is often used to facilitate high-resolution observations by optical microscopy. However, conventional optical microscopy is unable to visualize potential aberrations of chromosome structures caused by these physicochemical treatments. In this article, we use atomic force microscopy (AFM) in the tapping mode to obtain and analyze high-resolution images of chromosome surface structure damage associated with trypsinization and EB treatment. According to our results, the trypsin-based digestion effects became more severe as incubations increased across a range from 10 to 40 s; a digestion time of 10 to 20 s appeared to be most suitable for observation by AFM. In terms of chromosomal damage induced by EB treatment, addition of EB into the media of cultured human blood cells induced chromosomal breakage in a dose-dependent fashion, and the results indicate centromeric region damnifyed severer than arms. Together, these results indicate that EB staining and the standard chromosomal preparative techniques of trypsinization can induce chromosomal damage that may affect the observed results.

  9. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play, expe...... affects can be choreographed and designed intentionally or whether it arises from unpredictable circumstances within urbanity itself....

  10. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  11. Movement of chromosomes with severed kinetochore microtubules.

    Science.gov (United States)

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

    2015-05-01

    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.

  12. Genome architecture: domain organization of interphase chromosomes.

    Science.gov (United States)

    Bickmore, Wendy A; van Steensel, Bas

    2013-03-14

    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.

  13. Cognitive and medical features of chromosomal aneuploidy.

    Science.gov (United States)

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

    2013-01-01

    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.

  14. Research on automatic human chromosome image analysis

    Science.gov (United States)

    Ming, Delie; Tian, Jinwen; Liu, Jian

    2007-11-01

    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.

  15. Meiotic chromosome abnormalities in human spermatogenesis.

    Science.gov (United States)

    Martin, Renée H

    2006-08-01

    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.

  16. Chromosomal characterization of armored catfish Harttia longipinna (Siluriformes, Loricariidae): first report of B chromosomes in the genus.

    Science.gov (United States)

    Blanco, Daniel Rodrigues; Vicari, Marcelo Ricardo; Artoni, Roberto Ferreira; Traldi, Josiane Baccarin; Moreira-Filho, Orlando

    2012-09-01

    The B chromosomes are accessory elements that are widely distributed among eukaryotic genomes and often show non-Mendelian inheritance. They are considered dispensable for the growth, development, and reproduction of organisms. Some studies have suggested that these elements may affect sex determination. Harttia is a small armored catfish genus that shows sexual dimorphism, including hypertrophied odontodes on the pectoral fin spines and along the margins of the snout in mature males. They exhibit considerable karyotypic diversity with diploid number (2n) variation and heteromorphic sex system in H. carvalhoi. To date, no occurrences of B chromosomes in the Harttia genus were detected and no relation to sexual differentiation in Neotropical fish has been determined. To determine the validity of this claim, the present paper characterized specimens of Harttia longipinna by classical and molecular cytogenetic methods. The 2n found was 58 (16m + 12sm + 16st + 14a), but of the 50 specimens analyzed (30 male and 20 female), 23 specimens (16 males and seven females) show an intra-individual from 0 to 2 micro B chromosomes. The B chromosomes were completely heterochromatic. The single NORs were shown in the first acrocentric pair with silver staining and 18S rDNA probing. FISH performed with 5S rDNA probe showed a single cistron in the proximal region of the short arm of a small metacentric pair. Thus, the cytogenetic data obtained in this study of H. longipinna highlight the karyotypic diversity found within the genus Harttia, and represent the first description of B chromosomes for this genus.

  17. Conformation and Stability of Intramolecular Telomeric G-Quadruplexes: Sequence Effects in the Loops

    Science.gov (United States)

    Sattin, Giovanna; Artese, Anna; Nadai, Matteo; Costa, Giosuè; Parrotta, Lucia; Alcaro, Stefano; Palumbo, Manlio; Richter, Sara N.

    2013-01-01

    Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation restricted to loop bases, indicating that the variant telomeric sequences maintain the ability to fold into G-quadruplex. To assess the effect of mutations in loop bases on G-quadruplex folding and stability, we performed a comprehensive analysis of mutant telomeric sequences by spectroscopic techniques, molecular dynamics simulations and gel electrophoresis. We found that when the first position in the loop was mutated from T to C or A the resulting structure adopted a less stable antiparallel topology; when the second position was mutated to C or A, lower thermal stability and no evident conformational change were observed; in contrast, substitution of the third position from A to C induced a more stable and original hybrid conformation, while mutation to T did not significantly affect G-quadruplex topology and stability. Our results indicate that allelic variations generate G-quadruplex telomeric structures with variable conformation and stability. This aspect needs to be taken into account when designing new potential anticancer molecules. PMID:24367632

  18. Conformation and stability of intramolecular telomeric G-quadruplexes: sequence effects in the loops.

    Directory of Open Access Journals (Sweden)

    Giovanna Sattin

    Full Text Available Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation restricted to loop bases, indicating that the variant telomeric sequences maintain the ability to fold into G-quadruplex. To assess the effect of mutations in loop bases on G-quadruplex folding and stability, we performed a comprehensive analysis of mutant telomeric sequences by spectroscopic techniques, molecular dynamics simulations and gel electrophoresis. We found that when the first position in the loop was mutated from T to C or A the resulting structure adopted a less stable antiparallel topology; when the second position was mutated to C or A, lower thermal stability and no evident conformational change were observed; in contrast, substitution of the third position from A to C induced a more stable and original hybrid conformation, while mutation to T did not significantly affect G-quadruplex topology and stability. Our results indicate that allelic variations generate G-quadruplex telomeric structures with variable conformation and stability. This aspect needs to be taken into account when designing new potential anticancer molecules.

  19. Neurophysiological findings in a newborn with chromosome 10 trisomy.

    Science.gov (United States)

    Vidale, Simone; Di Palma, Franco; Sironi, Luigi; Arnaboldi, Marco

    2014-01-01

    The trisomy of the short arm of chromosome 10 is a rare condition. The phenotypic expression of this genetic aberration is characterised by growth and mental retardation with several neurological signs. We report the neurophysiological findings in a newborn affected by 10p chromosome trisomy who developed seizures. Serial EEGs showed a progressive reduction in burst-suppression activity and a slow rhythmic basal activity. At 1 year of age the recording showed for the first time spikes of high amplitude (up to 800 μV) in bilateral frontal regions. These findings could be related to an asymmetrical cerebral maturation in the context of perinatal sufferance and brain malformation due to the genetic aberration.

  20. HACking the centromere chromatin code: insights from human artificial chromosomes.

    Science.gov (United States)

    Bergmann, Jan H; Martins, Nuno M C; Larionov, Vladimir; Masumoto, Hiroshi; Earnshaw, William C

    2012-07-01

    The centromere is a specialized chromosomal region that serves as the assembly site of the kinetochore. At the centromere, CENP-A nucleosomes form part of a chromatin landscape termed centrochromatin. This chromatin environment conveys epigenetic marks regulating kinetochore formation. Recent work sheds light on the intricate relationship between centrochromatin state, the CENP-A assembly pathway and the maintenance of centromere function. Here, we review the emerging picture of how chromatin affects mammalian kinetochore formation. We place particular emphasis on data obtained from Human Artificial Chromosome (HAC) biology and the targeted engineering of centrochromatin using synthetic HACs. We discuss implications of these findings, which indicate that a delicate balance of histone modifications and chromatin state dictates both de novo centromere formation and the maintenance of centromere identity in dividing cell populations.

  1. Fitness cost of chromosomal drug resistance-conferring mutations.

    Science.gov (United States)

    Sander, Peter; Springer, Burkhard; Prammananan, Therdsak; Sturmfels, Antje; Kappler, Martin; Pletschette, Michel; Böttger, Erik C

    2002-05-01

    To study the cost of chromosomal drug resistance mutations to bacteria, we investigated the fitness cost of mutations that confer resistance to different classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2-deoxystreptamines, macrolides). We used a model system based on an in vitro competition assay with defined Mycobacterium smegmatis laboratory mutants; selected mutations were introduced by genetic techniques to address the possibility that compensatory mutations ameliorate the resistance cost. We found that the chromosomal drug resistance mutations studied often had only a small fitness cost; compensatory mutations were not involved in low-cost or no-cost resistance mutations. When drug resistance mutations found in clinical isolates were considered, selection of those mutations that have little or no fitness cost in the in vitro competition assay seems to occur. These results argue against expectations that link decreased levels of antibiotic consumption with the decline in the level of resistance.

  2. Stability Functions

    CERN Document Server

    Burns, Daniel; Wang, Zuoqin

    2008-01-01

    In this article we discuss the role of stability functions in geometric invariant theory and apply stability function techniques to problems in toric geometry. In particular we show how one can use these techniques to recover results of Burns-Guillemin-Uribe and Shiffman-Tate-Zelditch on asymptotic properties of sections of holomorphic line bundles over toric varieties.

  3. Selection and inertia in the evolution of holocentric chromosomes in sedges (Carex, Cyperaceae).

    Science.gov (United States)

    Escudero, Marcial; Hipp, Andrew L; Hansen, Thomas F; Voje, Kjetil L; Luceño, Modesto

    2012-07-01

    • Changes in chromosome number as a result of fission and fusion in holocentrics have direct and immediate effects on the recombination rate. We investigate the support for the classic hypothesis that environmental stability selects for increased recombination rates. • We employed a phylogenetic and cytogenetic data set from one of the most diverse angiosperm genera in the world, which has the largest nonpolyploid chromosome radiation (Carex, Cyperaceae; 2n = 12-124; 2100 spp.). We evaluated alternative Ornstein-Uhlenbeck models of chromosome number adaptation to the environment in an information-theoretic framework. • We found moderate support for a positive influence of lateral inflorescence unit size on chromosome number, which may be selected in a stable environment in which resources for reproductive investment are larger. We found weak support for a positive influence on chromosome number of water-saturated soils and among-month temperature constancy, which would be expected to be negatively select for pioneering species. Chromosome number showed a strong phylogenetic signal. • We argue that our finding of small but significant effects of life history and ecology is compatible with our original hypothesis regarding selection of optima in recombination rates: low recombination rate is optimal when inmediate fitness is required. By contrast, high recombination rate is optimal when stable environments allow for evolutionary innovation.

  4. Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males.

    Science.gov (United States)

    Modzelewski, Andrew J; Hilz, Stephanie; Crate, Elizabeth A; Schweidenback, Caterina T H; Fogarty, Elizabeth A; Grenier, Jennifer K; Freire, Raimundo; Cohen, Paula E; Grimson, Andrew

    2015-06-15

    Small RNAs play crucial roles in regulating gene expression during mammalian meiosis. To investigate the function of microRNAs (miRNAs) and small interfering RNAs (siRNAs) during meiosis in males, we generated germ-cell-specific conditional deletions of Dgcr8 and Dicer in mice. Analysis of spermatocytes from both conditional knockout lines revealed that there were frequent chromosomal fusions during meiosis, always involving one or both sex chromosomes. RNA sequencing indicates upregulation of Atm in spermatocytes from miRNA-deficient mice, and immunofluorescence imaging demonstrates an increased abundance of activated ATM kinase and mislocalization of phosphorylated MDC1, an ATM phosphorylation substrate. The Atm 3'UTR contains many potential microRNA target sites, and, notably, target sites for several miRNAs depleted in both conditional knockout mice were highly effective at promoting repression. RNF8, a telomere-associated protein whose localization is controlled by the MDC1-ATM kinase cascade, normally associates with the sex chromosomes during pachytene, but in both conditional knockouts redistributed to the autosomes. Taken together, these results suggest that Atm dysregulation in microRNA-deficient germ lines contributes to the redistribution of proteins involved in chromosomal stability from the sex chromosomes to the autosomes, resulting in sex chromosome fusions during meiotic prophase I.

  5. Stable X Chromosome Reactivation in Female Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Tahsin Stefan Barakat

    2015-02-01

    Full Text Available In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs leads to reactivation of the inactive X chromosome (Xi, we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas.

  6. The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals

    Energy Technology Data Exchange (ETDEWEB)

    Beskid, O. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Dusek, Z. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Solansky, I. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Sram, R.J. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic)]. E-mail: sram@biomed.cas.cz

    2006-02-22

    The pattern of chromosomal aberrations (CA) was studied by fluorescence in situ hybridization (FISH) technique (whole chromosomes 1 and 4 painting) in workers occupationally exposed to any of the four following conditions: acrylonitrile (ACN), ethyl benzene (EB), carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), and irradiation in nuclear power plants (NPP), respectively. Decrease in the relative frequency of translocations was observed in EB group, and an increase in reciprocal translocations in ACN and NPP-exposed groups. An increase in a relative number of insertions was registered under all four conditions (significant at ACN, EB, c-PAHs, quasisignificant at NPP-exposed groups). Significant differences in the percentage of lymphocytes with aberrations on chromosome 1 (58.8 {+-} 32.7%, versus 73.8 {+-} 33.6% in the controls, P < 0.05), and chromosome 4 (47.0 {+-} 34.1%, versus 29.4 {+-} 32.2%, P < 0.01) were found in workers exposed to ACN. Similarly, a decrease in the proportion of cells with aberration on chromosome 1 (61.0 {+-} 24.0%, versus 73.8 {+-} 33.6%, P < 0.05) and an increase on chromosome 4 (45.6 {+-} 24.6%, versus 29.4 {+-} 32.2%, P < 0.05) were observed in workers exposed to EB. Frequency of aberrant cells (%AB.C.) as well as genomic frequency of translocations (F {sub G}/100) increased with age (P < 0.001). Aging also increased the percentage of translocations and reciprocal translocations (P < 0.05), but decreased the relative number of acentric fragments (P < 0.01). Smoking led to significantly increased F {sub G}/100 (P < 0.05), but did not affect the pattern of chromosomal aberrations. Our results seem to indicate that different carcinogens may induce a different pattern of chromosomal aberrations.

  7. Effects of age on segregation of the X and Y chromosomes in cultured lymphocytes from Chinese men.

    Science.gov (United States)

    Song, Yaxian; Chen, Qian; Zhang, Zhen; Hou, Heli; Zhang, Ding; Shi, Qinghua

    2009-08-01

    Chromosome malsegregation in binucleated lymphocytes is a useful endpoint to evaluate age effect on genetic stability. However, the investigations on chromosome malsegregation in binucleated lymphocytes from Chinese are scarce. In this study, peripheral blood lymphocytes were collected from 14 old (60-70 years) and 10 young (22-26 years) healthy Chinese men. To detect malsegregation of the sex chromosomes, multi-color fluorescence in situ hybridization (FISH) was performed on binucleated lymphocytes, cytokinesis-blocked by cytochalasin B at the first mitosis after phytohaemagglutinin stimulation. Compared with that in young men, a significant increase in frequencies of loss of chromosome X (9.2 +/- 3.2 per thousand vs. 1.1 +/- 0.9 per thousand, P men. Similarly, nondisjunction of chromosome X (16.5 +/- 3.4 per thousand vs. 3.5 +/- 1.1 per thousand, P men than in young men. Regardless of donor's age, nondisjunction is more prevalent than loss for both chromosome X and Y. The frequencies of observed simultaneous malsegregation were relatively higher than the expected, suggesting an association between malsegregation. These results indicated that in Chinese men, malsegregation of the sex chromosomes increases with age in an associated fashion, and nondisjunction accounts for the majority of spontaneous chromosome malsegregation.

  8. 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)

    1997-03-04

    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.

  9. Chromosomal replicons of higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Van' t Hof, J.

    1987-03-16

    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.

  10. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    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.

  11. Conservation of chromosomes syntenic with avian autosomes in squamate reptiles revealed by comparative chromosome painting.

    Science.gov (United States)

    Pokorná, Martina; Giovannotti, Massimo; Kratochvíl, Lukáš; Caputo, Vincenzo; Olmo, Ettore; Ferguson-Smith, Malcolm A; Rens, Willem

    2012-08-01

    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.

  12. FISH studies of chromosome abnormalities in germ cells and its relevance in reproductive counseling

    Institute of Scientific and Technical Information of China (English)

    Zaida Sarrate; Joan Blanco; Ester Anton; Susana Egozcue; Josep Egozcue; Francesca Vidal

    2005-01-01

    Chromosome abnormalities are one of the major causes of human infertility. In infertile males, abnormal karyotypes are more frequent than in the general population. Furthermore, meiotic disorders affecting the germ cell-line have been observed in men with normal somatic karyotypes consulting for infertility. In both cases, the production of unbalanced spermatozoa has been demonstrated. Basically addressed to establish reproductive risks, fluorescence in situ hybridization (FISH) on decondensed sperm heads has become the most frequently used method to evaluate the chromosomal constitution of spermatozoa in carriers of numerical sex chromosome abnormalities, carriers of structural chromosome reorganizations and infertile males with normal karyotype. The aim of this review is to present updated figures of the information obtained through sperm FISH studies with an emphasis on its clinical significance. Furthermore, the incorporation of novel FISH-based techniques (Multiplex-FISH; Multi-FISH) in male infertility studies is also discussed.

  13. Extensive fragmentation of the X chromosome in the bed bug Cimex lectularius Linnaeus, 1758 (Heteroptera, Cimicidae): a survey across Europe.

    Science.gov (United States)

    Sadílek, David; Sťáhlavský, František; Vilímová, Jitka; Zima, Jan

    2013-10-03

    individuals carrying higher numbers of the X chromosome fragments could affect population dynamics of variable populations.

  14. Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage.

    Science.gov (United States)

    Sobol, Maria; Raykova, Doroteya; Cavelier, Lucia; Khalfallah, Ayda; Schuster, Jens; Dahl, Niklas

    2015-09-01

    Induced pluripotent stem cells (iPSCs) have brought great promises for disease modeling and cell-based therapies. One concern related to the use of reprogrammed somatic cells is the loss of genomic integrity and chromosome stability, a hallmark for cancer and many other human disorders. We investigated 16 human iPSC lines reprogrammed by nonintegrative Sendai virus (SeV) and another 16 iPSC lines generated by integrative lentivirus for genetic changes. At early passages we detected cytogenetic rearrangements in 44% (7/16) of iPSC lines generated by lentiviral integration whereas the corresponding figure was 6% (1/16) using SeV-based delivery. The rearrangements were numerical and/or structural with chromosomes 5 and 12 as the most frequently involved chromosomes. Three iPSC lines with chromosome 5 aberrations were derived from one and the same donor. We present in this study the aberrant karyotypes including a duplication of chromosome 5q13q33 that restricts a candidate region for growth advantage. Our results suggest that the use of integrative lentivirus confers a higher risk for cytogenetic abnormalities at early passages when compared to SeV-based reprogramming. In combination, our findings expand the knowledge on acquired cytogenetic aberrations in iPSC after reprogramming and during culture.

  15. 携带抗白粉病基因Pm21的小麦-簇毛麦小片段易位染色体在不同小麦背景中的传递率及遗传稳定性%Transmission and Genetic Stability of No-homoeologous Small Fragment Wheat-Haynaldia villosa Translocation Chromosomes with Pm21 in Various Cultivar Backgrounds of Common Wheat

    Institute of Scientific and Technical Information of China (English)

    王海燕; 肖进; 袁春霞; 徐涛; 于春艳; 孙昊杰; 陈佩度; 王秀娥

    2016-01-01

    抗白粉病基因Pm21来自小麦近缘种簇毛麦。小麦–簇毛麦小片段顶端易位系NAU418(T1AS×1AL-6VS)和小片段中间插入易位系NAU419(T4BS×4BL-6VS-4BL)携带Pm21,高抗白粉病,是小麦抗病育种新种质。为了对其育种利用提供依据,以NAU418和NAU419为亲本分别与来源于不同生态区的郑麦9023等12个小麦品种杂交,杂种F1再分别与来源于不同生态区的农艺亲本进行正、反回交,研究两种易位染色体在不同小麦背景中的遗传稳定性及其通过雌雄配子的传递规律。DNA分子原位杂交结果表明,在杂种F1花粉母细胞减数分裂中期I (Pollen Mother Cell, PMC MI),两种易位染色体分别可以与对应的小麦染色体配对形成棒状二价体。正、反交结果分析表明, NAU418中的小片段顶端易位染色体 T1AS×1AL-6VS 通过雌配子和雄配子的传递率分别为8.00%~50.98%和7.89%~45.07%, NAU419中的小片段中间插入易位染色体 T4BS×4BL-6VS-4BL通过雌配子和雄配子的传递率分别为29.17%~52.38%和7.69%~47.06%。表明2个易位系中的易位染色体都可以通过雌、雄配子传递,但是其通过雄配子的传递率均显著低于通过雌配子的传递率。%The powdery mildew resistance gene Pm21 comes from a diploid wheat related species, Haynaldia villosa. Two Pm21-carrying small fragment translocation lines, the terminal translocation line NAU418 and the small interstitial translocation line NAU419, have been developed. Both lines are highly resistant to powdery mildew and serve as new genetic resources for improvement of disease resistance. For understanding the transmission rate of the translocation chromosomes through male and female gametes and the genetic stabilities in different wheat genetic backgrounds, the two translocations were crossed to 12 com-mon wheat varieties from different wheat growing areas of China. The F1 hybrids were then backcrossed as reciprocally. Chro-mosome configurations of

  16. High chromosomal variation in wild horn fly Haematobia irritans (Linnaeus (Diptera, Muscidae populations

    Directory of Open Access Journals (Sweden)

    Natalia Forneris

    2015-02-01

    Full Text Available The horn fly, Haematobia irritans is an obligate haematophagous cosmopolitan insect pest. The first reports of attacks on livestock by H. irritans in Argentina and Uruguay occurred in 1991, and since 1993 it is considered an economically important pest. Knowledge on the genetic characteristics of the horn fly increases our understanding of the phenotypes resistant to insecticides that repeatedly develop in these insects. The karyotype of H. irritans, as previously described using flies from an inbred colony, shows a chromosome complement of 2n=10 without heterochromosomes (sex chromosomes. In this study, we analyze for the first time the chromosome structure and variation of four wild populations of H. irritans recently established in the Southern Cone of South America, collected in Argentina and Uruguay. In these wild type populations, we confirmed and characterized the previously published “standard” karyotype of 2n=10 without sex chromosomes; however, surprisingly a supernumerary element, called B-chromosome, was found in about half of mitotic preparations. The existence of statistically significant karyotypic diversity was demonstrated through the application of orcein staining, C-banding and H-banding. This study represents the first discovery and characterization of horn fly karyotypes with 2n=11 (2n=10+B. All spermatocytes analyzed showed 5 chromosome bivalents, and therefore, 2n=10 without an extra chromosome. Study of mitotic divisions showed that some chromosomal rearrangements affecting karyotype structure are maintained as polymorphisms, and multiple correspondence analyses demonstrated that genetic variation was not associated with geographic distribution. Because it was never observed during male meiosis, we hypothesize that B-chromosome is preferentially transmitted by females and that it might be related to sex determination.

  17. High chromosomal variation in wild horn fly Haematobia irritans (Linnaeus) (Diptera, Muscidae) populations

    Science.gov (United States)

    Forneris, Natalia S.; Otero, Gabriel; Pereyra, Ana; Repetto, Gustavo; Rabossi, Alejandro; Quesada-Allué, Luis A.; Basso, Alicia L.

    2015-01-01

    Abstract The horn fly, Haematobia irritans is an obligate haematophagous cosmopolitan insect pest. The first reports of attacks on livestock by Haematobia irritans in Argentina and Uruguay occurred in 1991, and since 1993 it is considered an economically important pest. Knowledge on the genetic characteristics of the horn fly increases our understanding of the phenotypes resistant to insecticides that repeatedly develop in these insects. The karyotype of Haematobia irritans, as previously described using flies from an inbred colony, shows a chromosome complement of 2n=10 without heterochromosomes (sex chromosomes). In this study, we analyze for the first time the chromosome structure and variation of four wild populations of Haematobia irritans recently established in the Southern Cone of South America, collected in Argentina and Uruguay. In these wild type populations, we confirmed and characterized the previously published “standard” karyotype of 2n=10 without sex chromosomes; however, surprisingly a supernumerary element, called B-chromosome, was found in about half of mitotic preparations. The existence of statistically significant karyotypic diversity was demonstrated through the application of orcein staining, C-banding and H-banding. This study represents the first discovery and characterization of horn fly karyotypes with 2n=11 (2n=10+B). All spermatocytes analyzed showed 5 chromosome bivalents, and therefore, 2n=10 without an extra chromosome. Study of mitotic divisions showed that some chromosomal rearrangements affecting karyotype structure are maintained as polymorphisms, and multiple correspondence analyses demonstrated that genetic variation was not associated with geographic distribution. Because it was never observed during male meiosis, we hypothesize that B-chromosome is preferentially transmitted by females and that it might be related to sex determination. PMID:25893073

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

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

  20. Cytological characterization of an Aspergillus Nidulans mutant from a strain with chromosomic duplication.

    Science.gov (United States)

    Giancoli, Agata Cristiane Huppert; de Azevedo, João Lúcio; Pizzirani-Kleiner, Aline Aparecida

    2010-01-01

    A development mutant, named V103, was obtained spontaneously from the A strain of A. nidulans. The A strain contains a duplicated segment of chromosome I that has undergone translocation to chromosome II (I II). It is mitotically unstable and generates phenotypically deteriorated types, some with enhanced stability. The deteriorated variants of A. nidulans show abnormal development, exhibiting slower colony growth, variations in colony pigmentation and changes in conidiophore structure. The alterations observed in the conidiophore include fewer metulae and phialides, further elongation and ramification of these structures, delayed nuclear migration and the presence of secondary conidiophores.

  1. Cytological characterization of an Aspergillus nidulans mutant from a strain with chromosomic duplication

    Directory of Open Access Journals (Sweden)

    Ágata Cristiane Huppert Giancoli

    2010-03-01

    Full Text Available A development mutant, named V103, was obtained spontaneously from the A strain of A. nidulans. The A strain contains a duplicated segment of chromosome I that has undergone translocation to chromosome II (I → II. It is mitotically unstable and generates phenotypically deteriorated types, some with enhanced stability. The deteriorated variants of A. nidulans show abnormal development, exhibiting slower colony growth, variations in colony pigmentation and changes in conidiophore structure. The alterations observed in the conidiophore include fewer metulae and phialides, further elongation and ramification of these structures, delayed nuclear migration and the presence of secondary conidiophores.

  2. The X chromosome: does it have a role in Bloom syndrome, a genomic instability disorder?

    Science.gov (United States)

    Aslan, Deniz

    2014-01-01

    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.

  3. Ensuring Stability

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    "Stable"will be a key word for China’s economy in 2012.That’s the beat set at the annual Central Economic Work Conference held in Beijing on December 12-14,which reviewed this year’s development and mapped out plans for the next year.Policymakers at the conference decided to keep macroeconomic policies stable,seek a stable and relatively fast economic growth,stabilize consumer prices and maintain social stability in 2012.On the basis of stability,the government will transform the development model,deepen reform and improve people’s livelihood.

  4. Inheritance of a ring 14 chromosome.

    Science.gov (United States)

    Riley, S B; Buckton, K E; Ratcliffe, S G; Syme, J

    1981-06-01

    A family is described in which the mother, her two live offspring, and a therapeutically aborted fetus each had a ring 14 chromosomes. The two children were mentally retarded and the mother's intelligence was at the lower end of the normal range. In addition, the mother had two spontaneous abortions, one of which was shown to be chromosomally normal.

  5. Inheritance of a ring 14 chromosome.

    OpenAIRE

    Riley, S B; Buckton, K E; Ratcliffe, S G; Syme, J.

    1981-01-01

    A family is described in which the mother, her two live offspring, and a therapeutically aborted fetus each had a ring 14 chromosomes. The two children were mentally retarded and the mother's intelligence was at the lower end of the normal range. In addition, the mother had two spontaneous abortions, one of which was shown to be chromosomally normal.

  6. Human male meiotic sex chromosome inactivation

    NARCIS (Netherlands)

    Vries, M. de; Vosters, S.; Merkx, G.F.M.; Hauwers, K.W.M. d'; Wansink, D.G.; Ramos, L.; Boer, P. de

    2012-01-01

    In mammalian male gametogenesis the sex chromosomes are distinctive in both gene activity and epigenetic strategy. At first meiotic prophase the heteromorphic X and Y chromosomes are placed in a separate chromatin domain called the XY body. In this process, X,Y chromatin becomes highly phosphorylate

  7. Dynamics of chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck

    2007-01-01

    Since the 1960’es the conformation and segregation of the chromosome in Escherichia coli has been a subject of interest for many scientists. However, after 40 years of research, we still know incredibly little about how the chromosome is organized inside the cell, how it manages to duplicate...

  8. Chromosome condensation: weaving an untangled web.

    Science.gov (United States)

    Thadani, Rahul; Uhlmann, Frank

    2015-08-03

    The compaction of diffuse interphase chromatin into stable mitotic chromosomes enables the segregation of replicated DNA to daughter cells. Two new studies characterise, both in vivo and in vitro, the essential contribution of the vertebrate condensin complex to chromosome organisation.

  9. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    Directory of Open Access Journals (Sweden)

    Maria Maurer

    2015-07-01

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

  10. Genomic Dark Matter Illuminated: Anopheles Y Chromosomes.

    Science.gov (United States)

    Redmond, Seth N; Neafsey, Daniel E

    2016-08-01

    Hall et al. have strategically used long-read sequencing technology to characterize the structure and highly repetitive content of the Y chromosome in Anopheles malaria mosquitoes. Their work confirms that this important but elusive heterochromatic sex chromosome is evolving extremely rapidly and harbors a remarkably small number of genes.

  11. Non-disjunction of chromosome 13

    DEFF Research Database (Denmark)

    Bugge, Merete; Collins, Andrew; Hertz, Jens Michael

    2007-01-01

    recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms...

  12. Paradigm Lost: The Human Chromosome Story.

    Science.gov (United States)

    Unger, Lawrence; Blystone, Robert V.

    1996-01-01

    Discusses whether the discovery in 1956 that humans have a chromosome number of 46, as opposed to 47 or 48 as previously thought, fits into a paradigm shift of the Kuhnian type. Concludes th