10 CFR 52.157 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2011 CFR

2011-01-01

...; technical information in final safety analysis report. The application must contain a final safety analysis...) Information sufficient to demonstrate compliance with the applicable requirements regarding testing, analysis... 10 Energy 2 2011-01-01 2011-01-01 false Contents of applications; technical information in final...

Dynamics of vertebrate sex chromosome evolution: from equal size to giants and dwarfs.

PubMed

Schartl, Manfred; Schmid, Michael; Nanda, Indrajit

2016-06-01

The Y and W chromosomes of mammals and birds are known to be small because most of their genetic content degenerated and were lost due to absence of recombination with the X or Z, respectively. Thus, a picture has emerged of ever-shrinking Ys and Ws that may finally even fade into disappearance. We review here the large amount of literature on sex chromosomes in vertebrate species and find by taking a closer look, particularly at the sex chromosomes of fishes, amphibians and reptiles where several groups have evolutionary younger chromosomes than those of mammals and birds, that the perception of sex chromosomes being doomed to size reduction is incomplete. Here, sex-determining mechanisms show a high turnover and new sex chromosomes appear repeatedly. In many species, Ys and Ws are larger than their X and Z counterparts. This brings up intriguing perspectives regarding the evolutionary dynamics of sex chromosomes. It can be concluded that, due to accumulation of repetitive DNA and transposons, the Y and W chromosomes can increase in size during the initial phase of their differentiation.

DNA-damage response during mitosis induces whole-chromosome missegregation.

PubMed

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

2014-11-01

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

Homoeologous chromosome pairing between the A and B genomes of Musa spp. revealed by genomic in situ hybridization

PubMed Central

Jeridi, Mouna; Bakry, Frédéric; Escoute, Jacques; Fondi, Emmanuel; Carreel, Françoise; Ferchichi, Ali; D'Hont, Angélique; Rodier-Goud, Marguerite

2011-01-01

Background and Aims Most cooking banana and several desert bananas are interspecific triploid hybrids between Musa acuminata (A genome) and Musa balbisiana (B genome). In addition, M. balbisiana has agronomical characteristics such as resistance to biotic and abiotic stresses that could be useful to improve monospecific acuminata cultivars. To develop efficient breeding strategies for improving Musa cultivars, it is therefore important to understand the possibility of chromosome exchange between these two species. Methods A protocol was developed to prepare chromosome at meiosis metaphase I suitable for genomic in situ hybridization. A series of technical challenges were encountered, the main ones being the hardness of the cell wall and the density of the microsporocyte's cytoplasm, which hampers accessibility of the probes to the chromosomes. Key parameters in solving these problems were addition of macerozyme in the enzyme mix, the duration of digestion and temperature during the spreading phase. Results and Conclusions This method was applied to analyse chromosome pairing in metaphase from triploid interspecific cultivars, and it was clearly demonstrated that interspecific recombinations between M. acuminata and M. balbisiana chromosomes do occur and may be frequent in triploid hybrids. These results provide new insight into Musa cultivar evolution and have important implications for breeding. PMID:21835815

Behavior of Aberrant Chromosome Configurations in Drosophila melanogaster Female Meiosis I

PubMed Central

Gilliland, William D.; Colwell, Eileen M.; Lane, Fiona M.; Snouffer, Ashley A.

2014-01-01

One essential role of the first meiotic division is to reduce chromosome number by half. Although this is normally accomplished by segregating homologous chromosomes from each other, it is possible for a genome to have one or more chromosomes that lack a homolog (such as compound chromosomes), or have chromosomes with multiple potential homologs (such as in XXY females). These configurations complete meiosis but engage in unusual segregation patterns. In Drosophila melanogaster females carrying two compound chromosomes, the compounds can accurately segregate from each other, a process known as heterologous segregation. Similarly, in XXY females, when the X chromosomes fail to cross over, they often undergo secondary nondisjunction, where both Xs segregate away from the Y. Although both of these processes have been known for decades, the orientation mechanisms involved are poorly understood. Taking advantage of the recent discovery of chromosome congression in female meiosis I, we have examined a number of different aberrant chromosome configurations. We show that these genotypes complete congression normally, with their chromosomes bioriented at metaphase I arrest at the same rates that they segregate, indicating that orientation must be established during prometaphase I before congression. We also show that monovalent chromosomes can move out on the prometaphase I spindle, but the dot 4 chromosomes appear required for this movement. Finally, we show that, similar to achiasmate chromosomes, heterologous chromosomes can be connected by chromatin threads, suggesting a mechanism for how heterochromatic homology establishes these unusual biorientation patterns. PMID:25491942

Behavior of aberrant chromosome configurations in Drosophila melanogaster female meiosis I.

PubMed

Gilliland, William D; Colwell, Eileen M; Lane, Fiona M; Snouffer, Ashley A

2014-12-09

One essential role of the first meiotic division is to reduce chromosome number by half. Although this is normally accomplished by segregating homologous chromosomes from each other, it is possible for a genome to have one or more chromosomes that lack a homolog (such as compound chromosomes), or have chromosomes with multiple potential homologs (such as in XXY females). These configurations complete meiosis but engage in unusual segregation patterns. In Drosophila melanogaster females carrying two compound chromosomes, the compounds can accurately segregate from each other, a process known as heterologous segregation. Similarly, in XXY females, when the X chromosomes fail to cross over, they often undergo secondary nondisjunction, where both Xs segregate away from the Y. Although both of these processes have been known for decades, the orientation mechanisms involved are poorly understood. Taking advantage of the recent discovery of chromosome congression in female meiosis I, we have examined a number of different aberrant chromosome configurations. We show that these genotypes complete congression normally, with their chromosomes bioriented at metaphase I arrest at the same rates that they segregate, indicating that orientation must be established during prometaphase I before congression. We also show that monovalent chromosomes can move out on the prometaphase I spindle, but the dot 4 chromosomes appear required for this movement. Finally, we show that, similar to achiasmate chromosomes, heterologous chromosomes can be connected by chromatin threads, suggesting a mechanism for how heterochromatic homology establishes these unusual biorientation patterns. Copyright © 2015 Gilliland et al.

Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution.

PubMed

Laughney, Ashley M; Elizalde, Sergi; Genovese, Giulio; Bakhoum, Samuel F

2015-08-04

Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due to experimental limitations, fundamental characteristics of karyotypic changes in cancer are poorly understood. Using an experimentally inspired stochastic model, based on the potency and chromosomal distribution of oncogenes and tumor suppressor genes, we show that cancer cells have evolved to exist within a narrow range of chromosome missegregation rates that optimizes phenotypic heterogeneity and clonal survival. Departure from this range reduces clonal fitness and limits subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly favorable, commonly observed, near-triploid state onto which evolving diploid- and tetraploid-derived populations spontaneously converge, albeit at a much lower fitness cost for the latter. Finally, by analyzing 1,368 chromosomal translocation events in five human cancers, we find that karyotypic evolution also shapes chromosomal translocation patterns by selecting for more oncogenic derivative chromosomes. Thus, chromosomal instability can generate the heterogeneity required for Darwinian tumor evolution. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Sex chromosome evolution: historical insights and future perspectives

PubMed Central

Nordén, Anna K.

2017-01-01

Many separate-sexed organisms have sex chromosomes controlling sex determination. Sex chromosomes often have reduced recombination, specialized (frequently sex-specific) gene content, dosage compensation and heteromorphic size. Research on sex determination and sex chromosome evolution has increased over the past decade and is today a very active field. However, some areas within the field have not received as much attention as others. We therefore believe that a historic overview of key findings and empirical discoveries will put current thinking into context and help us better understand where to go next. Here, we present a timeline of important conceptual and analytical models, as well as empirical studies that have advanced the field and changed our understanding of the evolution of sex chromosomes. Finally, we highlight gaps in our knowledge so far and propose some specific areas within the field that we recommend a greater focus on in the future, including the role of ecology in sex chromosome evolution and new multilocus models of sex chromosome divergence. PMID:28469017

Comparing methods of ploidy estimation in potato.

USDA-ARS?s Scientific Manuscript database

Ploidy manipulation and the resulting need for rapid ploidy screening is an important part of a potato research and breeding program. Determining ploidy by counting chromosomes or measuring DNA in individual cells is definitive, but takes time, technical skills and equipment. We tested three predi...

International workshop on Chromosome 12 held at St. Catherine`s College, Oxford, England, September 18--20, 1992. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gemmill, R.

1992-12-31

The First International Mapping Workshop on Human Chromosome 12 was held on Sept. 18--20, 1992, at St Catherine`s College, Oxford, UK. The meeting was hosted by Ian Craig and organized by Drs. Craig, Gemmill and Kutcherlapati. It was attended by 50 participants primarily from Europe and the USA. The workshop was highly successful and achieved the major goal of fostering direct and personal interactions between investigators with strong research interests in this chromosome. Participants reviewed the status of several critical aspects of chromosome mapping and prepared consensus views of the current state of knowledge. In addition, lists of resources availablemore » for this chromosome including somatic cell hybrids, individual DNA clones and libraries and genetic markers were prepared.« less

Translocations, inversions and other chromosome rearrangements.

PubMed

Morin, Scott J; Eccles, Jennifer; Iturriaga, Amanda; Zimmerman, Rebekah S

2017-01-01

Chromosomal rearrangements have long been known to significantly impact fertility and miscarriage risk. Advancements in molecular diagnostics are challenging contemporary clinicians and patients in accurately characterizing the reproductive risk of a given abnormality. Initial attempts at preimplantation genetic diagnosis were limited by the inability to simultaneously evaluate aneuploidy and missed up to 70% of aneuploidy in chromosomes unrelated to the rearrangement. Contemporary platforms are more accurate and less susceptible to technical errors. These techniques also offer the ability to improve outcomes through diagnosis of uniparental disomy and may soon be able to consistently distinguish between normal and balanced translocation karyotypes. Although an accurate projection of the anticipated number of unbalanced embryos is not possible at present, confirmation of normal/balanced status results in high pregnancy rates (PRs) and diagnostic accuracy. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Measuring mitotic forces.

PubMed

Ye, Anna A; Maresca, Thomas J

2018-01-01

Productive chromosome movements require that a large multiprotein complex called the kinetochore assemble on sister centromeres. The kinetochore fulfills two critical functions as (1) the physical linkage between chromosomes and spindle microtubules and (2) a mechanomolecular sensor that relays a spindle assembly checkpoint signal delaying anaphase onset until chromosomes are attached to spindle microtubules and bioriented. Given its central roles in such a vital process, the kinetochore is one of the most important force-transducing structures in cells; yet it has been technically challenging to measure kinetochore forces. Barriers to measuring cellular forces have begun to be broken by the development of fluorescence-based tension sensors. In this chapter, two methods will be described for measuring kinetochore forces in living cells and strategies for applying these sensors to other force-transducing processes and molecules will be discussed. © 2018 Elsevier Inc. All rights reserved.

Strategies for cloning and manipulating natural and synthetic chromosomes.

PubMed

Karas, Bogumil J; Suzuki, Yo; Weyman, Philip D

2015-02-01

Advances in synthetic biology methods to assemble and edit DNA are enabling genome engineering at a previously impracticable scale and scope. The synthesis of the Mycoplasma mycoides genome followed by its transplantation to convert a related cell into M. mycoides has transformed strain engineering. This approach exemplifies the combination of newly emerging chromosome-scale genome editing strategies that can be defined in three main steps: (1) chromosome acquisition into a microbial engineering platform, (2) alteration and improvement of the acquired chromosome, and (3) installation of the modified chromosome into the original or alternative organism. In this review, we outline recent progress in methods for acquiring chromosomes and chromosome-scale DNA molecules in the workhorse organisms Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae. We present overviews of important genetic strategies and tools for each of the three organisms, point out their respective strengths and weaknesses, and highlight how the host systems can be used in combination to facilitate chromosome assembly or engineering. Finally, we highlight efforts for the installation of the cloned/altered chromosomes or fragments into the target organism and present remaining challenges in expanding this powerful experimental approach to a wider range of target organisms.

Henry Taube and Coordination Chemistry

Science.gov Websites

Shifts Caused by Cr++ in Aqueous Solutions, DOE Technical Report, 1962 Reactions of Solvated Ions Final Report, DOE Technical Report, 1962 Isotopic Discrimination of Some Solutes in Liquid Ammonia, DOE Technical Report, 1966 Final Technical Report of Research, DOE Technical Report, 1972 Top Additional Web

George A. Olah, Carbocation and Hydrocarbon Chemistry

Science.gov Websites

. Final Technical Report. [HF:BF{sub 2}/H{sub 2}] , DOE Technical Report, 1980 Superacid Catalyzed Coal Conversion Chemistry. 1st and 2nd Quarterly Technical Progress Reports, September 1, 1983-March 30, 1984 , DOE Technical Report, 1984 Superacid Catalyzed Coal Conversion Chemistry. Final Technical Report

Risk of Gonadoblastoma Development in Patients with Turner Syndrome with Cryptic Y Chromosome Material.

PubMed

Kwon, Ahreum; Hyun, Sei Eun; Jung, Mo Kyung; Chae, Hyun Wook; Lee, Woo Jung; Kim, Tae Hyuk; Kim, Duk Hee; Kim, Ho-Seong

2017-06-01

Current guidelines recommend that testing for Y chromosome material should be performed only in patients with Turner syndrome harboring a marker chromosome and exhibiting virilization in order to detect individuals who are at high risk of gonadoblastoma. However, cryptic Y chromosome material is suggested to be a risk factor for gonadoblastoma in patients with Turner syndrome. Here, we aimed to estimate the frequency of cryptic Y chromosome material in patients with Turner syndrome and determine whether Y chromosome material increased the risk for development of gonadoblastoma. A total of 124 patients who were diagnosed with Turner syndrome by conventional cytogenetic techniques underwent additional molecular analysis to detect cryptic Y chromosome material. In addition, patients with Turner syndrome harboring Y chromosome cell lines had their ovaries removed prophylactically. Finally, we assessed the occurrence of gonadoblastoma in patients with Turner syndrome. Molecular analysis demonstrated that 10 patients had Y chromosome material among 118 patients without overt Y chromosome (8.5%). Six patients with overt Y chromosome and four patients with cryptic Y chromosome material underwent oophorectomy. Histopathological analysis revealed that the occurrence of gonadoblastoma in the total group was 2.4%, and gonadoblastoma occurred in one of six patients with an overt Y chromosome (16.7%) and 2 of 10 patients with cryptic Y chromosome material (20.0%). The risk of developing gonadoblastoma in patients with cryptic Y chromosome material was similar to that in patients with overt Y chromosome. Therefore, molecular screening for Y chromosome material should be recommended for all patients with Turner syndrome to detect individuals at a high risk of gonadoblastoma and to facilitate proper management of the disease.

Nucleotide diversity maps reveal variation in diversity among wheat genomes and chromosomes

USDA-ARS?s Scientific Manuscript database

Technical Abstract: 20-75 CHARACTER LINES A strategy for a genome-wide assessment of nucleotide diversity in a polyploid species must minimize the inclusion of homoeologous sequences into diversity estimates and reliably allocate individual haplotypes into respective genomes. In this study, nucle...

77 FR 46306 - Fluxapyroxad; Pesticide Tolerances Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

...; Pesticide Tolerances Technical Amendment AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule; technical amendment. SUMMARY: EPA issued a final rule in the Federal Register of May 14, 2012, concerning.... Inadvertently, the terminology for the oilseed crop group and for dried plums was incorrect. This technical...

The 14/15 association as a paradigmatic example of tracing karyotype evolution in New World monkeys.

PubMed

Capozzi, Oronzo; Archidiacono, Nicoletta; Lorusso, Nicola; Stanyon, Roscoe; Rocchi, Mariano

2016-09-01

Fluorescence in situ hybridization (FISH), especially chromosome painting, has been extensively exploited in the phylogenetic reconstruction of primate evolution. Although chromosome painting is a key method to map translocations, it is not effective in detecting chromosome inversions, which may be up to four times more frequent than other chromosomal rearrangements. BAC-FISH instead can economically delineate marker order and reveal intrachromosomal rearrangements. However, up to now, BAC-FISH was rarely used to study the chromosomes of New World monkeys partly due to technical difficulties. In this paper, we used BAC-FISH to disentangle the complex evolutionary history of the ancestral 14/15 association in NWMs, beginning from the squirrel monkey (Saimiri boliviensis). To improve the hybridization efficiency of BAC-FISH in NWMs, we "translated" the human BACs into Callithrix jacchus (CJA) BACs, which yielded much higher hybridization efficiencies on other NWM species than human BACs. Our results disclosed 14 synteny blocks in squirrel monkeys, 7 more than with chromosome painting. We then applied a subset of CJA BACs on six other NWM species. The comparison of the hybridization pattern of these species contained phylogenetic information to discriminate evolutionary relationships. Notably Aotus was found to share an inversion with Callithrix, thus definitely assigning the genus Aotus to Cebidae. The present study can be seen as a paradigmatic approach to investigate the phylogenetics of NWMs by molecular cytogenetics.

Micromechanical study of mitotic chromosome structure

NASA Astrophysics Data System (ADS)

Marko, John

2011-03-01

Our group has developed micromanipulation techniques for study of the highly compacted mitotic form of chromosome found in eukaryote cells during cell division. Each metaphase chromosome contains two duplicate centimeter-long DNA molecules, folded up by proteins into cylindrical structures several microns in length. Native chromosomes display linear and reversible stretching behavior over a wide range of extensions (up to 5x native length for amphibian chromosomes), described by a Young modulus of about 300 Pa. Studies using DNA-cutting and protein-cutting enzymes have revealed that metaphase chromosomes behave as a network of chromatin fibers held together by protein-based isolated crosslinks. Our results are not consistent with the more classical model of loops of chromatin attached to a protein-based structural organizer or ``scaffold". In short, our experiments indicate that metaphase chromosomes can be considered to be ``gels" of chromatin; the stretching modulus of a whole chromosome is consistent with stretching of the chromatin fibers contained within it. Experiments using topoisomerases suggest that topological constraints may play an appreciable role in confining chromatin in the metaphase chromosome. Finally, recent experiments on human chromosomes will be reviewed, including results of experiments where chromosome-folding proteins are specifically depleted using siRNA methods. Supported by NSF-MCB-1022117, DMR-0715099, PHY-0852130, DMR-0520513, NCI 1U54CA143869-01 (NU-PS-OC), and the American Heart Association.

The multiple sex chromosomes of platypus and echidna are not completely identical and several share homology with the avian Z.

PubMed

Rens, Willem; O'Brien, Patricia C M; Grützner, Frank; Clarke, Oliver; Graphodatskaya, Daria; Tsend-Ayush, Enkhjargal; Trifonov, Vladimir A; Skelton, Helen; Wallis, Mary C; Johnston, Steve; Veyrunes, Frederic; Graves, Jennifer A M; Ferguson-Smith, Malcolm A

2007-01-01

Sex-determining systems have evolved independently in vertebrates. Placental mammals and marsupials have an XY system, birds have a ZW system. Reptiles and amphibians have different systems, including temperature-dependent sex determination, and XY and ZW systems that differ in origin from birds and placental mammals. Monotremes diverged early in mammalian evolution, just after the mammalian clade diverged from the sauropsid clade. Our previous studies showed that male platypus has five X and five Y chromosomes, no SRY, and DMRT1 on an X chromosome. In order to investigate monotreme sex chromosome evolution, we performed a comparative study of platypus and echidna by chromosome painting and comparative gene mapping. Chromosome painting reveals a meiotic chain of nine sex chromosomes in the male echidna and establishes their order in the chain. Two of those differ from those in the platypus, three of the platypus sex chromosomes differ from those of the echidna and the order of several chromosomes is rearranged. Comparative gene mapping shows that, in addition to bird autosome regions, regions of bird Z chromosomes are homologous to regions in four platypus X chromosomes, that is, X1, X2, X3, X5, and in chromosome Y1. Monotreme sex chromosomes are easiest to explain on the hypothesis that autosomes were added sequentially to the translocation chain, with the final additions after platypus and echidna divergence. Genome sequencing and contig anchoring show no homology yet between platypus and therian Xs; thus, monotremes have a unique XY sex chromosome system that shares some homology with the avian Z.

Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

PubMed Central

Pongsavee, Malinee

2009-01-01

Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P < 0.05). Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human. PMID:19878537

Comparative Sex Chromosome Genomics in Snakes: Differentiation, Evolutionary Strata, and Lack of Global Dosage Compensation

PubMed Central

Zektser, Yulia; Mahajan, Shivani; Bachtrog, Doris

2013-01-01

Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae), but completely heteromorphic sex chromosomes in both garter snakes (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases). This demonstrates that mutation rates are male-biased in snakes (male-driven evolution), but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex chromosomes evolution. PMID:24015111

Cytogenetic studies on Metasequoia glyptostroboides, a living fossil species.

PubMed

He, Zican; Li, Jianqiang; Cai, Qing; Li, Xiaodong; Huang, Hongwen

2004-11-01

The chromosome morphology and meiotic pairing behavior in the pollen mother cells (PMCs) of Metasequoia glyptostroboides were investigated. The results showed that: (1) The chromosome number of the PMCs was 2n = 22. (2) The PMCs developed in the successive manner, and the nucleoids in the dynamic development were similar to those of the other gymnosperms. (3) At prophase, most of the chromosomes were unable to be identified distinctively because the chromosomes were long and tangled together. The chromosome segments were paired non-synchronously. At pachytene, the interstitial or terminal regions of some bivalents did not form synapsis and the paired chromosomes showed difference in sizes, indicating that there were structure differences between the homologous chromosomes. (4) At diakinesis, the ring bivalents showed complicated configurations due to the differences in location and number of chiasmata. In addition, there were cross-linked bivalents. (5) At metaphase I, the chromosome configuration of each cell was 8.2II(0) + 1.1II + 1.3II+ + 0.8I. Most of the chromosomes were ring bivalents, but some were cross-linked bivalents, rod bivalents, or univalents. (6) 15% PMCs at anaphase I and 22% PMCs at anaphase II presented chromosome bridges, chromosome fragments, micronuclei, and lagging chromosomes. Twenty seven percent microspores finally moved into one to three micronuclei. Twenty five percent pollens were abortive. The results indicated that the observed individual of M. glyptostroboides was probably a paracentric inversion heterozygote, and there were structural and behavioral differences between the homologous chromosomes. The chromosomal aberration of M. glyptostroboides may play an important role in the evolution of this relict species, which is known as a living fossil. Further evidence is needed to test whether the differences between homologous chromosomes were due to hybridization.

Massively Parallel Sequencing Reveals the Complex Structure of an Irradiated Human Chromosome on a Mouse Background in the Tc1 Model of Down Syndrome

PubMed Central

Clayton, Stephen; Prigmore, Elena; Langley, Elizabeth; Yang, Fengtang; Maguire, Sean; Fu, Beiyuan; Rajan, Diana; Sheppard, Olivia; Scott, Carol; Hauser, Heidi; Stephens, Philip J.; Stebbings, Lucy A.; Ng, Bee Ling; Fitzgerald, Tomas; Quail, Michael A.; Banerjee, Ruby; Rothkamm, Kai; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Carter, Nigel P.

2013-01-01

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439. PMID:23596509

[Research progress in lampbrush chromosomes and some suggestions for their use in genetics teaching].

PubMed

Chen, Fan-guo; Li, Qing-qing

2016-02-01

Lampbrush chromosomes (LBCs) are transient giant transcripts that exist at the diplotene stage of the first meiotic division in female gametocytes of almost all animals except mammals. LBCs are named for their lampbrush-like structure, however, they received the lowest research attention in studies of three classical cytogenetic chromosomes. They have been excellent models for studying the structure, organization, transcription, and transcriptional processing of chromosomes during meiosis. Here we briefly summarized these studies and LBCs forming mechanism and also discussed their possible functions, such as providing enough transcriptional products for embryonic development by oocytes LBCs or polyploidy demonstrated by previous reports. Finally, we discussed the possibility of introducing this typical case into our genetics teaching to inspire students' interest in genetics.

A Three-Dimensional Model of the Yeast Genome

NASA Astrophysics Data System (ADS)

Noble, William; Duan, Zhi-Jun; Andronescu, Mirela; Schutz, Kevin; McIlwain, Sean; Kim, Yoo Jung; Lee, Choli; Shendure, Jay; Fields, Stanley; Blau, C. Anthony

Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or factories for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.

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

PubMed Central

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

2017-01-01

Summary 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. PMID:25462900

The multiple sex chromosomes of platypus and echidna are not completely identical and several share homology with the avian Z

PubMed Central

Rens, Willem; O'Brien, Patricia CM; Grützner, Frank; Clarke, Oliver; Graphodatskaya, Daria; Tsend-Ayush, Enkhjargal; Trifonov, Vladimir A; Skelton, Helen; Wallis, Mary C; Johnston, Steve; Veyrunes, Frederic; Graves, Jennifer AM; Ferguson-Smith, Malcolm A

2007-01-01

Background Sex-determining systems have evolved independently in vertebrates. Placental mammals and marsupials have an XY system, birds have a ZW system. Reptiles and amphibians have different systems, including temperature-dependent sex determination, and XY and ZW systems that differ in origin from birds and placental mammals. Monotremes diverged early in mammalian evolution, just after the mammalian clade diverged from the sauropsid clade. Our previous studies showed that male platypus has five X and five Y chromosomes, no SRY, and DMRT1 on an X chromosome. In order to investigate monotreme sex chromosome evolution, we performed a comparative study of platypus and echidna by chromosome painting and comparative gene mapping. Results Chromosome painting reveals a meiotic chain of nine sex chromosomes in the male echidna and establishes their order in the chain. Two of those differ from those in the platypus, three of the platypus sex chromosomes differ from those of the echidna and the order of several chromosomes is rearranged. Comparative gene mapping shows that, in addition to bird autosome regions, regions of bird Z chromosomes are homologous to regions in four platypus X chromosomes, that is, X1, X2, X3, X5, and in chromosome Y1. Conclusion Monotreme sex chromosomes are easiest to explain on the hypothesis that autosomes were added sequentially to the translocation chain, with the final additions after platypus and echidna divergence. Genome sequencing and contig anchoring show no homology yet between platypus and therian Xs; thus, monotremes have a unique XY sex chromosome system that shares some homology with the avian Z. PMID:18021405

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2014 CFR

2014-07-01

... How is the final performance report to be sent to the Defense Technical Information Center? (a... 32 National Defense 1 2014-07-01 2014-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of...

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2011 CFR

2011-07-01

... How is the final performance report to be sent to the Defense Technical Information Center? (a... 32 National Defense 1 2011-07-01 2011-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of...

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2013 CFR

2013-07-01

... How is the final performance report to be sent to the Defense Technical Information Center? (a... 32 National Defense 1 2013-07-01 2013-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of...

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of... How is the final performance report to be sent to the Defense Technical Information Center? (a...

Chromosome Territories

PubMed Central

Cremer, Thomas; Cremer, Marion

2010-01-01

Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenomics is considered, followed by a historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT architecture, and of structural interactions with other CTs is provided as well as the dynamics of CT arrangements during cell cycle and postmitotic terminal differentiation. The article concludes with a discussion of open questions and new experimental strategies to answer them. PMID:20300217

Normalization of a chromosomal contact map.

PubMed

Cournac, Axel; Marie-Nelly, Hervé; Marbouty, Martial; Koszul, Romain; Mozziconacci, Julien

2012-08-30

Chromatin organization has been increasingly studied in relation with its important influence on DNA-related metabolic processes such as replication or regulation of gene expression. Since its original design ten years ago, capture of chromosome conformation (3C) has become an essential tool to investigate the overall conformation of chromosomes. It relies on the capture of long-range trans and cis interactions of chromosomal segments whose relative proportions in the final bank reflect their frequencies of interactions, hence their spatial proximity in a population of cells. The recent coupling of 3C with deep sequencing approaches now allows the generation of high resolution genome-wide chromosomal contact maps. Different protocols have been used to generate such maps in various organisms. This includes mammals, drosophila and yeast. The massive amount of raw data generated by the genomic 3C has to be carefully processed to alleviate the various biases and byproducts generated by the experiments. Our study aims at proposing a simple normalization procedure to minimize the influence of these unwanted but inevitable events on the final results. Careful analysis of the raw data generated previously for budding yeast S. cerevisiae led to the identification of three main biases affecting the final datasets, including a previously unknown bias resulting from the circularization of DNA molecules. We then developed a simple normalization procedure to process the data and allow the generation of a normalized, highly contrasted, chromosomal contact map for S. cerevisiae. The same method was then extended to the first human genome contact map. Using the normalized data, we revisited the preferential interactions originally described between subsets of discrete chromosomal features. Notably, the detection of preferential interactions between tRNA in yeast and CTCF, PolII binding sites in human can vary with the normalization procedure used. We quantitatively reanalyzed the genomic 3C data obtained for S. cerevisiae, identified some of the biases inherent to the technique and proposed a simple normalization procedure to analyse them. Such an approach can be easily generalized for genomic 3C experiments in other organisms. More experiments and analysis will be necessary to reach optimal resolution and accuracies of the maps generated through these approaches. Working with cell population presenting highest levels of homogeneity will prove useful in this regards.

Pooled-BAC sequencing of a black pod resistance region (cBPQTL12) in T. cacao

USDA-ARS?s Scientific Manuscript database

Whole genome sequencing (WGS) is an expensive and technically challenging endeavor. An alternative to WGS is to sequence specific chromosomal segments of biological interest (e.g. a QTL interval). This method is cheaper than WGS and reduces the risk of misassembly from distal parts of the genome. Us...

Sex Chromosome Evolution, Heterochiasmy, and Physiological QTL in the Salmonid Brook Charr Salvelinus fontinalis

PubMed Central

Sutherland, Ben J.G.; Rico, Ciro; Audet, Céline; Bernatchez, Louis

2017-01-01

Whole-genome duplication (WGD) can have large impacts on genome evolution, and much remains unknown about these impacts. This includes the mechanisms of coping with a duplicated sex determination system and whether this has an impact on increasing the diversity of sex determination mechanisms. Other impacts include sexual conflict, where alleles having different optimums in each sex can result in sequestration of genes into nonrecombining sex chromosomes. Sex chromosome development itself may involve sex-specific recombination rate (i.e., heterochiasmy), which is also poorly understood. The family Salmonidae is a model system for these phenomena, having undergone autotetraploidization and subsequent rediploidization in most of the genome at the base of the lineage. The salmonid master sex determining gene is known, and many species have nonhomologous sex chromosomes, putatively due to transposition of this gene. In this study, we identify the sex chromosome of Brook Charr Salvelinus fontinalis and compare sex chromosome identities across the lineage (eight species and four genera). Although nonhomology is frequent, homologous sex chromosomes and other consistencies are present in distantly related species, indicating probable convergence on specific sex and neo-sex chromosomes. We also characterize strong heterochiasmy with 2.7-fold more crossovers in maternal than paternal haplotypes with paternal crossovers biased to chromosome ends. When considering only rediploidized chromosomes, the overall heterochiasmy trend remains, although with only 1.9-fold more recombination in the female than the male. Y chromosome crossovers are restricted to a single end of the chromosome, and this chromosome contains a large interspecific inversion, although its status between males and females remains unknown. Finally, we identify quantitative trait loci (QTL) for 21 unique growth, reproductive, and stress-related phenotypes to improve knowledge of the genetic architecture of these traits important to aquaculture and evolution. PMID:28626004

Features of genomic organization in a nucleotide-resolution molecular model of the Escherichia coli chromosome.

PubMed

Hacker, William C; Li, Shuxiang; Elcock, Adrian H

2017-07-27

We describe structural models of the Escherichia coli chromosome in which the positions of all 4.6 million nucleotides of each DNA strand are resolved. Models consistent with two basic chromosomal orientations, differing in their positioning of the origin of replication, have been constructed. In both types of model, the chromosome is partitioned into plectoneme-abundant and plectoneme-free regions, with plectoneme lengths and branching patterns matching experimental distributions, and with spatial distributions of highly-transcribed chromosomal regions matching recent experimental measurements of the distribution of RNA polymerases. Physical analysis of the models indicates that the effective persistence length of the DNA and relative contributions of twist and writhe to the chromosome's negative supercoiling are in good correspondence with experimental estimates. The models exhibit characteristics similar to those of 'fractal globules,' and even the most genomically-distant parts of the chromosome can be physically connected, through paths combining linear diffusion and inter-segmental transfer, by an average of only ∼10 000 bp. Finally, macrodomain structures and the spatial distributions of co-expressed genes are analyzed: the latter are shown to depend strongly on the overall orientation of the chromosome. We anticipate that the models will prove useful in exploring other static and dynamic features of the bacterial chromosome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

76 FR 18624 - Research, Technical Assistance and Training Programs: Notice of Final Circular

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... to FTA Circular 6100.1D, Research and Technical Assistance Training Program: Application Instructions... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Research, Technical Assistance and Training Programs: Notice of Final Circular AGENCY: Federal Transit Administration (FTA), DOT. ACTION...

The Robertsonian phenomenon in the house mouse: mutation, meiosis and speciation.

PubMed

Garagna, Silvia; Page, Jesus; Fernandez-Donoso, Raul; Zuccotti, Maurizio; Searle, Jeremy B

2014-12-01

Many different chromosomal races with reduced chromosome number due to the presence of Robertsonian fusion metacentrics have been described in western Europe and northern Africa, within the distribution area of the western house mouse Mus musculus domesticus. This subspecies of house mouse has become the ideal model for studies to elucidate the processes of chromosome mutation and fixation that lead to the formation of chromosomal races and for studies on the impact of chromosome heterozygosities on reproductive isolation and speciation. In this review, we briefly describe the history of the discovery of the first and subsequent metacentric races in house mice; then, we focus on the molecular composition of the centromeric regions involved in chromosome fusion to examine the molecular characteristics that may explain the great variability of the karyotype that house mice show. The influence that metacentrics exert on the nuclear architecture of the male meiocytes and the consequences on meiotic progression are described to illustrate the impact that chromosomal heterozygosities exert on fertility of house mice-of relevance to reproductive isolation and speciation. The evolutionary significance of the Robertsonian phenomenon in the house mouse is discussed in the final section of this review.

Three sympatric karyomorphs in the fish Astyanax fasciatus (Teleostei, Characidae) do not seem to hybridize in natural populations

PubMed Central

Ferreira-Neto, Maressa; Artoni, Roberto Ferreira; Vicari, Marcelo Ricardo; Moreira-Filho, Orlando; Camacho, Juan Pedro Martínez; Bakkali, Mohammed; de Oliveira, Claudio; Foresti, Fausto

2012-01-01

Abstract Ninety individuals of the characid fish Astyanax fasciatus (Cuvier, 1819) were collected at Água da Madalena stream (Botucatu, São Paulo, Brazil) and analyzed for diploid chromosome number 2n and karyotype composition as well as for the chromosomal location of the 5S and 18S ribosomal DNA (rDNA). Whereas no chromosome differences were associated with sex, three different karyomorphs with diploid chromosome numbers 2n=46, 2n=48 and 2n=50 were found. No intermediate 2n numbers were discovered. The 2n=50 karyomorph showed some differences in 18S rDNA location compared to the two other karyomorphs. Finally, all specimens with the 2n=46 karyomorph showed the presence of a partly heterochromatic macro supernumerary chromosome, which was absent in all individuals with the two other karyomorphs. All these results suggest that indviduals of the three different karyomorphs are not likely to hybridize in the examined populations. Our findings strongly suggest the presence of three separate species (sensu biological species concept) easily diagnosed on the basis of differences in the diploid chromosome numbers and other chromosomal markers. PMID:24260650

Mapping Simple Repeated DNA Sequences in Heterochromatin of Drosophila Melanogaster

PubMed Central

Lohe, A. R.; Hilliker, A. J.; Roberts, P. A.

1993-01-01

Heterochromatin in Drosophila has unusual genetic, cytological and molecular properties. Highly repeated DNA sequences (satellites) are the principal component of heterochromatin. Using probes from cloned satellites, we have constructed a chromosome map of 10 highly repeated, simple DNA sequences in heterochromatin of mitotic chromosomes of Drosophila melanogaster. Despite extensive sequence homology among some satellites, chromosomal locations could be distinguished by stringent in situ hybridizations for each satellite. Only two of the localizations previously determined using gradient-purified bulk satellite probes are correct. Eight new satellite localizations are presented, providing a megabase-level chromosome map of one-quarter of the genome. Five major satellites each exhibit a multichromosome distribution, and five minor satellites hybridize to single sites on the Y chromosome. Satellites closely related in sequence are often located near one another on the same chromosome. About 80% of Y chromosome DNA is composed of nine simple repeated sequences, in particular (AAGAC)(n) (8 Mb), (AAGAG)(n) (7 Mb) and (AATAT)(n) (6 Mb). Similarly, more than 70% of the DNA in chromosome 2 heterochromatin is composed of five simple repeated sequences. We have also generated a high resolution map of satellites in chromosome 2 heterochromatin, using a series of translocation chromosomes whose breakpoints in heterochromatin were ordered by N-banding. Finally, staining and banding patterns of heterochromatic regions are correlated with the locations of specific repeated DNA sequences. The basis for the cytochemical heterogeneity in banding appears to depend exclusively on the different satellite DNAs present in heterochromatin. PMID:8375654

Molecular Marker Systems for Oenothera Genetics

PubMed Central

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G.; Greiner, Stephan

2008-01-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome–genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9·8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed. PMID:18791241

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venken, Koen J. T.; Popodi, Ellen; Holtzman, Stacy L.

We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using C31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are toleratedmore » at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.« less

Molecular cloning of metaphase chromosome protein 1 (MCP1), a novel human autoantigen that associates with condensed chromosomes during mitosis.

PubMed

Bronze-da-Rocha, E; Catita, J A; Sunkel, C E

1998-02-01

Systemic lupus erythematosus autoantibodies were used to identify and to characterize new human chromosome-associated proteins. Previous immunolocalization studies in human and murine tissue culture cells showed that some of these monoclonal antibodies recognize nuclear antigens that associate with condensed chromosomes during mitosis. One antibody was selected for screening a human HeLa S3 cDNA expression library, and cDNAs that code for an antigen of 31-33 kDa were isolated. Immunological, biochemical and cell fractionation data indicate that the 31- to 33-kDa antigen corresponds to the chromosome-associated protein recognized by the original monoclonal antibody. Sequence analysis shows that we isolated a novel human gene. Immunolocalization to human tissue culture cells shows that during interphase the antigen is dispersed in the nucleus and that during mitosis it associates exclusively with condensed chromosomes. A similar pattern of localization was also observed in mouse fibroblasts, suggesting that the antigen is conserved among different species. Finally, we show that part of the antigen remains bound to the scaffold/matrix component, even after high salt extraction.

Recognition and modification of seX chromosomes.

PubMed

Nusinow, Dmitri A; Panning, Barbara

2005-04-01

Flies, worms and mammals employ dosage compensation complexes that alter chromatin or chromosome structure to equalize X-linked gene expression between the sexes. Recent work has improved our understanding of how dosage compensation complexes achieve X chromosome-wide association and has provided significant insight into the epigenetic modifications directed by these complexes to modulate gene expression. In flies, the prevailing view that dosage compensation complexes assemble on the X chromosome at approximately 35 chromatin-entry sites and then spread in cis to cover the chromosome has been re-evaluated in light of the evidence that these chromatin-entry sites are not required for localization of the complex. By contrast, identification of discrete recruitment elements indicates that nucleation at and spread from a limited number of sites directs dosage compensation complex localization on the worm X-chromosome. Studies in flies and mammals have extended our understanding of how ribonucleoprotein complexes are used to modify X chromatin, for either activation or repression of transcription. Finally, evidence from mammals suggests that the chromatin modifications that mediate dosage compensation are very dynamic, because they are established, reversed and re-established early in development.

Molecular marker systems for Oenothera genetics.

PubMed

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G; Greiner, Stephan

2008-11-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome-genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9.8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed.

Chromosomal evolution and phylogeny in the Nullicauda group (Chiroptera, Phyllostomidae): evidence from multidirectional chromosome painting.

PubMed

Gomes, Anderson José Baia; Nagamachi, Cleusa Yoshiko; Rodrigues, Luis Reginaldo Ribeiro; Ferguson-Smith, Malcolm Andrew; Yang, Fengtang; O'Brien, Patricia Caroline Mary; Pieczarka, Julio Cesar

2018-04-25

The family Phyllostomidae (Chiroptera) shows wide morphological, molecular and cytogenetic variation; many disagreements regarding its phylogeny and taxonomy remains to be resolved. In this study, we use chromosome painting with whole chromosome probes from the Phyllostomidae Phyllostomus hastatus and Carollia brevicauda to determine the rearrangements among several genera of the Nullicauda group (subfamilies Gliphonycterinae, Carolliinae, Rhinophyllinae and Stenodermatinae). These data, when compared with previously published chromosome homology maps, allow the construction of a phylogeny comparable to those previously obtained by morphological and molecular analysis. Our phylogeny is largely in agreement with that proposed with molecular data, both on relationships between the subfamilies and among genera; it confirms, for instance, that Carollia and Rhinophylla, previously considered as part of the same subfamily are, in fact, distant genera. The occurrence of the karyotype considered ancestral for this family in several different branches suggests that the diversification of Phyllostomidae into many subfamilies has occurred in a short period of time. Finally, the comparison with published maps using human whole chromosome probes allows us to track some syntenic associations prior to the emergence of this family.

Minnesota Deaf-Blind Technical Assistance Project. Final Report.

ERIC Educational Resources Information Center

Kloos, Eric

This final report describes activities and accomplishments of the 3-year federally supported Minnesota Deaf-Blind Technical Assistance Project. The project provided training and technical assistance, information sharing, and support services to families of children with deaf-blindness. Activities and accomplishments included: collaboration with…

75 FR 56857 - Pilot, Flight Instructor, and Pilot School Certification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

... of part 141. Discussion of Technical Amendment Section 141.5(d) establishes the quality of training... Certification AGENCY: Federal Aviation Administration, DOT. ACTION: Final rule; technical amendment. SUMMARY: The Federal Aviation Administration (FAA) is making minor technical changes to a final rule published...

Rapid rise and fall of selfish sex-ratio X chromosomes in Drosophila simulans: spatiotemporal analysis of phenotypic and molecular data.

PubMed

Bastide, Héloïse; Cazemajor, Michel; Ogereau, David; Derome, Nicolas; Hospital, Frédéric; Montchamp-Moreau, Catherine

2011-09-01

Sex-ratio drive, which has been documented in several Drosophila species, is induced by X-linked segregation distorters. Contrary to Mendel's law of independent assortment, the sex-ratio chromosome (X(SR)) is inherited by more than half the offspring of carrier males, resulting in a female-biased sex ratio. This segregation advantage allows X(SR) to spread in populations, even if it is not beneficial for the carriers. In the cosmopolitan species D. simulans, the Paris sex-ratio is caused by recently emerged selfish X(SR) chromosomes. These chromosomes have triggered an intragenomic conflict, and their propagation has been halted over a large area by the evolution of complete drive suppression. Previous molecular population genetics analyses revealed a selective sweep indicating that the invasion of X(SR) chromosomes was very recent in Madagascar (likely less than 100 years ago). Here, we show that X(SR) chromosomes are now declining at this location as well as in Mayotte and Kenya. Drive suppression is complete in the three populations, which display little genetic differentiation and share swept haplotypes, attesting to a common and very recent ancestry of the X(SR) chromosomes. Patterns of DNA sequence variation also indicate a fitness cost of the segmental duplication involved in drive. The data suggest that X(SR) chromosomes started declining first on the African continent, then in Mayotte, and finally in Madagascar and strongly support a scenario of rapid cycling of X chromosomes. Once drive suppression has evolved, standard X(ST) chromosomes locally replace costly X(SR) chromosomes in a few decades.

Brown and polar bear Y chromosomes reveal extensive male-biased gene flow within brother lineages.

PubMed

Bidon, Tobias; Janke, Axel; Fain, Steven R; Eiken, Hans Geir; Hagen, Snorre B; Saarma, Urmas; Hallström, Björn M; Lecomte, Nicolas; Hailer, Frank

2014-06-01

Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes

PubMed Central

Bolzer, Andreas; Kreth, Gregor; Solovei, Irina; Koehler, Daniela; Saracoglu, Kaan; Fauth, Christine; Müller, Stefan; Eils, Roland; Cremer, Christoph; Speicher, Michael R

2005-01-01

Studies of higher-order chromatin arrangements are an essential part of ongoing attempts to explore changes in epigenome structure and their functional implications during development and cell differentiation. However, the extent and cell-type-specificity of three-dimensional (3D) chromosome arrangements has remained controversial. In order to overcome technical limitations of previous studies, we have developed tools that allow the quantitative 3D positional mapping of all chromosomes simultaneously. We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs) in nuclei of quiescent (G0) and cycling (early S-phase) human diploid fibroblasts (46, XY). Radial distance measurements showed a probabilistic, highly nonrandom correlation with chromosome size: small chromosomes—independently of their gene density—were distributed significantly closer to the center of the nucleus or prometaphase rosette, while large chromosomes were located closer to the nuclear or rosette rim. This arrangement was independently confirmed in both human fibroblast and amniotic fluid cell nuclei. Notably, these cell types exhibit flat-ellipsoidal cell nuclei, in contrast to the spherical nuclei of lymphocytes and several other human cell types, for which we and others previously demonstrated gene-density-correlated radial 3D CT arrangements. Modeling of 3D CT arrangements suggests that cell-type-specific differences in radial CT arrangements are not solely due to geometrical constraints that result from nuclear shape differences. We also found gene-density-correlated arrangements of higher-order chromatin shared by all human cell types studied so far. Chromatin domains, which are gene-poor, form a layer beneath the nuclear envelope, while gene-dense chromatin is enriched in the nuclear interior. We discuss the possible functional implications of this finding. PMID:15839726

A malformed child with a recombinant chromosome 7, rec(7) dup p, derived from a maternal pericentric inversion inv(7)(p15q36).

PubMed Central

Delicado, A; Escribano, E; Lopez Pajares, I; Diaz de Bustamante, A; Carrasco, S

1991-01-01

We report a child with facial dysmorphic features, hypoplasia of the external genitalia, intestinal malrotation, congenital cardiac defect, and minor limb anomalies. Chromosome studies showed a recombinant chromosome 7, rec(7) dup p, resulting from a maternal pericentric inversion inv(7)(p15 q36). Thus, this child had partial trisomy 7p in addition to a small distal monosomy 7. The clinical findings are compared with those found in previous reports of trisomy 7p. Finally, some general principles for genetic counselling are discussed. Images PMID:2002483

77 FR 29247 - Federal Motor Vehicle Safety Standards; Occupant Crash Protection

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

...). ACTION: Final rule; technical amendments. SUMMARY: This final rule makes technical amendments to Federal... advanced air bag requirements. As written now, the general warning label requirements contain an explicit... equipment requirements for restraint systems. This document makes technical amendments to several of the...

BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei

2009-03-09

Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relativelymore » rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.« less

International workshop on chromosome 3. Final report, April 15, 1991--April 14, 1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gemmill, R.M.

1992-07-01

The Second Workshop on Human Chromosome 3 was held on April 4--5, 1991 at Denver, Colorado. There were 43 participants representing 8 nations. The workshop participants reviewed the current state of the chromosome 3 map, both physical and genetic, and prepared lists of markers and cell lines to be made commonly available. These markers and cell lines should be incorporated into the mapping efforts of diverse groups to permit the integration of data and development of consensus maps at future workshops. Region specific efforts were described for sections of the chromosome harboring genes thought to be involved in certain diseasesmore » including Von Hippel-Lindau disease, 3p-syndrome, lung cancer and renal cancer. Selected papers have been processed separately for inclusion in the Energy Science and Technology Database.« less

Unprecedented within-species chromosome number cline in the Wood White butterfly Leptidea sinapis and its significance for karyotype evolution and speciation

PubMed Central

2011-01-01

Background Species generally have a fixed number of chromosomes in the cell nuclei while between-species differences are common and often pronounced. These differences could have evolved through multiple speciation events, each involving the fixation of a single chromosomal rearrangement. Alternatively, marked changes in the karyotype may be the consequence of within-species accumulation of multiple chromosomal fissions/fusions, resulting in highly polymorphic systems with the subsequent extinction of intermediate karyomorphs. Although this mechanism of chromosome number evolution is possible in theory, it has not been well documented. Results We present the discovery of exceptional intraspecific variability in the karyotype of the widespread Eurasian butterfly Leptidea sinapis. We show that within this species the diploid chromosome number gradually decreases from 2n = 106 in Spain to 2n = 56 in eastern Kazakhstan, resulting in a 6000 km-wide cline that originated recently (8,500 to 31,000 years ago). Remarkably, intrapopulational chromosome number polymorphism exists, the chromosome number range overlaps between some populations separated by hundreds of kilometers, and chromosomal heterozygotes are abundant. We demonstrate that this karyotypic variability is intraspecific because in L. sinapis a broad geographical distribution is coupled with a homogenous morphological and genetic structure. Conclusions The discovered system represents the first clearly documented case of explosive chromosome number evolution through intraspecific and intrapopulation accumulation of multiple chromosomal changes. Leptidea sinapis may be used as a model system for studying speciation by means of chromosomally-based suppressed recombination mechanisms, as well as clinal speciation, a process that is theoretically possible but difficult to document. The discovered cline seems to represent a narrow time-window of the very first steps of species formation linked to multiple chromosomal changes that have occurred explosively. This case offers a rare opportunity to study this process before drift, dispersal, selection, extinction and speciation erase the traces of microevolutionary events and just leave the final picture of a pronounced interspecific chromosomal difference. PMID:21507222

Mitotic chromosome condensation in vertebrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 themore » 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 of proteins and their co-operation in establishing the final mitotic chromosome structure.« less

The ultrastructure of mono- and holocentric plant centromeres: an immunological investigation by structured illumination microscopy and scanning electron microscopy.

PubMed

Wanner, Gerhard; Schroeder-Reiter, Elizabeth; Ma, Wei; Houben, Andreas; Schubert, Veit

2015-12-01

The spatial distribution of the three centromere-associated proteins α-tubulin, CENH3, and phosphorylated histone H2A (at threonine 120, H2AThr120ph) was analysed by indirect immunodetection at monocentric cereal chromosomes and at the holocentric chromosomes of Luzula elegans by super-resolution light microscopy and scanning electron microscopy (SEM). Using structured illumination microscopy (SIM) as the super-resolution technique on squashed specimens and SEM on uncoated isolated specimens, the three-dimensional (3D) distribution of the proteins was visualized at the centromeres. Technical aspects of 3D SEM are explained in detail. We show that CENH3 forms curved "pads" mainly around the lateral centromeric region in the primary constriction of metacentric chromosomes. H2AThr120ph is present in both the primary constriction and in the pericentromere. α-tubulin-labeled microtubule bundles attach to CENH3-containing chromatin structures, either in single bundles with a V-shaped attachment to the centromere or in split bundles to bordering pericentromeric flanks. In holocentric L. elegans chromosomes, H2AThr120ph is located predominantly in the centromeric groove of each chromatid as proven by subsequent FIB/FESEM ablation and 3D reconstruction. α-tubulin localizes to the edges of the groove. In both holocentric and monocentric chromosomes, no additional intermediate structures between microtubules and the centromere were observed. We established models of the distribution of CENH3, H2AThr120ph and the attachment sites of microtubules for metacentric and holocentric plant chromosomes.

A fresh look at the male-specific region of the human Y chromosome.

PubMed

Jangravi, Zohreh; Alikhani, Mehdi; Arefnezhad, Babak; Sharifi Tabar, Mehdi; Taleahmad, Sara; Karamzadeh, Razieh; Jadaliha, Mahdieh; Mousavi, Seyed Ahmad; Ahmadi Rastegar, Diba; Parsamatin, Pouria; Vakilian, Haghighat; Mirshahvaladi, Shahab; Sabbaghian, Marjan; Mohseni Meybodi, Anahita; Mirzaei, Mehdi; Shahhoseini, Maryam; Ebrahimi, Marzieh; Piryaei, Abbas; Moosavi-Movahedi, Ali Akbar; Haynes, Paul A; Goodchild, Ann K; Nasr-Esfahani, Mohammad Hossein; Jabbari, Esmaiel; Baharvand, Hossein; Sedighi Gilani, Mohammad Ali; Gourabi, Hamid; Salekdeh, Ghasem Hosseini

2013-01-04

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome's length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein-protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping.

Y choromosomal microdeletion screening in the workup of male infertility and its current status in India.

PubMed

Suganthi, Ramaswamy; Vijesh, Vijayabhavanath Vijayakumaran; Vandana, Nambiar; Fathima Ali Benazir, Jahangir

2014-01-01

Spermatogenesis is an essential stage in human male gamete development, which is regulated by many Y chromosome specific genes. Most of these genes are centred in a specific region located on the long arm of the human Y chromosome known as the azoospermia factor region (AZF). Deletion events are common in Y chromosome because of its peculiar structural organization. Astonishingly, among the several known genetic causes of male infertility, Y chromosomal microdeletions emerged as the most frequent structural chromosome anomaly associated with the quantitative reduction of sperm. The development of assisted reproductive techniques (ART) like intra-cytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) helps to bypass the natural barriers of fertilization, but it increases the concern about the transmission of genetic defects. Experimental evidence suggested that the men with Y chromosomal microdeletions vertically transmitted their deletion as well as related fertility disorders to their offspring via these ART techniques. In India, infertility is on alarming rise. ART centres have opened up in virtually every state but still most of the infertility centres in India do not choose to perform Y chromosomal microdeletion diagnosis because of some advanced theoretical reasons. Moreover, there is no consensus among the clinicians about the diagnosis and management of Y chromosomal microdeletion defects. The current review discusses thoroughly the role of Y chromosome microdeletion screening in the workup of male infertility, its significance as a diagnostic test, novel approaches for screening Y deletions and finally a systematic review on the current status of Y chromosome microdeletion deletion screening in India.

GeneBreak: detection of recurrent DNA copy number aberration-associated chromosomal breakpoints within genes.

PubMed

van den Broek, Evert; van Lieshout, Stef; Rausch, Christian; Ylstra, Bauke; van de Wiel, Mark A; Meijer, Gerrit A; Fijneman, Remond J A; Abeln, Sanne

2016-01-01

Development of cancer is driven by somatic alterations, including numerical and structural chromosomal aberrations. Currently, several computational methods are available and are widely applied to detect numerical copy number aberrations (CNAs) of chromosomal segments in tumor genomes. However, there is lack of computational methods that systematically detect structural chromosomal aberrations by virtue of the genomic location of CNA-associated chromosomal breaks and identify genes that appear non-randomly affected by chromosomal breakpoints across (large) series of tumor samples. 'GeneBreak' is developed to systematically identify genes recurrently affected by the genomic location of chromosomal CNA-associated breaks by a genome-wide approach, which can be applied to DNA copy number data obtained by array-Comparative Genomic Hybridization (CGH) or by (low-pass) whole genome sequencing (WGS). First, 'GeneBreak' collects the genomic locations of chromosomal CNA-associated breaks that were previously pinpointed by the segmentation algorithm that was applied to obtain CNA profiles. Next, a tailored annotation approach for breakpoint-to-gene mapping is implemented. Finally, dedicated cohort-based statistics is incorporated with correction for covariates that influence the probability to be a breakpoint gene. In addition, multiple testing correction is integrated to reveal recurrent breakpoint events. This easy-to-use algorithm, 'GeneBreak', is implemented in R ( www.cran.r-project.org ) and is available from Bioconductor ( www.bioconductor.org/packages/release/bioc/html/GeneBreak.html ).

Micromechanical study of protein-DNA interactions and chromosomes

NASA Astrophysics Data System (ADS)

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).

Systems-level chromosomal parameters represent a suprachromosomal basis for the non-random chromosomal arrangement in human interphase nuclei

PubMed Central

Fatakia, Sarosh N.; Mehta, Ishita S.; Rao, Basuthkar J.

2016-01-01

Forty-six chromosome territories (CTs) are positioned uniquely in human interphase nuclei, wherein each of their positions can range from the centre of the nucleus to its periphery. A non-empirical basis for their non-random arrangement remains unreported. Here, we derive a suprachromosomal basis of that overall arrangement (which we refer to as a CT constellation), and report a hierarchical nature of the same. Using matrix algebra, we unify intrinsic chromosomal parameters (e.g., chromosomal length, gene density, the number of genes per chromosome), to derive an extrinsic effective gene density matrix, the hierarchy of which is dominated largely by extrinsic mathematical coupling of HSA19, followed by HSA17 (human chromosome 19 and 17, both preferentially interior CTs) with all CTs. We corroborate predicted constellations and effective gene density hierarchy with published reports from fluorescent in situ hybridization based microscopy and Hi-C techniques, and delineate analogous hierarchy in disparate vertebrates. Our theory accurately predicts CTs localised to the nuclear interior, which interestingly share conserved synteny with HSA19 and/or HSA17. Finally, the effective gene density hierarchy dictates how permutations among CT position represents the plasticity within its constellations, based on which we suggest that a differential mix of coding with noncoding genome modulates the same. PMID:27845379

Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe.

PubMed

Marques, Catarina A; Dickens, Nicholas J; Paape, Daniel; Campbell, Samantha J; McCulloch, Richard

2015-10-19

DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania. Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins. The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture.

77 FR 30512 - Native American Career and Technical Education Program; Final Waivers and Extension of Project...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... DEPARTMENT OF EDUCATION Native American Career and Technical Education Program; Final Waivers and... American Career and Technical Education Program Catalog of Federal Domestic Assistance (CFDA) Number: 84.101A. SUMMARY: For 60-month projects funded in fiscal year (FY) 2007 under the Native American Career...

48 CFR 1852.235-73 - Final Scientific and Technical Reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Final Scientific and Technical Reports. 1852.235-73 Section 1852.235-73 Federal Acquisition Regulations System NATIONAL..., including recommendations and conclusions based on the experience and results obtained. The final report...

Coosa River Storage Annex, Talladega, Alabama Environmental Investigation, Final Management and Resources Utilization Plan

DTIC Science & Technology

1991-02-01

to adequately assess the health and environmental risks associated with the closure and transfer of the Annex forI other use; and 3) identification of...1990); Draft Final Technical Plan, Draft Final Sampling Design Plan and Draft Final Health and Safety Plan, USATHAMA, June 1990. 2.1.2 Draft Final...Final Technical Plan, Sampling Design Plan and Health and Safety Plan) supplied by USATHAMA. The estimate may be revised, with USATHAMA approval, as

Seed colour loci, homoeology and linkage groups of the C genome chromosomes revealed in Brassica rapa–B. oleracea monosomic alien addition lines

PubMed Central

Heneen, Waheeb K.; Geleta, Mulatu; Brismar, Kerstin; Xiong, Zhiyong; Pires, J. Chris; Hasterok, Robert; Stoute, Andrew I.; Scott, Roderick J.; King, Graham J.; Kurup, Smita

2012-01-01

Background and Aims Brassica rapa and B. oleracea are the progenitors of oilseed rape B. napus. The addition of each chromosome of B. oleracea to the chromosome complement of B. rapa results in a series of monosomic alien addition lines (MAALs). Analysis of MAALs determines which B. oleracea chromosomes carry genes controlling specific phenotypic traits, such as seed colour. Yellow-seeded oilseed rape is a desirable breeding goal both for food and livestock feed end-uses that relate to oil, protein and fibre contents. The aims of this study included developing a missing MAAL to complement an available series, for studies on seed colour control, chromosome homoeology and assignment of linkage groups to B. oleracea chromosomes. Methods A new batch of B. rapa–B. oleracea aneuploids was produced to generate the missing MAAL. Seed colour and other plant morphological features relevant to differentiation of MAALs were recorded. For chromosome characterization, Snow's carmine, fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH) were used. Key Results The final MAAL was developed. Morphological traits that differentiated the MAALs comprised cotyledon number, leaf morphology, flower colour and seed colour. Seed colour was controlled by major genes on two B. oleracea chromosomes and minor genes on five other chromosomes of this species. Homoeologous pairing was largely between chromosomes with similar centromeric positions. FISH, GISH and a parallel microsatellite marker analysis defined the chromosomes in terms of their linkage groups. Conclusions A complete set of MAALs is now available for genetic, genomic, evolutionary and breeding perspectives. Defining chromosomes that carry specific genes, physical localization of DNA markers and access to established genetic linkage maps contribute to the integration of these approaches, manifested in the confirmed correspondence of linkage groups with specific chromosomes. Applications include marker-assisted selection and breeding for yellow seeds. PMID:22628364

[Multiplexing mapping of human cDNAs]. Final report, September 1, 1991--February 28, 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

Using PCR with automated product analysis, 329 human brain cDNA sequences have been assigned to individual human chromosomes. Primers were designed from single-pass cDNA sequences expressed sequence tags (ESTs). Primers were used in PCR reactions with DNA from somatic cell hybrid mapping panels as templates, often with multiplexing. Many ESTs mapped match sequence database records. To evaluate of these matches, the position of the primers relative to the matching region (In), the BLAST scores and the Poisson probability values of the EST/sequence record match were determined. In cases where the gene product was stringently identified by the sequence match hadmore » already been mapped, the gene locus determined by EST was consistent with the previous position which strongly supports the validity of assigning unknown genes to human chromosomes based on the EST sequence matches. In the present cases mapping the ESTs to a chromosome can also be considered to have mapped the known gene product: rolipram-sensitive cAMP phosphodiesterase, chromosome 1; protein phosphatase 2A{beta}, chromosome 4; alpha-catenin, chromosome 5; the ELE1 oncogene, chromosome 10q11.2 or q2.1-q23; MXII protein, chromosome l0q24-qter; ribosomal protein L18a homologue, chromosome 14; ribosomal protein L3, chromosome 17; and moesin, Xp11-cen. There were also ESTs mapped that were closely related to non-human sequence records. These matches therefore can be considered to identify human counterparts of known gene products, or members of known gene families. Examples of these include membrane proteins, translation-associated proteins, structural proteins, and enzymes. These data then demonstrate that single pass sequence information is sufficient to design PCR primers useful for assigning cDNA sequences to human chromosomes. When the EST sequence matches previous sequence database records, the chromosome assignments of the EST can be used to make preliminary assignments of the human gene to a chromosome.« less

Mapping Our Genes: The Genome Projects: How Big, How Fast

DOE R&D Accomplishments Database

1988-04-01

For the past 2 years, scientific and technical journals in biology and medicine have extensively covered a debate about whether and how to determine the function and order of human genes on human chromosomes and when to determine the sequence of molecular building blocks that comprise DNA in those chromosomes. In 1987, these issues rose to become part of the public agenda. The debate involves science, technology, and politics. Congress is responsible for ?writing the rules? of what various federal agencies do and for funding their work. This report surveys the points made so far in the debate, focusing on those that most directly influence the policy options facing the US Congress. Congressional interest focused on how to assess the rationales for conducting human genome projects, how to fund human genome projects (at what level and through which mechanisms), how to coordinate the scientific and technical programs of the several federal agencies and private interests already supporting various genome projects, and how to strike a balance regarding the impact of genome projects on international scientific cooperation and international economic competition in biotechnology. The Office of Technology Assessment (OTA) prepared this report with the assistance of several hundred experts throughout the world.

Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour

PubMed Central

Pearse, Anne-Maree; Rens, Willem; O'Brien, Patricia C. M.; Ferguson-Smith, Malcolm A.; Cheng, Yuanyuan; Morris, Katrina; Taylor, Robyn; Stuart, Andrew; Belov, Katherine; Amemiya, Chris T.; Murchison, Elizabeth P.; Papenfuss, Anthony T.; Marshall Graves, Jennifer A.

2012-01-01

Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD. PMID:22359511

O-chromosome lethal frequencies in Serbian and Montenegrin Drosophila subobscura populations.

PubMed

Zivanovic, G; Arenas, C; Mestres, F

2011-10-01

Lethal chromosomal frequencies were obtained from three Drosophila subobscura samples from the Mt. Avala (Serbia) population in September 2003 (0.218), June 2004 (0.204) and September 2004 (0.250). These values and those from other Balkan populations studied previously (Petnica, Kamariste, Zanjic and Djerdap) were used to analyze the possible effect of population, year, month and altitude above sea level on lethal chromosomal frequencies. According to ANOVAS no effect were observed. Furthermore, the lethal frequencies of the Balkan populations did not vary according to latitude. This is probably due to the relative proximity and high gene flow between these populations. From a joint study of all the Palearctic D. subobscura populations so far analyzed, it can be deduced that the Balkan populations are located in the central area of the species distribution. Finally, it seems that lethal chromosomal frequencies are a consequence of the genetic structure of the populations.

Genetic Association Study of Ancestry-Matched African American Prostate Cancer Cases and Control

DTIC Science & Technology

2009-04-01

TO THE ABOVE ADDRESS. 1. REPORT DATE 1 April 2009 2 . REPORT TYPE Final 3. DATES COVERED 1 April 2008 – 31 March 2009 4. TITLE AND SUBTITLE...matching, we have identified and confirmed several prostate cancer susceptibility loci in this study population, on chromosomes 2 , 8 and 17. These and...prostate cancer susceptibility loci in these studies, on chromosomes 2 , 8, and 17. These and other ongoing studies will provide unprecedented insight

Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer—ready for prime-time?

PubMed Central

Pailler, Emma; Faugeroux, Vincent; Oulhen, Marianne; Catelain, Cyril

2017-01-01

In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis. Here we introduce the clinical needs in this disease that mainly consist of the diagnosis of epidermal growth factor receptor (EGFR) activating alterations and anaplastic lymphoma kinase (ALK) rearrangement. We present the proof-of-concept studies that explore the detection of these genetic alterations in CTCs from NSCLC patients. Finally, we discuss steps that are still required before CTCs are routinely used for diagnosis of EGFR-mutations and ALK-rearrangements in this disease. PMID:28904888

Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for prime-time?

PubMed

Pailler, Emma; Faugeroux, Vincent; Oulhen, Marianne; Catelain, Cyril; Farace, Françoise

2017-08-01

In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis. Here we introduce the clinical needs in this disease that mainly consist of the diagnosis of epidermal growth factor receptor ( EGFR ) activating alterations and anaplastic lymphoma kinase ( ALK ) rearrangement. We present the proof-of-concept studies that explore the detection of these genetic alterations in CTCs from NSCLC patients. Finally, we discuss steps that are still required before CTCs are routinely used for diagnosis of EGFR -mutations and ALK -rearrangements in this disease.

High-Resolution Analysis of Human Y-Chromosome Variation Shows a Sharp Discontinuity and Limited Gene Flow between Northwestern Africa and the Iberian Peninsula

PubMed Central

Bosch, Elena; Calafell, Francesc; Comas, David; Oefner, Peter J.; Underhill, Peter A.; Bertranpetit, Jaume

2001-01-01

In the present study we have analyzed 44 Y-chromosome biallelic polymorphisms in population samples from northwestern (NW) Africa and the Iberian Peninsula, which allowed us to place each chromosome unequivocally in a phylogenetic tree based on >150 polymorphisms. The most striking results are that contemporary NW African and Iberian populations were found to have originated from distinctly different patrilineages and that the Strait of Gibraltar seems to have acted as a strong (although not complete) barrier to gene flow. In NW African populations, an Upper Paleolithic colonization that probably had its origin in eastern Africa contributed 75% of the current gene pool. In comparison, ∼78% of contemporary Iberian Y chromosomes originated in an Upper Paleolithic expansion from western Asia, along the northern rim of the Mediterranean basin. Smaller contributions to these gene pools (constituting 13% of Y chromosomes in NW Africa and 10% of Y chromosomes in Iberia) came from the Middle East during the Neolithic and, during subsequent gene flow, from Sub-Saharan to NW Africa. Finally, bidirectional gene flow across the Strait of Gibraltar has been detected: the genetic contribution of European Y chromosomes to the NW African gene pool is estimated at 4%, and NW African populations may have contributed 7% of Iberian Y chromosomes. The Islamic rule of Spain, which began in a.d. 711 and lasted almost 8 centuries, left only a minor contribution to the current Iberian Y-chromosome pool. The high-resolution analysis of the Y chromosome allows us to separate successive migratory components and to precisely quantify each historical layer. PMID:11254456

77 FR 50589 - Agreements and Memoranda of Understanding Between the Food and Drug Administration and Other...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

...: Final rule. SUMMARY: This final rule makes technical changes that will update a requirement that many of the written agreements and memoranda of understanding (MOUs) between the Food and Drug Administration.... This final rule, accordingly, eliminates it. We are making these technical changes to conserve Agency...

77 FR 30514 - Native Hawaiian Career and Technical Education Program; Final Waiver and Extension of Project Period

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... DEPARTMENT OF EDUCATION Native Hawaiian Career and Technical Education Program; Final Waiver and.... ACTION: Notice. Overview Information Final Waiver and Extension of Project Period for the Native Hawaiian.... SUMMARY: For 36-month projects funded in fiscal year (FY) 2009 under the Native Hawaiian Career and...

The Genetic Content of Chromosomal Inversions across a Wide Latitudinal Gradient

PubMed Central

Simões, Pedro; Calabria, Gemma; Picão-Osório, João; Balanyà, Joan; Pascual, Marta

2012-01-01

There is increasing evidence regarding the role of chromosomal inversions in relevant biological processes such as local adaptation and speciation. A classic example of the adaptive role of chromosomal polymorphisms is given by the clines of inversion frequencies in Drosophila subobscura, repeatable across continents. Nevertheless, not much is known about the molecular variation associated with these polymorphisms. We characterized the genetic content of ca. 600 individuals from nine European populations following a latitudinal gradient by analysing 19 microsatellite loci from two autosomes (J and U) and the sex chromosome (A), taking into account their chromosomal inversions. Our results clearly demonstrate the molecular genetic uniformity within a given chromosomal inversion across a large latitudinal gradient, particularly from Groningen (Netherlands) in the north to Málaga (Spain) in the south, experiencing highly diverse environmental conditions. This low genetic differentiation within the same gene arrangement across the nine European populations is consistent with the local adaptation hypothesis for th evolutionof chromosomal polymorphisms. We also show the effective role of chromosomal inversions in maintaining different genetic pools within these inverted genomic regions even in the presence of high gene flow. Inversions represent thus an important barrier to gene flux and can help maintain specific allelic combinations with positive effects on fitness. Consistent patterns of microsatellite allele-inversion linkage disequilibrium particularly in loci within inversions were also observed. Finally, we identified areas within inversions presenting clinal variation that might be under selection. PMID:23272126

Relevance and limitations of crowding, fractal, and polymer models to describe nuclear architecture.

PubMed

Huet, Sébastien; Lavelle, Christophe; Ranchon, Hubert; Carrivain, Pascal; Victor, Jean-Marc; Bancaud, Aurélien

2014-01-01

Chromosome architecture plays an essential role for all nuclear functions, and its physical description has attracted considerable interest over the last few years among the biophysics community. These researches at the frontiers of physics and biology have been stimulated by the demand for quantitative analysis of molecular biology experiments, which provide comprehensive data on chromosome folding, or of live cell imaging experiments that enable researchers to visualize selected chromosome loci in living or fixed cells. In this review our goal is to survey several nonmutually exclusive models that have emerged to describe the folding of DNA in the nucleus, the dynamics of proteins in the nucleoplasm, or the movements of chromosome loci. We focus on three classes of models, namely molecular crowding, fractal, and polymer models, draw comparisons, and discuss their merits and limitations in the context of chromosome structure and dynamics, or nuclear protein navigation in the nucleoplasm. Finally, we identify future challenges in the roadmap to a unified model of the nuclear environment. © 2014 Elsevier Inc. All rights reserved.

TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment

PubMed Central

Milev, Miroslav P.; Hasaj, Benedeta; Saint-Dic, Djenann; Snounou, Sary; Zhao, Qingchuan

2015-01-01

Chromosome congression requires the stable attachment of microtubules to chromosomes mediated by the kinetochore, a large proteinaceous structure whose mechanism of assembly is unknown. In this paper, we present the finding that a protein called TRAMM (formerly known as TrappC12) plays a role in mitosis. Depletion of TRAMM resulted in noncongressed chromosomes and arrested cells in mitosis. Small amounts of TRAMM associated with chromosomes, and its depletion affected the localization of some kinetochore proteins, the strongest effect being seen for CENP-E. TRAMM interacts with CENP-E, and depletion of TRAMM prevented the recruitment of CENP-E to the kinetochore. TRAMM is phosphorylated early in mitosis and dephosphorylated at the onset of anaphase. Interestingly, this phosphorylation/dephosphorylation cycle correlates with its association/disassociation with CENP-E. Finally, we demonstrate that a phosphomimetic form of TRAMM recruited CENP-E to kinetochores more efficiently than did the nonphosphorylatable mutant. Our study identifies a moonlighting function for TRAMM during mitosis and adds a new component that regulates kinetochore stability and CENP-E recruitment. PMID:25918224

Simple Y-autosomal incompatibilities cause hybrid male sterility in reciprocal crosses between Drosophila virilis and D. americana.

PubMed

Sweigart, Andrea L

2010-03-01

Postzygotic reproductive isolation evolves when hybrid incompatibilities accumulate between diverging populations. Here, I examine the genetic basis of hybrid male sterility between two species of Drosophila, Drosophila virilis and D. americana. From these analyses, I reach several conclusions. First, neither species carries any autosomal dominant hybrid male sterility alleles: reciprocal F(1) hybrid males are perfectly fertile. Second, later generation (backcross and F(2)) hybrid male sterility between D. virilis and D. americana is not polygenic. In fact, I identified only three genetically independent incompatibilities that cause hybrid male sterility. Remarkably, each of these incompatibilities involves the Y chromosome. In one direction of the cross, the D. americana Y is incompatible with recessive D. virilis alleles at loci on chromosomes 2 and 5. In the other direction, the D. virilis Y chromosome causes hybrid male sterility in combination with recessive D. americana alleles at a single QTL on chromosome 5. Finally, in contrast with findings from other Drosophila species pairs, the X chromosome has only a modest effect on hybrid male sterility between D. virilis and D. americana.

Simple Y-Autosomal Incompatibilities Cause Hybrid Male Sterility in Reciprocal Crosses Between Drosophila virilis and D. americana

PubMed Central

Sweigart, Andrea L.

2010-01-01

Postzygotic reproductive isolation evolves when hybrid incompatibilities accumulate between diverging populations. Here, I examine the genetic basis of hybrid male sterility between two species of Drosophila, Drosophila virilis and D. americana. From these analyses, I reach several conclusions. First, neither species carries any autosomal dominant hybrid male sterility alleles: reciprocal F1 hybrid males are perfectly fertile. Second, later generation (backcross and F2) hybrid male sterility between D. virilis and D. americana is not polygenic. In fact, I identified only three genetically independent incompatibilities that cause hybrid male sterility. Remarkably, each of these incompatibilities involves the Y chromosome. In one direction of the cross, the D. americana Y is incompatible with recessive D. virilis alleles at loci on chromosomes 2 and 5. In the other direction, the D. virilis Y chromosome causes hybrid male sterility in combination with recessive D. americana alleles at a single QTL on chromosome 5. Finally, in contrast with findings from other Drosophila species pairs, the X chromosome has only a modest effect on hybrid male sterility between D. virilis and D. americana. PMID:20048051

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites.

PubMed

Feng, Wenyi; Chakraborty, Arijita

2017-01-01

Chromosome fragile sites are a fascinating cytogenetic phenomenon now widely implicated in a slew of human diseases ranging from neurological disorders to cancer. Yet, the paths leading to these revelations were far from direct, and the number of fragile sites that have been molecularly cloned with known disease-associated genes remains modest. Moreover, as more fragile sites were being discovered, research interests in some of the earliest discovered fragile sites ebbed away, leaving a number of unsolved mysteries in chromosome biology. In this review we attempt to recount some of the early discoveries of fragile sites and highlight those phenomena that have eluded intense scrutiny but remain extremely relevant in our understanding of the mechanisms of chromosome fragility. We then survey the literature for disease association for a comprehensive list of fragile sites. We also review recent studies addressing the underlying cause of chromosome fragility while highlighting some ongoing debates. We report an observed enrichment for R-loop forming sequences in fragile site-associated genes than genomic average. Finally, we will leave the reader with some lingering questions to provoke discussion and inspire further scientific inquiries.

Telomeres and mechanisms of Robertsonian fusion.

PubMed

Slijepcevic, P

1998-05-01

The Robertsonian (Rb) fusion, a chromosome rearrangement involving centric fusion of two acro-(telo)centric chromosomes to form a single metacentric, is one of the most frequent events in mammalian karyotype evolution. Since one of the functions of telomeres is to preserve chromosome integrity, a prerequisite for the formation of Rb fusions should be either telomere loss or telomere inactivation. Possible mechanisms underlying the formation of various types of Rb fusion are discussed here. For example, Rb fusion in wild mice involves complete loss of p-arm telomeres by chromosome breakage within minor satellite sequences. By contrast, interstitial telomeric sites are found in the pericentromeric regions of chromosomes originating from a number of vertebrate species, suggesting the occurrence of Rb-like fusion without loss of telomeres, a possibility consistent with some form of telomere inactivation. Finally, a recent study suggests that telomere shortening induced by the deletion of the telomerase RNA gene in the mouse germ-line leads to telomere loss and high frequencies of Rb fusion in mouse somatic cells. Thus, at least three mechanisms in mammalian cells lead to the formation of Rb fusions.

A Transient Rise in Free Mg2+ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation.

PubMed

Maeshima, Kazuhiro; Matsuda, Tomoki; Shindo, Yutaka; Imamura, Hiromi; Tamura, Sachiko; Imai, Ryosuke; Kawakami, Syoji; Nagashima, Ryosuke; Soga, Tomoyoshi; Noji, Hiroyuki; Oka, Kotaro; Nagai, Takeharu

2018-02-05

For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1-5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6-17], free divalent cations such as Mg 2+ and Ca 2+ , which condense chromatin or chromosomes in vitro [18-28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like "beads on a string" by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg 2+ , have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg 2+ indicator that monitors free Mg 2+ dynamics throughout the cell cycle. By combining this indicator with Ca 2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg 2+ , but not Ca 2+ , increase during mitosis. The Mg 2+ increase is coupled with a decrease in ATP, which is normally bound to Mg 2+ in the cell [33]. ATP inhibited Mg 2+ -dependent chromatin condensation in vitro. Chelating Mg 2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg 2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg 2+ -ATP balance. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup’ik) population

PubMed Central

Vaughan, Laura Kelly; Wiener, Howard W.; Aslibekyan, Stella; Allison, David B.; Havel, Peter J.; Stanhope, Kimber L.; O’Brien, Diane M.; Hopkins, Scarlett E.; Lemas, Dominick J.; Boyer, Bert B.; Tiwari, Hemant K.

2015-01-01

Objective To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup’ik people. Material and Methods We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. Results We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). Conclusions This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup’ik people. PMID:25772781

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.

PubMed

Vaughan, Laura Kelly; Wiener, Howard W; Aslibekyan, Stella; Allison, David B; Havel, Peter J; Stanhope, Kimber L; O'Brien, Diane M; Hopkins, Scarlett E; Lemas, Dominick J; Boyer, Bert B; Tiwari, Hemant K

2015-06-01

To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people. We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people. Copyright © 2015 Elsevier Inc. All rights reserved.

Interspecific chromosomal effects on agronomic traits in Gossypium hirsutum by AD analysis using intermated G. barbadense chromosome substitution lines.

PubMed

Saha, S; Wu, J; Jenkins, J N; McCarty, J C; Stelly, D M

2013-01-01

The untapped potential of the beneficial alleles from Gossypium barbadense L. has not been well utilized in G. hirsutum L. (often referred to as Upland cotton) breeding programs. This is primarily due to genomic incompatibility and technical challenges associated with conventional methods of interspecific introgression. In this study, we used a hypoaneuploid-based chromosome substitution line as a means for systematically introgressing G. barbadense doubled-haploid line '3-79' germplasm into a common Upland genetic background, inbred 'Texas marker-1' ('TM-1'). We reported on the chromosomal effects, lint percentage, boll weight, seedcotton yield and lint yield in chromosome substitution CS-B (G. barbadense L.) lines. Using an additive-dominance genetic model, we studied the interaction of alleles located on two alien substituted chromosomes versus one alien substituted chromosome using a partial diallel mating design of selected CS-B lines (CS-B05sh, CS-B06, CS-B09, CS-B10, CS-B12, CS-B17 and CS-B18). Among these parents, CS-B09 and CS-B10 were reported for the first time. The donor parent 3-79, had the lowest additive effect for all of the agronomic traits. All of the CS-B lines had significant additive effects with boll weight and lint percentage. CS-B10 had the highest additive effects for lint percentage, and seedcotton and lint yield among all of the lines showing a transgressive genetic mode of inheritance for these traits. CS-B09 had greater additive genetic effects on lint yield, while CS-B06, CS-B10 and CS-B17 had superior additive genetic effects on both lint and seedcotton yield compared to TM-1 parent. The 3-79 line had the highest dominance effects for boll weight (0.513 g) and CS-B10 had the lowest dominance effect for boll weight (-0.702). Some major antagonistic genetic effects for the agronomic traits were present with most of the substituted chromosomes and chromosome arms, a finding suggested their recalcitrance to conventional breeding efforts. The results revealed that the substituted chromosomes and arms of 3-79 carried some cryptic beneficial alleles with potential to improve agronomic traits including yield, whose effects were masked at the whole genome level in 3-79.

2005 v4.3 Technical Support Document

EPA Pesticide Factsheets

Emissions Modeling for the Final Mercury and Air Toxics Standards Technical Support Document describes how updated 2005 NEI, version 2 emissions were processed for air quality modeling in support of the final Mercury and Air Toxics Standards (MATS).

Phase II: Automated System for Aneuploidy Detection in Sperm Final Report CRADA No. TC-1554-98

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wyrobek, W. J.; Dunlay, R. T.

This was a collaborative effort between the University of California, Lawrence Livermore National Laboratory (LLNL) and Cellomics, Inc. (formerly BioDx and Biological Detection, Inc.) to develop an automated system for detecting human sperm aneuploidy. Aneuploidy (an abnormal number of chromosomes) is one of the major categories of chromosomally abnormal sperm, which results in chromosomally defective pregnancies and babies. An automated system would be used for testing the effects of toxic agents and for other research and clinical applications. This collaborated effort was funded by a National Institutes of Environmental Health Services, Phase II, Small Business Innovation Research Program (SBIR) grantmore » to Cellornics (Contract No. N44-ES-82004).« less

DNA intermediates and telomere addition during genome reorganization in Euplotes crassus.

PubMed

Roth, M; Prescott, D M

1985-06-01

Three gene-sized molecules cloned intact from macronuclear DNA served as hybridization probes to study excision of these molecules from chromosomes and their processing during macronuclear development in the hypotrich Euplotes crassus. These molecules occur in integrated forms within polytene chromosomal DNA during macronuclear developmental. After transection of the polytene chromosomes, the three molecules occur in intermediate forms. One of the three molecules first appeared in a large intermediate that was subsequently replaced by a second intermediate, approximately 140 bp larger than the final molecule. The other two macronuclear molecules were detected only in intermediates approximately 140 bp larger than the mature form. These penultimate intermediates are larger by virtue of oversized telomeres, which are pared to yield the mature gene-sized molecules.

Concise Review: Methods and Cell Types Used to Generate Down Syndrome Induced Pluripotent Stem Cells

PubMed Central

Hibaoui, Youssef; Feki, Anis

2015-01-01

Down syndrome (DS, trisomy 21), is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. Several models have been used to investigate the mechanisms by which the extra copy of chromosome 21 leads to the DS phenotype. In the last five years, several laboratories have been successful in reprogramming patient cells carrying the trisomy 21 anomaly into induced pluripotent stem cells, i.e., T21-iPSCs. In this review, we summarize the different T21-iPSCs that have been generated with a particular interest in the technical procedures and the somatic cell types used for the reprogramming. PMID:26239351

Comparison of prometaphase chromosome techniques with emphasis on the role of colcemid.

PubMed

Wiley, J E; Sargent, L M; Inhorn, S L; Meisner, L F

1984-12-01

Six different techniques were evaluated to define better those technical factors that are most critical for obtaining prometaphase cells for banding analysis. Our results demonstrate: colcemid exposures of 30 min or less have no effect on increasing the yield of prometaphase cells, colcemid exposures of greater than 0.1 microgram/ml can be toxic, methotrexate depresses the mitotic index significantly and seems to increase the incidence of prometaphase cells only because it suppresses later forms; and (d) the optimum number of cytogenetically satisfactory prometaphase cells can be obtained with a 4-h exposure to a combination of low concentration actinomycin D (0.5 microgram/ml) and colcemid (0.1 microgram/ml). This technique inhibits chromosome condensation while permitting prometaphase cells to accumulate for 4 h.

The Center for Space Telemetering and Telecommunications Systems

NASA Technical Reports Server (NTRS)

Horan, S.; DeLeon, P.; Borah, D.; Lyman, R.

2003-01-01

This report comprises the final technical report for the research grant 'Center for Space Telemetering and Telecommunications Systems' sponsored by the National Aeronautics and Space Administration's Goddard Space Flight Center. The grant activities are broken down into the following technology areas: (1) Space Protocol Testing; (2) Autonomous Reconfiguration of Ground Station Receivers; (3) Satellite Cluster Communications; and (4) Bandwidth Efficient Modulation. The grant activity produced a number of technical reports and papers that were communicated to NASA as they were generated. This final report contains the final summary papers or final technical report conclusions for each of the project areas. Additionally, the grant supported students who made progress towards their degrees while working on the research.

Promotion of the Equal Access of Girls and Women to Technical and Vocational Education. Studies on Technical and Vocational Education 7.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

This monograph includes the final report of the International Expert Meeting on the Promotion of Equal Access of Girls and Women to Technical and Vocational Education (TVE) held in Seoul, Republic of Korea, and country discussion papers. The final report is composed of an introduction that proposes that many Member States require special measures…

Air Quality Modeling Technical Support Document for the Final Cross State Air Pollution Rule Update

EPA Pesticide Factsheets

In this technical support document (TSD) we describe the air quality modeling performed to support the final Cross State Air Pollution Rule for the 2008 ozone National Ambient Air Quality Standards (NAAQS).

Distinct chromosome segregation roles for spindle checkpoint proteins.

PubMed

Warren, Cheryl D; Brady, D Michelle; Johnston, Raymond C; Hanna, Joseph S; Hardwick, Kevin G; Spencer, Forrest A

2002-09-01

The spindle checkpoint plays a central role in the fidelity of chromosome transmission by ensuring that anaphase is initiated only after kinetochore-microtubule associations of all sister chromatid pairs are complete. In this study, we find that known spindle checkpoint proteins do not contribute equally to chromosome segregation fidelity in Saccharomyces cerevisiae. Loss of Bub1 or Bub3 protein elicits the largest effect. Analysis of Bub1p reveals the presence of two molecular functions. An N-terminal 608-amino acid (nonkinase) portion of the protein supports robust checkpoint activity, and, as expected, contributes to chromosome segregation. A C-terminal kinase-encoding segment independently contributes to chromosome segregation through an unknown mechanism. Both molecular functions depend on association with Bub3p. A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay. An adjacent segment is required for Mad1p binding, detected by deletion analysis and coimmunoprecipitation. Finally, overexpression of wild-type BUB1 or MAD3 genes leads to chromosome instability. Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage.

Distinct Chromosome Segregation Roles for Spindle Checkpoint Proteins

PubMed Central

Warren, Cheryl D.; Brady, D. Michelle; Johnston, Raymond C.; Hanna, Joseph S.; Hardwick, Kevin G.; Spencer, Forrest A.

2002-01-01

The spindle checkpoint plays a central role in the fidelity of chromosome transmission by ensuring that anaphase is initiated only after kinetochore-microtubule associations of all sister chromatid pairs are complete. In this study, we find that known spindle checkpoint proteins do not contribute equally to chromosome segregation fidelity in Saccharomyces cerevisiae. Loss of Bub1 or Bub3 protein elicits the largest effect. Analysis of Bub1p reveals the presence of two molecular functions. An N-terminal 608-amino acid (nonkinase) portion of the protein supports robust checkpoint activity, and, as expected, contributes to chromosome segregation. A C-terminal kinase-encoding segment independently contributes to chromosome segregation through an unknown mechanism. Both molecular functions depend on association with Bub3p. A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay. An adjacent segment is required for Mad1p binding, detected by deletion analysis and coimmunoprecipitation. Finally, overexpression of wild-type BUB1 or MAD3 genes leads to chromosome instability. Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage. PMID:12221113

Rapid Evolution of a Coadapted Gene Complex: Evidence from the Segregation Distorter (Sd) System of Meiotic Drive in Drosophila Melanogaster

PubMed Central

Palopoli, M. F.; Wu, C. I.

1996-01-01

Segregation Distorter (SD) is a system of meiotic drive found in natural populations of Drosophila melanogaster. Males heterozygous for an SD second chromosome and a normal homologue (SD(+)) produce predominantly SD-bearing sperm. The coadapted gene complex responsible for this transmission advantage spans the second chromosome centromere, consisting of three major and several minor interacting loci. To investigate the evolutionary history of this system, we surveyed levels of polymorphism and divergence at six genes that together encompass this pericentromeric region and span seven map units. Interestingly, there was no discernible divergence between SD and SD(+) chromosomes for any of these molecular markers. Furthermore, SD chromosomes harbored much less polymorphism than did SD(+) chromosomes. The results suggest that the SD system evolved recently, swept to appreciable frequencies worldwide, and carried with it the entire second chromosome centromeric region (roughly 10% of the genome). Despite its well-documented genetic complexity, this coadapted system appears to have evolved on a time scale that is much shorter than can be gauged using nucleotide substitution data. Finally, the large genomic region hitchhiking with SD indicates that a multilocus, epistatically selected system could affect the levels of DNA polymorphism observed in regions of reduced recombination. PMID:8844155

Effect of sex, age and genetics on crossover interference in cattle

PubMed Central

Wang, Zhiying; Shen, Botong; Jiang, Jicai; Li, Jinquan; Ma, Li

2016-01-01

Crossovers generated by homologous recombination ensure proper chromosome segregation during meiosis. Crossover interference results in chiasmata being more evenly distributed along chromosomes, but the mechanism underlying crossover interference remains elusive. Based on large pedigrees of Holstein and Jersey cattle with genotype data, we extracted three-generation families, including 147,327 male and 71,687 female meioses in Holstein, and 108,163 male and 37,008 female meioses in Jersey, respectively. We identified crossovers in these meioses and fitted the Housworth-Stahl “interference-escape” model to study crossover interference patterns in the cattle genome. Our result reveals that the degree of crossover interference is stronger in females than in males. We found evidence for inter-chromosomal variation in the level of crossover interference, with smaller chromosomes exhibiting stronger interference. In addition, crossover interference levels decreased with maternal age. Finally, sex-specific GWAS analyses identified one locus near the NEK9 gene on chromosome 10 to have a significant effect on crossover interference levels. This locus has been previously associated with recombination rate in cattle. Collectively, this large-scale analysis provided a comprehensive description of crossover interference across chromosome, sex and age groups, identified associated candidate genes, and produced useful insights into the mechanism of crossover interference. PMID:27892966

7 CFR 614.7 - Preliminary technical determinations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Preliminary technical determinations. 614.7 Section... Preliminary technical determinations. (a) A preliminary technical determination becomes final 30 days after... purpose of gathering additional information and discussing the facts relating to the preliminary technical...

Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia

PubMed Central

Papaemmanuil, Elli; Robinson, Hazel M.; Jacobs, Patricia; Moorman, Anthony V.; Dyer, Sara; Borrow, Julian; Griffiths, Mike; Heerema, Nyla A.; Carroll, Andrew J.; Talley, Polly; Bown, Nick; Telford, Nick; Ross, Fiona M.; Gaunt, Lorraine; McNally, Richard J. Q.; Young, Bryan D.; Sinclair, Paul; Rand, Vikki; Teixeira, Manuel R.; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Dastugue, Nicole; Vandenberghe, Peter; Stephens, Philip J.; Cheng, Jiqiu; Van Loo, Peter; Stratton, Michael R.

2014-01-01

Changes in gene dosage are a major driver of cancer, engineered from a finite, but increasingly well annotated, repertoire of mutational mechanisms1. This can potentially generate correlated copy number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21)2,3. We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. We find that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have ~2700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimised for leukemic potential, showing constrained copy number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can co-ordinate to fashion copy number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. PMID:24670643

Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

PubMed

Li, Yilong; Schwab, Claire; Ryan, Sarra; Papaemmanuil, Elli; Robinson, Hazel M; Jacobs, Patricia; Moorman, Anthony V; Dyer, Sara; Borrow, Julian; Griffiths, Mike; Heerema, Nyla A; Carroll, Andrew J; Talley, Polly; Bown, Nick; Telford, Nick; Ross, Fiona M; Gaunt, Lorraine; McNally, Richard J Q; Young, Bryan D; Sinclair, Paul; Rand, Vikki; Teixeira, Manuel R; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Dastugue, Nicole; Vandenberghe, Peter; Stephens, Philip J; Cheng, Jiqiu; Van Loo, Peter; Stratton, Michael R; Campbell, Peter J; Harrison, Christine J

2014-04-03

Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

A cytological approach to study meiotic recombination and chromosome dynamics of Arabidopsis thaliana male meiocytes in three dimensions.

PubMed

Hurel, Aurélie; Phillips, Dylan; Vrielynck, Nathalie; Mézard, Christine; Grelon, Mathilde; Christophorou, Nicolas

2018-04-22

During meiotic prophase I chromosomes undergo dramatic conformational changes that accompany chromosome condensation, pairing and recombination between homologs. These changes include the anchoring of telomeres to the nuclear envelope and their clustering to form a bouquet. In plants, these events have been studied and illustrated in intact meiocytes of large genome species. Arabidopsis thaliana is an excellent genetic model where major molecular pathways that control synapsis and recombination between homologs have been uncovered. Yet the study of chromosome dynamics is hampered by current cytological methods that disrupt the 3D architecture of the nucleus. Here we set up a protocol to preserve the 3D configuration of A. thaliana meiocytes. We showed that this technique is compatible with the use of a variety of antibodies that label structural and recombination proteins and were able to highlight the presence of clustered synapsis initiation centers at the nuclear periphery. By using fluorescence in situ hybridization (FISH) we also studied chromosome behavior during premeiotic G2 and prophase I, revealing the existence of a telomere bouquet during A. thaliana male meiosis. In addition we showed that the number of telomeres in a bouquet and its volume vary greatly thus revealing the complexity of telomere behavior during meiotic prophase I. Finally, by using probes that label subtelomeric regions of individual chromosomes we revealed differential localization behaviors of chromosome ends. Our protocol opens new areas of research to investigate chromosome dynamics in A. thaliana meiocytes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution.

PubMed

Guillén, Yolanda; Ruiz, Alfredo

2012-02-01

Chromosomal inversions have been pervasive during the evolution of the genus Drosophila, but there is significant variation between lineages in the rate of rearrangement fixation. D. mojavensis, an ecological specialist adapted to a cactophilic niche under extreme desert conditions, is a chromosomally derived species with ten fixed inversions, five of them not present in any other species. In order to explore the causes of the rapid chromosomal evolution in D. mojavensis, we identified and characterized all breakpoints of seven inversions fixed in chromosome 2, the most dynamic one. One of the inversions presents unequivocal evidence for its generation by ectopic recombination between transposon copies and another two harbor inverted duplications of non-repetitive DNA at the two breakpoints and were likely generated by staggered single-strand breaks and repair by non-homologous end joining. Four out of 14 breakpoints lay in the intergenic region between preexisting duplicated genes, suggesting an adaptive advantage of separating previously tightly linked duplicates. Four out of 14 breakpoints are associated with transposed genes, suggesting these breakpoints are fragile regions. Finally two inversions contain novel genes at their breakpoints and another three show alterations of genes at breakpoints with potential adaptive significance. D. mojavensis chromosomal inversions were generated by multiple mechanisms, an observation that does not provide support for increased mutation rate as explanation for rapid chromosomal evolution. On the other hand, we have found a number of gene alterations at the breakpoints with putative adaptive consequences that directly point to natural selection as the cause of D. mojavensis rapid chromosomal evolution.

Genetics of the connective tissue proteins: Assignment of the gene for human type I procollagen to chromosome 17 by analysis of cell hybrids and microcell hybrids*

PubMed Central

Raj, Cholappadi V. Sundar; Church, Robert L.; Klobutcher, Lawrence A.; Ruddle, Frank H.

1977-01-01

Somatic cell hybrids between mouse and human cell lines have been used to identify the specific chromosome that governs the synthesis of type I procollagen. Fourteen hybrid clones and subclones were derived independently from crosses between mouse parents [LM (thymidine kinase-negative) or A9 (hypoxanthine phosphoribosyltransferase-negative)] and human cells (human diploid lung fibroblasts WI-38 or diploid skin fibroblasts GM5, GM17, and GM9). The cultures were labeled with [3H]proline in modified Eagle's medium without serum. Radioactive procollagens were purified from the medium by the method of Church et al. [(1974) J. Mol. Biol. 86, 785-799]. DEAE-cellulose chromatography was used to separate collagen and type I and type III procollagen. Human type I procollagen was assayed by double immunodiffusion analysis with type I procollagen antibodies prepared by immunizing rabbits with purified human type I procollagen. These analyses combined with karyology and isozyme analyses of each hybrid line have produced evidence for the assignment of the gene for human type I procollagen to chromosome 17. A human microcell-mouse hybrid cell line containing only human chromosome 17 was positive for human type I procollagen, lending further support to the assignment of the human type I procollagen gene to chromosome 17. Finally, by using a hybrid line containing only the long arm of human chromosome 17 translocated onto a mouse chromosome, the type I procollagen gene can be assigned more specifically to the long arm of chromosome 17. Images PMID:412188

Programs of Study as a State Policy Mandate: A Longitudinal Study of the South Carolina Personal Pathways to Success Initiative. Final Technical Report: Major Findings and Implications

ERIC Educational Resources Information Center

Hammond, Cathy; Drew, Sam F.; Withington, Cairen; Griffith, Cathy; Swiger, Caroline M.; Mobley, Catherine; Sharp, Julia L.; Stringfield, Samuel C.; Stipanovic, Natalie; Daugherty, Lindsay

2013-01-01

This is the final technical report from the National Research Center for Career and Technical Education's (NRCCTE's) five-year longitudinal study of South Carolina's Personal Pathway to Success initiative, which was authorized by the state's Education and Economic Development Act (EEDA) in 2005. NRCCTE-affiliated researchers at the National…

Direct Final Rule: Nonroad Diesel Technical Amendments and Tier 3 Technical Relief Provision

EPA Pesticide Factsheets

Rule making certain technical corrections to the rules establishing emission standards for nonroad diesel engines and amending those rules to provide manufacturers with a production technical relief provision for Tier 3 equipment.

Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study.

PubMed

Inaba, Yoshimi; Herlihy, Amy S; Schwartz, Charles E; Skinner, Cindy; Bui, Quang M; Cobb, Joanna; Shi, Elva Z; Francis, David; Arvaj, Alison; Amor, David J; Pope, Kate; Wotton, Tiffany; Cohen, Jonathan; Hewitt, Jacqueline K; Hagerman, Randi J; Metcalfe, Sylvia A; Hopper, John L; Loesch, Danuta Z; Slater, Howard R; Godler, David E

2013-04-01

We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening. Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls. At the 0.435 threshold, fragile X-related epigenetic element 2 analysis in males was robust on both blood DNA and newborn blood spots, with specificity and sensitivity of ~100% for full-mutation genotype. In females, the specificity was 99%, whereas half of full-mutation females were above the 0.435 threshold in both blood DNA and newborn blood spots. Furthermore, at this threshold, the test could not differentiate individuals with Klinefelter syndrome from female controls without using the SRY marker. When combined with SRY analysis, the test was consistent with most results for sex chromosome aneuploidies from karyotyping. Setting specific thresholds for fragile X-related epigenetic element 2 analysis and including the SRY marker provides the option to either include or exclude detection of sex chromosome aneuploidies as part of fragile X syndrome newborn screening.

If the cap fits, wear it: an overview of telomeric structures over evolution.

PubMed

Fulcher, Nick; Derboven, Elisa; Valuchova, Sona; Riha, Karel

2014-03-01

Genome organization into linear chromosomes likely represents an important evolutionary innovation that has permitted the development of the sexual life cycle; this process has consequently advanced nuclear expansion and increased complexity of eukaryotic genomes. Chromosome linearity, however, poses a major challenge to the internal cellular machinery. The need to efficiently recognize and repair DNA double-strand breaks that occur as a consequence of DNA damage presents a constant threat to native chromosome ends known as telomeres. In this review, we present a comparative survey of various solutions to the end protection problem, maintaining an emphasis on DNA structure. This begins with telomeric structures derived from a subset of prokaryotes, mitochondria, and viruses, and will progress into the typical telomere structure exhibited by higher organisms containing TTAGG-like tandem sequences. We next examine non-canonical telomeres from Drosophila melanogaster, which comprise arrays of retrotransposons. Finally, we discuss telomeric structures in evolution and possible switches between canonical and non-canonical solutions to chromosome end protection.

Polymer physics of chromosome large-scale 3D organisation

NASA Astrophysics Data System (ADS)

Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

2016-07-01

Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins

PubMed Central

Kim, Yumi; Rosenberg, Scott C.; Kugel, Christine L.; Kostow, Nora; Rog, Ofer; Davydov, Vitaliy; Su, Tiffany Y.; Dernburg, Abby F.; Corbett, Kevin D.

2014-01-01

Summary Proteins of the HORMA domain family play central but poorly understood roles in chromosome organization and dynamics during meiosis. In C. elegans, four such proteins (HIM-3, HTP-1, HTP-2, and HTP-3) have distinct but overlapping functions. Through combined biochemical, structural, and in vivo analysis, we find that these proteins form hierarchical complexes through binding of their HORMA domains to cognate peptides within their partners’ C-terminal tails, analogous to the “safety belt” binding mechanism of Mad2. These interactions are critical for recruitment of HIM-3, HTP-1, and HTP-2 to chromosome axes. HTP-3, in addition to recruiting the other HORMA domain proteins to the axis, plays an independent role in sister chromatid cohesion and double-strand break formation. Finally, we find that mammalian HORMAD1 binds a peptide motif found both at its own C-terminus and that of HORMAD2, indicating that this mode of intermolecular association is a conserved feature of meiotic chromosome structure in eukaryotes. PMID:25446517

Could Digital PCR Be an Alternative as a Non-Invasive Prenatal Test for Trisomy 21: A Proof of Concept Study.

PubMed

El Khattabi, Laïla Allach; Rouillac-Le Sciellour, Christelle; Le Tessier, Dominique; Luscan, Armelle; Coustier, Audrey; Porcher, Raphael; Bhouri, Rakia; Nectoux, Juliette; Sérazin, Valérie; Quibel, Thibaut; Mandelbrot, Laurent; Tsatsaris, Vassilis; Vialard, François; Dupont, Jean-Michel

2016-01-01

NIPT for fetal aneuploidy by digital PCR has been hampered by the large number of PCR reactions needed to meet statistical requirements, preventing clinical application. Here, we designed an octoplex droplet digital PCR (ddPCR) assay which allows increasing the number of available targets and thus overcomes statistical obstacles. After technical optimization of the multiplex PCR on mixtures of trisomic and euploid DNA, we performed a validation study on samples of plasma DNA from 213 pregnant women. Molecular counting of circulating cell-free DNA was performed using a mix of hydrolysis probes targeting chromosome 21 and a reference chromosome. The results of our validation experiments showed that ddPCR detected trisomy 21 even when the sample's trisomic DNA content is as low as 5%. In a validation study of plasma samples from 213 pregnant women, ddPCR discriminated clearly between the trisomy 21 and the euploidy groups. Our results demonstrate that digital PCR can meet the requirements for non-invasive prenatal testing of trisomy 21. This approach is technically simple, relatively cheap, easy to implement in a diagnostic setting and compatible with ethical concerns regarding access to nucleotide sequence information. These advantages make it a potential technique of choice for population-wide screening for trisomy 21 in pregnant women.

Mapping our genes: The genome projects: How big, how fast

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

For the past 2 years, scientific and technical journals in biology and medicine have extensively covered a debate about whether and how to determine the function and order of human genes on human chromosomes and when to determine the sequence of molecular building blocks that comprise DNA in those chromosomes. In 1987, these issues rose to become part of the public agenda. The debate involves science, technology, and politics. Congress is responsible for /open quotes/writing the rules/close quotes/ of what various federal agencies do and for funding their work. This report surveys the points made so far in the debate,more » focusing on those that most directly influence the policy options facing the US Congress. Congressional interest focused on how to assess the rationales for conducting human genome projects, how to fund human genome projects (at what level and through which mechanisms), how to coordinate the scientific and technical programs of the several federal agencies and private interests already supporting various genome projects, and how to strike a balance regarding the impact of genome projects on international scientific cooperation and international economic competition in biotechnology. OTA prepared this report with the assistance of several hundred experts throughout the world. 342 refs., 26 figs., 11 tabs.« less

Insights into the karyotype evolution and speciation of the beetle Euchroma gigantea (Coleoptera: Buprestidae).

PubMed

Xavier, Crislaine; Soares, Rógean Vinícius Santos; Amorim, Igor Costa; Cabral-de-Mello, Diogo Cavalcanti; de Cássia de Moura, Rita

2018-03-09

Euchroma Dejean, 1833 (Buprestidae: Coleoptera) is a monotypic genus comprising the species Euchroma gigantea, with populations presenting a degree of karyotypic variation/polymorphism rarely found within a single taxonomic (specific) unit, as well as drastically incompatible meiotic configurations in populations from extremes of the species range. To better understand the complex karyotypic evolution of E. gigantea, the karyotypes of specimens from five populations in Brazil were investigated using molecular cytogenetics and phylogenetic approaches. Herein, we used FISH with histone genes as well as sequencing of the COI to determine differential distribution of markers and relationships among populations. The analyses revealed new karyotypes, with variability for chromosome number and morphology of multiple sex chromosome mechanisms, occurrence of B chromosome variants (punctiform and large ones), and high dispersion of histone genes in different karyotypes. These data indicate that chromosomal polymorphism in E. gigantea is greater than previously reported, and that the species can be a valuable model for cytogenetic studies. The COI phylogenetic and haplotype analyses highlighted the formation of three groups with chromosomally polymorphic individuals. Finally, we compared the different karyotypes and proposed a model for the chromosomal evolution of this species. The species E. gigantea includes at least three cytogenetically polymorphic lineages. Moreover, in each of these lineages, different chromosomal rearrangements have been fixed. Dispersion of repetitive sequences may have favored the high frequency of these rearrangements, which could be related to both adaptation of the species to different habitats and the speciation process.

Y-Chromosome Haplogroups in the Bosnian-Herzegovinian Population Based on 23 Y-STR Loci.

PubMed

Doğan, Serkan; Ašić, Adna; Doğan, Gulsen; Besic, Larisa; Marjanovic, Damir

2016-07-01

In a study of the Bosnian-Herzegovinian (B&H) population, Y-chromosome marker frequencies for 100 individuals, generated using the PowerPlex Y23 kit, were used to perform Y-chromosome haplogroup assignment via Whit Athey's Haplogroup Predictor. This algorithm determines Y-chromosome haplogroups from Y-chromosome short tandem repeat (Y-STR) data using a Bayesian probability-based approach. The most frequent haplogroup appeared to be I2a, with a prevalence of 49%, followed by R1a and E1b1b, each accounting for 17% of all haplogroups within the population. Remaining haplogroups were J2a (5%), I1 (4%), R1b (4%), J2b (2%), G2a (1%), and N (1%). These results confirm previously published preliminary B&H population data published over 10 years ago, especially the prediction about the B&H population being a part of the Western Balkan area, which served as the Last Glacial Maximum refuge for the Paleolithic human European population. Furthermore, the results corroborate the hypothesis that this area was a significant stopping point on the "Middle East-Europe highway" during the Neolithic farmer migrations. Finally, since these results are almost completely in accordance with previously published data on B&H and neighboring populations generated by Y-chromosome single nucleotide polymorphism analysis, it can be concluded that in silico analysis of Y-STRs is a reliable method for approximation of the Y-chromosome haplogroup diversity of an examined population.

Thirty years of Batten disease research: present status and future goals.

PubMed

Rider, J A; Rider, D L

1999-04-01

From a meager beginning in 1968, when Batten disease or neuronal ceroid lipofuscinosis was practically unheard of, tremendous advances have been made. It is now recognized worldwide as the most common neurodegenerative disease in children and young adults. It is recognized as a genetic disease. The infantile form has been localized to chromosome 1 p32 and the juvenile form, to 16p12.1; the gene for the late infantile is on chromosome 11p15 and for a variant form of the late infantile, the gene lies on chromosome 15q21-23. Finally, the molecular basis of the late infantile form is probably a pepstatin-insensitive lysomal peptidase. The future is to identify carriers, prevent the disease, and develop treatment by gene and enzyme replacement. Copyright 1999 Academic Press.

Polarized light scattering as a probe for changes in chromosome structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, Daniel Benjamin

1993-10-01

Measurements and calculations of polarized light scattering are applied to chromosomes. Calculations of the Mueller matrix, which completely describes how the polarization state of light is altered upon scattering, are developed for helical structures related to that of chromosomes. Measurements of the Mueller matrix are presented for octopus sperm heads, and dinoflagellates. Comparisons of theory and experiment are made. A working theory of polarized light scattering from helices is developed. The use of the first Born approximation vs the coupled dipole approximation are investigated. A comparison of continuous, calculated in this work, and discrete models is also discussed. By comparingmore » light scattering measurements with theoretical predictions the average orientation of DNA in an octopus sperm head is determined. Calculations are made for the Mueller matrix of DNA plectonemic helices at UV, visible and X-ray wavelengths. Finally evidence is presented that the chromosomes of dinoflagellates are responsible for observed differential scattering of circularly-polarized light. This differential scattering is found to vary in a manner that is possibly correlated to the cell cycle of the dinoflagellates. It is concluded that by properly choosing the wavelength probe polarized light scattering can provide a useful tool to study chromosome structure.« less

Scc2 regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis

PubMed Central

Lin, Weiqiang; Jin, Hui; Liu, Xiuwen; Hampton, Kristin; Yu, Hong-Guo

2011-01-01

To tether sister chromatids, a protein-loading complex, including Scc2, recruits cohesin to the chromosome at discrete loci. Cohesin facilitates the formation of a higher-order chromosome structure that could also influence gene expression. How cohesin directly regulates transcription remains to be further elucidated. We report that in budding yeast Scc2 is required for sister-chromatid cohesion during meiosis for two reasons. First, Scc2 is required for activating the expression of REC8, which encodes a meiosis-specific cohesin subunit; second, Scc2 is necessary for recruiting meiotic cohesin to the chromosome to generate sister-chromatid cohesion. Using a heterologous reporter assay, we have found that Scc2 increases the activity of its target promoters by recruiting cohesin to establish an upstream cohesin-associated region in a position-dependent manner. Rec8-associated meiotic cohesin is required for the full activation of the REC8 promoter, revealing that cohesin has a positive feedback on transcriptional regulation. Finally, we provide evidence that chromosomal binding of cohesin is sufficient for target-gene activation during meiosis. Our data support a noncanonical role for cohesin as a transcriptional activator during cell differentiation. PMID:21508318

Constructing a 'Chromonome' of Yellowtail (Seriola quinqueradiata) for Comparative Analysis of Chromosomal Rearrangements

PubMed Central

Kawase, Junya; Aoki, Jun-ya; Araki, Kazuo

2018-01-01

To investigate chromosome evolution in fish species, we newly mapped 181 markers that allowed us to construct a yellowtail (Seriola quinqueradiata) radiation hybrid (RH) physical map with 1,713 DNA markers, which was far denser than a previous map, and we anchored the de novo assembled sequences onto the RH physical map. Finally, we mapped a total of 13,977 expressed sequence tags (ESTs) on a genome sequence assembly aligned with the physical map. Using the high-density physical map and anchored genome sequences, we accurately compared the yellowtail genome structure with the genome structures of five model fishes to identify characteristics of the yellowtail genome. Between yellowtail and Japanese medaka (Oryzias latipes), almost all regions of the chromosomes were conserved and some blocks comprising several markers were translocated. Using the genome information of the spotted gar (Lepisosteus oculatus) as a reference, we further documented syntenic relationships and chromosomal rearrangements that occurred during evolution in four other acanthopterygian species (Japanese medaka, zebrafish, spotted green pufferfish and three-spined stickleback). The evolutionary chromosome translocation frequency was 1.5-2-times higher in yellowtail than in medaka, pufferfish, and stickleback. PMID:29290830

Cryptic breakpoint identified by whole-genome mate-pair sequencing in a rare paternally inherited complex chromosomal rearrangement.

PubMed

Aristidou, Constantia; Theodosiou, Athina; Ketoni, Andria; Bak, Mads; Mehrjouy, Mana M; Tommerup, Niels; Sismani, Carolina

2018-01-01

Precise characterization of apparently balanced complex chromosomal rearrangements in non-affected individuals is crucial as they may result in reproductive failure, recurrent miscarriages or affected offspring. We present a family, where the non-affected father and daughter were found, using FISH and karyotyping, to be carriers of a three-way complex chromosomal rearrangement [t(6;7;10)(q16.2;q34;q26.1), de novo in the father]. The family suffered from two stillbirths, one miscarriage, and has a son with severe intellectual disability. In the present study, the family was revisited using whole-genome mate-pair sequencing. Interestingly, whole-genome mate-pair sequencing revealed a cryptic breakpoint on derivative (der) chromosome 6 rendering the rearrangement even more complex. FISH using a chromosome (chr) 6 custom-designed probe and a chr10 control probe confirmed that the interstitial chr6 segment, created by the two chr6 breakpoints, was translocated onto der(10). Breakpoints were successfully validated with Sanger sequencing, and small imbalances as well as microhomology were identified. Finally, the complex chromosomal rearrangement breakpoints disrupted the SIM1 , GRIK2 , CNTNAP2 , and PTPRE genes without causing any phenotype development. In contrast to the majority of maternally transmitted complex chromosomal rearrangement cases, our study investigated a rare case where a complex chromosomal rearrangement, which most probably resulted from a Type IV hexavalent during the pachytene stage of meiosis I, was stably transmitted from a fertile father to his non-affected daughter. Whole-genome mate-pair sequencing proved highly successful in identifying cryptic complexity, which consequently provided further insight into the meiotic segregation of chromosomes and the increased reproductive risk in individuals carrying the specific complex chromosomal rearrangement. We propose that such complex rearrangements should be characterized in detail using a combination of conventional cytogenetic and NGS-based approaches to aid in better prenatal preimplantation genetic diagnosis and counseling in couples with reproductive problems.

Gametocidal Factor Transferred from Aegilops geniculata Roth Can Be Adapted for Large-Scale Chromosome Manipulations in Cereals

PubMed Central

Kwiatek, Michał T.; Wiśniewska, Halina; Ślusarkiewicz-Jarzina, Aurelia; Majka, Joanna; Majka, Maciej; Belter, Jolanta; Pudelska, Hanna

2017-01-01

Segregation distorters are curious, evolutionarily selfish genetic elements, which distort Mendelian segregation in their favor at the expense of others. Those agents include gametocidal factors (Gc), which ensure their preferential transmission by triggering damages in cells lacking them via chromosome break induction. Hence, we hypothesized that the gametocidal system can be adapted for chromosome manipulations between Triticum and Secale chromosomes in hexaploid triticale (×Triticosecale Wittmack). In this work we studied the little-known gametocidal action of a Gc factor located on Aegilops geniculata Roth chromosome 4Mg. Our results indicate that the initiation of the gametocidal action takes place at anaphase II of meiosis of pollen mother cells. Hence, we induced androgenesis at postmeiotic pollen divisions (via anther cultures) in monosomic 4Mg addition plants of hexaploid triticale (AABBRR) followed by production of doubled haploids, to maintain the chromosome aberrations caused by the gametocidal action. This approach enabled us to obtain a large number of plants with two copies of particular chromosome translocations, which were identified by the use of cytomolecular methods. We obtained 41 doubled haploid triticale lines and 17 of them carried chromosome aberrations that included plants with the following chromosome sets: 40T+Dt2RS+Dt2RL (5 lines), 40T+N2R (1), 38T+D4RS.4BL (3), 38T+D5BS-5BL.5RL (5), and 38T+D7RS.3AL (3). The results show that the application of the Gc mechanism in combination with production of doubled haploid lines provides a sufficiently large population of homozygous doubled haploid individuals with two identical copies of translocation chromosomes. In our opinion, this approach will be a valuable tool for the production of novel plant material, which could be used for gene tracking studies, genetic mapping, and finally to enhance the diversity of cereals. PMID:28396677

FISH-Based Analysis of Clonally Derived CHO Cell Populations Reveals High Probability for Transgene Integration in a Terminal Region of Chromosome 1 (1q13).

PubMed

Li, Shengwei; Gao, Xiaoping; Peng, Rui; Zhang, Sheng; Fu, Wei; Zou, Fangdong

A basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. Here, we constructed engineered Chinese hamster ovary cell lines (CHO-S) with a pCHO-hVR1 vector that carried an extracellular domain of a VEGF receptor (VR) fusion gene. Forty-five clones with high hVR1 expression were selected for karyotype analysis. Using fluorescence in situ hybridization (FISH) and G-banding, we found that pCHO-hVR1 was integrated into three chromosomes, including chromosomes 1, Z3 and Z4. Four clones were selected to evaluate their productivity under non-fed, non-optimized shake flask conditions. The results showed that clones 1 and 2 with integration sites on chromosome 1 revealed high levels of hVR1 products (shake flask of approximately 800 mg/L), whereas clones 3 and 4 with integration sites on chromosomes Z3 or Z4 had lower levels of hVR1 products. Furthermore, clones 1 and 2 maintained their productivity stabilities over a continuous period of 80 generations, and clones 3 and 4 showed significant declines in their productivities in the presence of selection pressure. Finally, pCHO-hVR1 localized to the same region at chromosome 1q13, the telomere region of normal chromosome 1. In this study, these results demonstrate that the integration of exogenous hVR1 gene on chromosome 1, band q13, may create a high protein-producing CHO-S cell line, suggesting that chromosome 1q13 may contain a useful target site for the high expression of exogenous protein. This study shows that the integration into the target site of chromosome 1q13 may avoid the problems of random integration that cause gene silencing or also overcome position effects, facilitating exogenous gene expression in CHO-S cells.

Arizona Deafblind Project, 1995-1999. Final Report.

ERIC Educational Resources Information Center

Arizona State School for the Deaf and Blind, Tucson.

This final report describes accomplishments of the four-year federally funded Arizona Deafblind Project which attempted to: (1) identify all deafblind children in Arizona; (2) deliver technical assistance to families; (3) deliver technical assistance to service providers; and (4) enhance community oversight, coordination, and collaboration with…

Joint Common Architecture Demonstration (JCA Demo) Final Report

DTIC Science & Technology

2016-07-28

approach for implementing open systems [16], formerly known as the Modular Open Systems Approach (MOSA). OSA is a business and technical strategy to... TECHNICAL REPORT RDMR-AD-16-01 JOINT COMMON ARCHITECTURE DEMONSTRATION (JCA DEMO) FINAL REPORT Scott A. Wigginton... Modular Avionics .......................................................................... 5 E. Model-Based Engineering

Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.

PubMed

Darrow, Emily M; Huntley, Miriam H; Dudchenko, Olga; Stamenova, Elena K; Durand, Neva C; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P; Lander, Eric S; Chadwick, Brian P; Aiden, Erez Lieberman

2016-08-02

During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging.

Distinct chromatin environment associated with phosphorylated H3S10 histone during pollen mitosis I in orchids.

PubMed

Sharma, Santosh Kumar; Yamamoto, Maki; Mukai, Yasuhiko

2017-01-01

Pollen developmental pathway in plants involving synchronized transferal of cellular divisions from meiosis (microsporogenesis) to mitosis (pollen mitosis I/II) eventually offers a unique "meiosis-mitosis shift" at pollen mitosis I. Since the cell type (haploid microspore) and fate of pollen mitosis I differ from typical mitosis (in meristem cells), it is immensely important to analyze the chromosomal distribution of phosphorylated H3S10 histone during atypical pollen mitosis I to comprehend the role of histone phosphorylation in pollen development. We investigated the chromosomal phosphorylation of H3S10 histone during pollen mitosis I in orchids using immunostaining technique. The chromosomal distribution of H3S10ph during pollen mitosis I revealed differential pattern than that of typical mitosis in plants, however, eventually following the similar trends of mitosis in animals where H3S10 phosphorylation begins in the pericentromeric regions first, later extending to the whole chromosomes, and finally declining at anaphase/early cytokinesis (differentiation of vegetative and generative cells). The study suggests that the chromosomal distribution of H3S10ph during cell division is not universal and can be altered between different cell types encoded for diverse cellular processes. During pollen development, phosphorylation of histone might play a critical role in chromosome condensation events throughout pollen mitosis I in plants.

APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability

PubMed Central

Sansregret, Laurent; López-García, Carlos; Koch, André; McGranahan, Nicholas; Chao, William Chong Hang; Barry, David J.; Rowan, Andrew; Instrell, Rachael; Horswell, Stuart; Way, Michael; Howell, Michael; Singleton, Martin R.; Medema, René H.; Nurse, Paul; Petronczki, Mark; Swanton, Charles

2017-01-01

Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization. APC/C impairment caused adaptation to MPS1 inhibitors, revealing a likely resistance mechanism to therapies targeting the spindle assembly checkpoint. Finally, CRISPR-mediated introduction of cancer somatic mutations in the APC/C subunit cancer driver gene CDC27 reduces chromosome segregation errors, whereas reversal of an APC/C subunit nonsense mutation increases CIN. Subtle variations in mitotic duration, determined by APC/C activity, influence the extent of CIN, allowing cancer cells to dynamically optimize fitness during tumor evolution. Significance We report a mechanism whereby cancers balance the evolutionary advantages associated with CIN against the fitness costs caused by excessive genome instability, providing insight into the consequence of CDC27 APC/C subunit driver mutations in cancer. Lengthening of mitosis through APC/C modulation may be a common mechanism of resistance to cancer therapeutics that increase chromosome segregation errors. PMID:28069571

A 3,000-loci transcription map of chromosome 3B unravels the structural and functional features of gene islands in hexaploid wheat.

PubMed

Rustenholz, Camille; Choulet, Frédéric; Laugier, Christel; Safár, Jan; Simková, Hana; Dolezel, Jaroslav; Magni, Federica; Scalabrin, Simone; Cattonaro, Federica; Vautrin, Sonia; Bellec, Arnaud; Bergès, Hélène; Feuillet, Catherine; Paux, Etienne

2011-12-01

To improve our understanding of the organization and regulation of the wheat (Triticum aestivum) gene space, we established a transcription map of a wheat chromosome (3B) by hybridizing a newly developed wheat expression microarray with bacterial artificial chromosome pools from a new version of the 3B physical map as well as with cDNA probes derived from 15 RNA samples. Mapping data for almost 3,000 genes showed that the gene space spans the whole chromosome 3B with a 2-fold increase of gene density toward the telomeres due to an increase in the number of genes in islands. Comparative analyses with rice (Oryza sativa) and Brachypodium distachyon revealed that these gene islands are composed mainly of genes likely originating from interchromosomal gene duplications. Gene Ontology and expression profile analyses for the 3,000 genes located along the chromosome revealed that the gene islands are enriched significantly in genes sharing the same function or expression profile, thereby suggesting that genes in islands acquired shared regulation during evolution. Only a small fraction of these clusters of cofunctional and coexpressed genes was conserved with rice and B. distachyon, indicating a recent origin. Finally, genes with the same expression profiles in remote islands (coregulation islands) were identified suggesting long-distance regulation of gene expression along the chromosomes in wheat.

Chromosome-wide linkage disequilibrium caused by an inversion polymorphism in the white-throated sparrow (Zonotrichia albicollis).

PubMed

Huynh, L Y; Maney, D L; Thomas, J W

2011-04-01

Chromosomal inversions have been of long-standing interest to geneticists because they are capable of suppressing recombination and facilitating the formation of adaptive gene complexes. An exceptional inversion polymorphism (ZAL2(m)) in the white-throated sparrow (Zonotrichia albicollis) is linked to variation in plumage, social behavior and mate choice, and is maintained in the population by negative assortative mating. The ZAL2(m) polymorphism is a complex inversion spanning > 100 Mb and has been proposed to be a strong suppressor of recombination, as well as a potential model for studying neo-sex chromosome evolution. To quantify and evaluate these features of the ZAL2(m) polymorphism, we generated sequence from 8 ZAL2(m) and 16 ZAL2 chromosomes at 58 loci inside and 4 loci outside the inversion. Inside the inversion we found that recombination was completely suppressed between ZAL2 and ZAL2(m), resulting in uniformly high levels of genetic differentiation (F(ST)=0.94), the formation of two distinct haplotype groups representing the alternate chromosome arrangements and extensive linkage disequilibrium spanning ~104 Mb within the inversion, whereas gene flow was not suppressed outside the inversion. Finally, although ZAL2(m) homozygotes are exceedingly rare in the population, occurring at a frequency of < 1%, we detected evidence of historical recombination between ZAL2(m) chromosomes inside the inversion, refuting its potential status as a non-recombining autosome.

Guideline recommendations for diagnosis and clinical management of Ring14 syndrome-first report of an ad hoc task force.

PubMed

Rinaldi, Berardo; Vaisfeld, Alessandro; Amarri, Sergio; Baldo, Chiara; Gobbi, Giuseppe; Magini, Pamela; Melli, Erto; Neri, Giovanni; Novara, Francesca; Pippucci, Tommaso; Rizzi, Romana; Soresina, Annarosa; Zampini, Laura; Zuffardi, Orsetta; Crimi, Marco

2017-04-11

Ring chromosome 14 syndrome is a rare chromosomal disorder characterized by early onset refractory epilepsy, intellectual disability, autism spectrum disorder and a number of diverse health issues. The aim of this work is to provide recommendations for the diagnosis and management of persons affected by ring chromosome 14 syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years subjects affected by ring chromosome 14 syndrome. The literature search was performed in 2016. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. Conventional cytogenetics is the primary tool to identify a ring chromosome. Children with a terminal deletion of chromosome 14q ascertained by molecular karyotyping (CGH/SNP array) should be tested secondarily by conventional cytogenetics for the presence of a ring chromosome. Early diagnosis should be pursued in order to provide medical and social assistance by a multidisciplinary team. Clinical investigations, including neurophysiology for epilepsy, should be performed at the diagnosis and within the follow-up. Following the diagnosis, patients and relatives/caregivers should receive regular care for health and social issues. Epilepsy should be treated from the onset with anticonvulsive therapy. Likewise, feeding difficulties should be treated according to need. Nutritional assessment is recommended for all patients and nutritional support for malnourishment can include gastrostomy feeding in selected cases. Presence of autistic traits should be carefully evaluated. Many patients with ring chromosome 14 syndrome are nonverbal and thus maintaining their ability to communicate is always essential; every effort should be made to preserve their autonomy.

A novel approach for Escherichia coli genome editing combining in vivo cloning and targeted long-length chromosomal insertion.

PubMed

Hook, Ch D; Samsonov, V V; Ublinskaya, A A; Kuvaeva, T M; Andreeva, E V; Gorbacheva, L Yu; Stoynova, N V

2016-11-01

Despite the abundance of genetic manipulation approaches, particularly for Escherichia coli, new techniques and increased flexibility in the application of existing techniques are required to address novel aims. The most widely used approaches for chromosome editing are based on bacteriophage site-specific and λRed/RecET-mediated homologous recombination. In the present study, these techniques were combined to develop a novel approach for in vivo cloning and targeted long-length chromosomal insertion. This approach permits direct λRed-mediated cloning of DNA fragment with lengths of 10kb or greater from the E. coli chromosome into the plasmid vector pGL2, which carries the ori of pSC101, the ϕ80-attP site of ϕ80 phage, and an excisable Cm R marker bracketed by λ-attL/attR sites. In pGL2-based recombinant plasmids, the origin of replication can be eliminated in vitro via hydrolysis by SceI endonuclease and recircularization by DNA ligase. The resulting ori-less circular recombinant DNA can be used for targeted insertion of the cloned sequence into the chromosome at a selected site via ϕ80 phage-specific integrase-mediated recombination using the Dual-In/Out approach (Minaeva et al., 2008). At the final stage of chromosomal editing, the Cm R -marker can be excised from the chromosome due to expression of the λint/xis genes. Notably, the desired fragment can be inserted as multiple copies in the chromosome by combining insertions at different sites in one strain using the P1 general transduction technique (Moore, 2011). The developed approach is useful for the construction of plasmidless, markerless recombinant strains for fundamental and industrial purposes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution

PubMed Central

2012-01-01

Background Chromosomal inversions have been pervasive during the evolution of the genus Drosophila, but there is significant variation between lineages in the rate of rearrangement fixation. D. mojavensis, an ecological specialist adapted to a cactophilic niche under extreme desert conditions, is a chromosomally derived species with ten fixed inversions, five of them not present in any other species. Results In order to explore the causes of the rapid chromosomal evolution in D. mojavensis, we identified and characterized all breakpoints of seven inversions fixed in chromosome 2, the most dynamic one. One of the inversions presents unequivocal evidence for its generation by ectopic recombination between transposon copies and another two harbor inverted duplications of non-repetitive DNA at the two breakpoints and were likely generated by staggered single-strand breaks and repair by non-homologous end joining. Four out of 14 breakpoints lay in the intergenic region between preexisting duplicated genes, suggesting an adaptive advantage of separating previously tightly linked duplicates. Four out of 14 breakpoints are associated with transposed genes, suggesting these breakpoints are fragile regions. Finally two inversions contain novel genes at their breakpoints and another three show alterations of genes at breakpoints with potential adaptive significance. Conclusions D. mojavensis chromosomal inversions were generated by multiple mechanisms, an observation that does not provide support for increased mutation rate as explanation for rapid chromosomal evolution. On the other hand, we have found a number of gene alterations at the breakpoints with putative adaptive consequences that directly point to natural selection as the cause of D. mojavensis rapid chromosomal evolution. PMID:22296923

76 FR 80226 - Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... final rule, effective upon publication. Generally, the Administrative Procedure Act (APA) requires a.... Additionally, the APA requires that a final rule must have a delayed effective date of 30 days from the date of... delayed effective date requirement under the APA. 5 U.S.C. 553(d)(3). Again the technical change conforms...

"Type Ia Supernovae: Tools for Studying Dark Energy" Final Technical Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woosley, Stan; Kasen, Dan

2017-05-10

Final technical report for project "Type Ia Supernovae: Tools for the Study of Dark Energy" awarded jointly to scientists at the University of California, Santa Cruz and Berkeley, for computer modeling, theory and data analysis relevant to the use of Type Ia supernovae as standard candles for cosmology.

76 FR 50202 - National Technical Assistance and Dissemination Center for Children Who Are Deaf-Blind; Final...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... DEPARTMENT OF EDUCATION [CFDA No. 84.326T] National Technical Assistance and Dissemination Center for Children Who Are Deaf-Blind; Final Extension of Project Period and Waiver AGENCY: Office of Special Education Programs, Office of Special Education and Rehabilitative Services, Department of...

TADS Final Evaluation Report, 1980-81. Appendix S.

ERIC Educational Resources Information Center

Suarez, Tanya M.; And Others

The document contains the final report of the Technical Assistance Development System (TADS), a program which provided technical assistance (TA) services to 53 Handicapped Children's Early Education Program (HCEEP) demonstration projects and 13 State Implementation Grants (SIGs). The evaluation report is divided into five sections. Section 1…

High Points of Human Genetics

ERIC Educational Resources Information Center

Stern, Curt

1975-01-01

Discusses such high points of human genetics as the study of chromosomes, somatic cell hybrids, the population formula: the Hardy-Weinberg Law, biochemical genetics, the single-active X Theory, behavioral genetics and finally how genetics can serve humanity. (BR)

Human autoantibody to topoisomerase II.

PubMed

Hoffmann, A; Heck, M M; Bordwell, B J; Rothfield, N F; Earnshaw, W C

1989-02-01

The rheumatic diseases are characterized by the production of autoantibodies that are usually directed against components of the cell nucleus. In this communication, we describe autoantibodies that recognize DNA topoisomerase II (anti-topoII) present in the serum of a patient with systemic lupus erythematosus. Several lines of evidence indicate that this antibody recognizes topoisomerase II. First, it binds to the native enzyme in soluble extracts prepared from isolated chromosomes and effectively depletes such extracts of active enzyme. Second, the serum binds to topoisomerase II in immunoblots of mitotic chromosomes and chromosome scaffolds. Finally, the antiserum binds strongly to a fusion protein encoded by a cloned cDNA and expressed in Escherichia coli that (based on immunological evidence) represents the carboxy-terminal portion of chicken topoisomerase II. Autoantibodies such as the one described here may provide useful reagents for the study of human topoisomerase II.

Model of chromosomal loci dynamics in bacteria as fractional diffusion with intermittent transport

NASA Astrophysics Data System (ADS)

Gherardi, Marco; Calabrese, Ludovico; Tamm, Mikhail; Cosentino Lagomarsino, Marco

2017-10-01

The short-time dynamics of bacterial chromosomal loci is a mixture of subdiffusive and active motion, in the form of rapid relocations with near-ballistic dynamics. While previous work has shown that such rapid motions are ubiquitous, we still have little grasp on their physical nature, and no positive model is available that describes them. Here, we propose a minimal theoretical model for loci movements as a fractional Brownian motion subject to a constant but intermittent driving force, and compare simulations and analytical calculations to data from high-resolution dynamic tracking in E. coli. This analysis yields the characteristic time scales for intermittency. Finally, we discuss the possible shortcomings of this model, and show that an increase in the effective local noise felt by the chromosome associates to the active relocations.

A disseminated alveolar rhabdomyosarcoma in a 9-year-old boy disclosed by chromosomal translocation (2;13) (q35;q14)

PubMed

Brichard, B; Ninane, J; Gosseye, S; Verellen-Dumoulin, C; Vermylen, C; Rodhain, J; Cornu, G

1991-01-01

A 9-year-old boy presented with a small subcutaneous tumor of the trunk and diffuse bone marrow involvement. The first histological diagnosis given was undifferentiated malignancy possibly of neural crest origin and chemotherapy was started immediately using vincristine, cyclophosphamide, cisplatin, and teniposide (OPEC). Complete response was achieved after four courses of chemotherapy. Histological slides were then reviewed and the final diagnosis of alveolar rhabdomyosarcoma (RMS) was retained. Moreover, chromosome analysis of malignant cells in the bone marrow revealed a translocation involving chromosomes 2 and 13:t(2;13) (q35;q14). This specific karyotype finding has been recently reported in a few cases and could be specific for alveolar RMS. The patient had a relapse 7 months after diagnosis and died 4 months later.

Multipolar Spindle Pole Coalescence Is a Major Source of Kinetochore Mis-Attachment and Chromosome Mis-Segregation in Cancer Cells

PubMed Central

Silkworth, William T.; Nardi, Isaac K.; Scholl, Lindsey M.; Cimini, Daniela

2009-01-01

Many cancer cells display a CIN (Chromosome Instability) phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s) underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed γ-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells. PMID:19668340

TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability.

PubMed

Choi, Minji; Min, Yoo Hong; Pyo, Jaehyuk; Lee, Chang-Woo; Jang, Chang-Young; Kim, Ja-Eun

2017-06-01

Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle assembly checkpoint (SAC). Pharmacological inhibition of Mps1 has been suggested as a cancer therapeutic; however, despite the existence of a novel Mps1 inhibitor, TC Mps1 12, no such studies have been performed. The effects of TC Mps1 12 on cell viability, chromosome alignment, centrosome number, mitotic duration, apoptosis and SAC were determined in hepatocellular carcinoma (HCC) cells. In addition, the association of Mps1 expression with the overall survival of HCC patients was analysed. Treatment of human HCC cells with TC Mps1 12 led to chromosome misalignment and missegregation, and disorganization of centrosomes. Even in the presence of these errors, TC Mps1 12-treated cells overrode the SAC, resulting in a shortened mitotic duration and mitotic slippage. This mitotic catastrophe triggered apoptosis and, finally, inhibited the growth of HCC cells. In addition, the expression of the Mps1-encoding TTK gene was associated with poor overall survival of HCC patients. TC Mps1 12 results in the accumulation of chromosomal instabilities and mitotic catastrophe in HCC cells. Overall, these data demonstrate that the inhibition of Mps1 kinase using TC Mps1 12 is a promising therapeutic approach for liver cancer. © 2017 The British Pharmacological Society.

Nutritional supplement chromium picolinate generates chromosomal aberrations and impedes progeny development in Drosophila melanogaster.

PubMed

Stallings, Dontarie M; Hepburn, Dion D D; Hannah, Meredith; Vincent, John B; O'Donnell, Janis

2006-11-07

Chromium picolinate, [Cr(pic)(3)], is a popular nutritional supplement found in a variety of consumer products. Despite its popularity, safety concerns over its use have arisen. The supplement has been shown to generate clastogenic damage, mitochondrial damage, oxidative damage, and mutagenic effects in cultured cells and oxidative DNA damage and lipid peroxidation in rats. Recently [Cr(pic)(3)] has been demonstrated to generate heritable genetic change and delays in progeny development in Drosophila melanogaster. Based on the damage to chromosomes of cultured cells and of animal models, similar chromosome damage appeared to be a likely source of the mutagenic effects of the supplement in Drosophila. The current three-part study examines the effects of several chromium-containing supplements and their components on hatching and eclosion rates and success of development of first generation progeny of adult Drosophila fed food containing these compounds. It further examines the effects of the compounds on longevity of virgin male and female adults. Finally, the chromosomes in the salivary glands of Drosophila late in the third instar larval stage, which were the progeny of Drosophila whose diets were supplemented with nutritional levels of [Cr(pic)(3)], are shown to contain on average over one chromosomal aberration per two identifiable chromosomal arms. No aberrations were observed in chromosomes of progeny of untreated flies. The results suggest that human consumption of the supplement should be a matter of concern and continued investigation to provide insight into the requirements of chromium-containing supplements to give rise to genotoxic effects.

Homologous pairing and chromosome dynamics in meiosis and mitosis.

PubMed

McKee, Bruce D

2004-03-15

Pairing of homologous chromosomes is an essential feature of meiosis, acting to promote high levels of recombination and to ensure segregation of homologs. However, homologous pairing also occurs in somatic cells, most regularly in Dipterans such as Drosophila, but also to a lesser extent in other organisms, and it is not known how mitotic and meiotic pairing relate to each other. In this article, I summarize results of recent molecular studies of pairing in both mitosis and meiosis, focusing especially on studies using fluorescent in situ hybridization (FISH) and GFP-tagging of single loci, which have allowed investigators to assay the pairing status of chromosomes directly. These approaches have permitted the demonstration that pairing occurs throughout the cell cycle in mitotic cells in Drosophila, and that the transition from mitotic to meiotic pairing in spermatogenesis is accompanied by a dramatic increase in pairing frequency. Similar approaches in mammals, plants and fungi have established that with few exceptions, chromosomes enter meiosis unpaired and that chromosome movements involving the telomeric, and sometimes centromeric, regions often precede the onset of meiotic pairing. The possible roles of proteins involved in homologous recombination, synapsis and sister chromatid cohesion in homolog pairing are discussed with an emphasis on those for which mutant phenotypes have permitted an assessment of effects on homolog pairing. Finally, I consider the question of the distribution and identity of chromosomal pairing sites, using recent data to evaluate possible relationships between pairing sites and other chromosomal sites, such as centromeres, telomeres, promoters and heterochromatin. I cite evidence that may point to a relationship between matrix attachment sites and homologous pairing sites.

Insights into the genetic architecture of morphological traits in two passerine bird species.

PubMed

Silva, C N S; McFarlane, S E; Hagen, I J; Rönnegård, L; Billing, A M; Kvalnes, T; Kemppainen, P; Rønning, B; Ringsby, T H; Sæther, B-E; Qvarnström, A; Ellegren, H; Jensen, H; Husby, A

2017-09-01

Knowledge about the underlying genetic architecture of phenotypic traits is needed to understand and predict evolutionary dynamics. The number of causal loci, magnitude of the effects and location in the genome are, however, still largely unknown. Here, we use genome-wide single-nucleotide polymorphism (SNP) data from two large-scale data sets on house sparrows and collared flycatchers to examine the genetic architecture of different morphological traits (tarsus length, wing length, body mass, bill depth, bill length, total and visible badge size and white wing patches). Genomic heritabilities were estimated using relatedness calculated from SNPs. The proportion of variance captured by the SNPs (SNP-based heritability) was lower in house sparrows compared with collared flycatchers, as expected given marker density (6348 SNPs in house sparrows versus 38 689 SNPs in collared flycatchers). Indeed, after downsampling to similar SNP density and sample size, this estimate was no longer markedly different between species. Chromosome-partitioning analyses demonstrated that the proportion of variance explained by each chromosome was significantly positively related to the chromosome size for some traits and, generally, that larger chromosomes tended to explain proportionally more variation than smaller chromosomes. Finally, we found two genome-wide significant associations with very small-effect sizes. One SNP on chromosome 20 was associated with bill length in house sparrows and explained 1.2% of phenotypic variation (V P ), and one SNP on chromosome 4 was associated with tarsus length in collared flycatchers (3% of V P ). Although we cannot exclude the possibility of undetected large-effect loci, our results indicate a polygenic basis for morphological traits.

Preliminary study of effects of military obscurant smokes on flora and fauna during field and laboratory exposures. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaeffer, D.J.; Lower, W.R.; Kapila, S.

1986-12-01

Since continued routine use of obscurant smokes could be detrimental to the native flora and fauna of training sites, a preliminary biological and chemical study of smokes was conducted to determine whether tests could be developed to demonstrate measurable changes in organisms exposed to smokes and to evaluate whether short exposures to smokes produced measurable changes in the organisms tested. Fog oil, hexachloroethane, and tank diesel smokes were tested. Tradescantia clones were examined for mutagenic effects indicated by micronuclei induction in developing pollen and pink somatic mutations in stamen hairs. Photosynthetic perturbations were measured in Tradescantia and Ambrosia dumosa usingmore » variable fluorescence induction. Animals were examined for sister chromatid exchanges and chromosome aberrations. It was found that all of the smokes tested exerted varying degrees of physiological and mutagenic effects in one or several of the assay systems at one or more of the exposure distances. These studies indicate that exposed ecological systems, or at least components of these systems, are at a higher risk than are control organisms for several types of damage attributed to obscurant smoke exposure.« less

Genomic patterns associated with paternal/maternal distribution of transposable elements

NASA Astrophysics Data System (ADS)

Jurka, Jerzy

2003-03-01

Transposable elements (TEs) are specialized DNA or RNA fragments capable of surviving in intragenomic niches. They are commonly, perhaps unjustifiably referred to as "selfish" or "parasitic" elements. TEs can be divided in two major classes: retroelements and DNA transposons. The former include non-LTR retrotransposons and retrovirus-like elements, using reverse transriptase for their reproduction prior to integration into host DNA. The latter depend mostly on host DNA replication, with possible exception of rolling-circle transposons recently discovered by our team. I will review basic information on TEs, with emphasis on human Alu and L1 retroelements discussed in the context of genomic organization. TEs are non-randomly distributed in chromosomal DNA. In particular, human Alu elements tend to prefer GC-rich regions, whereas L1 accumulate in AT-rich regions. Current explanations of this phenomenon focus on the so called "target effects" and post-insertional selection. However, the proposed models appear to be unsatisfactory and alternative explanations invoking "channeling" to different chromosomal regions will be a major focus of my presentation. Transposable elements (TEs) can be expressed and integrated into host DNA in the male or female germlines, or both. Different models of expression and integration imply different proportions of TEs on sex chromosomes and autosomes. The density of recently retroposed human Alu elements is around three times higher on chromosome Y than on chromosome X, and over two times higher than the average density for all human autosomes. This implies Alu activity in paternal germlines. Analogous inter-chromosomal proportions for other repeat families should determine their compatibility with one of the three basic models describing the inheritance of TEs. Published evidence indicates that maternally and paternally imprinted genes roughly correspond to GC-rich and AT-rich DNA. This may explain the observed chromosomal distribution of Alu and L1 elements. Finally, paternal models of inheritance predict rapid accumulation of active TEs on chromosome Y. I will discuss potential implications of this phenomenon for evolution of chromosome Y and transposable elements.

Contrasting the Chromosomal Organization of Repetitive DNAs in Two Gryllidae Crickets with Highly Divergent Karyotypes

PubMed Central

Palacios-Gimenez, Octavio M.; Carvalho, Carlos Roberto; Ferrari Soares, Fernanda Aparecida; Cabral-de-Mello, Diogo C.

2015-01-01

A large percentage of eukaryotic genomes consist of repetitive DNA that plays an important role in the organization, size and evolution. In the case of crickets, chromosomal variability has been found using classical cytogenetics, but almost no information concerning the organization of their repetitive DNAs is available. To better understand the chromosomal organization and diversification of repetitive DNAs in crickets, we studied the chromosomes of two Gryllidae species with highly divergent karyotypes, i.e., 2n(♂) = 29,X0 (Gryllus assimilis) and 2n = 9, neo-X1X2Y (Eneoptera surinamensis). The analyses were performed using classical cytogenetic techniques, repetitive DNA mapping and genome-size estimation. Conserved characteristics were observed, such as the occurrence of a small number of clusters of rDNAs and U snDNAs, in contrast to the multiple clusters/dispersal of the H3 histone genes. The positions of U2 snDNA and 18S rDNA are also conserved, being intermingled within the largest autosome. The distribution and base-pair composition of the heterochromatin and repetitive DNA pools of these organisms differed, suggesting reorganization. Although the microsatellite arrays had a similar distribution pattern, being dispersed along entire chromosomes, as has been observed in some grasshopper species, a band-like pattern was also observed in the E. surinamensis chromosomes, putatively due to their amplification and clustering. In addition to these differences, the genome of E. surinamensis is approximately 2.5 times larger than that of G. assimilis, which we hypothesize is due to the amplification of repetitive DNAs. Finally, we discuss the possible involvement of repetitive DNAs in the differentiation of the neo-sex chromosomes of E. surinamensis, as has been reported in other eukaryotic groups. This study provided an opportunity to explore the evolutionary dynamics of repetitive DNAs in two non-model species and will contribute to the understanding of chromosomal evolution in a group about which little chromosomal and genomic information is known. PMID:26630487

Contrasting the Chromosomal Organization of Repetitive DNAs in Two Gryllidae Crickets with Highly Divergent Karyotypes.

PubMed

Palacios-Gimenez, Octavio M; Carvalho, Carlos Roberto; Ferrari Soares, Fernanda Aparecida; Cabral-de-Mello, Diogo C

2015-01-01

A large percentage of eukaryotic genomes consist of repetitive DNA that plays an important role in the organization, size and evolution. In the case of crickets, chromosomal variability has been found using classical cytogenetics, but almost no information concerning the organization of their repetitive DNAs is available. To better understand the chromosomal organization and diversification of repetitive DNAs in crickets, we studied the chromosomes of two Gryllidae species with highly divergent karyotypes, i.e., 2n(♂) = 29,X0 (Gryllus assimilis) and 2n = 9, neo-X1X2Y (Eneoptera surinamensis). The analyses were performed using classical cytogenetic techniques, repetitive DNA mapping and genome-size estimation. Conserved characteristics were observed, such as the occurrence of a small number of clusters of rDNAs and U snDNAs, in contrast to the multiple clusters/dispersal of the H3 histone genes. The positions of U2 snDNA and 18S rDNA are also conserved, being intermingled within the largest autosome. The distribution and base-pair composition of the heterochromatin and repetitive DNA pools of these organisms differed, suggesting reorganization. Although the microsatellite arrays had a similar distribution pattern, being dispersed along entire chromosomes, as has been observed in some grasshopper species, a band-like pattern was also observed in the E. surinamensis chromosomes, putatively due to their amplification and clustering. In addition to these differences, the genome of E. surinamensis is approximately 2.5 times larger than that of G. assimilis, which we hypothesize is due to the amplification of repetitive DNAs. Finally, we discuss the possible involvement of repetitive DNAs in the differentiation of the neo-sex chromosomes of E. surinamensis, as has been reported in other eukaryotic groups. This study provided an opportunity to explore the evolutionary dynamics of repetitive DNAs in two non-model species and will contribute to the understanding of chromosomal evolution in a group about which little chromosomal and genomic information is known.

78 FR 57264 - Final Waiver and Extension of the Project Period for the Technical Assistance Coordination Center

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

...: 84.326Z.] Final Waiver and Extension of the Project Period for the Technical Assistance Coordination... project period. SUMMARY: The Secretary waives the requirements in the Education Department General Administrative Regulations that generally prohibit project periods exceeding five years and extensions of project...

77 FR 16923 - Agreements and Memoranda of Understanding Between the Food and Drug Administration and Other...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

...: Direct final rule. SUMMARY: This direct final rule makes technical changes that will update a requirement that many of our written agreements and memoranda of understanding (MOUs) with other departments..., accordingly, eliminates it. We are making these technical changes to conserve Agency time and resources...

1988 Underground Storage Tanks; Technical Requirements; Final Rule and Underground Storage Tanks Containing Petroleum-Financial Responsibility Requirements and State Program Approval Objective; Final Rule

EPA Pesticide Factsheets

EPA's 1988 regulations concerning USTs are contained in 40 CFR Part 280, 40 CFR Part 281 and 40 CFR Parts 282.50-282.105 and divided into three sections: technical requirements, financial responsibility requirements, and state program approval objectives.

PITTSBURGH TECHNICAL HEALTH TRAINING INSTITUTE DEMONSTRATION PROJECT. FINAL REPORT, VOLUME II.

ERIC Educational Resources Information Center

KISHKUNAS, LOUIS J.

APPENDIXES TO THE "FINAL REPORT," VOLUME I (VT 005 511), ARE INCLUDED--(1) A SCHEMATIC REPRESENTATION OF CURRICULUM DEVELOPMENT, (2) TECHNICAL BEHAVIOR CHECKLISTS, (3) PERFORMANCE INVENTORY FORMS USED IN ON-THE-JOB OBSERVATIONS, (4) REPORT FORM FOR TYPICAL JOB BEHAVIOR OF EMPLOYEE, (5) COOPERATING AREA HEALTH INSTITUTIONS, (6) TABLES OF Z SCORES…

Invention and Writing in Technical Work: Representing the Object.

ERIC Educational Resources Information Center

Winsor, Dorothy A.

1994-01-01

Describes the way invention is relevant to the practice of technical writing. Studies three engineering students engaged in a real-world project. Shows how the students' technical work and invention for the final report were simultaneous activities. Claims that invention for and through writing overlaps with technical invention. (HB)

Project T.E.A.M. (Technical Education Advancement Modules). Final Report.

ERIC Educational Resources Information Center

Greenville Technical Coll., SC.

Project TEAM (Technical Education Advancement Modules), a cooperative demonstration program for high technology training, created an introductory technical training program and a consumer education package emphasizing the benefits of technical training. The curriculum and training focus of the project began with an assessment of employee needs in…

DNA replication machinery is required for development in Drosophila.

PubMed

Kohzaki, Hidetsugu; Asano, Maki; Murakami, Yota

2018-01-01

 In Drosophila , some factors involved in chromosome replication seem to be involved in gene amplification and endoreplication, which are actively utilized in particular tissue development, but direct evidence has not been shown. Therefore, we examined the effect of depletion of replication factors on these processes. First, we confirmed RNAi knockdown can be used for the depletion of replication factors by comparing the phenotypes of RNAi knockdown and deletion or point mutants of the components of DNA licensing factor, MCM2, MCM4 and Cdt1. Next, we found that tissue-specific RNAi knockdown of replication factors caused tissue-specific defects, probably due to defects in DNA replication. In particular, we found that depletion inhibited gene amplification of the chorion gene in follicle cells and endoreplication in salivary glands, showing that chromosomal DNA replication factors are required for these processes. Finally, using RNAi, we screened the genes for chromosomal DNA replication that affected tissue development. Interestingly, wing specific knockdown of Mcm10 induced wing formation defects. These results suggest that some components of chromosomal replication machinery are directly involved in tissue development.

Kinetochore Dynein Is Required for Chromosome Motion and Congression Independent of the Spindle Checkpoint

PubMed Central

Yang, Zhenye; Tulu, U. Serdar; Wadsworth, Patricia; Rieder, Conly L.

2008-01-01

Summary During mitosis, the motor molecule cytoplasmic dynein plays key direct and indirect roles in organizing microtubules (MTs) into a functional spindle. At this time, dynein is also recruited to kinetochores, but its role or roles at these organelles remain vague, partly because inhibiting dynein globally disrupts spindle assembly [1-4]. However, dynein can be selectively depleted from kinetochores by disruption of ZW10 [5], and recent studies with this approach conclude that kinetochore-associated dynein (KD) functions to silence the spindle-assembly checkpoint (SAC) [6]. Here we use dynein-antibody microinjection and the RNAi of ZW10 to explore the role of KD in chromosome behavior during mitosis in mammals. We find that depleting or inhibiting KD prevents the rapid poleward motion of attaching kinetochores but not kinetochore fiber (K fiber) formation. However, after kinetochores attach to the spindle, KD is required for stabilizing kinetochore MTs, which it probably does by generating tension on the kinetochore, and in its absence, chromosome congression is defective. Finally, depleting KD reduces the velocity of anaphase chromosome motion by ∼40%, without affecting the rate of poleward MT flux. Thus, in addition to its role in silencing the SAC, KD is important for forming and stabilizing K fibers and in powering chromosome motion. PMID:17509882

Chromosome evolution in the Thermotogales: large-scale inversions and strain diversification of CRISPR sequences.

PubMed

DeBoy, Robert T; Mongodin, Emmanuel F; Emerson, Joanne B; Nelson, Karen E

2006-04-01

In the present study, the chromosomes of two members of the Thermotogales were compared. A whole-genome alignment of Thermotoga maritima MSB8 and Thermotoga neapolitana NS-E has revealed numerous large-scale DNA rearrangements, most of which are associated with CRISPR DNA repeats and/or tRNA genes. These DNA rearrangements do not include the putative origin of DNA replication but move within the same replichore, i.e., the same replicating half of the chromosome (delimited by the replication origin and terminus). Based on cumulative GC skew analysis, both the T. maritima and T. neapolitana lineages contain one or two major inverted DNA segments. Also, based on PCR amplification and sequence analysis of the DNA joints that are associated with the major rearrangements, the overall chromosome architecture was found to be conserved at most DNA joints for other strains of T. neapolitana. Taken together, the results from this analysis suggest that the observed chromosomal rearrangements in the Thermotogales likely occurred by successive inversions after their divergence from a common ancestor and before strain diversification. Finally, sequence analysis shows that size polymorphisms in the DNA joints associated with CRISPRs can be explained by expansion and possibly contraction of the DNA repeat and spacer unit, providing a tool for discerning the relatedness of strains from different geographic locations.

Combined DNA-RNA Fluorescent In situ Hybridization (FISH) to Study X Chromosome Inactivation in Differentiated Female Mouse Embryonic Stem Cells

PubMed Central

Barakat, Tahsin Stefan; Gribnau, Joost

2014-01-01

Fluorescent in situ hybridization (FISH) is a molecular technique which enables the detection of nucleic acids in cells. DNA FISH is often used in cytogenetics and cancer diagnostics, and can detect aberrations of the genome, which often has important clinical implications. RNA FISH can be used to detect RNA molecules in cells and has provided important insights in regulation of gene expression. Combining DNA and RNA FISH within the same cell is technically challenging, as conditions suitable for DNA FISH might be too harsh for fragile, single stranded RNA molecules. We here present an easily applicable protocol which enables the combined, simultaneous detection of Xist RNA and DNA encoded by the X chromosomes. This combined DNA-RNA FISH protocol can likely be applied to other systems where both RNA and DNA need to be detected. PMID:24961515

Modeling read counts for CNV detection in exome sequencing data.

PubMed

Love, Michael I; Myšičková, Alena; Sun, Ruping; Kalscheuer, Vera; Vingron, Martin; Haas, Stefan A

2011-11-08

Varying depth of high-throughput sequencing reads along a chromosome makes it possible to observe copy number variants (CNVs) in a sample relative to a reference. In exome and other targeted sequencing projects, technical factors increase variation in read depth while reducing the number of observed locations, adding difficulty to the problem of identifying CNVs. We present a hidden Markov model for detecting CNVs from raw read count data, using background read depth from a control set as well as other positional covariates such as GC-content. The model, exomeCopy, is applied to a large chromosome X exome sequencing project identifying a list of large unique CNVs. CNVs predicted by the model and experimentally validated are then recovered using a cross-platform control set from publicly available exome sequencing data. Simulations show high sensitivity for detecting heterozygous and homozygous CNVs, outperforming normalization and state-of-the-art segmentation methods.

Sex-reversed somatic cell cloning in the mouse.

PubMed

Inoue, Kimiko; Ogonuki, Narumi; Mekada, Kazuyuki; Yoshiki, Atsushi; Sado, Takashi; Ogura, Atsuo

2009-10-01

Somatic cell nuclear transfer has many potential applications in the fields of basic and applied sciences. However, it has a disadvantage that can never be overcome technically-the inflexibility of the sex of the offspring. Here, we report an accidental birth of a female mouse following nuclear transfer using an immature Sertoli cell. We produced a batch of 27 clones in a nuclear transfer experiment using Sertoli cells collected from neonatal male mice. Among them, one pup was female. This "male-derived female" clone grew into a normal adult and produced offspring by natural mating with a littermate. Chromosomal analysis revealed that the female clone had a 39,X karyotype, indicating that the Y chromosome had been deleted in the donor cell or at some early step during nuclear transfer. This finding suggests the possibility of resuming sexual reproduction after a single male is cloned, which should be especially useful for reviving extinct or endangered species.

Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: utility in uncovering cellular deficits in mental illness-associated chromosomal abnormalities

PubMed Central

Passeri, Eleonora; Wilson, Ashley M.; Primerano, Amedeo; Kondo, Mari A.; Sengupta, Srona; Srivastava, Rupali; Koga, Minori; Obie, Cassandra; Zandi, Peter P.; Goes, Fernando S.; Valle, David; Rapoport, Judith L.; Sawa, Akira; Kano, Shin-ichi; Ishizuka, Koko

2016-01-01

The novel technology of induced neuronal cells (iN cells) is promising for translational neuroscience, as it allows the conversion of human fibroblasts into cells with postmitotic neuronal traits. However, a major technical barrier is the low conversion rate. To overcome this problem, we optimized the conversion media. Using our improved formulation, we studied how major mental illness-associated chromosomal abnormalities may impact the characteristics of iN cells. We demonstrated that our new iN cell culture protocol enabled us to obtain more precise measurement of neuronal cellular phenotypes than previous iN cell methods. Thus, this iN cell culture provides a platform to efficiently obtain possible cellular phenotypes caused by genetic differences, which can be more thoroughly studied in research using other human cell models such as induced pluripotent stem cells. PMID:26260244

Chromosome phylogenies of man, great apes, and Old World monkeys.

PubMed

De Grouchy, J

1987-08-31

The karyotypes of man and of the closely related Pongidae--chimpanzee, gorilla, and orangutan--differ by a small number of well known rearrangements, mainly pericentric inversions and one fusion which reduced the chromosome number from 48 in the Pongidae to 46 in man. Dutrillaux et al. (1973, 1975, 1979) reconstructed the chromosomal phylogeny of the entire primate order. More and more distantly related species were compared thus moving backward in evolution to the common ancestors of the Pongidae, of the Cercopithecoidae, the Catarrhini, the Platyrrhini, the Prosimians, and finally the common ancestor of all primates. Descending the pyramid it becomes possible to assign the rearrangements that occurred in each phylum, and the one that led to man in particular. The main conclusions are that this phylogeny is compatible with the occurrence during evolution of simple chromosome rearrangements--inversions, fusions, reciprocal translocation, acquisition or loss of heterochromatin--and that it is entirely consistent with the known primate phylogeny based on physical morphology and molecular evolution. If heterochromatin is not taken into account, man has in common with the other primates practically all of his chromosomal material as determined by chromosome banding. However, it is arranged differently, according to species, on account of chromosome rearrangements. This interpretation has been confirmed by comparative gene mapping, which established that the same chromosome segments, identified by banding, carry the same genes (Finaz et al., 1973; Human Gene Mapping 8, 1985). A remarkable observation made by Dutrillaux is that different primate phyla seem to have adopted different chromosome rearrangements in the course of evolution: inversions for the Pongidae, Robertsonian fusions for the lemurs, etc. This observation may raise many questions, among which is that of an organized evolution. Also, the breakpoints of chromosomal rearrangements observed during evolution, in human chromosomal diseases, and after ionizing irradiation do not seem to be distributed at random. Chromosomal rearrangements observed in evolution are known to be harmful in humans, leading to complete or partial sterility through abnormal offspring in the heterozygous state but not in the homozygous state. They then become a robust reproductive barrier capable of creating new species, far more powerful than gene mutations advocated by neo-Darwinism. The homozygous state may be achieved especially through inbreeding, which must have played a major role during primate evolution.(ABSTRACT TRUNCATED AT 400 WORDS)

77 FR 39623 - Airworthiness Standards: Aircraft Engines; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

...] Airworthiness Standards: Aircraft Engines; Technical Amendment AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule; technical amendment. SUMMARY: This amendment clarifies aircraft engine... from applicants requesting FAA engine type certifications and aftermarket certifications, such as...

Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations.

PubMed

Carbone, Lucia; Chavez, Shawn L

2015-01-01

Pre-implantation embryo development in mammals begins at fertilization with the migration and fusion of the maternal and paternal pro-nuclei, followed by the degradation of inherited factors involved in germ cell specification and the activation of embryonic genes required for subsequent cell divisions, compaction, and blastulation. The majority of studies on early embryogenesis have been conducted in the mouse or non-mammalian species, often requiring extrapolation of the findings to human development. Given both conserved similarities and species-specific differences, however, even comparison between closely related mammalian species may be challenging as certain aspects, including susceptibility to chromosomal aberrations, varies considerably across mammals. Moreover, most human embryo studies are limited to patient samples obtained from in vitro fertilization (IVF) clinics and donated for research, which are generally of poorer quality and produced with germ cells that may be sub-optimal. Recent technical advances in genetic, epigenetic, chromosomal, and time-lapse imaging analyses of high quality whole human embryos have greatly improved our understanding of early human embryogenesis, particularly at the single embryo and cell level. This review summarizes the major characteristics of mammalian pre-implantation development from a chromosomal perspective, in addition to discussing the technological achievements that have recently been developed to obtain this data. We also discuss potential translation to clinical applications in reproductive medicine and conclude by examining the broader implications of these findings for the evolution of mammalian species and cancer pathology in somatic cells.

Could Digital PCR Be an Alternative as a Non-Invasive Prenatal Test for Trisomy 21: A Proof of Concept Study

PubMed Central

El Khattabi, Laïla Allach; Rouillac-Le Sciellour, Christelle; Le Tessier, Dominique; Luscan, Armelle; Coustier, Audrey; Porcher, Raphael; Bhouri, Rakia; Nectoux, Juliette; Sérazin, Valérie; Quibel, Thibaut; Mandelbrot, Laurent; Tsatsaris, Vassilis

2016-01-01

Objective NIPT for fetal aneuploidy by digital PCR has been hampered by the large number of PCR reactions needed to meet statistical requirements, preventing clinical application. Here, we designed an octoplex droplet digital PCR (ddPCR) assay which allows increasing the number of available targets and thus overcomes statistical obstacles. Method After technical optimization of the multiplex PCR on mixtures of trisomic and euploid DNA, we performed a validation study on samples of plasma DNA from 213 pregnant women. Molecular counting of circulating cell-free DNA was performed using a mix of hydrolysis probes targeting chromosome 21 and a reference chromosome. Results The results of our validation experiments showed that ddPCR detected trisomy 21 even when the sample’s trisomic DNA content is as low as 5%. In a validation study of plasma samples from 213 pregnant women, ddPCR discriminated clearly between the trisomy 21 and the euploidy groups. Conclusion Our results demonstrate that digital PCR can meet the requirements for non-invasive prenatal testing of trisomy 21. This approach is technically simple, relatively cheap, easy to implement in a diagnostic setting and compatible with ethical concerns regarding access to nucleotide sequence information. These advantages make it a potential technique of choice for population-wide screening for trisomy 21 in pregnant women. PMID:27167625

Stepwise occurrence of a complex unbalanced translocation in neuroblastoma leading to insertion of a telomere sequence and late chromosome 17q gain.

PubMed

Schleiermacher, Gudrun; Bourdeaut, Franck; Combaret, Valérie; Picrron, Gaelle; Raynal, Virginie; Aurias, Alain; Ribeiro, Agnes; Janoueix-Lerosey, Isabelle; Delattre, Olivier

2005-05-05

In neuroblastoma, the most frequent genetic alterations are unbalanced translocations involving chromosome 17. To gain insights into these rearrangements, we have characterized a previously identified der(1)t(1;17) of the CLB-Bar cell line. The 17q breakpoint was mapped by FISH. Subsequently, a rearranged fragment was identified by Southern analysis, cloned in a lambda vector and sequenced. The chromosome rearrangement is more complex than expected due to the presence of an interstitial 4p telomeric sequence between chromosome 1p and 17q. Three different genes, which may play a role in neuroblastoma development, are disrupted by the translocation breakpoints. Indeed, the 3'UTR of the PIP5K2B gene on chromosome 17q is directly fused to the (TTAGGG)n repeat of the chromosome 4p telomere, and the (1;4) fusion disrupts the MACF1 (microtubule-actin crosslinking factor 1) and POLN genes, respectively. Interestingly, the (1;4) fusion was present at diagnosis and at relapse, whereas the (4;17) fusion was detected at relapse only, leading to a secondary 17q gain confirmed by array CGH therefore indicating that 17q gain may not be a primary event in neuroblastoma. Finally, screening of a panel of neuroblastoma cell lines identified interstitial telomeric sequences in three other cases, suggesting that this may be a recurrent mechanism leading to unbalanced translocations in neuroblastoma.

Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

PubMed Central

Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga; Stamenova, Elena K.; Durand, Neva C.; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L.; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P.; Lander, Eric S.; Chadwick, Brian P.; Aiden, Erez Lieberman

2016-01-01

During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called “superdomains,” such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called “superloops.” DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

Detailed longitudinal sampling of glioma stem cells in situ reveals Chr7 gain and Chr10 loss as repeated events in primary tumor formation and recurrence.

PubMed

Baysan, Mehmet; Woolard, Kevin; Cam, Margaret C; Zhang, Wei; Song, Hua; Kotliarova, Svetlana; Balamatsias, Demosthenes; Linkous, Amanda; Ahn, Susie; Walling, Jennifer; Belova, Galina I; Fine, Howard A

2017-11-15

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. © 2017 UICC.

A three-dimensional structural dissection of Drosophila polytene chromosomes.

PubMed

Urata, Y; Parmelee, S J; Agard, D A; Sedat, J W

1995-10-01

We have analyzed the three-dimensional structural details of Drosophila melanogaster polytene chromosome bands and interbands using three-dimensional light microscopy and a novel method of sample preparation that does not involve flattening or stretching the chromosomes. Bands have been visualized in unfixed chromosomes stained with the DNA specific dye 4,6-Diamidino-2-phenylindole (DAPI). Interbands have been visualized using fixed chromosomes that have been immunostained with an antibody to RNA polymerase II. Additionally, these structures have been analyzed using in situ hybridization with probes from specific genetic loci (Notch and white). Bands are seen to be composed of approximately 36 substructural features that measure 0.2-0.4 micron in diameter. We suggest that these substructural features are in fact longitudinal fibers made up of bundles of chromatids. Band shape can be a reproducible characteristic of a particular band and is dependent on the spatial relationship of these bundles, varying from bands with a uniform distribution of bundles to bands with a peripheral concentration of chromatin. Interbands are composed of bundles of chromatids of a similar size and number as those seen in the bands. The distribution of bundles is similar between a band and the neighboring interband, implying that there is a long range organization to the DNA that includes both the coding and the noncoding portions of genes. Finally, we note that the polytene chromosome has a circular shape when viewed in cross section, whether there are one or two homologs present.

7 CFR 652.36 - Appeal of decertification decisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... technical service provider's written appeal, the Chief or his designee, will make a final determination, in... CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE SUPPORT ACTIVITIES TECHNICAL SERVICE PROVIDER ASSISTANCE... of the State Conservationist's decertification determination, the technical service provider may...

Capturing Cognitive Fingerprints for Active Authentication

DTIC Science & Technology

2014-10-01

CAPTURING COGNITIVE FINGERPRINTS FOR ACTIVE AUTHENTICATION IOWA STATE UNIVERSITY OF SCIENCE & TECHNOLOGY OCTOBER 2014 FINAL TECHNICAL REPORT...REPORT TYPE FINAL TECHNICAL REPORT 3. DATES COVERED (From - To) SEP 2013 – APR 2014 4. TITLE AND SUBTITLE CAPTURING COGNITIVE FINGERPRINTS FOR ACTIVE...The project ended before the IRB application was approved. 15. SUBJECT TERMS Active Authentication, Cognitive Fingerprints , Biometric Modalities

Application of Communications Satellites to Educational Development. Final Technical Report, September 1, 1969-August 31, 1975.

ERIC Educational Resources Information Center

Morgan, Robert P.

Research is summarized in a brief final report built around a four-section bibliography. The first section lists periodic progress reports and articles which provide an overview of the program, including articles which pertain primarily to educational rather than technical aspects of satellite utilization. Theses carried out in the fields of…

Head Start Impact Study. Technical Report

ERIC Educational Resources Information Center

Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Shapiro, Gary; Broene, Pam; Jenkins, Frank; Fletcher, Philip; Quinn, Liz; Friedman, Janet; Ciarico, Janet; Rohacek, Monica; Adams, Gina; Spier, Elizabeth

2010-01-01

This Technical Report is designed to provide technical detail to support the analysis and findings presented in the "Head Start Impact Study Final Report" (U.S. Department of Health and Human Services, January 2010). Chapter 1 provides an overview of the Head Start Impact Study and its findings. Chapter 2 provides technical information on the…

Matching Community and Technical College Professional/Technical Education Capacity to Employer Demand. Final Report.

ERIC Educational Resources Information Center

Sommers, Paul; Heg, Deena

A project was conducted to improve the state of Washington's community and technical college system by developing and using an improved occupational forecasting system to assess and respond to education and training needs. First, long-term occupational forecast data from Washington's Employment Security Department were matched with technical and…

75 FR 5784 - Guidance on Preparation of Market-Based Rate Filings and Electric Quarterly Reports by Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

... Preparation of Market-Based Rate Filings and Electric Quarterly Reports by Public Utilities; Notice of Technical Conference January 28, 2010. Take notice that Commission staff will convene a technical conference... final agenda of the technical conference. The March 3, 2010 technical conference will focus on the...

A Revision of Technical Mathematics Based on the NCTM Standards. Final Report.

ERIC Educational Resources Information Center

Near, Barbara

Between 1993 and 1996, Henry Ford Community College (Michigan) worked with business, industry, and technical instructors to revise their Technical Mathematics program in accordance with the National Council of Teachers of Mathematics (NCTM) Standards. The purpose of the project was to restructure the technical math curriculum and create a context…

76 FR 11327 - Technical Amendments to Rule 17a-8: Financial Recordkeeping and Reporting of Currency and Foreign...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... SECURITIES AND EXCHANGE COMMISSION 17 CFR Part 240 [Release No. 34-63949] Technical Amendments to...: Securities and Exchange Commission. ACTION: Final rule; technical amendments. SUMMARY: The Securities and Exchange Commission (``Commission'') is adopting technical amendments to Rule 17a-8 under the Securities...

Final priority; technical assistance to improve state data capacity--National Technical Assistance Center to improve state capacity to accurately collect and report IDEA data. Final priority.

PubMed

2013-05-20

The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Technical Assistance to Improve State Data Capacity program. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2013 and later years. We take this action to focus attention on an identified national need to provide technical assistance (TA) to States to improve their capacity to meet the data collection and reporting requirements of the Individuals with Disabilities Education Act (IDEA). We intend this priority to establish a TA center to improve State capacity to accurately collect and report IDEA data (Data Center).

Histone H2A is required for normal centromere function in Saccharomyces cerevisiae

PubMed Central

Pinto, Inés; Winston, Fred

2000-01-01

Histones are structural and functional components of the eukaryotic chromosome, and their function is essential for normal cell cycle progression. In this work, we describe the characterization of two Saccharomyces cerevisiae cold-sensitive histone H2A mutants. Both mutants contain single amino acid replacements of residues predicted to be on the surface of the nucleosome and in close contact with DNA. We show that these H2A mutations cause an increase-in-ploidy phenotype, an increased rate of chromosome loss, and a defect in traversing the G2–M phase of the cell cycle. Moreover, these H2A mutations show genetic interactions with mutations in genes encoding kinetochore components. Finally, chromatin analysis of these H2A mutants has revealed an altered centromeric chromatin structure. Taken together, these results strongly suggest that histone H2A is required for proper centromere–kinetochore function during chromosome segregation. PMID:10747028

Improved mutagen testing systems in mice. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roderick, T.H.

Our laboratory was the first to induce and ascertain a mammalian chromosomal inversion; we did this by searching for a high frequency of first meiotic anaphase bridges in testes of males whose fathers received post-spermatogonial radiation or mutagenesis from chromosomal breaking chemical mutagens. One test in was examined in each mouse, and those showing a high frequency were then mated to determine if the high frequency were passed on as a dominant and whether linkage analysis suggested the presence of an inversion. A very high incidence (exceeding 20% bridges in first meiotic anaphase bridges) was found in about 1 inmore » 150 males examined and this frequency was generally found to be passed on to the offspring an predicted. Later cytological banding techniques were developed elsewhere and we used them to show visually the inverted orders of the inverted chromosomal segments. Since that time we have induced inversions covering most of the mouse genome.« less

Estimate of the frequency of true incomplete exchanges in human lymphocytes exposed to 1 GeV/u Fe ions in vitro

NASA Technical Reports Server (NTRS)

Wu, H.; George, K.; Yang, T. C.

1999-01-01

PURPOSE: To study the frequency of true incomplete exchanges induced by high-LET radiation. MATERIALS AND METHODS: Human lymphocytes were exposed to 1 GeV/u Fe ions (LET = 140 keV/microm). Chromosome aberrations were analysed by a fluorescence in situ hybridization using a combination of whole-chromosome-specific probes and human telomere probes. Chromosomes 1, 3 and 4 were investigated. RESULTS: The percentage of incomplete exchanges was between 23 and 29% if telomere signals were not considered. The percentage decreased to approximately 10% after ruling out false incomplete exchanges containing telomere signals. The final estimation of true incomplete exchanges was <10%. CONCLUSION: Within a degree of uncertainty, the percentage of true incomplete exchanges in 1 GeV/u Fe ion-irradiated human lymphocytes was similar to that induced by gamma rays.

Technical Evaluation Motor No. 10 (TEM-10)

NASA Technical Reports Server (NTRS)

1993-01-01

Technical Evaluation Motor No. 10 (TEM-10) was static fired on 27 Apr. 1993 at the Thiokol Corporation full-scale motor static test bay, T-24. This final test report documents the procedures, performance, and results of the static test firing of TEM-10. All observations, discussions, conclusions, and recommendations contained are final. Included is a presentation and discussion of TEM-10 performance, anomalies, and test results in concurrence with the objectives outlined in CTP-0110, Revision D, Space Shuttle Technical Evaluation Motor No. 10 (TEM-10) Static Fire Test Plan.

Final priority; Technical Assistance on State Data Collection--IDEA Data Management Center. Final priority.

PubMed

2014-08-05

The Assistant Secretary for the Office of Special Education and Rehabilitative Services (OSERS) announces a priority under the Technical Assistance on State Data Collection program. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to fund a cooperative agreement to establish and operate an IDEA Data Management Center (Center) that will provide technical assistance (TA) to improve the capacity of States to meet the data collection requirements of the Individuals with Disabilities Education Act (IDEA).

Technical Topic 3.2.2.d Bayesian and Non-Parametric Statistics: Integration of Neural Networks with Bayesian Networks for Data Fusion and Predictive Modeling

DTIC Science & Technology

2016-05-31

and included explosives such as TATP, HMTD, RDX, RDX, ammonium nitrate , potassium perchlorate, potassium nitrate , sugar, and TNT. The approach...Distribution Unlimited UU UU UU UU 31-05-2016 15-Apr-2014 14-Jan-2015 Final Report: Technical Topic 3.2.2. d Bayesian and Non- parametric Statistics...of Papers published in non peer-reviewed journals: Final Report: Technical Topic 3.2.2. d Bayesian and Non-parametric Statistics: Integration of Neural

The prevalence of chromosomal deletions relating to developmental delay and/or intellectual disability in human euploid blastocysts.

PubMed

He, Wenyin; Sun, Xiaofang; Liu, Lian; Li, Man; Jin, Hua; Wang, Wei-Hua

2014-01-01

Chromosomal anomalies in human embryos produced by in vitro fertilization are very common, which include numerical (aneuploidy) and structural (deletion, duplication or others) anomalies. Our previous study indicated that chromosomal deletion(s) is the most common structural anomaly accounting for approximately 8% of euploid blastocysts. It is still unknown if these deletions in human euploid blastocysts have clinical significance. In this study, we analyzed 15 previously diagnosed euploid blastocysts that had chromosomal deletion(s) using Agilent oligonucleotide DNA microarray platform and localized the gene location in each deletion. Then, we used OMIM gene map and phenotype database to investigate if these deletions are related with some important genes that cause genetic diseases, especially developmental delay or intellectual disability. As results, we found that the detectable chromosomal deletion size with Agilent microarray is above 2.38 Mb, while the deletions observed in human blastocysts are between 11.6 to 103 Mb. With OMIM gene map and phenotype database information, we found that deletions can result in loss of 81-464 genes. Out of these genes, 34-149 genes are related with known genetic problems. Furthermore, we found that 5 out of 15 samples lost genes in the deleted region, which were related to developmental delay and/or intellectual disability. In conclusion, our data indicates that all human euploid blastocysts with chromosomal deletion(s) are abnormal and transfer of these embryos may cause birth defects and/or developmental and intellectual disabilities. Therefore, the embryos with chromosomal deletion revealed by DNA microarray should not be transferred to the patients, or further gene map and/or phenotype seeking is necessary before making a final decision.

TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability

PubMed Central

Choi, Minji; Min, Yoo Hong; Pyo, Jaehyuk; Lee, Chang‐Woo; Jang, Chang‐Young

2017-01-01

Background and Purpose Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle assembly checkpoint (SAC). Pharmacological inhibition of Mps1 has been suggested as a cancer therapeutic; however, despite the existence of a novel Mps1 inhibitor, TC Mps1 12, no such studies have been performed. Experimental Approach The effects of TC Mps1 12 on cell viability, chromosome alignment, centrosome number, mitotic duration, apoptosis and SAC were determined in hepatocellular carcinoma (HCC) cells. In addition, the association of Mps1 expression with the overall survival of HCC patients was analysed. Key Results Treatment of human HCC cells with TC Mps1 12 led to chromosome misalignment and missegregation, and disorganization of centrosomes. Even in the presence of these errors, TC Mps1 12‐treated cells overrode the SAC, resulting in a shortened mitotic duration and mitotic slippage. This mitotic catastrophe triggered apoptosis and, finally, inhibited the growth of HCC cells. In addition, the expression of the Mps1‐encoding TTK gene was associated with poor overall survival of HCC patients. Conclusion and Implications TC Mps1 12 results in the accumulation of chromosomal instabilities and mitotic catastrophe in HCC cells. Overall, these data demonstrate that the inhibition of Mps1 kinase using TC Mps1 12 is a promising therapeutic approach for liver cancer. PMID:28299790

A New Fractal Model of Chromosome and DNA Processes

NASA Astrophysics Data System (ADS)

Bouallegue, K.

Dynamic chromosome structure remains unknown. Can fractals and chaos be used as new tools to model, identify and generate a structure of chromosomes?Fractals and chaos offer a rich environment for exploring and modeling the complexity of nature. In a sense, fractal geometry is used to describe, model, and analyze the complex forms found in nature. Fractals have also been widely not only in biology but also in medicine. To this effect, a fractal is considered an object that displays self-similarity under magnification and can be constructed using a simple motif (an image repeated on ever-reduced scales).It is worth noting that the problem of identifying a chromosome has become a challenge to find out which one of the models it belongs to. Nevertheless, the several different models (a hierarchical coiling, a folded fiber, and radial loop) have been proposed for mitotic chromosome but have not reached a dynamic model yet.This paper is an attempt to solve topological problems involved in the model of chromosome and DNA processes. By combining the fractal Julia process and the numerical dynamical system, we have finally found out four main points. First, we have developed not only a model of chromosome but also a model of mitosis and one of meiosis. Equally important, we have identified the centromere position through the numerical model captured below. More importantly, in this paper, we have discovered the processes of the cell divisions of both mitosis and meiosis. All in all, the results show that this work could have a strong impact on the welfare of humanity and can lead to a cure of genetic diseases.

Cellular chromosome DNA interferes with fluorescence quantitative real-time PCR detection of HBV DNA in culture medium.

PubMed

Pan, Xiao-Ben; Wei, Lai; Han, Jin-Chao; Gao, Yan

2008-01-01

Fluorescence quantitative real-time PCR (FQ-PCR) is a recently developed technique increasingly used for clinical diagnosis by detection of hepatitis B virus (HBV) DNA in serum. FQ-PCR is also used in scientific research for detection of HBV DNA in cell culture. Understanding potential FQ-PCR interference factors can improve the accuracy of HBV DNA quantification in cell culture medium. HBV positive serum was diluted with culture medium to produce three test groups with HBV DNA levels of 5 x 10(7) copies/ml (high), 5 x 10(5) copies/ml (medium), and 5 x 10(3) copies/ml (low). Chromosome DNA was extracted from HepG2 cells and then added to high, medium, and low group samples at final concentrations of 0, 12.5, 25, 50, and 100 microg/ml. The samples were quantified by FQ-PCR and data were evaluated using statistical software. No marked changes were seen in the quantitative curves for high level HBV DNA samples when the samples were supplemented with 0-100 microg/ml of chromosome DNA. Interference was observed in medium level samples when 50 and 100 microg/ml of chromosome DNA was added. Interference was also observed in low level HBV DNA samples when the concentration of added chromosome DNA was greater than 25 microg/ml. The interference was eliminated when samples were digested by DNase I prior to PCR detection. In Conclusions, the presence of cellular chromosome DNA can interfere with the detection of HBV DNA by FQ-PCR. Removal of cellular chromosome DNA from culture media prior to FQ-PCR is necessary for reliable HBV DNA quantitative detection. (c) 2007 Wiley-Liss, Inc.

Origins of the Human Genome Project.

PubMed

Watson, J D; Cook-Deegan, R M

1991-01-01

The Human Genome Project has become a reality. Building on a debate that dates back to 1985, several genome projects are now in full stride around the world, and more are likely to form in the next several years. Italy began its genome program in 1987, and the United Kingdom and U.S.S.R. in 1988. The European communities mounted several genome projects on yeast, bacteria, Drosophila, and Arabidospis thaliana (a rapidly growing plant with a small genome) in 1988, and in 1990 commenced a new 2-year program on the human genome. In the United States, we have completed the first year of operation of the National Center for Human Genome Research at the National Institutes of Health (NIH), now the largest single funding source for genome research in the world. There have been dedicated budgets focused on genome-scale research at NIH, the U.S. Department of Energy, and the Howard Hughes Medical Institute for several years, and results are beginning to accumulate. There were three annual meetings on genome mapping and sequencing at Cold Spring Harbor, New York, in the spring of 1988, 1989, and 1990; the talks have shifted from a discussion about how to approach problems to presenting results from experiments already performed. We have finally begun to work rather than merely talk. The purpose of genome projects is to assemble data on the structure of DNA in human chromosomes and those of other organisms. A second goal is to develop new technologies to perform mapping and sequencing. There have been impressive technical advances in the past 5 years since the debate about the human genome project began. We are on the verge of beginning pilot projects to test several approaches to sequencing long stretches of DNA, using both automation and manual methods. Ordered sets of yeast artificial chromosome and cosmid clones have been assembled to span more than 2 million base pairs of several human chromosomes, and a region of 10 million base pairs has been assembled for Caenorhabditis elegans by a collaboration between Washington University and the Medical Research Council laboratory in Cambridge, U.K. This project is now turning to sequencing C. elegans DNA as a logical extension of this work. These are but the first fruits of the genome project. There is much more to come.

Final June Revisions Rule Significant Contribution Assessment TSD

EPA Pesticide Factsheets

This Technical Support Document (TSD) presents quantitative assessments of the relationship between the final February revisions to the Transport Rule, the final June revisions rule, and the original analysis conducted for the final Transport Rule.

Develop a Comprehensive Technical Training and Data Collection Program for Structural Welders and Fitters: Technical Proposal

DTIC Science & Technology

2006-05-30

implementation Final Report 4 TECHNICAL PLAN AND RESULTS Task 1: Initiate the Project Management System Two senior NGSS production management...1 Technical Plan and Results...Third the system is hosted on a handheld unit which provides the foremen with an efficient daily planning tool. The Pilot System which entails

Laser Technician Associate Degree Program. A Proposal Submitted to Wisconsin State Board of Vocational, Technical, and Adult Education. (Curriculum Development.) Final Report.

ERIC Educational Resources Information Center

North Central Technical Inst., Wausau, WI.

This final report contains the program proposal with supporting data for developing curriculum materials for and implementing an associate-degree laser technology program at the North Central Technical Institute. The proposal outline provides this information: (1) objectives for the program designed to prepare a technician to safely operate,…

California Deaf-Blind Services Final Report, October 1, 1995-September 30, 1999 [and] October 1, 1999-June 30, 2000 (No Cost Extension).

ERIC Educational Resources Information Center

Goertz, Lori; Franklin, Barbara

This final report describes the activities and outcomes of the California Deaf-Blind Services (CDBS) program, a regionally based, family focused technical assistance and training project designed to improve services to children with deaf-blindness. The project conducted the following activities: (1) provided technical assistance to families and…

New Jersey Technical Assistance Project (N.J. TAP): "Educational Resources and Support Services on Behalf of Children with Multiple Sensory Impairment." Final Report.

ERIC Educational Resources Information Center

New Jersey State Dept. of Education, Trenton.

This final report describes activities and accomplishments of the New Jersey Technical Assistance Project, a project to improve educational resources and support services for students with multiple sensory impairment (deaf-blindness). Activities and accomplishments are presented in a tabular format for each project goal and objective. The project…

SHOC1 is a ERCC4-(HhH)2-like protein, integral to the formation of crossover recombination intermediates during mammalian meiosis.

PubMed

Guiraldelli, Michel F; Felberg, Anna; Almeida, Luciana P; Parikh, Aniruddha; de Castro, Rodrigo O; Pezza, Roberto J

2018-05-01

Chromosome segregation errors during meiosis result in the formation of aneuploid gametes and are the leading cause of pregnancy loss and birth defects in humans. Proper chromosome segregation requires pairwise associations of maternal and paternal homologous chromosomes. Chiasmata, which are the cytological manifestations of crossovers (COs), provide a physical link that holds the homologs together as a pair, facilitating their orientation on the spindle at meiosis I. Although CO-promoting activities ensure a balanced number and position of COs, their identity and mechanism of action in mammals remain understudied. Previous work in yeast and Arabidopsis has shown that Zip2 and Shoc1 are ortholog proteins with an important role in promoting the formation of COs. Our work is the first study in mammals showing the in vivo and in vitro function of mouse and human SHOC1. We show that purified recombinant human SHOC1, an XPF/MUS81 family member, preferentially binds branched DNA molecules but apparently lacks in vitro endonuclease activity, despite its conserved ERCC4-(HhH)2 core structure. Cytological observations suggest that initial steps of recombination are normal in a majority of spermatocytes from SHOC1 hypomorphic mice. However, late stages of recombination appear abnormal, as chromosomal localization of MLH1 is reduced. In agreement, chiasma formation is reduced, and cells arrest at metaphase I with a few lagging chromosomes and subsequent apoptosis. This analysis of SHOC1-deficient mice and the selective localization of SHOC1 to a subset of recombination sites show that SHOC1 acts at key mid-stage steps of the CO formation process. The formation of chromosome axial elements and homologous pairing are apparently normal, but synapsis is altered with SYCP1 frequently failing to extend the full length of the chromosome axes. Finally, we describe that SHOC1 interacts with TEX11, another protein important for the formation of COs, connecting SHOC1 to chromosome axis and structure.

78 FR 77563 - Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... NATIONAL CREDIT UNION ADMINISTRATION 12 CFR Parts 700, 701, and 704 RIN 3133-AE33 Technical Amendments AGENCY: National Credit Union Administration (NCUA). ACTION: Final rule. SUMMARY: The NCUA Board... credit unions. The technical amendments conform the regulations to a recent policy change adopted by the...

75 FR 33682 - Export Administration Regulations; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

...-01] RIN 0694-AE93 Export Administration Regulations; Technical Amendments AGENCY: Bureau of Industry... Bureau of Industry and Security (BIS) makes a technical amendment to the Export Administration... review of final decisions and orders issued in BIS export control administrative enforcement proceedings...

78 FR 41331 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-10

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 225 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is making technical amendment to the Defense...

Final Revisions Rule Significant Contribution Assessment TSD

EPA Pesticide Factsheets

This Technical Support Document (TSD) presents quantitative assessments of the relationship between final revisions to the Transport Rule and the original analysis conducted for the final Transport Rule.

The hierarchically organized splitting of chromosome bands into sub-bands analyzed by multicolor banding (MCB).

PubMed

Lehrer, H; Weise, A; Michel, S; Starke, H; Mrasek, K; Heller, A; Kuechler, A; Claussen, U; Liehr, T

2004-01-01

To clarify the nature of chromosome sub-bands in more detail, the multicolor banding (MCB) probe-set for chromosome 5 was hybridized to normal metaphase spreads of GTG band levels at approximately 850, approximately 550, approximately 400 and approximately 300. It could be observed that as the chromosomes became shorter, more of the initial 39 MCB pseudo-colors disappeared, ending with 18 MCB pseudo-colored bands at the approximately 300-band level. The hierarchically organized splitting of bands into sub-bands was analyzed by comparing the disappearance or appearance of pseudo-color bands of the four different band levels. The regions to split first are telomere-near, centromere-near and in 5q23-->q31, followed by 5p15, 5p14, and all GTG dark bands in 5q apart from 5q12 and 5q32 and finalized by sub-band building in 5p15.2, 5q21.2-->q21.3, 5q23.1 and 5q34. The direction of band splitting towards the centromere or the telomere could be assigned to each band separately. Pseudo-colors assigned to GTG-light bands were resistant to band splitting. These observations are in concordance with the recently proposed concept of chromosome region-specific protein swelling. Copyright 2003 S. Karger AG, Basel

Genetic and epigenetic variation in 5S ribosomal RNA genes reveals genome dynamics in Arabidopsis thaliana

PubMed Central

Simon, Lauriane; Rabanal, Fernando A; Dubos, Tristan; Oliver, Cecilia; Lauber, Damien; Poulet, Axel; Vogt, Alexander; Mandlbauer, Ariane; Le Goff, Samuel; Sommer, Andreas; Duborjal, Hervé; Tatout, Christophe

2018-01-01

Abstract Organized in tandem repeat arrays in most eukaryotes and transcribed by RNA polymerase III, expression of 5S rRNA genes is under epigenetic control. To unveil mechanisms of transcriptional regulation, we obtained here in depth sequence information on 5S rRNA genes from the Arabidopsis thaliana genome and identified differential enrichment in epigenetic marks between the three 5S rDNA loci situated on chromosomes 3, 4 and 5. We reveal the chromosome 5 locus as the major source of an atypical, long 5S rRNA transcript characteristic of an open chromatin structure. 5S rRNA genes from this locus translocated in the Landsberg erecta ecotype as shown by linkage mapping and chromosome-specific FISH analysis. These variations in 5S rDNA locus organization cause changes in the spatial arrangement of chromosomes in the nucleus. Furthermore, 5S rRNA gene arrangements are highly dynamic with alterations in chromosomal positions through translocations in certain mutants of the RNA-directed DNA methylation pathway and important copy number variations among ecotypes. Finally, variations in 5S rRNA gene sequence, chromatin organization and transcripts indicate differential usage of 5S rDNA loci in distinct ecotypes. We suggest that both the usage of existing and new 5S rDNA loci resulting from translocations may impact neighboring chromatin organization. PMID:29518237

Genetic and epigenetic variation in 5S ribosomal RNA genes reveals genome dynamics in Arabidopsis thaliana.

PubMed

Simon, Lauriane; Rabanal, Fernando A; Dubos, Tristan; Oliver, Cecilia; Lauber, Damien; Poulet, Axel; Vogt, Alexander; Mandlbauer, Ariane; Le Goff, Samuel; Sommer, Andreas; Duborjal, Hervé; Tatout, Christophe; Probst, Aline V

2018-04-06

Organized in tandem repeat arrays in most eukaryotes and transcribed by RNA polymerase III, expression of 5S rRNA genes is under epigenetic control. To unveil mechanisms of transcriptional regulation, we obtained here in depth sequence information on 5S rRNA genes from the Arabidopsis thaliana genome and identified differential enrichment in epigenetic marks between the three 5S rDNA loci situated on chromosomes 3, 4 and 5. We reveal the chromosome 5 locus as the major source of an atypical, long 5S rRNA transcript characteristic of an open chromatin structure. 5S rRNA genes from this locus translocated in the Landsberg erecta ecotype as shown by linkage mapping and chromosome-specific FISH analysis. These variations in 5S rDNA locus organization cause changes in the spatial arrangement of chromosomes in the nucleus. Furthermore, 5S rRNA gene arrangements are highly dynamic with alterations in chromosomal positions through translocations in certain mutants of the RNA-directed DNA methylation pathway and important copy number variations among ecotypes. Finally, variations in 5S rRNA gene sequence, chromatin organization and transcripts indicate differential usage of 5S rDNA loci in distinct ecotypes. We suggest that both the usage of existing and new 5S rDNA loci resulting from translocations may impact neighboring chromatin organization.

75 FR 15342 - Advisory Committees; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 14 [Docket No. FDA-2010-N-0001] Advisory Committees; Technical Amendment Agency: Food and Drug Administration, HHS. ACTION: Final rule; technical amendment. SUMMARY: The Food and Drug Administration (FDA) is amending its...

Y-chromosome diversity in Catalan surname samples: insights into surname origin and frequency

PubMed Central

Solé-Morata, Neus; Bertranpetit, Jaume; Comas, David; Calafell, Francesc

2015-01-01

The biological behavior of the Y chromosome, which is paternally inherited, implies that males sharing the same surname may also share a similar Y chromosome. However, socio-cultural factors, such as polyphyletism, non-paternity, adoption, or matrilineal surname transmission, may prevent the joint transmission of the surname and the Y chromosome. By genotyping 17 Y-STRs and 68 SNPs in ~2500 male samples that each carried one of the 50 selected Catalan surnames, we could determine sets of descendants of a common ancestor, the population of origin of the common ancestor, and the date when such a common ancestor lived. Haplotype diversity was positively correlated with surname frequency, that is, rarer surnames showed the strongest signals of coancestry. Introgression rates of Y chromosomes into a surname by non-paternity, adoption, and transmission of the maternal surname were estimated at 1.5−2.6% per generation, with some local variation. Average ages for the founders of the surnames were estimated at ~500 years, suggesting a delay between the origin of surnames (twelfth and thirteenth centuries) and the systematization of their paternal transmission. We have found that, in general, a foreign etymology for a surname does not often result in a non-indigenous origin of surname founders; however, bearers of some surnames with an Arabic etymology show an excess of North African haplotypes. Finally, we estimate that surname prediction from a Y-chromosome haplotype, which may have interesting forensic applications, has a ~60% sensitivity but a 17% false discovery rate. PMID:25689924

APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability.

PubMed

Sansregret, Laurent; Patterson, James O; Dewhurst, Sally; López-García, Carlos; Koch, André; McGranahan, Nicholas; Chao, William Chong Hang; Barry, David J; Rowan, Andrew; Instrell, Rachael; Horswell, Stuart; Way, Michael; Howell, Michael; Singleton, Martin R; Medema, René H; Nurse, Paul; Petronczki, Mark; Swanton, Charles

2017-02-01

Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization. APC/C impairment caused adaptation to MPS1 inhibitors, revealing a likely resistance mechanism to therapies targeting the spindle assembly checkpoint. Finally, CRISPR-mediated introduction of cancer somatic mutations in the APC/C subunit cancer driver gene CDC27 reduces chromosome segregation errors, whereas reversal of an APC/C subunit nonsense mutation increases CIN. Subtle variations in mitotic duration, determined by APC/C activity, influence the extent of CIN, allowing cancer cells to dynamically optimize fitness during tumor evolution. We report a mechanism whereby cancers balance the evolutionary advantages associated with CIN against the fitness costs caused by excessive genome instability, providing insight into the consequence of CDC27 APC/C subunit driver mutations in cancer. Lengthening of mitosis through APC/C modulation may be a common mechanism of resistance to cancer therapeutics that increase chromosome segregation errors. Cancer Discov; 7(2); 218-33. ©2017 AACR.See related commentary by Burkard and Weaver, p. 134This article is highlighted in the In This Issue feature, p. 115. ©2017 American Association for Cancer Research.

2012 Technical Corrections Fact Sheet

EPA Pesticide Factsheets

Final Rule: 2012 Technical Corrections, Clarifying and Other Amendments to theGreenhouse Gas Reporting Rule, and Confidentiality Determinations for Certain DataElements of the Fluorinated Gas Source Category

The forensic value of X-linked markers in mixed-male DNA analysis.

PubMed

He, HaiJun; Zha, Lagabaiyila; Cai, JinHong; Huang, Jian

2018-05-04

Autosomal genetic markers and Y chromosome markers have been widely applied in analysis of mixed stains at crime scenes by forensic scientists. However, true genotype combinations are often difficult to distinguish using autosomal markers when similar amounts of DNA are contributed by multiple donors. In addition, specific individuals cannot be determined by Y chromosomal markers because male relatives share the same Y chromosome. X-linked markers, possessing characteristics somewhere intermediate between autosomes and the Y chromosome, are less universally applied in criminal casework. In this paper, X markers are proposed to apply to male mixtures because their true genes can be more easily and accurately recognized than the decision of the genotypes of AS markers. In this study, an actual two-man mixed stain from a forensic case file and simulated male-mixed DNA were examined simultaneously with the X markers and autosomal markers. Finally, the actual mixture was separated successfully by the X markers, although it was unresolved by AS-STRs, and the separation ratio of the simulated mixture was much higher using Chr X tools than with AS methods. We believe X-linked markers provide significant advantages in individual discrimination of male mixtures that should be further applied to forensic work.

Evaluation of Routine Atmospheric Sounding Measurements using Unmanned Systems (ERASMUS): Final Technical Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Boer, Gijs; Lawrence, Dale; Palo, Scott

2017-03-29

This final technical report details activities undertaken as part of the referenced project. Included is information on the preparation of aircraft for deployment to Alaska, summaries of the three deployments covered under this project, and a brief description of the dataset and science directions pursued. Additionally, we provide information on lessons learned, publications, and presentations resulting from this work.

Vocational Curriculum Modification. Teaching Technical Language to Learning Handicapped Students. Project HIRE: A Curriculum Management System for Instructing the Handicapped. Final Report, Volume 1.

ERIC Educational Resources Information Center

Gardner, David C.; And Others

Volume 1 of the final report on Project HIRE reports the design, development, field-testing, and refining of self-instructional packages to teach entry level technical vocabulary to learning handicapped students mainstreamed in vocational programs. Volume 2, a management handbook, reports the methods and findings concerning development of…

Joint Technical Architecture for Robotic Systems (JTARS)-Final Report

NASA Technical Reports Server (NTRS)

Bradley, Arthur T.; Holloway, Sidney E., III

2006-01-01

This document represents the final report for the Joint Technical Architecture for Robotic Systems (JTARS) project, funded by the Office of Exploration as part of the Intramural Call for Proposals of 2005. The project was prematurely terminated, without review, as part of an agency-wide realignment towards the development of a Crew Exploration Vehicle (CEV) and meeting the near-term goals of lunar exploration.

Review of Final Year MSP Evaluations, Performance Period 2007. Analytic and Technical Support for Mathematics and Science Partnerships

ERIC Educational Resources Information Center

Bobronnikov, Ellen; Rhodes, Hilary; Bradley, Cay

2010-01-01

This final report culminates the evaluation and technical assistance provided for the U.S. Department of Education's Mathematics and Science Partnership (MSP) Program and its projects since 2005. As part of this support, Abt Associates looked across the portfolio of projects funded by the MSP program to draw lessons on best practices. This…

Pacific Educational Computer Network Study. Final Report.

ERIC Educational Resources Information Center

Hawaii Univ., Honolulu. ALOHA System.

The Pacific Educational Computer Network Feasibility Study examined technical and non-technical aspects of the formation of an international Pacific Area computer network for higher education. The technical study covered the assessment of the feasibility of a packet-switched satellite and radio ground distribution network for data transmission…

Development of pachytene FISH maps for six maize chromosomes and their integration with other maize maps for insights into genome structure variation.

PubMed

Figueroa, Debbie M; Bass, Hank W

2012-05-01

Integrated cytogenetic pachytene fluorescence in situ hybridization (FISH) maps were developed for chromosomes 1, 3, 4, 5, 6, and 8 of maize using restriction fragment length polymorphism marker-selected Sorghum propinquum bacterial artificial chromosomes (BACs) for 19 core bin markers and 4 additional genetic framework loci. Using transgenomic BAC FISH mapping on maize chromosome addition lines of oats, we found that the relative locus position along the pachytene chromosome did not change as a function of total arm length, indicative of uniform axial contraction along the fibers during mid-prophase for tested loci on chromosomes 4 and 5. Additionally, we cytogenetically FISH mapped six loci from chromosome 9 onto their duplicated syntenic regions on chromosomes 1 and 6, which have varying amounts of sequence divergence, using sorghum BACs homologous to the chromosome 9 loci. We found that successful FISH mapping was possible even when the chromosome 9 selective marker had no counterpart in the syntenic block. In total, these 29 FISH-mapped loci were used to create the most extensive pachytene FISH maps to date for these six maize chromosomes. The FISH-mapped loci were then merged into one composite karyotype for direct comparative analysis with the recombination nodule-predicted cytogenetic, genetic linkage, and genomic physical maps using the relative marker positions of the loci on all the maps. Marker colinearity was observed between all pair-wise map comparisons, although marker distribution patterns varied widely in some cases. As expected, we found that the recombination nodule-based predictions most closely resembled the cytogenetic map positions overall. Cytogenetic and linkage map comparisons agreed with previous studies showing a decrease in marker spacing in the peri-centromeric heterochromatin region on the genetic linkage maps. In fact, there was a general trend with most loci mapping closer towards the telomere on the linkage maps than on the cytogenetic maps, regardless of chromosome number or maize inbred line source, with just some of the telomeric loci exempted. Finally and somewhat surprisingly, we observed considerable variation between the relative arm positions of loci when comparing our cytogenetic FISH map to the B73 genomic physical maps, even where comparisons were to a B73-derived cytogenetic map. This variation is more evident between different chromosome arms, but less so within a given arm, ruling out any type of inbred-line dependent global features of linear deoxyribonucleic acid compared with the meiotic fiber organization. This study provides a means for analyzing the maize genome structure by producing new connections for integrating the cytogenetic, linkage, and physical maps of maize.

Comparative cytogenetic analysis of some species of the Dendropsophus microcephalus group (Anura, Hylidae) in the light of phylogenetic inferences

PubMed Central

2013-01-01

Background Dendropsophus is a monophyletic anuran genus with a diploid number of 30 chromosomes as an important synapomorphy. However, the internal phylogenetic relationships of this genus are poorly understood. Interestingly, an intriguing interspecific variation in the telocentric chromosome number has been useful in species identification. To address certain uncertainties related to one of the species groups of Dendropsophus, the D. microcephalus group, we carried out a cytogenetic analysis combined with phylogenetic inferences based on mitochondrial sequences, which aimed to aid in the analysis of chromosomal characters. Populations of Dendropsophus nanus, Dendropsophus walfordi, Dendropsophus sanborni, Dendropsophus jimi and Dendropsophus elianeae, ranging from the extreme south to the north of Brazil, were cytogenetically compared. A mitochondrial region of the ribosomal 12S gene from these populations, as well as from 30 other species of Dendropsophus, was used for the phylogenetic inferences. Phylogenetic relationships were inferred using maximum parsimony and Bayesian analyses. Results The species D. nanus and D. walfordi exhibited identical karyotypes (2n = 30; FN = 52), with four pairs of telocentric chromosomes and a NOR located on metacentric chromosome pair 13. In all of the phylogenetic hypotheses, the paraphyly of D. nanus and D. walfordi was inferred. D. sanborni from Botucatu-SP and Torres-RS showed the same karyotype as D. jimi, with 5 pairs of telocentric chromosomes (2n = 30; FN = 50) and a terminal NOR in the long arm of the telocentric chromosome pair 12. Despite their karyotypic similarity, these species were not found to compose a monophyletic group. Finally, the phylogenetic and cytogenetic analyses did not cluster the specimens of D. elianeae according to their geographical occurrence or recognized morphotypes. Conclusions We suggest that a taxonomic revision of the taxa D. nanus and D. walfordi is quite necessary. We also observe that the number of telocentric chromosomes is useful to distinguish among valid species in some cases, although it is unchanged in species that are not necessarily closely related phylogenetically. Therefore, inferences based on this chromosomal character must be made with caution; a proper evolutionary analysis of the karyotypic variation in Dendropsophus depends on further characterization of the telocentric chromosomes found in this group. PMID:23822759

Community College Technical Mathematics Project. Final Report.

ERIC Educational Resources Information Center

Self, Samuel L.

The purpose of the research project was to develop an applied or technical mathematics curriculum which would meet the needs of vocational-technical students at the community college level. The research project was divided into three distinct phases: Identifying the mathematical concepts requisite for job-entry competencies in each of the…

7 CFR 614.10 - Appeals before the Farm Service Agency county committee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... section are completed, provide the FSA county committee with a written technical determination in the form... part 780, a participant may appeal a final technical determination or a program decision to the FSA... appeal requests review of the technical determination by the applicable State Conservationist prior to...

77 FR 47495 - Final Priority; Technical Assistance on State Data Collection, Analysis, and Reporting-National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

... intervention and preschool service providers with data on their qualifications, certification, and preparation... Priority; Technical Assistance on State Data Collection, Analysis, and Reporting--National IDEA Technical Assistance Center on Early Childhood Longitudinal Data Systems; Rule #0;#0;Federal Register / Vol. 77, No...

77 FR 18716 - Transportation Security Administration Postal Zip Code Change; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... organizational changes and it has no substantive effect on the public. DATES: Effective March 28, 2012. FOR... No. 1572-9] Transportation Security Administration Postal Zip Code Change; Technical Amendment AGENCY: Transportation Security Administration, DHS. ACTION: Final rule. SUMMARY: This rule is a technical change to...

Studying the Cost and Value of Library Services: Final Report. Technical Report APLAB/94-3/1,2,3,4.

ERIC Educational Resources Information Center

Kantor, Paul B.; And Others

This is the final technical report (in three parts) of a 15-month long project to study the costs and value of library functions at five major research libraries. Twenty-one services or service aspects were studied, and numerous measures of the importance or benefit of the service to the users were made. These measures were studied together to lay…

An Inquiry into Testing of Information Retrieval Systems. Comparative Systems Laboratory Final Technical Report, Part III: CSL Related Studies.

ERIC Educational Resources Information Center

Zull, Carolyn Gifford, Ed.; And Others

This third volume of the Comparative Systems Laboratory (CSL) Final Technical Report is a collection of relatively independent studies performed on CSL materials. Covered in this document are studies on: (1) properties of files, including a study of the growth rate of a dictionary of index terms as influenced by number of documents in the file and…

Programs of Study as a State Policy Mandate: A Longitudinal Study of the South Carolina Personal Pathways to Success Initiative. Unabridged Final Technical Report (Years 1-5)

ERIC Educational Resources Information Center

Hammond, Cathy; Withington, Cairen; Sharp, Julia L.; Mobley, Catherine; Drew, Sam F.; Stringfield, Samuel C.; Stipanovic, Natalie; Swiger, Caroline M.; Daugherty, Lindsay; Griffith, Cathy

2014-01-01

This final report presents findings from data collection and analysis conducted during a five-year study by the National Dropout Prevention Center (NDPC) at Clemson University, in conjunction with colleagues from the National Research Center for Career and Technical Education (NRCCTE) at the University of Louisville. This project was one of three…

Ground-Based Radiometric Measurements of Slant Path Attenuation in the V/W Bands

DTIC Science & Technology

2016-04-01

GROUND-BASED RADIOMETRIC MEASUREMENTS OF SLANT PATH ATTENUATION IN THE V/W BANDS APRIL 2016 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE...2. REPORT TYPE FINAL TECHNICAL REPORT 3. DATES COVERED (From - To) OCT 2012 – SEP 2015 4. TITLE AND SUBTITLE GROUND-BASED RADIOMETRIC MEASUREMENTS ...SUPPLEMENTARY NOTES 14. ABSTRACT Ground-based radiometric techniques were applied to measure the slant path attenuation cumulative distribution function to

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders.

PubMed

Fonda Allen, Jill; Stoll, Katie; Bernhardt, Barbara A

2016-02-01

Genetic carrier screening, prenatal screening for aneuploidy, and prenatal diagnostic testing have expanded dramatically over the past 2 decades. Driven in part by powerful market forces, new complex testing modalities have become available after limited clinical research. The responsibility for offering these tests lies primarily on the obstetrical care provider and has become more burdensome as the number of testing options expands. Genetic testing in pregnancy is optional, and decisions about undergoing tests, as well as follow-up testing, should be informed and based on individual patients' values and needs. Careful pre- and post-test counseling is central to supporting informed decision-making. This article explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for fetal aneuploidies using cell-free DNA, and diagnostic testing using fetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular karyotyping of the 2La inversion in Anopheles gambiae.

PubMed

White, Bradley J; Santolamazza, Federica; Kamau, Luna; Pombi, Marco; Grushko, Olga; Mouline, Karine; Brengues, Cecile; Guelbeogo, Wamdaogo; Coulibaly, Mamadou; Kayondo, Jonathan K; Sharakhov, Igor; Simard, Frederic; Petrarca, Vincenzo; Della Torre, Alessandra; Besansky, Nora J

2007-02-01

The African malaria vector Anopheles gambiae is polymorphic for alternative arrangements on the left arm of chromosome 2 (2La and 2L+(a)) that are non-randomly distributed with respect to degree of aridity. Detailed studies on the ecological role of inversion 2La have been hindered by the technical demands of traditional karyotype analysis and by sex- and stage-specific limitations on the availability of polytene chromosomes favorable for analysis. Recent molecular characterization of both inversion breakpoints presented the opportunity to develop a polymerase chain reaction (PCR)-based method for karyotype analysis. Here we report the development of this molecular diagnostic assay and the results of extensive field validation. When tested on 765 An. gambiae specimens sampled across Africa, the molecular approach compared favorably with traditional cytologic methods, correctly scoring > 94% of these specimens. By providing ready access to the 2La karyotype, this tool lays groundwork for future studies of the ecological genomics of this medically important species.

Advanced Transportation System Studies Technical Area 2 (TA-2) Heavy Lift Launch Vehicle Development Contract. Volume 2; Technical Results

NASA Technical Reports Server (NTRS)

1995-01-01

The purpose of the Advanced Transportation System Studies (ATSS) Technical Area 2 (TA-2) Heavy Lift Launch Vehicle Development contract was to provide advanced launch vehicle concept definition and analysis to assist NASA in the identification of future launch vehicle requirements. Contracted analysis activities included vehicle sizing and performance analysis, subsystem concept definition, propulsion subsystem definition (foreign and domestic), ground operations and facilities analysis, and life cycle cost estimation. This document is Volume 2 of the final report for the contract. It provides documentation of selected technical results from various TA-2 analysis activities, including a detailed narrative description of the SSTO concept assessment results, a user's guide for the associated SSTO sizing tools, an SSTO turnaround assessment report, an executive summary of the ground operations assessments performed during the first year of the contract, a configuration-independent vehicle health management system requirements report, a copy of all major TA-2 contract presentations, a copy of the FLO launch vehicle final report, and references to Pratt & Whitney's TA-2 sponsored final reports regarding the identification of Russian main propulsion technologies.

Technical Evaluation Motor No. 7 (TEM-7)

NASA Technical Reports Server (NTRS)

Hughes, Phil

1991-01-01

The Technical Evaluation Motor No. 7 (TEM-7) test was a full-scale, full duration static test firing of a high performance motor-configuration solid rocket motor with nozzle vectoring. The final test report documents the procedures, performance, and results of the static test firing of TEM-7. All observations, discussions, conclusions, and recommendations included in the report are complete and final except for the TEM-7 fixed housing unbond investigation. A presentation and discussion of TEM-7 performance, anomalies, and test result concurrence with the objectives outlined in CTP-0107, Rev A, Space Shuttle Technical Evaluation Motor No. 7 (TEM-7) Static Fire Test Plan are included.

Building Stronger State Energy Partnerships with the U.S. Department of Energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, Kate

2011-09-30

This final technical report details the results of total work efforts and progress made from October 2007 – September 2011 under the National Association of State Energy Officials (NASEO) cooperative agreement DE-FC26-07NT43264, Building Stronger State Energy Partnerships with the U.S. Department of Energy. Major topical project areas in this final report include work efforts in the following areas: Energy Assurance and Critical Infrastructure, State and Regional Technical Assistance, Regional Initiative, Regional Coordination and Technical Assistance, and International Activities in China. All required deliverables have been provided to the National Energy Technology Laboratory and DOE program officials.

Final Technical Report of Project DE-FG02-96ER14647

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundeen, Stephen R.

This is the final technical report of work completed under DOE support over the period Sept. 1, 1996 until May 31, 2015. The title of the project was "Ion/Excited Atom Collision Studies with a Rydberg Target and a CO2 Laser" from 9/1/96 to 10/31/06, and "Properties of Actinide Ions from Measurements of Rydberg Ion Fine Structure" from 11/1/06 until 5/31/15. The primary technical results were a detailed experimental study of resonant charge transfer between Rydberg atoms and highly-charged ions, and unique measurements of many properties of multiply-charged Thorium ions.

PATTERNS OF GENETIC VARIATION IN LUPINUS PERENNIS REVEALED BY MICROSATELLITE LOCI ISOLATED WITH A NOVEL CHROMOSOME-WALKING APPROACH. (R826596)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

The genetics of inviability and male sterility in hybrids between Anopheles gambiae and An. arabiensis.

PubMed

Slotman, M; Della Torre, A; Powell, J R

2004-05-01

Male hybrids between Anopheles gambiae and An. arabiensis suffer from hybrid sterility, and inviability effects are sometimes present as well. We examined the genetic basis of these reproductive barriers between the two species, using 21 microsatellite markers. Generally, recessive inviability effects were found on the X chromosome of gambiae that are incompatible with at least one factor on each arabiensis autosome. Inviability is complete when the gambiae and arabiensis inviability factors are hemi- or homozygous. Using a QTL mapping approach, regions that contribute to male hybrid sterility were also identified. The X chromosome has a disproportionately large effect on male hybrid sterility. Additionally, several moderate-to-large autosomal QTL were found in both species. The effect of these autosomal QTL is contingent upon the presence of an X chromosome from the other species. Substantial regions of the autosomes do not contribute markedly to male hybrid sterility. Finally, no evidence for epistatic interactions between conspecific sterility loci was found.

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

PubMed

Tonini, Gian Paolo

2017-01-05

Neuroblastoma is a pediatric cancer with a low survival rate of patients with metastatic stage 4 disease. Tumor aggressiveness and progression have been associated with structural copy number variations (CNVs) that are observed in malignant cells. In contrast, localized Neuroblastomas, which are associated with a low number of structural CNVs but frequent numerical CNVs, are less aggressive, and patients have good outcomes. Finally, whole-genome and whole-exome sequencing of Neuroblastoma tissues have shown few damaging mutations in these tumors. In the present report it is proposed that chromosome instability (CIN) plays a major role in Neuroblastoma tumorigenesis and that CIN is already present in the early phases of tumor development. High CIN can promote several types of chromosomal damage including chromothripsis, gene deletion, amplification and rearrangements, which deregulate gene expression. Indeed, gene rearrangements have been reported as a new scenario in the development of Neuroblastoma, which supports the hypothesis that CIN is an early step preliminary to the late catastrophic events leading to tumor development.

Mechanisms and Consequences of Double-strand DNA Break Formation in Chromatin

PubMed Central

Cannan, Wendy J.; Pederson, David S.

2016-01-01

All organisms suffer double-strand breaks (DSBs) in their DNA as a result of exposure to ionizing radiation. DSBs can also form when replication forks encounter DNA lesions or repair intermediates. The processing and repair of DSBs can lead to mutations, loss of heterozygosity, and chromosome rearrangements that result in cell death or cancer. The most common pathway used to repair DSBs in metazoans (non-homologous DNA end joining) is more commonly mutagenic than the alternative pathway (homologous recombination mediated repair). Thus, factors that influence the choice of pathways used DSB repair can affect an individual’s mutation burden and risk of cancer. This review describes radiological, chemical and biological mechanisms that generate DSBs, and discusses the impact of such variables as DSB etiology, cell type, cell cycle, and chromatin structure on the yield, distribution, and processing of DSBs. The final section focuses on nucleosome-specific mechanisms that influence DSB production, and the possible relationship between higher order chromosome coiling and chromosome shattering (chromothripsis). PMID:26040249

RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts

PubMed Central

Luciano, Pierre; Coulon, Stéphane; Faure, Virginie; Corda, Yves; Bos, Julia; Brill, Steven J; Gilson, Eric; Simon, Marie-Noelle; Géli, Vincent

2012-01-01

In Saccharomyces cerevisiae, the telomerase complex binds to chromosome ends and is activated in late S-phase through a process coupled to the progression of the replication fork. Here, we show that the single-stranded DNA-binding protein RPA (replication protein A) binds to the two daughter telomeres during telomere replication but only its binding to the leading-strand telomere depends on the Mre11/Rad50/Xrs2 (MRX) complex. We further demonstrate that RPA specifically co-precipitates with yKu, Cdc13 and telomerase. The interaction of RPA with telomerase appears to be mediated by both yKu and the telomerase subunit Est1. Moreover, a mutation in Rfa1 that affects both the interaction with yKu and telomerase reduces the dramatic increase in telomere length of a rif1Δ, rif2Δ double mutant. Finally, we show that the RPA/telomerase association and function are conserved in Schizosaccharomyces pombe. Our results indicate that in both yeasts, RPA directly facilitates telomerase activity at chromosome ends. PMID:22354040

RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts.

PubMed

Luciano, Pierre; Coulon, Stéphane; Faure, Virginie; Corda, Yves; Bos, Julia; Brill, Steven J; Gilson, Eric; Simon, Marie-Noelle; Géli, Vincent

2012-04-18

In Saccharomyces cerevisiae, the telomerase complex binds to chromosome ends and is activated in late S-phase through a process coupled to the progression of the replication fork. Here, we show that the single-stranded DNA-binding protein RPA (replication protein A) binds to the two daughter telomeres during telomere replication but only its binding to the leading-strand telomere depends on the Mre11/Rad50/Xrs2 (MRX) complex. We further demonstrate that RPA specifically co-precipitates with yKu, Cdc13 and telomerase. The interaction of RPA with telomerase appears to be mediated by both yKu and the telomerase subunit Est1. Moreover, a mutation in Rfa1 that affects both the interaction with yKu and telomerase reduces the dramatic increase in telomere length of a rif1Δ, rif2Δ double mutant. Finally, we show that the RPA/telomerase association and function are conserved in Schizosaccharomyces pombe. Our results indicate that in both yeasts, RPA directly facilitates telomerase activity at chromosome ends.

Genetics in methylotrophic bacteria: Appendix. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lidstrom, M.E.

This research has focused primarily on promoters in Methylobacterium extorquens AM1 and in methanotrophic bacteria. In Methylobacterium extorquens work continued on the moxF promoter. The author constructed chromosomal lacZ fusions of this promoter to avoid the regulation problems of plasmid-borne fragments and has shown that this is regulated normally in the chromosome. She has constructed lacZ fusions to some of the mox genes involved in the synthesis of the cofactor, PQQ, in order to carry out similar analysis of transcription of PQQ genes. The author has continued to isolate mox genes in methanotrophs for the purpose of studying their promotersmore » and transcriptional regulation.« less

BRG1 and LKB1: tales of two tumor suppressor genes on chromosome 19p and lung cancer.

PubMed

Rodriguez-Nieto, Salvador; Sanchez-Cespedes, Montse

2009-04-01

Losses of heterozygosity (LOH) of the short arm of chromosome 19 are frequent in lung cancer, suggesting that one or more tumor suppressor genes are present in this region. The LKB1 gene, also called STK11, is somatically inactivated through point mutations and large deletions in lung tumors, demonstrating that LKB1 is a target of the LOH of this chromosomal arm. Data from several independent groups have provided information about the profiles of lung tumors with LKB1 inactivation and it is generally agreed that this alteration strongly predominates in non-small cell lung cancer, in particular adenocarcinomas, in smokers. The LKB1 protein has serine-threonine kinase activity and is involved in the regulation of the cell energetic checkpoint through the phosphorylation and activation of adenosine monophosphate-dependent kinase (AMPK). LKB1 is also involved in other processes such as cell polarization, probably through substrates other than AMPK. Interestingly, another gene on chromosome 19p, BRG1, encoding a component of the SWI/SNF chromatin-remodeling complex, has emerged as a tumor suppressor gene that is altered in lung tumors. Similar to LKB1, BRG1 is somatically inactivated by point mutations or large deletions in lung tumors featuring LOH of chromosome 19p. These observations suggest an important role for BRG1 in lung cancer and highlight the need to further our understanding of the function of Brahma/SWI2-related gene 1 (BRG1) in cancer. Finally, simultaneous mutations at LKB1 and BRG1 are common in lung cancer cells, which exemplifies how a single event, LOH of chromosome 19p in this instance, targets two different tumor suppressors.

High-resolution chromosome mapping of BACs using multi-colour FISH and pooled-BAC FISH as a backbone for sequencing tomato chromosome 6.

PubMed

Szinay, Dóra; Chang, Song-Bin; Khrustaleva, Ludmila; Peters, Sander; Schijlen, Elio; Bai, Yuling; Stiekema, Willem J; van Ham, Roeland C H J; de Jong, Hans; Klein Lankhorst, René M

2008-11-01

Within the framework of the International Solanaceae Genome Project, the genome of tomato (Solanum lycopersicum) is currently being sequenced. We follow a 'BAC-by-BAC' approach that aims to deliver high-quality sequences of the euchromatin part of the tomato genome. BACs are selected from various libraries of the tomato genome on the basis of markers from the F2.2000 linkage map. Prior to sequencing, we validated the precise physical location of the selected BACs on the chromosomes by five-colour high-resolution fluorescent in situ hybridization (FISH) mapping. This paper describes the strategies and results of cytogenetic mapping for chromosome 6 using 75 seed BACs for FISH on pachytene complements. The cytogenetic map obtained showed discrepancies between the actual chromosomal positions of these BACs and their markers on the linkage group. These discrepancies were most notable in the pericentromere heterochromatin, thus confirming previously described suppression of cross-over recombination in that region. In a so called pooled-BAC FISH, we hybridized all seed BACs simultaneously and found a few large gaps in the euchromatin parts of the long arm that are still devoid of seed BACs and are too large for coverage by expanding BAC contigs. Combining FISH with pooled BACs and newly recruited seed BACs will thus aid in efficient targeting of novel seed BACs into these areas. Finally, we established the occurrence of repetitive DNA in heterochromatin/euchromatin borders by combining BAC FISH with hybridization of a labelled repetitive DNA fraction (Cot-100). This strategy provides an excellent means to establish the borders between euchromatin and heterochromatin in this chromosome.

Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

PubMed Central

Buganim, Yosef; Solomon, Hilla; Goldfinger, Naomi; Hovland, Randi; Ke, Xi-Song; Oyan, Anne M.; Kalland, Karl-H.; Rotter, Varda; Domany, Eytan

2011-01-01

Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification. PMID:21297939

78 FR 34392 - Guidance for Industry and Food and Drug Administration Staff: Technical Considerations for Pen...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

...] Guidance for Industry and Food and Drug Administration Staff: Technical Considerations for Pen, Jet, and... availability of a final guidance document entitled ``Technical Considerations for Pen, Jet, and Related... developing information to support a marketing application for a pen, jet, or related injector device intended...

Florida Study of Career and Technical Education. Final Report

ERIC Educational Resources Information Center

Jacobson, Louis; Mokher, Christine

2014-01-01

A key goal of the "Carl D. Perkins Career and Technical Education Act of 2006" ("Perkins IV") is to ensure career and technical education (CTE) programs are widely available for preparing high school and college students for "high skill, high wage, or high demand occupations in current or emerging professions"…

Analysis of the Ambient Particulate Matter-induced Chromosomal Aberrations Using an In Vitro System.

PubMed

Miousse, Isabelle R; Koturbash, Igor; Chalbot, Marie-Cécile; Hauer-Jensen, Martin; Kavouras, Ilias; Pathak, Rupak

2016-12-21

Exposure to particulate matter (PM) is a major world health concern, which may damage various cellular components, including the nuclear genetic material. To assess the impact of PM on nuclear genetic integrity, structural chromosomal aberrations are scored in the metaphase spreads of mouse RAW264.7 macrophage cells. PM is collected from ambient air with a high volume total suspended particles sampler. The collected material is solubilized and filtered to retain the water-soluble, fine portion. The particles are characterized for chemical composition by nuclear magnetic resonance (NMR) spectroscopy. Different concentrations of particle suspension are added onto an in vitro culture of RAW264.7 mouse macrophages for a total exposure time of 72 hr, along with untreated control cells. At the end of exposure, the culture is treated with colcemid to arrest cells in metaphase. Cells are then harvested, treated with hypotonic solution, fixed in acetomethanol, dropped onto glass slides and finally stained with Giemsa solution. Slides are examined to assess the structural chromosomal aberrations (CAs) in metaphase spreads at 1,000X magnification using a bright-field microscope. 50 to 100 metaphase spread are scored for each treatment group. This technique is adapted for the detection of structural chromosomal aberrations (CAs), such as chromatid-type breaks, chromatid-type exchanges, acentric fragments, dicentric and ring chromosomes, double minutes, endoreduplication, and Robertsonian translocations in vitro after exposure to PM. It is a powerful method to associate a well-established cytogenetic endpoint to epigenetic alterations.

The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes.

PubMed

Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

2016-01-01

Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects.

Meiotic drive impacts expression and evolution of x-linked genes in stalk-eyed flies.

PubMed

Reinhardt, Josephine A; Brand, Cara L; Paczolt, Kimberly A; Johns, Philip M; Baker, Richard H; Wilkinson, Gerald S

2014-01-01

Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (XSR) or a standard X chromosome (XST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that XSR and XST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on XSR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.

[Tripartite motif-containing protein 34 (TRIM34) colocalized with micronuclei chromosome and hampers its movement to equatorial plate during the metaphase stage of mitosis].

PubMed

Sun, Dakang; An, Xinye; Ji, Bing; Cheng, Yanli; Gao, Honglian; Tian, Mingming

2016-06-01

Objective To examine whether tripartite motif-containing protein 34 (TRIM34) is colocalized with micronuclei and investigate the influence on the movement of micronuclei chromosome in mitosis. Methods The eukaryotic expression vector TRIM34-pEGFP-N3 was constructed, identified and then transfected into HEK293T cells. With 4', 6-diamidino-2-phenylindole 2HCI (DAPI) staining, the colocalization between TRIM34 and micronuclei was observed under a fluorescence microscope. Moreover, MitoTracker(R)Deep Red was used to identify the colocalization between the complex of TRIM34-micronulei and mitochondria under a confocal microscope. Finally, the effect of TRIM34 on the movement of micronuclei chromosome in mitosis was examined. Results DNA sequencing confirmed that the vector TRIM34-pEGFP-N3 was constructed successfully. A fluorescence microscope revealed that TRIM34 could be colocalized with micronuclei in HEK293T cells transfected with TRIM34-pEGFP-N3. In the same manner, a confocal microscope distinctly showed that TRIM34 was colocalized with micronuclei similarly in appearance. However, there was no distinguished colocalization relationship between the complex of TRIM34-micronulei and mitochondria. Interestingly, the micronuclei chromosome conjugated with TRIM34 was hardly transferred to equatorial plate during the metaphase stage of mitosis. Conclusion TRIM34 is colocalized with micronuclei chromosome and hampers its movement to equatorial plate in mitosis.

Regulatory RNAs and chromatin modification in dosage compensation: a continuous path from flies to humans?

PubMed

Angelopoulou, Roxani; Lavranos, Giagkos; Manolakou, Panagiota

2008-03-20

Chromosomal sex determination is a widely distributed strategy in nature. In the most classic scenario, one sex is characterized by a homologue pair of sex chromosomes, while the other includes two morphologically and functionally distinct gonosomes. In mammalian diploid cells, the female is characterized by the presence of two identical X chromosomes, while the male features an XY pair, with the Y bearing the major genetic determinant of sex, i.e. the SRY gene. In other species, such as the fruitfly, sex is determined by the ratio of autosomes to X chromosomes. Regardless of the exact mechanism, however, all these animals would exhibit a sex-specific gene expression inequality, due to the different number of X chromosomes, a phenomenon inhibited by a series of genetic and epigenetic regulatory events described as "dosage compensation". Since adequate available data is currently restricted to worms, flies and mammals, while for other groups of animals, such as reptiles, fish and birds it is very limited, it is not yet clear whether this is an evolutionary conserved mechanism. However certain striking similarities have already been observed among evolutionary distant species, such as Drosophila melanogaster and Mus musculus. These mainly refer to a) the need for a counting mechanism, to determine the chromosomal content of the cell, i.e. the ratio of autosomes to gonosomes (a process well understood in flies, but still hypothesized in mammals), b) the implication of non-translated, sex-specific, regulatory RNAs (roX and Xist, respectively) as key elements in this process and the location of similar mediators in the Z chromosome of chicken c) the inclusion of a chromatin modification epigenetic final step, which ensures that gene expression remains stably regulated throughout the affected area of the gonosome. This review summarizes these points and proposes a possible role for comparative genetics, as they seem to constitute proof of maintained cell economy (by using the same basic regulatory elements in various different scenarios) throughout numerous centuries of evolutionary history.

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome

PubMed Central

2013-01-01

Background It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. Methods This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n =  93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n =  34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. Results Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. Conclusions The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals. PMID:23731950

Whole-comparative genomic hybridization in domestic sheep (Ovis aries) breeds.

PubMed

Dávila-Rodríguez, M I; Cortés-Gutiérrez, E I; López-Fernández, C; Pita, M; Mezzanotte, R; Gosálvez, J

2009-01-01

Whole-comparative genomic hybridization (W-CGH) allows identification of chromosomal polymorphisms related to highly repetitive DNA sequences localized in constitutive heterochromatin. Such polymorphisms are detected establishing competition between genomic DNAs in an in situ hybridization environment without subtraction of highly repetitive DNA sequences, when comparing two species from closely related taxa (same species, sub-species, or breeds) or somewhat related taxa. This experimental approach was applied to investigating differences in highly repetitive sequences of three sheep breeds (Castellana, Ojalada, and Assaf). To this end, W-CGH was carried out using mouflon (sheep ancestor) chromosomes as a common target to co-hybridize equimolar quantities of two genomic DNAs obtained from either Castellana, Ojalada or Assaf sheep breeds. The results showed that the amount of constitutive heterochromatin is greater in all pericentromeric heterochromatin regions of acrocentric chromosomes than in metacentric or sex chromosomes. Additionally, when W-CGH was performed using DNAs from the Iberian breeds Castellana and Ojalada, chromosomal pericentromeric regions revealed quantitatively and qualitatively a presence of DNA families similar to that obtained from any of the above-cited breeds. On the contrary, when the DNA used in W-CGH experiments was obtained from Assaf, as compared to either Castellana or Ojalada, two different pericentromeric DNA families of highly repetitive sequences could be detected. Lastly, sex chromosomes were shown to be homogeneous among all breeds and thus revealed no detectable constitutive heterochromatin. W-CGH results were confirmed using DNA breakage detection-FISH experiments (DBD-FISH) carried out on lymphocytes. As a whole, the results showed that two different repetitive DNA families are present in the pericentromeric heterochromatin of the sheep breeds studied here. Additionally, they suggest a differential presence of these distinct repetitive DNA families in Castellana and Ojalada breeds as compared to the Assaf breed. Finally, the results of W-CGH after using mouflon as the targeted chromosomes also show that the two DNA families are present in the ancestor. Copyright 2009 S. Karger AG, Basel.

A foetus with 18p11.32-q21.2 duplication and Xp22.33-p11.1 deletion derived from a maternal reciprocal translocation t(X;18)(q13;q21.3).

PubMed

Chen, Jun-Kun; Liu, Ping; Hu, Li-Qin; Xie, Qing; Huang, Quan-Fei; Liu, Hai-Liang

2018-01-01

Non-invasive prenatal testing (NIPT) evaluates circulating cell-free DNA (cfDNA) and has been widely applied, with highly accurate results for detecting foetal trisomies 21, 18 and 13. Recently, increasing attention has been paid to the clinical application of the non-invasive detection of foetal sub-chromosomal duplications and deletions beyond common aneuploidies. A 32-year-old healthy pregnant woman was referred to the Medical Genetic Centre of Ganzhou Maternal and Child Health Care Hospital. As routine practice, ultrasound examination at a gestational age of 16 weeks showed that the foetus is normal. To avoid invasive prenatal diagnosis procedures, an NIPT was offered to further screen for common foetal chromosomal abnormalities. The result showed that there was an approximately 50.94 Mb duplication in p11.32-q21.2 of chromosome 18 and an approximately 58.46 Mb deletion in p22.33-p11.1 of chromosome X. In addition, the chromosome karyotypes of the parents and foetus were also analysed. Chromosome karyotype analysis results showed that foetal karyotype was 46,X,der(18), the maternal karyotype was 46,XX,t(X;18)(q13;q21.3), and the paternal karyotype revealed no obvious abnormality. In this case, we successfully detected a healthy pregnant woman with balanced translocation X;18(q13;q21.3) and described the foetal karyotype as 46,X,der(18)t(X;18)(q11;q21.1)mat. Our report illustrated these cases which present complex X;autosome balance translocation and X;autosome unbalance translocation which may contribute to severe clinical phenotypes. In addition, our report also proved that the interruption of genes in the Xq critical region is not only reason of primary infertility. Finally, we prompted that NIPT might play a role in the first trimester screening of sub-chromosomal rearrangement.

Final Technical Report for Award DESC0011912, "Trimodal Tapping Mode Atomic Force Microscopy: Simultaneous 4D Mapping of Conservative and Dissipative Probe-Sample Interactions of Energy-Relevant Materials”

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solares, Santiago D.

The final project report covering the period 7/1/14-6/30/17 provides an overview of the technical accomplishments in the areas of (i) fundamental viscoelasticity, (ii) multifrequency atomic force microscopy, and (iii) characterization of energy-relevant materials with atomic force microscopy. A list of publications supported by the project is also provided.

Application of Knowledge-Based Techniques to Tracking Function

DTIC Science & Technology

2006-09-01

38394041 42434445 46474849 505152 53545556 57585960 616263 646566 676869 707172 737475 7677 7879 8081 8283 8485 8687 8889 9091 9293 9495 969798 99100...Knowledge-based applications to adaptive space-time processing. Volume I: Summary”, AFRL-SN-TR-2001-146 Vol. I (of Vol. VI ), Final Technical Report, July...2001-146 Vol. IV (of Vol. VI ), Final Technical Report, July 2001. [53] C. Morgan, L. Moyer, “Knowledge-based applications to adaptive space-time

Forecasting the Future Food Service World of Work. Final Report. Volume III. Technical Papers on the Future of the Food Service Industry. Service Management Reports.

ERIC Educational Resources Information Center

Powers, Thomas F., Ed.; Swinton, John R., Ed.

This third and final volume of a study on the future of the food service industry contains the technical papers on which the information in the previous two volumes was based. The papers were written by various members of the Pennsylvania State University departments of economics, food science, nutrition, social psychology, and engineering and by…

Final Technical Report for contract number DE-FG02-05ER15670

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glazebrook, Jane

This is the final technical report for contract number DE-FG02-05ER15670. The project is now complete, and results of the project have been published. Two papers were published based on work done in the last three-year funding period. The DOIs of these papers are included below. The abstracts of the papers, providing summaries of the work, are included in the body of the report.

Analysis of mutagenic activity of biohazardous organics in Kanawha River sediments. Technical completion report

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, A.R.; Waldron, M.C.

1988-01-01

Residual chemical contamination of Kanawha River sediments may constitute a health hazard. Sediment cores have been analyzed using a coupled bioassay/chemical fractionation procedure. Both bacterial mutagenicity and sister chromatid exchange (SCE) analyses were conducted on sediment samples. Pocatalico River sediments extracts showed no response in either bacterial mutagenicity assay or SCE assay. Extracts from Armour Creek and the Kanawha River induced mutagenicities in the presence of S9 enzymes. The same extracts produced a significant increase in human chromosomal cross-over events.

Astrobee Periodic Technical Review (PTR) Delta 3

NASA Technical Reports Server (NTRS)

Provencher, Christopher; Smith, Marion F.; Smith, Ernest Everett; Bualat, Maria Gabriele; Barlow, Jonathan Spencer

2017-01-01

Astrobee is a free flying robot for the inside of the International Space Station (ISS). The Periodic Technical Review (PTR) delta 3 is the final design review of the system presented to stakeholders.

Polar source analysis : technical memorandum

DOT National Transportation Integrated Search

2017-09-29

The following technical memorandum describes the development, testing and analysis of various polar source data sets. The memorandum also includes recommendation for potential inclusion in future releases of AEDT. This memorandum is the final deliver...

2005 v4.2 Technical Support Document

EPA Pesticide Factsheets

Technical Support Document for the Final Transport Rule describes how updated 2005 NEI, version 2 emissions and were processed for air quality modeling in support of the Cross-state Air Pollution Rule (CSAPR).

Direct Final Rule for Technical Amendments for Marine Spark-Ignition Engines and Vessels

EPA Pesticide Factsheets

Rule published September 16, 2010 to make technical amendments to the design standard for portable marine fuel tanks. This rule incorporates safe recommended practices, developed through industry consensus.

SHOC1 is a ERCC4-(HhH)2-like protein, integral to the formation of crossover recombination intermediates during mammalian meiosis

PubMed Central

Almeida, Luciana P.; Parikh, Aniruddha; de Castro, Rodrigo O.

2018-01-01

Chromosome segregation errors during meiosis result in the formation of aneuploid gametes and are the leading cause of pregnancy loss and birth defects in humans. Proper chromosome segregation requires pairwise associations of maternal and paternal homologous chromosomes. Chiasmata, which are the cytological manifestations of crossovers (COs), provide a physical link that holds the homologs together as a pair, facilitating their orientation on the spindle at meiosis I. Although CO-promoting activities ensure a balanced number and position of COs, their identity and mechanism of action in mammals remain understudied. Previous work in yeast and Arabidopsis has shown that Zip2 and Shoc1 are ortholog proteins with an important role in promoting the formation of COs. Our work is the first study in mammals showing the in vivo and in vitro function of mouse and human SHOC1. We show that purified recombinant human SHOC1, an XPF/MUS81 family member, preferentially binds branched DNA molecules but apparently lacks in vitro endonuclease activity, despite its conserved ERCC4-(HhH)2 core structure. Cytological observations suggest that initial steps of recombination are normal in a majority of spermatocytes from SHOC1 hypomorphic mice. However, late stages of recombination appear abnormal, as chromosomal localization of MLH1 is reduced. In agreement, chiasma formation is reduced, and cells arrest at metaphase I with a few lagging chromosomes and subsequent apoptosis. This analysis of SHOC1-deficient mice and the selective localization of SHOC1 to a subset of recombination sites show that SHOC1 acts at key mid-stage steps of the CO formation process. The formation of chromosome axial elements and homologous pairing are apparently normal, but synapsis is altered with SYCP1 frequently failing to extend the full length of the chromosome axes. Finally, we describe that SHOC1 interacts with TEX11, another protein important for the formation of COs, connecting SHOC1 to chromosome axis and structure. PMID:29742103

Physical mapping of chromosome 12q breakpoints in lipoma, pleomorphic salivary gland adenoma, uterine leiomyoma, and myxoid liposarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenmakers, E.F.P.M.; Kools, P.F.J.; Mols, R.

1994-03-15

The authors report here the physical mapping of recurrent chromosome 12q13-q15 breakpoints in cell lines derived from primary myxoid liposarcoma, lipoma, uterine leiomyoma, and pleomorphic adenoma of the salivary glands. In fluorescence in situ hybridization (FISH) experiments, they first mapped the position of the chromosome 12 translocation breakpoint in uterine leiomyoma cell line LM-30.1/SV40 relative to loci COL2A1, D12S4, D12S17, D12S6, D12S19, D12S8, and D12S7. It mapped between linkage probes CRI-C86 (D12S19) and p7G11 (D12S8). They then isolated YAC clones using CRI-C86- and p7G11-derived sequence-tagged sites, constructed corresponding YAC contigs of 310 and 800 kb, respectively, and a mixture ofmore » them was used to routinely study the various tumor cell lines by FISH analysis. The chromosome 12 breakpoints of all tumor cell lines tested mapped between cosmids LLNL12NCO1-98C10 and LLNL12NCO1-113D12. None of the breakpoints appeared to map within any of the isolated YAC clones. Furthermore, FISH analysis using cosmid LLNL12-NCO1-144G3, which maps at the CHOP locus, revealed that the chromosome 12 breakpoints in all cell lines of the three benign solid tumors that were tested were located distal to the chromosome 12 translocation breakpoint with the CHOP gene in myxoid liposarcoma cells with t(12;16). In conclusion, the studies seem to indicate that the chromosome 12 breakpoints of myxoid liposarcoma, lipoma, uterine leiomyoma, and pleomorphic adenoma of the salivary glands are all clustered within the 7-cM interval between D12S19 and D12S8, with those of the benign solid tumors distal to CHOP. Finally, the MYF5 gene mapped telomeric to LLNL12NCO1-113D12, and the MIP gene mapped centromeric to the chromosome 12 translocation breakpoint in myxoid liposarcoma cells. 56 refs., 5 figs., 3 tabs.« less

Cas9 Nickase-Assisted RNA Repression Enables Stable and Efficient Manipulation of Essential Metabolic Genes in Clostridium cellulolyticum.

PubMed

Xu, Tao; Li, Yongchao; He, Zhili; Van Nostrand, Joy D; Zhou, Jizhong

2017-01-01

Essential gene functions remain largely underexplored in bacteria. Clostridium cellulolyticum is a promising candidate for consolidated bioprocessing; however, its genetic manipulation to reduce the formation of less-valuable acetate is technically challenging due to the essentiality of acetate-producing genes. Here we developed a Cas9 nickase-assisted chromosome-based RNA repression to stably manipulate essential genes in C. cellulolyticum . Our plasmid-based expression of antisense RNA (asRNA) molecules targeting the phosphotransacetylase ( pta ) gene successfully reduced the enzymatic activity by 35% in cellobiose-grown cells, metabolically decreased the acetate titer by 15 and 52% in wildtype transformants on cellulose and xylan, respectively. To control both acetate and lactate simultaneously, we transformed the repression plasmid into lactate production-deficient mutant and found the plasmid delivery reduced acetate titer by more than 33%, concomitant with negligible lactate formation. The strains with pta gene repression generally diverted more carbon into ethanol. However, further testing on chromosomal integrants that were created by double-crossover recombination exhibited only very weak repression because DNA integration dramatically lessened gene dosage. With the design of a tandem repetitive promoter-driven asRNA module and the use of a new Cas9 nickase genome editing tool, a chromosomal integrant (LM3P) was generated in a single step and successfully enhanced RNA repression, with a 27% decrease in acetate titer on cellulose in antibiotic-free medium. These results indicate the effectiveness of tandem promoter-driven RNA repression modules in promoting gene repression in chromosomal integrants. Our combinatorial method using a Cas9 nickase genome editing tool to integrate the gene repression module demonstrates easy-to-use and high-efficiency advantages, paving the way for stably manipulating genes, even essential ones, for functional characterization and microbial engineering.

Cas9 Nickase-Assisted RNA Repression Enables Stable and Efficient Manipulation of Essential Metabolic Genes in Clostridium cellulolyticum

PubMed Central

Xu, Tao; Li, Yongchao; He, Zhili; Van Nostrand, Joy D.; Zhou, Jizhong

2017-01-01

Essential gene functions remain largely underexplored in bacteria. Clostridium cellulolyticum is a promising candidate for consolidated bioprocessing; however, its genetic manipulation to reduce the formation of less-valuable acetate is technically challenging due to the essentiality of acetate-producing genes. Here we developed a Cas9 nickase-assisted chromosome-based RNA repression to stably manipulate essential genes in C. cellulolyticum. Our plasmid-based expression of antisense RNA (asRNA) molecules targeting the phosphotransacetylase (pta) gene successfully reduced the enzymatic activity by 35% in cellobiose-grown cells, metabolically decreased the acetate titer by 15 and 52% in wildtype transformants on cellulose and xylan, respectively. To control both acetate and lactate simultaneously, we transformed the repression plasmid into lactate production-deficient mutant and found the plasmid delivery reduced acetate titer by more than 33%, concomitant with negligible lactate formation. The strains with pta gene repression generally diverted more carbon into ethanol. However, further testing on chromosomal integrants that were created by double-crossover recombination exhibited only very weak repression because DNA integration dramatically lessened gene dosage. With the design of a tandem repetitive promoter-driven asRNA module and the use of a new Cas9 nickase genome editing tool, a chromosomal integrant (LM3P) was generated in a single step and successfully enhanced RNA repression, with a 27% decrease in acetate titer on cellulose in antibiotic-free medium. These results indicate the effectiveness of tandem promoter-driven RNA repression modules in promoting gene repression in chromosomal integrants. Our combinatorial method using a Cas9 nickase genome editing tool to integrate the gene repression module demonstrates easy-to-use and high-efficiency advantages, paving the way for stably manipulating genes, even essential ones, for functional characterization and microbial engineering. PMID:28936208

Evolution of Sex Chromosome Dosage Compensation in Animals: A Beautiful Theory, Undermined by Facts and Bedeviled by Details

PubMed Central

Gu, Luiqi

2017-01-01

Abstract Many animals with genetic sex determination harbor heteromorphic sex chromosomes, where the heterogametic sex has half the gene dose of the homogametic sex. This imbalance, if reflected in the abundance of transcripts or proteins, has the potential to deleteriously disrupt interactions between X-linked and autosomal loci in the heterogametic sex. Classical theory predicts that molecular mechanisms will evolve to provide dosage compensation that recovers expression levels comparable to ancestral expression prior to sex chromosome divergence. Such dosage compensating mechanisms may also, secondarily, result in balanced sex-linked gene expression between males and females. However, numerous recent studies addressing sex chromosome dosage compensation (SCDC) in a diversity of animals have yielded a surprising array of patterns concerning dosage compensation in the heterogametic sex, as well as dosage balance between sexes. These results substantially contradict longstanding theory, catalyzing both novel perspectives and new approaches in dosage compensation research. In this review, we summarize the theory, analytical approaches, and recent results concerning evolutionary patterns of SCDC in animals. We also discuss methodological challenges and discrepancies encountered in this research, which often underlie conflicting results. Finally, we discuss what outstanding questions and opportunities exist for future research on SCDC. PMID:28961969

An efficient algorithm for sorting by block-interchanges and its application to the evolution of vibrio species.

PubMed

Lin, Ying Chih; Lu, Chin Lung; Chang, Hwan-You; Tang, Chuan Yi

2005-01-01

In the study of genome rearrangement, the block-interchanges have been proposed recently as a new kind of global rearrangement events affecting a genome by swapping two nonintersecting segments of any length. The so-called block-interchange distance problem, which is equivalent to the sorting-by-block-interchange problem, is to find a minimum series of block-interchanges for transforming one chromosome into another. In this paper, we study this problem by considering the circular chromosomes and propose a Omicron(deltan) time algorithm for solving it by making use of permutation groups in algebra, where n is the length of the circular chromosome and delta is the minimum number of block-interchanges required for the transformation, which can be calculated in Omicron(n) time in advance. Moreover, we obtain analogous results by extending our algorithm to linear chromosomes. Finally, we have implemented our algorithm and applied it to the circular genomic sequences of three human vibrio pathogens for predicting their evolutionary relationships. Consequently, our experimental results coincide with the previous ones obtained by others using a different comparative genomics approach, which implies that the block-interchange events seem to play a significant role in the evolution of vibrio species.

Structural aspects of the inactive X chromosome.

PubMed

Bonora, Giancarlo; Disteche, Christine M

2017-11-05

A striking difference between male and female nuclei was recognized early on by the presence of a condensed chromatin body only in female cells. Mary Lyon proposed that X inactivation or silencing of one X chromosome at random in females caused this structural difference. Subsequent studies have shown that the inactive X chromosome (Xi) does indeed have a very distinctive structure compared to its active counterpart and all autosomes in female mammals. In this review, we will recap the discovery of this fascinating biological phenomenon and seminal studies in the field. We will summarize imaging studies using traditional microscopy and super-resolution technology, which revealed uneven compaction of the Xi. We will then discuss recent findings based on high-throughput sequencing techniques, which uncovered the distinct three-dimensional bipartite configuration of the Xi and the role of specific long non-coding RNAs in eliciting and maintaining this structure. The relative position of specific genomic elements, including genes that escape X inactivation, repeat elements and chromatin features, will be reviewed. Finally, we will discuss the position of the Xi, either near the nuclear periphery or the nucleolus, and the elements implicated in this positioning.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'. © 2017 The Authors.

A High-Resolution SNP Array-Based Linkage Map Anchors a New Domestic Cat Draft Genome Assembly and Provides Detailed Patterns of Recombination.

PubMed

Li, Gang; Hillier, LaDeana W; Grahn, Robert A; Zimin, Aleksey V; David, Victor A; Menotti-Raymond, Marilyn; Middleton, Rondo; Hannah, Steven; Hendrickson, Sher; Makunin, Alex; O'Brien, Stephen J; Minx, Pat; Wilson, Richard K; Lyons, Leslie A; Warren, Wesley C; Murphy, William J

2016-06-01

High-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species. A high-resolution map would aid in validating and ordering chromosome scaffolds from existing and new genome assemblies. Here, we describe a high-resolution genetic linkage map of the domestic cat genome based on genotyping 453 domestic cats from several multi-generational pedigrees on the Illumina 63K SNP array. The final maps include 58,055 SNP markers placed relative to 6637 markers with unique positions, distributed across all autosomes and the X chromosome. Our final sex-averaged maps span a total autosomal length of 4464 cM, the longest described linkage map for any mammal, confirming length estimates from a previous microsatellite-based map. The linkage map was used to order and orient the scaffolds from a substantially more contiguous domestic cat genome assembly (Felis catus v8.0), which incorporated ∼20 × coverage of Illumina fragment reads. The new genome assembly shows substantial improvements in contiguity, with a nearly fourfold increase in N50 scaffold size to 18 Mb. We use this map to report probable structural errors in previous maps and assemblies, and to describe features of the recombination landscape, including a massive (∼50 Mb) recombination desert (of virtually zero recombination) on the X chromosome that parallels a similar desert on the porcine X chromosome in both size and physical location. Copyright © 2016 Li et al.

Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression.

PubMed

Dicker, Frank; Schnittger, Susanne; Haferlach, Torsten; Kern, Wolfgang; Schoch, Claudia

2006-11-01

Compared with fluorescence in situ hybridization (FISH), conventional metaphase cytogenetics play only a minor prognostic role in chronic lymphocytic leukemia (CLL) so far, due to technical problems resulting from limited proliferation of CLL cells in vitro. Here, we present a simple method for in vitro stimulation of CLL cells that overcomes this limitation. In our unselected patient population, 125 of 132 cases could be successfully stimulated for metaphase generation by culture with the immunostimulatory CpG-oligonucleotide DSP30 plus interleukin 2. Of 125 cases, 101 showed chromosomal aberrations. The aberration rate is comparable to the rate detected by parallel interphase FISH. In 47 patients, conventional cytogenetics detected additional aberrations not detected by FISH analysis. A complex aberrant karyotype, defined as one having at least 3 aberrations, was detected in 30 of 125 patients, compared with only one such case as defined by FISH. Conventional cytogenetics frequently detected balanced and unbalanced translocations. A significant correlation of the poor-prognosis unmutated IgV(H) status with unbalanced translocations and of the likewise poor-prognosis CD38 expression to balanced translocations and complex aberrant karyotype was found. We demonstrate that FISH analysis underestimates the complexity of chromosomal aberrations in CLL. Therefore, conventional cytogenetics may define subgroups of patients with high risk of progression.

Computational Model Prediction and Biological Validation Using Simplified Mixed Field Exposures for the Development of a GCR Reference Field

NASA Technical Reports Server (NTRS)

Hada, M.; Rhone, J.; Beitman, A.; Saganti, P.; Plante, I.; Ponomarev, A.; Slaba, T.; Patel, Z.

2018-01-01

The yield of chromosomal aberrations has been shown to increase in the lymphocytes of astronauts after long-duration missions of several months in space. Chromosome exchanges, especially translocations, are positively correlated with many cancers and are therefore a potential biomarker of cancer risk associated with radiation exposure. Although extensive studies have been carried out on the induction of chromosomal aberrations by low- and high-LET radiation in human lymphocytes, fibroblasts, and epithelial cells exposed in vitro, there is a lack of data on chromosome aberrations induced by low dose-rate chronic exposure and mixed field beams such as those expected in space. Chromosome aberration studies at NSRL will provide the biological validation needed to extend the computational models over a broader range of experimental conditions (more complicated mixed fields leading up to the galactic cosmic rays (GCR) simulator), helping to reduce uncertainties in radiation quality effects and dose-rate dependence in cancer risk models. These models can then be used to answer some of the open questions regarding requirements for a full GCR reference field, including particle type and number, energy, dose rate, and delivery order. In this study, we designed a simplified mixed field beam with a combination of proton, helium, oxygen, and iron ions with shielding or proton, helium, oxygen, and titanium without shielding. Human fibroblasts cells were irradiated with these mixed field beam as well as each single beam with acute and chronic dose rate, and chromosome aberrations (CA) were measured with 3-color fluorescent in situ hybridization (FISH) chromosome painting methods. Frequency and type of CA induced with acute dose rate and chronic dose rates with single and mixed field beam will be discussed. A computational chromosome and radiation-induced DNA damage model, BDSTRACKS (Biological Damage by Stochastic Tracks), was updated to simulate various types of CA induced by acute exposures of the mixed field beams used for the experiments. The chromosomes were simulated by a polymer random walk algorithm with restrictions to their respective domains in the nucleus [1]. The stochastic dose to the nucleus was calculated with the code RITRACKS [2]. Irradiation of a target volume by a mixed field of ions was implemented within RITRACKs, and the fields of ions can be delivered over specific periods of time, allowing the simulation of dose-rate effects. Similarly, particles of various types and energies extracted from a pre-calculated spectra of galactic cosmic rays (GCR) can be used in RITRACKS. The number and spatial location of DSBs (DNA double-strand breaks) were calculated in BDSTRACKS using the simulated chromosomes and local (voxel) dose. Assuming that DSBs led to chromosome breaks, and simulating the rejoining of damaged chromosomes occurring during repair, BDSTRACKS produces the yield of various types of chromosome aberrations as a function of time (only final yields are presented). A comparison between experimental and simulation results will be shown.

Seattle To Portland Inter-City ITS Corridor Study And Communications Plan, Final Report

DOT National Transportation Integrated Search

1996-03-01

THIS DOCUMENT IS THE FINAL REPORT PRESENTING THE SEATTLE TO PORTLAND INTELLIGENT TRANSPORTATION SYSTEM (ITS) EARLY DEPLOYMENT PLAN. THE FINAL REPORT SYNTHESIZES INFORMATION FROM TECHNICAL MEMORANDUMS 1 THROUGH 5; INCLUDING EXISTING AND FUTURE CONDITI...

Benchmark Analysis of Career and Technical Education in Lenawee County. Final Report.

ERIC Educational Resources Information Center

Hollenbeck, Kevin

The career and technical education (CTE) provided in grades K-12 in the county's vocational-technical center and 12 local public school districts of Lenawee County, Michigan, was benchmarked with respect to its attention to career development. Data were collected from the following sources: structured interviews with a number of key respondents…

International Project on Technical and Vocational Education (UNEVOC). International Advisory Committee (Third Session, Paris, France, October 2-4, 1995). Final Report = Projet International pour l'Enseignement Technique et Professionnel (UNEVOC). Comite Consultatif International (Troisieme Session, Paris, France, 2-4 octobre 1995). Rapport Final.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

The international advisory committee of the International Project on Technical and Vocational Education (UNEVOC) held its third session in Paris in October 1995. Advisory committee members and observers from the United Nations' specialized, intergovernmental, and nongovernmental organizations reviewed the major UNEVOC project activities undertaken…

International Project on Technical and Vocational Education (UNEVOC). International Advisory Committee (Second Session, Paris, France, December 12-14, 1994). Final Report = Projet International pour l'Enseignement Technique et Professionnel (UNEVOC). Comite Consultatif International (Deuxieme Session, Paris, France, 12-14 decembre 1994). Rapport Final.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

The international advisory committee of the International Project on Technical and Vocational Education (UNEVOC) held its second session in Paris in December 1994. Nine advisory committee members and observers from the United Nations' specialized, intergovernmental, and nongovernmental organizations reviewed the major UNEVOC project activities…

Final Technical Report for ARRA Funding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusack, Roger; Mans, Jeremiah; Poling, Ronald

Final technical report of the University of Minnesota experimental high energy physics group for ARRA support. The Cryogenic Dark Matter Experiment (CDMS) used the funds received to construct a new passive shield to protect a high-purity germanium detector located in the Soudan mine in Northern Minnesota from cosmic rays. The BESIII and the CMS groups purchased computing hardware to assemble computer farms for data analysis and to generate large volumes of simulated data for comparison with the data collected.

Making a Difference in the Lives of Infants and Toddlers and Their Families: The Impacts of Early Head Start. Volumes I-III: Final Technical Report [and] Appendixes [and] Local Contributions to Understanding the Programs and Their Impacts.

ERIC Educational Resources Information Center

Love, John M.; Kisker, Ellen Eliason; Ross, Christine M.; Schochet, Peter Z.; Brooks-Gunn, Jeanne; Paulsell, Diane; Boller, Kimberly; Constantine, Jill; Vogel, Cheri; Fuligni, Alison Sidle; Brady-Smith, Christy

Early Head Start was designed in 1994 as a 2-generation program to enhance children's development and health, strengthen family and community partnerships, and support the staff delivering new services to low-income families with pregnant women, infants, or toddlers. This document contains the final technical report, appendixes, and local…

International Project on Technical and Vocational Education (UNEVOC). International Advisory Committee (First Session, Berlin, Germany, September 20-22, 1993). Final Report = Projet International pour l'Enseignement Technique et Professionnel (UNEVOC). Comite Consultatif International (Premiere Session, Berlin, Germany, 20-22 septembre 1993). Rapport Final.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

The international advisory committee of the International Project on Technical and Vocational Education (UNEVOC) held its first session in Berlin in September 1993. The advisory committee's 10 members and observers from the United Nations' specialized, intergovernmental, and nongovernmental organizations discussed educational policy, links between…

Illinois Clean Coal Institute 2005 annual report. Final technical report for the period September 1st, 2004, through August 31, 2005 on projects funded by the Illinois Department of Commerce and Economic Opportunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2005-11-08

This final technical report contains the abstracts and executive summaries of projects funded through the Illinois Clean Coal Institute solicitation entitled 'Request for proposals No. 04-1(ICCI/RFP04-1)'. Support of these projects is by the Office of Coal Development and Department of Commerce and Economic Opportunity. The projects fall into the following categories: advanced coal mining technologies; coal preparation and coal production business practice; management of coal combustion byproducts; commercialization and technology transfer. Final project extensions are also recorded.

Renewable Fuel Standard (RFS2): Final Rule Additional Resources

EPA Pesticide Factsheets

The final rule of fuels and fuel additives: renewable fuel standard program is published on March 26, 2010 and is effective on July 1, 2010. You will find the links to this final rule and technical amendments supporting this rule.

75 FR 48273 - Technical Service Provider Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service 7 CFR Part 652 RIN 0578-AA48 Technical Service Provider Assistance AGENCY: Natural Resources Conservation Service, United States Department of Agriculture. ACTION: Final rule; Correcting amendment. SUMMARY: The Natural Resources...

Partial Withdrawal and Final Rule for Nonroad Technical Amendments

EPA Pesticide Factsheets

Amendments to the technical hardship provisions under the Transition Program for Equipment Manufacturers related to the Tier 4 standards for nonroad diesel engines, and to the replacement engine exemption generally applicable to new nonroad engines.

A Pilot Program to Provide Ownership Skills to Seniors in the Vocational Technical Schools and Other Educational Institutions, Year Two. Final Report.

ERIC Educational Resources Information Center

Norwich Regional Vocational Technical School, CT.

Responding to a Small Business Administration statement that technical school graduates lack knowledge of business principles, the Norwich (Connecticut) Regional Vocational Technical School conducted a course in small business ownership/management for all of its seniors. The required course, a fifty-four-hour module, replaced one English,…

A Case Study of Technical Assistance to Demonstration Programs for Young Handicapped Children. Part III.

ERIC Educational Resources Information Center

Behr, Shirley K.; And Others

The report describes the third and final year of a 3-year case study of the technical assistance process as implemented by the Technical Assistance Development System (TADS) for the staffs of two demonstration programs for preschool handicapped children and their families. Following a review of TADS and the two demonstration programs, the…

Chemical Durability Improvement and Static Fatigue of Glasses.

DTIC Science & Technology

1982-08-01

Afl-Alla 837 RENSSELAER POLYIECmfJ!C INST TRtOY NY DEPT OF MATERIAL--ETC F/6 ii/ CHEMICAL DURABILITY IMPROVEMENT AND STATIC FATIGUE OF GLASSESW AUC2...82 M TOMOZAWA NOGGIN 7A-C-0315 UNC LASS IF IED N ENEEEEEE FINAL TECHNICAL REPORT For the period April 1, 1978 "u March 31, 198200 CHEMICAL DURABILITY...REPORT A PERIOD COVERED Chemical Durability Improvement and Static Final Technical Report Fatiue o GlasesApril 1, 1978"’,March 31, 1982 S. PERFORMING ORG

Experimental Program Final Technical Progress Report: 15 February 2007 to 30 September 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinney, Edward R.

2014-09-12

This is the final technical report of the grant DE-FG02-04ER41301 to the University of Colorado at Boulder entitled "Intermediate Energy Nuclear Physics" and describes the results of our funded activities during the period 15 February 2007 to 30 September 2012. These activities were primarily carried out at Fermilab, RHIC, and the German lab DESY. Significant advances in these experiments were carried out by members of the Colorado group and are described in detail.

Final Technical Report - Center for Technology for Advanced Scientific Component Software (TASCS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sussman, Alan

2014-10-21

This is a final technical report for the University of Maryland work in the SciDAC Center for Technology for Advanced Scientific Component Software (TASCS). The Maryland work focused on software tools for coupling parallel software components built using the Common Component Architecture (CCA) APIs. Those tools are based on the Maryland InterComm software framework that has been used in multiple computational science applications to build large-scale simulations of complex physical systems that employ multiple separately developed codes.

Iowa Hill Pumped Storage Project Investigations - Final Technical Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, David

2016-07-01

This Final Technical Report is a summary of the activities and outcome of the Department of Energy (DOE) Assistance Agreement DE-EE0005414 with the Sacramento Municipal Utility District (SMUD). The Assistance Agreement was created in 2012 to support investigations into the Iowa Hill Pumped-storage Project (Project), a new development that would add an additional 400 MW of capacity to SMUD’s existing 688MW Upper American River Hydroelectric Project (UARP) in the Sierra Nevada mountains east of Sacramento, California.

Renewable Fuel Standard Program (RFS1): Final Rule Additional Resources

EPA Pesticide Factsheets

The final rule of fuels and fuel additives: renewable fuel standard program is published on May 1, 2007 and is effective on September 1, 2007. You will find the links to this final rule and technical amendments supporting this rule.

Male Mutation Bias Is the Main Force Shaping Chromosomal Substitution Rates in Monotreme Mammals

PubMed Central

Link, Vivian; Aguilar-Gómez, Diana; Ramírez-Suástegui, Ciro; Hurst, Laurence D.

2017-01-01

Abstract In many species, spermatogenesis involves more cell divisions than oogenesis, and the male germline, therefore, accumulates more DNA replication errors, a phenomenon known as male mutation bias. The extent of male mutation bias (α) is estimated by comparing substitution rates of the X, Y, and autosomal chromosomes, as these chromosomes spend different proportions of their time in the germlines of the two sexes. Male mutation bias has been characterized in placental and marsupial mammals as well as birds, but analyses in monotremes failed to detect any such bias. Monotremes are an ancient lineage of egg-laying mammals with distinct biological properties, which include unique germline features. Here, we sought to assess the presence and potential characteristics of male mutation bias in platypus and the short-beaked echidna based on substitution rate analyses of X, Y, and autosomes. We established the presence of moderate male mutation bias in monotremes, corresponding to an α value of 2.12–3.69. Given that it has been unclear what proportion of the variation in substitution rates on the different chromosomal classes is really due to differential number of replications, we analyzed the influence of other confounding forces (selection, replication-timing, etc.) and found that male mutation bias is the main force explaining the between-chromosome classes differences in substitution rates. Finally, we estimated the proportion of variation at the gene level in substitution rates that is owing to replication effects and found that this phenomenon can explain >68% of these variations in monotremes, and in control species, rodents, and primates. PMID:28922870

Calling Chromosome Alterations, DNA Methylation Statuses, and Mutations in Tumors by Simple Targeted Next-Generation Sequencing: A Solution for Transferring Integrated Pangenomic Studies into Routine Practice?

PubMed

Garinet, Simon; Néou, Mario; de La Villéon, Bruno; Faillot, Simon; Sakat, Julien; Da Fonseca, Juliana P; Jouinot, Anne; Le Tourneau, Christophe; Kamal, Maud; Luscap-Rondof, Windy; Boeva, Valentina; Gaujoux, Sebastien; Vidaud, Michel; Pasmant, Eric; Letourneur, Franck; Bertherat, Jérôme; Assié, Guillaume

2017-09-01

Pangenomic studies identified distinct molecular classes for many cancers, with major clinical applications. However, routine use requires cost-effective assays. We assessed whether targeted next-generation sequencing (NGS) could call chromosomal alterations and DNA methylation status. A training set of 77 tumors and a validation set of 449 (43 tumor types) were analyzed by targeted NGS and single-nucleotide polymorphism (SNP) arrays. Thirty-two tumors were analyzed by NGS after bisulfite conversion, and compared to methylation array or methylation-specific multiplex ligation-dependent probe amplification. Considering allelic ratios, correlation was strong between targeted NGS and SNP arrays (r = 0.88). In contrast, considering DNA copy number, for variations of one DNA copy, correlation was weaker between read counts and SNP array (r = 0.49). Thus, we generated TARGOMICs, optimized for detecting chromosome alterations by combining allelic ratios and read counts generated by targeted NGS. Sensitivity for calling normal, lost, and gained chromosomes was 89%, 72%, and 31%, respectively. Specificity was 81%, 93%, and 98%, respectively. These results were confirmed in the validation set. Finally, TARGOMICs could efficiently align and compute proportions of methylated cytosines from bisulfite-converted DNA from targeted NGS. In conclusion, beyond calling mutations, targeted NGS efficiently calls chromosome alterations and methylation status in tumors. A single run and minor design/protocol adaptations are sufficient. Optimizing targeted NGS should expand translation of genomics to clinical routine. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Assurance Penalty Level Analysis Final Rule TSD

EPA Pesticide Factsheets

This Technical Support Document (TSD) supports EPA’s determination that the final Transport Rule’s assurance provision penalty requirement provides sufficient deterrence against a state exceeding its assurance level.

Final Rule for Technical Amendments to the Highway and Nonroad Diesel Regulations

EPA Pesticide Factsheets

This action corrects errors and omissions from the previous rules, makes minor changes to the regulations to assist entities with regulatory compliance, and makes technical amendments that resulted from discussions with various diesel stakeholders.

Fine organization of genomic regions tagged to the 5S rDNA locus of the bread wheat 5B chromosome.

PubMed

Sergeeva, Ekaterina M; Shcherban, Andrey B; Adonina, Irina G; Nesterov, Michail A; Beletsky, Alexey V; Rakitin, Andrey L; Mardanov, Andrey V; Ravin, Nikolai V; Salina, Elena A

2017-11-14

The multigene family encoding the 5S rRNA, one of the most important structurally-functional part of the large ribosomal subunit, is an obligate component of all eukaryotic genomes. 5S rDNA has long been a favored target for cytological and phylogenetic studies due to the inherent peculiarities of its structural organization, such as the tandem arrays of repetitive units and their high interspecific divergence. The complex polyploid nature of the genome of bread wheat, Triticum aestivum, and the technically difficult task of sequencing clusters of tandem repeats mean that the detailed organization of extended genomic regions containing 5S rRNA genes remains unclear. This is despite the recent progress made in wheat genomic sequencing. Using pyrosequencing of BAC clones, in this work we studied the organization of two distinct 5S rDNA-tagged regions of the 5BS chromosome of bread wheat. Three BAC-clones containing 5S rDNA were identified in the 5BS chromosome-specific BAC-library of Triticum aestivum. Using the results of pyrosequencing and assembling, we obtained six 5S rDNA- containing contigs with a total length of 140,417 bp, and two sets (pools) of individual 5S rDNA sequences belonging to separate, but closely located genomic regions on the 5BS chromosome. Both regions are characterized by the presence of approximately 70-80 copies of 5S rDNA, however, they are completely different in their structural organization. The first region contained highly diverged short-type 5S rDNA units that were disrupted by multiple insertions of transposable elements. The second region contained the more conserved long-type 5S rDNA, organized as a single tandem array. FISH using probes specific to both 5S rDNA unit types showed differences in the distribution and intensity of signals on the chromosomes of polyploid wheat species and their diploid progenitors. A detailed structural organization of two closely located 5S rDNA-tagged genomic regions on the 5BS chromosome of bread wheat has been established. These two regions differ in the organization of both 5S rDNA and the neighboring sequences comprised of transposable elements, implying different modes of evolution for these regions.

Final priority. Rehabilitation Training: Job-Driven Vocational Rehabilitation Technical Assistance Center. Final priority.

PubMed

2014-08-19

The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Rehabilitation Training program to establish a Job-Driven Vocational Rehabilitation Technical Assistance Center (JDVRTAC). The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to focus on training in an area of national need. Specifically, this priority responds to the Presidential Memorandum to Federal agencies directing them to take action to address job-driven training for the Nation's workers. The JDVRTAC will provide technical assistance (TA) to State vocational rehabilitation (VR) agencies to help them develop for individuals with disabilities training and employment opportunities that meet the needs of today's employers.

A Molecular View of Kinetochore Assembly and Function

PubMed Central

Musacchio, Andrea; Desai, Arshad

2017-01-01

Kinetochores are large protein assemblies that connect chromosomes to microtubules of the mitotic and meiotic spindles in order to distribute the replicated genome from a mother cell to its daughters. Kinetochores also control feedback mechanisms responsible for the correction of incorrect microtubule attachments, and for the coordination of chromosome attachment with cell cycle progression. Finally, kinetochores contribute to their own preservation, across generations, at the specific chromosomal loci devoted to host them, the centromeres. They achieve this in most species by exploiting an epigenetic, DNA-sequence-independent mechanism; notable exceptions are budding yeasts where a specific sequence is associated with centromere function. In the last 15 years, extensive progress in the elucidation of the composition of the kinetochore and the identification of various physical and functional modules within its substructure has led to a much deeper molecular understanding of kinetochore organization and the origins of its functional output. Here, we provide a broad summary of this progress, focusing primarily on kinetochores of humans and budding yeast, while highlighting work from other models, and present important unresolved questions for future studies. PMID:28125021

Transcription of tandemly repetitive DNA: functional roles.

PubMed

Biscotti, Maria Assunta; Canapa, Adriana; Forconi, Mariko; Olmo, Ettore; Barucca, Marco

2015-09-01

A considerable fraction of the eukaryotic genome is made up of satellite DNA constituted of tandemly repeated sequences. These elements are mainly located at centromeres, pericentromeres, and telomeres and are major components of constitutive heterochromatin. Although originally satellite DNA was thought silent and inert, an increasing number of studies are providing evidence on its transcriptional activity supporting, on the contrary, an unexpected dynamicity. This review summarizes the multiple structural roles of satellite noncoding RNAs at chromosome level. Indeed, satellite noncoding RNAs play a role in the establishment of a heterochromatic state at centromere and telomere. These highly condensed structures are indispensable to preserve chromosome integrity and genome stability, preventing recombination events, and ensuring the correct chromosome pairing and segregation. Moreover, these RNA molecules seem to be involved also in maintaining centromere identity and in elongation, capping, and replication of telomere. Finally, the abnormal variation of centromeric and pericentromeric DNA transcription across major eukaryotic lineages in stress condition and disease has evidenced the critical role that these transcripts may play and the potentially dire consequences for the organism.

Confirmation of Down syndrome critical region by FISH analysis in a patient with add(21)(p11)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumoto, Naomichi; Niikawa, Norio; Mikawa, Makoto

1995-12-04

We have studied a patient with clinical Down syndrome (DS) who has a mosaic 46, XX/46, XX, 21p+ karyotype. The patient was born at 39 weeks of gestation with a birth weight of 3,025 g to healthy parents. At age 2 months, she was diagnosed clinically to have DS; she had flat facies, upslanted palpebral fissures, epicanthal folds, telecanthus, flat nasal bridge, abnormal dentition, malformed ears, short neck, short fingers, clinodactyly with single flexion crease of the fifth fingers, hyperextension of joints, pes planus, distal axial triradii, and bilateral tibial arch patterns. Chromosome analysis showed mosaicism consisting of a normalmore » 46,XX cell line and a line with a 21p+ chromosome, the final karyotype being mos46,XX[57]/46,XX,add(21)(p11)[43]. Although the origin of an additional segment on chromosome 21 was not identified with conventional banding analyses, it was suspected to represent partial trisomy 21 on the basis of clinical manifestations. 6 refs., 2 figs.« less

A complex of serine protease genes expressed preferentially in cytotoxic T-lymphocytes is closely linked to the T-cell receptor alpha- and delta-chain genes on mouse chromosome 14.

PubMed

Crosby, J L; Bleackley, R C; Nadeau, J H

1990-02-01

A complex of genes encoding serine proteases that are preferentially expressed in cytotoxic T-cells was shown to be closely linked to the T-cell receptor alpha- and delta-chain genes on mouse chromosome 14. A striking difference in recombination frequencies among linkage crosses was reported. Two genes, Np-1 and Tcra, which fail to recombine in crosses involving conventional strains of mice, were shown to recombine readily in interspecific crosses involving Mus spretus. This difference in recombination frequency suggests chromosomal rearrangements that suppress recombination in conventional crosses, recombination hot spots in interspecific crosses, or selection against recombinant haplotypes during development of recombinant inbred strains. Finally, a mutation called disorganization, which is located near the serine protease complex, is of considerable interest because it causes an extraordinarily wide variety of congenital defects. Because of the involvement of serine protease loci in several homeotic mutations in Drosophila, disorganization must be considered a candidate for a mutation in a serine protease-encoding gene.

Meiotic recombination hotspots - a comparative view.

PubMed

Choi, Kyuha; Henderson, Ian R

2015-07-01

During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

NASA's Pursuit of Low-Noise Propulsion for Low-Boom Commercial Supersonic Vehicles

NASA Technical Reports Server (NTRS)

Bridges, James; Brown, Clifford A.; Seidel, Jonathan A.

2018-01-01

Since 2006, when the Fundamental Aeronautics Program was instituted within NASA's Aeronautics Mission Directorate, there has been a Project looking at the technical barriers to commercial supersonic flight. Among the barriers is the noise produced by aircraft during landing and takeoff. Over the years that followed, research was carried out at NASA aeronautics research centers, often in collaboration with academia and industry, addressing the problem. In 2013, a high-level milestone was established, described as a Technical Challenge, with the objective of demonstrating the feasibility of a low-boom supersonic airliner that could meet current airport noise regulations. The Technical Challenge was formally called "Low Noise Propulsion for Low Boom Aircraft", and was completed in late 2016. This paper reports the technical findings from this Technical Challenge, reaching back almost 10 years to review the technologies and tools that were developed along the way. It also discusses the final aircraft configuration and propulsion systems required for a supersonic civilian aircraft to meet noise regulations using the technologies available today. Finally, the paper documents the model-scale tests that validated the acoustic performance of the study aircraft.

NASA's Pursuit of Low-Noise Propulsion for Low-Boom Commercial Supersonic Vehicles

NASA Technical Reports Server (NTRS)

Bridges, James; Brown, Clifford A.; Seidel, Jonathan

2018-01-01

Since 2006, when the Fundamental Aeronautics Program was instituted within NASA's Aeronautics Mission Directorate, there has been a Project looking at the technical barriers to commercial supersonic flight. Among the barriers is the noise produced by aircraft during landing and takeoff. Over the years that followed, research was carried out at NASA aeronautics research centers, often in collaboration with academia and industry, addressing the problem. In 2013, a high-level milestone was established, described as a Technical Challenge, with the objective of demonstrating the feasibility of a low-boom supersonic airliner that could meet current airport noise regulations. The Technical Challenge was formally called a Low Noise Propulsion for Low Boom Aircraft and was completed in late 2016. This paper reports the technical findings from this Technical Challenge, reaching back almost 10 years to review the technologies and tools that were developed along the way. It also discusses the final aircraft configuration and propulsion systems required for a supersonic civilian aircraft to meet noise regulations using the technologies available today. Finally, the paper documents the model-scale tests that validated the acoustic performance of the study aircraft.

Final Revisions Rule State Budgets and New Unit Set-Asides TSD

EPA Pesticide Factsheets

This technical support document shows the underlying data and calculations used to quantify the state budget revisions and new unit set-aside revisions made in the final revisions rule, as well as those revisions included in the direct final revisions rule

77 FR 37284 - Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF LABOR Office of Workers' Compensation Programs 20 CFR Parts 701, 702, 703, 725, and 726 RIN 1240-AA05 Technical Amendments AGENCY: Office of Workers' Compensation Programs, Labor. ACTION: Final rule. SUMMARY: The Office of Workers' Compensation Programs is making [[Page 37285

Vehicle infrastructure integration proof of concept : technical description--vehicle : final report

DOT National Transportation Integrated Search

2009-05-19

This report provides the technical description of the VII system developed for the Cooperative Agreement VII Program between the USDOT and the VII Consortium. The basic architectural elements are summarized and detailed descriptions of the hardware a...

Novel embryo selection techniques to increase embryo implantation in IVF attempts.

PubMed

Sigalos, George Α; Triantafyllidou, Olga; Vlahos, Nikos F

2016-11-01

The final success of an IVF attempt depends on several steps and decisions taken during the ovarian stimulation, the oocyte retrieval, the embryo culture and the embryo transfer. The final selection of the embryos most likely to implant is the final step in this process and the responsibility of the lab. Apart from strict morphologic criteria that historically have been used in embryo selection, additional information on genetic, metabolomic and morphokinetic characteristics of the embryo is recently combined to morphology to select the embryo most likely to produce a pregnancy. In this manuscript, we review the most recent information on the current methods used for embryo selection presenting the predictive capability of each one. A literature search was performed on Pubmed, Medline and Cochrane Database of Systematic Reviews for published studies using appropriate key words and phrases with no limits placed on time. It seems that the combination of morphologic criteria in conjunction to embryo kinetics as documented by time-lapse technology provides the most reliable information on embryo quality. Blastocyst biopsy with subsequent comprehensive chromosome analysis allows the selection of the euploid embryos with the higher implantation potential. Embryo time-lapse imaging and blastocyst biopsy combined to comprehensive chromosome analysis are the most promising technologies to increase pregnancy rates and reduce the possibility of multiple pregnancies. However, further studies will demonstrate the capability of routinely using these technologies to significantly improve IVF outcomes.

NetView technical research

NASA Technical Reports Server (NTRS)

1993-01-01

This is the Final Technical Report for the NetView Technical Research task. This report is prepared in accordance with Contract Data Requirements List (CDRL) item A002. NetView assistance was provided and details are presented under the following headings: NetView Management Systems (NMS) project tasks; WBAFB IBM 3090; WPAFB AMDAHL; WPAFB IBM 3084; Hill AFB; McClellan AFB AMDAHL; McClellan AFB IBM 3090; and Warner-Robins AFB.

Inventory of greenhouse gas emissions from on-road vehicles in Midwestern USA States and integrated approach to achieving environmental sustainability in transportation : USDOT Region V Regional University Transportation Center final report : technical su

DOT National Transportation Integrated Search

2016-12-29

Two project objectives one technical and one educational- were laid out in this project. The technical objective was to assess current inventory of greenhouse gases (GHG) in the six Midwestern states of the nation and to estimate improvements as ...

CARD-FISH for Environmental Microorganisms: Technical Advancement and Future Applications

PubMed Central

Kubota, Kengo

2013-01-01

Fluorescence in situ hybridization (FISH) has become a standard technique in environmental microbiology. More than 20 years have passed since this technique was first described, and it is currently used for the detection of ribosomal RNA, messenger RNA, and functional genes encoded on chromosomes. This review focuses on the advancement and applications of FISH combined with catalyzed reporter deposition (CARD, also known as tyramide signal amplification or TSA), in the detection of environmental microorganisms. Significant methodological improvements have been made in CARD-FISH technology, including its combination with other techniques and instruments. PMID:23124765

Emissions Inventory Final Rule TSD

EPA Pesticide Factsheets

This technical support document (TSD) provides the details of emissions data processing done in support of EPA's final rulemaking effort for the Federal Transport Rule, now known as the Cross-State Air Pollution Rule.

InterB multigenic family, a gene repertoire associated with subterminal chromosome regions of Encephalitozoon cuniculi and conserved in several human-infecting microsporidian species.

PubMed

Dia, Ndongo; Lavie, Laurence; Méténier, Guy; Toguebaye, Bhen S; Vivarès, Christian P; Cornillot, Emmanuel

2007-03-01

Microsporidia are fungi-related obligate intracellular parasites that infect numerous animals, including man. Encephalitozoon cuniculi harbours a very small genome (2.9 Mbp) with about 2,000 coding sequences (CDSs). Most repeated CDSs are of unknown function and are distributed in subterminal regions that mark the transitions between subtelomeric rDNA units and chromosome cores. A potential multigenic family (interB) encoding proteins within a size range of 579-641 aa was investigated by PCR and RT-PCR. Thirty members were finally assigned to the E. cuniculi interB family and a predominant interB transcript was found to originate from a newly identified gene on chromosome III. Microsporidian species from eight different genera infecting insects, fishes or mammals, were tested for a possible intra-phylum conservation of interB genes. Only representatives of the Encephalitozoon, Vittaforma and Brachiola genera, differing in host range but all able to invade humans, were positive. Molecular karyotyping of Brachiola algerae showed a complex set of chromosome bands, providing a haploid genome size estimate of 15-20 Mbp. In spite of this large difference in genome complexity, B. algerae and E. cuniculi shared some similar interB gene copies and a common location of interB genes in near-rDNA subterminal regions.

Altered LINE-1 Methylation in Mothers of Children with Down Syndrome

PubMed Central

Babić Božović, Ivana; Stanković, Aleksandra; Živković, Maja; Vraneković, Jadranka; Kapović, Miljenko; Brajenović-Milić, Bojana

2015-01-01

Down syndrome (DS, also known as trisomy 21) most often results from chromosomal nondisjunction during oogenesis. Numerous studies sustain a causal link between global DNA hypomethylation and genetic instability. It has been suggested that DNA hypomethylation might affect the structure and dynamics of chromatin regions that are critical for chromosome stability and segregation, thus favouring chromosomal nondisjunction during meiosis. Maternal global DNA hypomethylation has not yet been analyzed as a potential risk factor for chromosome 21 nondisjunction. This study aimed to asses the risk for DS in association with maternal global DNA methylation and the impact of endogenous and exogenous factors that reportedly influence DNA methylation status. Global DNA methylation was analyzed in peripheral blood lymphocytes by quantifying LINE-1 methylation using the MethyLight method. Levels of global DNA methylation were significantly lower among mothers of children with maternally derived trisomy 21 than among control mothers (P = 0.000). The combination of MTHFR C677T genotype and diet significantly influenced global DNA methylation (R2 = 4.5%, P = 0.046). The lowest values of global DNA methylation were observed in mothers with MTHFR 677 CT+TT genotype and low dietary folate. Although our findings revealed an association between maternal global DNA hypomethylation and trisomy 21 of maternal origin, further progress and final conclusions regarding the role of global DNA methylation and the occurrence of trisomy 21 are facing major challenges. PMID:26017139

Core exosome-independent roles for Rrp6 in cell cycle progression.

PubMed

Graham, Amy C; Kiss, Daniel L; Andrulis, Erik D

2009-04-01

Exosome complexes are 3' to 5' exoribonucleases composed of subunits that are critical for numerous distinct RNA metabolic (ribonucleometabolic) pathways. Several studies have implicated the exosome subunits Rrp6 and Dis3 in chromosome segregation and cell division but the functional relevance of these findings remains unclear. Here, we report that, in Drosophila melanogaster S2 tissue culture cells, dRrp6 is required for cell proliferation and error-free mitosis, but the core exosome subunit Rrp40 is not. Micorarray analysis of dRrp6-depleted cell reveals increased levels of cell cycle- and mitosis-related transcripts. Depletion of dRrp6 elicits a decrease in the frequency of mitotic cells and in the mitotic marker phospho-histone H3 (pH3), with a concomitant increase in defects in chromosome congression, separation, and segregation. Endogenous dRrp6 dynamically redistributes during mitosis, accumulating predominantly but not exclusively on the condensed chromosomes. In contrast, core subunits localize predominantly to MTs throughout cell division. Finally, dRrp6-depleted cells treated with microtubule poisons exhibit normal kinetochore recruitment of the spindle assembly checkpoint protein BubR1 without restoring pH3 levels, suggesting that these cells undergo premature chromosome condensation. Collectively, these data support the idea that dRrp6 has a core exosome-independent role in cell cycle and mitotic progression.

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

NASA Technical Reports Server (NTRS)

Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

1996-01-01

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys.

PubMed

Lucas, J N; Hill, F S; Burk, C E; Cox, A B; Straume, T

1996-09-01

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Chromosome number variation of the Italian endemic vascular flora. State-of-the-art, gaps in knowledge and evidence for an exponential relationship among even ploidy levels.

PubMed

Bedini, Gianni; Garbari, Fabio; Peruzzi, Lorenzo

2012-01-01

The Italian endemic vascular flora is composed of 1,286 specific and subspecific taxa. From the critical analysis of "Chrobase.it", 711 of them (about 55%) have been studied from a karyological point of view. These taxa belong to 52 out of 56 families and 204 out of 284 genera. These data suggest that endemic species are more studied than the flora as a whole. Mean chromosome number for Italian endemics is 2n = 30.68 ± 20.27 (median: 2n = 26, mode: 2n = 18). These values are very close to those known for the whole flora. Similar variation ranges, among endemics and species with wider distribution, are likely to reflect similar evolutionary trends. Known chromosome numbers in Italian endemics range from 2n = 8 to 2n = 182. About 9% of taxa show more than one cytotype and the frequency of Bs in the Italian endemic vascular flora is 3.3%. These values are slightly smaller compared with the whole Italian flora. Finally, for the basic chromosome numbers x = 7, 8, 9, the proportion of diploids (2n = 2x) to even polyploids (2n = 4x, 6x, 8x and 10x) can be described by the exponential function f(p) = e((5.539 - 0.637p)) (R(2) = 0.984).

Cancer Cytogenetics: Methodology Revisited

PubMed Central

2014-01-01

The Philadelphia chromosome was the first genetic abnormality discovered in cancer (in 1960), and it was found to be consistently associated with CML. The description of the Philadelphia chromosome ushered in a new era in the field of cancer cytogenetics. Accumulating genetic data have been shown to be intimately associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is now considered a mandatory investigation for all newly diagnosed leukemias. The development of FISH in the 1980s overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell. However, subsequent methodological advances in molecular cytogenetics based on the principle of FISH that were initiated in the early 1990s have greatly enhanced the efficiency and accuracy of karyotype analysis by marrying conventional cytogenetics with molecular technologies. In this review, the development, current utilization, and technical pitfalls of both the conventional and molecular cytogenetics approaches used for cancer diagnosis over the past five decades will be discussed. PMID:25368816

Histological analysis and ancient DNA amplification of human bone remains found in caius iulius polybius house in pompeii.

PubMed

Cipollaro, M; Di Bernado, G; Forte, A; Galano, G; De Masi, L; Galderisi, U; Guarino, F M; Angelini, F; Cascino, A

1999-09-01

Thirteen skeletons found in the Caius Iulius Polybius house, which has been the object of intensive study since its discovery in Pompeii 250 years ago, have provided an opportunity to study either bone diagenesis by histological investigation or ancient DNA by polymerase chain reaction analysis. DNA analysis was done by amplifying both X- and Y-chromosomes amelogenin loci and Y-specific alphoid repeat locus. The von Willebrand factor (vWF) microsatellite locus on chromosome 12 was also analyzed for personal identification in two individuals showing alleles with 10/11 and 12/12 TCTA repeats, respectively. Technical problems were the scarcity of DNA content from osteocytes, DNA molecule fragmentation, microbial contamination which change bone structure, contaminating human DNA which results from mishandling, and frequent presence of Taq DNA polymerase inhibiting molecules like polyphenols and heavy metals. The results suggest that the remains contain endogenous human DNA that can be amplified and analyzed. The amplifiability of DNA corresponds to the bone preservation and dynamics of the burial conditions subsequent to the 79 A.D. eruption.

5S rRNA Promoter for Guide RNA Expression Enabled Highly Efficient CRISPR/Cas9 Genome Editing in Aspergillus niger.

PubMed

Zheng, Xiaomei; Zheng, Ping; Zhang, Kun; Cairns, Timothy C; Meyer, Vera; Sun, Jibin; Ma, Yanhe

2018-04-30

The CRISPR/Cas9 system is a revolutionary genome editing tool. However, in eukaryotes, search and optimization of a suitable promoter for guide RNA expression is a significant technical challenge. Here we used the industrially important fungus, Aspergillus niger, to demonstrate that the 5S rRNA gene, which is both highly conserved and efficiently expressed in eukaryotes, can be used as a guide RNA promoter. The gene editing system was established with 100% rates of precision gene modifications among dozens of transformants using short (40-bp) homologous donor DNA. This system was also applicable for generation of designer chromosomes, as evidenced by deletion of a 48 kb gene cluster required for biosynthesis of the mycotoxin fumonisin B1. Moreover, this system also facilitated simultaneous mutagenesis of multiple genes in A. niger. We anticipate that the use of the 5S rRNA gene as guide RNA promoter can broadly be applied for engineering highly efficient eukaryotic CRISPR/Cas9 toolkits. Additionally, the system reported here will enable development of designer chromosomes in model and industrially important fungi.

Capturing Three-Dimensional Genome Organization in Individual Cells by Single-Cell Hi-C.

PubMed

Nagano, Takashi; Wingett, Steven W; Fraser, Peter

2017-01-01

Hi-C is a powerful method to investigate genome-wide, higher-order chromatin and chromosome conformations averaged from a population of cells. To expand the potential of Hi-C for single-cell analysis, we developed single-cell Hi-C. Similar to the existing "ensemble" Hi-C method, single-cell Hi-C detects proximity-dependent ligation events between cross-linked and restriction-digested chromatin fragments in cells. A major difference between the single-cell Hi-C and ensemble Hi-C protocol is that the proximity-dependent ligation is carried out in the nucleus. This allows the isolation of individual cells in which nearly the entire Hi-C procedure has been carried out, enabling the production of a Hi-C library and data from individual cells. With this new method, we studied genome conformations and found evidence for conserved topological domain organization from cell to cell, but highly variable interdomain contacts and chromosome folding genome wide. In addition, we found that the single-cell Hi-C protocol provided cleaner results with less technical noise suggesting it could be used to improve the ensemble Hi-C technique.

Examination of the health status of populations from depleted-uranium-contaminated regions.

PubMed

Milacić, Snezana; Petrović, Dragana; Jovicić, Dubravka; Kovacević, Radomir; Simić, Jadranko

2004-05-01

During the NATO air strikes on the Federal Republic of Yugoslavia (Serbia and Montenegro) in 1999, depleted-uranium ammunition was used on 112 locations, mainly Kosovo, in the south of Serbia, and one location in Montenegro. Blood samples of residents from depleted-uranium-contaminated areas were gathered and blood cell and chromosomal aberrations were analyzed. During the last 3 years blood samples from 21 residents of Kosovo (Strpce), from 29 residents from the south of Serbia (the Vranje and Bujanovac regions), and from 19 technical television workers from the site of Pljackovica, in the vicinity of Vranje, were collected. Blood samples from 33 residents of central Serbia and 46 occupational workers exposed to X-rays were used as controls. All subjects studied were without any clinical symptoms of disease. The examinations included general clinical assessment; urine samples for alpha-and gamma-spectrometry analysis; complete blood counts; ratio-percentages of blood cells in stained (Giemsa) capillary smears, individual leukocyte line elements; morphological changes observed under a microscope; the presence of immature forms or blasts; and leukocyte enzyme activity [alkaline phosphatase leukocyte (APL)]. Chromosomal aberrations were evaluated in 200 peripheral blood lymphocytes in mitosis. An increased incidence of rogue cells and chromosomal aberrations was found in the blood of the residents of Vranje and Bujanovac, but this was below the incidence of chromosomal aberrations in individuals occupationally exposed to ionizing irradiation. Blast cells were not found. Blood counts were decreased in only a few samples, while morphological changes of both nuclei and cytoplasm were marked in individuals in south and central Serbia. Enzymatic activity (as measured by the APL score) was decreased in samples with chromosomal aberrations and cyto-morphological changes in subjects from the south of Serbia. The contamination level measured by this examination was low. Because of the presence of depleted uranium (uranium-238) in the soil and in plants, the prevention of consequences necessitates the identification of the initial biological effects on sensitive tissues. Early identification of serious blood cell changes is important for appropriate medical treatment.

Transportation Network Data Requirements for Assessing Criticality for Resiliency and Adaptation Planning

DOT National Transportation Integrated Search

2017-11-01

This report is one of two NCST Research Report documents produced as part of a project to advance the technical modeling tools for resiliency and adaptation planning, especially those used for criticality rankings. The official final technical report...

Comment Deadlines Established Regarding the LightSquared Technical Working Group Report

DOT National Transportation Integrated Search

2011-06-30

On June 30, 2011, LightSquared Subsidiary LLC (LightSquared) submitted a final report of the : technical working group co-chaired by LightSquared and the United States Global Positioning System : (GPS) Industry Council (USGIC)1 and organized in respo...

Technical report on prototype intelligent network flow optimization (INFLO) dynamic speed harmonization and queue warning.

DOT National Transportation Integrated Search

2015-06-01

This Technical Report on Prototype Intelligent Network Flow Optimization (INFLO) Dynamic Speed Harmonization and Queue Warning is the final report for the project. It describes the prototyping, acceptance testing and small-scale demonstration of the ...

NUSC Technical Publications Guide.

DTIC Science & Technology

1985-05-01

Facility personnel especially that of A. Castelluzzo, E. Deland, J. Gesel , and E. Szlosek (all of Code 4343). Reviewed and Approved: 14 July 1980 D...their technical content and format. Review and approve the manual outline, the review manuscript, and the final camera - reproducible copy. Conduct in

Cross-State Air Pollution Rule Update Allowance Allocation Final Rule TSD

EPA Pesticide Factsheets

This Technical Support Document (TSD) provides information that supports EPA’s determination of unit-level allocations for existing and new units under the final Cross-State Air Pollution Rule Update.

Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis.

PubMed

Sliedrecht, Tale; Zhang, Chao; Shokat, Kevan M; Kops, Geert J P L

2010-04-22

Proper execution of chromosome segregation relies on tight control of attachment of chromosomes to spindle microtubules. This is monitored by the mitotic checkpoint that allows chromosome segregation only when all chromosomes are stably attached. Proper functioning of the attachment and checkpoint processes is thus important to prevent chromosomal instability. Both processes rely on the mitotic kinase Mps1. We present here two cell lines in which endogenous Mps1 has been stably replaced with a mutant kinase (Mps1-as) that is specifically inhibited by bulky PP1 analogs. Mps1 inhibition in these cell lines is highly penetrant and reversible. Timed inhibition during bipolar spindle assembly shows that Mps1 is critical for attachment error-correction and confirms its role in Aurora B regulation. We furthermore show that Mps1 has multiple controls over mitotic checkpoint activity. Mps1 inhibition precludes Mad1 localization to unattached kinetochores but also accelerates mitosis. This acceleration correlates with absence of detectable mitotic checkpoint complex after Mps1 inhibition. Finally, we show that short-term inhibition of Mps1 catalytic activity is sufficient to kill cells. Mps1 is involved in the regulation of multiple key processes that ensure correct chromosome segregation and is a promising target for inhibition in anti-cancer strategies. We report here two cell lines that allow specific and highly penetrant inhibition of Mps1 in a reproducible manner through the use of chemical genetics. Using these cell lines we confirm previously suggested roles for Mps1 activity in mitosis, present evidence for novel functions and examine cell viability after short and prolonged Mps1 inhibition. These cell lines present the best cellular model system to date for investigations into Mps1 biology and the effects of penetrance and duration of Mps1 inhibition on cell viability.

Guidelines for producing training films and videos.

PubMed

Harper, P B

1991-01-01

Drawing from experience in producing a film on the surgical procedure of female sterilization, 4 guidelines to technical film production for training purposes are presented and discussed in this paper. In order of presentation in the text, the paper 1st encourages identifying and securing a technical expert, then clearly identifying steps of the technical procedure, involving trainees and trainers in the production process, and working with experienced producers, scriptwriters, and crew members. Returning to the 1st guideline, the technical advisor will have a central presence during all photography and editing, and ideally should not have any personal investment in the procedure being shown. Prior to script finalization and sorting, research is urged to ensure concrete procedural steps. Printed materials, slides, interviews of experienced clinicians, procedure observation, and test videotape shooting may be called upon and employed as parts of the research phase. Trainees should participate during preliminary research, script development, and pretesting of early film versions, their suggestions for change incorporated where appropriate in the final version. On the final point of securing experienced workers, country nationals sensitive to relevant cultural and background dynamics should be included in the team. The special concerns of airport security regulation and customs requirements knowledge are essential, as well as their attention to assuring adequate on-site electricity for camera equipment.

Site-specific integration of Streptomyces PhiC31 integrase-based vectors in the chromosome of Rhodococcus equi.

PubMed

Hong, Yang; Hondalus, Mary K

2008-10-01

Streptomyces PhiC31-based site-specific integration was used to transform the facultative intracellular pathogen Rhodococcus equi. The transformation efficiency of vectors incorporating the PhiC31 integrase and attP sites was comparable to that of replication plasmids using the same electroporation procedure. A single attB integration site was identified within an ORF encoding a pirin-like protein, which deviates slightly from the consensus sequence of Streptomyces attB sites. Vector integration was stably maintained in the R. equi chromosome for as many as 100 generations during unselected passage in vitro. In addition, integration does not appear to affect the replication of bacteria inside macrophages. Finally, this integration system was also used to successfully complement an R. equi mutant.

Toward a framework linkage map of the canine genome.

PubMed

Langston, A A; Mellersh, C S; Wiegand, N A; Acland, G M; Ray, K; Aguirre, G D; Ostrander, E A

1999-01-01

Selective breeding to maintain specific physical and behavioral traits has made the modern dog one of the most physically diverse species on earth. One unfortunate consequence of the common breeding practices used to develop lines of dogs with the desired traits is amplification and propagation of genetic diseases within distinct breeds. To map disease loci we have constructed a first-generation framework map of the canine genome. We developed large numbers of highly polymorphic markers, constructed a panel of canine-rodent hybrid cell lines, and assigned those markers to chromosome groups using the hybrid cell lines. Finally, we determined the order and spacing of markers on individual canine chromosomes by linkage analysis using a reference panel of 17 outbred pedigrees. This article describes approaches and strategies to accomplish these goals.

Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development.

PubMed

Vera-Rodriguez, M; Diez-Juan, A; Jimenez-Almazan, J; Martinez, S; Navarro, R; Peinado, V; Mercader, A; Meseguer, M; Blesa, D; Moreno, I; Valbuena, D; Rubio, C; Simon, C

2018-04-01

What is the origin and composition of cell-free DNA in human embryo spent culture media? Cell-free DNA from human embryo spent culture media represents a mix of maternal and embryonic DNA, and the mixture can be more complex for mosaic embryos. In 2016, ~300 000 human embryos were chromosomally and/or genetically analyzed using preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders (PGT-M) before transfer into the uterus. While progress in genetic techniques has enabled analysis of the full karyotype in a single cell with high sensitivity and specificity, these approaches still require an embryo biopsy. Thus, non-invasive techniques are sought as an alternative. This study was based on a total of 113 human embryos undergoing trophectoderm biopsy as part of PGT-A analysis. For each embryo, the spent culture media used between Day 3 and Day 5 of development were collected for cell-free DNA analysis. In addition to the 113 spent culture media samples, 28 media drops without embryo contact were cultured in parallel under the same conditions to use as controls. In total, 141 media samples were collected and divided into two groups: one for direct DNA quantification (53 spent culture media and 17 controls), the other for whole-genome amplification (60 spent culture media and 11 controls) and subsequent quantification. Some samples with amplified DNA (N = 56) were used for aneuploidy testing by next-generation sequencing; of those, 35 samples underwent single-nucleotide polymorphism (SNP) sequencing to detect maternal contamination. Finally, from the 35 spent culture media analyzed by SNP sequencing, 12 whole blastocysts were analyzed by fluorescence in situ hybridization (FISH) to determine the level of mosaicism in each embryo, as a possible origin for discordance between sample types. Trophectoderm biopsies and culture media samples (20 μl) underwent whole-genome amplification, then libraries were generated and sequenced for an aneuploidy study. For SNP sequencing, triads including trophectoderm DNA, cell-free DNA, and follicular fluid DNA were analyzed. In total, 124 SNPs were included with 90 SNPs distributed among all autosomes and 34 SNPs located on chromosome Y. Finally, 12 whole blastocysts were fixed and individual cells were analyzed by FISH using telomeric/centromeric probes for the affected chromosomes. We found a higher quantity of cell-free DNA in spent culture media co-cultured with embryos versus control media samples (P ≤ 0.001). The presence of cell-free DNA in the spent culture media enabled a chromosomal diagnosis, although results differed from those of trophectoderm biopsy analysis in most cases (67%). Discordant results were mainly attributable to a high percentage of maternal DNA in the spent culture media, with a median percentage of embryonic DNA estimated at 8%. Finally, from the discordant cases, 91.7% of whole blastocysts analyzed by FISH were mosaic and 75% of the analyzed chromosomes were concordant with the trophectoderm DNA diagnosis instead of the cell-free DNA result. This study was limited by the sample size and the number of cells analyzed by FISH. This is the first study to combine chromosomal analysis of cell-free DNA, SNP sequencing to identify maternal contamination, and whole-blastocyst analysis for detecting mosaicism. Our results provide a better understanding of the origin of cell-free DNA in spent culture media, offering an important step toward developing future non-invasive karyotyping that must rely on the specific identification of DNA released from human embryos. This work was funded by Igenomix S.L. There are no competing interests.

Northeast Corridor Improvement Project Electrification - New Haven, CT to Boston, MA : Final Environmental Statement/Report : v. 2. Technical Studies

DOT National Transportation Integrated Search

1994-10-31

This document is the final environmental impact statement and final environmental impact report (FEIS/R) on the proposal by the National Railroad Passenger Corporation (Amtrak) to complete the electrification of the Northeast Corridor main line by ex...

Health care fraud and abuse data collection program: technical revisions to Healthcare Integrity and Protection Data Bank data collection activities. Final rule.

PubMed

2004-09-21

The rule finalizes technical changes to the Healthcare Integrity and Protection Data Bank (HIPDB) data collection reporting requirements by clarifying the types of personal numeric identifiers that may be reported to the data bank in connection with adverse actions. The rule clarifies that in lieu of a Social Security Number (SSN), an individual taxpayer identification number (ITIN) may be reported to the data bank when, in those limited situations, an individual does not have an SSN.

Recovery Act-SmartGrid regional demonstration transmission and distribution (T&D) Infrastructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hedges, Edward T.

This document represents the Final Technical Report for the Kansas City Power & Light Company (KCP&L) Green Impact Zone SmartGrid Demonstration Project (SGDP). The KCP&L project is partially funded by Department of Energy (DOE) Regional Smart Grid Demonstration Project cooperative agreement DE-OE0000221 in the Transmission and Distribution Infrastructure application area. This Final Technical Report summarizes the KCP&L SGDP as of April 30, 2015 and includes summaries of the project design, implementation, operations, and analysis performed as of that date.

Final Technical Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobecky, Patricia A; Taillefert, Martial

This final technical report describes results and findings from a research project to examine the role of microbial phosphohydrolase enzymes in naturally occurring subsurface microorganisms for the purpose of promoting the immobilization of the radionuclide uranium through the production of insoluble uranium phosphate minerals. The research project investigated the microbial mechanisms and the physical and chemical processes promoting uranium biomineralization and sequestration in oxygenated subsurface soils. Uranium biomineralization under aerobic conditions can provide a secondary biobarrier strategy to immobilize radionuclides should the metal precipitates formed by microbial dissimilatory mechanisms remobilize due to a change in redox state.

Waveguide Studies for Fiber Optics and Optical Signal Processing Applications.

DTIC Science & Technology

1980-04-01

AO-A086 115 UNI!VERtSIT? OF SOUTIUR CALEPCRNA LOS AMUSS / 5 WAVGUIDE STUIES15 FOR FEB53 OpTECS AND OpTICAL SEOSA.o P /0Ksu-y "/6 UNLSIIDAPR N0 E...SAMUE Flola-??-c-sa UNCASZFIORAC-M-8042 U Final Technical Report (1 1April 1950 L V ~ WAVEGUIDE STUDIES FOR FIBER OPTICS AND OPTICAL SIGNAL PROCESSING...and Subtitle) 081 6&4𔃾JODO )EI YAVECUIDESTUDIES FOR JIBER OPTICS ANDL 7 Final ,T/echnical epoErt, OPTICAL SI’tNAL PROCESSING APPLICATIONS.4 11 Se 77

SELECTIVE DISSEMINATION OF INFORMATION (SDI). VOLUME I, PILOT TEST AT U.S. ARMY NATICK LABORATORIES. FINAL REPORT. ARMY TECHNICAL LIBRARY IMPROVEMENT STUDIES (ATLIS), REPORT NO. 15.

ERIC Educational Resources Information Center

BIVONA, WILLIAM A.

THIS VOLUME PRESENTS THE RESULTS OF A NINE-MONTH TEST OF A PROTOTYPE SELECTIVE DISSEMINATION OF INFORMATION (SDI) SYSTEM DEVELOPED FOR THE ARMY TECHNICAL LIBRARIES. DURING THE PILOT TEST ONE THOUSAND DOCUMENTS WERE CATALOGED, INDEXED, AND DISSEMINATED TO TWENTY-FIVE SCIENTIFIC AND TECHNICAL PERSONNEL. MATCHING OF THE INTEREST PROFILES OF THESE…

Ceramic High Efficiency Particulate Air (HEPA) Filter Final Report CRADA No. TC02160.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitchell, M.; Bergman, W.

2017-08-25

The technical objective of this project was to develop a ceramic HEPA filter technology, by initially producing and testing coupon ceramics, small scale prototypes, and full scale prototype HEPA filters, and to address relevant manufacturing and commercialization technical issues.

7 CFR 614.6 - Agency records and decision notices.

Code of Federal Regulations, 2010 CFR

2010-01-01

... notifies participants of the agency's preliminary and final technical determinations and program decisions... decision notice within 10 working days of rendering a technical determination or program decision. In lieu of certified mail, NRCS may hand deliver notices to participants with written acknowledgment of...

ECOS E-MATRIX Methane and Volatile Organic Carbon (VOC) Emissions Best Practices Database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parisien, Lia

2016-01-31

This final scientific/technical report on the ECOS e-MATRIX Methane and Volatile Organic Carbon (VOC) Emissions Best Practices Database provides a disclaimer and acknowledgement, table of contents, executive summary, description of project activities, and briefing/technical presentation link.

77 FR 18914 - National Motor Vehicle Title Information System (NMVTIS): Technical Corrections

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-29

... 1121-AA79 National Motor Vehicle Title Information System (NMVTIS): Technical Corrections AGENCY... (OJP) is promulgating this direct final rule for its National Motor Vehicle Title Information System... INFORMATION CONTACT paragraph. II. Background The National Motor Vehicle Title Information System was...

Intelligent transportation system (ITS) study for the Buffalo and Niagara Falls metropolitan area, Erie and Niagara Counties, New York : final report, technical summary

DOT National Transportation Integrated Search

1997-06-18

This document provides a technical summary for the seven working papers prepared for the New York State Department of Transportation (NYSDOT) Buffalo and Niagara Falls Intelligent Transportation System (ITS) Study.

77 FR 8095 - Technical Corrections to Commission Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission 18 CFR Part 2 [Docket No. RM11-30-000; Order No. 756] Technical Corrections to Commission Regulations Issued February 8, 2012. AGENCY: Federal Energy Regulatory Commission, DOE. ACTION: Final rule: correcting amendment. SUMMARY: This document adds...

78 FR 13543 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 201, 204, 215, 225, 227, 242, 245, and 252 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is...

Determination of the Optimal Chromosomal Location(s) for a DNA Element in Escherichia coli Using a Novel Transposon-mediated Approach.

PubMed

Frimodt-Møller, Jakob; Charbon, Godefroid; Krogfelt, Karen A; Løbner-Olesen, Anders

2017-09-11

The optimal chromosomal position(s) of a given DNA element was/were determined by transposon-mediated random insertion followed by fitness selection. In bacteria, the impact of the genetic context on the function of a genetic element can be difficult to assess. Several mechanisms, including topological effects, transcriptional interference from neighboring genes, and/or replication-associated gene dosage, may affect the function of a given genetic element. Here, we describe a method that permits the random integration of a DNA element into the chromosome of Escherichia coli and select the most favorable locations using a simple growth competition experiment. The method takes advantage of a well-described transposon-based system of random insertion, coupled with a selection of the fittest clone(s) by growth advantage, a procedure that is easily adjustable to experimental needs. The nature of the fittest clone(s) can be determined by whole-genome sequencing on a complex multi-clonal population or by easy gene walking for the rapid identification of selected clones. Here, the non-coding DNA region DARS2, which controls the initiation of chromosome replication in E. coli, was used as an example. The function of DARS2 is known to be affected by replication-associated gene dosage; the closer DARS2 gets to the origin of DNA replication, the more active it becomes. DARS2 was randomly inserted into the chromosome of a DARS2-deleted strain. The resultant clones containing individual insertions were pooled and competed against one another for hundreds of generations. Finally, the fittest clones were characterized and found to contain DARS2 inserted in close proximity to the original DARS2 location.

Chromosomal Rearrangements as Barriers to Genetic Homogenization between Archaic and Modern Humans

PubMed Central

Rogers, Rebekah L.

2015-01-01

Chromosomal rearrangements, which shuffle DNA throughout the genome, are an important source of divergence across taxa. Using a paired-end read approach with Illumina sequence data for archaic humans, I identify changes in genome structure that occurred recently in human evolution. Hundreds of rearrangements indicate genomic trafficking between the sex chromosomes and autosomes, raising the possibility of sex-specific changes. Additionally, genes adjacent to genome structure changes in Neanderthals are associated with testis-specific expression, consistent with evolutionary theory that new genes commonly form with expression in the testes. I identify one case of new-gene creation through transposition from the Y chromosome to chromosome 10 that combines the 5′-end of the testis-specific gene Fank1 with previously untranscribed sequence. This new transcript experienced copy number expansion in archaic genomes, indicating rapid genomic change. Among rearrangements identified in Neanderthals, 13% are transposition of selfish genetic elements, whereas 32% appear to be ectopic exchange between repeats. In Denisovan, the pattern is similar but numbers are significantly higher with 18% of rearrangements reflecting transposition and 40% ectopic exchange between distantly related repeats. There is an excess of divergent rearrangements relative to polymorphism in Denisovan, which might result from nonuniform rates of mutation, possibly reflecting a burst of transposable element activity in the lineage that led to Denisovan. Finally, loci containing genome structure changes show diminished rates of introgression from Neanderthals into modern humans, consistent with the hypothesis that rearrangements serve as barriers to gene flow during hybridization. Together, these results suggest that this previously unidentified source of genomic variation has important biological consequences in human evolution. PMID:26399483

Male Mutation Bias Is the Main Force Shaping Chromosomal Substitution Rates in Monotreme Mammals.

PubMed

Link, Vivian; Aguilar-Gómez, Diana; Ramírez-Suástegui, Ciro; Hurst, Laurence D; Cortez, Diego

2017-09-01

In many species, spermatogenesis involves more cell divisions than oogenesis, and the male germline, therefore, accumulates more DNA replication errors, a phenomenon known as male mutation bias. The extent of male mutation bias (α) is estimated by comparing substitution rates of the X, Y, and autosomal chromosomes, as these chromosomes spend different proportions of their time in the germlines of the two sexes. Male mutation bias has been characterized in placental and marsupial mammals as well as birds, but analyses in monotremes failed to detect any such bias. Monotremes are an ancient lineage of egg-laying mammals with distinct biological properties, which include unique germline features. Here, we sought to assess the presence and potential characteristics of male mutation bias in platypus and the short-beaked echidna based on substitution rate analyses of X, Y, and autosomes. We established the presence of moderate male mutation bias in monotremes, corresponding to an α value of 2.12-3.69. Given that it has been unclear what proportion of the variation in substitution rates on the different chromosomal classes is really due to differential number of replications, we analyzed the influence of other confounding forces (selection, replication-timing, etc.) and found that male mutation bias is the main force explaining the between-chromosome classes differences in substitution rates. Finally, we estimated the proportion of variation at the gene level in substitution rates that is owing to replication effects and found that this phenomenon can explain >68% of these variations in monotremes, and in control species, rodents, and primates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Mapping-by-sequencing in complex polyploid genomes using genic sequence capture: a case study to map yellow rust resistance in hexaploid wheat.

PubMed

Gardiner, Laura-Jayne; Bansept-Basler, Pauline; Olohan, Lisa; Joynson, Ryan; Brenchley, Rachel; Hall, Neil; O'Sullivan, Donal M; Hall, Anthony

2016-08-01

Previously we extended the utility of mapping-by-sequencing by combining it with sequence capture and mapping sequence data to pseudo-chromosomes that were organized using wheat-Brachypodium synteny. This, with a bespoke haplotyping algorithm, enabled us to map the flowering time locus in the diploid wheat Triticum monococcum L. identifying a set of deleted genes (Gardiner et al., 2014). Here, we develop this combination of gene enrichment and sliding window mapping-by-synteny analysis to map the Yr6 locus for yellow stripe rust resistance in hexaploid wheat. A 110 MB NimbleGen capture probe set was used to enrich and sequence a doubled haploid mapping population of hexaploid wheat derived from an Avalon and Cadenza cross. The Yr6 locus was identified by mapping to the POPSEQ chromosomal pseudomolecules using a bespoke pipeline and algorithm (Chapman et al., 2015). Furthermore the same locus was identified using newly developed pseudo-chromosome sequences as a mapping reference that are based on the genic sequence used for sequence enrichment. The pseudo-chromosomes allow us to demonstrate the application of mapping-by-sequencing to even poorly defined polyploidy genomes where chromosomes are incomplete and sub-genome assemblies are collapsed. This analysis uniquely enabled us to: compare wheat genome annotations; identify the Yr6 locus - defining a smaller genic region than was previously possible; associate the interval with one wheat sub-genome and increase the density of SNP markers associated. Finally, we built the pipeline in iPlant, making it a user-friendly community resource for phenotype mapping. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Chromosomal studies on 2 mL of celomic fluid obtained during the fifth week of development in the timed-pregnant baboon model.

PubMed

Santolaya-Forgas, Joaquin; De Leon-Luis, Juan; Shen, Zhion; McCorquodale, Maureen

2005-09-01

To determine if chromosomal studies could be performed using 2 mL of celomicfluid obtained during the fifth postfertilization week in pregnant baboons. Nine ultrasound-guided celocenteses were performed. The initial 0.5 mL of celomic fluid was discarded to decrease maternal cell contamination. Approximately 2 mL of celomic fluid was then collected. The fluid was centrifuged and the supernatant removed to a final volume of 0.5 mL. The celomic fluid sample was placed in either a small plastic flaskette chamber slide with a mix of 0.5 mL celomic fluid, 1 mL of Amniomax, and 1 mL of usedfibroblast culture medium to spread on the entire surface (n=4), or a 3.5 x 1-cm plastic Petri dish with a 24 x 30-mm glass coverslip to keep the 0.5 mL celomic fluid mixed with 1 mL of Amniomax (Invitrogen, Carlsbad, California) within a 1 cm2 area (n=5). The medium was changed on day 5 and thereafter every second to third day. The cells were harvested when the number of cells appeared sufficient for chromosomal analysis. Standard chromosomal studies were possible in 5 of the 9 celomicfluid samples. Mean (+/-SD) celomic fluid volume used for culture was 1.85 +/- 0.3 mL. Mean (+/-SD) time to karyotype result was 18.8 +/- 1.8 days. The findings of this study suggest that there are living cells at 36-42 days of embryonic development in the extraembryonic celomic fluid of primates and that they can be cultured for chromosomal studies. However, significant improvements in understanding the biology of cells present at 5 weeks after fertilization in celomic fluid are needed to improve culture conditions.

The Renilla luciferase gene as a reference gene for normalization of gene expression in transiently transfected cells.

PubMed

Jiwaji, Meesbah; Daly, Rónán; Pansare, Kshama; McLean, Pauline; Yang, Jingli; Kolch, Walter; Pitt, Andrew R

2010-12-31

The importance of appropriate normalization controls in quantitative real-time polymerase chain reaction (qPCR) experiments has become more apparent as the number of biological studies using this methodology has increased. In developing a system to study gene expression from transiently transfected plasmids, it became clear that normalization using chromosomally encoded genes is not ideal, at it does not take into account the transfection efficiency and the significantly lower expression levels of the plasmids. We have developed and validated a normalization method for qPCR using a co-transfected plasmid. The best chromosomal gene for normalization in the presence of the transcriptional activators used in this study, cadmium, dexamethasone, forskolin and phorbol-12-myristate 13-acetate was first identified. qPCR data was analyzed using geNorm, Normfinder and BestKeeper. Each software application was found to rank the normalization controls differently with no clear correlation. Including a co-transfected plasmid encoding the Renilla luciferase gene (Rluc) in this analysis showed that its calculated stability was not as good as the optimised chromosomal genes, most likely as a result of the lower expression levels and transfection variability. Finally, we validated these analyses by testing two chromosomal genes (B2M and ActB) and a co-transfected gene (Rluc) under biological conditions. When analyzing co-transfected plasmids, Rluc normalization gave the smallest errors compared to the chromosomal reference genes. Our data demonstrates that transfected Rluc is the most appropriate normalization reference gene for transient transfection qPCR analysis; it significantly reduces the standard deviation within biological experiments as it takes into account the transfection efficiencies and has easily controllable expression levels. This improves reproducibility, data validity and most importantly, enables accurate interpretation of qPCR data.

Transcriptome profiling of Nasonia vitripennis testis reveals novel transcripts expressed from the selfish B chromosome, paternal sex ratio.

PubMed

Akbari, Omar S; Antoshechkin, Igor; Hay, Bruce A; Ferree, Patrick M

2013-09-04

A widespread phenomenon in nature is sex ratio distortion of arthropod populations caused by microbial and genetic parasites. Currently little is known about how these agents alter host developmental processes to favor one sex or the other. The paternal sex ratio (PSR) chromosome is a nonessential, paternally transmitted centric fragment that segregates in natural populations of the jewel wasp, Nasonia vitripennis. To persist, PSR is thought to modify the hereditary material of the developing sperm, with the result that all nuclear DNA other than the PSR chromosome is destroyed shortly after fertilization. This results in the conversion of a fertilized embryo--normally a female--into a male, thereby insuring transmission of the "selfish" PSR chromosome, and simultaneously leading to wasp populations that are male-biased. To begin to understand this system at the mechanistic level, we carried out transcriptional profiling of testis from WT and PSR-carrying males. We identified a number of transcripts that are differentially expressed between these conditions. We also discovered nine transcripts that are uniquely expressed from the PSR chromosome. Four of these PSR-specific transcripts encode putative proteins, whereas the others have very short open reading frames and no homology to known proteins, suggesting that they are long noncoding RNAs. We propose several different models for how these transcripts could facilitate PSR-dependent effects. Our analyses also revealed 15.71 MB of novel transcribed regions in the N. vitripennis genome, thus increasing the current annotation of total transcribed regions by 53.4%. Finally, we detected expression of multiple meiosis-related genes in the wasp testis, despite the lack of conventional meiosis in the male sex.

Transcriptome Profiling of Nasonia vitripennis Testis Reveals Novel Transcripts Expressed from the Selfish B Chromosome, Paternal Sex Ratio

PubMed Central

Akbari, Omar S.; Antoshechkin, Igor; Hay, Bruce A.; Ferree, Patrick M.

2013-01-01

A widespread phenomenon in nature is sex ratio distortion of arthropod populations caused by microbial and genetic parasites. Currently little is known about how these agents alter host developmental processes to favor one sex or the other. The paternal sex ratio (PSR) chromosome is a nonessential, paternally transmitted centric fragment that segregates in natural populations of the jewel wasp, Nasonia vitripennis. To persist, PSR is thought to modify the hereditary material of the developing sperm, with the result that all nuclear DNA other than the PSR chromosome is destroyed shortly after fertilization. This results in the conversion of a fertilized embryo—normally a female—into a male, thereby insuring transmission of the “selfish” PSR chromosome, and simultaneously leading to wasp populations that are male-biased. To begin to understand this system at the mechanistic level, we carried out transcriptional profiling of testis from WT and PSR-carrying males. We identified a number of transcripts that are differentially expressed between these conditions. We also discovered nine transcripts that are uniquely expressed from the PSR chromosome. Four of these PSR-specific transcripts encode putative proteins, whereas the others have very short open reading frames and no homology to known proteins, suggesting that they are long noncoding RNAs. We propose several different models for how these transcripts could facilitate PSR-dependent effects. Our analyses also revealed 15.71 MB of novel transcribed regions in the N. vitripennis genome, thus increasing the current annotation of total transcribed regions by 53.4%. Finally, we detected expression of multiple meiosis-related genes in the wasp testis, despite the lack of conventional meiosis in the male sex. PMID:23893741

Natural Genetic Variation and Candidate Genes for Morphological Traits in Drosophila melanogaster

PubMed Central

Carreira, Valeria Paula; Mensch, Julián; Hasson, Esteban; Fanara, Juan José

2016-01-01

Body size is a complex character associated to several fitness related traits that vary within and between species as a consequence of environmental and genetic factors. Latitudinal and altitudinal clines for different morphological traits have been described in several species of Drosophila and previous work identified genomic regions associated with such variation in D. melanogaster. However, the genetic factors that orchestrate morphological variation have been barely studied. Here, our main objective was to investigate genetic variation for different morphological traits associated to the second chromosome in natural populations of D. melanogaster along latitudinal and altitudinal gradients in Argentina. Our results revealed weak clinal signals and a strong population effect on morphological variation. Moreover, most pairwise comparisons between populations were significant. Our study also showed important within-population genetic variation, which must be associated to the second chromosome, as the lines are otherwise genetically identical. Next, we examined the contribution of different candidate genes to natural variation for these traits. We performed quantitative complementation tests using a battery of lines bearing mutated alleles at candidate genes located in the second chromosome and six second chromosome substitution lines derived from natural populations which exhibited divergent phenotypes. Results of complementation tests revealed that natural variation at all candidate genes studied, invected, Fasciclin 3, toucan, Reticulon-like1, jing and CG14478, affects the studied characters, suggesting that they are Quantitative Trait Genes for morphological traits. Finally, the phenotypic patterns observed suggest that different alleles of each gene might contribute to natural variation for morphological traits. However, non-additive effects cannot be ruled out, as wild-derived strains differ at myriads of second chromosome loci that may interact epistatically with mutant alleles. PMID:27459710

Sperm Scoring Using Multi-Spectral Flow Imaging and FISH-IS Final Report CRADA No. TC02088.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchetti, F.; Morrissey, P. J.

This was to be a collaborative effort between The Regents of the University of California, Lawrence Livermore National Laboratory (LLNL) and Amnis Corporation, to develop an automated system for scoring sperm interphase cells for the presence of chromosomal abnormalities using fluorescence in situ hybridization and the Amnis ImageStream technology platform.

[Turner syndrome: Study of 42 cases].

PubMed

Bahíllo-Curieses, M Pilar; Prieto-Matos, Pablo; Quiroga González, Rocío; Regueras Santos, Laura; Blanco Barrio, Amaya; Rupérez Peña, Sara

2016-10-21

Turner syndrome (TS) is characterized by short stature, gonadal dysgenesis, and total or partial loss of X chromosome. A historical cohorts study of patients with TS≤18 years old followed up in public hospitals in Castilla y Leon was undertaken. Forty-two female patients were included (prenatal diagnosis 11.9%, neonatal diagnosis 14.3%) with current median age 11.9±4.2 years. Short stature was the reason for consultation in 87.1%. Total monosomy of X chromosome was present in 40.5%. The most frequently associated comorbidity was opthalmological (50%), with heart defects in 23.8%. Ninety-three percent were treated with growth hormone (GH), mean age at the beginning of treatment was 7.43±3.4 years and mean height standard deviation was -2.84±1.08. Final height was reached in 10 patients only (mean final height 151.47±6.09cm). Chronological age of puberty induction was 13.2±0.94 years (bone age 12.47±1.17 years). Short stature was an important clinical sign for the diagnosis of TS, accompanied in some cases by other findings, with good response to GH treatment. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Normal pelvic ultrasound or MRI does not rule out neoplasm in patients with gonadal dysgenesis and Y chromosome material.

PubMed

Ebert, Kristin M; Hewitt, Geri D; Indyk, Justin A; McCracken, Katherine A; Nahata, Leena; Jayanthi, Venkata R

2018-04-01

Patients with gonadal dysgenesis (GD) with a Y chromosome have an increased risk of gonadal neoplasm. Few data exist on the ability of imaging to detect malignancy in intra-abdominal gonads in these patients. We aimed to determine the correlation between preoperative imaging findings and gonadal pathology in GD patients with Y chromosome material. A retrospective review was performed of patients with XY or XO/XY GD who underwent gonadectomy at our institution from 2003 to 2017. Patients were assessed preoperatively with ultrasonography; some additionally underwent MRI. The series consisted of 10 patients, all with female gender and non-palpable gonads. Median age was 13.1 years (range 2.4-18.3 years). Overall, four of the ten patients (40%) had a tumor (gonadoblastoma or dysgerminoma) on final pathology. Four patients had a gonad or gonads that were definitively seen on ultrasonography. All visualized gonads were described as "normal" or "small" with the exception of one patient, who had a normal MRI. Three of the four patients in this group had a tumor on final pathology. The remaining six patients had a gonad or gonads that were not definitively visualized on ultrasound; one patient in this group had a tumor on final pathology. Overall, five of seven gonads (71%) definitively visualized on ultrasound had tumor on final pathology, and two of thirteen gonads (15%) not visualized on ultrasound had tumor on final pathology; this difference was statistically significant (p = 0.012). Three patients were imaged with MRI. Of the gonads that could be visualized on MRI, no definitive abnormalities were seen. All patients imaged with MRI had tumors on final pathology. Both ultrasound and MRI are relatively poor at identifying and characterizing intra-abdominal gonads in GD patients. The majority of patients who had a neoplasm had normal imaging findings. Gonads that were definitively visualized on ultrasound were more likely to contain neoplasms that could not be visualized, which perhaps because of tumor growth. No other consistent imaging findings of malignancy were found. Our study included ultrasound evaluations that were completed over 10 years ago and not performed by pediatric ultrasonographers, which may have biased the results. However, results suggest that when discussing gonadectomy with GD patients, one should not be reassured by "normal" imaging findings. Neither ultrasound nor MRI should be relied on for surveillance in GD patients who decide against gonadectomy. A normal ultrasound or MRI does not rule out neoplasm in GD patients with intra-abdominal gonads. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Alternatives for Jet Engine Control. Volume 1: Modelling and Control Design with Jet Engine Data

NASA Technical Reports Server (NTRS)

Sain, M. K.

1985-01-01

This document compiles a comprehensive list of publications supported by, or related to, National Aeronautics and Space Administration Grant NSG-3048, entitled "Alternatives for Jet Engine Control". Dr. Kurt Seldner was the original Technical Officer for the grant, at Lewis Research Center. Dr. Bruce Lehtinen was the final Technical Officer. At the University of Notre Dame, Drs. Michael K. Sain and R. Jeffrey Leake were the original Project Directors, with Dr. Sain becoming the final Project Director. Publications cover work over a ten-year period. The Final Report is divided into two parts. Volume i, "Modelling and Control Design with Jet Engine Data", follows in this report. Volume 2, "Modelling and Control Design with Tensors", has been bound separately.

48 CFR 252.235-7011 - Final scientific or technical report.

Code of Federal Regulations, 2014 CFR

2014-10-01

... technical report. 252.235-7011 Section 252.235-7011 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT... of the report; and (c) For submission of reports in other than paper copy, contact the Defense...

48 CFR 252.235-7011 - Final scientific or technical report.

Code of Federal Regulations, 2012 CFR

2012-10-01

... technical report. 252.235-7011 Section 252.235-7011 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT... of the report; and (c) For submission of reports in other than paper copy, contact the Defense...

48 CFR 252.235-7011 - Final scientific or technical report.

Code of Federal Regulations, 2010 CFR

2010-10-01

... technical report. 252.235-7011 Section 252.235-7011 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT... of the report; and (c) For submission of reports in other than paper copy, contact the Defense...

48 CFR 252.235-7011 - Final scientific or technical report.

Code of Federal Regulations, 2011 CFR

2011-10-01

... technical report. 252.235-7011 Section 252.235-7011 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT... of the report; and (c) For submission of reports in other than paper copy, contact the Defense...

48 CFR 252.235-7011 - Final scientific or technical report.

Code of Federal Regulations, 2013 CFR

2013-10-01

... technical report. 252.235-7011 Section 252.235-7011 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT... of the report; and (c) For submission of reports in other than paper copy, contact the Defense...

Vocational Outreach Involving Community Exchange (VOICE). Final Report.

ERIC Educational Resources Information Center

Huckabee, Johnni

A Jonesboro, Arkansas project was designed and implemented to increase the awareness of vocational education, increase community support and involvement in vocational education, and establish improved communication in the vocational-technical education field. Interaction between the vocational-technical school and the local school community was a…

Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation.

PubMed

Liao, Gary J W; Gronowski, Ann M; Zhao, Zhen

2014-01-20

The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible. Maternal plasma cell free DNA is a mixture of maternal and fetal DNA, of which, fetal DNA represents a minor population in maternal plasma. Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice.

King County Metro Transit Hybrid Articulated Buses: Final Evaluation Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chandler, K.; Walkowicz, K.

2006-12-01

Final technical report compares and evaluates new diesel and diesel hybrid-electric articulated buses operated as part of the King County Metro Transit (KC Metro) fleet in Seattle, Washington. The evaluation lasted 12 months.

78 FR 1143 - Explosive Siting Requirements; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

... launch site operators in site planning for the storage and handling of energetic liquids and explosives...: For technical questions concerning this final rule, contact Yvonne Tran, Commercial Space... this final rule, contact Laura Montgomery, AGC 200, [[Page 1144

Final June Revisions Rule State Budgets and New Unit Set-Asides TSD

EPA Pesticide Factsheets

This technical support document (TSD) for the final revisions to the Transport Rule shows the underlying data and calculations used to quantify the state budget revisions and new unit set-aside revisions.

Micromanipulation by laser microbeam and optical tweezers: from plant cells to single molecules.

PubMed

Greulich, K O; Pilarczyk, G; Hoffmann, A; Meyer Zu Hörste, G; Schäfer, B; Uhl, V; Monajembashi, S

2000-06-01

Complete manipulation by laser light allows precise and gentle treatment of plant cells, subcellular structures, and even individual DNA molecules. Recently, affordable lasers have become available for the construction of microbeams as well as for optical tweezers. This may generate new interest in these tools for plant biologists. Early experiments, reviewed in this journal, showed that laser supported microinjection of material into plant cells or tissues circumvents mechanical problems encountered in microinjection by fragile glass capillaries. Plant protoplasts could be fused with each other when under microscopical observation, and it was no major problem to generate a triple or quadruple fusion product. In the present paper we review experiments where membrane material was prepared from root hair tips and microgravity was simulated in algae. As many plant cells are transparent, it is possible to work inside living, intact cells. New experiments show that it is possible to release by optical micromanipulation, with high spatial resolutions, intracellular calcium from caged compounds and to study calcium oscillations. An example for avian cardiac tissue is given, but the technique is also suitable for plant cell research. As a more technical tool, optical tweezers can be used to spatially fix subcellular structures otherwise moving inside a cell and thus make them available for investigation with a confocal microscope even when the time for image formation is extended (for example at low fluorescence emission). A molecular biological example is the handling of chromosomes and isolated individual DNA molecules by laser microtools. For example, chromosomes can be cut along complex trajectories, not only perpendicular to their long axis. Single DNA molecules are cut by the laser microbeam and, after coupling such a molecule to a polystrene microbead, are handled in complex geometries. Here, the individual DNA molecules are made visible with a conventional fluorescence microscope by fluorescent dyes such as SYBRGreen. The cutting of a single DNA molecule by molecules of the restriction endonuclease EcoRI can be observed directly, i.e. a type of single molecule restriction analysis is possible. Finally, mechanical properties of individual DNA molecules can be observed directly.

Department of Defense Access to Intellectual Property for Weapon Systems Sustainment

DTIC Science & Technology

2017-05-01

and acquiring technical data rights …  The cost benefit analysis of including a priced contract option for the future delivery of technical data...entail in terms of cost and benefits , while one of the activities to be finalized is the contract-specific technical data elements.66...Virginia 22311-1882 May 2017 Approved for public release; distribution is unlimited. IDA Paper P-8266 Log: H 17-000030 About This Publication This

10 CFR 51.92 - Supplement to the final environmental impact statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... changes in the proposed action that are relevant to environmental concerns; or (2) There are new and..., technical, and other benefits and costs of the proposed action, to the extent that the final environmental... costs; (5) Include an analysis of other energy alternatives, to the extent that the final environmental...

Dissemination of Continuing Education Materials Via Television Delivery Systems. Final Technical Report and Final Report.

ERIC Educational Resources Information Center

Munushian, Jack

In 1972, the University of Southern California School of Engineering established a 4-channel interactive instructional television network. It was designed to allow employees of participating industries to take regular university science and engineering courses and special continuing education courses at or near their work locations. Final progress…

Pregnancy Outcome of Abnormal Nuchal Translucency: A Systematic Review

PubMed Central

Roozbeh, Nasibeh; Azizi, Maryam

2017-01-01

Introduction Nuchal Translucency (NT) is the sonographic form of subcutaneous gathering of liquid behind the foetal neck in the first trimester of pregnancy. There is association of increased NT with chromosomal and non-chromosomal abnormalities. Aim The purpose of this systemic review was to review the pregnancy outcome of abnormal nuchal translucency. Materials and Methods The present systematic review was conducted by searching English language articles from sources such as International Medical Sciences, Medline, Web of science, Scopus, Google Scholar, PubMed, Index Copernicus, DOAJ, EBSCO-CINAHL. Persian articles were searched from Iranmedex and SID sources. Related key words were “outcome”, “pregnancy”, “abnormal”, and “Nuchal Translucency” (NT). All, randomized, descriptive, analytic-descriptive, case control study conducted during 1997-2015 were included. Results Including duplicate articles, 95 related articles were found. After reviewing article titles, 30 unrelated article and abstracts were removed, and 65 articles were evaluated of which 30 articles were duplicate. Finally 22 articles were selected for final analysis. Exclusion criteria were, case studies and reports and quasi experimental designs. This evaluation has optioned negative relationship between nuchal translucency and pregnancy result. Rate of cardiac, chromosomal and other defects are correlated with increased NT≥2.5mm. Cardiac disease which were associated to the increased NT are heart murmur, systolic organic murmur, Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), tricuspid valve insufficiency and pulmonary valve insufficiency, Inferior Vena Cava (IVC) and Patent Ductus Arteriosus (PDA). The most common problems that related with increased NT were allergic symptoms. Conclusion According to this systematic review, increased NT is associated with various foetal defects. To verify the presence of malformations, birth defect consultations with a perinatologist and additional tests are required. PMID:28511453

Pregnancy Outcome of Abnormal Nuchal Translucency: A Systematic Review.

PubMed

Roozbeh, Nasibeh; Azizi, Maryam; Darvish, Leili

2017-03-01

Nuchal Translucency (NT) is the sonographic form of subcutaneous gathering of liquid behind the foetal neck in the first trimester of pregnancy. There is association of increased NT with chromosomal and non-chromosomal abnormalities. The purpose of this systemic review was to review the pregnancy outcome of abnormal nuchal translucency. The present systematic review was conducted by searching English language articles from sources such as International Medical Sciences, Medline, Web of science, Scopus, Google Scholar, PubMed, Index Copernicus, DOAJ, EBSCO-CINAHL. Persian articles were searched from Iranmedex and SID sources. Related key words were "outcome", "pregnancy", "abnormal", and "Nuchal Translucency" (NT). All, randomized, descriptive, analytic-descriptive, case control study conducted during 1997-2015 were included. Including duplicate articles, 95 related articles were found. After reviewing article titles, 30 unrelated article and abstracts were removed, and 65 articles were evaluated of which 30 articles were duplicate. Finally 22 articles were selected for final analysis. Exclusion criteria were, case studies and reports and quasi experimental designs. This evaluation has optioned negative relationship between nuchal translucency and pregnancy result. Rate of cardiac, chromosomal and other defects are correlated with increased NT≥2.5mm. Cardiac disease which were associated to the increased NT are heart murmur, systolic organic murmur, Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), tricuspid valve insufficiency and pulmonary valve insufficiency, Inferior Vena Cava (IVC) and Patent Ductus Arteriosus (PDA). The most common problems that related with increased NT were allergic symptoms. According to this systematic review, increased NT is associated with various foetal defects. To verify the presence of malformations, birth defect consultations with a perinatologist and additional tests are required.

The role of non-technical skills in surgery

PubMed Central

Agha, Riaz A.; Fowler, Alexander J.; Sevdalis, Nick

2015-01-01

Non-technical skills are of increasing importance in surgery and surgical training. A traditional focus on technical skills acquisition and competence is no longer enough for the delivery of a modern, safe surgical practice. This review discusses the importance of non-technical skills and the values that underpin successful modern surgical practice. This narrative review used a number of sources including written and online, there was no specific search strategy of defined databases. Modern surgical practice requires; technical and non-technical skills, evidence-based practice, an emphasis on lifelong learning, monitoring of outcomes and a supportive institutional and health service framework. Finally these requirements need to be combined with a number of personal and professional values including integrity, professionalism and compassionate, patient-centred care. PMID:26904193

75 FR 16345 - Administrative Practices and Procedures; Good Guidance Practices; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

.... FDA-1999-N-3539] (formerly Docket No. 1999N-4783) Administrative Practices and Procedures; Good Guidance Practices; Technical Amendment AGENCY: Food and Drug Administration, HHS. ACTION: Final rule... Subjects in 21 CFR Part 10 Administrative practice and procedure, News media. 0 Therefore, under the...

Final report : for the period of December 1999 through November 30, 2000 : Florida Transit Training Program (1999/2000) : Florida Technical Assistance Program (1999/2000)

DOT National Transportation Integrated Search

2000-01-01

The following progress report is intended to highlight the significant activities of the Florida Transit Training Program and Florida Technical Assistant Program. The following progress report is intended to highlight the significant activities of th...

78 FR 34264 - Technical Corrections to the HIPAA Privacy, Security, and Enforcement Rules

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

...-AA03 Technical Corrections to the HIPAA Privacy, Security, and Enforcement Rules AGENCY: Office for... corrections address certain inadvertent errors and omissions in the HIPAA Privacy, Security, and Enforcement... (HHS or ``the Department'') published a final rule to implement changes to the HIPAA Privacy, Security...

76 FR 11414 - Defense Federal Acquisition Regulation Supplement; Independent Research and Development Technical...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... Acquisition Regulation Supplement; Independent Research and Development Technical Descriptions (DFARS Case... (DFARS) to require contractors to report independent research and development (IR&D) projects generating... the address shown below on or before May 2, 2011, to be considered in the formation of the final rule...

Professional Personnel Evaluation System: 1983-84 Final Technical Report.

ERIC Educational Resources Information Center

Doss, David A.

This technical report summarizes the evaluation ratings given to professionals on probation or up for contract renewal in the Austin Independent School District. Graphs, tables, and rankings are presented for each specified population: all district teachers combined; teachers by school level (elementary, junior high, senior high); teachers by…

High School Graduation Minimum Competency Requirements. Final Technical Report.

ERIC Educational Resources Information Center

Austin Independent School District, TX. Office of Research and Evaluation.

This technical report details the testing results and analyses supporting the evaluation findings related to the Austin (Texas) Independent School District (AISD) minimum competency graduation requirements. The graduation competency status of all AISD students in grades 8 to 12 are documented. The report provides additional information on the data…

76 FR 16531 - Technical Correction for Neurological Listing Cross-Reference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

... 1-800-325-0778, or visit our Internet site, Social Security Online, at http://www.socialsecurity.gov... SOCIAL SECURITY ADMINISTRATION 20 CFR Part 404 [Docket No. SSA-2011-0019] RIN 0960-AH33 Technical Correction for Neurological Listing Cross-Reference AGENCY: Social Security Administration. ACTION: Final...

Improving Vocational Education in Post-High School Institutions. Final Report.

ERIC Educational Resources Information Center

MacArthur, Earl W.

Four ongoing programs in postsecondary vocational-technical education were examined in a national institute attended by 59 representatives from 31 states. Institutions reporting programs were: (1) Los Angeles Trade and Technical College, California, (2) Washtenaw Community College, Ann Arbor, Michigan, (3) Rockingham Community College, Wentworth,…

Chicago Manufacturing Tech Prep. Fiscal Year 1991 Final Report.

ERIC Educational Resources Information Center

Chicago City Colleges, IL.

During its first year of development in 1991, the Chicago Manufacturing Technical Preparation (Tech Prep) Program established a plan for implementing an industry-driven, articulated 4-year manufacturing technology course of study that integrates applied academic courses with technical courses and meets industry hiring standards. The project…

78 FR 29239 - Final Priority; Technical Assistance To Improve State Data Capacity-National Technical Assistance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

... reporting requirements. Changes: None. Focus TA on Assessment and Discipline Data Comment: Three commenters agreed with the importance of focusing on assessment and discipline data, and two commenters agreed with... decisions and actions associated with data collection and reporting. One commenter stated that assessment...

Modular Radioisotope Thermoelectric Generator (RTG) Program. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-12-31

Section 2.0 of this report summarizes the MOD-RTG reference flight design, and Section 3.0 discusses the Ground Demonstration System design. Multicouple technology development is discussed in Section 4.0, and Section 5.0 lists all published technical papers prepared during the course of the contract.

Methodology in Seeking Stakeholder Perceptions of Effective Technical Oral Presentations: An Exploratory Pilot Study

ERIC Educational Resources Information Center

Bhattacharyya, Ena; Patil, Arun; Sargunan, Rajeswary Appacutty

2010-01-01

Engineering communication studies indicate the importance of oral presentations as an indispensable component of workplace oral communication activities; however, since there is limited literature regarding stakeholder perceptions of effective presentation skills and attributes in technical oral presentations or final year engineering project…

Additional Final Area Designations and Technical Amendment for the 2012 Annual Fine Particle Standard Established in 2012 - Mar 2015

EPA Pesticide Factsheets

EPA is establishing or revising initial area designations and a technical amendment to correct an inadvertent error in the initial designation for one area for the 2012 annual national ambient air quality standards for fine particle pollution.

75 FR 41404 - List of Approved Spent Fuel Storage Casks: NUHOMS®

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

.... The NRC is taking this action because the applicant identified that a certain Technical Specification (TS) for Boral characterization was not written precisely. Specifically, the requirements for meeting... changes to the technical specifications. The NRC also published a direct final rule on May 6, 2010 (75 FR...

Research in Automatic Russian-English Scientific and Technical Lexicography. Final Report.

ERIC Educational Resources Information Center

Wayne State Univ., Detroit, MI.

Techniques of reversing English-Russian scientific and technical dictionaries into Russian-English versions through semi-automated compilation are described. Sections on manual and automatic processing discuss pre- and post-editing, the task program, updater (correction of errors and revision by specialist in a given field), the system employed…

National Data Program for the Marine Environment Technical Development Plan. Final Report, Volume Two.

ERIC Educational Resources Information Center

System Development Corp., Santa Monica, CA.

A national data program for the marine environment is recommended. Volume 2 includes: (1) objectives, scope, and methodology; (2) summary of the technical development plan; (3) agency development plans - Great Lakes and coastal development and (4) marine data network development plans. (Author)

Course of Study Project. Final Report. Vocational-Technical Education Departmental Report, Vol. 17, No. 18.

ERIC Educational Resources Information Center

Pennsylvania State Univ., University Park. Div. of Occupational and Vocational Studies.

Designed for use by area vocational-technical schools and other vocational programs, this project developed courses of study in eight occupational areas: commercial art, appliance repair, automotive mechanics, graphic arts, building trades maintenance, building construction trades, diesel mechanics, and welding. Course-of-study development…

Seminar for Preparation of Professional Personnel for Vocational-Technical Education. Final Report.

ERIC Educational Resources Information Center

Dillon, Roy D.; Horner, James T.

Seminar participants included college administrative officers, state vocational education directors, vocational-technical teacher educators, and Office of Education staff. The purpose of the June, 1968 seminar was to consider strategies for resolving critical vocational education personnel supply and demand problems. Presentations included in the…

75 FR 33167 - Technical Amendment Language Change From “Wholly” to “Fully”

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... SOCIAL SECURITY ADMINISTRATION 20 CFR Parts 404, 405, 408, 416, and 418 [Docket No. SSA-2009-0062] RIN 0960-AH16 Technical Amendment Language Change From ``Wholly'' to ``Fully'' AGENCY: Social Security... these final rules, call Brian J. Rudick, Office of Regulations, Social Security Administration, 6401...

76 FR 58144 - Defense Federal Acquisition Regulation Supplement; Presumption of Development Exclusively at...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... technical data package, in cases where the Government may have funded only a small portion of the... subcontractor's asserted restrictions on technical data and computer software. DATES: Effective date: September... data and computer software. More specifically, the final rule affects these validation procedures in...

75 FR 49408 - Navigation and Navigable Waters; Technical, Organizational, and Conforming Amendments, Bridges

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-13

... Conforming Amendments, Bridges AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: This rule makes non... technical corrections to Coast Guard bridge and navigable waters regulations. This rule will have no... announces or gathers public opinion or other information regarding bridge matters, nor will it change the...

Research in network management techniques for tactical data communications networks

NASA Astrophysics Data System (ADS)

Boorstyn, R.; Kershenbaum, A.; Maglaris, B.; Sarachik, P.

1982-09-01

This is the final technical report for work performed on network management techniques for tactical data networks. It includes all technical papers that have been published during the control period. Research areas include Packet Network modelling, adaptive network routing, network design algorithms, network design techniques, and local area networks.

A System for Evaluating Microcomputer Courseware for Vocational and Technical Education. Final Report.

ERIC Educational Resources Information Center

Chase, Shirley A.; And Others

A project was conducted to design a system for evaluating microcomputer courseware for vocational and technical education. Through a literature review and contacts with organizations and individuals involved in courseware evaluation and use, project staff identified and acquired for review documents pertaining to courseware evaulation, vocational…

Chromosome 13q deletion and IgH abnormalities may be both masked by near-tetraploidy in a high proportion of multiple myeloma patients: a combined morphology and I-FISH analysis.

PubMed

Koren-Michowitz, Maya; Hardan, Izhar; Berghoff, Janina; Yshoev, Galina; Amariglio, Ninette; Rechavi, Gideon; Nagler, Arnon; Trakhtenbrot, Luba

2007-10-08

Ploidy status and chromosomal aberrations involving chromosome 13q and the immunoglobulin heavy chain locus (IgH) are important prognostic features in multiple myeloma (MM). However, conventional cytogenetic studies are often not reveling and determination of plasma cells (PC) ploidy status in MM is technically difficult. We have used a combined cell morphology and interphase FISH (I-FISH) analysis in 184 consecutive BM samples from 136 MM patients for the diagnosis of chromosome 13q deletion [del (13q)] and IgH abnormalities. We have found a high prevalence (37%) of near-tetraploid (NT) PC in the BM samples studied. NT status of PC was verified with DNA index (DI) measurements. del (13q) was found in 69% and a total absence of one IgH copy (loss of IgH) in 20% of NT samples. We have shown that the presence of del (13q) and loss of IgH can be masked in NT cases: in 12 NT samples originally identified as normal for del (13q) the abnormality was obscured in the majority of plasma cells due to the presence of NT. Similarly, loss of IgH was masked in four samples with a large population of NT cells. Moreover, in one case the appearance of a 100% tetraploidy during disease progression masked the presence of del (13q), originally present, and could therefore falsely appear as disappearance of this prognostic marker. In conclusion, we have shown that a combination of three abnormalities, i.e., del (13q), loss of IgH and NT, all of potential prognostic significance, can be overlooked unless NT is specifically searched for and ruled out. Therefore, we suggest that a search for NT should be added to the routine BM assessment in MM patients.

Chromosomal mutagenesis in human somatic cells: 30-year cytogenetic monitoring after Chornobyl accident.

PubMed

Pilinska, M A; Shemetun, G M; Shemetun, O V; Dybsky, S S; Dybska, O B; Talan, O O; Pedan, L R; Kurinnyi, D А

2016-12-01

In the lecture we have generalized and analyzed the data of cytogenetic laboratory of National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine on 30-year selective cytogenetic monitoring among the priority contingents of different ages exposed to radiation after Chornobyl accident in Ukraine. It is highlighted that not only targeted but also untargeted radiation-induced cytogenetic effects should be explored, especially in delayed terms following radiation exposure. The new methodical approaches for studying "bystander effect", individual radiosensitivity, and various forms of radiation-induced chromosomal instability (delayed, hidden, transmissible) have been proposed. These approaches proved to be advantageous for analyzing cytogenetic patterns of induction and persistence of chromosomal instability in human somatic cells because of "bystander effect" and "bystander type effect". The phenomenon of positive "reverse" bystander effect has been found. The possibility of modifying the inherited individual human susceptibility to mutagenic exposure by ionizing radiation has been estimated. Finally, the association between hypersensitivity to radiation exposure and realization of oncopathology in exposed individuals has been revealed. The increased intensity of human somatic chromosomal mutagenesis was confirmed not only in the nearest but in the delayed terms following Chornobyl accident as a result of radiation-induced both targeted and untargeted cytogenetic effects. Such effects can be considered as risk factors for malignant transformation of cells, hereditary diseases, birth defects, and multifactorial somatic pathology. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

A new twist in the coil: functions of the coiled-coil domain of structural maintenance of chromosome (SMC) proteins.

PubMed

Matityahu, Avi; Onn, Itay

2018-02-01

The higher-order organization of chromosomes ensures their stability and functionality. However, the molecular mechanism by which higher order structure is established is poorly understood. Dissecting the activity of the relevant proteins provides information essential for achieving a comprehensive understanding of chromosome structure. Proteins of the structural maintenance of chromosome (SMC) family of ATPases are the core of evolutionary conserved complexes. SMC complexes are involved in regulating genome dynamics and in maintaining genome stability. The structure of all SMC proteins resembles an elongated rod that contains a central coiled-coil domain, a common protein structural motif in which two α-helices twist together. In recent years, the imperative role of the coiled-coil domain to SMC protein activity and regulation has become evident. Here, we discuss recent advances in the function of the SMC coiled coils. We describe the structure of the coiled-coil domain of SMC proteins, modifications and interactions that are mediated by it. Furthermore, we assess the role of the coiled-coil domain in conformational switches of SMC proteins, and in determining the architecture of the SMC dimer. Finally, we review the interplay between mutations in the coiled-coil domain and human disorders. We suggest that distinctive properties of coiled coils of different SMC proteins contribute to their distinct functions. The discussion clarifies the mechanisms underlying the activity of SMC proteins, and advocates future studies to elucidate the function of the SMC coiled coil domain.

Epigenetic modification and inheritance in sexual reversal of fish.

PubMed

Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei; Zhang, Yong; Wang, Jun; Zhang, Guojie

2014-04-01

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

Ancestral Asian source(s) of new world Y-chromosome founder haplotypes.

PubMed Central

Karafet, T M; Zegura, S L; Posukh, O; Osipova, L; Bergen, A; Long, J; Goldman, D; Klitz, W; Harihara, S; de Knijff, P; Wiebe, V; Griffiths, R C; Templeton, A R; Hammer, M F

1999-01-01

Haplotypes constructed from Y-chromosome markers were used to trace the origins of Native Americans. Our sample consisted of 2,198 males from 60 global populations, including 19 Native American and 15 indigenous North Asian groups. A set of 12 biallelic polymorphisms gave rise to 14 unique Y-chromosome haplotypes that were unevenly distributed among the populations. Combining multiallelic variation at two Y-linked microsatellites (DYS19 and DXYS156Y) with the unique haplotypes results in a total of 95 combination haplotypes. Contra previous findings based on Y- chromosome data, our new results suggest the possibility of more than one Native American paternal founder haplotype. We postulate that, of the nine unique haplotypes found in Native Americans, haplotypes 1C and 1F are the best candidates for major New World founder haplotypes, whereas haplotypes 1B, 1I, and 1U may either be founder haplotypes and/or have arrived in the New World via recent admixture. Two of the other four haplotypes (YAP+ haplotypes 4 and 5) are probably present because of post-Columbian admixture, whereas haplotype 1G may have originated in the New World, and the Old World source of the final New World haplotype (1D) remains unresolved. The contrasting distribution patterns of the two major candidate founder haplotypes in Asia and the New World, as well as the results of a nested cladistic analysis, suggest the possibility of more than one paternal migration from the general region of Lake Baikal to the Americas. PMID:10053017

Mechanisms and genetic control of interspecific crossing barriers in Lycopersicon. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mutschler, M.A.

Deficiency of Lycopersicon esculentum allele (E) was observed from the RFLP and isozyme data of the F{sub 2} populations derived from the cross L. esculentum x L. pennellii. The genome composition of the F{sub 2} populations containing L. pennellii cytoplasm (F{sub 2}{sup Lp4}) has a lower proportion of the homozygous L. pennellii (PP) genotypes and a higher proportion of heterozygote (EP) genotypes than that of the F{sub 2} populations containing L. esculentum cytoplasm (F{sub 2}{sup Le}). A lower proportion of the L. pennellii alleles (P) was also observed in F{sub 2}{sup Lp4} as compared to F{sub 2}{sup Le} when eachmore » marker locus was tested individually. To study the effects of gametic and zygotic selection on segregation distortion, the expected patterns of segregation at a marker locus were derived for ten selection models with gametic or zygotic selection at a hidden linked locus. Segregation distortion caused by four of the selection models studied can be uniquely identified by the patterns of significance expected for the likelihood ratio tests at the marker loci. Comparison of the chromosomal regions associated with specific selection models across populations (of this experiment and previous publications) indicated that the segregation distortion observed in chromosome 10 is associated with zygotic selection affecting both arms of the chromosome, and cytoplasm substitution has the effect of decreasing the segregation distortion on the long arm of the chromosome.« less

Differentially-dimensioned furrow formation by zygotic gene expression and the MBT

PubMed Central

Xie, Yi

2018-01-01

Despite extensive work on the mechanisms that generate plasma membrane furrows, understanding how cells are able to dynamically regulate furrow dimensions is an unresolved question. Here, we present an in-depth characterization of furrow behaviors and their regulation in vivo during early Drosophila morphogenesis. We show that the deepening in furrow dimensions with successive nuclear cycles is largely due to the introduction of a new, rapid ingression phase (Ingression II). Blocking the midblastula transition (MBT) by suppressing zygotic transcription through pharmacological or genetic means causes the absence of Ingression II, and consequently reduces furrow dimensions. The analysis of compound chromosomes that produce chromosomal aneuploidies suggests that multiple loci on the X, II, and III chromosomes contribute to the production of differentially-dimensioned furrows, and we track the X-chromosomal contribution to furrow lengthening to the nullo gene product. We further show that checkpoint proteins are required for furrow lengthening; however, mitotic phases of the cell cycle are not strictly deterministic for furrow dimensions, as a decoupling of mitotic phases with periods of active ingression occurs as syncytial furrow cycles progress. Finally, we examined the turnover of maternal gene products and find that this is a minor contributor to the developmental regulation of furrow morphologies. Our results suggest that cellularization dynamics during cycle 14 are a continuation of dynamics established during the syncytial cycles and provide a more nuanced view of developmental- and MBT-driven morphogenesis. PMID:29337989

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

Best's vitelliform dystrophy (VMD2) maps between D11S903 and PYGM: No evidence for locus heterogeneity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, B.H.F.; Walker, D.; Mar, L.

1994-03-15

Vitelliform macular dystrophy, also known as Best's disease (BD), is an autosomal dominant disorder typically characterized by an accumulation of yellowish material in the macular area. The disease is slowly progressive and eventually results in atrophy of the retinal pigment epithelium and photoreceptor cells, thus severely impairing central vision. The biochemical defect underlying this condition is unknown. More recently, the BD locus (VMD2) was mapped to chromosome 11 by genetic analysis in three multigeneration Best's disease families using eight microsatellite markers spanning approximately 26 cM around the putative BD locus. The authors demonstrate linkage between Best's disease and the markersmore » used. Furthermore, haplotype analysis in unrelated Best's disease families identified three distinct haplotypes associated with the disease, strongly suggesting independent origins of the BD mutation. Finally, they characterized two recombinant BD chromosomes that significantly refine the location of the disease gene to a 3.7-cM interval between markers at D11S903 and PYGM. PCR-hybrid mapping sublocalized this interval to the pericentromeric region of chromosome 11. 47 refs., 4 figs., 1 tab.« less

Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array.

PubMed

Serio, Gabriella; Pezzuto, Federica; Marzullo, Andrea; Scattone, Anna; Cavone, Domenica; Punzi, Alessandra; Fortarezza, Francesco; Gentile, Mattia; Buonadonna, Antonia Lucia; Barbareschi, Mattia; Vimercati, Luigi

2017-08-22

Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1→q13, 8p23.1, 9p12→p11, 9q21.33→q33.1, 9q12→q21.33, and 17p12→p11.2 are observed. Chromosome band 3p21 ( BAP1 ), 9p21 ( CDKN2A ) and 22q12 ( NF2 ) are not affected. Conclusions: the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM).

The anticancer homeopathic composite "Canova Method" is not genotoxic for human lymphocytes in vitro.

PubMed

Seligmann, Igor C; Lima, Patrícia D L; Cardoso, Plínio C S; Khayat, André S; Bahia, Marcelo O; Buchi, Dorli de Freitas; Cabral, Isabel R; Burbano, Rommel R

2003-06-30

The Canova Method (CM) is a homeopathic medicine indicated for the treatment of patients with cancer and for pathologies that involve a depressed immune system, such as AIDS. This product is composed of homeopathic dilutions of Aconitum napellus, Arsenicum album (arsenic trioxide), Bryonia alba, Lachesis muta venom and Thuya occidentalis. It stimulates the immune system by activating macrophages. Activated macrophages stimulate the lymphocytes so that they increase their cytotoxic action in response to tumoral growth or infection. Given that the CM stimulates and accelerates the activity of macrophages and lymphocytes, we evaluated genotoxic effects induced in human lymphocytes treated with this homeopathic medication in vitro. Structural and numerical chromosomal aberrations were scored for the assessment of induced genotoxic effects, while the variation in mitotic index was considered as a monitor for induced cellular toxicity. The lymphocytes were cultivated for 24, 48 or 72 h in the following final concentrations of the medicinal composite CM: 4, 8 and 12%. Treatments with the CM did not affect mitotic indexes, nor did they provoke chromosomal aberrations, when compared with untreated controls. There was no cytotoxicity or genotoxicity at the chromosomal level.

Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer

PubMed Central

Turnbull, Clare; Rapley, Elizabeth A.; Seal, Sheila; Pernet, David; Renwick, Anthony; Hughes, Deborah; Ricketts, Michelle; Linger, Rachel; Nsengimana, Jeremie; Deloukas, Panagiotis; Huddart, Robert A.; Bishop, D Timothy; Easton, Douglas F.; Stratton, Michael R.; Rahman, Nazneen

2013-01-01

We conducted a genome-wide association study for testicular germ cell tumor genotyping 298,782 SNPs in 979 cases and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three novel susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5 which has been associated with multiple other cancers (rs4635969, OR=1.54 (95%CI 1.33-1.79), P=1.14×10−23 and rs2736100, OR 1.33 (1.18-1.50) P=7.55 ×10−15). We also identified a locus on chromosome 12 (rs2900333, OR=1.27 (95%CI 1.12-1.44), P=6.16×10−10) that contains ATF7IP, a regulator of TERT expression. Finally we identified a locus on chromosome 9 (rs755383, OR=1.37 (95%CI 1.21-1.55), P=1.12×10−23) containing the sex determination gene DMRT1, which has been linked with teratoma susceptibility in mice. PMID:20543847

The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast

PubMed Central

Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert

2017-01-01

Abstract Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. PMID:28383696

Final Technical Report, Wind Generator Project (Ann Arbor)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geisler, Nathan

A Final Technical Report (57 pages) describing educational exhibits and devices focused on wind energy, and related outreach activities and programs. Project partnership includes the City of Ann Arbor, MI and the Ann Arbor Hands-on Museum, along with additional sub-recipients, and U.S. Department of Energy/Office of Energy Efficiency and Renewable Energy (EERE). Report relays key milestones and sub-tasks as well as numerous graphics and images of five (5) transportable wind energy demonstration devices and five (5) wind energy exhibits designed and constructed between 2014 and 2016 for transport and use by the Ann Arbor Hands-on Museum.

Final Technical Report- Virginia Solar Pathways Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, Katharine; Cosby, Sarah

This Report provides a technical review of the final results of a funding award to Virginia Electric and Power Company (Dominion Energy Virginia (DEV) or the Company) for a project under the U.S. Department of Energy’s Solar Energy Technologies Office. The three-year project was formally known as the Virginia Solar Pathways Project (VSPP or the Project). The purpose of the VSPP was to develop a collaborative utility-administered solar strategy (Solar Strategy) for DEV’s service territory in the Commonwealth that could serve as a replicable model for other states with similar policy environments.

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

PubMed Central

Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A; Gwerder, Myriam; Gutsche, Katrin; Altmeyer, Matthias; Jungmichel, Stephanie; Toledo, Luis I; Fink, Daniel; Rask, Maj-Britt; Grøfte, Merete; Lukas, Claudia; Nielsen, Michael L; Smerdon, Stephen J; Lukas, Jiri; Stucki, Manuel

2016-01-01

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in-trans signaling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identified TCOF1-Treacle, a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle-dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in-trans in the presence of distant chromosome breaks. PMID:25064736

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage.

PubMed

Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A; Gwerder, Myriam; Gutsche, Katrin; Altmeyer, Matthias; Jungmichel, Stephanie; Toledo, Luis I; Fink, Daniel; Rask, Maj-Britt; Grøfte, Merete; Lukas, Claudia; Nielsen, Michael L; Smerdon, Stephen J; Lukas, Jiri; Stucki, Manuel

2014-08-01

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.

Biological Bases of Space Radiation Risk

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session JP4, the discussion focuses on the following topics: Hematopoiesis Dynamics in Irradiated Mammals, Mathematical Modeling; Estimating Health Risks in Space from Galactic Cosmic Rays; Failure of Heavy Ions to Affect Physiological Integrity of the Corneal Endothelial Monolayer; Application of an Unbiased Two-Gel CDNA Library Screening Method to Expression Monitoring of Genes in Irradiated Versus Control Cells; Detection of Radiation-Induced DNA Strand Breaks in Mammalian Cells By Enzymatic Post-Labeling; Evaluation of Bleomycin-Induced Chromosome Aberrations Under Microgravity Conditions in Human Lymphocytes, Using "Fish" Techniques; Technical Description of the Space Exposure Biology Assembly Seba on ISS; and Cytogenetic Research in Biological Dosimetry.

M-X Environmental Technical Report. Socioeconomic Impact Estimates for White Pine County, Nevada. Detailed Tables.

DTIC Science & Technology

1980-12-22

8217AP0A095 772 HENNINGSON DURHAM AND RICHARDSON SANTA BARBARA CA F/G 16/1 B-B ENVIRONMENTAL TECHNICAL REPORT. SOCIOECONOMIC IMPACT ESTIMA--ETC(U) DEC... Environmental Technical Reports,. 53ocioeconctnic’ Final r1eport Impact . Estimates for White Pine County, Nevada. ____________ Detailed Tables 6. PERFORMING...background information for the analysis contained in the M-X Deploment Area Selection and Land Withirawal/Acquisition Draft Environmental Impact Statement

Optical fiber sensors for materials and structures characterization

NASA Technical Reports Server (NTRS)

Lindner, D. K.; Claus, R. O.

1991-01-01

The final technical report on Optical Fiber Sensors for Materials and Structures Characterization, covering the period August 1990 through August 1991 is presented. Research programs in the following technical areas are described; sapphire optical fiber sensors; vibration analysis using two-mode elliptical core fibers and sensors; extrinsic Fabry-Perot interferometer development; and coatings for fluorescent-based sensor. Research progress in each of these areas was substantial, as evidenced by the technical publications which are included as appendices.

A joint university-government technical editing program

NASA Technical Reports Server (NTRS)

Stohrer, Freda F.; Pinelli, Thomas E.

1978-01-01

The NASA Langley Research Center (LaRC) and Old Dominion University have designed a mutually useful technical editing program. A university team made up of an English instructor and two graduate students - one from English, one from engineering - works with a senior editor from LaRC to prepare technical reports for publication. A round-robin technique gives the university team editorial commentary from both language and technical specialists; the senior editor from LaRC supervises reports through final publication. To date, the system has provided LaRC with a respectable product and university students with valuable on-the-job training.

A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q

PubMed Central

Wiltshire, Steven; Hattersley, Andrew T.; Hitman, Graham A.; Walker, Mark; Levy, Jonathan C.; Sampson, Michael; O’Rahilly, Stephen; Frayling, Timothy M.; Bell, John I.; Lathrop, G. Mark; Bennett, Amanda; Dhillon, Ranjit; Fletcher, Christopher; Groves, Christopher J.; Jones, Elizabeth; Prestwich, Philip; Simecek, Nikol; Rao, Pamidighantam V. Subba; Wishart, Marie; Foxon, Richard; Howell, Simon; Smedley, Damian; Cardon, Lon R.; Menzel, Stephan; McCarthy, Mark I.

2001-01-01

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores ⩾1.18 (P⩽.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest. PMID:11484155

Engineering of a Highly Efficient Escherichia coli Strain for Mevalonate Fermentation through Chromosomal Integration

PubMed Central

Wang, Jilong; Niyompanich, Suthamat; Tai, Yi-Shu; Wang, Jingyu; Bai, Wenqin; Mahida, Prithviraj; Gao, Tuo

2016-01-01

ABSTRACT Chromosomal integration of heterologous metabolic pathways is optimal for industrially relevant fermentation, as plasmid-based fermentation causes extra metabolic burden and genetic instabilities. In this work, chromosomal integration was adapted for the production of mevalonate, which can be readily converted into β-methyl-δ-valerolactone, a monomer for the production of mechanically tunable polyesters. The mevalonate pathway, driven by a constitutive promoter, was integrated into the chromosome of Escherichia coli to replace the native fermentation gene adhE or ldhA. The engineered strains (CMEV-1 and CMEV-2) did not require inducer or antibiotic and showed slightly higher maximal productivities (0.38 to ∼0.43 g/liter/h) and yields (67.8 to ∼71.4% of the maximum theoretical yield) than those of the plasmid-based fermentation. Since the glycolysis pathway is the first module for mevalonate synthesis, atpFH deletion was employed to improve the glycolytic rate and the production rate of mevalonate. Shake flask fermentation results showed that the deletion of atpFH in CMEV-1 resulted in a 2.1-fold increase in the maximum productivity. Furthermore, enhancement of the downstream pathway by integrating two copies of the mevalonate pathway genes into the chromosome further improved the mevalonate yield. Finally, our fed-batch fermentation showed that, with deletion of the atpFH and sucA genes and integration of two copies of the mevalonate pathway genes into the chromosome, the engineered strain CMEV-7 exhibited both high maximal productivity (∼1.01 g/liter/h) and high yield (86.1% of the maximum theoretical yield, 30 g/liter mevalonate from 61 g/liter glucose after 48 h in a shake flask). IMPORTANCE Metabolic engineering has succeeded in producing various chemicals. However, few of these chemicals are commercially competitive with the conventional petroleum-derived materials. In this work, chromosomal integration of the heterologous pathway and subsequent optimization strategies ensure stable and efficient (i.e., high-titer, high-yield, and high-productivity) production of mevalonate, which demonstrates the potential for scale-up fermentation. Among the optimization strategies, we demonstrated that enhancement of the glycolytic flux significantly improved the productivity. This result provides an example of how to tune the carbon flux for the optimal production of exogenous chemicals. PMID:27736790

Mature Programs of Study: Examining Policy Implementation at the Local Level. Final Report

ERIC Educational Resources Information Center

Alfeld, Corinne; Bhattacharya, Sharika

2013-01-01

The 2006 Carl D. Perkins Career and Technical Education Act required that all career technical education (CTE) programs offer secondary to postsecondary programs of study (POS), which integrate rigorous academics, offer dual enrollment options, and lead to an industry-recognized degree or credential. Focused on improving students' transition to…

75 FR 37722 - OMB Approvals Under the Paperwork Reduction Act; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-30

... since its last update. B. Why is this Technical Amendment Issued as a Final Rule? The information... provisions since the last update of this table. The paperwork burden associated with these new provisions was... amendment updates the table that lists the Office of Management and Budget (OMB) control numbers issued...

United States Air Force Training Line Simulator. Final Report.

ERIC Educational Resources Information Center

Nauta, Franz; Pierce, Michael B.

This report describes the technical aspects and potential applications of a computer-based model simulating the flow of airmen through basic training and entry-level technical training. The objective of the simulation is to assess the impacts of alternative recruit classification and training policies under a wide variety of assumptions regarding…

Final recovery plan of the southwestern willow flycatcher (Empidonax traillii extimus)

Treesearch

Deborah M. Finch; Stephen I. Rothstein; Jon C. Boren; William L. Graf; Jerry L. Holechek; Barbara E. Kus; Robert M. Marshall; Molly M. Pohl; Susan J. Sferra; Mark K. Sogge; Julie C. Stromberg; Bradley A. Valentine; Mary J. Whitfield; Sartor O. Williams

2002-01-01

The Southwestern Willow Flycatcher Recovery Team is composed of a Technical Subgroup (pg. ii), six Implementation Subgroups (Appendix A), and a Tribal Working Group. The Technical Subgroup consists of 14 academic scientists, researchers, and resource managers with a wide range of expertise in avian biology and ecology, southwestern willow flycatcher ecology, cowbird...

Local/State Bilingual Project. 1981-82 Final Technical Report. Appendixes.

ERIC Educational Resources Information Center

Austin Independent School District, TX. Office of Research and Evaluation.

The 1981-82 Local/State Bilingual Program Technical Report addresses the evaluation questions of the Local/State Bilingual Program Evaluation Design. It is organized into six appendixes. Each appendix reports the information collected by a specific measure. Each appendix consists of (1) an instrument description, (2) purpose of the measure, (3)…

77 FR 26444 - Revisions to Final Response To Petition From New Jersey Regarding SO2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-04

... modeling or other technical analyses and no new analyses were necessary to make the revisions. III. Public... this modeling approach. Therefore, no new technical analyses or any changes to the modeling are...) modeling analysis submitted with the September 2010 petition identified NAAQS violations at receptors in...

77 FR 45282 - NRC Position on the Relationship Between General Design Criteria and Technical Specification...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

..., are described in the final safety analysis report (FSAR). The staff safety evaluation documents the acceptability of these analyses, and it is the combination of the FSAR analyses and the staff safety evaluation... analysis, maintain their capability to perform their safety functions. Technical Specification Operability...

A Dissemination Model for New Technical Education Programs. Final Report.

ERIC Educational Resources Information Center

Hull, Daniel M.

The Technical Education Research Center-SW has conceived, tested, and refined a model for disseminating newly developed programs and materials throughout the nation. The model performed successfully in the dissemination of more than 50,000 educational units (modules) of Laser/Electro-Optics Technician (LEOT) materials during a four-year period…

75 FR 28499 - Medical Certification Requirements as Part of the Commercial Driver's License (CDL); Technical...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... Driver's License (CDL); Technical, Organizational, and Conforming Amendments AGENCY: Federal Motor... ``medical examiner's license or certificate number'' to refer to the number on a medical examiner's license... examiner qualifies him or her to drive. This inconsistency has been clarified in today's final rule so that...

A Simulation of DNA Sequencing Utilizing 3M Post-It[R] Notes

ERIC Educational Resources Information Center

Christensen, Doug

2009-01-01

An inexpensive and equipment free approach to teaching the technical aspects of DNA sequencing. The activity described requires an instructor with a familiarity of DNA sequencing technology but provides a straight forward method of teaching the technical aspects of sequencing in the absence of expensive sequencing equipment. The final sequence…

Installation and Assimilation of Educational Innovations in Vocational/Technical Programs in Post-Secondary Institutions. Final Report.

ERIC Educational Resources Information Center

Appel, Victor H.; Roueche, John E.

The factors which contribute to the successful installation and assimilation of educational innovations were examined in relation to vocational/technical programs in eight post-secondary institutions. About 555 instructors, administrators, and non-teaching professional staff were surveyed regarding the level and extent of use of individualized…

Final Technical Report on the Institute for Advanced Study in Student Personnel Work.

ERIC Educational Resources Information Center

Callis, Robert

This document reports the planning, implementation, and evaluation of a 9-month institute held at the University of Missouri-Columbia to prepare participants (approximately 20) for leadership positions in student personnel work at junior colleges and technical institutes. The following aspects of the instructional program are discussed and…

Demonstration and Research Program for Teaching Young String Players. Final Report.

ERIC Educational Resources Information Center

Yarborough, William

This report explains a system for rapidly training beginning students in the technical aspects of playing a stringed instrument. The program also affords them a well-rounded, basic knowledge of music. A "numerical" method of notation and concentrated muscular exercises greatly speeded the technical learning process. The daily coordination of ear…

Troubleshooting Instruction in Vocational-Technical Education Via Dynamic Simulation. Final Report.

ERIC Educational Resources Information Center

Finch, Curtis R.

This study was designed to examine the feasibility of using simulation as a means of teaching vocational-technical students to detect and identify malfunctions in selected electrical and mechanical systems. A dynamic simulator was employed which features interchangeable panels and logic that permits the simulation of electrical or mechanical…

Special Project for Research Training in Vocational Education: Research Training Series. Final Report.

ERIC Educational Resources Information Center

Vivian, Neal E.

To upgrade research and research utilization competence of vocational educators, The Center for Vocational and Technical Education and The American Vocational Association planned four 1-week research training programs on: (1) Planning Vocational/Technical Education Programs Based on Manpower Research, (2) Patterns of Career Development as Applied…

78 FR 4030 - Designation of Low-Income Status; Acceptance of Secondary Capital Accounts by Low-Income...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-18

... writing that it wishes to accept the designation. The final rule extends an FCU's response time from 30..., nonsubstantive technical amendments to NCUA's requirements for insurance regulation to reflect current agency... requirements for insurance regulation. These technical corrections are necessary to reflect current agency...

SURVEY OF INFORMATION ON VOCATIONAL AND TECHNICAL EDUCATION IN THE STATE OF ILLINOIS. FINAL REPORT.

ERIC Educational Resources Information Center

Corplan Associates, Chicago, IL. Technology Center.

THE BASIC OBJECTIVE OF THE SURVEY WAS TO GATHER INFORMATION HELPFUL IN PLANNING AND DEVELOPING VOCATIONAL AND TECHNICAL EDUCATION PRIMARILY WITHIN THE PUBLIC SCHOOL SYSTEM. OCCUPATIONAL NEEDS WERE IDENTIFIED FROM FORECASTS OF CHANGES IN CURRENT OCCUPATIONS, AN ANALYSIS OF THE IMPLICATIONS OF SCIENTIFIC AND TECHNOLOGICAL DEVELOPMENTS, AND…

75 FR 47211 - Navigation and Navigable Waters; Technical, Organizational, and Conforming Amendments, Sector...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... Puget Sound, WA AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: This rule makes non-substantive... technical corrections to reflect the renaming of Sector Seattle to Sector Puget Sound as part of the Coast... organizational structure. Sector Seattle has been disestablished and Sector Puget Sound has been established in...

Statewide Curriculum Articulation Project for Vocational-Technical Education in Minnesota. Final Report.

ERIC Educational Resources Information Center

Burger, Laura J.; And Others

The goal of this project was to develop, validate, and utilize a process for vertically articulating curriculum between secondary and post secondary levels of vocational technical education throughout the state of Minnesota. Procedures involved the identification of two areas of staff responsibility: research and development, and service to local…

Delivery of Instruction via Television. Final Report.

ERIC Educational Resources Information Center

Wisconsin State Board of Vocational, Technical, and Adult Education, Madison.

During 1985, the Wisconsin Board of Vocational, Technical, and Adult Education (VTAE) expanded its delivery of instruction via television. Approximately 3,000 persons at 170 sites throughout the United States and Canada participated in the VTAE's Technical School of the Air. In addition to delivering six to eight courses per semester, the network…

O*NET Final Technical Report. Volume I [and] Volume II [and] Volume III.

ERIC Educational Resources Information Center

Peterson, Norman G.; Mumford, Michael D.; Borman, Walter C.; Jeanneret, P. Richard; Fleishman, Edwin A.; Levin, Kerry Y.

This document contains the three volumes of the technical report for development of the prototype of the Occupational Information Network (O*NET), which is intended to replace the "Dictionary of Occupational Titles.""General Introduction" (Norman G. Peterson) presents an overview of O*NET's purpose, content, and structure.…

78 FR 34920 - Technical Amendments To Reflect the Authorizing Legislation of the Institute of Museum and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES Institute of Museum and Library Services 45 CFR... Museum and Library Services AGENCY: Institute of Museum and Library Services (IMLS), NFAH. ACTION: Technical amendment; final rule. SUMMARY: The Institute of Museum and Library amends its grants regulations...

Final report on technical work accomplished under contract NASw-2953

NASA Technical Reports Server (NTRS)

Fredricks, R. W.

1977-01-01

A report is given on the technical work accomplished in the area of plasma physics. The subjects covered are: (1) oblique whistler instabilities, (2) current-limited electron beam injection, (3) three-dimensional ion sound turbulence, (4) theoretical aspects of sounder antenna operation and (5) whistler modes in bow shock structures.

Development of German-English Machine Translation System. Final Technical Report.

ERIC Educational Resources Information Center

Lehmann, Winfred P.; Stachowitz, Rolf A.

This report describes work on a pilot system for a fully automatic, high-quality translation of German scientific and technical text into English and gives the results of an experiment designed to show the system's capability to produce quality mechanical translation. The areas considered were: (1) grammar formalism, mainly involving the addition…

Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course

PubMed Central

Dymond, Jessica S.; Scheifele, Lisa Z.; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S.; Boeke, Jef D.

2009-01-01

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ∼750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science. PMID:19015540

Teaching synthetic biology, bioinformatics and engineering to undergraduates: the interdisciplinary Build-a-Genome course.

PubMed

Dymond, Jessica S; Scheifele, Lisa Z; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S; Boeke, Jef D

2009-01-01

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into approximately 750-bp fragments. Once trained in assembly of such DNA "building blocks" by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular "lab meeting" sessions help prepare them for future roles in laboratory science.

The Independent Technical Analysis Process Final Report 2006-2007.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duberstein, Corey; Ham, Kenneth; Dauble, Dennis

2007-03-01

The Bonneville Power Administration (BPA) contracted with the Pacific Northwest National Laboratory (PNNL) to provide technical analytical support for system-wide fish passage information (BPA Project No. 2006-010-00). The goal of this project was to produce rigorous technical analysis products using independent analysts and anonymous peer reviewers. This project provided an independent technical source for non-routine fish passage analyses while allowing routine support functions to be performed by other well-qualified entities. The Independent Technical Analysis Process (ITAP) was created to provide non-routine analysis for fish and wildlife agencies and tribes in particular and the public in general on matters related tomore » juvenile and adult salmon and steelhead passage through the mainstem hydrosystem. The process was designed to maintain the independence of analysts and reviewers from parties requesting analyses, to avoid potential bias in technical products. The objectives identified for this project were to administer a rigorous, transparent process to deliver unbiased technical assistance necessary to coordinate recommendations for storage reservoir and river operations that avoid potential conflicts between anadromous and resident fish. Seven work elements, designated by numbered categories in the Pisces project tracking system, were created to define and accomplish project goals as follows: (1) 118 Coordination - Coordinate technical analysis and review process: (a) Retain expertise for analyst/reviewer roles. (b) Draft research directives. (c) Send directive to the analyst. (d) Coordinate two independent reviews of the draft report. (e) Ensure reviewer comments are addressed within the final report. (2) 162 Analyze/Interpret Data - Implement the independent aspects of the project. (3) 122 Provide Technical Review - Implement the review process for the analysts. (4) 132 Produce Annual Report - FY06 annual progress report with Pisces Disseminate (5) 161 Disseminate Raw/Summary Data and Results - Post technical products on the ITAP web site. (6) 185-Produce Pisces Status Report - Provide periodic status reports to BPA. (7) 119 Manage and Administer Projects - project/contract administration.« less

Site Operator technical report. Final report (1992--1996)

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-12-01

The Southern California Edison Company (SCE) and the US Department of Energy (DOE) entered into cooperative agreement No. DE-FC07-91ID13077 on August 23, 1991, which expired on August 3, 1996. This cooperative agreement provided SCE with DOE cofunding for participation in the DOE`s Electric and Hybrid Vehicle Site Operator Program. In return, SCE provided the DOE with quarterly progress reports which include operating and maintenance data for the electric (EVs) vehicles in SCE`s fleet. Herein is SCE`s final report for the 1992 to 1996 agreement period. As of September 1, 1996 the SCE fleet had 65 electric vehicles in service. Amore » total of 578,200 miles had been logged. During the agreement period, SCE sent the DOE a total of 19 technical reports (Appendix B). This report summarizes the technical achievements which took place during a long, productive and rewarding, relationship with the DOE.« less

7 CFR 1944.419 - Final grantee evaluation.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) PROGRAM REGULATIONS (CONTINUED) HOUSING Self-Help Technical Assistance Grants § 1944.419 Final grantee... Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS..., application, this regulation, and any amendments. (a) This is a quantitative evaluation of the grantee to...

ECLSS medical support activities

NASA Technical Reports Server (NTRS)

Crump, William J.; Kilgore, Melvin V., Jr.

1991-01-01

During the period from April 10, 1990 to April 9, 1991, the Consortium for the Space Life Sciences provided technical assistance to the NASA/MSFC water recovery efforts. This assistance was in the form of literature reviews, technical recommendations, and presentations. This final report summarizes the activities completed during this period and identifies those areas requiring additional efforts. The tasks which the University of Alabama in Huntsville (UAH) water recovery team addressed were either identified by MSFC technical representatives or chosen from those outlined in the subject statement of work.

Switching gears and changing lanes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammock, Earlene C.

2002-01-01

From musing over Shakespeare's fine lines and metaphors to teaching technical writing and editing, and finally, to cranking out scientific and technical documents, writing articles, and editing publications-how'd a nice girl like me end up in a place like this? Twice, after having prepared for an academic career of teaching and research, I found myself in a technical communications position-first, at the University of Texas at El Paso College of Engineering and later, at Los Alamos National Laboratory. What happened?

Spliced synthetic genes as internal controls in RNA sequencing experiments.

PubMed

Hardwick, Simon A; Chen, Wendy Y; Wong, Ted; Deveson, Ira W; Blackburn, James; Andersen, Stacey B; Nielsen, Lars K; Mattick, John S; Mercer, Tim R

2016-09-01

RNA sequencing (RNA-seq) can be used to assemble spliced isoforms, quantify expressed genes and provide a global profile of the transcriptome. However, the size and diversity of the transcriptome, the wide dynamic range in gene expression and inherent technical biases confound RNA-seq analysis. We have developed a set of spike-in RNA standards, termed 'sequins' (sequencing spike-ins), that represent full-length spliced mRNA isoforms. Sequins have an entirely artificial sequence with no homology to natural reference genomes, but they align to gene loci encoded on an artificial in silico chromosome. The combination of multiple sequins across a range of concentrations emulates alternative splicing and differential gene expression, and it provides scaling factors for normalization between samples. We demonstrate the use of sequins in RNA-seq experiments to measure sample-specific biases and determine the limits of reliable transcript assembly and quantification in accompanying human RNA samples. In addition, we have designed a complementary set of sequins that represent fusion genes arising from rearrangements of the in silico chromosome to aid in cancer diagnosis. RNA sequins provide a qualitative and quantitative reference with which to navigate the complexity of the human transcriptome.

NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 32: A new era in international technical communication: American-Russian collaboration

NASA Technical Reports Server (NTRS)

Flammia, Madelyn; Barclay, Rebecca O.; Pinelli, Thomas E.; Keene, Michael L.; Burger, Robert H.; Kennedy, John M.

1993-01-01

Until the recent dissolution of the Soviet Union, the Communist Party exerted a strict control of access to and dissemination of scientific and technical information (STI). This article presents models of the Soviet-style information society and the Western-style information society and discusses the effects of centralized governmental control of information on Russian technical communication practices. The effects of political control on technical communication are then used to interpret the results of a survey of Russian and U.S. aerospace engineers and scientists concerning the time devoted to technical communication, their collaborative writing practices and their attitudes toward collaboration, the kinds of technical documents they produce and use, their views regarding the appropriate content for an undergraduate technical communication course, and their use of computer technology. Finally, the implications of these findings for future collaboration between Russian and U.S. engineers and scientists are examined.

NASA/DoD Aerospace Knowledge Diffusion Research Project. XXXII - A new era in international technical communication: American-Russian collaboration

NASA Technical Reports Server (NTRS)

Flammia, Madelyn; Barclay, Rebecca O.; Pinelli, Thomas E.; Keene, Michael L.; Burger, Robert H.; Kennedy, John M.

1993-01-01

Until the recent dissolution of the Soviet Union, the Communist Party exerted a strict control of access to and dissemination of scientific and technical information. This article presents models of the Soviet-style information society and the Western-style information society and discusses the effects of centralized governmental control of information on Russian technical communication practices. The effects of political control on technical communication are then used to interpret the results of a survey of Russian and U.S. aerospace engineers and scientists concerning the time devoted to technical communication, their collaborative writing practices and their attitudes toward collaboration, the kinds of technical documents they produce and use, their views regarding the appropriate content for an undergraduate technical communication course, and their use of computer technology. Finally, the implications of these findings for future collaboration between Russian and U.S. engineers and scientists are examined.

A triallelic genetic male sterility locus in Brassica napus: an integrative strategy for its physical mapping and possible local chromosome evolution around it

PubMed Central

Lu, Wei; Liu, Jun; Xin, Qiang; Wan, Lili; Hong, Dengfeng; Yang, Guangsheng

2013-01-01

Background and Aims Spontaneous male sterility is an advantageous trait for both constructing efficient pollination control systems and for understanding the developmental process of the male reproductive unit in many crops. A triallelic genetic male-sterile locus (BnMs5) has been identified in Brassica napus; however, its complicated genome structure has greatly hampered the isolation of this locus. The aim of this study was to physically map BnMs5 through an integrated map-based cloning strategy and analyse the local chromosomal evolution around BnMs5. Methods A large F2 population was used to integrate the existing genetic maps around BnMs5. A map-based cloning strategy in combination with comparative mapping among B. napus, Arabidopsis, Brassica rapa and Brassica oleracea was employed to facilitate the identification of a target bacterial artificial chromosome (BAC) clone covering the BnMs5 locus. The genomic sequences from the Brassica species were analysed to reveal the regional chromosomal evolution around BnMs5. Key Results BnMs5 was finally delimited to a 0·3-cM genetic fragment from an integrated local genetic map, and was anchored on the B. napus A8 chromosome. Screening of a B. napus BAC clone library and identification of the positive clones validated that JBnB034L06 was the target BAC clone. The closest flanking markers restrict BnMs5 to a 21-kb region on JBnB034L06 containing six predicted functional genes. Good collinearity relationship around BnMs5 between several Brassica species was observed, while violent chromosomal evolutionary events including insertions/deletions, duplications and single nucleotide mutations were also found to have extensively occurred during their divergence. Conclusions This work represents major progress towards the molecular cloning of BnMs5, as well as presenting a powerful, integrative method to mapping loci in plants with complex genomic architecture, such as the amphidiploid B. napus. PMID:23243189

Functional Characterization of CENP-A Post-Translational Modifications in Chromosome Segregation

DTIC Science & Technology

2016-09-01

our overall findings in discussion part, and finally we will explain major materials and methods we used. Results CENP-A α-amino methylation...centromere and kinetochore and accurate segregation of the genetic materials . Moreover, we established that centromere/kinetochore defects in the absence...developed. Materials and methods: Creation of CENP-A complete replacement RPE cells: RPE CENP-A knockout cell line generated by Don Cleaveland Lab7 used

Regulating positioning and orientation of mitotic spindles via cell size and shape

NASA Astrophysics Data System (ADS)

Li, Jingchen; Jiang, Hongyuan

2018-01-01

Proper location of the mitotic spindle is critical for chromosome segregation and the selection of the cell division plane. However, how mitotic spindles sense cell size and shape to regulate their own position and orientation is still largely unclear. To investigate this question systematically, we used a general model by considering chromosomes, microtubule dynamics, and forces of various molecular motors. Our results show that in cells of various sizes and shapes, spindles can always be centered and oriented along the long axis robustly in the absence of other specified mechanisms. We found that the characteristic time of positioning and orientation processes increases with cell size. Spindles sense the cell size mainly by the cortical force in small cells and by the cytoplasmic force in large cells. In addition to the cell size, the cell shape mainly influences the orientation process. We found that more slender cells have a faster orientation process, and the final orientation is not necessarily along the longest axis but is determined by the radial profile and the symmetry of the cell shape. Finally, our model also reproduces the separation and repositioning of the spindle poles during the anaphase. Therefore, our work provides a general tool for studying the mitotic spindle across the whole mitotic phase.

Inbreeding and thermal adaptation in Drosophila subobscura.

PubMed

Zivanovic, Goran; Arenas, Conxita; Mestres, Francesc

2014-09-01

Using a well-adapted Drosophila subobscura population (Avala, Serbia), a drastic experiment of inbreeding was carried out to assess whether the expected level of homozygosity could be reached or if other evolutionary forces affected the process. In general, no significant changes of inversion (or arrangement) frequencies were detected after 12 brother-sister mating generations. Furthermore, no significant differences were obtained between observed and expected (under the inbreeding model) karyotypic frequencies. Thus, these results seemed to indicate that the main evolutionary factor in the experiment was inbreeding. However, in the G12 generation, complete chromosomal fixation was reached only in two out of the eight final inbred lines. In these lines, the chromosomal compositions were difficult to interpret, but they could be likely a consequence of adaptation to particular laboratory conditions (constant 18 °C, food, light period, etc.). Finally, in a second experiment, the inbred lines presented higher fertility at 18 °C than at 13 °C. Also, there was a significant line effect on fertility: inbred line number 6 (A1, J1, U1+2; U1+2+6, E8, and O3+4+7) presented the highest values, which maybe the result of an adaptation to laboratory conditions. Thus, the results obtained in our experiments reflect the adaptive potential of D. subobscura inversions.

Communication Platform Payload Definition (CPPD) study. Volume 2: Technical report

NASA Technical Reports Server (NTRS)

Hunter, E. M.; Driggers, T.; Jorasch, R.

1986-01-01

This is Volume 2 (Technical Report) of the Ford Aerospace & Communications Corporation Final Report for the Communication Platform Payload Definition (CPPD) Study program conducted for NASA Lewis Research Center under contract No. NAS3-24235. This report presents the results of the study effort leading to five potential platform payloads to service CONUS and WARC Region 2 traffic demand as projected to the year 2008. The report addresses establishing the data bases, developing service aggregation scenarios, selecting and developing 5 payload concepts, performing detailed definition of the 5 payloads, costing them, identifying critical technology, and finally comparing the payloads with each other and also with non-aggregated equivalent services.

Best Practices for Continuous Monitoring of Temperature and Flow in Wadeable Streams (Final Report)

EPA Science Inventory

This final report is a technical "best practices" document describing sensor deployment for and collection of continuous temperature and flow data at ungaged sites in wadeable streams. This document addresses questions related to equipment needs; configuration, placement, and ins...

Hazardous Waste Management System - Identification and Listing of Hazardous Waste - Recycled Used Oil Management Standards - Federal Register Notice, May 3, 1993

EPA Pesticide Factsheets

This action corrects several technical errors and provides clarifying amendments to the final recycled used oil management standards rule. The final rule was published on September 10, 1992 (57 FR 41566).

75 FR 6839 - Technical Service Provider Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-12

... Executive Order 12866, the Office of Management and Budget determined that this final rule is not a... or are eligible to participate in conservation programs to help them make land management decisions...: Covered Programs. The interim final rule incorporated reference to the Agricultural Management Assistance...

Charlotte Circle Outreach. Final Report.

ERIC Educational Resources Information Center

Calhoun, Mary Lynne; Rose, Terry L.; Prendergast, Donna

This final report details the activities of the Charlotte Circle Outreach, a program designed to provide technical assistance and training to early intervention programs offering services to infants and young children with substantial disabilities, ages birth through two years. This mission was accomplished through cooperative planning with…

Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments (Final Report)

EPA Science Inventory

The Ecological Risk Assessment Support Center (ERASC) announced the release of the final report, Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments. This technical paper provides defensible approximations fo...

A Program of Technical Assistance to Industry in Twenty-Six Mississippi Counties and the Choctaw Indian Reservation. Final Report.

ERIC Educational Resources Information Center

Phillips, Jane; Sewell, Charles

A broad technical assistance program has been established in 25 EDA (Economic Development Administration) contract counties and on the Choctaw Indian Reservation Nashoba County) to stimulate new job opportunities by solving operational problems which limit the expansion and diversification of existing industry; professional services in evaluating…

For Work-Force Training, a Plan to Give College Credit Where It's Due

ERIC Educational Resources Information Center

Sander, Libby

2008-01-01

After nearly three years of planning, Ohio's higher-education officials are finalizing an ambitious program to grant college credit for some technical courses offered at the state's adult-education centers. The program, called the Career-Technical Credit Transfer, is the latest in a string of state efforts to more closely link work-force training…

Improving the Dissemination of Scientific and Technical Information: A Practitioner's Guide to Innovation. (Final Report).

ERIC Educational Resources Information Center

Capital Systems Group, Inc., Rockville, MD.

The aim of this guide is to alert persons with an operational interest in scientific communication to new ideas, techniques, and equipment in the field of communication media and publications. The focus is on the dissemination of scientific information via the technical journal or its equivalent. Secondary dissemination of information such as…

Unified Technical Concepts--Phase II. Expand Application to Industrial Technologies and Adult Education. Final Report.

ERIC Educational Resources Information Center

Technical Education Research Center, Waco, TX.

A project was conducted to develop a laboratory-based instructional system in physics for two-year technician programs that emphasizes both the analogies between basic physical principles and the applications of the principles in modern technology. The Unified Technical Concepts (UTC) system that was developed is (1) a reorganization of physics…

THE DEVELOPMENT OF ACHIEVEMENT MEASURES FOR TRADE AND TECHNICAL EDUCATION. PROGRESS REPORT NUMBER THREE.

ERIC Educational Resources Information Center

BALDWIN, THOMAS S.

DURING THIS PERIOD FROM SEPTEMBER 1 THROUGH NOVEMBER 30, 1966, 35 FIELD CONSULTANTS COMPLETED ANALYSIS OF THEIR INDIVIDUAL TRADE AND TECHNICAL CURRICULUMS. THESE ANALYSES WERE DEVELOPED INTO AN OUTLINE TO SERVE AS A GUIDE FOR DEVELOPING ACHIEVEMENT TESTS. THE FINAL OUTLINE WAS DIVIDED INTO AS MANY DIFFERENT AREAS AS THE CONSULTANTS FELT NECESSARY…

Word Lists to Simplify Vocabulary of Technical Information. Final Report.

ERIC Educational Resources Information Center

Kincaid, J. Peter; And Others

This report describes eight word lists developed for use as part of the computer readability editing system (CRES), which was developed to serve as an author's aid in improving the ease of comprehending Navy technical manuals and training materials. The system has features which flag uncommon and misspelled words and long sentences, suggest simple…

77 FR 1889 - Drivers of CMVs: Restricting the Use of Cellular Phones; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-12

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration 49 CFR Part 391 [Docket No. FMCSA-2010-0096] RIN 2126-AB29 Drivers of CMVs: Restricting the Use of Cellular Phones; Technical... Cellular Phones final rule (76 FR 75470) had a clerical error in Sec. 391.15(f)(1) that stated ``paragraph...

27 Years of Impact: Vocational-Technical Education in Ohio. Final Annual Report under Federal Law.

ERIC Educational Resources Information Center

Ohio State Council on Vocational Education, Westerville.

The Ohio Council on Vocational Education (OCOVE) was created to strengthen the career, vocational, and technical education services provided for Ohioans as a practical, efficient, and sure way to enhance the competitiveness of individual workers and the state and national economy. Some of the accomplishments of OCOVE during its 27 years of…

Vocational-Technical Education Interface with Ohio's High Technology Business and Industrial Sector. Final Report.

ERIC Educational Resources Information Center

McCormick, Robert W.

This study explored the relationship of vocational-technical educational institutions in Ohio with business and industry using high-technology applications. The study attempted to determine what high-technology applications will be adopted by Ohio's business and industry in the next 5 years, what experience the schools have had in working with…

National Institute of Statistical Sciences Data Confidentiality Technical Panel: Final Report. NCES 2011-608

ERIC Educational Resources Information Center

Karr, Alan

2011-01-01

NCES asked the National Institute of Statistical Sciences (NISS) to convene a technical panel of survey and policy experts to examine the NCES current and planned data dissemination strategies for confidential data with respect to: mandates and directives that NCES make data available; current and prospective technologies for protecting and…

[Municipalities as a Model for New Careers and Redirection of Vocational-Technical Education Programs.] Final Report.

ERIC Educational Resources Information Center

Institute for Local Self Government, Berkeley, CA.

To meet the manpower needs of local governments, the model developed for this project redirects national and technical education toward new careers programs. Designed by task forces of professional personnel, the model utilizes existing local government resources, including funds for new career activities. Accomplishments of the project include:…

Social Science Research Institutes in the Quality American University. Final Technical Report.

ERIC Educational Resources Information Center

Totman, Theodore L.

The technical report presents a chapter outline and thesis summary of an investigation of social science research institutes in American universities. The bulk of the report presents the thesis in four sections. Section I proposes a typology of organized social research units (OSRUs) in the 11 universities studied. Dimensions used to classify the…

Expanding Horizons: A Program for Students Entering Nontraditional Technical Occupations. PY95 Final Detailed Report.

ERIC Educational Resources Information Center

Austin Community Coll., TX.

The Expanding Horizons Project at Austin Community College successfully achieved its goals for Project Year 1994-95. During the year, the project accomplished the following: raised public awareness of the need to overcome gender bias, promoted career opportunities in nontraditional technical occupations to more than 1,200 prospective students,…

Technical Assistance and Training from the Document Design Project. Final Report.

ERIC Educational Resources Information Center

American Institutes for Research, Washington, DC.

Contained in this report is a description of the technical assistance and training phase of the Document Design Project, a program funded by the National Institute of Education and intended to address and correct the readability problems posed by public documents. The first section of the report provides background material on the assistance and…