Sample records for features high mitotic

  1. A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma

    PubMed Central

    Kadota, Kyuichi; Suzuki, Kei; Kachala, Stefan S.; Zabor, Emily C.; Sima, Camelia S.; Moreira, Andre L.; Yoshizawa, Akihiko; Riely, Gregory J.; Rusch, Valerie W.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    The IASLC/ATS/ERS has recently proposed a new lung adenocarcinoma classification. We investigated whether nuclear features can stratify prognostic subsets. Slides of 485 stage I lung adenocarcinoma patients were reviewed. We evaluated nuclear diameter, nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, prominence of nucleoli, intranuclear inclusions, mitotic count/10 high-power fields (HPF) or 2.4 mm2, and atypical mitoses. Tumors were classified into histologic subtypes according to the IASLC/ATS/ERS classification and grouped by architectural grade into low (adenocarcinoma in situ, minimally invasive adenocarcinoma or lepidic predominant), intermediate (papillary or acinar), and high (micropapillary or solid). Log-rank tests and Cox regression models evaluated the ability of clinicopathologic factors to predict recurrence-free probability. In univariate analyses, nuclear diameter (p=0.007), nuclear atypia (p=0.006), mitotic count (p<0.001), and atypical mitoses (p<0.001) were significant predictors of recurrence. The recurrence-free probability of patients with high mitotic count (?5/10HPF: n=175) was the lowest (5-year recurrence-free probability=73%), followed by intermediate (2–4/10HPF: n=106, 80%), and low (0–1/10HPF: n=204, 91%, p<0.001). Combined architectural/mitotic grading system stratified patient outcomes (p<0.001): low grade (low architectural grade with any mitotic count and intermediate architectural grade with low mitotic count: n=201, 5-year recurrence-free probability=92%), intermediate grade (intermediate architectural grade with intermediate-high mitotic counts: n=206, 78%), and high grade (high architectural grade with any mitotic count: n=78, 68%). The advantage of adding mitotic count to architectural grade is in stratifying patients with intermediate architectural grade into two prognostically distinct categories (p=0.001). After adjusting for clinicopathologic factors including sex, stage, pleural/lymphovascular invasion, and necrosis, mitotic count was not an independent predictor of recurrence (p=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs. low: p=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice. PMID:22499226

  2. Classification of mitotic figures with convolutional neural networks and seeded blob features

    PubMed Central

    Malon, Christopher D.; Cosatto, Eric

    2013-01-01

    Background: The mitotic figure recognition contest at the 2012 International Conference on Pattern Recognition (ICPR) challenges a system to identify all mitotic figures in a region of interest of hematoxylin and eosin stained tissue, using each of three scanners (Aperio, Hamamatsu, and multispectral). Methods: Our approach combines manually designed nuclear features with the learned features extracted by convolutional neural networks (CNN). The nuclear features capture color, texture, and shape information of segmented regions around a nucleus. The use of a CNN handles the variety of appearances of mitotic figures and decreases sensitivity to the manually crafted features and thresholds. Results: On the test set provided by the contest, the trained system achieves F1 scores up to 0.659 on color scanners and 0.589 on multispectral scanner. Conclusions: We demonstrate a powerful technique combining segmentation-based features with CNN, identifying the majority of mitotic figures with a fair precision. Further, we show that the approach accommodates information from the additional focal planes and spectral bands from a multi-spectral scanner without major redesign. PMID:23858384

  3. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells.

    PubMed

    Mazzio, E; Badisa, R; Mack, N; Deiab, S; Soliman, K F A

    2014-06-01

    Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust National Cancer Institute botanical screenings. In this study, a high-through put microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015-0.5?mg/mL) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % of the extracts tested showed inhibitory growth (IG50 ) properties <0.0183?mg/mL. The most potent anti-mitotics (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja twigs (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu Cao [symbol: see text] Speranskia herb (Speranskia tuberculata), Bentonite clay, Bunge root (Pulsatilla chinensis), Brucea fruit (Brucea javanica), Madder root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane root (Inula Helenium), Yuan Zhi [symbol: see text] root (Polygala tenuifolia), Pagoda Tree fruit (Melia Toosendan), Stone root (Collinsonia Canadensis), and others such as American Witchhazel, Arjun, and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth root (Trillium Pendulum), and alkanet root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (S. tuberculata), which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis, leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of anti-mitotic natural plants that are effective against human breast carcinoma MDA-MB-231 cell division. PMID:24105850

  4. Temporal models for mitotic phase labelling.

    PubMed

    El-Labban, A; Zisserman, A; Toyoda, Y; Bird, A W; Hyman, A

    2014-10-01

    With the widespread use of time-lapse data to understand cellular function, there is a need for tools which facilitate high-throughput analysis of data. Fluorescence microscopy of genetically engineered cell lines in culture can be used to visualise the progression of these cells through the cell cycle, including distinctly identifiable sequential stages of cell division (mitotic phases). We present a system for automated segmentation and mitotic phase labelling using temporal models. This work takes the novel approach of using temporal features evaluated over the whole of the mitotic phases rather than over single frames, thereby capturing the distinctive behaviour over the phases. We compare and contrast three different temporal models: Dynamic Time Warping, Hidden Markov Models, and Semi Markov Models. A new loss function is proposed for the Semi Markov model to make it more robust to inconsistencies in data annotation near transition boundaries. The models are tested under two different experimental conditions to explore robustness to changes in biological conditions. PMID:24972376

  5. Leiomyosarcoma arising in a patient with prior mitotically active leiomyoma.

    PubMed

    Kim, Jin Hwi; Choi, Young Jin; Kim, Dong Chul; Lee, Sung Jong

    2010-02-01

    Mitotically active leiomyomas exhibiting insignificant cytologic atypia (none to mild) with an increased mitotic count of 5-20 mitotic figures per 10 high power fields, and without coagulative tumor cell necrosis or atypical mitoses, tend to have a benign clinical course. We encountered a case of a mitotically active leiomyoma and malignant transformation after a total hysterectomy. The recurrent multiple abdominal masses were removed surgically; most of them were benign leiomyomas, but some were leiomyosarcomas. Although most mitotically active leiomyomas have a benign clinical course, these lesions can recur and have the potential for malignant transformation. Therefore, patients with mitotically active leiomyomas require close follow-up. PMID:20178549

  6. PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells.

    PubMed

    Simons-Evelyn, M; Bailey-Dell, K; Toretsky, J A; Ross, D D; Fenton, R; Kalvakolanu, D; Rapoport, A P

    2001-01-01

    PBK/TOPK is a recently cloned serine/threonine kinase which is phosphorylated during mitosis. Earlier work indicated that this kinase is upregulated in a Burkitt's lymphoma cell line (GA-10). To determine whether PBK/TOPK is upregulated in other mitotically active neoplastic cell lines and tissues, Northern analysis was performed on a panel of malignant cell lines and on clinical samples from patients with leukemia or lymphoma. While PBK/TOPK mRNA was not detectable in normal peripheral blood cells and was weakly expressed in hyperplastic tonsillar B-cells, significantly higher levels of mRNA were detected in 8 Burkitt's lymphoma cell lines, 10 other neoplastic cell lines, and 2 clinical samples-one derived from a patient with ALL and a second derived from a patient with relapsed myeloma. In addition, Northern analysis of fetal tissues showed upregulated expression of PBK/TOPK in fetal kidney, lung, spleen, brain, and testis. These data suggest that PBK/TOPK expression is increased in highly proliferative malignant cells and during normal fetal development. PMID:11783945

  7. PBK\\/TOPK Is a Novel Mitotic Kinase Which Is Upregulated in Burkitt's Lymphoma and Other Highly Proliferative Malignant Cells

    Microsoft Academic Search

    Michelle Simons-Evelyn; Kim Bailey-Dell; Jeffrey A. Toretsky; Douglas D. Ross; Robert Fenton; Dhan Kalvakolanu; Aaron P. Rapoport

    2001-01-01

    ABSTRACTPBK\\/TOPK is a recently cloned serine\\/threonine kinase which is phosphorylated during mitosis. Earlier work indicated that this kinase is upregulated in a Burkitt's lymphoma cell line (GA-10). To determine whether PBK\\/TOPK is upregulated in other mitotically active neoplastic cell lines and tissues, Northern analysis was performed on a panel of malignant cell lines and on clinical samples from patients with

  8. 4D-networking by mitotic phosphatases.

    PubMed

    Qian, Junbin; Winkler, Claudia; Bollen, Mathieu

    2013-12-01

    Faithful progression through mitosis is critically dependent on the timely phosphorylation and dephosphorylation of a host of proteins. The involved protein kinases and phosphatases are embedded in interconnected feedback and feedforward circuits that ensure swift and robust phase transitions. Here we review recent evidence showing that protein phosphatases are modulators of the mitotic entry but also organize the mitotic exit through an orderly dephosphorylation of their substrates. In addition, phosphatases spatiotemporally restrict the phosphorylation of key regulatory proteins and oppose kinases to control highly dynamic mitotic processes, including chromosome congression and checkpoint signaling. In accordance with their important role as nodes in phosphorylation networks, mitotic protein phosphatases are tightly regulated in four dimensions. PMID:23849679

  9. P2P-R protein overexpression restricts mitotic progression at prometaphase and promotes mitotic apoptosis.

    PubMed

    Gao, Sizhi; Scott, Robert E

    2002-11-01

    Mitotic cells show a tenfold increase in immunoreactive P2P-R protein. During mitosis, the distribution of P2P-R protein also changes from a primary nucleolar localization in interphase cells to the periphery of chromosome in mitotic cells. These findings suggest that P2P-R might serve a functional role in mitosis. To test this possibility, human Saos2 cells were stably transfected with P2P-R DNA constructs and the biological effects of P2P-R overexpression were evaluated. Overexpression of near full-length P2P-R was found to have paradoxical effects on the relationship between proliferation and mitosis in the nine Saos2 cell clones that were studied. A significant repression in the population doubling rates was observed in all nine clones even though a significant increase in the frequency of easily detached cells with a mitotic morphology was apparent. Flow cytometric analysis confirmed that greater than two thirds of the cells with a mitotic morphology had a 4n DNA content. Confocal microscopy further established that 85% of the mitotic cell population had prometaphase characteristics suggesting that P2P-R overexpression restricts mitotic progression at prometaphase. Many cells with a mitotic morphology also showed signs of apoptosis with prominent cell surface blebs. Confocal microscopy confirmed that 25-40% of such mitotic cells were apoptotic with chromosomal abnormalities and cell surface blebbing. In association with mitotic apoptosis, P2P-R protein appears to dissociate from the periphery of chromosomes and localize in the cytoplasm and in cell surface blebs. The presence of P2P-R in cell surface blebs was confirmed by analysis of highly enriched populations of apoptotic cell surface blebs wherein Western blotting documented the presence of 250 kDa P2P-R. These results therefore suggest that P2P-R overexpression promotes both prometaphase arrest in mitosis and mitotic apoptosis. PMID:12384997

  10. Continued Stabilization of the Nuclear Higher-Order Structure of Post-Mitotic Neurons In Vivo

    PubMed Central

    Alva-Medina, Janeth; Maya-Mendoza, Apolinar; Dent, Myrna A. R.; Aranda-Anzaldo, Armando

    2011-01-01

    Background Cellular terminal differentiation (TD) correlates with a permanent exit from the cell cycle and so TD cells become stably post-mitotic. However, TD cells express the molecular machinery necessary for cell proliferation that can be reactivated by experimental manipulation, yet it has not been reported the stable proliferation of any type of reactivated TD cells. Neurons become post-mitotic after leaving the ventricular zone. When neurons are forced to reenter the cell cycle they invariably undergo cell death. Wider evidence indicates that the post-mitotic state cannot solely depend on gene products acting in trans, otherwise mutations in the corresponding genes may lead to reentry and completion of the cell cycle in TD cells, but this has not been observed. In the interphase, nuclear DNA of metazoan cells is organized in supercoiled loops anchored to a nuclear nuclear matrix (NM). The DNA-NM interactions define a higher-order structure in the cell nucleus (NHOS). We have previously compared the NHOS of aged rat hepatocytes with that of early post-mitotic rat neurons and our results indicated that a very stable NHOS is a common feature of both senescent and post-mitotic cells in vivo. Principal Findings In the present work we compared the NHOS in rat neurons from different post-natal ages. Our results show that the trend towards further stabilization of the NHOS in neurons continues throughout post-natal life. This phenomenon occurs in absence of overt changes in the post-mitotic state and transcriptional activity of neurons, suggesting that it is independent of functional constraints. Conclusions Apparently the continued stabilization of the NHOS as a function of time is basically determined by thermodynamic and structural constraints. We discuss how the resulting highly stable NHOS of neurons may be the structural, non-genetic basis of their permanent and irreversible post-mitotic state. PMID:21731716

  11. Identification of Small Molecule Inhibitors of the Mitotic Kinase Haspin by High Throughput Screening using a Homogeneous Time-Resolved Fluorescence Resonance Energy Transfer Assay

    PubMed Central

    Patnaik, Debasis; Xian, Jun; Glicksman, Marcie A.; Cuny, Gregory D.; Stein, Ross L.; Higgins, Jonathan M.G.

    2008-01-01

    Summary Haspin/Gsg2 is a kinase that phosphorylates Histone H3 at Thr-3 (H3T3ph) during mitosis. Its depletion by RNA interference results in failure of chromosome alignment and a block in mitosis. Haspin therefore is a novel target for development of anti-mitotic agents. We report the development of a high throughput time-resolved fluorescence resonance energy transfer (TR-FRET) kinase assay for Haspin. Histone H3 peptide was used as a substrate, and a Europium-labeled H3T3ph phosphospecific monoclonal antibody was used to detect phosphorylation. A library of 137632 small molecules was screened at Km concentrations of ATP and peptide to allow identification of diverse inhibitor types. Reconfirmation of hits and IC50 determinations were carried out with the TR-FRET assay and by a radiometric assay using recombinant Histone H3 as the substrate. A preliminary assessment of specificity was made by testing inhibition of two unrelated kinases. EC50 values in cells were determined using a cell-based ELISA assay of H3T3ph. Five compounds were selected as leads based on potency and chemical structure considerations. These leads form the basis for the development of specific inhibitors of Haspin that will have clear utility in basic research and possible use as starting points for development of anti-mitotic anticancer therapeutics. PMID:18978305

  12. Building mitotic chromosomes.

    PubMed

    Ohta, Shinya; Wood, Laura; Bukowski-Wills, Jimi-Carlo; Rappsilber, Juri; Earnshaw, William C

    2011-02-01

    Mitotic chromosomes are the iconic structures into which the genome is packaged to ensure its accurate segregation during mitosis. Although they have appeared on countless journal cover illustrations, there remains no consensus on how the chromatin fiber is packaged during mitosis. In fact, work in recent years has both added to existing controversies and sparked new ones. By contrast, there has been very significant progress in determining the protein composition of isolated mitotic chromosomes. Here, we discuss recent studies of chromosome organization and provide an in depth description of the latest proteomics studies, which have at last provided us with a definitive proteome for vertebrate chromosomes. PMID:20974528

  13. Mitotically active cellular fibroma of the ovary: a case report and a review of the literature.

    PubMed

    Wu, H; Xie, J; Huang, W; Wu, J

    2014-01-01

    Mitotically active cellular fibroma (MACF) is characterized by increased cellularity, mitotic activity, and less frequently, nuclear atypia, which comprises 10% of ovarian fibromatous tumors. The authors report the case of a 76-year-old woman who presented at the present hospital with a two-month pelvic mass. B ultrasound disclosed a 75 x 52 x 41 mm mass in the right accessories. A hysterectomy and bilateral salpingo-oophorectomy was performed. Histologically, the tumor was composed of a densely cellular proliferation of fibrolastic-like cells with bland nuclear features and arranged in a fascicular pattern. There were more than four mitotic figures per ten high-power fields (HPFs). The histological diagnosis for the mass of the right ovary was MACF. MACF should be distinguished from ovarian fibrosarcoma. MACF is a recent histopathologic entity. Despite the high count of mitotic figures, the clinical course of the tumor is typically uneventful. Long-term clinical follow-up is recommended. PMID:24654469

  14. Sparse SVM FGM Experiments Structural Feature Selection for Very High

    E-print Network

    Tsang Wai Hung "Ivor"

    Sparse SVM FGM Experiments Structural Feature Selection for Very High Dimensional Problems Ivor W Feature Selection for Very High Dimensional Problems #12;Sparse SVM FGM Experiments Support Vector W. Tsang Structural Feature Selection for Very High Dimensional Problems #12;Sparse SVM FGM

  15. Mitotic chromosome condensation in vertebrates

    SciTech Connect

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

    2012-07-15

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

  16. Mitotic Illegitimate Recombination Is a Mechanism for Novel Changes in High-Molecular-Weight Glutenin Subunits in Wheat-Rye Hybrids

    PubMed Central

    Yuan, Zhongwei; Liu, Dengcai; Zhang, Lianquan; Zhang, Li; Chen, Wenjie; Yan, Zehong; Zheng, Youliang; Zhang, Huaigang; Yen, Yang

    2011-01-01

    Wide hybrids can have novel traits or changed expression of a quantitative trait that their parents do not have. These phenomena have long been noticed, yet the mechanisms are poorly understood. High-molecular-weight glutenin subunits (HMW-GS) are seed storage proteins encoded by Glu-1 genes that only express in endosperm in wheat and its related species. Novel HMW-GS compositions have been observed in their hybrids. This research elucidated the molecular mechanisms by investigating the causative factors of novel HMW-GS changes in wheat-rye hybrids. HMW-GS compositions in the endosperm and their coding sequences in the leaves of F1 and F2 hybrids between wheat landrace Shinchunaga and rye landrace Qinling were investigated. Missing and/or additional novel HMW-GSs were observed in the endosperm of 0.5% of the 2078 F1 and 22% of 36 F2 hybrid seeds. The wildtype Glu-1Ax null allele was found to have 42 types of short repeat sequences of 3-60 bp long that appeared 2 to 100 times. It also has an in-frame stop codon in the central repetitive region. Analyzing cloned allele sequences of HMW-GS coding gene Glu-1 revealed that deletions involving the in-frame stop codon had happened, resulting in novel ?1.8-kb Glu-1Ax alleles in some F1 and F2 plants. The cloned mutant Glu-1Ax alleles were expressed in Escherichia coli, and the HMW-GSs produced matched the novel HMW-GSs found in the hybrids. The differential changes between the endosperm and the plant of the same hybrids and the data of E. coli expression of the cloned deletion alleles both suggested that mitotic illegitimate recombination between two copies of a short repeat sequence had resulted in the deletions and thus the changed HMW-GS compositions. Our experiments have provided the first direct evidence to show that mitotic illegitimate recombination is a mechanism that produces novel phenotypes in wide hybrids. PMID:21887262

  17. Mitotic Exit Control as an Evolved Complex System

    SciTech Connect

    Bosl, W; Li, R

    2005-04-25

    The exit from mitosis is the last critical decision a cell has to make during a division cycle. A complex regulatory system has evolved to evaluate the success of mitotic events and control this decision. Whereas outstanding genetic work in yeast has led to rapid discovery of a large number of interacting genes involved in the control of mitotic exit, it has also become increasingly difficult to comprehend the logic and mechanistic features embedded in the complex molecular network. Our view is that this difficulty stems in part from the attempt to explain mitotic exit control using concepts from traditional top-down engineering design, and that exciting new results from evolutionary engineering design applied to networks and electronic circuits may lend better insights. We focus on four particularly intriguing features of the mitotic exit control system: the two-stepped release of Cdc14; the self-activating nature of Tem1 GTPase; the spatial sensor associated with the spindle pole body; and the extensive redundancy in the mitotic exit network. We attempt to examine these design features from the perspective of evolutionary design and complex system engineering.

  18. Mitotic Spindle Form and Function

    PubMed Central

    Winey, Mark; Bloom, Kerry

    2012-01-01

    The Saccharomyces cerevisiae mitotic spindle in budding yeast is exemplified by its simplicity and elegance. Microtubules are nucleated from a crystalline array of proteins organized in the nuclear envelope, known as the spindle pole body in yeast (analogous to the centrosome in larger eukaryotes). The spindle has two classes of nuclear microtubules: kinetochore microtubules and interpolar microtubules. One kinetochore microtubule attaches to a single centromere on each chromosome, while approximately four interpolar microtubules emanate from each pole and interdigitate with interpolar microtubules from the opposite spindle to provide stability to the bipolar spindle. On the cytoplasmic face, two to three microtubules extend from the spindle pole toward the cell cortex. Processes requiring microtubule function are limited to spindles in mitosis and to spindle orientation and nuclear positioning in the cytoplasm. Microtubule function is regulated in large part via products of the 6 kinesin gene family and the 1 cytoplasmic dynein gene. A single bipolar kinesin (Cin8, class Kin-5), together with a depolymerase (Kip3, class Kin-8) or minus-end-directed kinesin (Kar3, class Kin-14), can support spindle function and cell viability. The remarkable feature of yeast cells is that they can survive with microtubules and genes for just two motor proteins, thus providing an unparalleled system to dissect microtubule and motor function within the spindle machine. PMID:22491889

  19. Phosphatases: providing safe passage through mitotic exit

    Microsoft Academic Search

    Claudia Wurzenberger; Daniel W. Gerlich

    2011-01-01

    The mitosis-to-interphase transition involves dramatic cellular reorganization from a state that supports chromosome segregation to a state that complies with all functions of an interphase cell. This process, termed mitotic exit, depends on the removal of mitotic phosphorylations from a broad range of substrates. Mitotic exit regulation involves inactivation of mitotic kinases and activation of counteracting protein phosphatases. The key

  20. Caspase-Independent Mitotic Death

    Microsoft Academic Search

    Katsumi Kitagawa

    The spindle checkpoint ensures proper chromosomal segregation by monitoring kinetochore–microtubule attachment. A failure\\u000a of this checkpoint causes aneuploidy, which leads to tumorigenesis. The cell death that prevents the aneuploidy caused by\\u000a failure of the spindle checkpoint is yet unknown. We have identified a novel type of mitotic cell death, which we term caspase-independent\\u000a mitotic death (CIMD). When BUB1 but not

  1. Mitotic cell recognition with hidden Markov models

    NASA Astrophysics Data System (ADS)

    Gallardo, Greg M.; Yang, Fuxing; Ianzini, Fiorenza; Mackey, Michael; Sonka, Milan

    2004-05-01

    This work describes a method for detecting mitotic cells in time-lapse microscopy images of live cells. The image sequences are from the Large Scale Digital Cell Analysis System (LSDCAS) at the University of Iowa. LSDCAS is an automated microscope system capable of monitoring 1000 microscope fields over time intervals of up to one month. Manual analysis of the image sequences can be extremely time consuming. This work is part of a larger project to automate the image sequence analysis. A three-step approach is used. In the first step, potential mitotic cells are located in the image sequences. In the second step, object border segmentation is performed with the watershed algorithm. Objects in adjacent frames are grouped into object sequences for classification. In the third step, the image sequences are converted to feature vector sequences. The feature vectors contain spatial and temporal information. Hidden Markov Models (HMMs) are used to classify the feature vector sequences into dead cells, cell edges, and dividing cells. Discrete and continuous HMMs were trained on 500 sequences. The discrete HMM recognition rates were 62% for dead cells, 77% for cell edges, and 75% for dividing cells. The continuous HMM results were 68%, 88% and 77%.

  2. Energy Conservation Featured in Illinois High School

    ERIC Educational Resources Information Center

    Modern Schools, 1976

    1976-01-01

    The William Fremd High School in Palatine, Illinois, scheduled to open in 1977, is being built with energy conservation uppermost in mind. In this system, 70 heat pumps will heat and cool 300,000 square feet of educational facilities. (Author/MLF)

  3. Measuring mitotic spindle dynamics in budding yeast

    NASA Astrophysics Data System (ADS)

    Plumb, Kemp

    In order to carry out its life cycle and produce viable progeny through cell division, a cell must successfully coordinate and execute a number of complex processes with high fidelity, in an environment dominated by thermal noise. One important example of such a process is the assembly and positioning of the mitotic spindle prior to chromosome segregation. The mitotic spindle is a modular structure composed of two spindle pole bodies, separated in space and spanned by filamentous proteins called microtubules, along which the genetic material of the cell is held. The spindle is responsible for alignment and subsequent segregation of chromosomes into two equal parts; proper spindle positioning and timing ensure that genetic material is appropriately divided amongst mother and daughter cells. In this thesis, I describe fluorescence confocal microscopy and automated image analysis algorithms, which I have used to observe and analyze the real space dynamics of the mitotic spindle in budding yeast. The software can locate structures in three spatial dimensions and track their movement in time. By selecting fluorescent proteins which specifically label the spindle poles and cell periphery, mitotic spindle dynamics have been measured in a coordinate system relevant to the cell division. I describe how I have characterised the accuracy and precision of the algorithms by simulating fluorescence data for both spindle poles and the budding yeast cell surface. In this thesis I also describe the construction of a microfluidic apparatus that allows for the measurement of long time-scale dynamics of individual cells and the development of a cell population. The tools developed in this thesis work will facilitate in-depth quantitative analysis of the non-equilibrium processes in living cells.

  4. OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems

    PubMed Central

    Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.

    2009-01-01

    Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937

  5. PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors

    PubMed Central

    Shin, Yooju; Hyeon, Jiyeon; Lee, Boram; Ha, Sang Yun; Hong, Min Eui; Do, In Gu; Kim, Kyoung-Mee

    2015-01-01

    Background: Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

  6. Phosphatases: providing safe passage through mitotic exit.

    PubMed

    Wurzenberger, Claudia; Gerlich, Daniel W

    2011-08-01

    The mitosis-to-interphase transition involves dramatic cellular reorganization from a state that supports chromosome segregation to a state that complies with all functions of an interphase cell. This process, termed mitotic exit, depends on the removal of mitotic phosphorylations from a broad range of substrates. Mitotic exit regulation involves inactivation of mitotic kinases and activation of counteracting protein phosphatases. The key mitotic exit phosphatase in budding yeast, Cdc14, is now well understood. By contrast, in animal cells, it is now emerging that mitotic exit relies on distinct regulatory networks, including the protein phosphatases PP1 and PP2A. PMID:21750572

  7. Micromechanics of human mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Sun, Mingxuan; Kawamura, Ryo; Marko, John F.

    2011-02-01

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

  8. The structural mechanisms that underpin mitotic kinase activation.

    PubMed

    Dodson, Charlotte A; Haq, Tamanna; Yeoh, Sharon; Fry, Andrew M; Bayliss, Richard

    2013-08-01

    In eukaryotic cells, the peak of protein phosphorylation occurs during mitosis, switching the activities of a significant proportion of proteins and orchestrating a wholesale reorganization of cell shape and internal architecture. Most mitotic protein phosphorylation events are catalysed by a small subset of serine/threonine protein kinases. These include members of the Cdk (cyclin-dependent kinase), Plk (Polo-like kinase), Aurora, Nek (NimA-related kinase) and Bub families, as well as Haspin, Greatwall and Mps1/TTK. There has been steady progress in resolving the structural mechanisms that regulate the catalytic activities of these mitotic kinases. From structural and biochemical perspectives, kinase activation appears not as a binary process (from inactive to active), but as a series of states that exhibit varying degrees of activity. In its lowest activity state, a mitotic kinase may exhibit diverse autoinhibited or inactive conformations. Kinase activation proceeds via phosphorylation and/or association with a binding partner. These remodel the structure into an active conformation that is common to almost all protein kinases. However, all mitotic kinases of known structure have divergent features, many of which are key to understanding their specific regulatory mechanisms. Finally, mitotic kinases are an important class of drug target, and their structural characterization has facilitated the rational design of chemical inhibitors. PMID:23863175

  9. Feature selection in high dimensional regression problems for genomics

    E-print Network

    Paris-Sud XI, Université de

    Feature selection in high dimensional regression problems for genomics Julie Hamon1,2,3 , Clarisse, France julien.jacques@lifl.fr Abstract. In the context of genomic selection in animal breeding and "closed to real" datasets. Keywords: Feature selection, combinatorial optimization, regression, genomic. 1

  10. Feature Extraction for Carbide Classification of High Speed Steel

    Microsoft Academic Search

    Klaus Wiltschi

    1995-01-01

    :A new feature extraction method for the purpose of carbide classification of high speed steels is introduced.By means of thresholding, filtering, closing and region labeling we generate a characteristicstructure of the carbides. Shape parameters of this structure and other features based on the skeletonand on linear projections are evaluated. Furthermore, the degree of orientation of the carbide distributionis determined in

  11. Highly sensitive feature detection for high resolution LC\\/MS

    Microsoft Academic Search

    Ralf Tautenhahn; Christoph Böttcher; Steffen Neumann

    2008-01-01

    BACKGROUND: Liquid chromatography coupled to mass spectrometry (LC\\/MS) is an important analytical technology for e.g. metabolomics experiments. Determining the boundaries, centres and intensities of the two-dimensional signals in the LC\\/MS raw data is called feature detection. For the subsequent analysis of complex samples such as plant extracts, which may contain hundreds of compounds, corresponding to thousands of features – a

  12. Unsupervised Feature Learning for High-Resolution Satellite Image Classification

    SciTech Connect

    Cheriyadat, Anil M [ORNL

    2013-01-01

    The rich data provided by high-resolution satellite imagery allow us to directly model geospatial neighborhoods by understanding their spatial and structural patterns. In this paper we explore an unsupervised feature learning approach to model geospatial neighborhoods for classification purposes. While pixel and object based classification approaches are widely used for satellite image analysis, often these approaches exploit the high-fidelity image data in a limited way. In this paper we extract low-level features to characterize the local neighborhood patterns. We exploit the unlabeled feature measurements in a novel way to learn a set of basis functions to derive new features. The derived sparse feature representation obtained by encoding the measured features in terms of the learned basis function set yields superior classification performance. We applied our technique on two challenging image datasets: ORNL dataset representing one-meter spatial resolution satellite imagery representing five land-use categories and, UCMERCED dataset consisting of 21 different categories representing sub-meter resolution overhead imagery. Our results are highly promising and, in the case of UCMERCED dataset we outperform the best results obtained for this dataset. We show that our feature extraction and learning methods are highly effective in developing a detection system that can be used to automatically scan large-scale high-resolution satellite imagery for detecting large-facility.

  13. The Zebra fish cassiopeia Mutant Reveals that SIL Is Required for Mitotic Spindle Organization? §

    PubMed Central

    Pfaff, Kathleen L.; Straub, Christian T.; Chiang, Ken; Bear, Daniel M.; Zhou, Yi; Zon, Leonard I.

    2007-01-01

    A critical step in cell division is formation of the mitotic spindle, which is a bipolar array of microtubules that mediates chromosome separation. Here, we report that the SCL-interrupting locus (SIL), a vertebrate-specific cytosolic protein, is necessary for proper mitotic spindle organization in zebrafish and human cells. A homozygous lethal zebrafish mutant, cassiopeia (csp), was identified by a genetic screen for mitotic mutant. csp mutant embryos have an increased mitotic index, have highly disorganized mitotic spindles, and often lack one or both centrosomes. These phenotypes are caused by a loss-of-function mutation in zebrafish sil. To determine if the requirement for SIL in mitotic spindle organization is conserved in mammals, we generated an antibody against human SIL, which revealed that SIL localizes to the poles of the mitotic spindle during metaphase. Furthermore, short hairpin RNA knockdown of SIL in human cells recapitulates the zebrafish csp mitotic spindle defects. These data, taken together, identify SIL as a novel, vertebrate-specific regulator of mitotic spindle assembly. PMID:17576815

  14. Advanced Induction Motor Endring Design Features for High Speed Applications

    Microsoft Academic Search

    Matthew Caprio; Vasileios Lelos; John Herbst; Jim Upshaw

    2005-01-01

    This paper presents advancements in induction motor endring design to overcome mechanical limitations and extend the operating speed range and joint reliability of induction machines. A novel endring design met the challenging mechanical requirements of this high speed, high temperature, power dense application, without compromising electrical performance. Analysis is presented of the advanced endring design features including a non uniform

  15. EGF Induced Centrosome Separation Promotes Mitotic Progression and Cell Survival

    PubMed Central

    Mardin, Balca R.; Isokane, Mayumi; Cosenza, Marco R.; Krämer, Alwin; Ellenberg, Jan; Fry, Andrew M.; Schiebel, Elmar

    2014-01-01

    Summary Timely and accurate assembly of the mitotic spindle is critical for the faithful segregation of chromosomes and centrosome separation is a key step in this process. The timing of centrosome separation varies dramatically between cell types; however, the mechanisms responsible for these differences and its significance are unclear. Here, we show that activation of epidermal growth factor receptor (EGFR) signaling determines the timing of centrosome separation. Premature separation of centrosomes decreases the requirement for the major mitotic kinesin Eg5 for spindle assembly, accelerates mitosis and decreases the rate of chromosome missegregation. Importantly, EGF stimulation impacts upon centrosome separation and mitotic progression to different degrees in different cell lines. Cells with high EGFR levels fail to arrest in mitosis upon Eg5 inhibition. This has important implications for cancer therapy since cells with high centrosomal response to EGF are more susceptible to combinatorial inhibition of EGFR and Eg5. PMID:23643362

  16. Mitotic Kinases and p53 Signaling

    PubMed Central

    Ha, Geun-Hyoung; Breuer, Eun-Kyoung Yim

    2012-01-01

    Mitosis is tightly regulated and any errors in this process often lead to aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic kinases is significantly associated with improper cell division and aneuploidy. Because of their importance during mitosis and the relevance to cancer, mitotic kinase signaling has been extensively studied over the past few decades and, as a result, several mitotic kinase inhibitors have been developed. Despite promising preclinical results, targeting mitotic kinases for cancer therapy faces numerous challenges, including safety and patient selection issues. Therefore, there is an urgent need to better understand the molecular mechanisms underlying mitotic kinase signaling and its interactive network. Increasing evidence suggests that tumor suppressor p53 functions at the center of the mitotic kinase signaling network. In response to mitotic spindle damage, multiple mitotic kinases phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53 can also regulate the expression and function of mitotic kinases, suggesting the existence of a network of mutual regulation, which can be positive or negative, between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory network will provide knowledge to overcome current limitations of targeting mitotic kinases and further improve the results of targeted therapy. PMID:22852086

  17. How do anti-mitotic drugs kill cancer cells?

    PubMed

    Gascoigne, Karen E; Taylor, Stephen S

    2009-08-01

    In 2007, over 12-million people were diagnosed with cancer. According to the American Cancer Society, at least one third of these individuals are not expected to survive the disease, making cancer the second most prevalent cause of death worldwide. Systemic chemotherapy forms the mainstay of cancer treatment, and agents that disrupt mitotic spindle assembly - so called ;anti-mitotics' - are commonly used to treat a wide variety of cancers. Traditional anti-mitotic agents include the microtubule toxins such as taxol, other taxanes and the vinca alkaloids, all of which have proven successful in the clinic. However, patient response remains highly unpredictable, and drug resistance is common. In addition, toxicity is a problem. To address these limitations, a new generation of anti-mitotic drugs is being developed. As the first wave of these new agents enters clinical trails, much hope rests on their outcome. Meanwhile, significant attention is being focused on trying to predict which tumour types are likely to respond. In this Commentary, we outline recent advances in our understanding of how cancer cells respond to anti-mitotic drugs, and discuss the relevance of these studies to their use in the clinic. PMID:19625502

  18. Loops determine the mechanical properties of mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Heermann, Dieter W.

    2013-03-01

    In mitosis, chromosomes undergo a condensation into highly compacted, rod-like objects. Many models have been put forward for the higher-order organization of mitotic chromosomes including radial loop and hierarchical folding models. Additionally, mechanical properties of mitotic chromosomes under different conditions were measured. However, the internal organization of mitotic chromosomes still remains unclear. Here we present a polymer model for mitotic chromosomes and show how chromatin loops play a major role for their mechanical properties. The key assumption of the model is the ability of the chromatin fibre to dynamically form loops with the help of binding proteins. Our results show that looping leads to a tight compaction and significantly increases the bending rigidity of chromosomes. Moreover, our qualitative prediction of the force elongation behaviour is close to experimental findings. This indicates that the internal structure of mitotic chromosomes is based on self-organization of the chromatin fibre. We also demonstrate how number and size of loops have a strong influence on the mechanical properties. We suggest that changes in the mechanical characteristics of chromosomes can be explained by an altered internal loop structure.

  19. Building high-level features using large scale unsupervised learning

    E-print Network

    Le, Quoc V; Devin, Matthieu; Corrado, Greg; Chen, Kai; Ranzato, Marc'Aurelio; Dean, Jeff; Ng, Andrew Y

    2011-01-01

    We consider the problem of building detectors for high-level concepts using only unsupervised feature learning. For example, we would like to understand if it is possible to learn a face detector using only unlabeled images downloaded from the internet. To answer this question, we trained a simple feature learning algorithm on a large dataset of images (10 million images, each image is 200x200). The simulation is performed on a cluster of 1000 machines with fast network hardware for one week. Extensive experimental results reveal surprising evidence that such high-level concepts can indeed be learned using only unlabeled data and a simple learning algorithm.

  20. Mitotically Active Plexiform Fibrohistiocytic Tumor

    PubMed Central

    Zemheri, Ebru; Özkanl?, ?eyma; ?enol, Serkan; Ozen, Filiz; Ulukaya Durakba?a, Cigdem; Zindanc?, ?lkin; Okur, Hamit

    2013-01-01

    Plexiform fibrohistiocytic tumor is an intermediate malignant tumor situated in superficial soft tissues. It affects children and young adults. The tumor is most commonly located on upper extremities, whereas involvement of back region is rare. Mitotic activity is generally low (~3/10 HPF). It is rare, but it can exhibit aggressive behavior, so total excision with clear surgical margins and long-term followup is necessary to detect local recurrence and metastases. We report a child with a solid mass on back region which was found to be a mitotically active plexiform fibrohistiocytic tumor (6/10 HPF) after excision. Plexiform fibrohistiocytic tumor (PFT) is a mesenchymal neoplasm of children, adolescents, and young adults. It is characterized by fibrohistiocytic cytomorphology and multinodular growth pattern. Clinically it is usually a slow-growing mass of upper extremities with frequent local recurrence and rare regional lymphatic and systemic metastasis (Fletcher et al. (2002), Enzinger and Zhang (1988), Remstein et al. (1999)). PMID:23607025

  1. Spectral feature design in high dimensional multispectral data

    NASA Technical Reports Server (NTRS)

    Chen, Chih-Chien Thomas; Landgrebe, David A.

    1988-01-01

    The High resolution Imaging Spectrometer (HIRIS) is designed to acquire images simultaneously in 192 spectral bands in the 0.4 to 2.5 micrometers wavelength region. It will make possible the collection of essentially continuous reflectance spectra at a spectral resolution sufficient to extract significantly enhanced amounts of information from return signals as compared to existing systems. The advantages of such high dimensional data come at a cost of increased system and data complexity. For example, since the finer the spectral resolution, the higher the data rate, it becomes impractical to design the sensor to be operated continuously. It is essential to find new ways to preprocess the data which reduce the data rate while at the same time maintaining the information content of the high dimensional signal produced. Four spectral feature design techniques are developed from the Weighted Karhunen-Loeve Transforms: (1) non-overlapping band feature selection algorithm; (2) overlapping band feature selection algorithm; (3) Walsh function approach; and (4) infinite clipped optimal function approach. The infinite clipped optimal function approach is chosen since the features are easiest to find and their classification performance is the best. After the preprocessed data has been received at the ground station, canonical analysis is further used to find the best set of features under the criterion that maximal class separability is achieved. Both 100 dimensional vegetation data and 200 dimensional soil data were used to test the spectral feature design system. It was shown that the infinite clipped versions of the first 16 optimal features had excellent classification performance. The overall probability of correct classification is over 90 percent while providing for a reduced downlink data rate by a factor of 10.

  2. Dynamical modeling of syncytial mitotic cycles in Drosophila embryos

    PubMed Central

    Calzone, Laurence; Thieffry, Denis; Tyson, John J; Novak, Bela

    2007-01-01

    Immediately following fertilization, the fruit fly embryo undergoes 13 rapid, synchronous, syncytial nuclear division cycles driven by maternal genes and proteins. During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. In this paper, we propose a dynamical model for the molecular events underlying these early nuclear division cycles in Drosophila. The model distinguishes nuclear and cytoplasmic compartments of the embryo and permits exploration of a variety of rules for protein transport between the compartments. Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. The model is consistent with mutations that introduce subtle changes in the number of mitotic cycles before interphase arrest. Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations. The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism. PMID:17667953

  3. Polar-Molecule-Dominated Electrorheological Fluids Featuring High Yield Stresses

    E-print Network

    Zexian, Cao

    Polar-Molecule-Dominated Electrorheological Fluids Featuring High Yield Stresses By Rong Shen of the external electric field, and the yield stress displays a quadratic dependence on the field strength been made to improve the performance of ER fluids, however, the yield stresses available were still

  4. The effects of high presentation levels on consonant feature transmission.

    PubMed

    Hornsby, Benjamin W Y; Trine, Timothy D; Ohde, Ralph N

    2005-09-01

    The effect of high speech presentation levels on consonant recognition and feature transmission was assessed in eight participants with normal hearing. Consonant recognition in noise (0 dB signal-to-noise ratio) was measured at five overall speech levels ranging from 65 to 100 dB SPL. Consistent with the work of others, overall percent correct performance decreased as the presentation level of speech increased [e.g., G. A. Studebaker, R. L. Sherbecoe, D. M. McDaniel, and C. A. Gwaltney, J. Acoust. Soc. Am. 105(4), 2431-2444 (1999)]. Confusion matrices were analyzed in terms of relative percent information transmitted at each speech presentation level, as a function of feature. Six feature sets (voicing, place, nasality, duration, frication, and sonorance) were analyzed. Results showed the feature duration (long consonant duration fricatives) to be most affected by increases in level, while the voicing feature was relatively unaffected by increases in level. In addition, alveolar consonants were substantially affected by level, while palatal consonants were not. While the underlying mechanisms responsible for decreases in performance with level increases are unclear, an analysis of common error patterns at high levels suggests that saturation of the neural response and/or a loss of neural synchrony may play a role. PMID:16240830

  5. The effects of high presentation levels on consonant feature transmission

    NASA Astrophysics Data System (ADS)

    Hornsby, Benjamin W. Y.; Trine, Timothy D.; Ohde, Ralph N.

    2005-09-01

    The effect of high speech presentation levels on consonant recognition and feature transmission was assessed in eight participants with normal hearing. Consonant recognition in noise (0 dB signal-to-noise ratio) was measured at five overall speech levels ranging from 65 to 100 dB SPL. Consistent with the work of others, overall percent correct performance decreased as the presentation level of speech increased [e.g., G. A. Studebaker, R. L. Sherbecoe, D. M. McDaniel, and C. A. Gwaltney, J. Acoust. Soc. Am. 105(4), 2431-2444 (1999)]. Confusion matrices were analyzed in terms of relative percent information transmitted at each speech presentation level, as a function of feature. Six feature sets (voicing, place, nasality, duration, frication, and sonorance) were analyzed. Results showed the feature duration (long consonant duration fricatives) to be most affected by increases in level, while the voicing feature was relatively unaffected by increases in level. In addition, alveolar consonants were substantially affected by level, while palatal consonants were not. While the underlying mechanisms responsible for decreases in performance with level increases are unclear, an analysis of common error patterns at high levels suggests that saturation of the neural response and/or a loss of neural synchrony may play a role.

  6. Feature extraction and classification algorithms for high dimensional data

    NASA Technical Reports Server (NTRS)

    Lee, Chulhee; Landgrebe, David

    1993-01-01

    Feature extraction and classification algorithms for high dimensional data are investigated. Developments with regard to sensors for Earth observation are moving in the direction of providing much higher dimensional multispectral imagery than is now possible. In analyzing such high dimensional data, processing time becomes an important factor. With large increases in dimensionality and the number of classes, processing time will increase significantly. To address this problem, a multistage classification scheme is proposed which reduces the processing time substantially by eliminating unlikely classes from further consideration at each stage. Several truncation criteria are developed and the relationship between thresholds and the error caused by the truncation is investigated. Next an approach to feature extraction for classification is proposed based directly on the decision boundaries. It is shown that all the features needed for classification can be extracted from decision boundaries. A characteristic of the proposed method arises by noting that only a portion of the decision boundary is effective in discriminating between classes, and the concept of the effective decision boundary is introduced. The proposed feature extraction algorithm has several desirable properties: it predicts the minimum number of features necessary to achieve the same classification accuracy as in the original space for a given pattern recognition problem; and it finds the necessary feature vectors. The proposed algorithm does not deteriorate under the circumstances of equal means or equal covariances as some previous algorithms do. In addition, the decision boundary feature extraction algorithm can be used both for parametric and non-parametric classifiers. Finally, some problems encountered in analyzing high dimensional data are studied and possible solutions are proposed. First, the increased importance of the second order statistics in analyzing high dimensional data is recognized. By investigating the characteristics of high dimensional data, the reason why the second order statistics must be taken into account in high dimensional data is suggested. Recognizing the importance of the second order statistics, there is a need to represent the second order statistics. A method to visualize statistics using a color code is proposed. By representing statistics using color coding, one can easily extract and compare the first and the second statistics.

  7. Identifying high-level features of texture perception

    NASA Astrophysics Data System (ADS)

    Rao, A. Ravishankar; Lohse, Gerald L.

    1992-08-01

    A fundamental issue in texture analysis is that of deciding what textural features are important in texture perception, and how they are used. Experiments on human pre-attentive vision have identified several low-level features (such as orientation on blobs, and size of line segments), which are used in texture perception. However, the question of what higher level features of texture are used has not been adequately addressed. We designed an experiment to help identify the relevant higher order features of texture perceived by humans. We used twenty subjects, who were asked to perform an unsupervised classification of thirty pictures from Brodatz's album on texture. Each subject was asked to group these pictures into as many classes as desired. Both hierarchical cluster analysis and non-metric MDS were applied to the pooled similarity matrix generated from the subjects' groupings. A surprising outcome is that the MDS solutions fit the data very well. The stress in the two dimensional case is 0.10, and in the three dimensional case is 0.045. We rendered the original textures in these coordinate systems, and interpreted the (rotated) axes. It appears that the axes in the 2D case correspond to periodicity versus irregularity, and directional versus non-directional. In the 3D case, the third dimension represents the structural complexity of the texture. Furthermore, the clusters identified by the hierarchical cluster analysis remain virtually intact in the MDS solution. The results of our experiment indicate that people use three high level features for texture perception. Future studies are needed to determine the appropriateness of these high-level features for computational texture analysis and classification.

  8. Mitotic force generators and chromosome segregation

    PubMed Central

    Civelekoglu-Scholey, Gul

    2010-01-01

    The mitotic spindle uses dynamic microtubules and mitotic motors to generate the pico-Newton scale forces that are needed to drive the mitotic movements that underlie chromosome capture, alignment and segregation. Here, we consider the biophysical and molecular basis of force-generation for chromosome movements in the spindle, and, with reference to the Drosophila embryo mitotic spindle, we briefly discuss how mathematical modeling can complement experimental analysis to illuminate the mechanisms of chromosome-to-pole motility during anaphase A and spindle elongation during anaphase B. PMID:20221784

  9. Axin localizes to mitotic spindles and centrosomes in mitotic cells

    SciTech Connect

    Kim, Shi-Mun; Choi, Eun-Jin; Song, Ki-Joon [Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Sewoon; Seo, Eunjeong; Jho, Eek-Hoon [Department of Life Science, University of Seoul, Seoul, 130-743 (Korea, Republic of); Kee, Sun-Ho [Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of)], E-mail: keesh@korea.ac.kr

    2009-04-01

    Wnt signaling plays critical roles in cell proliferation and carcinogenesis. In addition, numerous recent studies have shown that various Wnt signaling components are involved in mitosis and chromosomal instability. However, the role of Axin, a negative regulator of Wnt signaling, in mitosis has remained unclear. Using monoclonal antibodies against Axin, we found that Axin localizes to the centrosome and along mitotic spindles. This localization was suppressed by siRNA specific for Aurora A kinase and by Aurora kinase inhibitor. Interestingly, Axin over-expression altered the subcellular distribution of Plk1 and of phosphorylated glycogen synthase kinase (GSK3{beta}) without producing any notable changes in cellular phenotype. In the presence of Aurora kinase inhibitor, Axin over-expression induced the formation of cleavage furrow-like structures and of prominent astral microtubules lacking midbody formation in a subset of cells. Our results suggest that Axin modulates distribution of Axin-associated proteins such as Plk1 and GSK3{beta} in an expression level-dependent manner and these interactions affect the mitotic process, including cytokinesis under certain conditions, such as in the presence of Aurora kinase inhibitor.

  10. Prospects & Overviews Meiotic versus mitotic recombination

    E-print Network

    Sekelsky, Jeff

    Prospects & Overviews Meiotic versus mitotic recombination: Two different routes for double. However, most non-crossover (NCO) recombinants generated during S. cerevisiae meiosis do not arise via for recombinational repair of DSBs that occur in mitotically- proliferating cells and that the synthesis

  11. Centromeric Barrier Disruption Leads to Mitotic Defects in Schizosaccharomyces pombe

    PubMed Central

    Gaither, Terilyn L.; Merrett, Stephanie L.; Pun, Matthew J.; Scott, Kristin C.

    2014-01-01

    Centromeres are cis-acting chromosomal domains that direct kinetochore formation, enabling faithful chromosome segregation and preserving genome stability. The centromeres of most eukaryotic organisms are structurally complex, composed of nonoverlapping, structurally and functionally distinct chromatin subdomains, including the specialized core chromatin that underlies the kinetochore and pericentromeric heterochromatin. The genomic and epigenetic features that specify and preserve the adjacent chromatin subdomains critical to centromere identity are currently unknown. Here we demonstrate that chromatin barriers regulate this process in Schizosaccharomyces pombe. Reduced fitness and mitotic chromosome segregation defects occur in strains that carry exogenous DNA inserted at centromere 1 chromatin barriers. Abnormal phenotypes are accompanied by changes in the structural integrity of both the centromeric core chromatin domain, containing the conserved CENP-ACnp1 protein, and the flanking pericentric heterochromatin domain. Barrier mutant cells can revert to wild-type growth and centromere structure at a high frequency after the spontaneous excision of integrated exogenous DNA. Our results reveal a previously undemonstrated role for chromatin barriers in chromosome segregation and in the prevention of genome instability. PMID:24531725

  12. Topoisomerase II does not play a scaffolding role in the organization of mitotic chromosomes assembled in Xenopus egg extracts

    Microsoft Academic Search

    Tatsuya Hirano; Timothy J. Mitchison

    1993-01-01

    We have investigated the role of topoisom- erase II (topo II) in mitotic chromosome assembly and organization in vitro using Xenopus egg extracts. When sperm chromatin was incubated with mitotic extracts, the highly compact chromatin rapidly swelled and con- comitantly underwent local condensation. Further incubation induced the formation of entangled thin chromatin fibers that eventually resolved into highly condensed individual

  13. The chromosomal passenger complex (CPC) as a key orchestrator of orderly mitotic exit and cytokinesis

    PubMed Central

    Kitagawa, Mayumi; Lee, Sang Hyun

    2015-01-01

    Understanding the molecular network of orderly mitotic exit to re-establish a functional interphase nucleus is critical because disordered mitotic exit inevitably leads to genomic instability. In contrast to the mechanisms of the entrance to mitosis, however, little is known about what controls the orderly exit from mitosis, particularly in mammalian cells. The chromosomal passenger complex (CPC), which is composed of Aurora B, INCENP, Borealin and Survivin, is one of the most widely studied and highly conserved hetero-tetrameric complexes. The CPC orchestrates proper chromosome segregation with cytokinesis by targeting to specific locations at different stages of mitosis. Recent studies reveal that controlling CPC localization and Aurora B kinase activity also serves as a key surveillance mechanism for the orderly mitotic exit. This ensures the reformation of a functional interphase nucleus from condensed mitotic chromosomes by delaying mitotic exit and cytokinetic processes in response to defects in chromosome segregation. In this review, we will summarize the latest insight into the molecular mechanisms that regulate CPC localization during mitotic exit and discuss how targeting Aurora B activity to different locations at different times impacts executing multiple mitotic exit events in order and recently proposed surveillance mechanisms. Finally, we briefly discuss the potential implication of deregulated Aurora B in inducing genomic damage and tumorigenesis with current efforts in targeting Aurora B activity for anti-cancer therapy.

  14. The chromosomal passenger complex (CPC) as a key orchestrator of orderly mitotic exit and cytokinesis.

    PubMed

    Kitagawa, Mayumi; Lee, Sang Hyun

    2015-01-01

    Understanding the molecular network of orderly mitotic exit to re-establish a functional interphase nucleus is critical because disordered mitotic exit inevitably leads to genomic instability. In contrast to the mechanisms of the entrance to mitosis, however, little is known about what controls the orderly exit from mitosis, particularly in mammalian cells. The chromosomal passenger complex (CPC), which is composed of Aurora B, INCENP, Borealin and Survivin, is one of the most widely studied and highly conserved hetero-tetrameric complexes. The CPC orchestrates proper chromosome segregation with cytokinesis by targeting to specific locations at different stages of mitosis. Recent studies reveal that controlling CPC localization and Aurora B kinase activity also serves as a key surveillance mechanism for the orderly mitotic exit. This ensures the reformation of a functional interphase nucleus from condensed mitotic chromosomes by delaying mitotic exit and cytokinetic processes in response to defects in chromosome segregation. In this review, we will summarize the latest insight into the molecular mechanisms that regulate CPC localization during mitotic exit and discuss how targeting Aurora B activity to different locations at different times impacts executing multiple mitotic exit events in order and recently proposed surveillance mechanisms. Finally, we briefly discuss the potential implication of deregulated Aurora B in inducing genomic damage and tumorigenesis with current efforts in targeting Aurora B activity for anti-cancer therapy. PMID:25798441

  15. NudC Deacetylation Regulates Mitotic Progression

    PubMed Central

    Chuang, Carol; Pan, Jing; Hawke, David H.; Lin, Sue-Hwa; Yu-Lee, Li-yuan

    2013-01-01

    Mitosis is largely driven by posttranslational modifications of proteins. Recent studies suggest that protein acetylation is prevalent in mitosis, but how protein acetylation/deacetylation regulates mitotic progression remains unclear. Nuclear distribution protein C (NudC), a conserved protein that regulates cell division, was previously shown to be acetylated. We found that NudC acetylation was decreased during mitosis. Using mass spectrometry analysis, we identified K39 to be an acetylation site on NudC. Reconstitution of NudC-deficient cells with wild-type or K39R acetylation-defective NudC rescued mitotic phenotypes, including chromosome misalignment, chromosome missegregation, and reduced spindle width, observed after NudC protein knockdown. In contrast, the K39Q acetylation-mimetic NudC was unable to rescue these mitotic phenotypes, suggesting that NudC deacetylation is important for mitotic progression. To examine proteins that may play a role in NudC deacetylation during mitosis, we found that NudC co-localizes on the mitotic spindle with the histone deacetylase HDAC3, an HDAC shown to regulate mitotic spindle stability. Further, NudC co-immunoprecipitates with HDAC3 and loss of function of HDAC3 either by protein knockdown or inhibition with a small molecule inhibitor increased NudC acetylation. These observations suggest that HDAC3 may be involved in NudC deacetylation during mitosis. Cells with NudC or HDAC3 knockdown exhibited overlapping mitotic abnormalities, including chromosomes arranged in a “dome-like” configuration surrounding a collapsed mitotic spindle. Our studies suggest that NudC acetylation/deacetylation regulates mitotic progression and NudC deacetylation, likely through HDAC3, is critical for spindle function and chromosome congression. PMID:24069238

  16. On the molecular mechanisms of mitotic kinase activation

    PubMed Central

    Bayliss, Richard; Fry, Andrew; Haq, Tamanna; Yeoh, Sharon

    2012-01-01

    During mitosis, human cells exhibit a peak of protein phosphorylation that alters the behaviour of a significant proportion of proteins, driving a dramatic transformation in the cell's shape, intracellular structures and biochemistry. These mitotic phosphorylation events are catalysed by several families of protein kinases, including Auroras, Cdks, Plks, Neks, Bubs, Haspin and Mps1/TTK. The catalytic activities of these kinases are activated by phosphorylation and through protein–protein interactions. In this review, we summarize the current state of knowledge of the structural basis of mitotic kinase activation mechanisms. This review aims to provide a clear and comprehensive primer on these mechanisms to a broad community of researchers, bringing together the common themes, and highlighting specific differences. Along the way, we have uncovered some features of these proteins that have previously gone unreported, and identified unexplored questions for future work. The dysregulation of mitotic kinases is associated with proliferative disorders such as cancer, and structural biology will continue to play a critical role in the development of chemical probes used to interrogate disease biology and applied to the treatment of patients. PMID:23226601

  17. On the molecular mechanisms of mitotic kinase activation.

    PubMed

    Bayliss, Richard; Fry, Andrew; Haq, Tamanna; Yeoh, Sharon

    2012-11-01

    During mitosis, human cells exhibit a peak of protein phosphorylation that alters the behaviour of a significant proportion of proteins, driving a dramatic transformation in the cell's shape, intracellular structures and biochemistry. These mitotic phosphorylation events are catalysed by several families of protein kinases, including Auroras, Cdks, Plks, Neks, Bubs, Haspin and Mps1/TTK. The catalytic activities of these kinases are activated by phosphorylation and through protein-protein interactions. In this review, we summarize the current state of knowledge of the structural basis of mitotic kinase activation mechanisms. This review aims to provide a clear and comprehensive primer on these mechanisms to a broad community of researchers, bringing together the common themes, and highlighting specific differences. Along the way, we have uncovered some features of these proteins that have previously gone unreported, and identified unexplored questions for future work. The dysregulation of mitotic kinases is associated with proliferative disorders such as cancer, and structural biology will continue to play a critical role in the development of chemical probes used to interrogate disease biology and applied to the treatment of patients. PMID:23226601

  18. Study of features of high intensity noise effects during spaceflight

    NASA Technical Reports Server (NTRS)

    Yuganov, Y. M.; Krylov, Y. V.; Kuznetsov, V. S.

    1973-01-01

    Experiments were performed to study the effect on man of high intensity noises whose frequency range, length and volume corresponded to the conditions of the active period of spaceflight. The effect of 125-126 and 114-116 db of noise on the auditory and motor analyzers, and also on the condition of the pulse and blood pressure of 24 subjects was studied in 105 experiments during exposure for 20 minutes. It was found that noise at 125-126 db during the given exposure time causes unfavorable reactions on the part of the above mentioned indices. It was concluded that there is no danger from noise at 114-116 db for 20 minutes, considering the demands and particular features of spaceflight.

  19. Mitotic Waves in Laticifers of Euphorbia marginata.

    PubMed

    Mahlberg, P; Sabharwal, P

    1966-04-22

    A successive pattern of nuclear divisions that result in mitotic waves has been observed within the coenocytic nonarticulated laticifers of embryos of Euphorbia marginata Pursh. These waves originate independently in the cotyledonary or hypocotyl portion of the laticifer and exhibit uni-or bidirectional movement at variable velocities. Individual nuclei or groups of neighoring nuclei in a laticifer were observed in a sequence of mitotic stages ranging from prophase to telophase; division activity varied with individual laticifers in an embryo. Two mitotic patterns were apparent in the embryo: a random pattern associated with various cells in the meristematic area, and a successive pattern restricted to the laticifer. A substance, synthesized by and restricted to the laticifer, may be associated with this mitotic pattern. PMID:17815080

  20. Radar-anomalous, high-altitude features on Venus

    NASA Technical Reports Server (NTRS)

    Muhleman, Duane O.; Butler, Bryan J.

    1992-01-01

    Over nearly all of the surface of Venus the reflectivity and emissivity at centimeter wavelengths are about 0.15 and 0.85 respectively. These values are consistent with moderately dense soils and rock populations, but the mean reflectivity is about a factor of 2 greater than that for the Moon and other terrestrial planets. Pettingill and Ford, using Pioneer Venus reflectivities and emissivities, found a number of anomalous features on Venus that showed much higher reflectivities and much lower emissivities with both values approaching 0.5. These include Maxwell Montes, a number of high regions in Aphrodite Terra and Beta Regio, and several isolated mountain peaks. Most of the features are at altitudes above the mean radius by 2 to 3 km or more. However, such features have been found in the Magellan data at low altitudes and the anomalies do not exist on all high structures, Maat Mons being the most outstanding example. A number of papers have been written that attempt to explain the phenomena in terms of the geochemistry balance of weathering effects on likely surface minerals. The geochemists have shown that the fundamentally basaltic surface would be stable at the temperatures and pressures of the mean radius in the form of magnetite, but would evolve to pyrite and/or pyrrhotite in the presence of sulfur-bearing compounds such as SO2. Pyrite will be stable at altitudes above 4 or 5 km on Venus. Although the geochemical arguments are rather compelling, it is vitally important to rationally look at other explanations for radar and radio emission measurements such as that presented by Tryka and Muhleman. The radar reflectivity values are retrieved from the raw Magellan backscatter measurements by fitting the Hagfors' radar scattering model in which a surface roughness parameters and a normal incidence electrical reflectivity are estimated. The assumptions of the theory behind the model must be considered carefully before the results can be believed. These include that the surface roughness exists only at horizontal scales large compared to the wavelength, the vertical deviations are gaussianly distributed, there is no shadowing, and that the reflection occurs at the interface of two homogeneous dielectric half-spaces. Probably all these conditions are violated at the anomalous features under discussion. The most important of these is the homogeneity of the near surface of Venus, particularly in highlands. Under the assumptions of the theory, all of the radio energy is reflected by the impedance jump at the very boundary. However, in heterogeneous soil some fraction of the illuminating energy is propagated into the soil and then scattered back out by impedance discontinuities such as rock, voids, and cracks. In light soils, the latter effect can overwhelm the scattering effects of the true surface and greatly enhance the backscatter power, suggesting a much higher value of an effective dielectric constant that would be estimated from Hagfors' model.

  1. Highly Nonrandom Features of Synaptic Connectivity in Local Cortical Circuits

    PubMed Central

    2005-01-01

    How different is local cortical circuitry from a random network? To answer this question, we probed synaptic connections with several hundred simultaneous quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual cortex. Analysis of this dataset revealed several nonrandom features in synaptic connectivity. We confirmed previous reports that bidirectional connections are more common than expected in a random network. We found that several highly clustered three-neuron connectivity patterns are overrepresented, suggesting that connections tend to cluster together. We also analyzed synaptic connection strength as defined by the peak excitatory postsynaptic potential amplitude. We found that the distribution of synaptic connection strength differs significantly from the Poisson distribution and can be fitted by a lognormal distribution. Such a distribution has a heavier tail and implies that synaptic weight is concentrated among few synaptic connections. In addition, the strengths of synaptic connections sharing pre- or postsynaptic neurons are correlated, implying that strong connections are even more clustered than the weak ones. Therefore, the local cortical network structure can be viewed as a skeleton of stronger connections in a sea of weaker ones. Such a skeleton is likely to play an important role in network dynamics and should be investigated further. PMID:15737062

  2. Robust linear regression model of Ki-67 for mitotic rate in gastrointestinal stromal tumors

    PubMed Central

    KEMMERLING, RALF; WEYLAND, DENIS; KIESSLICH, TOBIAS; ILLIG, ROMANA; KLIESER, ECKHARD; JÄGER, TARKAN; DIETZE, OTTO; NEUREITER, DANIEL

    2014-01-01

    Risk stratification of gastrointestinal stromal tumors (GISTs) by tumor size, lymph node and metastasis status is crucially affected by mitotic activity. To date, no studies have quantitatively compared mitotic activity in hematoxylin and eosin (H&E)-stained tissue sections with immunohistochemical markers, such as phosphohistone H3 (PHH3) and Ki-67. According to the TNM guidelines, the mitotic count on H&E sections and immunohistochemical PHH3-stained slides has been assessed per 50 high-power fields of 154 specimens of clinically documented GIST cases. The Ki-67-associated proliferation rate was evaluated on three digitalized hot spots using image analysis. The H&E-based mitotic rate was found to correlate significantly better with Ki-67-assessed proliferation activity than with PHH3-assessed proliferation activity (r=0.780; P<0.01). A linear regression model (analysis of variance; P<0.001) allowed reliable predictions of the H&E-associated mitoses based on the Ki-67 expression alone. Additionally, the Ki-67-associated proliferation revealed a higher and significant impact on the recurrence and metastasis rate of the GIST cases than by the classical H&E-based mitotic rate. The results of the present study indicated that the mitotic rate may be reliably and time-efficiently estimated by immunohistochemistry of Ki-67 using only three hot spots. PMID:24527082

  3. Quantitative Site-specific Phosphorylation Dynamics of Human Protein Kinases during Mitotic Progression*

    PubMed Central

    Dulla, Kalyan; Daub, Henrik; Hornberger, Renate; Nigg, Erich A.; Körner, Roman

    2010-01-01

    Reversible protein phosphorylation is a key regulatory mechanism of mitotic progression. Importantly, protein kinases themselves are also regulated by phosphorylation-dephosphorylation processes; hence, phosphorylation dynamics of kinases hold a wealth of information about phosphorylation networks. Here, we investigated the site-specific phosphorylation dynamics of human kinases during mitosis using synchronization of HeLa suspension cells, kinase enrichment, and high resolution mass spectrometry. In biological triplicate analyses, we identified 206 protein kinases and more than 900 protein kinase phosphorylation sites, including 61 phosphorylation sites on activation segments, and quantified their relative abundances across three specific mitotic stages. Around 25% of the kinase phosphorylation site ratios were found to be changed by at least 50% during mitotic progression. Further network analysis of jointly regulated kinase groups suggested that Cyclin-dependent kinase- and mitogen-activated kinase-centered interaction networks are coordinately down- and up-regulated in late mitosis, respectively. Importantly, our data cover most of the already known mitotic kinases and, moreover, identify attractive candidates for future studies of phosphorylation-based mitotic signaling. Thus, the results of this study provide a valuable resource for cell biologists and provide insight into the system properties of the mitotic phosphokinome. PMID:20097925

  4. The STARD9/Kif16a Kinesin Associates With Mitotic Microtubules and Regulates Spindle Pole Assembly

    PubMed Central

    Torres, Jorge Z.; Summers, Matthew K.; Peterson, David; Brauer, Matthew J.; Lee, James; Senese, Silvia; Gholkar, Ankur A.; Lo, Yu-Chen; Lei, Xingye; Jung, Kenneth; Anderson, David C.; Davis, David P.; Belmont, Lisa; Jackson, Peter K.

    2011-01-01

    SUMMARY During cell division cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule co-purifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential anti-mitotic target. PMID:22153075

  5. Meiotic and Mitotic Recombination in Meiosis Kathryn P. Kohl* and Jeff Sekelsky*,,,1

    E-print Network

    Sekelsky, Jeff

    REVIEW Meiotic and Mitotic Recombination in Meiosis Kathryn P. Kohl* and Jeff Sekelsky*,,,1 evolved to incorporate special features unique to meiosis. MEIOSIS is essential to maintaining the proper replication with two rounds of cellular division, meiosis effectively halves the chromosome content

  6. AN EVALUATION OF FEATURE LEARNING METHODS FOR HIGH RESOLUTION IMAGE CLASSIFICATION

    E-print Network

    Schindler, Konrad

    AN EVALUATION OF FEATURE LEARNING METHODS FOR HIGH RESOLUTION IMAGE CLASSIFICATION P. Tokarczyk*, J concentrate on the features. Several methods are evaluated which allow one to learn suitable features from several methods for feature extraction from the image data. An end-to-end evaluation is carried out

  7. Unusual features of the high light acclimation of Chromera velia.

    PubMed

    Mann, Marcus; Hoppenz, Paul; Jakob, Torsten; Weisheit, Wolfram; Mittag, Maria; Wilhelm, Christian; Goss, Reimund

    2014-11-01

    In the present study, the high light (HL) acclimation of Chromera velia (Chromerida) was studied. HL-grown cells exhibited an increased cell volume and dry weight compared to cells grown at medium light (ML). The chlorophyll (Chl) a-specific absorption spectra ([Formula: see text]) of the HL cells showed an increased absorption efficiency over a wavelength range from 400 to 750 nm, possibly due to differences in the packaging of Chl a molecules. In HL cells, the size of the violaxanthin (V) cycle pigment pool was strongly increased. Despite a higher concentration of de-epoxidized V cycle pigments, non-photochemical quenching (NPQ) of the HL cells was slightly reduced compared to ML cells. The analysis of NPQ recovery during low light (LL) after a short illumination with excess light showed a fast NPQ relaxation and zeaxanthin epoxidation. Purification of the pigment-protein complexes demonstrated that the HL-synthesized V was associated with the chromera light-harvesting complex (CLH). However, the difference absorption spectrum of HL minus ML CLH, together with the 77 K fluorescence excitation spectra, suggested that the additional V was not protein bound but localized in a lipid phase associated with the CLH. The polypeptide analysis of the pigment-protein complexes showed that one out of three known LHCr proteins was associated in higher concentration with photosystem I in the HL cells, whereas in ML cells, it was enriched in the CLH fraction. In conclusion, the acclimation of C. velia to HL illumination shows features that are comparable to those of diatoms, while other characteristics more closely resemble those of higher plants and green algae. PMID:24906888

  8. Nonnegative Mixed-Norm Convex Optimization for Mitotic Cell Detection in Phase Contrast Microscopy

    PubMed Central

    Hao, Tong; Gao, Zan; Su, Yuting; Yang, Zhaoxuan

    2013-01-01

    This paper proposes a nonnegative mix-norm convex optimization method for mitotic cell detection. First, we apply an imaging model-based microscopy image segmentation method that exploits phase contrast optics to extract mitotic candidates in the input images. Then, a convex objective function regularized by mix-norm with nonnegative constraint is proposed to induce sparsity and consistence for discriminative representation of deformable objects in a sparse representation scheme. At last, a Support Vector Machine classifier is utilized for mitotic cell modeling and detection. This method can overcome the difficulty in feature formulation for deformable objects and is independent of tracking or temporal inference model. The comparison experiments demonstrate that the proposed method can produce competing results with the state-of-the-art methods. PMID:24348733

  9. Mitotic rate is a more reliable unfavorable prognosticator than ulceration for early cutaneous melanoma: a 5-year survival analysis.

    PubMed

    Donizy, Piotr; Kaczorowski, Maciej; Leskiewicz, Marek; Zietek, Marcin; Pieniazek, Malgorzata; Kozyra, Cyprian; Halon, Agnieszka; Matkowski, Rafal

    2014-12-01

    The presence of ulceration has been considered as one of the most important primary tumor characteristics of cutaneous malignant melanoma (CMM) for predicting patient outcome. Yet recently, scientific attention has been drawn towards another microscopic feature of primary tumors, the mitotic rate (MR). The present study aimed to examine the relationship between the presence of ulceration and the mitotic rate and clinicopathological characteristics and melanoma patient survival, and to discuss the results in the context of AJCC melanoma staging recommendations. Tissue samples were obtained from 104 patients treated for CMM. In classical H&E staining, the mitotic rate and the presence of ulceration were evaluated. Non-mitogenic tumors were defined as having 0 mitoses/mm2, low mitogenic potential, 1-2 mitoses/mm2 and highly mitogenic tumors, ?3 mitoses/mm2. In the entire group of 104 patients, a high mitotic rate (hMR) and ulceration were highly negative prognostic factors, and indicated considerably shorter overall survival, cancer-specific overall survival and disease-free survival. Notably, hMR appeared to have a statistically significant negative impact on survival in early melanomas in both the pT1 (P=0.001) and pT2 subgroups (P=0.006). Kaplan?Meier analysis of the remaining subsets (pT3 and pT4) did not reveal any important differences in the 5-year survival with regard to MR values. The presence of ulceration also had a prognostic significance for early melanomas, but only for pT1 tumors (P=0.05). Multivariate analysis confirmed that hMR was strongly associated with an unfavorable prognosis. Ulceration had no prognostic significance in the Cox proportional hazards model. Considering the biology of melanoma, hMR seems to be a more reliable parameter than the presence of ulceration. The value of MR categorizes melanomas into tumors with low or high proliferative potential, thus giving direct information concerning their capacity to infiltrate deeper layers of the dermis and, potentially, to generate regional lymph node and distant metastases. PMID:25310673

  10. Mechanisms of Mitotic Spindle Disassembly and Positioning in Saccharomyces cerevisiae

    E-print Network

    Woodruff, Jeffrey Blake

    2011-01-01

    2: Mitotic spindle disassembly occurs via distinct subprocesses driven by the Anaphase-Promoting Complex, Aurora B kinase, and kinesin-2: Mitotic spindle disassembly occurs via distinct subprocesses driven by the Anaphase-Promoting Complex, Aurora B kinase, and kinesin-

  11. Rapid measurement of mitotic spindle orientation in cultured mammalian cells.

    PubMed

    Decarreau, Justin; Driver, Jonathan; Asbury, Charles; Wordeman, Linda

    2014-01-01

    Factors that influence the orientation of the mitotic spindle are important for the maintenance of stem cell populations and in cancer development. However, screening for these factors requires rapid quantification of alterations of the angle of the mitotic spindle in cultured cell lines. Here we describe a method to image mitotic cells and rapidly score the angle of the mitotic spindle using a simple MATLAB application to analyze a stack of Z-images. PMID:24633791

  12. Mitotic Waves in Laticifers of Euphorbia marginata

    Microsoft Academic Search

    Paul Mahlberg; Pritam Sabharwal

    1966-01-01

    A successive pattern of nuclear divisions that result in mitotic waves has been observed within the coenocytic nonarticulated laticifers of embryos of Euphorbia marginata Pursh. These waves originate independently in the cotyledonary or hypocotyl portion of the laticifer and exhibit uni- or bi-directional movement at variable velocities. Individual nuclei or groups of neighoring nuclei in a laticifer were observed in

  13. Mitotic Stress and Chromosomal Instability in Cancer

    PubMed Central

    Malumbres, Marcos

    2012-01-01

    Cell cycle deregulation is a common motif in human cancer, and multiple therapeutic strategies are aimed to prevent tumor cell proliferation. Whereas most current therapies are designed to arrest cell cycle progression either in G1/S or in mitosis, new proposals include targeting the intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) or aneuploidy (a genomic composition that differs from diploid) that many tumor cells display. Why tumors cells are chromosomally unstable or aneuploid and what are the consequences of these alterations are not completely clear at present. Several mitotic regulators are overexpressed as a consequence of oncogenic alterations, and they are likely to alter the proper regulation of chromosome segregation in cancer cells. In this review, we propose the relevance of TPX2, a mitotic regulator involved in the formation of the mitotic spindle, in oncogene-induced mitotic stress. This protein, as well as its partner Aurora-A, is frequently overexpressed in human cancer, and its deregulation may participate not only in chromosome numeric aberrations but also in other forms of genomic instability in cancer cells. PMID:23634259

  14. INTRODUCTION Mitotic metaphase chromosomes show sister chromatids

    E-print Network

    Villefranche sur mer

    . Meiosis I bivalents, as mitotic chromosomes, show sister-chromatid centromere and arm cohesions cohesion during meiosis I, and then release centromere cohesion during meiosis II (for review see Moore and Orr- Weaver, 1998). Consequently, this sequential loss of cohesion during meiosis might be precisely

  15. Arsenite-induced mitotic death involves stress response and is independent of tubulin polymerization

    SciTech Connect

    Taylor, B. Frazier; McNeely, Samuel C.; Miller, Heather L. [Department of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202 (United States); States, J. Christopher [Department of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202 (United States)], E-mail: jcstates@louisville.edu

    2008-07-15

    Arsenite, a known mitotic disruptor, causes cell cycle arrest and cell death at anaphase. The mechanism causing mitotic arrest is highly disputed. We compared arsenite to the spindle poisons nocodazole and paclitaxel. Immunofluorescence analysis of {alpha}-tubulin in interphase cells demonstrated that, while nocodazole and paclitaxel disrupt microtubule polymerization through destabilization and hyperpolymerization, respectively, microtubules in arsenite-treated cells remain comparable to untreated cells even at supra-therapeutic concentrations. Immunofluorescence analysis of {alpha}-tubulin in mitotic cells showed spindle formation in arsenite- and paclitaxel-treated cells but not in nocodazole-treated cells. Spindle formation in arsenite-treated cells appeared irregular and multi-polar. {gamma}-tubulin staining showed that cells treated with nocodazole and therapeutic concentrations of paclitaxel contained two centrosomes. In contrast, most arsenite-treated mitotic cells contained more than two centrosomes, similar to centrosome abnormalities induced by heat shock. Of the three drugs tested, only arsenite treatment increased expression of the inducible isoform of heat shock protein 70 (HSP70i). HSP70 and HSP90 proteins are intimately involved in centrosome regulation and mitotic spindle formation. HSP90 inhibitor 17-DMAG sensitized cells to arsenite treatment and increased arsenite-induced centrosome abnormalities. Combined treatment of 17-DMAG and arsenite resulted in a supra-additive effect on viability, mitotic arrest, and centrosome abnormalities. Thus, arsenite-induced abnormal centrosome amplification and subsequent mitotic arrest is independent of effects on tubulin polymerization and may be due to specific stresses that are protected against by HSP90 and HSP70.

  16. Comparative analysis of mitosis-specific antibodies for bulk purification of mitotic populations by fluorescence-activated cell sorting

    PubMed Central

    Blobel, Gerd A.

    2014-01-01

    Mitosis entails complex chromatin changes that have garnered increasing interest from biologists who study genome structure and regulation – fields that are being advanced by high-throughput sequencing (Seq) technologies. The application of such technologies to study the mitotic genome requires large numbers of highly pure mitotic cells with minimal contamination from interphase cells to ensure accurate measurements of phenomena specific to mitosis. Here, we optimized a fluorescence-activated cell sorting (FACS)-based method for isolating formaldehyde-fixed mitotic cells – at virtually 100% mitotic purity – in substantial quantities sufficient for high-throughput genomic studies. We compare several commercially available antibodies that react with mitosis-specific epitopes over a range of concentrations and cell numbers, and identify antibody MPM2 as the most robust and cost-effective. PMID:24502799

  17. Physicochemical features of ultra-high viscosity alginates

    Microsoft Academic Search

    Henning Storz; Kilian J. Müller; Friederike Ehrhart; Ivan Gómez; Stephen G. Shirley; Petra Gessner; Gertraud Zimmermann; Esther Weyand; Vladimir L. Sukhorukov; Thomas Forst; Matthias M. Weber; Heiko Zimmermann; Werner-Michael Kulicke; Ulrich Zimmermann

    2009-01-01

    The physicochemical characteristics of the ultra-high viscosity and highly biocompatible alginates extracted from Lessonia nigrescens (UHVN) and Lessonia trabeculata (UHVT) were analyzed. Fluorescence and 1H NMR spectroscopies, viscometry, and multi-angle light scattering (MALS) were used for elucidation of the chemical structure, molar mass, and coil size. The sequential structures from NMR spectroscopy showed high guluronate content for UHVT, but low

  18. High impedance fault detection using feature-pattern based relaying

    Microsoft Academic Search

    A. M. Sharaf; Guosheng Wang

    2003-01-01

    The paper presents a novel time domain high impedance fault (HIF) detection scheme based on low frequency (third, fifth harmonic excursion patterns and phase-portraits). The proposed relaying scheme utilizes a pattern\\/shape recognition method.

  19. Image feature point detection method based on the pixels of high-resolution sensors

    NASA Astrophysics Data System (ADS)

    Liu, Xingchun; Wang, Zhe; Hu, Zhipeng; Zhang, Jiancheng

    2014-11-01

    Through analyzing the characteristic of high resolution image obtained by high resolution sensor when the size of sensor is fixed, a new fast feature point detecting method is put forward. Firstly, detect effective points by sampling in fixed step, which are used to filter to get extreme feature points, and realize the extraction process of extreme feature points simplified, then take points with neighborhood domain features as the description of effective points, and obtain extreme feature points through the preset threshold calculation, finally, obtain correct feature points by filtering. At last the effect of the extraction method was validated by the image matching result. And the matching result shows that image's features extracted by this method could ensure the precision and decrease the computation at the same time.

  20. Unbiased Feature Selection in Learning Random Forests for High-Dimensional Data

    PubMed Central

    Nguyen, Thanh-Tung; Huang, Joshua Zhexue; Nguyen, Thuy Thi

    2015-01-01

    Random forests (RFs) have been widely used as a powerful classification method. However, with the randomization in both bagging samples and feature selection, the trees in the forest tend to select uninformative features for node splitting. This makes RFs have poor accuracy when working with high-dimensional data. Besides that, RFs have bias in the feature selection process where multivalued features are favored. Aiming at debiasing feature selection in RFs, we propose a new RF algorithm, called xRF, to select good features in learning RFs for high-dimensional data. We first remove the uninformative features using p-value assessment, and the subset of unbiased features is then selected based on some statistical measures. This feature subset is then partitioned into two subsets. A feature weighting sampling technique is used to sample features from these two subsets for building trees. This approach enables one to generate more accurate trees, while allowing one to reduce dimensionality and the amount of data needed for learning RFs. An extensive set of experiments has been conducted on 47 high-dimensional real-world datasets including image datasets. The experimental results have shown that RFs with the proposed approach outperformed the existing random forests in increasing the accuracy and the AUC measures. PMID:25879059

  1. Features of air conditioning systems with separation of a moisture on high pressure

    Microsoft Academic Search

    Yuriy Dyachenko; Alexander Chichindaev

    2000-01-01

    In activity the analysis of the literature, directional on study of features of activity of a AHRS with separation of a moisture on high pressure is executed. As a result of study of design features of a AHRS the describing systems of a sectional type are established four indication: 1) a way of cooling of air high-pressure; 2) a degree

  2. Automatic microscopy for mitotic cell location.

    NASA Technical Reports Server (NTRS)

    Herron, J.; Ranshaw, R.; Castle, J.; Wald, N.

    1972-01-01

    Advances are reported in the development of an automatic microscope with which to locate hematologic or other cells in mitosis for subsequent chromosome analysis. The system under development is designed to perform the functions of: slide scanning to locate metaphase cells; conversion of images of selected cells into binary form; and on-line computer analysis of the digitized image for significant cytogenetic data. Cell detection criteria are evaluated using a test sample of 100 mitotic cells and 100 artifacts.

  3. Optimal Feature Selection in High-Dimensional Discriminant Analysis

    PubMed Central

    Kolar, Mladen; Liu, Han

    2014-01-01

    We consider the high-dimensional discriminant analysis problem. For this problem, different methods have been proposed and justified by establishing exact convergence rates for the classification risk, as well as the ?2 convergence results to the discriminative rule. However, sharp theoretical analysis for the variable selection performance of these procedures have not been established, even though model interpretation is of fundamental importance in scientific data analysis. This paper bridges the gap by providing sharp sufficient conditions for consistent variable selection using the sparse discriminant analysis (Mai et al., 2012). Through careful analysis, we establish rates of convergence that are significantly faster than the best known results and admit an optimal scaling of the sample size n, dimensionality p, and sparsity level s in the high-dimensional setting. Sufficient conditions are complemented by the necessary information theoretic limits on the variable selection problem in the context of high-dimensional discriminant analysis. Exploiting a numerical equivalence result, our method also establish the optimal results for the ROAD estimator (Fan et al., 2012) and the sparse optimal scaling estimator (Clemmensen et al., 2011). Furthermore, we analyze an exhaustive search procedure, whose performance serves as a benchmark, and show that it is variable selection consistent under weaker conditions. Extensive simulations demonstrating the sharpness of the bounds are also provided. PMID:25620807

  4. Effect of Cell Shape and Dimensionality on Spindle Orientation and Mitotic Timing

    PubMed Central

    Charnley, Mirren; Anderegg, Fabian; Holtackers, René; Textor, Marcus; Meraldi, Patrick

    2013-01-01

    The formation and orientation of the mitotic spindle is a critical feature of mitosis. The morphology of the cell and the spatial distribution and composition of the cells' adhesive microenvironment all contribute to dictate the position of the spindle. However, the impact of the dimensionality of the cells' microenvironment has rarely been studied. In this study we present the use of a microwell platform, where the internal surfaces of the individual wells are coated with fibronectin, enabling the three-dimensional presentation of adhesive ligands to single cells cultured within the microwells. This platform was used to assess the effect of dimensionality and cell shape in a controlled microenvironment. Single HeLa cells cultured in circular microwells exhibited greater tilting of the mitotic spindle, in comparison to cells cultured in square microwells. This correlated with an increase in the time required to align the chromosomes at the metaphase plate due to prolonged activation of the spindle checkpoint in an actin dependent process. The comparison to 2D square patterns revealed that the dimensionality of cell adhesions alone affected both mitotic timings and spindle orientation; in particular the role of actin varied according to the dimensionality of the cells' microenvironment. Together, our data revealed that cell shape and the dimensionality of the cells' adhesive environment impacted on both the orientation of the mitotic spindle and progression through mitosis. PMID:23825020

  5. Revertant Somatic Mosaicism by Mitotic Recombination in Dyskeratosis Congenita

    PubMed Central

    Jongmans, Marjolijn C.J.; Verwiel, Eugene T.P.; Heijdra, Yvonne; Vulliamy, Tom; Kamping, Eveline J.; Hehir-Kwa, Jayne Y.; Bongers, Ernie M.H.F.; Pfundt, Rolph; van Emst, Liesbeth; van Leeuwen, Frank N.; van Gassen, Koen L.I.; Geurts van Kessel, Ad; Dokal, Inderjeet; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J.L.; Kuiper, Roland P.

    2012-01-01

    Revertant mosaicism is an infrequently observed phenomenon caused by spontaneous correction of a pathogenic allele. We have observed such reversions caused by mitotic recombination of mutant TERC (telomerase RNA component) alleles in six patients from four families affected by dyskeratosis congenita (DC). DC is a multisystem disorder characterized by mucocutaneous abnormalities, dystrophic nails, bone-marrow failure, lung fibrosis, liver cirrhosis, and cancer. We identified a 4 nt deletion in TERC in a family with an autosomal-dominant form of DC. In two affected brothers without bone-marrow failure, sequence analysis revealed pronounced overrepresentation of the wild-type allele in blood cells, whereas no such skewing was observed in the other tissues tested. These observations suggest that this mosaic pattern might have resulted from somatic reversion of the mutated allele to the normal allele in blood-forming cells. SNP-microarray analysis on blood DNA from the two brothers indeed showed independent events of acquired segmental isodisomy of chromosome 3q, including TERC, indicating that the reversions must have resulted from mitotic recombination events. Subsequently, after developing a highly sensitive method of detecting mosaic homozygosity, we have found four additional cases with a mosaic-reversion pattern in blood cells; these four cases are part of a cohort of 17 individuals with germline TERC mutations. This shows that revertant mosaicism is a recurrent event in DC. This finding has important implications for improving diagnostic testing and understanding the variable phenotype of DC. PMID:22341970

  6. Non-iridescent Transmissive Structural Color Filter Featuring Highly Efficient Transmission and High Excitation Purity

    NASA Astrophysics Data System (ADS)

    Shrestha, Vivek Raj; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2014-05-01

    Nanostructure based color filtering has been considered an attractive replacement for current colorant pigmentation in the display technologies, in view of its increased efficiencies, ease of fabrication and eco-friendliness. For such structural filtering, iridescence relevant to its angular dependency, which poses a detrimental barrier to the practical development of high performance display and sensing devices, should be mitigated. We report on a non-iridescent transmissive structural color filter, fabricated in a large area of 76.2 × 25.4 mm2, taking advantage of a stack of three etalon resonators in dielectric films based on a high-index cavity in amorphous silicon. The proposed filter features a high transmission above 80%, a high excitation purity of 0.93 and non-iridescence over a range of 160°, exhibiting no significant change in the center wavelength, dominant wavelength and excitation purity, which implies no change in hue and saturation of the output color. The proposed structure may find its potential applications to large-scale display and imaging sensor systems.

  7. Non-iridescent Transmissive Structural Color Filter Featuring Highly Efficient Transmission and High Excitation Purity

    PubMed Central

    Shrestha, Vivek Raj; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2014-01-01

    Nanostructure based color filtering has been considered an attractive replacement for current colorant pigmentation in the display technologies, in view of its increased efficiencies, ease of fabrication and eco-friendliness. For such structural filtering, iridescence relevant to its angular dependency, which poses a detrimental barrier to the practical development of high performance display and sensing devices, should be mitigated. We report on a non-iridescent transmissive structural color filter, fabricated in a large area of 76.2 × 25.4?mm2, taking advantage of a stack of three etalon resonators in dielectric films based on a high-index cavity in amorphous silicon. The proposed filter features a high transmission above 80%, a high excitation purity of 0.93 and non-iridescence over a range of 160°, exhibiting no significant change in the center wavelength, dominant wavelength and excitation purity, which implies no change in hue and saturation of the output color. The proposed structure may find its potential applications to large-scale display and imaging sensor systems. PMID:24815530

  8. Mechanisms promoting escape from mitotic stress-induced tumor cell death.

    PubMed

    Sinnott, Rebecca; Winters, Leah; Larson, Brittany; Mytsa, Daniela; Taus, Patrick; Cappell, Kathryn M; Whitehurst, Angelique W

    2014-07-15

    Non-small cell lung cancer (NSCLC) is notorious for its paltry responses to first-line therapeutic regimens. In contrast to acquired chemoresistance, little is known about the molecular underpinnings of the intrinsic resistance of chemo-naďve NSCLC. Here we report that intrinsic resistance to paclitaxel in NSCLC occurs at a cell-autonomous level because of the uncoupling of mitotic defects from apoptosis. To identify components that permit escape from mitotic stress-induced death, we used a genome-wide RNAi-based strategy, which combines a high-throughput toxicity screen with a live-cell imaging platform to measure mitotic fate. This strategy revealed that prolonging mitotic arrest with a small molecule inhibitor of the APC/cyclosome could sensitize otherwise paclitaxel-resistant NSCLC. We also defined novel roles for CASC1 and TRIM69 in supporting resistance to spindle poisons. CASC1, which is frequently co-amplified with KRAS in lung tumors, is essential for microtubule polymerization and satisfaction of the spindle assembly checkpoint. TRIM69, which associates with spindle poles and promotes centrosomal clustering, is essential for formation of a bipolar spindle. Notably, RNAi-mediated attenuation of CASC1 or TRIM69 was sufficient to inhibit tumor growth in vivo. On the basis of our results, we hypothesize that tumor evolution selects for a permissive mitotic checkpoint, which may promote survival despite chromosome segregation errors. Attacking this adaptation may restore the apoptotic consequences of mitotic damage to permit the therapeutic eradication of drug-resistant cancer cells. PMID:24860162

  9. Grading of Well-differentiated Pancreatic Neuroendocrine Tumors Is Improved by the Inclusion of Both Ki67 Proliferative Index and Mitotic Rate

    PubMed Central

    McCall, Chad M.; Shi, Chanjuan; Cornish, Toby C.; Klimstra, David S.; Tang, Laura H.; Basturk, Olca; Mun, Liew Jun; Ellison, Trevor A.; Wolfgang, Christopher L.; Choti, Michael A.; Schulick, Richard D.; Edil, Barish H.; Hruban, Ralph H.

    2013-01-01

    The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010 by the World Health Organization (WHO) mandates the use of both mitotic rate and Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In cases when these measures are not concordant for grade, it is recommended to assign the higher grade, but specific data justifying this approach do not exist. Thus, we counted mitotic figures and immunolabeled, using the Ki67 antibody, 297 WHO mitotic grade 1 and 2 PanNETs surgically resected at a single institution. We quantified the Ki67 proliferative index by marking at least 500 cells in “hot spots” and by using digital image analysis software to count each marked positive/negative cell and then compared the results with histologic features and overall survival. Of 264 WHO mitotic grade 1 PanNETs, 33% were WHO grade 2 by Ki67 proliferative index. Compared with concordant grade 1 tumors, grade-discordant tumors were more likely to have metastases to lymph node (56% vs. 34%) (P < 0.01) and to distant sites (46% vs. 12%) (P < 0.01). Discordant mitotic grade 1 PanNETs also showed statistically significantly more infiltrative growth patterns, perineural invasion, and small vessel invasion. Overall survival was significantly different (P < 0.01), with discordant mitotic grade 1 tumors showing a median survival of 12 years compared with 16.7 years for concordant grade 1 tumors. Conversely, mitotic grade 1/Ki67 grade 2 PanNETs showed few significant differences from tumors that were mitotic grade 2 and either Ki67 grade 1 or 2. Our data demonstrate that mitotic rate and Ki67-based grades of PanNETs are often discordant, and when the Ki67 grade is greater than the mitotic grade, clinical outcomes and histopathologic features are significantly worse than concordant grade 1 tumors. Patients with discordant mitotic grade 1/Ki67 grade 2 tumors have shorter overall survival and larger tumors with more metastases and more aggressive histologic features. These data strongly suggest that Ki67 labeling be performed on all PanNETs in addition to mitotic rate determination to define more accurately tumor grade and prognosis. PMID:24121170

  10. Phosphorylation of linker histones by cAMP-dependent protein kinase in mitotic micronuclei of Tetrahymena

    Microsoft Academic Search

    Melody T. Sweet; C. David Allis

    1993-01-01

    Linker histones (LHs) in transcriptionally inretive, mitotically dividing micronuclei of Tetrahymena thermophila, a, ß, ? and d, are highly phosphorylated in vivo. Analysis of the derived sequences of these LHs suggests that none of these polypeptides contain sites of phosphorylation by p34cdc2, the kinase thought to play an essential role governing the entry of all cells into mitosis. Suprisingly a,

  11. Mitotic Phosphorylation of Histone H3: Spatio-Temporal Regulation by Mammalian Aurora Kinases

    Microsoft Academic Search

    Claudia Crosio; Gian Maria Fimia; Romain Loury; Masashi Kimura; Yukio Okano; Hongyi Zhou; Subrata Sen; C. David Allis; Paolo Sassone-Corsi

    2002-01-01

    Phosphorylation at a highly conserved serine residue (Ser-10) in the histone H3 tail is considered to be a crucial event for the onset of mitosis. This modification appears early in the G2 phase within pericentromeric heterochromatin and spreads in an ordered fashion coincident with mitotic chromosome condensation. Mu- tation of Ser-10 is essential in Tetrahymena, since it results in abnormal

  12. High-level feature extraction using SVM with walk-based graph kernel

    Microsoft Academic Search

    Jean-Philippe Vert; Tomoko Matsui; Shin'ichi Satoh; Yuji Uchiyama

    2009-01-01

    We investigate a method using support vector machines (SVMs) with walk-based graph kernels for high-level feature extraction from images. In this method, each image is first segmented into a finite set of homogeneous segments and then represented as a segmentation graph where each vertex is a segment and edges connect adjacent segments. Given a set of features associated with each

  13. Amyloid Features and Neuronal Toxicity of Mature Prion Fibrils Are Highly Sensitive to High Pressure*

    PubMed Central

    El Moustaine, Driss; Perrier, Veronique; Van Ba, Isabelle Acquatella-Tran; Meersman, Filip; Ostapchenko, Valeriy G.; Baskakov, Ilia V.; Lange, Reinhard; Torrent, Joan

    2011-01-01

    Prion proteins (PrP) can aggregate into toxic and possibly infectious amyloid fibrils. This particular macrostructure confers on them an extreme and still unexplained stability. To provide mechanistic insights into this self-assembly process, we used high pressure as a thermodynamic tool for perturbing the structure of mature amyloid fibrils that were prepared from recombinant full-length mouse PrP. Application of high pressure led to irreversible loss of several specific amyloid features, such as thioflavin T and 8-anilino-1-naphthalene sulfonate binding, alteration of the characteristic proteinase K digestion pattern, and a significant decrease in the ?-sheet structure and cytotoxicity of amyloid fibrils. Partial disaggregation of the mature fibrils into monomeric soluble PrP was observed. The remaining amyloid fibrils underwent a change in secondary structure that led to morphologically different fibrils composed of a reduced number of proto-filaments. The kinetics of these reactions was studied by recording the pressure-induced dissociation of thioflavin T from the amyloid fibrils. Analysis of the pressure and temperature dependence of the relaxation rates revealed partly unstructured and hydrated kinetic transition states and highlighted the importance of collapsing and hydrating inter- and intramolecular cavities to overcome the high free energy barrier that stabilizes amyloid fibrils. PMID:21357423

  14. HOTEL AMENITIES AND FEATURES INCLUDE: Free wired and wireless high-speed Internet access

    E-print Network

    Taylor, Jerry

    HOTEL AMENITIES AND FEATURES INCLUDE: · Free wired and wireless high-speed Internet access · Free · Free 5:30 Kickback® Free Long Distance Phone Calls · Free Wireless Internet 2-Room Suites Available

  15. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells

    PubMed Central

    Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J

    2014-01-01

    Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC. Ablation of MELK selectively impairs proliferation of basal-like, but not luminal breast cancer cells both in vitro and in vivo. Mechanistically, depletion of MELK in BBC cells induces caspase-dependent cell death, preceded by defective mitosis. Finally, we find that Melk is not required for mouse development and physiology. Together, these data indicate that MELK is a normally non-essential kinase, but is critical for BBC and thus represents a promising selective therapeutic target for the most aggressive subtype of breast cancer. DOI: http://dx.doi.org/10.7554/eLife.01763.001 PMID:24844244

  16. Use of the high altitude Applications Technology Satellite (ATS-1) in identifying cloud features

    E-print Network

    Frazee, Donald William

    1968-01-01

    USE OF THE HIGH ALTITUDE APPLICATIONS TECHNOLOGY SATELLITE (ATS-I) IN IDENTIFYING CLOUD FEATURES A Thesis by DONAID WILL Jinni FRA"EE Major, USAI" Submitted to the Graduate College or the Texas ASM University in partial fulfillment... of the requi. rements for the degree of MASTER OF SCIENCE May 1968 Mn, jor Subject Meteorology USE OF THE HIGH ALTITUDE APPLICATIONS TECHNOLOGY SATELLITE (ATS-1) IN IDENTIFYING CLOUD FEATURES A Thesis by DONALD WILLIAM FRAZEE Major, USAF Approved...

  17. Induction of mitotic aneuploidy in lower eukaryotes

    SciTech Connect

    Kappas, A. [National Research Center Democritus, Athens (Greece)

    1993-12-31

    Genetic tests for induction of mitotic aneuploidy in lower eukarotes used mainly the fungal systems of Aspergillus nidulans and Saccharomyces cerevisiae. There are several differences between the two systems such as the greater tolerance for aneuploidy and the fertility of triploids in S. cerevisiae, the stability of diploids and the selective advantage of haploids over diploids in Aspergillus and the mycelial growth of Aspergillus. On the other hand several similarities also exist between the two systems such as the general instability and varying growth rate of disomics and the random loss of extra chromosomes which produces more competitive types or the most frequent recovery of certain specific aneuploids. In using lower eukaryotes as test systems for the identification of aneugens several points should be considered which concern the relevance of such systems to higher organisms, the ability to identify primary aneuploidy and distinguish this from events, such as chromosomal breaks, which lead to secondary aneuploidy and the ability to obtain repeatable results. Within the framework of an EEC comparative study for evaluating assays for aneuploidy, a number of chemicals were assayed in A. nidulans for mitotic instability due to malsegregation of chromosomes at cell division.

  18. Mitotic Spindle Motors J. M. Scholey and A. Mogilner

    E-print Network

    Mogilner, Alex

    14 Mitotic Spindle Motors J. M. Scholey and A. Mogilner 14.1 Microtubules, Motors and Mitosis Mitosis, the process by which identical copies of the replicated genome are distrib- uted to the daughter of chromosomes and the positioning of spindle poles throughout mitosis depend upon mitotic motors, proteins

  19. The Mitotic Spindle: A Self-Made Machine

    NSDL National Science Digital Library

    E. Karsenti (EMBL; Cell Biology and Biophysics Program)

    2001-10-19

    The mitotic spindle is a highly dynamic molecular machine composed of tubulin, motors, and other molecules. It assembles around the chromosomes and distributes the duplicated genome to the daughter cells during mitosis. The biochemical and physical principles that govern the assembly of this machine are still unclear. However, accumulated discoveries indicate that chromosomes play a key role. Apparently, they generate a local cytoplasmic state that supports the nucleation and growth of microtubules. Then soluble and chromosome-associated molecular motors sort them into a bipolar array. The emerging picture is that spindle assembly is governed by a combination of modular principles and that their relative contribution may vary in different cell types and in various organisms.

  20. The flavonoid eupatorin inactivates the mitotic checkpoint leading to polyploidy and apoptosis

    SciTech Connect

    Salmela, Anna-Leena [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland) [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Turku Graduate School of Biomedical Sciences, Turku (Finland); Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Pouwels, Jeroen; Kukkonen-Macchi, Anu [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland)] [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Waris, Sinikka; Toivonen, Pauliina [Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland)] [Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Jaakkola, Kimmo [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland)] [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Maeki-Jouppila, Jenni [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland) [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Drug Discovery Graduate School, University of Turku (Finland); Kallio, Lila, E-mail: lila.kallio@vtt.fi [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland)] [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Kallio, Marko J. [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland) [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Centre of Excellence for Translational Genome-Scale Biology, P.O. Box 106, Academy of Finland (Finland)

    2012-03-10

    The spindle assembly checkpoint (SAC) is a conserved mechanism that ensures the fidelity of chromosome distribution in mitosis by preventing anaphase onset until the correct bipolar microtubule-kinetochore attachments are formed. Errors in SAC function may contribute to tumorigenesis by inducing numerical chromosome anomalies (aneuploidy). On the other hand, total disruption of SAC can lead to massive genomic imbalance followed by cell death, a phenomena that has therapeutic potency. We performed a cell-based high-throughput screen with a compound library of 2000 bioactives for novel SAC inhibitors and discovered a plant-derived phenolic compound eupatorin (3 Prime ,5-dihydroxy-4 Prime ,6,7-trimethoxyflavone) as an anti-mitotic flavonoid. The premature override of the microtubule drug-imposed mitotic arrest by eupatorin is dependent on microtubule-kinetochore attachments but not interkinetochore tension. Aurora B kinase activity, which is essential for maintenance of normal SAC signaling, is diminished by eupatorin in cells and in vitro providing a mechanistic explanation for the observed forced mitotic exit. Eupatorin likely has additional targets since eupatorin treatment of pre-mitotic cells causes spindle anomalies triggering a transient M phase delay followed by impaired cytokinesis and polyploidy. Finally, eupatorin potently induces apoptosis in multiple cancer cell lines and suppresses cancer cell proliferation in organotypic 3D cell culture model.

  1. A new role for Rab GTPases during early mitotic stages.

    PubMed

    Das, Sanchaita; Hehnly, Heidi; Doxsey, Stephen

    2014-01-01

    A recent study revealed new roles for the Rab11 GTPase during mitosis. Rab11 is involved in recycling endosome localization to mitotic spindle poles via dynein-mediated transport. This process is in contrast to Golgi membranes, which disperse in mitosis and do not appear to directly contribute to mitotic functions. Rab11-depletion prevents recycling endosome organization at spindle poles, delays mitotic progression, and disrupts spindle pole protein recruitment, astral microtubule organization, and mitotic spindle orientation. However, Rab11 is not the only endocytic and/or trafficking protein that regulates mitotic progression. Clathrin and two small GTPases (Rab6A', Rab5) play key roles in spindle organization and function. In this commentary, we discuss the roles of all these canonical endocytic and membrane trafficking proteins during mitosis and speculate on possible cross-communication between them and their molecular pathways that ensure faithful progression through mitosis. PMID:24921241

  2. Random mitotic activities across human embryonic stem cell colonies.

    SciTech Connect

    Jin, Q.; Duggan, R.; Dasa, S.; Li, F.; Chen, L. (Biosciences Division)

    2010-08-01

    A systemic and quantitative study was performed to examine whether different levels of mitotic activities, assessed by the percentage of S-phase cells at any given time point, existed at different physical regions of human embryonic stem (hES) cell colonies at 2, 4, 6 days after cell passaging. Mitotically active cells were identified by the positive incorporation of 5-bromo-2-deoxyuridine (BrdU) within their newly synthesized DNA. Our data indicated that mitotically active cells were often distributed as clusters randomly across the colonies within the examined growth period, presumably resulting from local deposition of newly divided cells. This latter notion was further demonstrated by the confined growth of enhanced green florescence protein (EGFP) expressing cells amongst non-GFP expressing cells. Furthermore, the overall percentage of mitotically active cells remained constantly at about 50% throughout the 6-day culture period, indicating mitotic activities of hES cell cultures were time-independent under current growth conditions.

  3. Rohitukine inhibits in vitro adipogenesis arresting mitotic clonal expansion and improves dyslipidemia in vivo.

    PubMed

    Varshney, Salil; Shankar, Kripa; Beg, Muheeb; Balaramnavar, Vishal M; Mishra, Sunil Kumar; Jagdale, Pankaj; Srivastava, Shishir; Chhonker, Yashpal S; Lakshmi, Vijai; Chaudhari, Bhushan P; Bhatta, Rabi Shankar; Saxena, Anil Kumar; Gaikwad, Anil Nilkanth

    2014-03-19

    We developed a common feature pharmacophore model using known antiadipogenic compounds (CFPMA). We identified rohitukine, a reported chromone anticancer alkaloid as a potential hit through in silico mapping of the in-house natural product library on CFPMA. Studies were designed to assess the antiadipogenic potential of rohitukine. Rohitukine was isolated from Dysoxylum binacteriferum Hook. to ?95% purity. As predicted by CFPMA, rohitukine was indeed found to be an antiadipogenic molecule. Rohitukine inhibited lipid accumulation and adipogenic differentiation in a concentration- and exposure-time-dependent manner in 3T3-L1 and C3H10T1/2 cells. Rohitukine downregulated expression of PPAR?, CCAAT/enhancer binding protein ?, adipocyte protein 2 (aP2), FAS, and glucose transporter 4. It also suppressed mRNA expression of LPL, sterol-regulatory element binding protein (SREBP) 1c, FAS, and aP2, the downstream targets of PPAR?. Rohitukine arrests cells in S phase during mitotic clonal expansion. Rohitukine was bioavailable, and 25.7% of orally administered compound reached systemic circulation. We evaluated the effect of rohitukine on dyslipidemia induced by high-fat diet in the hamster model. Rohitukine increased hepatic expression of liver X receptor ? and decreased expression of SREBP-2 and associated targets. Rohitukine decreased hepatic and gonadal lipid accumulation and ameliorated dyslipidemia significantly. In summary, our strategy to identify a novel antiadipogenic molecule using CFPMA successfully resulted in identification of rohitukine, which confirmed antiadipogenic activity and also exhibited in vivo antidyslipidemic activity. PMID:24646949

  4. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade.

    PubMed

    Purrington, Kristen S; Slettedahl, Seth; Bolla, Manjeet K; Michailidou, Kyriaki; Czene, Kamila; Nevanlinna, Heli; Bojesen, Stig E; Andrulis, Irene L; Cox, Angela; Hall, Per; Carpenter, Jane; Yannoukakos, Drakoulis; Haiman, Christopher A; Fasching, Peter A; Mannermaa, Arto; Winqvist, Robert; Brenner, Hermann; Lindblom, Annika; Chenevix-Trench, Georgia; Benitez, Javier; Swerdlow, Anthony; Kristensen, Vessela; Guénel, Pascal; Meindl, Alfons; Darabi, Hatef; Eriksson, Mikael; Fagerholm, Rainer; Aittomäki, Kristiina; Blomqvist, Carl; Nordestgaard, Břrge G; Nielsen, Sune F; Flyger, Henrik; Wang, Xianshu; Olswold, Curtis; Olson, Janet E; Mulligan, Anna Marie; Knight, Julia A; Tchatchou, Sandrine; Reed, Malcolm W R; Cross, Simon S; Liu, Jianjun; Li, Jingmei; Humphreys, Keith; Clarke, Christine; Scott, Rodney; Fostira, Florentia; Fountzilas, George; Konstantopoulou, Irene; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Ekici, Arif B; Hartmann, Arndt; Beckmann, Matthias W; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Jukkola-Vuorinen, Arja; Pylkäs, Katri; Kauppila, Saila; Dieffenbach, Aida Karina; Stegmaier, Christa; Arndt, Volker; Margolin, Sara; Balleine, Rosemary; Arias Perez, Jose Ignacio; Pilar Zamora, M; Menéndez, Primitiva; Ashworth, Alan; Jones, Michael; Orr, Nick; Arveux, Patrick; Kerbrat, Pierre; Truong, Thérčse; Bugert, Peter; Toland, Amanda E; Ambrosone, Christine B; Labrčche, France; Goldberg, Mark S; Dumont, Martine; Ziogas, Argyrios; Lee, Eunjung; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Ficarazzi, Filomena; Barile, Monica; Peterlongo, Paolo; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Tollenaar, Robert A E M; Seynaeve, Caroline; Brüning, Thomas; Ko, Yon-Dschun; Van Deurzen, Carolien H M; Martens, John W M; Kriege, Mieke; Figueroa, Jonine D; Chanock, Stephen J; Lissowska, Jolanta; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Schneeweiss, Andreas; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Mclean, Catriona; Milne, Roger L; Baglietto, Laura; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Van'T Veer, Laura J; Cornelissen, Sten; Försti, Asta; Torres, Diana; Rüdiger, Thomas; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Weltens, Caroline; Floris, Giuseppe; Moisse, Matthieu; Dennis, Joe; Wang, Qin; Dunning, Alison M; Shah, Mitul; Brown, Judith; Simard, Jacques; Anton-Culver, Hoda; Neuhausen, Susan L; Hopper, John L; Bogdanova, Natalia; Dörk, Thilo; Zheng, Wei; Radice, Paolo; Jakubowska, Anna; Lubinski, Jan; Devillee, Peter; Brauch, Hiltrud; Hooning, Maartje; García-Closas, Montserrat; Sawyer, Elinor; Burwinkel, Barbara; Marmee, Frederick; Eccles, Diana M; Giles, Graham G; Peto, Julian; Schmidt, Marjanka; Broeks, Annegien; Hamann, Ute; Chang-Claude, Jenny; Lambrechts, Diether; Pharoah, Paul D P; Easton, Douglas; Pankratz, V Shane; Slager, Susan; Vachon, Celine M; Couch, Fergus J

    2014-11-15

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer. PMID:24927736

  5. NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Localizes to the Mitotic Spindle in Human Cells

    PubMed Central

    Siegel, David; Kepa, Jadwiga K.; Ross, David

    2012-01-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) is an FAD containing quinone reductase that catalyzes the 2-electron reduction of a broad range of quinones. The 2-electron reduction of quinones to hydroquinones by NQO1 is believed to be a detoxification process since this reaction bypasses the formation of the highly reactive semiquinone. NQO1 is expressed at high levels in normal epithelium, endothelium and adipocytes as well as in many human solid tumors. In addition to its function as a quinone reductase NQO1 has been shown to reduce superoxide and regulate the 20 S proteasomal degradation of proteins including p53. Biochemical studies have indicated that NQO1 is primarily located in the cytosol, however, lower levels of NQO1 have also been found in the nucleus. In these studies we demonstrate using immunocytochemistry and confocal imaging that NQO1 was found associated with mitotic spindles in cells undergoing division. The association of NQO1 with the mitotic spindles was observed in many different human cell lines including nontransformed cells (astrocytes, HUVEC) immortalized cell lines (HBMEC, 16HBE) and cancer (pancreatic adenocarcinoma, BXPC3). Confocal analysis of double-labeling experiments demonstrated co-localization of NQO1with alpha-tubulin in mitotic spindles. In studies with BxPc-3 human pancreatic cancer cells the association of NQO1 with mitotic spindles appeared to be unchanged in the presence of NQO1 inhibitors ES936 or dicoumarol suggesting that NQO1 can associate with the mitotic spindle and still retain catalytic activity. Analysis of archival human squamous lung carcinoma tissue immunostained for NQO1 demonstrated positive staining for NQO1 in the spindles of mitotic cells. The purpose of this study is to demonstrate for the first time the association of the quinone reductase NQO1 with the mitotic spindle in human cells. PMID:22984577

  6. Change detection in high resolution SAR images based on multiscale texture features

    NASA Astrophysics Data System (ADS)

    Wen, Caihuan; Gao, Ziqiang

    2011-12-01

    This paper studied on change detection algorithm of high resolution (HR) Synthetic Aperture Radar (SAR) images based on multi-scale texture features. Firstly, preprocessed multi-temporal Terra-SAR images were decomposed by 2-D dual tree complex wavelet transform (DT-CWT), and multi-scale texture features were extracted from those images. Then, log-ratio operation was utilized to get difference images, and the Bayes minimum error theory was used to extract change information from difference images. Lastly, precision assessment was done. Meanwhile, we compared with the result of method based on texture features extracted from gray-level cooccurrence matrix (GLCM). We had a conclusion that, change detection algorithm based on multi-scale texture features has a great more improvement, which proves an effective method to change detect of high spatial resolution SAR images.

  7. An unsupervised feature extraction method for high dimensional image data compaction

    NASA Technical Reports Server (NTRS)

    Ghassemian, Hassan; Landgrebe, David

    1987-01-01

    A new on-line unsupervised feature extraction method for high-dimensional remotely sensed image data compaction is presented. This method can be utilized to solve the problem of data redundancy in scene representation by satellite-borne high resolution multispectral sensors. The algorithm first partitions the observation space into an exhaustive set of disjoint objects. Then, pixels that belong to an object are characterized by an object feature. Finally, the set of object features is used for data transmission and classification. The example results show that the performance with the compacted features provides a slight improvement in classification accuracy instead of any degradation. Also, the information extraction method does not need to be preceded by a data decompaction.

  8. High-Level Intuitive Features (HLIFs) for Intuitive Skin Lesion Description.

    PubMed

    Amelard, Robert; Glaister, Jeffrey; Wong, Alexander; Clausi, David A

    2015-03-01

    A set of high-level intuitive features (HLIFs) is proposed to quantitatively describe melanoma in standard camera images. Melanoma is the deadliest form of skin cancer. With rising incidence rates and subjectivity in current clinical detection methods, there is a need for melanoma decision support systems. Feature extraction is a critical step in melanoma decision support systems. Existing feature sets for analyzing standard camera images are comprised of low-level features, which exist in high-dimensional feature spaces and limit the system's ability to convey intuitive diagnostic rationale. The proposed HLIFs were designed to model the ABCD criteria commonly used by dermatologists such that each HLIF represents a human-observable characteristic. As such, intuitive diagnostic rationale can be conveyed to the user. Experimental results show that concatenating the proposed HLIFs with a full low-level feature set increased classification accuracy, and that HLIFs were able to separate the data better than low-level features with statistical significance. An example of a graphical interface for providing intuitive rationale is given. PMID:25361498

  9. Feature of high flux engineering test reactor and its role in nuclear power development

    Microsoft Academic Search

    Guangquan

    1988-01-01

    The High Flux Engineering Test Reactor (HFETR) designed and built by China own efforts reached to its initial criticality on Dec. 27, 1979, and then achieved high power operation on Dec. 16, 1980. Until Nov. 11, 1986, the reactor had been operated for thirteen cycles. The paper presents briefly main feature of HFETR and its utilization during past years. The

  10. Mitotic centromere-associated kinesin (MCAK): a potential cancer drug target

    PubMed Central

    Sanhaji, Mourad; Friel, Claire T.; Wordeman, Linda; Louwen, Frank; Yuan, Juping

    2011-01-01

    The inability to faithfully segregate chromosomes in mitosis results in chromosome instability, a hallmark of solid tumors. Disruption of microtubule dynamics contributes highly to mitotic chromosome instability. The kinesin-13 family is critical in the regulation of microtubule dynamics and the best characterized member of the family, the mitotic centromere-associated kinesin (MCAK), has recently been attracting enormous attention. MCAK regulates microtubule dynamics as a potent depolymerizer of microtubules by removing tubulin subunits from the polymer end. This depolymerizing activity plays pivotal roles in spindle formation, in correcting erroneous attachments of microtubule-kinetochore and in chromosome movement. Thus, the accurate regulation of MCAK is important for ensuring the faithful segregation of chromosomes in mitosis and for safeguarding chromosome stability. In this review we summarize recent data concerning the regulation of MCAK by mitotic kinases, Aurora A/B, Polo-like kinase 1 and cyclin-dependent kinase 1. We propose a molecular model of the regulation of MCAK by these mitotic kinases and relevant phosphatases throughout mitosis. An ever-increasing quantity of data indicates that MCAK is aberrantly regulated in cancer cells. This deregulation is linked to increased malignance, invasiveness, metastasis and drug resistance, most probably due to increased chromosomal instability and remodeling of the microtubule cytoskeleton in cancer cells. Most interestingly, recent observations suggest that MCAK could be a novel molecular target for cancer therapy, as a new cancer antigen or as a mitotic regulator. This collection of new data indicates that MCAK could be a new star in the cancer research sky due to its critical roles in the control of genome stability and the cytoskeleton. Further investigations are required to dissect the fine details of the regulation of MCAK throughout mitosis and its involvements in oncogenesis. PMID:22249213

  11. Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma.

    PubMed

    Duregon, Eleonora; Molinaro, Luca; Volante, Marco; Ventura, Laura; Righi, Luisella; Bolla, Stefania; Terzolo, Massimo; Sapino, Anna; Papotti, Mauro G

    2014-09-01

    Mitotic count on hematoxylin and eosin slides is a fundamental morphological criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring system employed. Moreover, it is the unique term strongly associated with patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was already proven to facilitate mitotic count in melanoma and other tumors. Therefore, a study was designed to assess the diagnostic and prognostic role of phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and computerized count to standard manual hematoxylin- and eosin-based method and Ki-67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were highly correlated (r=0.9077, P<0.0001), better than computer-assisted phospho-histone H3 evaluations, and had an excellent inter-observer reproducibility at Bland-Altman analysis. Three of 15 cases having <5 mitotic figures per 50 high-power fields by standard count on hematoxylin and eosin gained the mitotic figure point of Weiss Score after a manual count on phospho-histone H3 slides. Traditional mitotic count confirmed to be a strong predictor of overall survival (P=0.0043), better than phospho-histone H3-based evaluation (P=0.051), but not as strong as the Ki-67 index (P<0.0001). The latter further segregated adrenocortical carcinomas into three prognostic groups, stratifying cases by low (<20%), intermediate (20-50%), and high (>50%) Ki-67 values. We conclude that (a) phospho-histone H3 staining is a useful diagnostic complementary tool to standard hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation (including atypical mitotic figures) even in adrenocortical carcinomas with a low mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the best prognostic indicator of overall survival, being superior to the mitotic index, irrespective of the method (standard on hematoxylin and eosin or phospho-histone H3-based) used to count mitotic figures. PMID:24434900

  12. Force and Length in the Mitotic Spindle

    PubMed Central

    Dumont, Sophie; Mitchison, Timothy J.

    2009-01-01

    The mitotic spindle assembles to a steady-state length at metaphase through the integrated action of molecular mechanisms that generate and respond to mechanical forces. While molecular mechanisms that produce force have been described, our understanding of how they integrate with each other, and with the assembly-disassembly mechanisms that regulate length, is poor. We review current understanding of the basic architecture and dynamics of the metaphase spindle, and some of the elementary force producing mechanisms. We then discuss models for force integration, and spindle length determination. We also emphasize key missing data that notably includes absolute values of forces, and how they vary as a function of position, within the spindle. PMID:19906577

  13. Touching from a distance: Evolution of interplay between the nuclear pore complex, nuclear basket, and the mitotic spindle.

    PubMed

    Holden, Jennifer M; Koreny, Ludek; Kelly, Steven; Chait, Brian T; Rout, Michael P; Field, Mark C; Obado, Samson O

    2014-07-31

    The nuclear pore complex (NPC) is the sole mediator of bidirectional nucleo-cytoplasmic transport and is also an important scaffold for chromatin organization and transcriptional regulation. Proteomic studies of numerous diverse eukaryotic species initially characterized the NPC as built with a number of remarkably similar structural features, suggesting its status as an ancient and conserved eukaryotic cell component. However, further detailed analyses now suggest that several key specific NPC features have a more convoluted evolutionary history than initially assumed. Recently we reported on TbNup92, a component in trypanosomes of one such conserved structural feature, a basket-like structure on the nuclear face of the NPC. We showed that TbNup92 has similar roles to nuclear basket proteins from yeasts and animals (Mlp and Tpr, respectively) in interacting with both the NPC and the mitotic spindle. However, comparative genomics suggests that TbNup92 and Mlp/Tpr may be products of distinct evolutionary histories, raising the possibility that these gene products are analogs rather than direct orthologs. Taken together with recent evidence for divergence in the nuclear lamina and kinetochores, it is apparent that the trypanosome nucleus functions by employing several novel or highly divergent protein complexes in parallel with conserved elements. These findings have major implications for how the trypanosomatid nucleus operates and the evolution of hierarchical nuclear organization. PMID:25079062

  14. Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus

    SciTech Connect

    Yang, Feng; Camp, David G.; Gritsenko, Marina A.; Luo, Quanzhou; Kelly, Ryan T.; Clauss, Therese RW; Brinkley, William R.; Smith, Richard D.; Stenoien, David L.

    2007-11-16

    The chromosomal passenger complex (CPC) is a critical regulator of chromosome, cytoskeleton and membrane dynamics during mitosis. Here, we identified phosphopeptides and phosphoprotein complexes recognized by a phosphorylation specific antibody that labels the CPC using liquid chromatography coupled to mass spectrometry. A mitotic phosphorylation motif (PX{G/T/S}{L/M}[pS]P or WGL[pS]P) was identified in 11 proteins including Fzr/Cdh1 and RIC-8, two proteins with potential links to the CPC. Phosphoprotein complexes contained known CPC components INCENP, Aurora-B and TD-60, as well as SMAD2, 14-3-3 proteins, PP2A, and Cdk1, a likely kinase for this motif. Protein sequence analysis identified phosphorylation motifs in additional proteins including SMAD2, Plk3 and INCENP. Mitotic SMAD2 and Plk3 phosphorylation was confirmed using phosphorylation specific antibodies, and in the case of Plk3, phosphorylation correlates with its localization to the mitotic apparatus. A mutagenesis approach was used to show INCENP phosphorylation is required for midbody localization. These results provide evidence for a shared phosphorylation event that regulates localization of critical proteins during mitosis.

  15. Arsenic Trioxide Suppresses Paclitaxel-Induced Mitotic Arrest

    PubMed Central

    Duan, Qing; Komissarova, Elena; Dai, Wei

    2014-01-01

    To human health, arsenic exhibits the property of a double-edged sword. Arsenic compounds such as As2O3 is effective for the treatment of relapsed/refractory acute promyelocytic leukemia, whereas chronic exposure to environmental arsenic is associated with the development of a variety of common cancers. Because As2O3 is capable of inhibiting tubulin polymerization and inducing mitotic arrest, we examined whether there existed any functional interaction between As2O3 and paclitaxel, a well-known microtubule poison. Flow cytometry and fluorescence microscopy revealed that although As2O3 alone caused a moderate level of mitotic arrest, it greatly attenuated paclitaxel-induced mitotic arrest in cells with p53 deficiency. Western blot analysis showed that As2O3 significantly blocked phosphorylation of BubR1, Cdc20, and Cdc27 in cells treated with paclitaxel, suggesting that arsenic compromised the activation of the spindle checkpoint. Our further studies revealed that the attenuation of paclitaxel-induced mitotic arrest by As2O3 resulted primarily from sluggish cell cycle progression at S phase but not enhanced mitotic exit. The clinical efficacy of taxol is associated with its ability to induce mitotic arrest and subsequent mitotic catastrophe. Our observations that As2O3 has a negative impact on the cell cycle checkpoint activation by taxol should have significant clinical implications. PMID:19397590

  16. A High Precision Feature Based on LBP and Gabor Theory for Face Recognition

    PubMed Central

    Xia, Wei; Yin, Shouyi; Ouyang, Peng

    2013-01-01

    How to describe an image accurately with the most useful information but at the same time the least useless information is a basic problem in the recognition field. In this paper, a novel and high precision feature called BG2D2LRP is proposed, accompanied with a corresponding face recognition system. The feature contains both static texture differences and dynamic contour trends. It is based on Gabor and LBP theory, operated by various kinds of transformations such as block, second derivative, direct orientation, layer and finally fusion in a particular way. Seven well-known face databases such as FRGC, AR, FERET and so on are used to evaluate the veracity and robustness of the proposed feature. A maximum improvement of 29.41% is achieved comparing with other methods. Besides, the ROC curve provides a satisfactory figure. Those experimental results strongly demonstrate the feasibility and superiority of the new feature and method. PMID:23552103

  17. Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

    SciTech Connect

    Komura, Jun-ichiro, E-mail: junkom@med.tohoku.ac.jp [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)] [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Ikehata, Hironobu [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)] [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Mori, Toshio [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan)] [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan); Ono, Tetsuya [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)] [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)

    2012-03-10

    During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: Black-Right-Pointing-Pointer Global genome repair of (6-4) photoproducts is fully active in mitotic cells. Black-Right-Pointing-Pointer DNA in condensed mitotic chromatin does not seem inaccessible or inert. Black-Right-Pointing-Pointer Mitotic transcriptional repression may impair transcription-coupled repair.

  18. Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential.

    PubMed

    Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Hara, Kieko; Suehara, Yoshiyuki; Takagi, Tatsuya; Mitani, Keiko; Kaneko, Kazuo; Yao, Takashi; Saito, Tsuyoshi

    2015-03-01

    The impact of NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion on the biological behavior and the mechanism of acquisition of malignant phenotype in solitary fibrous tumor (SFT) is not well understood. We examined variations of the NAB2-STAT6 fusion gene in 40 cases of SFT using formalin-fixed, paraffin-embedded tissues and secondary genetic alterations of tumor protein p53 (TP53),, platelet-derived growth factor receptor, ? polypeptide (PDGFRB), and telomerase reverse transcriptase (TERT) promoters. These gene variations were compared with the clinicopathological features. The 2-year and 5-year disease-free survival rates (DFSRs) were 91% and 83%, respectively. All 40 samples demonstrated nuclear staining for STAT6, including CD34-negative cases. Moreover, p53-positive staining was associated with a lower DFSR and was significantly associated with higher Ki-67 label index, higher mitotic rate (mitosis, >4/high-power field), and the presence of nuclear atypia/pleomorphism. NAB2-STAT6 fusions were detected in all of the cases; the NAB2 exon 4-STAT6 exon 2, the most common genotype, appeared in 18 cases, which was associated with thoracic tumor location and the less aggressive phenotype. In contrast, tumors with NAB2 exon 6-STAT6 exon 16/18 demonstrated an aggressive phenotype. Mutations in TP53 and PDGFRB were detected in 2 and 3 cases respectively, and these occurred in a mutually exclusive fashion. TERT promoter hot spot mutations were observed in 5 cases, which were associated with shorter DFSR. Two dedifferentiated SFT cases harbored both TP53 and TERT promoter mutations. TP53 mutations, which result in its overexpression, in combination with TERT promoter mutations seem to play an important role in the dedifferentiation process. PMID:25582503

  19. Mitotic spindle assembly by two different pathways in vitro

    PubMed Central

    1991-01-01

    We have used Xenopus egg extracts to study spindle morphogenesis in a cell-free system and have identified two pathways of spindle assembly in vitro using methods of fluorescent analogue cytochemistry. When demembranated sperm nuclei are added to egg extracts arrested in a mitotic state, individual nuclei direct the assembly of polarized microtubule arrays, which we term half-spindles; half-spindles then fuse pairwise to form bipolar spindles. In contrast, when sperm nuclei are added to extracts that are induced to enter interphase and arrested in the following mitosis, a single sperm nucleus can direct the assembly of a complete spindle. We find that microtubule arrays in vitro are strongly biased towards chromatin, but this does not depend on specific kinetochore-microtubule interactions. Indeed, although we have identified morphological and probably functional kinetochores in spindles assembled in vitro, kinetochores appear not to play an obligate role in the establishment of stable, bipolar microtubule arrays in either assembly pathway. Features of the two pathways suggest that spindle assembly involves a hierarchy of selective microtubule stabilization, involving both chromatin-microtubule interactions and antiparallel microtubule-microtubule interactions, and that fundamental molecular interactions are probably the same in both pathways. This in vitro reconstitution system should be useful for identifying the molecules regulating the generation of asymmetric microtubule arrays and for understanding spindle morphogenesis in general. PMID:1999463

  20. Assessing Teaching Practicum Reflections: Distinguishing Discourse Features of the "High" and "Low" Grade Reports

    ERIC Educational Resources Information Center

    Luk, Jasmine

    2008-01-01

    Using reflective journals to promote learning has been a common practice in the teaching profession. How learners present reflections in what are judged to be high-quality reflective writing remains under-researched. This paper explores the discourse features of teaching practicum reflective reports written by six pre-service student teachers of…

  1. Assessing Motor Skills as a Differentiating Feature between High Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Cid, Maria R.

    2011-01-01

    The purpose of this research was to investigate if motor skills could be used as a differentiating feature between Asperger's Disorder (AD) and High Functioning (HFA) in children under the age of 9 years, 0 months, in order to provide additional information regarding the usefulness and validity of distinguishing these two disorders. There is…

  2. On-Chip Feature Extraction for Spike Sorting in High Density Implantable Neural Recording Systems

    E-print Network

    Mason, Andrew

    On-Chip Feature Extraction for Spike Sorting in High Density Implantable Neural Recording Systems of implantable signal processing systems that enable on-chip data reduction while maintaining necessary. A hardware friendly architecture, feasible for implantation, is also presented for detecting neural spikes

  3. Low and High-Level Visual Feature Based Apple Detection from Multi-modal Images

    E-print Network

    Wachs, Juan

    1 Low and High-Level Visual Feature Based Apple Detection from Multi-modal Images J. P. Wachs1 , H discusses the development of a machine vision system, capable of recognizing occluded green apples within a tree canopy. This involves the detection of "green" apples within scenes of "green leaves", shadow

  4. Why School Based Assessment Is Not a Universal Feature of High Stakes Assessment Systems?

    ERIC Educational Resources Information Center

    Lamprianou, Iasonas; Christie, Thomas

    2009-01-01

    Accepting that school based assessment may have the potential to bring additional reliability to the assessment outcomes of an educational system, this research uses Generalizability Theory to address the question "why school based assessment is not a universal feature of high stakes assessment systems"? Three major issues are identified: (a)…

  5. Correlating microstructural features and mechanical properties with abrasion resistance of a high strength low alloy steel

    Microsoft Academic Search

    A. K. Jha; B. K. Prasad; O. P. Modi; S. Das; A. H. Yegneswaran

    2003-01-01

    A study towards the examination of the abrasive wear behaviour and other characteristics, viz. microstructure, tensile properties and hardness of a high strength low alloy steel has been carried out in order to establish a correlation amongst the parameters and to optimize the microstructural features and mechanical properties for superior wear performance. The steel was subjected to various heat treatment

  6. High-accuracy real-time pedestrian detection system using 2D and 3D features

    NASA Astrophysics Data System (ADS)

    Chambers, David R.; Flannigan, Clay; Wheeler, Benjamin

    2012-06-01

    We present a real time stereo-vision pedestrian detector implementation with a very high accuracy, the 2D component of which attains 99% recall with less than 10-6 false positives per window on the INRIA persons dataset. We utilize a sequence of classifiers which use different features, beginning with Haar-like features and a Haar-like feature implementation adapted to disparity images, and performing a final verification with Histogram-of-Oriented Gradient (HOG) features. We present a 2D Haar-like feature implementation that utilizes 2x2 kernel filters at multiple scales rather than integral images, and combines a quickly trained preliminary adaBoost classifier with a more accurate SVM classifier. We also show how these Haar-like features may be computed from a partially incomplete stereo disparity image in order to make use of 3-dimensional data. Finally, we discuss how these features, along with the HOG features, are computed rapidly and how the classifiers are combined in such a way as to enable real-time implementation with higher detection rates and lower false positive rates than typical systems. Our overall detector is a practical combination of speed and detection performance, operating on 544x409 image (10,425 windows) at a frame rate of 10-20fps, depending on scene complexity. The detector's overall false positive rate is less than 10-6, corresponding to about one false positive every 10-60s when testing on our non-training data. Additionally, the detector has shown usefulness for detecting other object types, and has been implemented for traffic cones, telephone poles, and vehicles.

  7. Feature of high flux engineering test reactor and its role in nuclear power development

    SciTech Connect

    Guangquan, L.

    1988-01-01

    The High Flux Engineering Test Reactor (HFETR) designed and built by China own efforts reached to its initial criticality on Dec. 27, 1979, and then achieved high power operation on Dec. 16, 1980. Until Nov. 11, 1986, the reactor had been operated for thirteen cycles. The paper presents briefly main feature of HFETR and its utilization during past years. The paper also deals with its role in nuclear power development. Finally, author gives his opinion on comprehensive utilization of HFETR.

  8. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation

    Microsoft Academic Search

    Michael J. Hendzel; Yi Wei; Michael A. Mancini; Aaron Van Hooser; Tamara Ranalli; B. R. Brinkley; David P. Bazett-Jones; C. David Allis

    1997-01-01

    .   We have generated and characterized a novel site-specific antibody highly specific for the phosphorylated form of the amino-terminus\\u000a of histone H3 (Ser10). In this study, we used this antibody to examine in detail the relationship between H3 phosphorylation\\u000a and mitotic chromosome condensation in mammalian cells. Our results extend previous biochemical studies by demonstrating that\\u000a mitotic phosphorylation of H3 initiates

  9. The bipolar assembly domain of the mitotic motor kinesin-5

    PubMed Central

    Acar, Seyda; Carlson, David B.; Budamagunta, Madhu S.; Yarov-Yarovoy, Vladimir; Correia, John J.; Nińonuevo, Milady R.; Jia, Weitao; Tao, Li; Leary, Julie A.; Voss, John C.; Evans, James E.; Scholey, Jonathan M.

    2013-01-01

    An outstanding unresolved question is how does the mitotic spindle utilize microtubules and mitotic motors to coordinate accurate chromosome segregation during mitosis? This process depends upon the mitotic motor, kinesin-5, whose unique bipolar architecture, with pairs of motor domains lying at opposite ends of a central rod, allows it to crosslink microtubules within the mitotic spindle and to coordinate their relative sliding during spindle assembly, maintenance and elongation. The structural basis of kinesin-5’s bipolarity is, however, unknown, as protein asymmetry has so far precluded its crystallization. Here we use electron microscopy of single molecules of kinesin-5 and its subfragments, combined with hydrodynamic analysis plus mass spectrometry, circular dichroism and site-directed spin label electron paramagnetic resonance spectroscopy, to show how a staggered antiparallel coiled-coil ‘BASS’ (bipolar assembly) domain directs the assembly of four kinesin-5 polypeptides into bipolar minifilaments. PMID:23299893

  10. TOPK and PTEN participate in CHFR mediated mitotic checkpoint?

    PubMed Central

    Shinde, Swapnil R.; Gangula, Narmadha Reddy; Kavela, Sridhar; Pandey, Vimal; Maddika, Subbareddy

    2013-01-01

    Mitotic progression is regulated by co-ordinated action of several proteins and is crucial for the maintenance of genomic stability. CHFR (Check point protein with FHA and RING domains) is an E3 ubiquitin ligase and a checkpoint protein that regulates entry into mitosis. But the molecular players involved in CHFR mediated mitotic checkpoint are not completely understood. In this study, we identified TOPK/PBK, a serine/threonine kinase and PTEN, a lipid phosphatase to play an important role in CHFR mediated mitotic transitions. We demonstrated that CHFR ubiquitinates and regulates TOPK levels, which is essential for its checkpoint function. Moreover, TOPK phosphorylates and inactivates PTEN, which in turn activates Akt that leads to proper G2/M progression. Collectively, our results reveal TOPK and PTEN as new players in CHFR mediated mitotic checkpoint. PMID:24012691

  11. TOPK and PTEN participate in CHFR mediated mitotic checkpoint.

    PubMed

    Shinde, Swapnil R; Gangula, Narmadha Reddy; Kavela, Sridhar; Pandey, Vimal; Maddika, Subbareddy

    2013-12-01

    Mitotic progression is regulated by co-ordinated action of several proteins and is crucial for the maintenance of genomic stability. CHFR (Check point protein with FHA and RING domains) is an E3 ubiquitin ligase and a checkpoint protein that regulates entry into mitosis. But the molecular players involved in CHFR mediated mitotic checkpoint are not completely understood. In this study, we identified TOPK/PBK, a serine/threonine kinase and PTEN, a lipid phosphatase to play an important role in CHFR mediated mitotic transitions. We demonstrated that CHFR ubiquitinates and regulates TOPK levels, which is essential for its checkpoint function. Moreover, TOPK phosphorylates and inactivates PTEN, which in turn activates Akt that leads to proper G2/M progression. Collectively, our results reveal TOPK and PTEN as new players in CHFR mediated mitotic checkpoint. PMID:24012691

  12. Identification of novel regulators of mitotic exit in Saccharomyces cerevisiae

    E-print Network

    D'Aquino, Katharine E

    2006-01-01

    The division of a eukaryotic cell into two daughter cells is controlled by cyclin dependent kinase (CDK). Entry into mitosis is promoted by the activity of CDK complexed with mitotic cyclins. Upon faithful segregation of ...

  13. Control of the mitotic exit network during meiosis

    E-print Network

    Attner, Michelle Andrea

    The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to ...

  14. CDK control of mitotic progression in Saccharomyces cerevisiae

    E-print Network

    Rahal, Rami S

    2008-01-01

    Mitotic cyclin-dependent kinases (CDKs) are best known for their essential functions in triggering entry into M-phase, where they have established roles in nuclear envelope breakdown, chromosome condensation, and Golgi ...

  15. Aurora B Regulates MCAK at the Mitotic Centromere

    Microsoft Academic Search

    Paul D Andrews; Yulia Ovechkina; Nick Morrice; Michael Wagenbach; Karen Duncan; Linda Wordeman; Jason R Swedlow

    2004-01-01

    Chromosome orientation and alignment within the mitotic spindle requires the Aurora B protein kinase and the mitotic centromere-associated kinesin (MCAK). Here, we report the regulation of MCAK by Aurora B. Aurora B inhibited MCAK's microtubule depolymerizing activity in vitro, and phospho-mimic (S\\/E) mutants of MCAK inhibited depolymerization in vivo. Expression of either MCAK (S\\/E) or MCAK (S\\/A) mutants increased the

  16. Timeless links replication termination to mitotic kinase activation.

    PubMed

    Dheekollu, Jayaraju; Wiedmer, Andreas; Hayden, James; Speicher, David; Gotter, Anthony L; Yen, Tim; Lieberman, Paul M

    2011-01-01

    The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication. PMID:21573113

  17. Micromechanical-biochemical studies of mitotic chromosome elasticity and structure

    NASA Astrophysics Data System (ADS)

    Poirier, Michael Guy

    The structure of mitotic chromosomes was studied by combining micromechanical force measurements with microfluidic biochemical exposures. Our method is to use glass micropipettes attached to either end of a single chromosome to do mechanical experiments in the extracellular buffer. A third pipette can be used to locally 'spray' reactants so as to carry out dynamical mechanical-chemical experiments. The following elastic properties of mitotic chromosomes are found: Young's modulus, Y = 300 Pa; Poisson ratio, sigma = 0.1; Bending rigidity, B = 1 x 10 -22 J·m; Internal viscosity, eta' = 100 kg/m·sec; Volume fraction, ? = 0.7; Extensions of less than 3 times the relaxed length are linear and reversible; Extensions beyond 30 fold exhibit a force plateau at 15 nN and convert the chromosome to a disperse ghost-like state with little change in chromatin structure; Mitotic chromosomes are relatively isotropic; dsDNA cuts of at least every 3 kb cause the a mitotic chromosomes to fall apart; dsDNA cuts less frequently than every 50 kb do not affect mitotic chromosome structure. These results lead to the conclusion that mitotic chromosomes are a network crosslinked every 50 kb between which chromatin is fold by chromatin folding proteins, which are likely to be condensins.

  18. A PLANETARY LENSING FEATURE IN CAUSTIC-CROSSING HIGH-MAGNIFICATION MICROLENSING EVENTS

    SciTech Connect

    Chung, Sun-Ju; Hwang, Kyu-Ha; Ryu, Yoon-Hyun; Lee, Chung-Uk, E-mail: sjchung@kasi.re.kr, E-mail: kyuha@kasi.re.kr, E-mail: yhryu@kasi.re.kr, E-mail: leecu@kasi.re.kr [Korea Astronomy and Space Science Institute, Hwaam-Dong, Yuseong-Gu, Daejeon 305-348 (Korea, Republic of)

    2012-05-20

    Current microlensing follow-up observations focus on high-magnification events because of the high efficiency of planet detection. However, central perturbations of high-magnification events caused by a planet can also be produced by a very close or a very wide binary companion, and the two kinds of central perturbations are not generally distinguished without time consuming detailed modeling (a planet-binary degeneracy). Hence, it is important to resolve the planet-binary degeneracy that occurs in high-magnification events. In this paper, we investigate caustic-crossing high-magnification events caused by a planet and a wide binary companion. From this investigation, we find that because of the different magnification excess patterns inside the central caustics induced by the planet and the binary companion, the light curves of the caustic-crossing planetary-lensing events exhibit a feature that is discriminated from those of the caustic-crossing binary-lensing events, and the feature can be used to immediately distinguish between the planetary and binary companions. The planetary-lensing feature appears in the interpeak region between the two peaks of the caustic-crossings. The structure of the interpeak region for the planetary-lensing events is smooth and convex or boxy, whereas the structure for the binary-lensing events is smooth and concave. We also investigate the effect of a finite background source star on the planetary-lensing feature in the caustic-crossing high-magnification events. From this, we find that the convex-shaped interpeak structure appears in a certain range that changes with the mass ratio of the planet to the planet-hosting star.

  19. High-Velocity Features of Calcium and Silicon in the Spectra of Type Ia Supernovae

    E-print Network

    Silverman, Jeffrey M; Marion, G H; Wheeler, J Craig; Barna, Barnabas; Szalai, Tamas; Mulligan, Brian; Filippenko, Alexei V

    2015-01-01

    "High-velocity features" (HVFs) are spectral features in Type Ia supernovae (SNe Ia) that have minima indicating significantly higher (by greater than about 6000 km/s) velocities than typical "photospheric-velocity features" (PVFs). The PVFs are absorption features with minima indicating typical photospheric (i.e., bulk ejecta) velocities (usually ~9000-15,000 km/s near B-band maximum brightness). In this work we undertake the most in-depth study of HVFs ever performed. The dataset used herein consists of 445 low-resolution optical and near-infrared (NIR) spectra (at epochs up to 5 d past maximum brightness) of 210 low-redshift SNe Ia that follow the "Phillips relation." A series of Gaussian functions is fit to the data in order to characterise possible HVFs of Ca II H&K, Si II {\\lambda}6355, and the Ca II NIR triplet. The temporal evolution of the velocities and strengths of the PVFs and HVFs of these three spectral features is investigated, as are possible correlations with other SN Ia observables. We f...

  20. High-resolution face verification using pore-scale facial features.

    PubMed

    Li, Dong; Zhou, Huiling; Lam, Kin-Man

    2015-08-01

    Face recognition methods, which usually represent face images using holistic or local facial features, rely heavily on alignment. Their performances also suffer a severe degradation under variations in expressions or poses, especially when there is one gallery per subject only. With the easy access to high-resolution (HR) face images nowadays, some HR face databases have recently been developed. However, few studies have tackled the use of HR information for face recognition or verification. In this paper, we propose a pose-invariant face-verification method, which is robust to alignment errors, using the HR information based on pore-scale facial features. A new keypoint descriptor, namely, pore-Principal Component Analysis (PCA)-Scale Invariant Feature Transform (PPCASIFT)-adapted from PCA-SIFT-is devised for the extraction of a compact set of distinctive pore-scale facial features. Having matched the pore-scale features of two-face regions, an effective robust-fitting scheme is proposed for the face-verification task. Experiments show that, with one frontal-view gallery only per subject, our proposed method outperforms a number of standard verification methods, and can achieve excellent accuracy even the faces are under large variations in expression and pose. PMID:25781876

  1. Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos.

    PubMed

    McCoy, Rajiv C; Demko, Zachary; Ryan, Allison; Banjevic, Milena; Hill, Matthew; Sigurjonsson, Styrmir; Rabinowitz, Matthew; Fraser, Hunter B; Petrov, Dmitri A

    2015-04-10

    Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency. PMID:25859044

  2. Mechanism and Regulation of Kinesin-5, an essential motor for the mitotic spindle

    PubMed Central

    Waitzman, Joshua S.; Rice, Sarah E.

    2014-01-01

    Mitotic cell division is the most fundamental task of all living cells. Cells have intricate and tightly regulated machinery to ensure that mitosis occurs with appropriate frequency and high fidelity. A core element of this machinery is the kinesin-5 motor protein, which plays essential roles in spindle formation and maintenance. In this review, we discuss how the structural and mechanical properties of kinesin-5 motors uniquely suit them to their mitotic role. We describe some of the small molecule inhibitors and regulatory proteins that act on kinesin-5, and discuss how these regulators may influence the process of cell division. Finally, we touch on some more recently described functions of kinesin-5 motors in non-dividing cells. Throughout, we highlight a number of open questions that impede our understanding of both this motor's function and the potential utility of kinesin-5 inhibitors. PMID:24125467

  3. Airborne LIDAR and high resolution satellite data for rapid 3D feature extraction

    NASA Astrophysics Data System (ADS)

    Jawak, S. D.; Panditrao, S. N.; Luis, A. J.

    2014-11-01

    This work uses the canopy height model (CHM) based workflow for individual tree crown delineation and 3D feature extraction approach (Overwatch Geospatial's proprietary algorithm) for building feature delineation from high-density light detection and ranging (LiDAR) point cloud data in an urban environment and evaluates its accuracy by using very high-resolution panchromatic (PAN) (spatial) and 8-band (multispectral) WorldView-2 (WV-2) imagery. LiDAR point cloud data over San Francisco, California, USA, recorded in June 2010, was used to detect tree and building features by classifying point elevation values. The workflow employed includes resampling of LiDAR point cloud to generate a raster surface or digital terrain model (DTM), generation of a hill-shade image and an intensity image, extraction of digital surface model, generation of bare earth digital elevation model (DEM) and extraction of tree and building features. First, the optical WV-2 data and the LiDAR intensity image were co-registered using ground control points (GCPs). The WV-2 rational polynomial coefficients model (RPC) was executed in ERDAS Leica Photogrammetry Suite (LPS) using supplementary *.RPB file. In the second stage, ortho-rectification was carried out using ERDAS LPS by incorporating well-distributed GCPs. The root mean square error (RMSE) for the WV-2 was estimated to be 0.25 m by using more than 10 well-distributed GCPs. In the second stage, we generated the bare earth DEM from LiDAR point cloud data. In most of the cases, bare earth DEM does not represent true ground elevation. Hence, the model was edited to get the most accurate DEM/ DTM possible and normalized the LiDAR point cloud data based on DTM in order to reduce the effect of undulating terrain. We normalized the vegetation point cloud values by subtracting the ground points (DEM) from the LiDAR point cloud. A normalized digital surface model (nDSM) or CHM was calculated from the LiDAR data by subtracting the DEM from the DSM. The CHM or the normalized DSM represents the absolute height of all aboveground urban features relative to the ground. After normalization, the elevation value of a point indicates the height from the ground to the point. The above-ground points were used for tree feature and building footprint extraction. In individual tree extraction, first and last return point clouds were used along with the bare earth and building footprint models discussed above. In this study, scene dependent extraction criteria were employed to improve the 3D feature extraction process. LiDAR-based refining/ filtering techniques used for bare earth layer extraction were crucial for improving the subsequent 3D features (tree and building) feature extraction. The PAN-sharpened WV-2 image (with 0.5 m spatial resolution) was used to assess the accuracy of LiDAR-based 3D feature extraction. Our analysis provided an accuracy of 98 % for tree feature extraction and 96 % for building feature extraction from LiDAR data. This study could extract total of 15143 tree features using CHM method, out of which total of 14841 were visually interpreted on PAN-sharpened WV-2 image data. The extracted tree features included both shadowed (total 13830) and non-shadowed (total 1011). We note that CHM method could overestimate total of 302 tree features, which were not observed on the WV-2 image. One of the potential sources for tree feature overestimation was observed in case of those tree features which were adjacent to buildings. In case of building feature extraction, the algorithm could extract total of 6117 building features which were interpreted on WV-2 image, even capturing buildings under the trees (total 605) and buildings under shadow (total 112). Overestimation of tree and building features was observed to be limiting factor in 3D feature extraction process. This is due to the incorrect filtering of point cloud in these areas. One of the potential sources of overestimation was the man-made structures, including skyscrapers and bridges, which were confounded and extracted as buildings. This can be

  4. Mitotic-Chromosome-Based Physical Mapping of the Culex quinquefasciatus Genome.

    PubMed

    Naumenko, Anastasia N; Timoshevskiy, Vladimir A; Kinney, Nicholas A; Kokhanenko, Alina A; deBruyn, Becky S; Lovin, Diane D; Stegniy, Vladimir N; Severson, David W; Sharakhov, Igor V; Sharakhova, Maria V

    2015-01-01

    The genome assembly of southern house mosquito Cx. quinquefasciatus is represented by a high number of supercontigs with no order or orientation on the chromosomes. Although cytogenetic maps for the polytene chromosomes of this mosquito have been developed, their utilization for the genome mapping remains difficult because of the low number of high-quality spreads in chromosome preparations. Therefore, a simple and robust mitotic-chromosome-based approach for the genome mapping of Cx. quinquefasciatus still needs to be developed. In this study, we performed physical mapping of 37 genomic supercontigs using fluorescent in situ hybridization on mitotic chromosomes from imaginal discs of 4th instar larvae. The genetic linkage map nomenclature was adopted for the chromosome numbering based on the direct positioning of 58 markers that were previously genetically mapped. The smallest, largest, and intermediate chromosomes were numbered as 1, 2, and 3, respectively. For idiogram development, we analyzed and described in detail the morphology and proportions of the mitotic chromosomes. Chromosomes were subdivided into 19 divisions and 72 bands of four different intensities. These idiograms were used for mapping the genomic supercontigs/genetic markers. We also determined the presence of length polymorphism in the q arm of sex-determining chromosome 1 in Cx. quinquefasciatus related to the size of ribosomal locus. Our physical mapping and previous genetic linkage mapping resulted in the chromosomal assignment of 13% of the total genome assembly to the chromosome bands. We provided the first detailed description, nomenclature, and idiograms for the mitotic chromosomes of Cx. quinquefasciatus. Further application of the approach developed in this study will help to improve the quality of the southern house mosquito genome. PMID:25768920

  5. Mitotic-Chromosome-Based Physical Mapping of the Culex quinquefasciatus Genome

    PubMed Central

    Naumenko, Anastasia N.; Timoshevskiy, Vladimir A.; Kinney, Nicholas A.; Kokhanenko, Alina A.; deBruyn, Becky S.; Lovin, Diane D.; Stegniy, Vladimir N.; Severson, David W.; Sharakhov, Igor V.; Sharakhova, Maria V.

    2015-01-01

    The genome assembly of southern house mosquito Cx. quinquefasciatus is represented by a high number of supercontigs with no order or orientation on the chromosomes. Although cytogenetic maps for the polytene chromosomes of this mosquito have been developed, their utilization for the genome mapping remains difficult because of the low number of high-quality spreads in chromosome preparations. Therefore, a simple and robust mitotic-chromosome-based approach for the genome mapping of Cx. quinquefasciatus still needs to be developed. In this study, we performed physical mapping of 37 genomic supercontigs using fluorescent in situ hybridization on mitotic chromosomes from imaginal discs of 4th instar larvae. The genetic linkage map nomenclature was adopted for the chromosome numbering based on the direct positioning of 58 markers that were previously genetically mapped. The smallest, largest, and intermediate chromosomes were numbered as 1, 2, and 3, respectively. For idiogram development, we analyzed and described in detail the morphology and proportions of the mitotic chromosomes. Chromosomes were subdivided into 19 divisions and 72 bands of four different intensities. These idiograms were used for mapping the genomic supercontigs/genetic markers. We also determined the presence of length polymorphism in the q arm of sex-determining chromosome 1 in Cx. quinquefasciatus related to the size of ribosomal locus. Our physical mapping and previous genetic linkage mapping resulted in the chromosomal assignment of 13% of the total genome assembly to the chromosome bands. We provided the first detailed description, nomenclature, and idiograms for the mitotic chromosomes of Cx. quinquefasciatus. Further application of the approach developed in this study will help to improve the quality of the southern house mosquito genome. PMID:25768920

  6. Mitotic catastrophe and cell death induced by depletion of centrosomal proteins

    PubMed Central

    Kimura, M; Yoshioka, T; Saio, M; Banno, Y; Nagaoka, H; Okano, Y

    2013-01-01

    Mitotic catastrophe, which refers to cell death or its prologue triggered by aberrant mitosis, can be induced by a heterogeneous group of stimuli, including chromosome damage or perturbation of the mitotic apparatus. We investigated the mechanism of mitotic catastrophe and cell death induced by depletion of centrosomal proteins that perturbs microtubule organization. We transfected cells harboring wild-type or mutated p53 with siRNAs targeting Aurora A, ninein, TOG, TACC3, ?-tubulin, or pericentriolar material-1, and monitored the effects on cell death. Knockdown of Aurora A, ninein, TOG, and TACC3 led to cell death, regardless of p53 status. Knockdown of Aurora A, ninein, and TOG, led to aberrant spindle formation and subsequent cell death, which was accompanied by several features of apoptosis, including nuclear condensation and Annexin V binding in HeLa cells. During this process, cleavage of poly(ADP-ribose) polymerase-1, caspase-3, and caspase-9 was detected, but cleavage of caspase-8 was not. Cell death, monitored by time-lapse imaging, occurred during both interphase and M phase. In cells depleted of a centrosomal protein (Aurora A, ninein, or TOG), the rate of cell death was higher if the cells were cotransfected with siRNA against BubR1 or Mad2 than if they were transfected with siRNA against Bub1 or a control siRNA. These results suggest that metaphase arrest is necessary for the mitotic catastrophe and cell death caused by depletion of centrosomal proteins. Knockdown of centrosomal proteins led to increased phosphorylation of Chk2. Enhanced p-Chk2 localization was also observed at the centrosome in cells arrested in M phase, as well as in the nuclei of dying cells. Cotransfection of siRNAs against Chk2, in combination with depletion of a centrosomal protein, decreased the amount of cell death. Thus, Chk2 activity is indispensable for apoptosis after mitotic catastrophe induced by depletion of centrosomal proteins that perturbs microtubule organization. PMID:23598415

  7. The Rabbit system: Low cost, high reliability front end electronics featuring 16 bit dynamic range

    SciTech Connect

    Drake, G.; Droege, T.F.; Nelson, C.A. Jr.; Turner, K.J.; Ohska, T.K.

    1986-02-01

    A new crate-based front end system has been built which features low cost, compact packaging, command capability, 16 bit dynamic range digitization, and a high degree of redundancy. The crate can contain a variety of instrumentation modules, and is designed to be situated close to the detector. The system is suitable for readout of a large number of channels via parallel multiprocessor data acquisition. The Rabbit system is being used at the CDF.

  8. ESC observations of SN 2005cf. II. Optical spectroscopy and the high-velocity features

    Microsoft Academic Search

    G. Garavini; S. Nobili; S. Taubenberger; A. Pastorello; N. Elias-Rosa; V. Stanishev; G. Blanc; S. Benetti; A. Goobar; P. A. Mazzali; S. F. Sanchez; M. Salvo; B. P. Schmidt; W. Hillebrandt

    2007-01-01

    The ESC-RTN optical spectroscopy data set for SN 2005cf is presented and analyzed. The observations range from -11.6 and +77.3 days with respect to B-band maximum light. The evolution of the spectral energy distribution of SN 2005cf is characterized by the presence of high velocity Si II and Ca II features. SYNOW synthetic spectra are used to investigate the ejecta

  9. The Effect of High vs Low Density Barium Preparations on the Quantitative Features of Swallowing

    Microsoft Academic Search

    Wylie J. Dodds; Benson T. Massey; Mark K. Kern

    1989-01-01

    We compared the effect of high-density and low-density barium preparations on the quantitative features of swallowing. The two barium preparations differed primarily in density but also differed somewhat in viscosity. Concurrent videofluoroscopic and manometric studies were done in nine healthy control subjects. Videofluoroscopy was recorded in the lateral projection at 30 frames\\/sec while concurrent manometry was done with five intraluminal

  10. Liquid fuel ignition features during its spilling on the metallic substrate heated up to high temperatures

    NASA Astrophysics Data System (ADS)

    Vysokomornaya, Olga; Scherbinina, Anastasia; Strizhak, Pavel

    2015-01-01

    Forecasting heat and mass transfer model for the numerical investigation of liquid fuel ignition features during its spilling on the metallic substrate heated up to high temperatures was developed. The dependences of liquid fuel (by the example of kerosene) ignition delay times on the velocity of its spilling, the liquid film (which is formed) thickness and the metallic substrate temperature were found. The least values of these parameters (whereby the ignition is possible under the heat and mass transfer conditions considered) were determined.

  11. High performance 32nm logic technology featuring 2nd generation high-k + metal gate transistors

    Microsoft Academic Search

    P. Packan; S. Akbar; M. Armstrong; D. Bergstrom; M. Brazier; H. Deshpande; K. Dev; G. Ding; T. Ghani; O. Golonzka; W. Han; J. He; R. Heussner; R. James; J. Jopling; C. Kenyon; S.-H. Lee; M. Liu; S. Lodha; B. Mattis; A. Murthy; L. Neiberg; J. Neirynck; S. Pae; C. Parker; L. Pipes; J. Sebastian; J. Seiple; B. Sell; A. Sharma; S. Sivakumar; B. Song; A. St. Amour; K. Tone; T. Troeger; C. Weber; K. Zhang; Y. Luo; S. Natarajan

    2009-01-01

    A 32 nm logic technology for high performance microprocessors is described. 2nd generation high-k + metal gate transistors provide record drive currents at the tightest gate pitch reported for any 32 nm or 28 nm logic technology. NMOS drive currents are 1.62 mA\\/um Idsat and 0.231 mA\\/um Idlin at 1.0 V and 100 nA\\/um Ioff. PMOS drive currents are 1.37

  12. Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition

    PubMed Central

    Lu, Xuemin; Li, Jennifer M.; Elemento, Olivier; Tavazoie, Saeed; Wieschaus, Eric F.

    2009-01-01

    Summary One of the most prominent features at the mid-blastula transition (MBT) observed in most embryos is a pause in cell cycle regulated by the nucleocytoplasmic (N/C) ratio. By using chromosome rearrangements to manipulate the DNA content of embryos, we determined that the threshold for this cell cycle pause in Drosophila is about 70% of the DNA content normally present at cycle 14. Embryos with DNA contents around this value show intermediate cell cycle behaviors. Some pause at cycle 14, some at cycle 15, and some form patches arrested in different mitotic cycles. A second feature at MBT is a massive increase in zygotic transcription and a parallel degradation of maternally supplied RNAs. To determine whether these changes in gene expression are governed by the same N/C ratio that controls cell cycle pause, we compared gene expression in haploid and diploid Drosophila embryos. We find that most maternal RNA degradation and most new transcription correlate with absolute time or developmental stage, and are timed independently of the N/C ratio. We identify a class of zygotically active genes whose expression depends on the N/C ratio and which are only expressed at cycle 15 in haploids. In embryos with patchy cell cycle behavior due to threshold DNA contents, the expression of these genes correlates tightly with the boundaries of the mitotic patches, suggesting either that the mechanism that pauses the mitotic cycle is the same as the one that measures the N/C ratio, or that it is tightly coupled to the mechanism controlling zygotic transcription of N/C ratio genes at the MBT. PMID:19465600

  13. p21-activated kinase 4 regulates mitotic spindle positioning and orientation

    PubMed Central

    Bompard, Guillaume; Morin, Nathalie

    2012-01-01

    During mitosis, microtubules (MTs) are massively rearranged into three sets of highly dynamic MTs that are nucleated from the centrosomes to form the mitotic spindle. Tight regulation of spindle positioning in the dividing cell and chromosome alignment at the center of the metaphase spindle are required to ensure perfect chromosome segregation and to position the cytokinetic furrow that will specify the two daughter cells. Spindle positioning requires regulation of MT dynamics, involving depolymerase activities together with cortical and kinetochore-mediated pushing and pulling forces acting on astral MTs and kinetochore fibres. These forces rely on MT motor activities. Cortical pulling forces exerted on astral MTs depend upon dynein/dynactin complexes and are essential in both symmetric and asymmetric cell division. A well-established spindle positioning pathway regulating the cortical targeting of dynein/dynactin involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA (microtubule binding nuclear mitotic apparatus protein) complex.1 Spindle orientation is also regulated by integrin-mediated cell adhesion2 and actin retraction fibres that respond to mechanical stress and are influenced by the microenvironment of the dividing cell.3 Altering the capture of astral MTs or modulating pulling forces affects spindle position, which can impair cell division, differentiation and embryogenesis.   In this general scheme, the activity of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial.4 Recently, the p21-activated kinases (PAKs) emerged as novel important players in mitotic progression. In our recent article, we demonstrated that PAK4 regulates spindle positioning in symmetric cell division.5 In this commentary, and in light of recent published studies, we discuss how PAK4 could participate in the regulation of mechanisms involved in spindle positioning and orientation. PMID:22960742

  14. Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C.

    PubMed

    Sackton, Katharine L; Dimova, Nevena; Zeng, Xing; Tian, Wei; Zhang, Mengmeng; Sackton, Timothy B; Meaders, Johnathan; Pfaff, Kathleen L; Sigoillot, Frederic; Yu, Hongtao; Luo, Xuelian; King, Randall W

    2014-10-30

    Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase-promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome. Because blocking mitotic exit is an effective approach for inducing tumour cell death, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc20 (ref. 5), which forms a co-receptor with the APC/C to recognize substrates containing a destruction box (D-box). Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identify a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-l-arginine methyl ester, a small molecule that blocks the APC/C-Cdc20 interaction. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine. PMID:25156254

  15. p21-activated kinase 4 regulates mitotic spindle positioning and orientation.

    PubMed

    Bompard, Guillaume; Morin, Nathalie

    2012-01-01

    During mitosis, microtubules (MTs) are massively rearranged into three sets of highly dynamic MTs that are nucleated from the centrosomes to form the mitotic spindle. Tight regulation of spindle positioning in the dividing cell and chromosome alignment at the center of the metaphase spindle are required to ensure perfect chromosome segregation and to position the cytokinetic furrow that will specify the two daughter cells. Spindle positioning requires regulation of MT dynamics, involving depolymerase activities together with cortical and kinetochore-mediated pushing and pulling forces acting on astral MTs and kinetochore fibres. These forces rely on MT motor activities. Cortical pulling forces exerted on astral MTs depend upon dynein/dynactin complexes and are essential in both symmetric and asymmetric cell division. A well-established spindle positioning pathway regulating the cortical targeting of dynein/dynactin involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA (microtubule binding nuclear mitotic apparatus protein) complex. Spindle orientation is also regulated by integrin-mediated cell adhesion and actin retraction fibres that respond to mechanical stress and are influenced by the microenvironment of the dividing cell. Altering the capture of astral MTs or modulating pulling forces affects spindle position, which can impair cell division, differentiation and embryogenesis. In this general scheme, the activity of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial. Recently, the p21-activated kinases (PAKs) emerged as novel important players in mitotic progression. In our recent article, we demonstrated that PAK4 regulates spindle positioning in symmetric cell division. In this commentary, and in light of recent published studies, we discuss how PAK4 could participate in the regulation of mechanisms involved in spindle positioning and orientation. PMID:22960742

  16. Cliques in mitotic spindle network bring kinetochore-associated complexes to form dependence pathway.

    PubMed

    Chen, Tzu-Chi; Lee, Sheng-An; Chan, Chen-Hsiung; Juang, Yue-Li; Hong, Yi-Ren; Huang, Yei-Hsuan; Lai, Jin-Mei; Kao, Cheng-Yan; Huang, Chi-Ying F

    2009-08-01

    The mitotic spindle is an essential molecular machine for chromosome segregation during mitosis. Achieving a better understanding of its organization at the topological level remains a daunting task. To determine the functional connections among 137 mitotic spindle proteins, a protein-protein interaction network among queries was constructed. Many hub proteins, which connect more than one query and serve as highly plausible candidates for expanding the mitotic spindle proteome, are ranked by conventional degree centrality and a new subnetwork specificity score. Evaluation of the ranking results by literature reviews and empirical verification of SEPT6, a novel top-ranked hub, suggests that the subnetwork specificity score could enrich for putative spindle-related proteins. Topological analysis of this expanded network shows the presence of 30 3-cliques and six 4-cliques (fully connected subgraphs) that, respectively, reside in eight kinetochore-associated complexes, of which seven are evolution conserved. Notably, these complexes strikingly form dependence pathways for the assembly of the kinetochore complex. These analyses indicate the feasibility of using network topology, i.e. cliques, to uncover novel pathways to accelerate our understanding of potential biological processes. PMID:19658104

  17. Disruption of IFT Complex A Causes Cystic Kidneys without Mitotic Spindle Misorientation

    PubMed Central

    Jonassen, Julie A.; SanAgustin, Jovenal; Baker, Stephen P.

    2012-01-01

    Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre–driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression. PMID:22282595

  18. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

    SciTech Connect

    DiCicco-Bloom, E.; Black, I.B. (Cornell Univ. Medical College, New York, NY (USA))

    1988-06-01

    While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating ({sup 3}H)thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of ({sup 3}H)thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain.

  19. High-resolution digital elevation models of the Flade Iceblink feature in NE Greenland

    NASA Astrophysics Data System (ADS)

    Willis, M. J.; Juntunen, T.; Porter, C. C.; Morin, P. J.

    2013-12-01

    We produce a time series of high-resolution digital elevation models (DEM) to examine the recent evolution of an 8.7 km2 sub-glacial lake collapse feature near the southern summit of the 8500 km2 Flade Isblink Ice Cap (FIIC) in northeastern Greenland [Figure 1]. Visible imagery from the MODerate-resolution Imaging Spectroradiometer (MODIS) indicates the collapse occurred between August 16th and September 6th, 2011 at the site of a recurring moulin. DEMs are extracted using the NASA Ames Stereo Pipeline for the period between June 2012 and late 2013 from 0.5 m resolution along-track stereo image pairs available via the NGA commercial imagery program. The DEMs are compared to a 1996 ERS InSAR derived DEM [Palmer et al., 2010], and to a contemporary airborne laser altimeter swath flown by NASA Icebridge in mid-April 2013 to derive the volume of the feature and the uncertainties on the high-resolution DEMs. The 'mitten' shaped feature is bounded by crevasses on three sides, with a shallow ramp to the south. It is ~70 m deep, 3.7 km north-to-south and 3 km east-to-west and has a volume of ~0.3 km3. Ice penetrating radar from a nearby Icebridge mission in May 2011, indicates the ice is approximately 550 m thick and that the bed is very flat and smooth about 1 km to the southeast of the feature. The nearby bed topography, local geology and lack of recorded seismicity in the area indicate it is unlikely that the feature is the result of either subglacial volcanic activity or the collapse of a limestone karst feature below the ice cap - the neighboring Princess Elizabeth Alps are composed of 420 Ma Caledonide fold belt gneisses. The presence of recurring supraglacial meltwater streams and drainage into the feature, its rapid formation and its steep sided nature instead suggest that it formed during the rapid drainage of a sub-glacial lake - which is, as far as we are aware, the first recorded instance of such an occurrence in Greenland. Meltwater observed using 250 m resolution MODIS imagery during the extensive melt seasons of both 2010 and 2011 flows northwards into the area of the feature before disappearing - presumably down a Moulin. We use RACMO2 to provide rough estimates of the volumes involved. We monitor the elevation of the floor of the feature to see if the subglacial lake is refilling and provide gross, low-resolution estimates of hydraulic head and drainage path calculations for the region. Flade Iceblink feature from IceBridge. Michael Studdinger/NASA mike.willis@cornell.edu Flade Ice Blink as taken by Michael Studdinger/NASA

  20. Centrin: another target of monastrol, an inhibitor of mitotic spindle.

    PubMed

    Duan, Lian; Wang, Tong-Qing; Bian, Wei; Liu, Wen; Sun, Yue; Yang, Bin-Sheng

    2015-02-25

    Monastrol, a cell-permeable inhibitor, considered to specifically inhibit kinesin Eg5, can cause mitotic arrest and monopolar spindle formation, thus exhibiting antitumor properties. Centrin, a ubiquitous protein associated with centrosome, plays a critical role in centrosome duplication. Moreover, a correlation between centrosome amplification and cancer has been reported. In this study, it is proposed for the first time that centrin may be another target of the anticancer drug monastrol since monastrol can effectively inhibit not only the growth of the transformed Escherichia coli cells in vivo, but also the Lu(3+)-dependent self-assembly of EoCen in vitro. The two closely related compounds (Compounds 1 and 2) could not take the same effect. Fluorescence titration experiments suggest that four monastrols per protein is the optimum binding pattern, and the binding constants at different temperatures were obtained. Detailed thermodynamic analysis indicates that hydrophobic force is the main acting force between monastrol and centrin, and the extent of monastrol inhibition of centrin self-assembly is highly dependent upon the hydrophobic region of the protein, which is largely exposed by the binding of metal ions. PMID:25300040

  1. Cloud field classification based upon high spatial resolution textural features. 2. Simplified vector approaches

    NASA Astrophysics Data System (ADS)

    Chen, D. W.; Sengupta, S. K.; Welch, R. M.

    1989-10-01

    The huge volume of data being collected in global climate studies makes it necessary to develop efficient automatic data analysis methods. While most cloud classification algorithms are based upon multispectral signatures, there is growing use of textural features. The results given in Part 1 of this study demonstrate that textural features computed from the Gray Level Cooccurrence Matrix (GLCM) approach produce high cloud classification accuracies. The present study compares classification results derived from two vector approaches, Sum and Difference Histogram (SADH) and Gray Level Difference Vector (GLDV), with those from the GLCM approach. It is found that the SADH approach produces accuracies equivalent to those obtained using GLCM, but with greater ability to resolve error clusters; also, there is a 30% savings in run time and a 50% savings in storage requirements. The GLDV approach suffers a slight degradation in classification accuracy but has a 40% savings in run time and an 87% savings in storage requirements. Textural features are not highly sensitive to moderate variations in cloud threshold selection. However, the whole cloud, rather than only the brightest portions of the cloud, produce the highest classification accuracies. A very important result is that spatial information content and classification accuracy are preserved even at lower radiometric resolutions with effective gray levels of 16. means that significantly low resolution digitized versions of satellite imagery retain essentially the full spatial information content of the original digital data. Substitution of digitized imagery can significantly reduce the expense of many remote sensing studies.

  2. Robust mitotic entry is ensured by a latching switch.

    PubMed

    Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novák, Béla

    2013-01-01

    Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust. PMID:24143279

  3. Robust mitotic entry is ensured by a latching switch

    PubMed Central

    Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novák, Béla

    2013-01-01

    Summary Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust. PMID:24143279

  4. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    PubMed Central

    Plitt, Mark; Barnes, Kelly Anne; Martin, Alex

    2014-01-01

    Objectives Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication. Results High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning. Conclusions While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing. PMID:25685703

  5. Mitotic remodeling of the replicon and chromosome structure.

    PubMed

    Lemaitre, Jean-Marc; Danis, Etienne; Pasero, Philippe; Vassetzky, Yegor; Méchali, Marcel

    2005-12-01

    Animal cloning by nuclear-transfer experiments frequently fails due to the inability of transplanted nuclei to support normal embryonic development. We show here that the formation of mitotic chromosomes in the egg context is crucial for adapting differentiated nuclei for early development. Differentiated erythrocyte nuclei replicate inefficiently in Xenopus eggs but do so as rapidly as sperm nuclei if a prior single mitosis is permitted. This mitotic remodeling involves a topoisomerase II-dependent shortening of chromatin loop domains and an increased recruitment of replication initiation factors onto chromatin, leading to a short interorigin spacing characteristic of early developmental stages. It also occurs within each early embryonic cell cycle and dominantly regulates initiation of DNA replication for the subsequent S phase. These results indicate that mitotic conditioning is crucial to reset the chromatin structure of differentiated adult donor cells for embryonic DNA replication and suggest that it is an important step in nuclear cloning. PMID:16325575

  6. Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae

    PubMed Central

    Symington, Lorraine S.; Rothstein, Rodney; Lisby, Michael

    2014-01-01

    Homology-dependent exchange of genetic information between DNA molecules has a profound impact on the maintenance of genome integrity by facilitating error-free DNA repair, replication, and chromosome segregation during cell division as well as programmed cell developmental events. This chapter will focus on homologous mitotic recombination in budding yeast Saccharomyces cerevisiae. However, there is an important link between mitotic and meiotic recombination (covered in the forthcoming chapter by Hunter et al. 2015) and many of the functions are evolutionarily conserved. Here we will discuss several models that have been proposed to explain the mechanism of mitotic recombination, the genes and proteins involved in various pathways, the genetic and physical assays used to discover and study these genes, and the roles of many of these proteins inside the cell. PMID:25381364

  7. Mutations in Genes Encoding Essential Mitotic Functions in DROSOPHILA MELANOGASTER

    PubMed Central

    Smith, David A.; Baker, Bruce S.; Gatti, Maurizio

    1985-01-01

    Temperature-sensitive mutations at 15 loci that affect the fidelity of mitotic chromosome behavior have been isolated in Drosophila melanogaster . These mitotic mutants were detected in a collection of 168 EMS-induced X-linked temperature-sensitive (ts) lethal and semilethal mutants. Our screen for mutations with mitotic effects was based upon the reasoning that under semirestrictive conditions such mutations could cause an elevated frequency of mitotic chromosome misbehavior and that such events would be detectable with somatic cell genetic techniques. Males hemizygous for each ts lethal and heterozygous for the recessive autosomal cell marker mwh were reared under semirestrictive conditions, and the wings of those individuals surviving to adulthood were examined for an increased frequency of mwh clones. Those mutations producing elevated levels of chromosome instability during growth of the wing imaginal disc were also examined for their effects on chromosome behavior in the cell lineages producing the abdominal cuticle. Fifteen mutations affect chromosome behavior in both wing and abdominal cells and thus identify loci generally required for the fidelity of mitotic chromosome transmission. Mapping and complementation tests show that these mutations represent 15 loci. One mutant is an allele of a locus (mus-101) previously identified by mutagensensitive mutants and a second mutant is an allele of the lethal locus zw10.—The 15 mutants were also examined cytologically for their effects on chromosomes in larval neuroblasts. Taken together, the results of our cytological and genetical studies show that these mutants identify loci with wild-type functions necessary for either (1) maintenance of chromosome integrity or (2) regular disjunction of chromosomes or (3) chromosome condensation. Thus, these mutations define a broad spectrum of genes required for the normal execution of the mitotic chromosome cycle. PMID:3928429

  8. High-Velocity Features in the Spectra of Type-Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Silverman, Jeffrey M.; Marion, Howie; Vinko, Jozsef; Mulligan, Brian W.; Wheeler, J. Craig; Filippenko, Alexei V.

    2015-01-01

    Spectra of Type-Ia supernovae (SNe Ia) obtained before maximum brightness sometimes show high-velocity features (HVFs). They are most often seen in Si II and Ca II and in the most obvious cases appear as a second, separate absorption feature at ~7000-10000 km/s higher expansion velocity than the more normal photospheric-velocity features (PVFs). We have investigated how often HVFs occur, at what epochs, and how they evolve with time using a large sample of low-resolution, optical and NIR spectra of nearby SNe Ia. Our ongoing study indicates that HVFs are quite common in SNe Ia spectra obtained prior to 5 days before maximum brightness. Correlations between photometric observables and the relative line strengths and expansion velocities of both HVFs and PVFs are currently being sought and some intriguing results have already been found and will be discussed. Various explanations for the existence and behavior of the HVFs are being considered, with possibilities including density enhancements in the outer portion of the SN ejecta and low levels of interaction with circumstellar material.

  9. Fully automatic 2D to 3D conversion with aid of high-level image features

    NASA Astrophysics Data System (ADS)

    Appia, Vikram; Batur, Umit

    2014-03-01

    With the recent advent in 3D display technology, there is an increasing need for conversion of existing 2D content into rendered 3D views. We propose a fully automatic 2D to 3D conversion algorithm that assigns relative depth values to the various objects in a given 2D image/scene and generates two different views (stereo pair) using a Depth Image Based Rendering (DIBR) algorithm for 3D displays. The algorithm described in this paper creates a scene model for each image based on certain low-level features like texture, gradient and pixel location and estimates a pseudo depth map. Since the capture environment is unknown, using low-level features alone creates inaccuracies in the depth map. Using such flawed depth map for 3D rendering will result in various artifacts, causing an unpleasant viewing experience. The proposed algorithm also uses certain high-level image features to overcome these imperfections and generates an enhanced depth map for improved viewing experience. Finally, we show several 3D results generated with our algorithm in the results section.

  10. DESIGN SAFETY FEATURES OF THE BNL HIGH-TEMPERATURE COMBUSTION FACILITY

    SciTech Connect

    GINSBERG,T.; CICCARELLI,G.; BOCCIO,J.

    2000-06-11

    The Brookhaven National Laboratory (BNL) High-Temperature Combustion Facility (HTCF) was used to perform hydrogen deflagration and detonation experiments at temperatures to 650 K. Safety features that were designed to ensure safe and reliable operation of the experimental program are described. Deflagration and detonation experiments have been conducted using mixtures of hydrogen, air, and steam. Detonation cell size measurements were made as a function of mixture composition and thermodynamic gas conditions. Deflagration-to-detonation transition experiments were also conducted. Results of the experimental program are presented, and implications with respect to hydrogen safety are discussed.

  11. Mitotic count by phosphohistone H3 immunohistochemical staining predicts survival and improves interobserver reproducibility in well-differentiated neuroendocrine tumors of the pancreas.

    PubMed

    Voss, Sarah M; Riley, Meghan P; Lokhandwala, Parvez M; Wang, Ming; Yang, Zhaohai

    2015-01-01

    Well-differentiated neuroendocrine tumors (WDNETs) of the pancreas are graded on the basis of mitotic count or Ki67 index. Mitotic count has a narrow cutoff; its assessment is time consuming and carries poor interobserver reproducibility. Phosphohistone H3 (PHH3) is a mitosis-specific marker whose value has been validated in several tumor types. We sought to assess the utility of PHH3 in histologic grading of pancreatic WDNETs. Sixty-three cases of surgically resected primary pancreatic WDNETs were retrieved, and immunohistochemical analysis for PHH3 and Ki67 was performed. Mitotic rate was independently assessed by 4 pathologists on hematoxylin and eosin (HE; in 50 high-power fields [HPFs], expressed as mitoses/10 HPF) and PHH3 stains (in 50 HPFs, one 10×, and one 20× hotspot). PHH3 and Ki67 labeling indices were determined on a single 20× hotspot and expressed as the percentage of positive cells to total cells. We found that mitotic counts by various methods significantly correlated with each other and also with PHH3 and Ki67 indices, with the best correlation seen within the 3 different PHH3 counts (in 50 HPFs, one 10× and one 20× hotspot). Moreover, mitotic count on PHH3 was less time consuming than that on HE (1.68 vs. 3.67 min for 50 HPFs, P<0.0001). Histologic grade determined by PHH3 significantly correlated with disease-specific and disease-free survivals, with the best cutoffs of ?4 mitoses/10 HPF (2 mm), ?7 mitoses/10× hotspot, ?5 mitoses/20× hotspot (log rank test, P<0.0001), and ?0.16% for PHH3 labeling index (log rank test, P<0.0006). Tumor grades based on PHH3 stain also showed significant correlation with patient survivals in multivariate Cox proportional hazards models (P<0.05). Histologic grades by mitotic counts on PHH3 demonstrated high concordance and ? agreement with grades determined by mitotic count on HE. PHH3 stain also showed improved interobserver agreement in both original mitotic count (intraclass correlation 0.98 vs. 0.79) and final grade assignment (Fleiss ? 0.69 vs. 0.46) as compared with HE. Thus, our data confirmed that histologic grading by PHH3 stain has practical and prognostic values and offers reduced time and improved interobserver reproducibility in mitotic rate assessment and grade assignment. Although larger series are needed for validation, mitotic rate can potentially be determined by counting 1 hotspot, which will greatly facilitate the assessment of histologic grade in pancreatic WDNETs. PMID:25353284

  12. Force and the spindle: Mechanical cues in mitotic spindle orientation

    PubMed Central

    Nestor-Bergmann, Alexander; Goddard, Georgina; Woolner, Sarah

    2014-01-01

    The mechanical environment of a cell has a profound effect on its behaviour, from dictating cell shape to driving the transcription of specific genes. Recent studies have demonstrated that mechanical forces play a key role in orienting the mitotic spindle, and therefore cell division, in both single cells and tissues. Whilst the molecular machinery that mediates the link between external force and the mitotic spindle remains largely unknown, it is becoming increasingly clear that this is a widely used mechanism which could prove vital for coordinating cell division orientation across tissues in a variety of contexts. PMID:25080021

  13. Cyclic development of igneous features and their relationship to high-temperature hydrothermal features in the Henderson porphyry molybdenum deposit, Colorado

    USGS Publications Warehouse

    Carten, R.B.; Geraghty, E.P.; Walker, B.M.

    1988-01-01

    The Henderson porphyry molybdenum deposit was formed by the superposition of coupled alteration and mineralization events, of varying intensity and size, that were associated with each of at least 11 intrusions. Deposition of molybdenite was accompanied by time-equivalent silicic and potassic alteration. High-temperature alteration and mineralization are spatially and temporally linked to the crystallization of compositionally zoned magma in the apex of stocks. Differences in hydrothermal features associated with each intrusion (e.g., mass of ore, orientation and type of veins, density of veins, and intensity of alteration) correlate with differences in primary igneous features (e.g., composition, texture, morphology, and size). The systematic relations between hydrothermal and magmatic features suggest that primary magma compositions, including volatile contents, largely control the geometry, volume, level of emplacement, and mechanisms of crystallization of stocks. These elements in turn govern the orientations and densities of fractures, which ultimately determine the distribution patterns of hydrothermal alteration and mineralization. -from Authors

  14. High-precision image aided inertial navigation with known features: observability analysis and performance evaluation.

    PubMed

    Jiang, Weiping; Wang, Li; Niu, Xiaoji; Zhang, Quan; Zhang, Hui; Tang, Min; Hu, Xiangyun

    2014-01-01

    A high-precision image-aided inertial navigation system (INS) is proposed as an alternative to the carrier-phase-based differential Global Navigation Satellite Systems (CDGNSSs) when satellite-based navigation systems are unavailable. In this paper, the image/INS integrated algorithm is modeled by a tightly-coupled iterative extended Kalman filter (IEKF). Tightly-coupled integration ensures that the integrated system is reliable, even if few known feature points (i.e., less than three) are observed in the images. A new global observability analysis of this tightly-coupled integration is presented to guarantee that the system is observable under the necessary conditions. The analysis conclusions were verified by simulations and field tests. The field tests also indicate that high-precision position (centimeter-level) and attitude (half-degree-level)-integrated solutions can be achieved in a global reference. PMID:25330046

  15. Physiological and genomic features of highly alkaliphilic hydrogen-utilizing Betaproteobacteria from a continental serpentinizing site

    PubMed Central

    Suzuki, Shino; Kuenen, J. Gijs; Schipper, Kira; van der Velde, Suzanne; Ishii, Shun’ichi; Wu, Angela; Sorokin, Dimitry Y.; Tenney, Aaron; Meng, XianYing; Morrill, Penny L.; Kamagata, Yoichi; Muyzer, Gerard; Nealson, Kenneth H.

    2014-01-01

    Serpentinization, or the aqueous alteration of ultramafic rocks, results in challenging environments for life in continental sites due to the combination of extremely high pH, low salinity and lack of obvious electron acceptors and carbon sources. Nevertheless, certain Betaproteobacteria have been frequently observed in such environments. Here we describe physiological and genomic features of three related Betaproteobacterial strains isolated from highly alkaline (pH 11.6) serpentinizing springs at The Cedars, California. All three strains are obligate alkaliphiles with an optimum for growth at pH 11 and are capable of autotrophic growth with hydrogen, calcium carbonate and oxygen. The three strains exhibit differences, however, regarding the utilization of organic carbon and electron acceptors. Their global distribution and physiological, genomic and transcriptomic characteristics indicate that the strains are adapted to the alkaline and calcium-rich environments represented by the terrestrial serpentinizing ecosystems. We propose placing these strains in a new genus ‘Serpentinomonas’. PMID:24845058

  16. Water Extraction in High Resolution Remote Sensing Image Based on Hierarchical Spectrum and Shape Features

    NASA Astrophysics Data System (ADS)

    Li, Bangyu; Zhang, Hui; Xu, Fanjiang

    2014-03-01

    This paper addresses the problem of water extraction from high resolution remote sensing images (including R, G, B, and NIR channels), which draws considerable attention in recent years. Previous work on water extraction mainly faced two difficulties. 1) It is difficult to obtain accurate position of water boundary because of using low resolution images. 2) Like all other image based object classification problems, the phenomena of "different objects same image" or "different images same object" affects the water extraction. Shadow of elevated objects (e.g. buildings, bridges, towers and trees) scattered in the remote sensing image is a typical noise objects for water extraction. In many cases, it is difficult to discriminate between water and shadow in a remote sensing image, especially in the urban region. We propose a water extraction method with two hierarchies: the statistical feature of spectral characteristic based on image segmentation and the shape feature based on shadow removing. In the first hierarchy, the Statistical Region Merging (SRM) algorithm is adopted for image segmentation. The SRM includes two key steps: one is sorting adjacent regions according to a pre-ascertained sort function, and the other one is merging adjacent regions based on a pre-ascertained merging predicate. The sort step is done one time during the whole processing without considering changes caused by merging which may cause imprecise results. Therefore, we modify the SRM with dynamic sort processing, which conducts sorting step repetitively when there is large adjacent region changes after doing merging. To achieve robust segmentation, we apply the merging region with six features (four remote sensing image bands, Normalized Difference Water Index (NDWI), and Normalized Saturation-value Difference Index (NSVDI)). All these features contribute to segment image into region of object. NDWI and NSVDI are discriminate between water and some shadows. In the second hierarchy, we adopt the shape features to remove more shadows. The water polygons are generated by vectorization algorithm after water segmentation, and then some shape parameters (Compact, Critical Point and Symmetry) are considered to remove shadow. To evaluate the performance of the proposed method, we collect several Quick Bird images at 0.61-m resolution which are acquired in May 2009 at GUANGZHOU province of China. The proposed method is compared with four other methods in water extraction, including pixel-based segmentation by NDWI, Mean-sift segmentation by NDWI, and SVM with different channels. Experimental results show that the proposed method can increase extraction accuracy and reduce the influence of shadows.

  17. Weighted simultaneous algebraic reconstruction technique for tomosynthesis imaging of objects with high-attenuation features

    SciTech Connect

    Levakhina, Y. M. [Institute of Medical Engineering, University of Luebeck, Luebeck 23562, Germany and Graduate School for Computing in Medicine and Life Sciences, Luebeck 23562 (Germany); Mueller, J.; Buzug, T. M. [Institute of Medical Engineering, University of Luebeck, Luebeck 23562 (Germany); Duschka, R. L.; Vogt, F.; Barkhausen, J. [Clinic for Radiology, University Clinics Schleswig-Holstein, Luebeck 23562 (Germany)

    2013-03-15

    Purpose: This paper introduces a nonlinear weighting scheme into the backprojection operation within the simultaneous algebraic reconstruction technique (SART). It is designed for tomosynthesis imaging of objects with high-attenuation features in order to reduce limited angle artifacts. Methods: The algorithm estimates which projections potentially produce artifacts in a voxel. The contribution of those projections into the updating term is reduced. In order to identify those projections automatically, a four-dimensional backprojected space representation is used. Weighting coefficients are calculated based on a dissimilarity measure, evaluated in this space. For each combination of an angular view direction and a voxel position an individual weighting coefficient for the updating term is calculated. Results: The feasibility of the proposed approach is shown based on reconstructions of the following real three-dimensional tomosynthesis datasets: a mammography quality phantom, an apple with metal needles, a dried finger bone in water, and a human hand. Datasets have been acquired with a Siemens Mammomat Inspiration tomosynthesis device and reconstructed using SART with and without suggested weighting. Out-of-focus artifacts are described using line profiles and measured using standard deviation (STD) in the plane and below the plane which contains artifact-causing features. Artifacts distribution in axial direction is measured using an artifact spread function (ASF). The volumes reconstructed with the weighting scheme demonstrate the reduction of out-of-focus artifacts, lower STD (meaning reduction of artifacts), and narrower ASF compared to nonweighted SART reconstruction. It is achieved successfully for different kinds of structures: point-like structures such as phantom features, long structures such as metal needles, and fine structures such as trabecular bone structures. Conclusions: Results indicate the feasibility of the proposed algorithm to reduce typical tomosynthesis artifacts produced by high-attenuation features. The proposed algorithm assigns weighting coefficients automatically and no segmentation or tissue-classification steps are required. The algorithm can be included into various iterative reconstruction algorithms with an additive updating strategy. It can also be extended to computed tomography case with the complete set of angular data.

  18. Adhesion signaling by a novel mitotic substrate of src kinases.

    PubMed

    Bhatt, Ami S; Erdjument-Bromage, Hediye; Tempst, Paul; Craik, Charles S; Moasser, Mark M

    2005-08-11

    Src kinases are activated and relocalize to the cytoplasm during mitosis, but their mitotic function has remained elusive. We describe here a novel mitotic substrate of src kinases. Trask (transmembrane and associated with src kinases) is a 140 kDa type I transmembrane glycoprotein unrelated to currently known protein families. Src kinases phosphorylate Trask in vitro and mediate its mitotic hyperphosphorylation in vivo. Trask associates with both yes and src, is localized to the cell membrane during interphase, and undergoes cytoplasmic relocalization during mitosis. Overexpression of Trask leads to cell rounding and a loss of adhesion phenotype. Consistent with a function in cell adhesion, Trask interacts with a number of adhesion and matrix proteins including cadherins, syndecans, and the membrane-type serine protease 1 (MT-SP1), and is proteolytically cleaved by MT-SP1. Trask is unique among cell adhesion molecules in that it is under cell cycle regulation and thus links src kinases with the mitotic regulation of cell adhesion. This suggests a potential pathway by which hyperactive src kinases in tumors can deregulate adhesion signaling and mediate the metastatic phenotype. PMID:16007225

  19. Tumor suppressor VHL functions in the control of mitotic fidelity.

    PubMed

    Hell, Michael P; Duda, Maria; Weber, Thomas C; Moch, Holger; Krek, Wilhelm

    2014-05-01

    The von Hippel-Lindau (VHL) tumor suppressor protein pVHL is commonly mutated in clear cell renal cell carcinoma (ccRCC) and has been implicated in the control of multiple cellular processes that might be linked to tumor suppression, including promoting proper spindle orientation and chromosomal stability. However, it is unclear whether pVHL exerts these mitotic regulatory functions in vivo as well. Here, we applied ischemic kidney injury to stimulate cell division in otherwise quiescent mouse adult kidneys. We show that in the short term (5.5 days after surgery), Vhl-deficient kidney cells demonstrate both spindle misorientation and aneuploidy. The spindle misorientation phenotype encompassed changes in directed cell division, which may manifest in the development of cystic lesions, whereas the aneuploidy phenotype involved the occurrence of lagging chromosomes but not chromosome bridges, indicative of mitotic checkpoint impairment. Intriguingly, in the long term (4 months after the ischemic insult), Vhl-deficient kidneys displayed a heterogeneous pattern of ccRCC precursor lesions, including cysts, clear cell-type cells, and dysplasia. Together, these data provide direct evidence for a key role of pVHL in mediating oriented cell division and faithful mitotic checkpoint function in the renal epithelium, emphasizing the importance of pVHL as a controller of mitotic fidelity in vivo. PMID:24362914

  20. The Distribution of Active Force Generators Controls Mitotic Spindle Position

    Microsoft Academic Search

    Stephan W. Grill; Jonathon Howard; Erik Schäffer; Ernst H. K. Stelzer; Anthony A. Hyman

    2003-01-01

    During unequal cell divisions a mitotic spindle is eccentrically positioned before cell cleavage. To determine the basis of the net force imbalance that causes spindle displacement in one-cell Caenorhabditis elegans embryos, we fragmented centrosomes with an ultraviolet laser. Analysis of the mean and variance of fragment speeds suggests that the force imbalance is due to a larger number of force

  1. Role of senescence and mitotic catastrophe in cancer therapy

    Microsoft Academic Search

    Richa Singh; Jasmine George; Yogeshwer Shukla

    2010-01-01

    Senescence and mitotic catastrophe (MC) are two distinct crucial non-apoptotic mechanisms, often triggered in cancer cells and tissues in response to anti-cancer drugs. Chemotherapeuticals and myriad other factors induce cell eradication via these routes. While senescence drives the cells to a state of quiescence, MC drives the cells towards death during the course of mitosis. The senescent phenotype distinguishes tumor

  2. Physical Theory of the Orientation of Astral Mitotic Spindles

    Microsoft Academic Search

    Matthew Bjerknes

    1986-01-01

    A physical theory was developed for mitotic spindle orientation. This is important because spindle position is known to determine the placement of the cleavage furrow separating the offspring of a mitosis. The theory is based on an equation for the force exerted on spindle poles by the interaction of astral microtubules with the cell surface. Expected spindle placements are positions

  3. A roller coaster ride with the mitotic cyclins

    Microsoft Academic Search

    Tsz Kan Fung; Randy Y. C. Poon

    2005-01-01

    Cyclins are discovered as proteins that accumulate progressively through interphase and disappear abruptly at mitosis during each cell cycle. In mammalian cells, cyclin A accumulates from late G1 phase and is destroyed before metaphase, and cyclin B is destroyed slightly later at anaphase. The abundance of the mitotic cyclins is mainly regulated at the levels of transcription and proteolysis. Transcription

  4. Control of the Mitotic Cleavage Plane by Local Epithelial Topology

    E-print Network

    Perrimon, Norbert

    Theory Control of the Mitotic Cleavage Plane by Local Epithelial Topology William T. Gibson,1 cleavage plane (e.g., Hofmeister, 1863). However, we still understand little about the complex interplay between cell shape and cleavage-plane orientation in epithelia, where polygonal cell geome- tries emerge

  5. Control of the mitotic cleavage plane by local epithelial topology

    E-print Network

    Napp, Nils

    1 Control of the mitotic cleavage plane by local epithelial topology William T. Gibson1 cleavage plane (e.g. Hofmeister, 1863). However, we still understand little about the complex interplay between cell shape and cleavage plane orientation in epithelia, where polygonal cell geometries emerge

  6. High Levels of KAP1 Expression Are Associated with Aggressive Clinical Features in Ovarian Cancer

    PubMed Central

    Cui, Yanfen; Yang, Shaobin; Fu, Xin; Feng, Jingwen; Xu, Shilei; Ying, Guoguang

    2014-01-01

    KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (?2 = 14.57, p < 0.0001), pathological grade (?2 = 6.06, p = 0.048) and metastases (?2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230–0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer. PMID:25548895

  7. MULTIPLE HIGH-VELOCITY SiO MASER FEATURES FROM THE HIGH-MASS PROTOSTAR W51 NORTH

    SciTech Connect

    Cho, Se-Hyung; Kim, Jaeheon; Byun, Do-Young, E-mail: cho@kasi.re.kr, E-mail: jhkim@kasi.re.kr, E-mail: bdy@kasi.re.kr [Korean VLBI Network, Korea Astronomy and Space Science Institute, P. O. Box 88, Yonsei University, Seongsan-ro 262, Seodaemun, Seoul 120-749 (Korea, Republic of)

    2011-02-01

    We present the detection of multiple high-velocity silicon monoxide (SiO v = 1, 2, J = 1-0) maser features in the high-mass protostar W51 North which are distributed over an exceedingly large velocity range from 105 to 230 km s{sup -1}. The SiO v = 1, J = 1-0 maser emission shows 3-5 narrow components which span a velocity range from 154 to 230 km s{sup -1} according to observational epochs. The SiO v = 2, J = 1-0 maser also shows 3-5 narrow components that do not correspond to the SiO v = 1 maser and span a velocity range from 105 to 154 km s{sup -1}. The multiple maser components show significant changes on very short timescales (<1 month) from epoch to epoch. We suggest that the high-velocity SiO masers may be emanated from massive star-forming activity of the W51 North protostar as SiO maser jets and will be a good probe of the earliest evolutionary stages of high-mass star formation via an accretion model. Further high angular resolution observations will be required for confirmation.

  8. Time Evolution, Dynamical Quantum Fluctuation and High-Order Squeezing Feature in Polariton System — I

    NASA Astrophysics Data System (ADS)

    Liang, Guo-Dong; Yu, Xiao-Min; Yu, Chao-Fan

    2010-11-01

    We have set up a new reduced model Hamiltonian for the polariton system, in which the nonlinear interaction contains the rotating term k1(a+b + ab+) and the attractive two-mode squeezed coupling -k2(a+b+ +ab). The dynamical evolution of this system has been solved and the nonclassical features relevant to the second-order and high-order squeezing have been obtained in an analytical form. For the first time, in contrast to the existing result, we have confirmed for the phonon field that the attractive two-mode squeezed interaction will not only result in the second-order and high-order squeezing in X-component with the time evolution, but also in time average. Furthermore, the phenomena of collapse and revival of inversion will occur as well in the time evolution of the average number of photon and phonon, as also in the second-order and high-order squeezing of photon field, particularly, in the high-order squeezing of phonon field.

  9. The crystal structure of archaeal serine hydroxymethyltransferase reveals idiosyncratic features likely required to withstand high temperatures.

    PubMed

    Angelucci, Francesco; Morea, Veronica; Angelaccio, Sebastiana; Saccoccia, Fulvio; Contestabile, Roberto; Ilari, Andrea

    2014-12-01

    Serine hydroxymethyltransferases (SHMTs) play an essential role in one-carbon unit metabolism and are used in biomimetic reactions. We determined the crystal structure of free (apo) and pyridoxal-5'-phosphate-bound (holo) SHMT from Methanocaldococcus jannaschii, the first from a hyperthermophile, from the archaea domain of life and that uses H4 MPT as a cofactor, at 2.83 and 3.0 Ĺ resolution, respectively. Idiosyncratic features were observed that are likely to contribute to structure stabilization. At the dimer interface, the C-terminal region folds in a unique fashion with respect to SHMTs from eubacteria and eukarya. At the active site, the conserved tyrosine does not make a cation-? interaction with an arginine like that observed in all other SHMT structures, but establishes an amide-aromatic interaction with Asn257, at a different sequence position. This asparagine residue is conserved and occurs almost exclusively in (hyper)thermophile SHMTs. This led us to formulate the hypothesis that removal of frustrated interactions (such as the Arg-Tyr cation-? interaction occurring in mesophile SHMTs) is an additional strategy of adaptation to high temperature. Both peculiar features may be tested by designing enzyme variants potentially endowed with improved stability for applications in biomimetic processes. PMID:25257552

  10. Cytotoxic effects of cylindrospermopsin in mitotic and non-mitotic Vicia faba cells.

    PubMed

    Garda, Tamás; Riba, Milán; Vasas, Gábor; Beyer, Dániel; M-Hamvas, Márta; Hajdu, Gréta; Tándor, Ildikó; Máthé, Csaba

    2015-02-01

    Cylindrospermopsin (CYN) is a cyanobacterial toxin known as a eukaryotic protein synthesis inhibitor. We aimed to study its effects on growth, stress responses and mitosis of a eukaryotic model, Vicia faba (broad bean). Growth responses depended on exposure time (3 or 6d), cyanotoxin concentration, culture conditions (dark or continuous light) and V. faba cultivar ("Standard" or "ARC Egypt Cross"). At 6d of exposure, CYN had a transient stimulatory effect on root system growth, roots being possibly capable of detoxification. The toxin induced nucleus fragmentation, blebbing and chromosomal breaks indicating double stranded DNA breaks and programmed cell death. Root necrotic tissue was observed at 0.1-20 ?g mL(-1) CYN that probably impeded toxin uptake into vascular tissue. Growth and cell death processes observed were general stress responses. In lateral root tip meristems, lower CYN concentrations (0.01-0.1 ?g mL(-1)) induced the stimulation of mitosis and distinct mitotic phases, irrespective of culture conditions or the cultivar used. Higher cyanotoxin concentrations inhibited mitosis. Short-term exposure of hydroxylurea-synchronized roots to 5 ?g mL(-1) CYN induced delay of mitosis that might have been related to a delay of de novo protein synthesis. CYN induced the formation of double, split and asymmetric preprophase bands (PPBs), in parallel with the alteration of cell division planes, related to the interference of cyanotoxin with protein synthesis, thus it was a plant- and CYN specific alteration. PMID:25016338

  11. A Small Mission Featuring an Imaging X-ray Polarimeter with High Sensitivity

    NASA Technical Reports Server (NTRS)

    Weisskopf, Martin C.; Baldini, Luca; Bellazini, Ronaldo; Brez, Alessandro; Costa, Enrico; Dissley, Richard; Elsner, Ronald; Fabiani, Sergio; Matt, Giorgio; Minuti, Massimo; Mulieri, Fabio; O'Dell, Steve; Pinchera, Michelle; Ramsey, Brian; Rubini, Alda; Sgro, Carmelo; Soffitta, Paolo; Spandre, Gloria

    2013-01-01

    We present a detailed description of a small mission capable of obtaining high precision and meaningful measurement of the X-ray polarization of a variety of different classes of cosmic X-ray sources. Compared to other ideas that have been suggested this experiment has demonstrated in the laboratory a number of extremely important features relevant to the ultimate selection of such a mission by a funding agency. The most important of these questions are: 1) Have you demonstrated the sensitivity to a polarized beam at the energies of interest (i.e. the energies which represent the majority (not the minority) of detected photons from the X-ray source of interest? 2) Have you demonstrated that the device's sensitivity to an unpolarized beam is really negligible and/or quantified the impact of any systematic effects upon actual measurements? We present our answers to these questions backed up by laboratory measurements and give an overview of the mission.

  12. Magnetic-field-induced microstructural features in a high carbon steel during diffusional phase transformation

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoxue; Zhang, Yudong; Gong, Minglong; Esling, Claude; Zhao, Xiang; Zuo, Liang

    2012-12-01

    In this work, a high purity, high carbon steel was heat treated without and with a 12-T magnetic field. The microstructural features induced by magnetic field during its diffusion-controlled austenite decomposition were investigated by means of optical microscopy and SEM/EBSD. It is found that the magnetic field increases the amount of the abnormal structure, which is composed of proeutectoid cementite along the prior austenite boundaries and ferrite around it, because magnetic field increases the austenite grain size and promotes the transformation of carbon-depleted austenite to ferrite. No specific orientation relationship between abnormal ferrite and cementite has been found in the non-field- or the field-treated specimens. Magnetic field evidently promotes the spheroidization of pearlite, due to its effect of enhancing carbon diffusion through raising the transformation temperature and its effect of increasing the relative ferrite/cementite interface energy. As magnetic field favors the nucleation of the high magnetization phase-pearlitic ferrite, the occurrence of the P-P2 OR that corresponds to the situation that ferrite nucleates prior to cementite during pearlitic transformation is enhanced by the magnetic field.

  13. A simple feature of yielding behavior of highly dense suspensions of soft micro-hydrogel particles.

    PubMed

    Urayama, Kenji; Saeki, Taku; Cong, Shen; Uratani, Shota; Takigawa, Toshikazu; Murai, Masaki; Suzuki, Daisuke

    2014-12-21

    The highly dense suspensions of soft micro-hydrogels with a narrow size distribution (typically ?eff > 0.9 where ?eff is the apparent volume fraction of the particle), which form a regular lattice structure, exhibit a simple feature in the yielding behavior: the yield strain ?c [ca. 2.5% and ca. 4.8% for poly(N-isopropylmethacrylamide) (PNIPMA) and poly(N-isopropylacrylamide) (PNIPA) hydrogel particles, respectively] is nearly insensitive to the cross-link concentration (cx), particle diameter (Dh), and particle concentration (c) in the limited c range examined here, and ?c is almost constant in a wide range of equilibrium shear moduli over two orders of magnitude. In addition, no appreciable difference in ?c is observed in the dense pastes with crystalline and glassy structures which are formed by mono- and bidisperse microgels, respectively. This is in contrast to a finite difference in ?c for the crystal and glass formed by the hard sphere reported by Koumakis et al. [Soft Matter, 4, 2008 (2008)]. Furthermore, the highly dense suspensions of NIPA core-NIPMA shell microgels are similar in ?c to those of NIPMA microgels. These results indicate that ?c for the highly dense suspensions of soft micro-hydrogels depends primarily on the kind of constituent polymer near the particle surface. The yield strain ?c is expected to be governed by short-range interactions such as adhesion and friction. PMID:25346296

  14. Cigarette Design Features in Low-, Middle-, and High-Income Countries

    PubMed Central

    Caruso, Rosalie V.; O'Connor, Richard J.

    2012-01-01

    Previous studies have shown that country income grouping is correlated with cigarette engineering. Cigarettes (N = 111 brands) were purchased during 2008–2010 from 11 low-, middle-, and high-income countries to assess physical dimensions and an array of cigarette design features. Mean ventilation varied significantly across low- (7.5%), middle- (15.3%), and high-income (26.2%) countries (P ? 0.001). Differences across income groups were also seen in cigarette length (P = 0.001), length of the tipping paper (P = 0.01), filter weight (P = 0.017), number of vent rows (P = 0.003), per-cigarette tobacco weight (P = 0.04), and paper porosity (P = 0.008). Stepwise linear regression showed ventilation and tobacco length as major predictors of ISO tar yields in low-income countries (P = 0.909, 0.047), while tipping paper (P < 0.001), filter length (P < 0.001), number of vent rows (P = 0.014), and per-cigarette weight (P = 0.015) were predictors of tar yields in middle-income countries. Ventilation (P < 0.001), number of vent rows (P = 0.009), per-cigarette weight (P < 0.001), and filter diameter (P = 0.004) predicted tar yields in high-income countries. Health officials must be cognizant of cigarette design issues to provide effective regulation of tobacco products. PMID:22645621

  15. Design features and performance of the LAMPF high-intensity beam area

    SciTech Connect

    Agnew, L.; Grisham, D.; Macek, R.J.; Sommer, W.F.; Werbeck, R.D.

    1983-01-01

    LAMPF is a multi-purpose high-intensity meson factory capable of producing a 1 mA beam of 800-MeV protons. The three target cells and the beam stop facilities in the high intensity area have many special design features that are required for operation in the presence of high heat loads and intense radiation fields where accessibility is extremely limited. Reliable targets, beam windows, beam stops, beam transport and diagnostic components, vacuum enclosures, and auxiliary systems have been developed. Sophisticated remote-handling systems are employed for maintenance. Complex protection systems have been developed to guard against damage caused by errant beam. Beam availability approaching 90% has been achieved at currents of 600 to 700 ..mu..A. A new facility for direct proton and neutron radiation effects studies will be installed in 1985. The new facility will provide an integrated spallation neutron flux of up to 5 x 10/sup 17/ m/sup -2/s/sup -1/ and will anable proton irradiation studies in the primary beam.

  16. Prioritizing spatial accuracy in high-resolution fMRI data using multivariate feature weight mapping

    PubMed Central

    Buschmann, Tilo; Lohmann, Gabriele; Margulies, Daniel S.; Trampel, Robert; Turner, Robert

    2014-01-01

    Although ultra-high-field fMRI at field strengths of 7T or above provides substantial gains in BOLD contrast-to-noise ratio, when very high-resolution fMRI is required such gains are inevitably reduced. The improvement in sensitivity provided by multivariate analysis techniques, as compared with univariate methods, then becomes especially welcome. Information mapping approaches are commonly used, such as the searchlight technique, which take into account the spatially distributed patterns of activation in order to predict stimulus conditions. However, the popular searchlight decoding technique, in particular, has been found to be prone to spatial inaccuracies. For instance, the spatial extent of informative areas is generally exaggerated, and their spatial configuration is distorted. We propose the combination of a non-parametric and permutation-based statistical framework with linear classifiers. We term this new combined method Feature Weight Mapping (FWM). The main goal of the proposed method is to map the specific contribution of each voxel to the classification decision while including a correction for the multiple comparisons problem. Next, we compare this new method to the searchlight approach using a simulation and ultra-high-field 7T experimental data. We found that the searchlight method led to spatial inaccuracies that are especially noticeable in high-resolution fMRI data. In contrast, FWM was more spatially precise, revealing both informative anatomical structures as well as the direction by which voxels contribute to the classification. By maximizing the spatial accuracy of ultra-high-field fMRI results, global multivariate methods provide a substantial improvement for characterizing structure-function relationships. PMID:24795548

  17. Reinforcement Learning on Slow Features of High-Dimensional Input Streams

    PubMed Central

    Legenstein, Robert; Wilbert, Niko; Wiskott, Laurenz

    2010-01-01

    Humans and animals are able to learn complex behaviors based on a massive stream of sensory information from different modalities. Early animal studies have identified learning mechanisms that are based on reward and punishment such that animals tend to avoid actions that lead to punishment whereas rewarded actions are reinforced. However, most algorithms for reward-based learning are only applicable if the dimensionality of the state-space is sufficiently small or its structure is sufficiently simple. Therefore, the question arises how the problem of learning on high-dimensional data is solved in the brain. In this article, we propose a biologically plausible generic two-stage learning system that can directly be applied to raw high-dimensional input streams. The system is composed of a hierarchical slow feature analysis (SFA) network for preprocessing and a simple neural network on top that is trained based on rewards. We demonstrate by computer simulations that this generic architecture is able to learn quite demanding reinforcement learning tasks on high-dimensional visual input streams in a time that is comparable to the time needed when an explicit highly informative low-dimensional state-space representation is given instead of the high-dimensional visual input. The learning speed of the proposed architecture in a task similar to the Morris water maze task is comparable to that found in experimental studies with rats. This study thus supports the hypothesis that slowness learning is one important unsupervised learning principle utilized in the brain to form efficient state representations for behavioral learning. PMID:20808883

  18. A Mitotic Kinase TOPK Enhances Cdk1\\/cyclin B1-dependent Phosphorylation of PRC1 and Promotes Cytokinesis

    Microsoft Academic Search

    Yasuhito Abe; Takashi Takeuchi; Lisa Kagawa-Miki; Norifumi Ueda; Kazuhiro Shigemoto; Masaki Yasukawa; Katsumi Kito

    2007-01-01

    A MAPKK-like mitotic kinase, TOPK, implies the formation of mitotic spindles and spindle midzone and accomplishing cytokinesis, however, its underlying mechanism remains unclear. A microtubule bundling protein, PRC1, plays a pivotal role in the formation of mitotic spindles and spindle midzone. Because of their functional resemblance, we attempted to clarify the links between these two molecules. TOPK supported mitotic advance

  19. Extraction of Airport Features from High Resolution Satellite Imagery for Design and Risk Assessment

    NASA Technical Reports Server (NTRS)

    Robinson, Chris; Qiu, You-Liang; Jensen, John R.; Schill, Steven R.; Floyd, Mike

    2001-01-01

    The LPA Group, consisting of 17 offices located throughout the eastern and central United States is an architectural, engineering and planning firm specializing in the development of Airports, Roads and Bridges. The primary focus of this ARC project is concerned with assisting their aviation specialists who work in the areas of Airport Planning, Airfield Design, Landside Design, Terminal Building Planning and design, and various other construction services. The LPA Group wanted to test the utility of high-resolution commercial satellite imagery for the purpose of extracting airport elevation features in the glide path areas surrounding the Columbia Metropolitan Airport. By incorporating remote sensing techniques into their airport planning process, LPA wanted to investigate whether or not it is possible to save time and money while achieving the equivalent accuracy as traditional planning methods. The Affiliate Research Center (ARC) at the University of South Carolina investigated the use of remotely sensed imagery for the extraction of feature elevations in the glide path zone. A stereo pair of IKONOS panchromatic satellite images, which has a spatial resolution of 1 x 1 m, was used to determine elevations of aviation obstructions such as buildings, trees, towers and fence-lines. A validation dataset was provided by the LPA Group to assess the accuracy of the measurements derived from the IKONOS imagery. The initial goal of this project was to test the utility of IKONOS imagery in feature extraction using ERDAS Stereo Analyst. This goal was never achieved due to problems with ERDAS software support of the IKONOS sensor model and the unavailability of imperative sensor model information from Space Imaging. The obstacles encountered in this project pertaining to ERDAS Stereo Analyst and IKONOS imagery will be reviewed in more detail later in this report. As a result of the technical difficulties with Stereo Analyst, ERDAS OrthoBASE was used to derive aviation obstruction measurements for this project. After collecting ancillary data such as GPS locations, South Carolina Geodetic Survey and Aero Dynamics ground survey points to set up the OrthoBASE Block File, measurements were taken of the various glide path obstructions and compared to the validation dataset. This process yielded the following conclusions: The IKONOS stereo model in conjunction with Imagine OrthoBASE can provide The LPA Group with a fast and cost efficient method for assessing aviation obstructions. Also, by creating our own stereo model we achieved any accuracy better currently available commercial products.

  20. Application Prospects and Microstructural Features in Laser-Induced Rapidly Solidified High-Entropy Alloys

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Pan, Ye; He, Yi-Zhu; Wu, Ji-Li; Yue, T. M.; Guo, Sheng

    2014-10-01

    Recently, high-entropy alloys (HEAs) have attracted much interest in the materials community, as they offer massive opportunities to observe new phenomena, explore new structure, and develop new materials. Particularly, it is attractive to prepare high-performance HEA coatings by laser-induced rapid solidification, which can be formed on the surface of components and parts in a variety of sizes and shapes with a lower cost in comparison with those bulk material fabrication methods. From the technical point of view, laser-induced rapid solidification could hamper the compositional segregation, improve the solubility in solid-solution phases, and lead to the strengthening effect by the grain refinement. This article reviews the recent work on the typical microstructural features and the mechanical and chemical properties in laser-induced rapidly solidified HEAs, and these data are compared with conventional Co- and Ni-based alloy coatings. The article concludes with suggestions for future research and development in HEAs, from considerations of their characteristic properties.

  1. Proteins related to the spindle and checkpoint mitotic emphasize the different pathogenesis of hypoplastic MDS.

    PubMed

    Heredia, Fabiola Fernandes; de Sousa, Juliana Cordeiro; Ribeiro Junior, Howard Lopes; Carvalho, Alex Fiorini; Magalhaes, Silvia Maria Meira; Pinheiro, Ronald Feitosa

    2014-02-01

    Some studies show that alterations in expression of proteins related to mitotic spindle (AURORAS KINASE A and B) and mitotic checkpoint (CDC20 and MAD2L1) are involved in chromosomal instability and tumor progression in various solid and hematologic malignancies. This study aimed to evaluate these genes in MDS patients. The cytogenetics analysis was carried out by G-banding, AURKA and AURKB amplification was performed using FISH, and AURKA, AURKB, CDC20 and MAD2L1 gene expression was performed by qRT-PCR in 61 samples of bone marrow from MDS patients. AURKA gene amplification was observed in 10% of the cases, which also showed higher expression levels than the control group (p=0.038). Patients with normo/hypercellular BM presented significantly higher expression levels than hypocellular BM patients, but normo and hypercellular BM groups did not differ. After logistic regression analysis, our results showed that HIGH expression levels were associated with increased risk of developing normo/hypercellular MDS. It also indicated that age is associated with AURKA, CDC20 and MAD2L1 HIGH expression levels. The distinct expression of hypocellular patients emphasizes the prognostic importance of cellularity to MDS. The amplification/high expression of AURKA suggests that the increased expression of this gene may be related to the pathogenesis of disease. PMID:24314588

  2. Proteomic Analysis of Mitotic RNA Polymerase II Reveals Novel Interactors and Association With Proteins Dysfunctional in Disease*

    PubMed Central

    Möller, André; Xie, Sheila Q.; Hosp, Fabian; Lang, Benjamin; Phatnani, Hemali P.; James, Sonya; Ramirez, Francisco; Collin, Gayle B.; Naggert, Jürgen K.; Babu, M. Madan; Greenleaf, Arno L.; Selbach, Matthias; Pombo, Ana

    2012-01-01

    RNA polymerase II (RNAPII) transcribes protein-coding genes in eukaryotes and interacts with factors involved in chromatin remodeling, transcriptional activation, elongation, and RNA processing. Here, we present the isolation of native RNAPII complexes using mild extraction conditions and immunoaffinity purification. RNAPII complexes were extracted from mitotic cells, where they exist dissociated from chromatin. The proteomic content of native complexes in total and size-fractionated extracts was determined using highly sensitive LC-MS/MS. Protein associations with RNAPII were validated by high-resolution immunolocalization experiments in both mitotic cells and in interphase nuclei. Functional assays of transcriptional activity were performed after siRNA-mediated knockdown. We identify >400 RNAPII associated proteins in mitosis, among these previously uncharacterized proteins for which we show roles in transcriptional elongation. We also identify, as novel functional RNAPII interactors, two proteins involved in human disease, ALMS1 and TFG, emphasizing the importance of gene regulation for normal development and physiology. PMID:22199231

  3. Universal features in the photoemission spectroscopy of high-temperature superconductors

    PubMed Central

    Zhao, Junjing; Chatterjee, Utpal; Ai, Dingfei; Hinks, David G.; Zheng, Hong; Gu, G. D.; Castellan, John-Paul; Rosenkranz, Stephan; Claus, Helmut; Norman, Michael R.; Randeria, Mohit; Campuzano, Juan Carlos

    2013-01-01

    The energy gap for electronic excitations is one of the most important characteristics of the superconducting state, as it directly reflects the pairing of electrons. In the copper–oxide high-temperature superconductors (HTSCs), a strongly anisotropic energy gap, which vanishes along high-symmetry directions, is a clear manifestation of the d-wave symmetry of the pairing. There is, however, a dramatic change in the form of the gap anisotropy with reduced carrier concentration (underdoping). Although the vanishing of the gap along the diagonal to the square Cu–O bond directions is robust, the doping dependence of the large gap along the Cu–O directions suggests that its origin might be different from pairing. It is thus tempting to associate the large gap with a second-order parameter distinct from superconductivity. We use angle-resolved photoemission spectroscopy to show that the two-gap behavior and the destruction of well-defined electronic excitations are not universal features of HTSCs, and depend sensitively on how the underdoped materials are prepared. Depending on cation substitution, underdoped samples either show two-gap behavior or not. In contrast, many other characteristics of HTSCs, such as the dome-like dependence of on doping, long-lived excitations along the diagonals to the Cu–O bonds, and an energy gap at the Brillouin zone boundary that decreases monotonically with doping while persisting above (the pseudogap), are present in all samples, irrespective of whether they exhibit two-gap behavior or not. Our results imply that universal aspects of high- superconductivity are relatively insensitive to differences in the electronic states along the Cu–O bond directions. PMID:24101464

  4. High-Resolution Infrared Space Observatory Spectroscopy of the Unidentified 21 Micron Feature

    NASA Technical Reports Server (NTRS)

    Volk, Kevin; Kwok, Sun; Hrivnak, Bruce

    1999-01-01

    We present Infrared Space Observatory SWS06 mode observations of the 21 micron feature in eight sources, including a first "detection of the feature in IRAS Z02229+6208. The observed feature peak-to-continuum ratios range from 0.13 in IRAS Z02229+6208 to 1.30 in IRAS 07134+1005. The normalized spectra, obtained by the removal of the underlying continua and by scaling the features to the same peak flux value. show that all features have the same intrinsic profile and peak wavelength. There is no evidence for any discrete substructure due to molecular bands in the observed spectra, suggesting that the 21 micron feature is due to either a solid substance or a mixture of many similarly structured large molecules.

  5. Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism

    Microsoft Academic Search

    Robert V. Skibbens; Victoria Petrie Skeen; E. D. Salmon

    1993-01-01

    Most models of mitotic congression and segregation assume that only poleward pulling forces occur at kinetochores. However, there are reports for several different cell types that both mono-oriented and bi-oriented chromosomes oscillate toward and away from the pole throughout mitosis. We used new methods of high resolution video microscopy and computer-assisted tracking techniques to measure the positions over time of

  6. Mitotic and polytene chromosome analysis in the Mexican fruit fly, Anastrepha ludens (Loew) (Diptera: Tephritidae).

    PubMed

    Garcia-Martinez, V; Hernandez-Ortiz, E; Zepeta-Cisneros, C S; Robinson, A S; Zacharopoulou, A; Franz, G

    2009-01-01

    The present study constitutes the first attempt to construct a polytene chromosome map of an Anastrepha species, Anastrepha ludens (Loew), a major agricultural pest. The mitotic karyotype has a diploid complement of 12 acrocentric chromosomes, including five pairs of autosomes and an XX/XY sex chromosome pair. The analysis of salivary gland polytene chromosomes has shown a total number of five polytene elements that correspond to the five autosomes. The characteristic features and the most prominent landmarks of each chromosome are described. By comparing chromosome banding patterns, the possible chromosomal homology between A. ludens and Ceratitis capitata (Wiedemann) is presented. This work shows that polytene maps of A. ludens are suitable for cytogenetic studies in this species and may be used as reference for other Anastrepha species, most of which are also serious agricultural pests. PMID:19132068

  7. Mitotic activity in the growing red deer antler.

    PubMed

    Matich, Jessica; Basford Nicholson, Louise Frances; Barling, Peter Michael

    2003-01-01

    Antlers grow rapidly through the coordinated development of both osseocartilage and skin (velvet). The regional patterns of cell division in these two compartments were assessed by immunochemical detection of proliferating cell nuclear antigen (PCNA) in antlers from one-year-old red deer. The whole antler integument was in a state of growth and/or renewal, particularly the keratinocytes of the basal cell layer of the epidermis near the tip, and hair bulbs and sebaceous glands. More proximally, a zone of weaker mitotic activity was detected. Within the osseocartilagenous compartment, rapid mitosis was particularly apparent within the distal mesenchyme, visible as a dome-shaped band of staining. Mitotic activity of chondrocytes and osteoblasts was more extensive in peripheral areas of developing bone than in the centre. We conclude that the antler tip is the site of most active epidermal growth, and hypothesise that other mechanisms in addition to mechanical stretching play a role in growth of the integument. PMID:12867154

  8. Molecular pathways regulating mitotic spindle orientation in animal cells

    PubMed Central

    Lu, Michelle S.; Johnston, Christopher A.

    2013-01-01

    Orientation of the cell division axis is essential for the correct development and maintenance of tissue morphology, both for symmetric cell divisions and for the asymmetric distribution of fate determinants during, for example, stem cell divisions. Oriented cell division depends on the positioning of the mitotic spindle relative to an axis of polarity. Recent studies have illuminated an expanding list of spindle orientation regulators, and a molecular model for how cells couple cortical polarity with spindle positioning has begun to emerge. Here, we review both the well-established spindle orientation pathways and recently identified regulators, focusing on how communication between the cell cortex and the spindle is achieved, to provide a contemporary view of how positioning of the mitotic spindle occurs. PMID:23571210

  9. Mitotic indexes as prognostic predictors in female breast cancer

    Microsoft Academic Search

    S. Aaltomaa; P. Lipponen; M. Eskelinen; V.-M. Kosma; S. Marin; E. Alhava; K. Syrjänen

    1992-01-01

    Summary A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, axillary lymph node status, histological grade, histological type and two mitotic indexes (M\\/V; MAI) were assessed and related to disease outcome. Primary tumour size (PPP=0.0001), and histological grade (P=0.0074) predicted axillary lymph node status. Recurrence as well as recurrence-free survival was

  10. Mitotic activity in dorsal epidermis of Rana pipiens.

    NASA Technical Reports Server (NTRS)

    Garcia-Arce, H.; Mizell, S.

    1972-01-01

    Study of statistically significant rhythms of mitotic division in dorsal epidermis of frogs, Rana pipiens, exposed to a 12:12 light:dark environment for 14 days. The results include the findings that (1) male animals have a primary period of 22 hr in summer and 18 hr in winter, (2) female animals have an 18 hr period, and (3) parapinealectomy and blinding abolish the rhythm.

  11. Fission yeast pkl1 is a kinesin-related protein involved in mitotic spindle function.

    PubMed Central

    Pidoux, A L; LeDizet, M; Cande, W Z

    1996-01-01

    We have used anti-peptide antibodies raised against highly conserved regions of the kinesin motor domain to identify kinesin-related proteins in the fission yeast Schizosaccharomyces pombe. Here we report the identification of a new kinesin-related protein, which we have named pkl1. Sequence homology and domain organization place pkl1 in the Kar3/ncd subfamily of kinesin-related proteins. Bacterially expressed pkl1 fusion proteins display microtubule-stimulated ATPase activity, nucleotide-sensitive binding, and bundling of microtubules. Immunofluorescence studies with affinity-purified antibodies indicate that the pkl1 protein localizes to the nucleus and the mitotic spindle. Pkl1 null mutants are viable but have increased sensitivity to microtubule-disrupting drugs. Disruption of pkl1+ suppresses mutations in another kinesin-related protein, cut7, which is known to act in the spindle. Overexpression of pkl1 to very high levels causes a similar phenotype to that seen in cut7 mutants: V-shaped and star-shaped microtubule structures are observed, which we interpret to be spindles with unseparated spindle poles. These observations suggest that pkl1 and cut7 provide opposing forces in the spindle. We propose that pkl1 functions as a microtubule-dependent motor that is involved in microtubule organization in the mitotic spindle. Images PMID:8898367

  12. Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes

    PubMed Central

    Zhen, Chao Yu; Duc, Huy Nguyen; Kokotovic, Marko; Phiel, Christopher J.; Ren, Xiaojun

    2014-01-01

    Polycomb group (PcG) proteins are epigenetic transcriptional factors that repress key developmental regulators and maintain cellular identity through mitosis via a poorly understood mechanism. Using quantitative live-cell imaging in mouse ES cells and tumor cells, we demonstrate that, although Polycomb repressive complex (PRC) 1 proteins (Cbx-family proteins, Ring1b, Mel18, and Phc1) exhibit variable capacities of association with mitotic chromosomes, Cbx2 overwhelmingly binds to mitotic chromosomes. The recruitment of Cbx2 to mitotic chromosomes is independent of PRC1 or PRC2, and Cbx2 is needed to recruit PRC1 complex to mitotic chromosomes. Quantitative fluorescence recovery after photobleaching analysis indicates that PRC1 proteins rapidly exchange at interphasic chromatin. On entry into mitosis, Cbx2, Ring1b, Mel18, and Phc1 proteins become immobilized at mitotic chromosomes, whereas other Cbx-family proteins dynamically bind to mitotic chromosomes. Depletion of PRC1 or PRC2 protein has no effect on the immobilization of Cbx2 on mitotic chromosomes. We find that the N-terminus of Cbx2 is needed for its recruitment to mitotic chromosomes, whereas the C-terminus is required for its immobilization. Thus these results provide fundamental insights into the molecular mechanisms of epigenetic inheritance. PMID:25232004

  13. Microdevice having interior cavity with high aspect ratio surface features and associated methods of manufacture and use

    DOEpatents

    Morales, Alfredo M. (Pleasanton, CA)

    2002-01-01

    A microdevice having interior cavity with high aspect ratio features and ultrasmooth surfaces, and associated method of manufacture and use is described. An LIGA-produced shaped bit is used to contour polish the surface of a sacrificial mandrel. The contoured sacrificial mandrel is subsequently coated with a structural material and the mandrel removed to produce microdevices having micrometer-sized surface features and sub-micrometer RMS surface roughness.

  14. The overlooked greatwall: a new perspective on mitotic control.

    PubMed

    Glover, David M

    2012-03-01

    The role of the dual specificity protein phosphatase, Cdc25, in activating the cyclin-dependent kinase-cyclin B complex (Cdk1-CycB) by overcoming the inhibitory Wee1 kinase is a long-established principle for mitotic entry. Recently, however, evidence has emerged of a regulatory network that facilitates Cdk1-CycB activity by inhibiting the form of protein phosphatase 2A having a B55 regulatory subunit (PP2A-B55). Here, I review the genetic and biochemical evidence for Greatwall kinase and its substrate Endosulphine as the key components of this previously obscure regulatory network. Not only is the inhibition of PP2A-B55 by phospho-endosulphine required to prevent dephosphorylation of Cdk1-CycB substrates until mitotic exit, but it is also required to promote Cdc25 activity and inhibit Wee1 at mitotic entry. I discuss how these alternating states of preferential PP2A-B55 or Cdk1-CycB activity can have an impact upon the regulation of Polo kinase and its ability to bind different partner proteins as mitosis progresses. PMID:22754657

  15. SUMOylation inhibits FOXM1 activity and delays mitotic transition.

    PubMed

    Myatt, S S; Kongsema, M; Man, C W-Y; Kelly, D J; Gomes, A R; Khongkow, P; Karunarathna, U; Zona, S; Langer, J K; Dunsby, C W; Coombes, R C; French, P M; Brosens, J J; Lam, E W-F

    2014-08-21

    The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response. PMID:24362530

  16. SUMOylation inhibits FOXM1 activity and delays mitotic transition

    PubMed Central

    Myatt, S S; Kongsema, M; Man, C W-Y; Kelly, D J; Gomes, A R; Khongkow, P; Karunarathna, U; Zona, S; Langer, J K; Dunsby, C W; Coombes, R C; French, P M; Brosens, J J; Lam, E W-F

    2014-01-01

    The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response. PMID:24362530

  17. Multiscale analysis of geomorphological and geological features in high resolution digital elevation models using the wavelet transform

    E-print Network

    Multiscale analysis of geomorphological and geological features in high resolution digital the context of high precision geomorphological analysis. These new elevation models permitted to reveal struc of the wavelet decomposition as an ap- proach for the analysis of geomorphological multiscale structures

  18. High Energy Break and Reflection Features in the Seyfert Galaxy MCG+8-11-11

    E-print Network

    P. Grandi; F. Haardt; G. Ghisellini; E. J. Grove; L. Maraschi; C. M. Urry

    1997-11-20

    We present the results from ASCA and OSSE simultaneous observations of the Seyfert 1.5 galaxy MCG+8-11-11 performed in August-September 1995. The ASCA observations indicate a modest flux increase (20%) in 3 days, possibly correlated to a softening of the 0.6-9 keV spectrum. The spectrum is well described by a hard power law (Gamma=1.64) absorbed by a column density slightly larger than the Galactic value, with an iron line at 6.4 keV of EW=400 eV. The simultaneous OSSE data are characterized by a much softer power law with photon index Gamma=3.0, strongly suggesting the presence of a spectral break in the hard X/soft gamma-ray band. A joint fit to OSSE and ASCA data clearly shows an exponential cut-off at about 300 keV, and strong reflection component. MCG+8-11-11 features a spectral break in the underlying continuum unambiguously. This, together with the inferred low compactness of this source, favours thermal or quasi-thermal electron Comptonization in a structured Corona as the leading process of high energy radiation production.

  19. Etching of Silicon in HBr Plasmas for High Aspect Ratio Features

    NASA Technical Reports Server (NTRS)

    Hwang, Helen H.; Meyyappan, M.; Mathad, G. S.; Ranade, R.

    2002-01-01

    Etching in semiconductor processing typically involves using halides because of the relatively fast rates. Bromine containing plasmas can generate high aspect ratio trenches, desirable for DRAM and MEMS applications, with relatively straight sidewalk We present scanning electron microscope images for silicon-etched trenches in a HBr plasma. Using a feature profile simulation, we show that the removal yield parameter, or number of neutrals removed per incident ion due to all processes (sputtering, spontaneous desorption, etc.), dictates the profile shape. We find that the profile becomes pinched off when the removal yield is a constant, with a maximum aspect ratio (AR) of about 5 to 1 (depth to height). When the removal yield decreases with increasing ion angle, the etch rate increases at the comers and the trench bottom broadens. The profiles have ARs of over 9:1 for yields that vary with ion angle. To match the experimentally observed etched time of 250 s for an AR of 9:1 with a trench width of 0.135 microns, we find that the neutral flux must be 3.336 x 10(exp 17)sq cm/s.

  20. Interaction-based feature selection and classification for high-dimensional biological data

    PubMed Central

    Hu, Inchi

    2012-01-01

    Motivation: Epistasis or gene–gene interaction has gained increasing attention in studies of complex diseases. Its presence as an ubiquitous component of genetic architecture of common human diseases has been contemplated. However, the detection of gene–gene interaction is difficult due to combinatorial explosion. Results: We present a novel feature selection method incorporating variable interaction. Three gene expression datasets are analyzed to illustrate our method, although it can also be applied to other types of high-dimensional data. The quality of variables selected is evaluated in two ways: first by classification error rates, then by functional relevance assessed using biological knowledge. We show that the classification error rates can be significantly reduced by considering interactions. Secondly, a sizable portion of genes identified by our method for breast cancer metastasis overlaps with those reported in gene-to-system breast cancer (G2SBC) database as disease associated and some of them have interesting biological implication. In summary, interaction-based methods may lead to substantial gain in biological insights as well as more accurate prediction. Contact: imichu@ust.hk; slo@stat.columnbia.edu Supplementary information: Supplementary data are available at the Bioinformatics online. PMID:22945786

  1. Some features of bulk melt-textured high-temperature superconductors subjected to alternating magnetic fields

    NASA Astrophysics Data System (ADS)

    Vanderbemden, P.; Molenberg, I.; Simeonova, P.; Lovchinov, V.

    2014-12-01

    Monolithic, large grain, (RE)Ba2Cu3O7 high-temperature superconductors (where RE denotes a rare-earth ion) are known to be able to trap fields in excess of several teslas and represent thus an extremely promising competing technology for permanent magnet in several applications, e.g. in motors and generators. In any rotating machine, however, the superconducting permanent magnet is subjected to variable (transient, or alternating) parasitic magnetic fields. These magnetic fields interact with the superconductor, which yields a reduction of the remnant magnetization. In the present work we quantify these effects by analysing selected experimental data on bulk melt-textured superconductors subjected to AC fields. Our results indicate that the non-uniformity of superconducting properties in rather large samples might lead to unusual features and need to be taken into account to analyse the experimental data. We also investigate the evolution of the DC remnant magnetization of the bulk sample when it is subjected to a large number of AC magnetic field cycles, and investigate the experimental errors that result from a misorientation of the sample or a mispositioning of the Hall probe. The time-dependence of the remnant magnetization over 100000 cycles of the AC field is shown to display distinct regimes which all differ strongly from the usual decay due to magnetic relaxation.

  2. Specific features of intervalley scattering of charge carriers in n-Si at high temperatures

    SciTech Connect

    Fedosov, A. V.; Luniov, S. V., E-mail: luniovser@mail.ru [Lutsk National Technical University (Ukraine); Fedosov, S. A., E-mail: ftt@univer.lutsk.ua [Lesya Ukrainka Volyn National University (Ukraine)

    2010-10-15

    In n-Si, intervalley scattering of electrons can be of two types, f scattering and g scattering. With the purpose of establishing the contributions of f- and g-type transitions to intervalley scattering, the piezoresistance of n-Si crystals is studied in the temperature range T = 295-363 K. The initial concentration of charge carriers in the n-Si samples is 1.1 x 10{sup 14} cm{sup -3}, and the resistivity at 300 K is {rho} = 30 {Omega} cm. As the temperature is increased, the region of leveling-off of the piezoresistance shifts to lower voltages. The characteristic feature of the dependence {rho} = {rho}(T) plotted in the double logarithmic coordinates (log{rho} = f(logT)) is the transition from the slope 1.68 to the slope 1.83 at T > 330 K. This is attributed to the substantial contribution of g transitions to intervalley scattering in the high-temperature region. For verification of the interpretation of the dependence {rho} = {rho}(T), the dependence is calculated on the basis of the theory of anisotropic scattering with consideration for intervalley transitions.

  3. Human Nek7-interactor RGS2 is required for mitotic spindle organization.

    PubMed

    de Souza, Edmarcia Elisa; Hehnly, Heidi; Perez, Arina Marina; Meirelles, Gabriela Vaz; Smetana, Juliana Helena Costa; Doxsey, Stephen; Kobarg, Jörg

    2015-01-01

    The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced ?-tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization. PMID:25664600

  4. An improved high order texture features extraction method with application to pathological diagnosis of colon lesions for CT colonography

    NASA Astrophysics Data System (ADS)

    Song, Bowen; Zhang, Guopeng; Lu, Hongbing; Wang, Huafeng; Han, Fangfang; Zhu, Wei; Liang, Zhengrong

    2014-03-01

    Differentiation of colon lesions according to underlying pathology, e.g., neoplastic and non-neoplastic, is of fundamental importance for patient management. Image intensity based textural features have been recognized as a useful biomarker for the differentiation task. In this paper, we introduce high order texture features, beyond the intensity, such as gradient and curvature, for that task. Based on the Haralick texture analysis method, we introduce a virtual pathological method to explore the utility of texture features from high order differentiations, i.e., gradient and curvature, of the image intensity distribution. The texture features were validated on database consisting of 148 colon lesions, of which 35 are non-neoplastic lesions, using the random forest classifier and the merit of area under the curve (AUC) of the receiver operating characteristics. The results show that after applying the high order features, the AUC was improved from 0.8069 to 0.8544 in differentiating non-neoplastic lesion from neoplastic ones, e.g., hyperplastic polyps from tubular adenomas, tubulovillous adenomas and adenocarcinomas. The experimental results demonstrated that texture features from the higher order images can significantly improve the classification accuracy in pathological differentiation of colorectal lesions. The gain in differentiation capability shall increase the potential of computed tomography (CT) colonography for colorectal cancer screening by not only detecting polyps but also classifying them from optimal polyp management for the best outcome in personalized medicine.

  5. Analysis of breast lesions on contrast-enhanced magnetic resonance images using high-dimensional texture features

    NASA Astrophysics Data System (ADS)

    Nagarajan, Mahesh B.; Huber, Markus B.; Schlossbauer, Thomas; Leinsinger, Gerda; Wismueller, Axel

    2010-03-01

    Haralick texture features derived from gray-level co-occurrence matrices (GLCM) were used to classify the character of suspicious breast lesions as benign or malignant on dynamic contrast-enhanced MRI studies. Lesions were identified and annotated by an experienced radiologist on 54 MRI exams of female patients where histopathological reports were available prior to this investigation. GLCMs were then extracted from these 2D regions of interest (ROI) for four principal directions (0°, 45°, 90° & 135°) and used to compute Haralick texture features. A fuzzy k-nearest neighbor (k- NN) classifier was optimized in ten-fold cross-validation for each texture feature and the classification performance was calculated on an independent test set as a function of area under the ROC curve. The lesion ROIs were characterized by texture feature vectors containing the Haralick feature values computed from each directional-GLCM; and the classifier results obtained were compared to a previously used approach where the directional-GLCMs were summed to a nondirectional GLCM which could further yield a set of texture feature values. The impact of varying the inter-pixel distance while generating the GLCMs on the classifier's performance was also investigated. Classifier's AUC was found to significantly increase when the high-dimensional texture feature vector approach was pursued, and when features derived from GLCMs generated using different inter-pixel distances were incorporated into the classification task. These results indicate that lesion character classification accuracy could be improved by retaining the texture features derived from the different directional GLCMs rather than combining these to yield a set of scalar feature values instead.

  6. Cascaded ensemble of convolutional neural networks and handcrafted features for mitosis detection

    NASA Astrophysics Data System (ADS)

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-03-01

    Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is mitotic count, which involves quantifying the number of cells in the process of dividing (i.e. undergoing mitosis) at a specific point in time. Currently mitosis counting is done manually by a pathologist looking at multiple high power fields on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical or textural attributes of mitoses or features learned with convolutional neural networks (CNN). While handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely unsupervised feature generation methods, there is an appeal to attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. In this paper, we present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 High Power Fields (HPF, x400 magnification) by several pathologists and 15 testing HPFs yielded an F-measure of 0.7345. Apart from this being the second best performance ever recorded for this MITOS dataset, our approach is faster and requires fewer computing resources compared to extant methods, making this feasible for clinical use.

  7. Cloud field classification based upon high spatial resolution textural features. I - Gray level co-occurrence matrix approach

    NASA Technical Reports Server (NTRS)

    Welch, R. M.; Sengupta, S. K.; Chen, D. W.

    1988-01-01

    Stratocumulus, cumulus, and cirrus clouds were identified on the basis of cloud textural features which were derived from a single high-resolution Landsat MSS NIR channel using a stepwise linear discriminant analysis. It is shown that, using this method, it is possible to distinguish high cirrus clouds from low clouds with high accuracy on the basis of spatial brightness patterns. The largest probability of misclassification is associated with confusion between the stratocumulus breakup regions and the fair-weather cumulus.

  8. Intracellular Targets for a Phosphotyrosine Peptidomimetic include the Mitotic Kinesin, MCAK

    PubMed Central

    Huang, Rong; Oh, Hyunju; Arrendale, Allison; Martin, Victoria A.; Galan, Jacob; Workman, Eric J.; Stout, Jane R.; Walczak, Claire E.; Tao, W. Andy; Borch, Richard F.; Geahlen, Robert L.

    2013-01-01

    SH2 domains are attractive targets for chemotherapeutic agents due to their involvement in the formation of protein-protein interactions critical to many signal transduction cascades. Little is known, however, about how synthetic SH2 domain ligands would influence the growth properties of tumor cells or with which intracellular proteins they would interact due to their highly charged nature and enzymatic lability. In this study, a prodrug delivery strategy was used to introduce an enzymatically stable, phosphotyrosine peptidomimetic into tumor cells. When tested in a human tumor cell panel, the prodrug exhibited a preference for inhibiting the growth of leukemia and lymphoma cells. In these cells, it was largely cytostatic and induced endoreduplication and the appearance of midbodies. Proteomic analyses identified multiple targets that included mitotic centromere-associated kinesin (MCAK). Molecular modeling studies suggested the ATP-binding site on MCAK as the likely site of drug interaction. Consistent with this, ATP inhibited the drug-MCAK interaction and the drug inhibited MCAK ATPase activity. Accordingly, the effects of the prodrug on the assembly of the mitotic spindle and alignment of chromosomes were consistent with the identification of MCAK as an important intracellular target. PMID:23830822

  9. MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes

    PubMed Central

    He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B.; Zhang, Yaou

    2013-01-01

    MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the expression of these genes by directly targeting their 3?-UTRs. Over-expression of exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. Taken together, these results implicate that miR-210 disturbs mitosis through targeting multi-genes involved in mitotic progression, which may contribute to its inhibitory role on tumor formation. PMID:23125370

  10. The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C.

    PubMed

    Izawa, Daisuke; Pines, Jonathon

    2015-01-29

    The spindle assembly checkpoint (SAC) maintains genomic stability by delaying chromosome segregation until the last chromosome has attached to the mitotic spindle. The SAC prevents the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase from recognizing cyclin B and securin by catalysing the incorporation of the APC/C co-activator, CDC20, into a complex called the mitotic checkpoint complex (MCC). The SAC works through unattached kinetochores generating a diffusible 'wait anaphase' signal that inhibits the APC/C in the cytoplasm, but the nature of this signal remains a key unsolved problem. Moreover, the SAC and the APC/C are highly responsive to each other: the APC/C quickly targets cyclin B and securin once all the chromosomes attach in metaphase, but is rapidly inhibited should kinetochore attachment be perturbed. How this is achieved is also unknown. Here, we show that the MCC can inhibit a second CDC20 that has already bound and activated the APC/C. We show how the MCC inhibits active APC/C and that this is essential for the SAC. Moreover, this mechanism can prevent anaphase in the absence of kinetochore signalling. Thus, we propose that the diffusible 'wait anaphase' signal could be the MCC itself, and explain how reactivating the SAC can rapidly inhibit active APC/C. PMID:25383541

  11. A phenotypic screen identifies microtubule plus end assembly regulators that can function in mitotic spindle orientation.

    PubMed

    Stolz, Ailine; Ertych, Norman; Bastians, Holger

    2015-03-19

    Proper regulation of microtubule dynamics during mitosis is essential for faithful chromosome segregation. In fact, recently we discovered increased microtubule plus end assembly rates that are frequently observed in human cancer cells as an important mechanism leading to whole chromosome missegregation and chromosomal instability (CIN). However, the genetic alterations responsible for increased microtubule polymerization rates in cancer cells remain largely unknown. The identification of such lesions is hampered by the fact that determining dynamic parameters of microtubules usually involves analyses of living cells, which is technically difficult to perform in large-scale screening settings. Therefore, we sought to identify alternative options to systematically identify regulators of microtubule plus end polymerization. Here, we introduce a simple and robust phenotypic screening assay that is based on the analyses of monopolar mitotic spindle structures that are induced upon inhibition of the mitotic kinesin Eg5/KIF11. We show that increased microtubule polymerization causes highly asymmetric monoasters in the presence of Eg5/KIF11 inhibition and this phenotype can be reliably assessed in living as well as in fixed cells. Using this assay we performed a siRNA screen, in which we identify several microtubule plus end binding proteins as well as centrosomal and cortex associated proteins as important regulators of microtubule plus end assembly. Interestingly, we demonstrate that a subgroup of these regulators function in the regulation of spindle orientation through their role in dampening microtubule plus end polymerization. PMID:25590964

  12. Reversal of cell determination in yeast meiosis: postcommitment arrest allows return to mitotic growth.

    PubMed Central

    Honigberg, S M; Esposito, R E

    1994-01-01

    When yeast from the early stages of meiosis are transferred from sporulation to growth medium, they can reenter the mitotic cell cycle directly. In contrast, cells from later stages of meiosis (after the initiation of the first nuclear division) will complete meiosis and sporulation despite the shift to growth medium, a phenomenon known as "commitment to meiosis." This study reports the surprising finding that when the normal progression of meiosis is arrested, cells from later stages of meiosis can return to growth. Cells were arrested after the first or second meiotic division by three independent means: the spo14 mutation, the spo3-1 mutation, and a high-temperature arrest of wild-type cells. In every case, the arrested cells were able to form buds after transfer to growth medium. These cells, however, experienced a delay upon return to growth relative to uncommitted cells. We propose that the commitment phenomenon results from a transient delay of mitotic growth, which occurs specifically during meiosis, and that commitment does not involve an irreversible inhibition of mitosis as previously thought. Images PMID:8022820

  13. Lgr5 Marks Post-Mitotic, Lineage Restricted Cerebellar Granule Neurons during Postnatal Development

    PubMed Central

    Miller, Tyler E.; Wang, Jun; Sukhdeo, Kumar; Horbinski, Craig; Tesar, Paul J.; Wechsler-Reya, Robert J.; Rich, Jeremy N.

    2014-01-01

    Wnt signaling regulates self-renewal and fate commitment of stem and progenitor cells in development and homeostasis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a co-receptor for Wnt signaling that marks highly proliferative stem and progenitor cells in many epithelial tissue types. Wnt signaling instructs neural developmental and homeostatic processes; however, Lgr5 expression in the developing and adult brain has not been characterized. Here we report that Lgr5 is expressed in the postnatal cerebellum during the maturation and synaptogenesis of cerebellar granule neurons (CGNs), processes controlled by Wnt signaling. Using a transgenic reporter mouse for in vivo Lgr5 expression analysis and lineage tracing, we reveal that Lgr5 specifically identified CGNs and was restricted temporally to the CGN maturation phase within the internal granule layer, but absent in the adult brain. Cells marked by Lgr5 were lineage restricted, post-mitotic and long-lived. The ligand for Lgr5, R-spondin, was secreted in a paracrine fashion that evolved during the maturation of CGNs, which coincided with the Lgr5 expression pattern. Our findings provide potential new insight into the critical regulation of Wnt signaling in the developing cerebellum and support a novel role for Lgr5 in the regulation of post-mitotic cells. PMID:25493560

  14. Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo

    SciTech Connect

    Rubin, N.H.

    1982-01-01

    Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, to a lesser extent, degree of recovery.

  15. Listeria bacteriophage peptidoglycan hydrolases feature high thermoresistance and reveal increased activity after divalent metal cation substitution.

    PubMed

    Schmelcher, Mathias; Waldherr, Florian; Loessner, Martin J

    2012-01-01

    The ability of the bacteriophage-encoded peptidoglycan hydrolases (endolysins) to destroy Gram-positive bacteria from without makes these enzymes promising antimicrobials. Recombinant endolysins from Listeria monocytogenes phages have been shown to rapidly lyse and kill the pathogen in all environments. To determine optimum conditions regarding application of recombinant Listeria phage endolysins in food or production equipments, properties of different Listeria endolysins were studied. Optimum NaCl concentration for the amidase HPL511 was 200 nM and 300 mM for the peptidases HPL118, HPL500, and HPLP35. Unlike most other peptidoglycan hydrolases, all four enzymes exhibited highest activity at elevated pH values at around pH 8-9. Lytic activity was abolished by EDTA and could be restored by supplementation with various divalent metal cations, indicating their role in catalytic function. While substitution of the native Zn(2+) by Ca(2+) or Mn(2+) was most effective in case of HPL118, HPL500, and HPLP35, supplementation with Co(2+) and Mn(2+) resulted in an approximately 5-fold increase in HPL511 activity. Interestingly, the glutamate peptidases feature a conserved SxHxxGxAxD zinc-binding motif, which is not present in the amidases, although they also require centrally located divalent metals for activity. The endolysins HPL118, HPL511, and HPLP35 revealed a surprisingly high thermostability, with up to 35% activity remaining after 30 min incubation at 90°C. The available data suggest that denaturation at elevated temperatures is reversible and may be followed by rapid refolding into a functional state. PMID:21720825

  16. Deltex-1 Activates Mitotic Signaling and Proliferation and Increases the Clonogenic and Invasive Potential of U373 and LN18 Glioblastoma Cells and Correlates with Patient Survival

    PubMed Central

    Huber, Roland M.; Rajski, Michal; Sivasankaran, Balasubramanian; Moncayo, Gerald; Hemmings, Brian A.; Merlo, Adrian

    2013-01-01

    Glioblastoma (GBM) is a highly malignant primary tumor of the central nervous system originating in glial cells. GBM results in more years of life lost than any other cancer type. Low levels of Notch receptor expression correlates with prolonged survival in various high grade gliomas independent of other markers. Different downstream pathways of Notch receptors have been identified. We tested if the Notch/Deltex pathway, which is distinct from the canonical, CSL-mediated pathway, has a role in GBM. We show that the alternative or non-canonical Notch pathway functioning through Deltex1 (DTX1) mediates key features of glioblastoma cell aggressiveness. For example, DTX1 activates the RTK/PI3K/PKB and the MAPK/ERK mitotic pathways and induces anti-apoptotic Mcl-1. The clonogenic and growth potential of established glioma cells correlated with DTX1 levels. Microarray gene expression analysis further identified a DTX1-specific, MAML1-independent transcriptional program - including microRNA-21- which is functionally linked to the changes in tumor cell aggressiveness. Over-expression of DTX1 increased cell migration and invasion correlating to ERK activation, miR-21 levels and endogenous Notch levels. In contrast to high and intermediate expressors, patients with low DTX1 levels have a more favorable prognosis. The alternative Notch pathway via DTX1 appears to be an oncogenic factor in glioblastoma and these findings offer new potential therapeutic targets. PMID:23451269

  17. A hybrid feature extraction selection approach for high-dimensional non-Gaussian data clustering.

    PubMed

    Boutemedjet, Sabri; Bouguila, Nizar; Ziou, Djemel

    2009-08-01

    This paper presents an unsupervised approach for feature selection and extraction in mixtures of generalized Dirichlet (GD) distributions. Our method defines a new mixture model that is able to extract independent and non-Gaussian features without loss of accuracy. The proposed model is learned using the Expectation-Maximization algorithm by minimizing the message length of the data set. Experimental results show the merits of the proposed methodology in the categorization of object images. PMID:19542577

  18. Suppression of ser/thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death

    PubMed Central

    Theobald, Benjamin; Bonness, Kathy; Musiyenko, Alla; Andrews, Joel F.; Urban, Gudrun; Huang, Xizhong; Dean, Nicholas M.; Honkanen, Richard E.

    2013-01-01

    Fostriecin is a natural product purified from Sterptomyces extracts with antitumor activity sufficient to warrant human clinical trials. Unfortunately, difficulties associated with supply and stable drug formulation stalled further development. At a molecular level, fostriecin is known to act as a catalytic inhibitor of four PPP-family-phosphatases, and reports describing the syntheses of designed molecules in the class suggest derivatives targeting enzymes within the fostriecin sensitive sub-family can be produced. However, it is not clear if the tumor selective cytotoxicity of fostriecin results from the inhibition of a specific phosphatase, multiple phosphatases, or a limited subset of fostriecin sensitive phosphatases. How the inhibition of sensitive phosphatases contributes to tumor selective cytotoxicity is also not clear. Here, high-content time-lapse imaging of live cells reveals novel insight into the cellular actions of fostriecin, showing that fostriecin induced apoptosis is not simply induced following a sustained mitotic arrest. Rather, apoptosis occurs in an apparent second interphase produced when tetraploid cells undergo mitotic slippage. Comparison of the actions of fostriecin and antisense-oligonucleotides specifically targeting human fostriecin-sensitive phosphatases revealed that the suppression PP4C alone is sufficient to mimic many actions of fostriecin. Importantly, antisense-oligonucleotides targeting PP4C induce apoptosis, with death occurring in tetraploid cells produced following mitotic slippage. This affect was not observed following the suppression of PP1C, PP2AC or PP5C. Although future studies are needed to clarify how the suppression of PP4C triggers mitotic slippage/apoptosis, our observations suggest further development of fostriecin class inhibitors should consider PP4C as a potentially important target. PMID:23671329

  19. The ant colony algorithm for feature selection in high-dimension gene expression data for disease classification.

    PubMed

    Robbins, K R; Zhang, W; Bertrand, J K; Rekaya, R

    2007-12-01

    The use of gene expression data to diagnose complex diseases represents an exciting area of medicine; however, such data sets are often noisy, requiring the selection of feature subsets to obtain maximum classification accuracy. Due to the high dimensions of many expression data sets, filter-based methods are commonly used, but often yield inconsistent results. Optimization algorithms can outperform filter methods, but often require preselection of features to achieve good results. To address the problems of many commonly used feature selection methods, the ant colony algorithm (ACA) is proposed for use on data sets with large numbers of features. The ACA is an optimization algorithm capable of incorporating prior information, allowing it to search the sample space more efficiently than other optimization methods. When applied to several high-dimensional data sets, the ACA was able to identify small subsets of highly predictive and biologically relevant genes without the need for extensive preselection of features. Using the selected genes to train a latent variable model yielded substantial increases in prediction accuracy when compared to several rank-based methods and results obtained in previous studies. The superiority of the ACA algorithm was validated through simulation. PMID:18296718

  20. Flupoxam Induces Classic Club Root Morphology but Is Not a Mitotic Disrupter Herbicide

    PubMed

    Hoffman; Vaughn

    1996-05-01

    Flupoxam, an herbicide representative of a powerful new class of herbicides intended for control of broad-leaved weeds in cereals, has been identified as a mitotic disrupter herbicide. Flupoxam was evaluated on watercress seedlings for evidence of antimicrotubule effects characteristic of mitotic disrupter herbicides. At 1 ?M, flupoxam inhibited root elongation and induced club root morphology. However, examination by light microscopy and tubulin immunofluorescent microscopy revealed that flupoxam is not a mitotic disrupter herbicide. PMID:8980029

  1. Enhancement of spontaneous mitotic recombination by the meiotic mutant spo11-1 in Saccharomyces cerevisiae

    SciTech Connect

    Bruschi, C.V.; Esposito, M.S.

    1983-12-01

    Both nonreciprocal and reciprocal mitotic recombination are enhanced by the recessive mutant spo11-1, which was previously shown to affect meiosis by decreasing recombination and increasing nondisjunction. The mitotic effects are not distributed equally in all chromosomal regions. The genotypes of mitotic recombinants in spo11-1/spo11-1 diploid cells provide further evidence that widely spaced chromosomal markers undergo coincident conversion in mitosis.

  2. Cloud field classification based upon high spatial resolution textural features: 1. Gray level co-occurrence matrix approach

    NASA Astrophysics Data System (ADS)

    Welch, R. M.; Sengupta, S. K.; Chen, D. W.

    1988-10-01

    Standard cloud algorithms rely on multispectral signatures to identify high, medium, and low clouds. In contrast, the present study classifies stratocumulus, cumulus, and cirrus clouds, using textural features alone, derived from a single high-resolution Landsat Multispectral Scanner near-infrared channel. Applying stepwise linear discriminant analysis, classification accuracies of 92-95%, with standard deviations of about 1.5%, are achieved using the random subregion hold-out pattern. Accuracies of 83-88%, with standard deviations of about 7%, are achieved using the random scene hold-out pattern. The theoretical accuracy of the approach is estimated by treating the simulation on a non-parametric basis, using the bootstrap method. It is significant that the present method is capable of distinguishing high cirrus clouds from low clouds strictly on the basis of spatial brightness patterns. In fact, cirrus has the highest classification accuracy with this approach. The largest probability of misclassification is associated with confusion between stratocumulus breakup regions and fair-weather cumulus. The present study is based upon textural features computed from Gray Level Co-occurrence Matrix (GLCM) statistics defined at various pixel displacement distances. It is found that textural features defined at pixel separations of 0.5 km produce classification accuracies equal to or better than those defined at separations of 57 m. Some slight improvement (2-3%) in classification accuracy is achieved by inclusion of textural features defined at multiple pixel separations. In general, stratocumulus classification is improved by inclusion of additional features defined at pixel separations d < 0.25 km, cirrus by features at d ? 1 km, and cumulus by features at d ? 2 km.

  3. Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation

    PubMed Central

    Spencer, Charlotte A.; Kruhlak, Michael J.; Jenkins, Heather L.; Sun, Xuejun; Bazett-Jones, David P.

    2000-01-01

    All nuclear RNA synthesis is repressed during the mitotic phase of the cell cycle. In addition, RNA polymerase II (RNAP II), nascent RNA and many transcription factors disengage from DNA during mitosis. It has been proposed that mitotic transcription repression and disengagement of factors are due to either mitotic chromatin condensation or biochemical modifications to the transcription machinery. In this study, we investigate the requirement for chromatin condensation in establishing mitotic transcription repression and factor loss, by analyzing transcription and RNAP II localization in mitotic cells infected with herpes simplex virus type 1. We find that virus-infected cells enter mitosis and that mitotic viral DNA is maintained in a nucleosome-free and noncondensed state. Our data show that RNAP II transcription is repressed on cellular genes that are condensed into mitotic chromosomes and on viral genes that remain nucleosome free and noncondensed. Although RNAP II may interact indirectly with viral DNA during mitosis, it remains transcriptionally unengaged. This study demonstrates that mitotic repression of transcription and loss of transcription factors from mitotic DNA can occur independently of nucleosomal chromatin condensation. PMID:10893252

  4. Delaying mitotic exit downregulates FLIP expression and strongly sensitizes tumor cells to TRAIL.

    PubMed

    Sánchez-Pérez, T; Medema, R H; López-Rivas, A

    2015-01-29

    Many of the current antitumor therapeutic strategies are based on the perturbation of the cell cycle, especially during mitosis. Antimitotic drugs trigger mitotic checkpoint activation, mitotic arrest and eventually cell death. However, mitotic slippage represents a major mechanism of resistance to these treatments. In an attempt to circumvent the process of slippage, targeting mitotic exit has been proposed as a better strategy to kill tumor cells. In this study, we show that treatments that induce mitotic checkpoint activation and mitotic arrest downregulate FLICE-like inhibitory protein (FLIP) levels and sensitize several tumor cell lines to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis. Interestingly, we also demonstrate that in absence of mitotic checkpoint activation, mitotic arrest induced either by Cdc20 knockdown or overexpression of nondegradable cyclin B is sufficient to induce both FLIP downregulation and sensitivity to TRAIL. In summary, our data suggest that a combination of antimitotic drugs targeting cyclin B degradation and TRAIL might prevent mitotic slippage and allow tumor cells to reach the threshold for apoptosis induction, thereby facilitating tumor suppression. PMID:24488010

  5. 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic cytotoxicity with arsenic trioxide in human urothelial carcinoma cells.

    PubMed

    Kuo, Kuan-Lin; Lin, Wei-Chou; Ho, I-Lin; Chang, Hong-Chiang; Lee, Ping-Yi; Chung, Yuan-Ting; Hsieh, Ju-Ton; Pu, Yeong-Shiau; Shi, Chung-Sheng; Huang, Kuo-How

    2013-01-01

    2-Methoxyestradiol (2-ME), an endogenous derivative of 17?-estradiol, has been reported to elicit antiproliferative responses in various tumors. In this study, we investigated the effects of 2-ME on cell viability, proliferation, cell cycle, and apoptosis in human urothelial carcinoma (UC) cell lines. We used two high-grade human bladder UC cell lines (NTUB1 and T24). After treatment with 2-ME, the cell viability and apoptosis were measured by MTT assay and flow cytometry (fluorescence-activated cell sorting), with annexin V-FITC staining and propidium iodide (PI) labeling. DNA fragmentation was analyzed by agarose gel electrophoresis. Flow cytometry with PI labeling was used for the cell cycle analyses. The protein levels of caspase activations, poly (ADP-ribose) polymerase (PARP) cleavage, phospho-histone H2A.X, phospho-Bad, and cell cycle regulatory molecules were measured by Western blot. The effects of the drug combinations were analyzed using the computer software, CalcuSyn. We demonstrated that 2-ME effectively induces dose-dependent cytotoxicity and apoptosis in human UC cells after 24 h exposure. DNA fragmentation, PARP cleavage, and caspase-3, 7, 8, 9 activations can be observed with 2-ME-induced apoptosis. The decreased phospho-Bad (Ser136 and Ser155) and mitotic arrest of the cell cycle in the process of apoptosis after 2-ME treatment was remarkable. In response to mitotic arrest, the mitotic forms of cdc25C, phospho-cdc2, cyclin B1, and phospho-histone H3 (Ser10) were activated. In combination with arsenic trioxide (As2O3), 2-ME elicited synergistic cytotoxicity (combination index <1) in UC cells. We concluded that 2-ME significantly induces apoptosis through decreased phospho-Bad and arrests bladder UC cells at the mitotic phase. The synergistic antitumor effect with As2O3 provides a novel implication in clinical treatment of UC. PMID:23967052

  6. Computationally efficient neural feature extraction for spike sorting in implantable high-density recording systems.

    PubMed

    Kamboh, Awais M; Mason, Andrew J

    2013-01-01

    Modern microelectrode arrays acquire neural signals from hundreds of neurons in parallel that are subsequently processed for spike sorting. It is important to identify, extract, and transmit appropriate features that allow accurate spike sorting while using minimum computational resources. This paper describes a new set of spike sorting features, explicitly framed to be computationally efficient and shown to outperform principal component analysis (PCA)-based spike sorting. A hardware friendly architecture, feasible for implantation, is also presented for detecting neural spikes and extracting features to be transmitted for off chip spike classification. The proposed feature set does not require any off-chip training, and requires about 5% of computations as compared to the PCA-based features for the same classification accuracy, tested for spike trains with a broad range of signal-to-noise ratio. Our simulations show a reduction of required bandwidth to about 2% of original data rate, with an average classification accuracy of greater than 94% at a typical signal to noise ratio of 5 dB. PMID:22899586

  7. Anthropometric features and body composition of young athletes practicing karate at a high and medium competitive level

    Microsoft Academic Search

    M. Giampietro; A. Pujia; I. Bertini

    2003-01-01

    The aim of the study was to examine the anthropometric features and body composition of athletes practising karate at a high and medium competitive level. Our study was carried out on a sample of 35 subjects practising karate and aged from 16.0 to 32.5 years. This sample was divided into two groups: group 1 ( n=14 elite athletes) and group

  8. Control of high oceanic features and subduction channel on earthquake ruptures along the Chile–Peru subduction zone

    Microsoft Academic Search

    Eduardo Contreras-Reyes; Daniel Carrizo

    2011-01-01

    We discuss the earthquake rupture behavior along the Chile–Peru subduction zone in terms of the buoyancy of the subducting high oceanic features (HOF's), and the effect of the interplay between HOF and subduction channel thickness on the degree of interplate coupling. We show a strong relation between subduction of HOF's and earthquake rupture segments along the Chile–Peru margin, elucidating how

  9. Comparison of Aerosol Classification from Airborne High Spectral Resolution Lidar and the CALIPSO Vertical Feature Mask

    NASA Astrophysics Data System (ADS)

    Burton, S. P.; Ferrare, R. A.; Omar, A. H.; Hostetler, C. A.; Hair, J. W.; Rogers, R.; Obland, M. D.; Butler, C. F.; Cook, A. L.; Harper, D. B.

    2012-12-01

    The NASA Langley Research Center (LaRC) airborne High Spectral Resolution Lidar (HSRL-1) on the NASA B200 aircraft has acquired large datasets of aerosol extinction (532nm), backscatter (532 and 1064nm), and depolarization (532 and 1064nm) profiles during 349 science flights in 19 field missions across North America since 2006. The extinction-to-backscatter ratio ("lidar ratio"), aerosol depolarization ratios, and backscatter color ratio measurements from HSRL-1 are scale-invariant parameters that depend on aerosol type but not concentration. These four aerosol intensive parameters are combined to qualitatively classify HSRL aerosol measurements into eight separate composition types. The classification methodology uses models formed from "training cases" with known aerosol type. The remaining measurements are then compared with these models using the Mahalanobis distance. Aerosol products from the CALIPSO satellite include aerosol type information as well, which is used as input to the CALIPSO aerosol retrieval. CALIPSO aerosol types are inferred using a mix of aerosol loading-dependent parameters, estimated aerosol depolarization, and location, altitude, and surface type information. The HSRL instrument flies beneath the CALIPSO satellite orbit track, presenting the opportunity for comparisons between the HSRL aerosol typing and the CALIPSO Vertical Feature Mask Aerosol Subtype product, giving insight into the performance of the CALIPSO aerosol type algorithm. We find that the aerosol classification from the two instruments frequently agree for marine aerosols and pure dust, and somewhat less frequently for pollution and smoke. In addition, the comparison suggests that the CALIPSO polluted dust type is overly inclusive, encompassing cases of dust combined with marine aerosol as well as cases without much evidence of dust. Qualitative classification of aerosol type combined with quantitative profile measurements of aerosol backscatter and extinction has many useful applications. The HSRL products are used to apportion AOT by type and vertical location in the column, and to characterize the frequency of cases where multiple types are present in the column. Resolving scenes with multiple types in the column is not possible with passive imaging radiometer and polarimeter measurements. The HSRL aerosol type also has higher resolution than the CALIPSO layer-wise product and provides insight into the performance of CALIPSO layer separation. Information about the vertical distribution of aerosol types is useful for estimating radiative forcing, understanding aerosol lifetime and transport, and assessing the predictions of transport models. CALIPSO has been a pathfinder, providing the first long-term global data set of aerosol vertical distribution. Based on our results, a future satellite lidar similar to CALIPSO, but with the addition of polarization sensitivity at 1064 nm and the HSRL technique at 532 nm, could provide a significant advance in characterizing the vertical distribution of aerosol.

  10. Association of N-glycosylation with breast carcinoma and systemic features using high-resolution quantitative UPLC.

    PubMed

    Saldova, Radka; Asadi Shehni, Akram; Haakensen, Vilde D; Steinfeld, Israel; Hilliard, Mark; Kifer, Ilona; Helland, Aslaug; Yakhini, Zohar; Břrresen-Dale, Anne-Lise; Rudd, Pauline M

    2014-05-01

    An improved separation of the human serum N-glycome using hydrophilic interaction chromatography technology with UPLC is described, where more than 140 N-glycans were assigned. Using this technique, serum samples from 107 healthy controls and 62 newly diagnosed breast cancer patients were profiled. The most statistically significant alterations were observed in cancer patients compared with healthy controls: an increase in sialylation, branching, and outer-arm fucosylation and a decrease in high-mannosylated and biantennary core-fucosylated glycans. In the controls and cases combined systemic features were analyzed; serum estradiol was associated with increase in digalactosylated glycans, and higher mammographic density was associated with increase in biantennary digalactosylated glycans and with decrease in trisialylated and in outer-arm fucosylated glycans. Furthermore, particular glycans were altered in some features of the breast carcinomas; bisected biantennary nonfucosylated glycans were decreased in patients with progesterone receptor positive tumors, and core-fucosylated biantennary bisected monogalactosylated glycans were decreased in patients with the TP53 mutation. Systemic features show more significant associations with the serum N-glycome than do the features of the breast carcinomas. In conclusion, the UPLC-based glycan analysis technique described here reveals highly significant differences between healthy women and breast cancer patients. Significant associations with breast carcinoma and systemic features are described. PMID:24669823

  11. Incremental high pressure torsion as a novel severe plastic deformation process: Processing features and application to copper

    PubMed Central

    Hohenwarter, A.

    2015-01-01

    High pressure torsion is known as one of the most popular severe plastic deformation processes. However, it has certain size limitations, especially regarding the thickness of the processed samples. In this contribution incremental high pressure torsion is introduced as a novel severe plastic deformation process. This further development of conventional high pressure torsion is capable of delivering specimens having an extraordinarily high aspect-ratio of thickness to diameter. The features of this process combined with a case-study on a pure copper specimen with a deformed diameter of 50 mm and a thickness of 40 mm is presented.

  12. Analyzing fine-scale wetland composition using high resolution imagery and texture features

    NASA Astrophysics Data System (ADS)

    Szantoi, Zoltan; Escobedo, Francisco; Abd-Elrahman, Amr; Smith, Scot; Pearlstine, Leonard

    2013-08-01

    In order to monitor natural and anthropogenic disturbance effects to wetland ecosystems, it is necessary to employ both accurate and rapid mapping of wet graminoid/sedge communities. Thus, it is desirable to utilize automated classification algorithms so that the monitoring can be done regularly and in an efficient manner. This study developed a classification and accuracy assessment method for wetland mapping of at-risk plant communities in marl prairie and marsh areas of the Everglades National Park. Maximum likelihood (ML) and Support Vector Machine (SVM) classifiers were tested using 30.5 cm aerial imagery, the normalized difference vegetation index (NDVI), first and second order texture features and ancillary data. Additionally, appropriate window sizes for different texture features were estimated using semivariogram analysis. Findings show that the addition of NDVI and texture features increased classification accuracy from 66.2% using the ML classifier (spectral bands only) to 83.71% using the SVM classifier (spectral bands, NDVI and first order texture features).

  13. The high prevalence of “Soft” bipolar (II) features in atypical depression

    Microsoft Academic Search

    G Perugi; H. S Akiskal; L Lattanzi; D Cecconi; C Mastrocinque; A Patronelli; S Vignoli; E Bemi

    1998-01-01

    Seventy-two percent of 86 major depressive patients with atypical features as defined by the DSM-IV and evaluated systematically were found to meet our criteria for bipolar 11 and related “soft” bipolar disorders; nearly 60% had antecedent cyclothymic or hyperthymic temperaments. The family history for bipolar disorder validated these clinical findings. Even if we limit the diagnosis of bipolar II to

  14. AUTOMATIC BUILDIND DETECTION FROM HIGH RESOLUTION IMAGES BASED ON MULTIPLE FEATURES

    Microsoft Academic Search

    Shi Tao

    Automatic recognition and reconstruction of buildings from aerial and space images is of great practical interest for many of applications such as cartography and photo-interpretation. Building detection is the first and very difficult step in building recognition and reconstruction. It is to find buildings and separating them from the background in the presence of distractions caused by other features such

  15. Identification of the oncogenic kinase TOPK/PBK as a master mitotic regulator of C2H2 zinc finger proteins.

    PubMed

    Rizkallah, Raed; Batsomboon, Paratchata; Dudley, Gregory B; Hurt, Myra M

    2015-01-30

    TOPK/PBK is an oncogenic kinase upregulated in most human cancers and its high expression correlates with poor prognosis. TOPK is known to be activated by Cdk1 and needed for mitotic cell division; however, its mitotic functions are not yet fully understood. In this study, we show that TOPK plays a global mitotic role by simultaneously regulating hundreds of DNA binding proteins. C2H2 zinc finger proteins (ZFPs) constitute the largest family of human proteins. All C2H2 ZFPs contain a highly conserved linker sequence joining their multi-zinc finger domains. We have previously shown that phosphorylation of this conserved motif serves as a global mechanism for the coordinate dissociation of C2H2 ZFPs from condensing chromatin, during mitosis. Here, using a panel of kinase inhibitors, we identified K252a as a potent inhibitor of mitotic ZFP linker phosphorylation. We generated a biotinylated form of K252a and used it to purify candidate kinases. From these candidates we identified TOPK/PBK, in vitro and in vivo, as the master ZFP linker kinase. Furthermore, we show precise temporal correlation between TOPK activating phosphorylation by Cdk1 and linker phosphorylation in mitosis. The identification of this fundamental role of TOPK underscores its significance as a promising novel target of cancer therapeutics. PMID:25575812

  16. Identification of the oncogenic kinase TOPK/PBK as a master mitotic regulator of C2H2 zinc finger proteins

    PubMed Central

    Rizkallah, Raed; Batsomboon, Paratchata; Dudley, Gregory B.; Hurt, Myra M.

    2015-01-01

    TOPK/PBK is an oncogenic kinase upregulated in most human cancers and its high expression correlates with poor prognosis. TOPK is known to be activated by Cdk1 and needed for mitotic cell division; however, its mitotic functions are not yet fully understood. In this study, we show that TOPK plays a global mitotic role by simultaneously regulating hundreds of DNA binding proteins. C2H2 zinc finger proteins (ZFPs) constitute the largest family of human proteins. All C2H2 ZFPs contain a highly conserved linker sequence joining their multi-zinc finger domains. We have previously shown that phosphorylation of this conserved motif serves as a global mechanism for the coordinate dissociation of C2H2 ZFPs from condensing chromatin, during mitosis. Here, using a panel of kinase inhibitors, we identified K252a as a potent inhibitor of mitotic ZFP linker phosphorylation. We generated a biotinylated form of K252a and used it to purify candidate kinases. From these candidates we identified TOPK/PBK, in vitro and in vivo, as the master ZFP linker kinase. Furthermore, we show precise temporal correlation between TOPK activating phosphorylation by Cdk1 and linker phosphorylation in mitosis. The identification of this fundamental role of TOPK underscores its significance as a promising novel target of cancer therapeutics. PMID:25575812

  17. Malignant glioma with angiocentric features.

    PubMed

    Lu, Jian-Qiang; Patel, Samir; Wilson, Beverly A; Pugh, Jeffrey; Mehta, Vivek

    2013-03-01

    Angiocentric glioma is a recently recognized benign brain tumor with unknown histogenesis. Most of these tumors are mitotically low in activity in accord with their benign clinical course. However, increased mitotic activity has been noted in several cases, one of which had an ultimately fatal outcome. Here, the authors present a tumor showing angiocentric glioma and glioblastoma-like features, with recurrence of the lower-grade component after radiotherapy. A 15-year-old boy presented with a 3-month history of progressive left-sided weakness and headache. Magnetic resonance imaging showed a large heterogeneous mass in the right frontal lobe, with mild post-Gd enhancement. A gross-total resection was obtained. Histopathological examination of the resected tissue revealed a tumor with 2 distinct appearances: 1) a mildly to moderately cellular infiltrating tumor with angiocentric glioma characteristics, and 2) a markedly cellular glioblastoma-like tissue with necrosis and microvascular proliferation. The patient received a course of postoperative radiotherapy to 59.4 Gy in 33 fractions administered over the course of 6.5 weeks, but his tumor recurred 4 months after resection. A second resection was then performed. The recurrent tumor exhibited radiation-induced changes and persistent characteristics of angiocentric glioma, but it had fewer malignant features; the mitotic activity was lower, and there was no necrosis or microvascular proliferation. The findings in this case, along with those in several previously reported cases, suggest that angiocentric gliomas may have a malignant variant or malignant transformation. Angiocentric gliomas with malignant features tend to recur, for which surgical intervention followed by radiotherapy and chemotherapy should be offered as a therapeutic option. PMID:23240849

  18. Development of a Computational High-Throughput Tool for the Quantitative Examination of Dose-Dependent Histological Features.

    PubMed

    Nault, Rance; Colbry, Dirk; Brandenberger, Christina; Harkema, Jack R; Zacharewski, Timothy R

    2014-10-01

    High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT validation was demonstrated by comparison with manual quantitation using liver sections from mice orally gavaged with sesame oil vehicle or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.001-30 ?g/kg) every 4 days for 28 days, which elicits hepatic steatosis with mild fibrosis. A quality control module of QuHAnT reduced the number of quantifiable Oil Red O (ORO)-stained images from 3,123 to 2,756. Increased ORO staining was measured at 10 and 30 ?g/kg TCDD with a high correlation between manual and computational volume densities (Vv ), although the dynamic range of QuHAnT was 10-fold greater. Additionally, QuHAnT determined the size of each ORO vacuole, which could not be accurately quantitated by visual examination or manual point counting. PicroSirius Red quantitation demonstrated superior collagen deposition detection due to the ability to consider all images within each section. QuHAnT dramatically reduced analysis time and facilitated the comprehensive assessment of features improving accuracy and sensitivity and represents a complementary tool for tissue/cellular features that are difficult and tedious to assess via subjective or semiquantitative methods. PMID:25274660

  19. Spatial Correlation of High Density EMG Signals Provides Features Robust to Electrode Number and Shift in Pattern Recognition for Myocontrol.

    PubMed

    Stango, Antonietta; Negro, Francesco; Farina, Dario

    2015-03-01

    Research on pattern recognition for myoelectric control has usually focused on a small number of electromyography (EMG) channels because of better clinical acceptability and low computational load with respect to multi-channel EMG. However, recently, high density (HD) EMG technology has substantially improved, also in practical usability, and can thus be applied in myocontrol. HD EMG provides several closely spaced recordings in multiple locations over the skin surface. This study considered the use of HD EMG for controlling upper limb prostheses, based on pattern recognition. In general, robustness and reliability of classical pattern recognition systems are influenced by electrode shift in dons and doff, and by the presence of malfunctioning channels. The aim of this study is to propose a new approach to attenuate these issues. The HD EMG grid of electrodes is an ensemble of sensors that records data spatially correlated. The experimental variogram, which is a measure of the degree of spatial correlation, was used as feature for classification, contrary to previous approaches that are based on temporal or frequency features. The classification based on the variogram was tested on seven able-bodied subjects and one subject with amputation, for the classification of nine and seven classes, respectively. The performance of the proposed approach was comparable with the classic methods based on time-domain and autoregressive features (average classification accuracy over all methods  ? 95% for nine classes). However, the new spatial features demonstrated lower sensitivity to electrode shift ( ± 1 cm) with respect to the classic features . When even just one channel was noisy, the classification accuracy dropped by  ? 10% for all methods. However, the new method could be applied without any retraining to a subset of high-quality channels whereas the classic methods require retraining when some channels are omitted. In conclusion, the new spatial feature space proposed in this study improved the robustness to electrode number and shift in myocontrol with respect to previous approaches. PMID:25389242

  20. A molecular mechanism of mitotic centrosome assembly in Drosophila

    PubMed Central

    Conduit, Paul T; Richens, Jennifer H; Wainman, Alan; Holder, James; Vicente, Catarina C; Pratt, Metta B; Dix, Carly I; Novak, Zsofia A; Dobbie, Ian M; Schermelleh, Lothar; Raff, Jordan W

    2014-01-01

    Centrosomes comprise a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, but it is unclear how this occurs. In this study, we show that the centriole protein Asl initiates the recruitment of DSpd-2 and Cnn to mother centrioles; both proteins then assemble into co-dependent scaffold-like structures that spread outwards from the mother centriole and recruit most, if not all, other PCM components. In the absence of either DSpd-2 or Cnn, mitotic PCM assembly is diminished; in the absence of both proteins, it appears to be abolished. We show that DSpd-2 helps incorporate Cnn into the PCM and that Cnn then helps maintain DSpd-2 within the PCM, creating a positive feedback loop that promotes robust PCM expansion around the mother centriole during mitosis. These observations suggest a surprisingly simple mechanism of mitotic PCM assembly in flies. DOI: http://dx.doi.org/10.7554/eLife.03399.001 PMID:25149451

  1. Bod1 regulates protein phosphatase 2A at mitotic kinetochores

    PubMed Central

    Porter, Iain M.; Schleicher, Katharina; Porter, Michael; Swedlow, Jason R.

    2013-01-01

    Mitotic entry and progression require the activation of several mitotic kinases and the proper regulation and localization of several phosphatases. The activity and localization of each of these enzymes is tightly controlled through a series of specific activators, inhibitors and regulatory subunits. Two proteins, Ensa and Arpp-19, were recently identified as specific inhibitors of PP2A-B55 and are critical for allowing full activity of Cdk1/cyclin B and entry into mitosis. Here we show that Bod1, a protein required for proper chromosome alignment at mitosis, shares sequence similarity with Ensa and Arpp-19 and specifically inhibits the kinetochore-associated PP2A-B56 holoenzyme. PP2A-B56 regulates the stability of kinetochore-microtubule attachments by dephosphorylating several kinetochore proteins. Loss of Bod1 changes the balance of phosphorylation at kinetochores, causing defects in kinetochore function. Bod1, Ensa and Arpp-19 define a family of specific PP2A inhibitors that regulate specific PP2A holoenzymes at distinct locations and points in the cell cycle. PMID:24157919

  2. Inhibition of mitotic-specific histone phophorylation by sodium arsenite

    SciTech Connect

    Cobo, J.M. [Universidad de Alcala de Henares, Madrid (Spain); Valdez, J.G.; Gurley, L.R. [Los Alamos National Lab., NM (United States)

    1994-10-01

    Synchronized cultures of Chinese hamster cells (line CHO) were used to measure the effects of 10{mu}M sodium arsenite on histone phosphorylation. This treatment caused cell proliferation to be temporarily arrested, after which the cells spontaneously resumed cell proliferation in a radiomimetric manner. Immediately following treatment, it was found that sodium arsenite affected only mitotic-specific HI and H3 phosphorylations. Neither interphase, nor mitotic, H2A and H4 phosphorylations were affected, nor was interphase HI Phosphorylation affected. The phosphorylation of HI was inhibited only in mitosis, reducing HI phosphorylation to 38.1% of control levels, which was the level of interphase HI phosphorylation. The phosphorylation of both H3 variants was inhibited in mitosis, the less hydrophobic H3 to 19% and the more hydrophobic H3 to 24% of control levels. These results suggest that sodium arsenite may inhibite cell proliferation by interfering with the cyclin B/p34{sup cdc2} histone kinase activity which is thought to play a key role in regulating the cell cycle. It has been proposed by our laboratory that HI and H3 phosphorylations play a role in restructuring interphase chromatin into metaphase chromosomes. Interference of this process by sodium arsenite may lead to structurally damaged chromosomes resulting in the increased cancer risks known to be produced by arsenic exposure from the environment.

  3. Endogenous localizome identifies 43 mitotic kinesins in a plant cell.

    PubMed

    Miki, Tomohiro; Naito, Haruko; Nishina, Momoko; Goshima, Gohta

    2014-03-18

    Kinesins are microtubule (MT)-based motor proteins that have been identified in every eukaryotic species. Intriguingly, land plants have more than 60 kinesins in their genomes, many more than that in yeasts or animals. However, many of these have not yet been characterized, and their cellular functions are unknown. Here, by using endogenous tagging, we comprehensively determined the localization of 72 kinesins during mitosis in the moss Physcomitrella patens. We found that 43 kinesins are localized to mitotic structures such as kinetochores, spindle MTs, or phragmoplasts, which are MT-based structures formed during cytokinesis. Surprisingly, only one of them showed an identical localization pattern to the animal homolog, and many were enriched at unexpected sites. RNA interference and live-cell microscopy revealed postanaphase roles for kinesin-5 in spindle/phragmoplast organization, chromosome segregation, and cytokinesis, which have not been observed in animals. Our study thus provides a list of MT-based motor proteins associated with the cell division machinery in plants. Furthermore, our data challenge the current generalization of determining mitotic kinesin function based solely on studies using yeast and animal cells. PMID:24591632

  4. Endogenous localizome identifies 43 mitotic kinesins in a plant cell

    PubMed Central

    Miki, Tomohiro; Naito, Haruko; Nishina, Momoko; Goshima, Gohta

    2014-01-01

    Kinesins are microtubule (MT)-based motor proteins that have been identified in every eukaryotic species. Intriguingly, land plants have more than 60 kinesins in their genomes, many more than that in yeasts or animals. However, many of these have not yet been characterized, and their cellular functions are unknown. Here, by using endogenous tagging, we comprehensively determined the localization of 72 kinesins during mitosis in the moss Physcomitrella patens. We found that 43 kinesins are localized to mitotic structures such as kinetochores, spindle MTs, or phragmoplasts, which are MT-based structures formed during cytokinesis. Surprisingly, only one of them showed an identical localization pattern to the animal homolog, and many were enriched at unexpected sites. RNA interference and live-cell microscopy revealed postanaphase roles for kinesin-5 in spindle/phragmoplast organization, chromosome segregation, and cytokinesis, which have not been observed in animals. Our study thus provides a list of MT-based motor proteins associated with the cell division machinery in plants. Furthermore, our data challenge the current generalization of determining mitotic kinesin function based solely on studies using yeast and animal cells. PMID:24591632

  5. Formation of coastline features by large-scale instabilities induced by high-angle waves.

    PubMed

    Ashton, A; Murray, A B; Arnault, O

    2001-11-15

    Along shore sediment transport that is driven by waves is generally assumed to smooth a coastline. This assumption is valid for small angles between the wave crest lines and the shore, as has been demonstrated in shoreline models. But when the angle between the waves and the shoreline is sufficiently large, small perturbations to a straight shoreline will grow. Here we use a numerical model to investigate the implications of this instability mechanism for large-scale morphology over long timescales. Our simulations show growth of coastline perturbations that interact with each other to produce large-scale features that resemble various kinds of natural landforms, including the capes and cuspate forelands observed along the Carolina coast of southeastern North America. Wind and wave data from this area support our hypothesis that such an instability mechanism could be responsible for the formation of shoreline features at spatial scales up to hundreds of kilometres and temporal scales up to millennia. PMID:11713526

  6. Extracting building features from high resolution aerial imagery for natural hazards risk assessment

    Microsoft Academic Search

    Keping Chen; Russell Blong

    2002-01-01

    Natural hazards risk assessment requires data on the built environment. This paper reports an image analysis method that can extract building features, mainly roof plan areas, for potential vulnerability analysis. Both pixel- and object-based image processing methods are adopted. First, red\\/green\\/blue colour bands and image textures are incorporated in a supervised artificial neural network classifier to achieve good classification results

  7. Silver staining in transcriptionally active NORs of meiotic and mitotic cells in Acheta domesticus (L.) (Orthoptera)

    Microsoft Academic Search

    R. Czaker; Universitfit Wien

    1978-01-01

    The behaviour of the NOR material in mitotic and meiotic cells of Acheta domesticus was studied by silver staining. — In mitotic chromosomes black silver staining is observed in the centromeric region of 2 pairs of acrocentric chromosomes. Additionally a polymorphic silver positive region is found at the telomere of a large submetacentric chromosome. — The Ag-pattern of the amplified

  8. Cyclin-Dependent Kinase 8 Regulates Mitotic Commitment in Fission Yeast

    PubMed Central

    Banyai, Gabor; Lopez, Marcela Davila; McInerny, Christopher J.

    2012-01-01

    Temporal changes in transcription programs are coupled to control of cell growth and division. We here report that Mediator, a conserved coregulator of eukaryotic transcription, is part of a regulatory pathway that controls mitotic entry in fission yeast. The Mediator subunit cyclin-dependent kinase 8 (Cdk8) phosphorylates the forkhead 2 (Fkh2) protein in a periodic manner that coincides with gene activation during mitosis. Phosphorylation prevents degradation of the Fkh2 transcription factor by the proteasome, thus ensuring cell cycle-dependent variations in Fkh2 levels. Interestingly, Cdk8-dependent phosphorylation of Fkh2 controls mitotic entry, and mitotic entry is delayed by inactivation of the Cdk8 kinase activity or mutations replacing the phosphorylated serine residues of Fkh2. In addition, mutations in Fkh2, which mimic protein phosphorylation, lead to premature mitotic entry. Therefore, Fkh2 regulates not only the onset of mitotic transcription but also the correct timing of mitotic entry via effects on the Wee1 kinase. Our findings thus establish a new pathway linking the Mediator complex to control of mitotic transcription and regulation of mitotic entry in fission yeast. PMID:22451489

  9. Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation

    Microsoft Academic Search

    Joshua B Stevens; Batoul Y Abdallah; Sarah M Regan; Guo Liu; Steven W Bremer; Christine J Ye; Henry H Heng

    2010-01-01

    Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused

  10. DEVELOPING PHYLOGENIES FOR INTEGRATING MITOTIC FUNGI IN THE HYPOCREALES AND DIAPORTHALES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent comprehensive studies of the Hypocreales and Diaporthales using both morphological and molecular characters present the opportunity to integrate the mitotic fungi and to evaluate character evolution of both teleomorphic and anamorphic states. The majority of plant-associated fungi are mitotic...

  11. The diurnal rhythm of mitotic activity in the regenerating liver during acute radiation sickness

    Microsoft Academic Search

    V. I. Bulgak; Head-ProL V. P. Mikhailov

    1965-01-01

    In experiments on albino rats a study was made of the 24 h thythm in the mitotic activity of hepatic cells and in the percentage of binuclear cells in the regenerating liver following a single total exposure to X-irradiation in a dose of 600 r. The finding was that at the peak of acute radiation sickness the 24 h mitotic

  12. Mitotic and Polytene Chromosomes: Comparisons Between Drosophila Melanogaster and Drosophila Simulans

    Microsoft Academic Search

    Sylvie Aulard; Laurence Monti; Nicole Chaminade; Françoise Lemeunier

    2004-01-01

    This review deals with the differences between Drosophila melanogaster and Drosophila simulans in their mitotic and polytene chromosomes. The description of the mitotic karyotypes of D. melanogaster and D. simulans is mainly based on the methods that allow to differentiate their euchromatin from their heterochromatin: banding patterns, distribution of satellite DNAs and location of the rDNA. The polytene chromosomes karyotypes

  13. Localization by Q-banding of mitotic chiasmata in cases of Bloom's syndrome.

    PubMed

    Kuhn, E M

    1976-08-01

    The distribution of mitotic chiasmata from the lymphocytes of three patients with Bloom's syndrome was studied by Q-banding. An estimate was made of the average brightness of the human chromosomes and of the brightness and length of the Q-regions. A strong relationship was found between the average darkness of a chromosome and its chiasma density. The shorter and darker Q-regions contained more chiasmata, with the exception of the chromosome tips which had lower chiasma densities. A few "hot spots" had particularly high chiasma densities. Centric regions contained 17% of the chiasmata. The data are consistent with the assumptions that chiasmata are favored in darker regions and at borders between light and dark regions. PMID:954549

  14. ETV6/RUNX1 abrogates mitotic checkpoint function and targets its key player MAD2L1

    PubMed Central

    Krapf, G; Kaindl, U; Kilbey, A; Fuka, G; Inthal, A; Joas, R; Mann, G; Neil, JC; Haas, OA; Panzer-Grümayer, ER

    2014-01-01

    Approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia have an ETV6/RUNX1 (E/R) gene fusion that results from a t(12;21). This genetic subgroup of leukemia is associated with near-triploidy, near-tetraploidy, and trisomy 21 as rather specific types of secondary changes. Here, we show that, unlike various controls, E/R-expressing Ba/F3 clones acquire a tetraploid karyotype on prolonged culture, corroborating the assumption that E/R may attenuate the mitotic checkpoint (MC). Consistent with this notion, E/R-expressing diploid murine and human cell lines have decreased proportions of cells with 4N DNA content and a lower mitotic index when treated with spindle toxins. Moreover, both RUNX1 and E/R regulate mitotic arrest-deficient 2 L1 (MAD2L1), an essential MC component, by binding to promoter-inherent RUNX1 sites, which results in down-regulation of MAD2L1 mRNA and protein in E/R-expressing cells. Forced expression of E/R also abolishes RUNX1-induced reporter activation, whereas E/R with a mutant DNA-binding site leads to only minor effects. Our data link for the first time E/R, MC, and MAD2L1 and provide new insights into the function of the E/R fusion gene product. Although tetraploidy is an almost exclusive feature of E/R-positive leukemias, its rarity within this particular subgroup implies that further yet unknown factors are required for its manifestation. PMID:20190817

  15. Gene-specific factors determine mitotic expression and bookmarking via alternate regulatory elements

    PubMed Central

    Arampatzi, Panagiota; Gialitakis, Manolis; Makatounakis, Takis; Papamatheakis, Joseph

    2013-01-01

    Transcriptional silencing during mitosis is caused by inactivation of critical transcriptional regulators and/or chromatin condensation. Inheritance of gene expression patterns through cell division involves various bookmarking mechanisms. In this report, we have examined the mitotic and post-mitotic expression of the DRA major histocompatibility class II (MHCII) gene in different cell types. During mitosis the constitutively MHCII-expressing B lymphoblastoid cells showed sustained occupancy of the proximal promoter by the cognate enhanceosome and general transcription factors. In contrast, although mitotic epithelial cells were depleted of these proteins irrespectively of their MHCII transcriptional activity, a distal enhancer selectively recruited the PP2A phosphatase via NFY and maintained chromatin accessibility. Based on our data, we propose a novel chromatin anti-condensation role for this element in mitotic bookmarking and timing of post-mitotic transcriptional reactivation. PMID:23303784

  16. Preparing a cell for nuclear envelope breakdown: Spatio-temporal control of phosphorylation during mitotic entry.

    PubMed

    Alvarez-Fernández, Mónica; Malumbres, Marcos

    2014-08-01

    Chromosome segregation requires the ordered separation of the newly replicated chromosomes between the two daughter cells. In most cells, this requires nuclear envelope (NE) disassembly during mitotic entry and its reformation at mitotic exit. Nuclear envelope breakdown (NEB) results in the mixture of two cellular compartments. This process is controlled through phosphorylation of multiple targets by cyclin-dependent kinase 1 (Cdk1)-cyclin B complexes as well as other mitotic enzymes. Experimental evidence also suggests that nucleo-cytoplasmic transport of critical cell cycle regulators such as Cdk1-cyclin B complexes or Greatwall, a kinase responsible for the inactivation of PP2A phosphatases, plays a major role in maintaining the boost of mitotic phosphorylation thus preventing the potential mitotic collapse derived from NEB. These data suggest the relevance of nucleo-cytoplasmic transport not only to communicate cytoplasmic and nuclear compartments during interphase, but also to prepare cells for the mixture of these two compartments during mitosis. PMID:24889070

  17. Acrylamide effects on kinesin-related proteins of the mitotic/meiotic spindle

    SciTech Connect

    Sickles, Dale W. [Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912-2000 (United States)]. E-mail: dsickles@mcg.edu; Sperry, Ann O. [Department of Anatomy and Cell Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)]. E-mail: sperrya@ecu.edu; Testino, Angie [Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912-2000 (United States); Friedman, Marvin [SNF SAS, 2932 Bayhead Run, Oviedo, FL 32765 (United States)

    2007-07-01

    The microtubule (MT) motor protein kinesin is a vital component of cells and organs expressing acrylamide (ACR) toxicity. As a mechanism of its potential carcinogenicity, we determined whether kinesins involved in cell division are inhibited by ACR similar to neuronal kinesin [Sickles, D.W., Brady, S.T., Testino, A.R., Friedman, M.A., and Wrenn, R.A. (1996). Direct effect of the neurotoxicant acrylamide on kinesin-based microtubule motility. Journal of Neuroscience Research 46, 7-17.] Kinesin-related genes were isolated from rat testes [Navolanic, P.M., and Sperry, A.O. (2000). Identification of isoforms of a mitotic motor in mammalian spermatogenesis. Biology of Reproduction 62, 1360-1369.], their kinesin-like proteins expressed in bacteria using recombinant DNA techniques and the effects of ACR, glycidamide (GLY) and propionamide (a non-neurotoxic metabolite) on the function of two of the identified kinesin motors were tested. KIFC5A MT bundling activity, required for mitotic spindle formation, was measured in an MT-binding assay. Both ACR and GLY caused a similar concentration-dependent reduction in the binding of MT; concentrations of 100 {mu}M ACR or GLY reduced its activity by 60%. KRP2 MT disassembling activity was assayed using the quantity of tubulin disassembled from taxol-stabilized MT. Both ACR and GLY inhibited KRP2-induced MT disassembly. GLY was substantially more potent; significant reductions of 60% were achieved by 500 {mu}M, a comparable inhibition by ACR required a 5 mM concentration. Propionamide had no significant effect on either kinesin, except KRP2 at 10 mM. This is the first report of ACR inhibition of a mitotic/meiotic motor protein. ACR (or GLY) inhibition of kinesin may be an alternative mechanism to DNA adduction in the production of cell division defects and potential carcinogenicity. We conclude that ACR may act on multiple kinesin family members and produce toxicities in organs highly dependent on microtubule-based functions.

  18. Urban land cover mapping by spatial-spectral feature analysis of high resolution hyperspectral data with decision directed acyclic graph SVM

    Microsoft Academic Search

    Y. C. Huang; Pingxiang Li; Liangpei Zhang; Y. Zhong

    2009-01-01

    Classification and extraction of spatial and spectral features are investigated in urban areas from for high resolution hyperspectral imagery (HHR). The approach consists of two steps. First, the shape expansion and texture features were extracted by PSI and GLCM respectively; and spectral information was expressed by parts-based component feature generated by nonnegative matrix factorization or constrained energy match filter, which

  19. NUCLEIC ACID AND PROTEIN METABOLISM DURING THE MITOTIC CYCLE IN VICIA FABA

    PubMed Central

    Woodard, John; Rasch, Ellen; Swift, Hewson

    1961-01-01

    In order to investigate some of the cytochemical processes involved in interphase growth and culminating in cell division, a combined autoradiographic and microphotometric study of nucleic acids and proteins was undertaken on statistically seriated cells of Vicia faba root meristems. Adenine-8-C14 and uridine-H3 were used as ribonucleic acid (RNA) precursors, thymidine-H3 as a deoxyribonucleic acid (DNA) precursor, and phenylalanine-3-C14 as a protein precursor. Stains used in microphotometry were Feulgen (DNA), azure B (RNA), pH 2.0 fast green (total protein), and pH 8.1 fast green (histone). The autoradiographic data (representing rate of incorporation per organelle) and the microphotometric data (representing changes in amounts of the various components) indicate that the mitotic cycle may be divided into several metabolic phases, three predominantly anabolic (net increase), and a fourth phase predominantly catabolic (net decrease). The anabolic periods are: 1. Telophase to post-telophase during which there are high rates of accumulation of cytoplasmic and nucleolar RNA and nucleolar and chromosomal total protein. 2. Post-telophase to preprophase characterized by histone synthesis and a diphasic synthesis of DNA with the peak of synthesis at mid-interphase and a minor peak just preceding prophase. The minor peak is coincident with a relatively localized DNA synthesis in several chromosomal regions. This period is also characterized by minimal accumulations of cytoplasmic RNA and chromosomal and nucleolar total protein and RNA. 3. Preprophase to prophase in which there are again high rates of accumulation of cytoplasmic RNA, and nucleolar and chromosomal total protein and RNA. The catabolic phase is: 4. The mitotic division during which there are marked losses of cytoplasmic RNA and chromosomal and nucleolar total protein and RNA. PMID:13786522

  20. High resolution CT and histological findings in idiopathic pleuroparenchymal fibroelastosis: Features and differential diagnosis

    PubMed Central

    2011-01-01

    Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described clinical-pathologic entity characterized by pleural and subpleural parenchymal fibrosis, mainly in the upper lobes. As this disease is extremely rare (only 7 cases have been described in the literature to date) poorly defined cases of IPPFE can go unrecognized. The clinical course of disease is progressive and prognosis is poor, with no therapeutic options other than lung transplantation currently available, yet. The aim of this report is to describe two further cases of this rare disease, reviewing CT, clinical and histological features. PMID:21861891

  1. Numerical simulation and investigation of working process features in high-duty combustion chambers

    Microsoft Academic Search

    G. P. Kalmykov; A. A. Larionov; D. A. Sidlerov; L. A. Yanchilin

    2008-01-01

    Basic concepts of a numerical simulation method of two-phase turbulent flows with combustion are stated. Results of computations\\u000a in gas generators and combustion chambers of liquid-propellant rocket engines operating on oxygen and methane are presented.\\u000a Features of the processes of evaporation, mixture, flow, and combustion of the propellant within chambers with tree types\\u000a of injectors, i.e., coaxial-jet gas-liquid, liquid-liquid monopropellant

  2. Mitotic rate in melanoma: prognostic value of immunostaining and computer-assisted image analysis.

    PubMed

    Hale, Christopher S; Qian, Meng; Ma, Michelle W; Scanlon, Patrick; Berman, Russell S; Shapiro, Richard L; Pavlick, Anna C; Shao, Yongzhao; Polsky, David; Osman, Iman; Darvishian, Farbod

    2013-06-01

    The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67. We used light microscopy and computer-assisted image analysis software to quantify MPM-2 and PHH3 staining in melanoma. We then compared mitotic rates by each method with conventional H&E-based mitotic rate for correlation with clinical outcomes. Our study included primary tissues from 190 nonconsecutive cutaneous melanoma patients who were prospectively enrolled at New York University Langone Medical Center with information on age, gender, and primary tumor characteristics. The mitotic rate was quantified manually by light microscopy of corresponding H&E-stained, MPM-2-stained, and PHH3-stained sections. Computer-assisted image analysis was then used to quantify immunolabeled mitoses on the previously examined PHH3 and MPM-2 slides. We then analyzed the association between mitotic rate and both progression-free and melanoma-specific survival. Univariate analysis of PHH3 found significant correlation between increased PHH3 mitotic rate and decreased progression-free survival (P=0.04). Computer-assisted image analysis enhanced the correlation of PHH3 mitotic rate with progression-free survival (P=0.02). Regardless of the detection method, neither MPM-2 nor PHH3 offered significant advantage over conventional H&E determination of mitotic rate. PMID:23629443

  3. Okadaic acid induced cyclin B1 expression and mitotic catastrophe in rat cortex.

    PubMed

    Chen, Bo; Cheng, Min; Hong, Dao-Jun; Sun, Feng-Yan; Zhu, Cui-Qing

    2006-10-01

    Accumulating evidence indicates that the aberrant re-entry of post-mitotic neurons into the G2/M phase of cell cycle and the resulting mitotic catastrophe may contribute to the pathogenesis of Alzheimer's disease. However, the cellular event that drives the differentiated neurons to abnormally enter G2/M phase remains elusive. Similarly, whether mitotic catastrophe is indeed one of the death pathways for differentiated neurons is not clear. Previous studies revealed that okadaic acid (OA), a phosphatase inhibitor that induces AD like pathological changes, evokes mitotic changes in neuroblastoma cells. In this study, we examined the in vivo effects of OA on cyclin B1 expression, the induction of mitosis, and subsequent mitotic catastrophe. We found that cyclin B1 expression in adult neurons was significantly increased after injecting OA into rat frontal cortex, which also increased tau protein phosphorylation. Interestingly, cyclin B1 and phosphorylated tau were well co-localized around the OA injection site, but were only partially co-localized in other brain regions. Staining with toluidine blue, Giemsa dye or propidium iodide revealed typical mitotic and mitotic catastrophe-like morphological changes with irregular arrangement of condensed chromatin and chromosome fibers in a few cells. Furthermore, the strong cyclin B1 staining in these cells suggests that cyclin B1 promoted G2 to M phase transition is required for the mitotic catastrophe. The detection of neuron-specific enolase in a portion of these cells demonstrated that at least part them are neuron. All together, our results suggest that the disturbance of the protein kinase-phosphatase system caused by OA is sufficient to induce neuronal cyclin B1 expression, force neurons into the mitotic phase of cell cycle, and cause mitotic catastrophe. PMID:16919876

  4. Object-based gully feature extraction using high spatial resolution imagery

    NASA Astrophysics Data System (ADS)

    Shruthi, Rajesh B. V.; Kerle, Norman; Jetten, Victor

    2011-11-01

    Gully erosion is responsible for a substantial amount of soil loss and is generally considered an indicator of desertification. Hence, mapping these gully features provides essential information needed on sediment production, identification of vulnerable areas for gully formation, land degradation, and environmental and socio-economical effects. This paper investigates the use of object-oriented image analysis (OOA) to extract gully erosion features from satellite imagery, using a combination of topographic, spectral, shape (geometric) and contextual information obtained from IKONOS and GEOEYE-1 data. A rule-set was developed and tested for a semi-arid to sub-humid region in Morocco. The percentage of gully system area indicated negligible overestimations between the reference area and the OOA area in two sub-watersheds (0.03% and 1.77%). We also observed that finer gully-related edges within the complex gully systems were better identified semi-automatically than was possible by manual digitization, suggesting higher detection accuracy. OOA-based gully mapping is quicker and more objective than traditional methods, and is thus better suited to provide essential information for land managers to support their decision making processes, and for the erosion research community.

  5. Bimodal fusion of low-level visual features and high-level semantic features for near-duplicate video clip detection

    Microsoft Academic Search

    Hyun-seok Min; Jae Young Choi; Wesley De Neve; Yong Man Ro

    2011-01-01

    The detection of near-duplicate video clips (NDVCs) is an area of current research interest and intense development. Most NDVC detection methods represent video clips with a unique set of low-level visual features, typically describing color or texture information. However, low-level visual features are sensitive to transformations of the video content. Given the observation that transformations tend to preserve the semantic

  6. Applicability of data mining algorithms in the identification of beach features/patterns on high-resolution satellite data

    NASA Astrophysics Data System (ADS)

    Teodoro, Ana C.

    2015-01-01

    The available beach classification algorithms and sediment budget models are mainly based on in situ parameters, usually unavailable for several coastal areas. A morphological analysis using remotely sensed data is a valid alternative. This study focuses on the application of data mining techniques, particularly decision trees (DTs) and artificial neural networks (ANNs) to an IKONOS-2 image in order to identify beach features/patterns in a stretch of the northwest coast of Portugal. Based on knowledge of the coastal features, five classes were defined. In the identification of beach features/patterns, the ANN algorithm presented an overall accuracy of 98.6% and a kappa coefficient of 0.97. The best DTs algorithm (with pruning) presents an overall accuracy of 98.2% and a kappa coefficient of 0.97. The results obtained through the ANN and DTs were in agreement. However, the ANN presented a classification more sensitive to rip currents. The use of ANNs and DTs for beach classification from remotely sensed data resulted in an increased classification accuracy when compared with traditional classification methods. The association of remotely sensed high-spatial resolution data and data mining algorithms is an effective methodology with which to identify beach features/patterns.

  7. The high frequency and clinical feature of seronegative myasthenia gravis in Southern China.

    PubMed

    Feng, Hui-Yu; Wang, Hai-Yan; Liu, Wei-Bin; He, Xue-Tao; Huang, Xin; Luo, Chuan-Ming; Li, Yan

    2013-06-01

    Anti-acetylcholine receptor antibodies (anti-AChR-Ab) are responsible for the failure of neuromuscular junction in myasthenia gravis (MG). Some anti-AChR-Ab-seronegative MG patients have anti-muscle-specific tyrosine kinase antibodies (anti-MuSk-Ab). Here, the anti-AChR-Ab was tested in 250 MG outpatients from Southern China. While anti-MuSk-Ab was tested in 66 patients who had no anti-AChR-Ab in blood serum, but none of them was positive. The antibodies were measured by a radioimmunoprecipitation assay. The frequency of anti-AChR-Ab was 51.2 %. The percentage of anti-AChR-Ab in ocular type was lower than generalized type (44.9 vs. 66.2 %, P = 0.002). Seronegative MG was characterized by a lower percentage of thymoma than seropositive patients (P = 0.013). It seemed to be less severe in seronegative MG than seropositive MG in these 250 patients. In ocular type, seronegative MG mainly manifesting blepharoptosis but seldom diplopia or eyeball fixation related to ocular movement disability (P = 0.016). While in generalized type, seronegative MG was characterized by a lower percentage of bulbar muscle involvements than seropositive patients (P = 0.005). Logistic regression analysis revealed that bulbar weakness was affected by the existence of anti-AChR antibodies (OR = 3.524, P = 0.015). Besides, seronegative MG tended to be characterized by a lower percentage of neck extensor involvement, but this did not reach significance. The percentage of anti-AChR antibodies was much lower than other countries. Seronegative MG has characteristic clinical features that are different from features of the remaining seropositive MG. This emphasises the predictive value of anti-AChR antibodies analysis in MG patients. PMID:22829131

  8. Brochothrix thermosphacta bacteriophages feature heterogeneous and highly mosaic genomes and utilize unique prophage insertion sites.

    PubMed

    Kilcher, Samuel; Loessner, Martin J; Klumpp, Jochen

    2010-10-01

    Brochothrix belongs to the low-GC branch of Gram-positive bacteria (Firmicutes), closely related to Listeria, Staphylococcus, Clostridium, and Bacillus. Brochothrix thermosphacta is a nonproteolytic food spoilage organism, adapted to growth in vacuum-packaged meats. We report the first genome sequences and characterization of Brochothrix bacteriophages. Phage A9 is a myovirus with an 89-nm capsid diameter and a 171-nm contractile tail; it belongs to the Spounavirinae subfamily and shares significant homologies with Listeria phage A511, Staphylococcus phage Twort, and others. The A9 unit genome is 127 kb long with 11-kb terminal redundancy; it encodes 198 proteins and 6 tRNAs. Phages BL3 and NF5 are temperate siphoviruses with a head diameter of 56 to 59 nm. The BL3 tail is 270 nm long, whereas NF5 features a short tail of only 94 nm. The NF5 genome (36.95 kb) encodes 57 gene products, BL3 (41.52 kb) encodes 65 products, and both are arranged in life cycle-specific modules. Surprisingly, BL3 and NF5 show little relatedness to Listeria phages but rather demonstrate relatedness to lactococcal phages. Peptide mass fingerprinting of viral proteins indicate programmed -1 translational frameshifts in the NF5 capsid and the BL3 major tail protein. Both NF5 and BL3 feature circularly permuted, terminally redundant genomes, packaged by a headful mechanism, and integrases of the serine (BL3) and tyrosine (NF5) types. They utilize unique target sequences not previously described: BL3 inserts into the 3' end of a RNA methyltransferase, whereas NF5 integrates into the 5'-terminal part of a putative histidinol-phosphatase. Interestingly, both genes are reconstituted by phage sequence. PMID:20709901

  9. A prognosis based classification of undifferentiated uterine sarcomas: Identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival.

    PubMed

    Gremel, Gabriela; Liew, Markus; Hamzei, Farzaneh; Hardell, Elin; Selling, Jonas; Ghaderi, Mehran; Stemme, Sten; Pontén, Fredrik; Carlson, Joseph W

    2015-04-01

    Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, "Kurihara" diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M?=?36.8, SD?=?5.4) and a low mitotic index group (16 cases, M?=?8.7, SD?=?5.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights. PMID:25130488

  10. Model scenarios for switch-like mitotic transitions.

    PubMed

    Vinod, P K; Novak, Bela

    2015-03-12

    To facilitate rapid accumulation of Cdk1-phosphorylated substrate proteins, the Cdk1 counter-acting phosphatase, PP2A-B55 is inhibited during M phase by stoichiometric inhibitors (ENSA and Arpp19). These inhibitors are activated when phosphorylated by Cdk1-activated Greatwall-kinase. Recent experiments show that ENSA is dephosphorylated and inactivated by the PP2A-B55 itself, and acts as an unfair substrate inhibiting PP2A-B55 activity towards other Cdk1 substrates. Mathematical modelling shows that this mutual antagonism between the phosphatase and its inhibitor is insufficient to explain the switch-like characteristics of mitotic entry and exit. We show that the feedback regulation of Greatwall activating kinase and/or inactivating phosphatase can explain the abruptness of these cell cycle transitions. PMID:25683003

  11. Resurrecting remnants: The lives of post-mitotic midbodies

    PubMed Central

    Chen, Chun-Ting; Ettinger, Andreas W.; Huttner, Wieland B.; Doxsey, Stephen J.

    2014-01-01

    Around a century ago, the midbody was described as a structural assembly within the intercellular bridge during cytokinesis, which served to connect the two future daughter cells. The midbody has become the focus of intense investigation through the identification of a growing number of diverse cellular and molecular pathways that localize to the midbody and contribute to its cytokinetic functions ranging from selective vesicle trafficking, regulated microtubule, actin and ESCRT filament assembly and disassembly, and post-translational modification, such as ubiquitination. More recent studies revealed new and unexpected functions of midbodies that occur in post-mitotic cells. In this article, we provide a historical perspective, discuss exciting new roles for midbodies beyond their cytokinetic function and speculate on their potential contributions to pluripotency. PMID:23245592

  12. THE NUCLEOLI IN MITOTIC DIVISIONS OF MAMMALIAN CELLS IN VITRO

    PubMed Central

    Hsu, T. C.; Arrighi, Frances E.; Klevecz, Robert R.; Brinkley, B. R.

    1965-01-01

    In a number of mammalian cell strains nucleoli persisted through mitosis. This phenomenon was especially pronounced in several cell lines derived from Chinese hamster tissues. All the methods employed, including radioautography with tritiated uridine, cytochemical stains (methyl green-pyronin and azure B), fluorescent microscopy (coriphosphine O), ribonuclease digestion, and electron microscopy, demonstrated that the bodies identified as persistent nucleoli in the mitotic stages had the same characteristics as did the nucleoli in the interphase. Persistent nucleoli may attach to the chromosomes or may be free in the cytoplasm. In cells where no persistent nucleoli as such were noted, nucleolar material was observed to attach to the chromosomes in shapeless masses which moved with the chromosomes during anaphase. At least a portion of the nucleolar material was included in the daughter nuclei, presumably for immediate use for protein synthesis after cell division. PMID:4222282

  13. Mitotic wavefronts mediated by mechanical signaling in early Drosophila embryos

    NASA Astrophysics Data System (ADS)

    Kang, Louis; Idema, Timon; Liu, Andrea; Lubensky, Tom

    2013-03-01

    Mitosis in the early Drosophila embryo demonstrates spatial and temporal correlations in the form of wavefronts that travel across the embryo in each cell cycle. This coordinated phenomenon requires a signaling mechanism, which we suggest is mechanical in origin. We have constructed a theoretical model that supports nonlinear wavefront propagation in a mechanically-excitable medium. Previously, we have shown that this model captures quantitatively the wavefront speed as it varies with cell cycle number, for reasonable values of the elastic moduli and damping coefficient of the medium. Now we show that our model also captures the displacements of cell nuclei in the embryo in response to the traveling wavefront. This new result further supports that mechanical signaling may play an important role in mediating mitotic wavefronts.

  14. Stochastic simulation and graphic visualization of mitotic processes.

    PubMed

    Gardner, Melissa K; Odde, David J

    2010-06-01

    Computational modeling can be extremely useful in interpreting experimental results. Here we describe how a relatively sophisticated stochastic model for microtubule dynamic instability in the mitotic spindle can be developed starting with straightforward rules and simple programming code. Once this model is developed, the method for comparing simulation results to experimental data must be carefully considered. The ultimate utility of any computational model relies on its predictive power and the ability to assist in designing new experiments. We describe how "deconstructing" the model through the use of quantitative animations contributes to a better qualitative understanding of model behavior. By extracting key qualitative elements of the model in this fashion, model predictions and new experiments can be more easily extracted from model results. PMID:20096783

  15. A Genetic Map of DICTYOSTELIUM DISCOIDEUM Based on Mitotic Recombination

    PubMed Central

    Welker, Dennis L.; Williams, Keith L.

    1982-01-01

    A genetic map of the cellular slime mold Dictyostelium discoideum is presented in which 42 loci are ordered on five of the seven linkage groups. Although most of the loci were ordered using standing mitotic crossing-over techniques in which recessive selective markers were employed, use was also made of unselected recombined haploid strains. Consistent with cytological studies in which the chromosomes appear to be acrocentric, only a single arm has been found for each of the five linkage groups studied. The mating-type locus, matA, has been located in the tsgE-sprA interval on linkage group I on the basis of studies on diploids formed between strains of opposite mating type that have escaped from vegetative incompatibility. PMID:7187362

  16. Mitotic recombination and segregation of satellites in Bloom's syndrome.

    PubMed

    Therman, E; Otto, P G; Shahidi, N T

    1981-01-01

    Mitotic recombination in satellite stalks--a phenomenon often difficult to distinguish from satellite association--was studied in a sister and a brother with Bloom's syndrome. Segregation after recombination was analyzed in the lymphocytes of the sister who had Q-bright satellites. Her cells varied greatly both in regard to the acrocentrics which displayed Q-bright satellites and the number of such satellites per cell. In 58 cells a total of 31 different patterns were seen. In 83 cells of 6 controls who also had Q-bright satellites on at least one acrocentric chromosome, not one cell was found in which the pattern differed from that characteristic of the person. Obviously exchanges between satellite stalks in patients with Bloom's syndrome are fairly frequent (estimated lower limit 6/1000) and very rare in persons who do not have this syndrome (estimated 0.1/1000). PMID:7261713

  17. Effect of the Major Repeat Sequence on Mitotic Recombination in Candida albicans

    PubMed Central

    Lephart, Paul R.; Magee, Paul T.

    2006-01-01

    The major repeat sequence (MRS) is known to play a role in karyotypic variation in Candida albicans. The MRS affects karyotypic variation by expanding and contracting internal repeats, by altering the frequency of chromosome loss, and by serving as a hotspot for chromosome translocation. We proposed that the effects of the MRS on translocation could be better understood by examination of the effect of the MRS on a similar event, mitotic recombination between two chromosome homologs. We examined the frequency of mitotic recombination across an MRS of average size (?50 kb) as well as the rate of recombination in a 325-kb stretch of DNA adjacent to the MRS. Our results indicate that mitotic recombination frequencies across the MRS were not enhanced compared to the frequencies measured across the 325-kb region adjacent to the MRS. Mitotic recombination events were found to occur throughout the 325-kb region analyzed as well as within the MRS itself. This analysis of mitotic recombination frequencies across a large portion of chromosome 5 is the first large-scale analysis of mitotic recombination done in C. albicans and indicates that mitotic recombination frequencies are similar to the rates found in Saccharomyces cerevisiae. PMID:17028326

  18. High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features.

    PubMed

    Sciallis, Andrew P; Bedroske, Patrick P; Schoolmeester, John K; Sukov, William R; Keeney, Gary L; Hodge, Jennelle C; Bell, Debra A

    2014-09-01

    The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management. PMID:25133706

  19. Spectral and spatial feature integrated edge extraction method for high-resolution remote sensing image

    NASA Astrophysics Data System (ADS)

    Li, Qiqing; Ma, Jianwen; Bagan, Hasi; Han, Xiuzhen; Liu, Zhili

    2003-09-01

    With urban and township development and E-Government program promotion in China city remote sensing as base data has developed rapidly. The technique demands in accuracy and effective edge detection and extraction from higher resolution image become important focal area. In the current popular image processing software packages there are some existing edge detection convolution kernels suchc as Sobel, Robert, Prewitt, Kirsch, Gauss-Laplace kernels. In general the kernels all work based on algorithm of convolution kernel in spatial territory of the image. However, satellite sensors capture spatial and spectral signatures of surfaces at same time. Use of both spatial and spectral features to establish a edge detection process is a new notion for achieving more accuracy results. In the paper we introduce a spatial and spectral integrated method which is designed in four stages. The result suggests that four stages process can achieve more cleanly and accuracy edges of city construction than that results of using other algorithms. The procedure is summarized in figure 1.

  20. MOVING MAGNETIC FEATURES AROUND AR 10930 FROM HIGH-RESOLUTION DATA OBSERVED BY HINODE/SOT

    SciTech Connect

    Li Xiaobo; Zhang Hongqi, E-mail: xiaobo_li_naoc@yahoo.com [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

    2013-07-01

    We investigate the origin, configuration, and evolution of moving magnetic features (MMFs) in the moat and penumbra regions of NOAA AR 10930 using Hinode/SOT filtergrams and magnetograms. We differentiate MMFs into four types in terms of the location of first appearance and the source of initial flux. The main results are summed up as follows: (1) 50% of the MMFs are produced from or within the penumbra, while 50% are produced within the moat. The MMFs formed in the penumbra normally move outward along radial directions. The MMFs formed in the moat have more dispersed directions of motion. The average speed of most MMFs decreases radially. (2) About 63% of moat fluxes are input by flux emergences. Newly emerged MMFs are normally smaller in size. In their rise phase, they gain flux by adding newly emerging flux or merging other elements, and in the decline phase they lose flux by flux cancellation or fragmentation. The MMFs that are fragments separated from penumbra or other magnetic elements usually have larger flux and longer lifetime. They start their decay process once they are formed. Frequent merging and flux cancellation between MMFs are the dominant factors in MMFs' evolution. (3) Cancellations between opposite-polarity magnetic elements are responsible for most of the low chromospheric bright points. Bipole emergence and MMFs' severance from the penumbra also produce bright points. Elongated or horn-shaped micro-filaments may appear during the separation or cancellation process between magnetic elements.

  1. Arsenic trioxide induces abnormal mitotic spindles through a PIP4KII?/Rho pathway.

    PubMed

    Yih, Ling-Huei; Wu, Yi-Chen; Hsu, Nai-Chi; Kuo, Hsiao-Hui

    2012-07-01

    Arsenite-induced spindle abnormalities result in mitotic cell apoptosis in several cancer cell lines, but how arsenite induces these effects is not known. Evidence to date has revealed that arsenite activates Rho guanosine triphosphatases (GTPases). Because Rho GTPases regulate spindle orientation, chromosome congression, and cytokinesis, we therefore examined the involvement of Rho GTPases and their modulators in arsenite-induced mitotic abnormalities. We demonstrated that arsenic trioxide (ATO) disrupted the positioning of bipolar mitotic spindles and induced centrosome and spindle abnormalities. ATO increased the level of the active guanosine triphosphate-bound form of Rho. Inhibition of Rho-associated protein kinases (ROCKs) by Y-27632 ameliorated ATO-induced spindle defects, mitotic arrest, and cell death. These results indicate that ATO may induce spindle abnormalities and mitotic cell death through a Rho/ROCK pathway. In addition, screening of a human kinase and phosphatase shRNA library to select genes that mediate ATO induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KII?), a phosphatidylinositol 4,5-biphosphate (PIP2) synthesis enzyme that belongs to the phosphatidylinositol phosphate kinase (PIPK) family. Sequestration of PIP2 by ectopic overexpression of the pleckstrin homology domain of phospholipase C-?1 protected cells from ATO-induced cell death. Furthermore, depletion of PIP4KII?, but not other isoforms of the PIPK family, not only reduced Rho GTPase activation in ATO-treated cells but also alleviated ATO-induced spindle defects, mitotic arrest, and mitotic cell apoptosis. Thus, our results imply that ATO induces abnormalities in mitotic spindles through a PIP4KII?/Rho pathway, leading to apoptosis of mitotic cells. PMID:22496355

  2. Reproducible magnetic features of high-T/sub c/ superconductors in weak fields

    SciTech Connect

    Jeffery, M.; Green, C.; Tyagi, S.; Gilmore, R.

    1989-05-01

    The microwave absorption spectrum of the high-T/sub c/ granular superconductor YBa/sub 2/Cu/sub 3/O/sub 7-//sub delta/ measured in a weak magnetic field with small modulation exhibits reproducible oscillations as a function of external field. We have modeled the high-T/sub c/ ceramics as a network of superconducting wires weakly coupled at randomly placed nodes. Quantum network simulations of the behavior of this system in a magnetic field reveal strong similarities between the computed magnetoconductance, magnetization, and susceptibility and the experimentally observed microwave absorption spectrum.

  3. Atomic Force Microscopy to Study Mechanics of Living Mitotic Mammalian Cells

    NASA Astrophysics Data System (ADS)

    Toyoda, Yusuke; Stewart, Martin P.; Hyman, Anthony A.; Müller, Daniel J.

    2011-08-01

    While biochemical pathways within mitotic cells have been intensively studied, the mechanics of dividing cells is only poorly understood. In our recent report, an experimental system combining fluorescence and atomic force microscopy was set up to study dynamics of mitotic rounding of mammalian cells. We show that cells have a rounding pressure that increases upon mitotic entry. Using specific inhibitors or perturbations, we revealed biological processes required for force generation that underpin the cell rounding shape change during mitosis. The significance of the finding and an outlook are discussed.

  4. Odysseus: a High-Performance ORDBMS Tightly-Coupled with Spatial Database Features

    E-print Network

    Whang, Kyu-Young

    -coupling architecture, the high-level inter- face causes the following problems. First, inter-process communication are. The Pseudo (Built-in) Type We call a data type defined in the extensible type layer as the pseudo built-in type (simply, the pseudo type). The reason for including the term "pseudo" is as follows

  5. Automated face analysis by feature point tracking has high concurrent validity with manual FACS coding

    E-print Network

    Cohn, Jeffrey F.

    for variation in position, orientation, and scale. The image sequences were randomly divided into a training set tracking demonstrated high concurrent validity with manual FACS coding. Descriptors: Facial expression. Facial displays indicate emotion ~Ekman, 1993; Russell, 1994! and pain ~Craig, Hyde, & Patrick, 1991

  6. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

  7. Urban building damage detection from very high resolution imagery using OCSVM and spatial features

    Microsoft Academic Search

    Peijun Li; Haiqing Xu; Jiancong Guo

    2010-01-01

    The availability of commercial very high resolution (VHR) satellite imagery makes it possible to detect and assess building damage in the aftermath of earthquake disasters using these data. Although conventional change detection methods may be used to assess the building damage, the analysis is directed to all classes, both damaged and undamaged, but is not focused on the class of

  8. Collecting Inexpensive High Resolution Aerial and Stereo Images of Small- to Mid-Scale Geomorphic and Tectonic Features

    NASA Astrophysics Data System (ADS)

    Wheelwright, R. J.; White, W. S.; Willis, J. B.

    2010-12-01

    Methods for collecting accurate, mm- to cm-scale stereoscopic aerial imagery of both small- and mid-scale geomorphic features are developed for a one-time cost of under $1500. High resolution aerial images are valuable for documenting and analyzing small- to mid-scale geomorphic and tectonic features. However, collecting images of mid-scale features such as landslides, rock glaciers, fault scarps, and cinder cones is expensive and makes studies that rely on high resolution repeat imagery prohibitive for undergraduate geology departments with limited budgets. In addition to cost, collecting images of smaller scale geomorphic features such as gravel bars is often impeded by overhanging vegetation or other features in the immediate environment that make impractical the collection of aerial images using standard airborne techniques. The methods provide high resolution stereo photos suitable for image processing and stereographic analysis; the images are potentially suitable for change analyses, velocity tracking, and construction of lidar-resolution digital elevation models. We developed two techniques. The technique suitable for small-scale features (such as gravel bars) utilizes two Nikon D3000 digital single-lens reflex (DSLR) cameras attached to a system of poles that suspends the cameras at a height of 4 meters with a variable camera separation of 0.6 to 0.9 m. The poles are oriented such that they do not appear in the photographs. The cameras are simultaneously remotely activated to collect stereo pairs at a resolution of 64 pixels/cm2 (pixel length is 1.2 mm). Ground control on the images is provided by pegs placed 5 meters apart, GPS positioning, and a meter-stick included in each photograph. Initial photo data gathered of a gravel bar on the Henry’s Fork of the Snake River, north of Rexburg, Idaho is sharp and readily segmented using the MatLab-based CLASTS image processing algorithm. The technique developed for imaging mid-scale features (such as cinder cones) consists of a tethered weather balloon with a gimbal that keeps the camera oriented vertically. A single DSLR camera is suspended at an elevation of approximately 45 m. The camera is operated via a radio-controlled apparatus that enables the user to view the area being photographed prior to activating the shutter. The balloon is physically moved to capture the second image of the stereo pair. Resolution of the images is 3600 pixels/m2 (pixel length is 1.6 cm). The techniques demonstrate that collecting high-resolution stereographic aerial photographs can be accomplished on a limited budget. The techniques and equipment will be used to collect repeat images for several multi-year studies, including monitoring gravel bar evolution, vector tracking of landslide and rock glacier motion, and monitoring fault scarp and cinder cone degradation.

  9. Characteristic features of wear in tools made of high-speed steels with surface engineered coatings I. Wear characteristics of surface engineered high-speed steel cutting tools

    Microsoft Academic Search

    G. S. Fox-Rabinovich; A. I. Kovalev; S. N. Afanasyev

    1996-01-01

    Characteristic features of wear in tools made of high-speed steels with surface engineered coatings incorporating ion nitriding and (Ti, Cr) nitride CAPDP (cathode arc plasma deposition process) coatings were investigated at increased cutting speeds in the vicinity of 50–100 m min?1. The wear kinetics, the change of micro-relief of cutter surface and the depth of the unhardened zone of cutting

  10. Integrated siRNA design based on surveying of features associated with high RNAi effectiveness

    Microsoft Academic Search

    Wuming Gong; Yongliang Ren; Qiqi Xu; Yejun Wang; Dong Lin; Haiyan Zhou; Tongbin Li

    2006-01-01

    BACKGROUND: Short interfering RNAs have allowed the development of clean and easily regulated methods for disruption of gene expression. However, while these methods continue to grow in popularity, designing effective siRNA experiments can be challenging. The various existing siRNA design guidelines suffer from two problems: they differ considerably from each other, and they produce high levels of false-positive predictions when

  11. Structural inheritance and special features of fracture of high-speed steels

    Microsoft Academic Search

    A. S. Chaus; F. I. Rudnitskii; M. Murgas

    1997-01-01

    Interest in the problem of improving the mechanical properties of high-speed steels has increased due to newly opened opportunities\\u000a to manufacture inexpensive cast tools by utilizing waste of grinding production. Modification is a simple and effective means\\u000a of improving the properties of cast alloys of various classes. The present paper is devoted to the effect of structural inheritance\\u000a on the

  12. Gas Dynamic Features of Self Ignition of Non Diluted Fuel\\/Air Mixtures at High Pressure

    Microsoft Academic Search

    R. BLUMENTHAL; K. FIEWEGER; K. H. KOMP; G. ADOMEIT

    1997-01-01

    – The self ignition of several non diluted fuel\\/air mixtures at high pressureis studied. Hydrogen,rsc-ocrane and n-heptane have been used as fuels. Experimentshave been performedusing the shock tube technique. Various observation methods, such as recording of pressure and of light band emission and shadow cinematography have been applied. The type of self ignition 35 well as the ignition delay times

  13. Gas Dynamic Features of Self Ignition of Non Diluted Fuel\\/Air Mixtures at High Pressure

    Microsoft Academic Search

    R. BLUMENTHAL; K. FIEWEGER; K. H. KOMP; G. ADOMEIT

    1996-01-01

    The self ignition of several non diluted fuel\\/air mixtures at high pressure is studied. Hydrogen, iso-octane and n-heptane have been used as fuels. Experiments have been performed using the shock tube technique. Various observation methods, such as recording of pressure and of light band emission and shadow cinematography have been applied. The type of self ignition as well as the

  14. Very compact, high-stability electrostatic actuator featuring contact-free self-limiting displacement

    DOEpatents

    Rodgers, M. Steven (Albuquerque, NM); Miller, Samuel L. (Albuquerque, NM)

    2003-01-01

    A compact electrostatic actuator is disclosed for microelectromechanical (MEM) applications. The actuator utilizes stationary and moveable electrodes, with the stationary electrodes being formed on a substrate and the moveable electrodes being supported above the substrate on a frame. The frame provides a rigid structure which allows the electrostatic actuator to be operated at high voltages (up to 190 Volts) to provide a relatively large actuation force compared to conventional electrostatic comb actuators which are much larger in size. For operation at its maximum displacement, the electrostatic actuator is relatively insensitive to the exact value of the applied voltage and provides a self-limiting displacement.

  15. A small mission featuring an imaging x-ray polarimeter with high sensitivity

    NASA Astrophysics Data System (ADS)

    Weisskopf, Martin C.; Baldini, Luca; Bellazini, Ronaldo; Brez, Alessandro; Costa, Enrico; Dissly, Richard; Elsner, Ronald F.; Fabiani, Sergio; Matt, Giorgio; Minuti, Massimo; Muleri, Fabio; O'Dell, Steve; Pinchera, Michele; Ramsey, Brian; Rubini, Alda; Sgro', Carmelo; Soffitta, Paolo; Spandre, Gloria

    2013-09-01

    We show that meaningful, highly sensitive x-ray polarimetry with imaging capability is possible with a small mission tailored to the NASA Explorer program. Such a mission—derived from the Imaging X-ray Polarimetry Explorer (IXPE) proposed to a previous NASA call—takes advantage of progress in light-weight x-ray optics and in gas pixel detectors to achieve sensitive time-resolved, spectrometric, imaging polarimetry. We outline the main characteristics and requirements of this mission and provide a realistic assessment of its scientific utility for modeling point-like and extended x-ray sources and for studying physical processes (including questions of fundamental physics).

  16. Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases.

    PubMed

    Matsuhashi, A; Ohno, T; Kimura, M; Hara, A; Saio, M; Nagano, A; Kawai, G; Saitou, M; Takigami, I; Yamada, K; Okano, Y; Shimizu, K

    2012-07-01

    Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, endoreduplication, and apoptosis. In the present study, we further investigated the molecular mechanisms underlying these effects. The inhibitor arrested various cells at G2 phase at low concentration, and at both G1 and G2 phases at high concentration. JNJ-7706621 did not prevent localization of Aurora A to the spindle poles, but did inhibit other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase. Similarly, the drug did not prevent localization of Aurora B to the kinetochore, but did inhibit other chromosomal passenger proteins such as Survivin and INCENP. In the cells exposed to JNJ-7706621 after nocodazole release, Aurora B, INCENP, and Survivin became relocated to the peripheral region of chromosomes, but Plk1 and Prc1 were localized on microtubules in later mitotic phase. Treatment of nocodazole-synchronized cells with JNJ-7706621 was able to override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation. Injection of the drug significantly inhibited the growth of TC135 Ewing's sarcoma cells transplanted into athymic mice by cell cycle arrest and apoptosis. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at multiple points, suggesting that it could be useful for cell cycle analysis and therapy of various cancers, including Ewing's sarcoma. PMID:22463590

  17. Quantitative analysis of anthropogenic relief features: automated mapping of charcoal kiln sites from high-resolution ALS data

    NASA Astrophysics Data System (ADS)

    Schneider, Anna; Takla, Melanie; Nicolay, Alexander; Raab, Alexandra; Raab, Thomas

    2014-05-01

    High-resolution digital elevation data from airborne laser scanning (ALS) allow for identification and mapping of so far unknown small-scale relief features that are hidden by forest cover. Especially as a result of historic land use, small anthropogenic landforms can occur, e.g., remains of charcoal kilns on sites that were used for charcoal production or ridge and furrow systems in former farmland areas. Mapping such relief features and analyzing their spatial distribution patterns can help to understand past land-use systems and their effects on landscapes. To efficiently detect and quantify small-scale relief features from high-resolution DEMs for larger areas, (semi-) automated mapping routines are required. In order to describe the number and spatial distribution of historic charcoal kiln sites in the area around Cottbus, Germany, we developed a GIS-based routine for the detection and mapping of kiln remnants from ALS elevation models with a resolution of 1 or 2 meters. The method is based on a template matching algorithm, using a combination of morphometric parameters, and is implemented within ArcGIS. The mapping results could be validated against a comprehensive database of kiln sites and diameters recorded from archaeological excavations in the forefield of the opencast mine Jänschwalde and from manual digitization of kiln remnants from Shaded Relief maps for the Jänschwalder Heide and the Tauersche Forst, north of Cottbus. A considerably high number of charcoal kiln sites could be detected in ALS data, and the diameters of the identified charcoal kilns are remarkable large in the area. For the Jänschwalder Heide, more than 5000 kiln sites in an area of 32 km2 were detected by manual digitization, with 1355 kiln sites that are wider than 12 m. These relatively large kiln sites could be mapped with detection rates that are close to those of manual digitization using the automated mapping routine. Detection quality was improved by the combination of several morphometric parameters used for template matching, as compared to a mapping based on elevation values only. In comparison to manual digitization, a combination of the described detection routine and a manual removal of falsely detected sites can considerably facilitate the mapping and distribution analysis of kiln sites or other small-scale relief features.

  18. High efficiency n-type silicon solar cells featuring passivated contact to laser doped regions

    NASA Astrophysics Data System (ADS)

    Yang, Xinbo; Bullock, James; Bi, Qunyu; Weber, Klaus

    2015-03-01

    Minimizing carrier recombination at cell contacts becomes increasingly important for reaching high efficiency. In this work, the passivated contact concept is implemented into n-type silicon solar cells with laser-processed local back surface fields. The passivation and contact characteristics of the SiO2/amorphous silicon (a-Si:H) stack on localized laser doped n+ regions are investigated. We find that the SiO2/a-Si:H stack provides not only good passivation to laser doped n+ regions but also allows a low contact resistivity after thermal annealing. With the implementation of the SiO2/a-Si:H passivated contact, an absolute efficiency gain of up to 1.5% is achieved for n-type solar cells.

  19. DE/ISIS conjunction comparisons of high-latitude electron density features

    NASA Technical Reports Server (NTRS)

    Hoegy, Walter R.; Benson, Robert F.

    1988-01-01

    This paper presents a comparison between the ISIS-1 and -2 topside sounder measurements of electron number density, N(e), with the in situ ion and N(e) measurements by the Langmuir probe aboard the Dynamics Explorer 2 (DE 2) during four high-latitude ISIS/DE magnetic field-aligned conjunctions. The ISIS-derived N(e) values, even at the greatest distance from the sounder, were found to agree with the Langmuir probe measurements to within about 30 percent over a density range of more than two decades on three of the four comparisons; the fourth comparison which included data with strong N(e) irregularities, showed a difference of 60 percent.

  20. Experimental investigation of primary and secondary features in high-mach-number shock-bubble interaction.

    PubMed

    Ranjan, Devesh; Niederhaus, John; Motl, Bradley; Anderson, Mark; Oakley, Jason; Bonazza, Riccardo

    2007-01-12

    Experiments to study the compression and unstable evolution of an isolated soap-film bubble containing helium, subjected to a strong planar shock wave (M=2.95) in ambient nitrogen, have been performed in a vertical shock tube of square internal cross section using planar laser diagnostics. The early phase of the interaction process is dominated by the formation of a primary vortex ring due to the baroclinic source of vorticity deposited during the shock-bubble interaction, and the mass transfer from the body of the bubble to the vortex ring. The late time (long after shock interaction) study reveals the presence of a secondary baroclinic source of vorticity at high Mach number which is responsible for the formation of counterrotating secondary and tertiary vortex rings and the subsequent larger rate of elongation of the bubble. PMID:17358611

  1. Microstructure features of high-entropy equiatomic cast AlCrFeCoNiCu alloys

    NASA Astrophysics Data System (ADS)

    Ivchenko, M. V.; Pushin, V. G.; Uksusnikov, A. N.; Wanderka, N.

    2013-06-01

    The structural and phase transformations that take place in the cast high-entropy equiatomic alloy AlCrFeCoNiCu after solidification, homogenizing heat treatment, and cooling have been studied. Analytical transmission microscopy, scanning electron microscopy, X-ray energy dispersive spectroscopy, and X-ray diffraction analysis were used to conduct the studies. The elastic modulus, nano-, and microhardness have been measured. The alloy decomposition has been found to occur with the precipitation of no less than six nanoscale phases with different morphologies, structures ( A2, B2, L12), and chemical compositions. All the nanophases are multicomponent solid solutions enriched with several elements, which indicates the pronounced elemental and phase nanomodulation over the alloy volume.

  2. The importance of study design for detecting differentially abundant features in high-throughput experiments.

    PubMed

    Luo, Huaien; Li, Juntao; Chia, Burton Kuan Hui; Robson, Paul; Nagarajan, Niranjan

    2014-01-01

    High-throughput assays, such as RNA-seq, to detect differential abundance are widely used. Variable performance across statistical tests, normalizations, and conditions leads to resource wastage and reduced sensitivity. EDDA represents a first, general design tool for RNA-seq, Nanostring, and metagenomic analysis, that rationally selects tests, predicts performance, and plans experiments to minimize resource wastage. Case studies highlight EDDA's ability to model single-cell RNA-seq, suggesting ways to reduce sequencing costs up to five-fold and improving metagenomic biomarker detection through improved test selection. EDDA's novel mode-based normalization for detecting differential abundance improves robustness by 10% to 20% and precision by up to 140%. PMID:25517037

  3. Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus

    PubMed Central

    Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

    2014-01-01

    The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

  4. Immunopathology features of chronic rhinosinusitis in high-altitude dwelling Tibetans

    PubMed Central

    Luo, Ba; Feng, Liu; Jintao, Du; Shixi, Liu; Nan, Zhang; Bachert, Claus

    2013-01-01

    Chronic rhinosinusitis (CRS) presents distinct inflammatory and remodeling patterns in different populations and environments. Tibetan ethnic groups live at high altitudes and in cold weather conditions. We sought to examine whether Tibetans exhibit distinct CRS pathology or characteristics. Sinonasal polyps and mucosal tissue were obtained from 14 Tibetan patients with CRS and nasal polyps (CRSwNPs), 13 patients with CRS without nasal polyps (CRSsNPs), and 12 Tibetan controls. Tissue homogenates and serum samples were assayed for several T-helper (TH) cell cytokines and mediators using enzyme linked immunosorbent assay profiles were measured using quantity polymerase chain reaction. Several key inflammatory cells were examined for immunohistochemical markers. CRSwNPs were characterized by increased mediator promoting eosinophilic inflammation (interleukin [IL]-5, eosinophil cationic protein, and total immunoglobulin E) and slight synergism with expression of IL-8, IL-2sRa, IL-1beta, IL-6, and myeloperoxidase, and a predominance of eosinophils, mast cells, and neutrophils. GATA-3 transcription factor was significantly increased and Foxp3 showed a tendency to be impaired in CRSwNPs compared with controls. CRSsNPs were characterized by significantly high levels of transforming growth factor beta1, increased interferon ?, and a significant enhancement of Foxp3 and T-beta compared with CRSwNPs. There were reduced numbers of inflammatory cells but increased levels of macrophages in CRSsNPs. Compared with CRSsNPs, CRSwNPs present a severe inflammatory reaction and show a TH2 milieu with apparently impaired regulatory T cells (Treg) function and increased inflammatory cells infiltration predominated by eosinophilic and mast cells. In contrast, TH1 polarization with enhanced Treg function and increased levels of macrophages appear in CRSsNPs. PMID:24124640

  5. Why do granites stand out as high elevation features of the landscape ?

    NASA Astrophysics Data System (ADS)

    Braun, J.; Murray, K. E.; Reiners, P. W.; Simon-Labric, T.

    2013-12-01

    We propose a simple mechanism to explain why granitic igneous intrusions, despite being denser than the rocks they usually intrude, stand out as topographic highs in the landscape. This mechanism is predicted to be far more important than hardness or erodibility variations in many cases. We derived a very simple expression for the relationship between isostatically-driven surface uplift and erosion rates as a function of surface rock density that implies that the denser the surface rocks the faster the isostatic rebound. Using a surface process model coupled to a flexural isostatic model, we show how variations in surface rock density may result in substantial differential isostatic rebound and thus surface uplift rate and topography. We demonstrate that the contribution of this isostatic effect can be distinguished from that arising from the stronger resistance of denser rocks to erosion by estimating the enhanced rate of erosion predicted by our theory through variations in cooling ages from low temperature thermochonometers. We illustrate our proposition through a large number of examples where variations in surface rock density may have led to differential uplift and topography, including various granitic intrusions, but also the exhumation of denser rocks such as basaltic intrusions or gneiss domes or the emergence of continental areas from below sea level at the transition between the subduction and collision phases at active plate margins. Predicted steady-state surface topography in an area intruded by four dense granites that appear as topographic highs. Note that the granites have the same resistance to erosion than the surrounding rocks; they are denser.

  6. Simulating thermal stress features on hot planetary surfaces in vacuum at high temperature facility in the PEL laboratory

    NASA Astrophysics Data System (ADS)

    Maturilli, A.; Ferrari, S.; Helbert, J.; D'Incecco, P.; D'Amore, M.

    2011-12-01

    In the Planetary Emissivity Laboratory (PEL) at the Institute for Planetary Research of the German Aerospace Center (DLR) in Berlin, we set-up a simulation chamber for the spectroscopic investigation of minerals separates under Mercurial conditions. The chamber can be evacuated to 10-4 bar and the target samples heated to 700 K within few minutes, thanks to the innovative inductive heating system. While developing the protocol for the high temperature spectroscopy measurements we discovered interesting "morphologies" on the sample surfaces. The powders are poured into stainless steel cups of 50 mm internal diameter, 8 mm height and 3 mm depth, having a 5 mm thick base (thus leaving 3 mm free space for the minerals), and rim 1 mm thick. We selected several minerals of interest for Mercurial surface composition and for each of them we analyzed various grain size separates, to study the influence of grain dimensions to the process of thermal stressing. We observed that for the smaller grain size separate (0-25 ?m) the thermal stress mainly induces large depressions and fractures, while on larger grain sizes (125-250 ?m) small depressions and a cratered surface. Our current working hypothesis is that these features are mainly caused by thermal stress induced by a radiatively quickly cooling surface layer covering the much hotter bulk material. Further investigation is ongoing to understand the processes better. The observed morphologies exhibit surprising similarities to features observed at planetary scale size for example on Mercury and even on Venus. Especially the high resolution images provided currently from MESSENGER'S Mercury Dual Imaging System (MDIS) instrument has revealed plains dominated by polygonal fractures whose origin still have to be determined. Our laboratory analogue studies might in the future provide some insight into the processes creating those features

  7. Inhibition of a Mitotic Motor Protein: Where, How, and Conformational Consequences

    SciTech Connect

    Yan, Youwei; Sardana, Vinod; Xu, Bei; Homnick, Carl; Halczenko, Wasyl; Buser, Carolyn A.; Schaber, Michael; Hartman, George D.; Huber, Hans E.; Kuo, Lawrence C. (Merck)

    2010-11-16

    We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 {angstrom} resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg{sup 2+} {center_dot} ADP, reveals that monastrol confers inhibition by 'induced-fitting' onto the protein some 12 {angstrom} away from the catalytic center of the enzyme, resulting in the creation of a previously non-existing binding pocket. The structure provides new insights into the biochemical and mechanical mechanisms of the mitotic motor domain. Inhibition of KSP provides a novel mechanism to arrest mitotic spindle formation, a target of several approved and investigative anti-cancer agents. The structural information gleaned from this novel pocket offers a new angle for the design of anti-mitotic agents.

  8. Microcephaly Disease Gene Wdr62 Regulates Mitotic Progression of Embryonic Neural Stem Cells and Brain Size

    PubMed Central

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk; Lai, Fan; Niswander, Lee

    2014-01-01

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly. PMID:24875059

  9. Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold

    E-print Network

    Poirier, Michael

    Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold) chromosomes were studied by using micromechanical force measurement during nu- clease digestion. Micrococcal response of, and then to go on to completely disintegrate, single metaphase newt chromosomes

  10. Modulation of mitotic progression and cell cycle checkpoints by phosphorylation-dependent protein-protein interactions

    E-print Network

    Lowery, Drew M

    2007-01-01

    Alteration of mitotic gene function has recently been discovered to play a key role in tumor formation and cancer progression through the induction of chromosomal aberrations and genomic instability. Polo-like-kinase-1 is ...

  11. Spatial and temporal coordination of genome segregation with activation of the Mitotic Exit Network

    E-print Network

    Rock, Jeremy M. (Jeremy Michael)

    2012-01-01

    In budding yeast, an essential Hippo-like signal transduction cascade known as the Mitotic Exit Network (MEN) governs the final cell cycle transition, the mitosis to G1 transition. To ensure the accurate execution of ...

  12. The discovery and optimization of hexahydro-2 H-pyrano[3,2- c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5

    Microsoft Academic Search

    Kai Schiemann; Dirk Finsinger; Frank Zenke; Christiane Amendt; Thorsten Knöchel; David Bruge; Hans-Peter Buchstaller; Ulrich Emde; Wolfgang Stähle; Soheila Anzali

    2010-01-01

    Here we describe the discovery and optimization of hexahydro-2H-pyrano[3,2-c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5 originally found during a high-throughput screening (HTS) campaign sampling our in-house compound collection. The compounds optimized subsequently and characterized herein were potently inhibiting the ATPase activity of Kinesin-5 and also exhibited consistent cellular activity, in that cells arrested in mitosis and

  13. Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization†

    PubMed Central

    2010-01-01

    We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2. PMID:20936789

  14. New spectral features of stratospheric trace gases identified from high-resolution infrared balloon-borne and laboratory spectra

    NASA Technical Reports Server (NTRS)

    Goldman, A.; Murcray, F. J.; Blatherwick, R. D.; Kosters, J. J.; Murcray, F. H.; Murcray, D. G.; Rinsland, C. P.

    1989-01-01

    A new Michelson-type interferometer system operating in the infrared at very high resolution has been used to record numerous balloon-borne solar absorption spectra of the stratosphere, ground-based solar absorption spectra, and laboratory spectra of molecules of atmospheric interest. In the present work results obtained for several important stratospheric trace gases, HNO3, CIONO2, HO2NO2, NO2, and COF2, in the 8- to 12-micron spectral region are reported. Many new features of these gases have been identified in the stratospheric spectra. Comparison of the new spectra with line-by-line simulations shows that previous spectral line parameters are often inadequate and that new analysis of high-resolution laboratory and atmospheric spectra and improved theoretical calculations will be required for many bands. Preliminary versions of several sets of improved line parameters under development are discussed.

  15. High-resolution transcriptome maps reveal strain-specific regulatory features of multiple Campylobacter jejuni isolates.

    PubMed

    Dugar, Gaurav; Herbig, Alexander; Förstner, Konrad U; Heidrich, Nadja; Reinhardt, Richard; Nieselt, Kay; Sharma, Cynthia M

    2013-05-01

    Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA-seq (dRNA-seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA-seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA-seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA-seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into strain-specific transcriptome organization and sRNAs, and reveals genes that could modulate phenotypic variation among strains despite high conservation at the DNA level. PMID:23696746

  16. High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Campylobacter jejuni Isolates

    PubMed Central

    Förstner, Konrad U.; Heidrich, Nadja; Reinhardt, Richard; Nieselt, Kay; Sharma, Cynthia M.

    2013-01-01

    Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA–seq (dRNA–seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA–seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA–seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA–seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into strain-specific transcriptome organization and sRNAs, and reveals genes that could modulate phenotypic variation among strains despite high conservation at the DNA level. PMID:23696746

  17. Naf1? is phosphorylated in mitotic phase and required to protect cells against apoptosis

    Microsoft Academic Search

    Shengliang Zhang; Marthandan Mahalingam; Nobuo Tsuchida

    2008-01-01

    Naf1? is an HIV Nef-associated factor expressed ubiquitously in human cells. Previously, we reported that Naf1? is phosphorylated with EGF through MEK\\/ERK2 pathway. In this study, we found an additional phosphorylation of Naf1? when cells are in mitotic phase (M phase) or arrested in M phase with anti-mitosis reagents, and disappeared when the cells exit from mitotic phase to G1

  18. Continued Stabilization of the Nuclear Higher-Order Structure of PostMitotic Neurons In Vivo

    Microsoft Academic Search

    Janeth Alva-Medina; Apolinar Maya-Mendoza; Myrna A. R. Dent; Armando Aranda-Anzaldo; Hui Zou

    2011-01-01

    BackgroundCellular terminal differentiation (TD) correlates with a permanent exit from the cell cycle and so TD cells become stably post-mitotic. However, TD cells express the molecular machinery necessary for cell proliferation that can be reactivated by experimental manipulation, yet it has not been reported the stable proliferation of any type of reactivated TD cells. Neurons become post-mitotic after leaving the

  19. Kinetics of mitotic arrest and apoptosis in murine mammary and ovarian tumors treated with taxol

    Microsoft Academic Search

    Luka Milas; Nancy R. Hunter; Belma Kurdoglu; Kathryn A. Mason; Raymond E. Meyn; L. C. Stephens; Lester J. Peters

    1995-01-01

    The kinetics of taxol-induced mitotic arrest and apoptosis in murine mammary carcinoma MCA-4 and ovarian carcinoma OCA-I tumors were determined to establish a possible causative relationship between mitotic arrest and apoptosis and to see whether these cellular effects of taxol would correlate with the extent of its antitumor efficacy. Mice bearing 8-mm tumors in a hind leg were given taxol

  20. Mitotic and polytene chromosomes: comparisons between Drosophila melanogaster and Drosophila simulans

    Microsoft Academic Search

    Sylvie Aulard; Laurence Monti; Nicole Chaminade; Françise Lemeunier

    \\u000a This review deals with the differences between Drosophila melanogaster and Drosophila simulans in their mitotic and polytene chromosomes. The description of the mitotic karyotypes of D. melanogaster and D. simulans is mainly based on the methods that allow to differentiate their euchromatin from their heterochromatin: banding patterns,\\u000a distribution of satellite DNAs and location of the rDNA. The polytene chromosomes karyotypes

  1. High-resolution PFPE-based molding techniques for nanofabrication of high-pattern density, sub-20 nm features: a fundamental materials approach.

    PubMed

    Williams, Stuart S; Retterer, Scott; Lopez, Rene; Ruiz, Ricardo; Samulski, Edward T; DeSimone, Joseph M

    2010-04-14

    Several perfluoropolyether (PFPE)-based elastomers for high-resolution replica molding applications are explored. The modulus of the elastomeric materials was increased through synthetic and additive approaches while maintaining relatively low surface tension values (<25 mN/m). Using large area (>4 in.(2)) master templates, we experimentally show the relationship between mold resolution and material properties such as modulus and surface tension for materials used in this study. A composite mold approach was used to form flexible molds out of stiff, high modulus materials that allow for replication of sub-20 nm post structures. Sub-100 nm line grating master templates, formed using e-beam lithography, were used to determine the experimental stability of the molding materials. It was observed that as the feature spacing decreased, high modulus PFPE tetramethacrylate (TMA) composite molds were able to effectively replicate the nanograting structures without cracking or tear-out defects that typically occur with high modulus elastomers. PMID:20178369

  2. Features of High-Temperature Calibration of W/Re Thermocouples

    NASA Astrophysics Data System (ADS)

    Ulanovskiy, A.; Edler, F.; Fischer, J.; Oleynikov, P.; Zaytsev, P.; Pokhodun, A.

    2015-03-01

    Investigations of Type A (W-5 %Re/W-20 %Re) thermocouples were performed at several laboratories to validate their reference function before its standardization in the new issue of the international standard IEC 60584. The Type A thermocouples investigated were equipped with sealed protection tubes made of sapphire which were filled with an inert gas (argon). The investigations at Russian laboratories were performed mainly in carbon-free high-temperature furnaces. The calibration results obtained in the temperature range (600 to 1850) in the carbon-free environment were within % tolerance limits and confirmed the suitability of Type A thermocouples for industrial applications. In contrast, the Type A thermocouple 89/95-P investigated at PTB (Germany) was exposed to a carbon environment when annealed at and when it was calibrated at metal-carbon eutectic (Me-C) fixed points. Measurements made at Me-C fixed points did not deviate from the reference function by more than about 6 K at the first stage when temperatures were below . However, the inhomogeneity of the thermoelements increased continuously after the calibration at the Me-C eutectic fixed points. The additional measurements at the peritectic fixed point () resulted in a continuous emf drift to deviations from the reference function of about (100 to 150) which corresponds to a temperature equivalent of about (9 to 14) K. The thermoelectric stability and homogeneity of the thermocouple 89/95-P during these investigations was checked by repeated measurements at the freezing point of copper ().

  3. Features charge states of heavy energetic particles for high number of events.

    NASA Astrophysics Data System (ADS)

    Nymmik, Rikho

    The solar energetic particle (SEP) C, O and Fe ion charge states in 51 gradual events of solar cycle 23 were determined using an original method based on a modified form of the particle energy spectra, consisting of two power law spectra separated by a knee. The experimental data from the GOES satellites (protons) as well as from the ULEIS (all particles) and SIS instruments aboard the ACE satellite (ions He, C, O and Fe) were used to calculate the average charge states of C ions (5.88 ± 0.06; with standard deviation of the experimental data ?total=0.35), O ions (6.80 ± 0.07; ?total = 0.59) and Fe ions (14.44 ± 0.25; ?total = 1.61). We found that the charge states of high-energy heavy ions of the Sun do not depend on the size (capacity) of SEP events, on the particle energy (in the interval 0.3-30 MeV / nucleon), or on the variation of the relative composition of heavy ion fluxes.

  4. Vibrational Features of Water at the Low-Density/High-Density Liquid Structural Transformations

    E-print Network

    Khusnutdinoff, Ramil M

    2011-01-01

    A structural transformation in water upon compression was recently observed at the temperature $T=277$~K in the vicinity of the pressure $p \\approx 2\\;000$~Atm [R.M. Khusnutdinoff, A.V. Mokshin, J. Non-Cryst. Solids \\textbf{357}, 1677 (2011)]. It was found that the transformations are related with the principal structural changes within the first two coordination shells as well as the deformation of the hydrogen-bond network. In this work we study in details the influence of these structural transformations on the vibrational molecular dynamics of water by means of molecular dynamics simulations on the basis of the model Amoeba potential ($T=290$~K, $p=1.0 \\div 10\\;000$~Atm). The equation of state and the isothermal compressibility are found for the considered ($p$,$T$)-range. The vibrational density of states extracted for $THz$-frequency range manifests the two distinct modes, where the high-frequency mode is independent on pressure whereas the low-frequency one has the strong, non-monotonic pressure-depend...

  5. Vibrational features of water at the low-density/high-density liquid structural transformations

    NASA Astrophysics Data System (ADS)

    Khusnutdinoff, Ramil M.; Mokshin, Anatolii V.

    2012-05-01

    A structural transformation in water upon compression was recently observed at the temperature T=277 K in the vicinity of the pressure p?2 000 atm [R.M. Khusnutdinoff, A.V. Mokshin, J. Non-Cryst. Solids 357 (2011) 1677]. It was found that the transformations are related with the principal structural changes within the first two coordination shells as well as the deformation of the hydrogen-bond network. In this work, we study in detail the influence of these structural transformations on the vibrational molecular dynamics of water by means of molecular dynamics simulations on the basis of the model Amoeba potential (T=290 K, p=1.0÷10 000 atm). The equation of state and the isothermal compressibility are found for the considered (p, T)-range. The vibrational density of states extracted for THz-frequency range manifests two distinct modes, where the high-frequency mode is independent of pressure whereas the low-frequency one has the strong, non-monotonic pressure-dependence and exhibits a step-like behavior at the pressure p?2000 atm. The extended analysis of the local structural and vibrational properties discovers that there is a strong correlation between the primary structural and vibrational aspects of the liquid-liquid structural transformation related with the molecular rearrangement within the range of the second coordination shell.

  6. The FlyCatwalk: A High-Throughput Feature-Based Sorting System for Artificial Selection in Drosophila

    PubMed Central

    Medici, Vasco; Vonesch, Sibylle Chantal; Fry, Steven N.; Hafen, Ernst

    2015-01-01

    Experimental evolution is a powerful tool for investigating complex traits. Artificial selection can be applied for a specific trait and the resulting phenotypically divergent populations pool-sequenced to identify alleles that occur at substantially different frequencies in the extreme populations. To maximize the proportion of loci that are causal to the phenotype among all enriched loci, population size and number of replicates need to be high. These requirements have, in fact, limited evolution studies in higher organisms, where the time investment required for phenotyping is often prohibitive for large-scale studies. Animal size is a highly multigenic trait that remains poorly understood, and an experimental evolution approach may thus aid in gaining new insights into the genetic basis of this trait. To this end, we developed the FlyCatwalk, a fully automated, high-throughput system to sort live fruit flies (Drosophila melanogaster) based on morphometric traits. With the FlyCatwalk, we can detect gender and quantify body and wing morphology parameters at a four-old higher throughput compared with manual processing. The phenotyping results acquired using the FlyCatwalk correlate well with those obtained using the standard manual procedure. We demonstrate that an automated, high-throughput, feature-based sorting system is able to avoid previous limitations in population size and replicate numbers. Our approach can likewise be applied for a variety of traits and experimental settings that require high-throughput phenotyping. PMID:25556112

  7. Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression.

    PubMed

    Armistead, Joy; Patel, Nehal; Wu, Xiaoli; Hemming, Richard; Chowdhury, Biswajit; Basra, Gagandeep Singh; Del Bigio, Marc R; Ding, Hao; Triggs-Raine, Barbara

    2015-05-01

    Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G, p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to characterize the effects of EMG1 deficiency, particularly in the brain, where EMG1 expression is high. Embryos homozygous for the mutation in Emg1 were small for gestational age with neural tube defects, and died between embryonic days 8.5 and 12.5. These embryos exhibited dramatically reduced cell proliferation, which we also detected in autopsy brain tissue and bone marrow of BCS patients, consistent with a requirement for high levels of EMG1 in tissues with rapid cell proliferation. In fibroblasts derived from the BCS mouse embryos, we detected a high proportion of binucleated cells, indicating that a mitotic defect underlies the growth arrest in BCS. These studies add to growing evidence of a link between ribosome biogenesis, mitotic progression, and brain development that is currently unexplored. PMID:25708872

  8. MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.

    PubMed

    Voets, Erik; Wolthuis, Rob M F

    2010-09-01

    Greatwall (Gwl) was originally discovered in Drosophila as an essential kinase for correct chromosome condensation and mitotic progression. In Xenopus, Gwl may influence the positive-feedback loop that directs cyclin B1-Cdk1 activation and the mitotic state by inhibiting the phosphatase PP 2A. Here, we describe the human orthologue of Gwl called microtubule-associated serine/threonine kinase-like (MASTL). We found that MASTL localizes to the nucleus in interphase and re-localizes in part to centrosomes in mitosis, when it is active. Cells strongly depleted of MASTL by RNAi delay in G(2) phase and reveal slow chromosome condensation. MASTL RNAi cells that enter and progress through mitosis often fail to completely separate their sister chromatids in anaphase. This causes chromatin to be trapped in the cleavage furrow, which may lead to the formation of 4N G(1) cells by cytokinesis failure. Further, our experiments indicate that MASTL supports the phosphorylation state of mitotic phospho-proteins downstream of cyclin B1-Cdk1, including the APC/C. Cyclin B1 destruction is incomplete when mitotic cells that are strongly depleted of MASTL exit mitosis. We propose that MASTL enhances cyclin B1-Cdk1-dependent mitotic phosphorylation events, directing mitotic entry, anaphase and cytokinesis in human cells. PMID:20818157

  9. Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm

    PubMed Central

    Daniels, Brian R.; Rikhy, Richa; Renz, Malte; Dobrowsky, Terrence M.; Lippincott-Schwartz, Jennifer

    2012-01-01

    Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional “compartmentalization” has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial Drosophila embryo on the effective diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of transient mitotic membrane furrows results in a multiscale diffusion effect that has a significant impact on effective diffusion rates across the embryo. Using a combination of live-cell experiments and computational modeling, we characterize these effects and relate effective bulk diffusion rates to instantaneous diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of the early embryo. This multiscale effect may be related to the effect of interphase nuclei on effective diffusion, and thus we propose that an as-yet-unidentified role of syncytial membrane furrows is to temporally regulate bulk embryonic diffusion rates to balance the multiscale effect of interphase nuclei, which ultimately stabilizes the shapes of various morphogen gradients. PMID:22592793

  10. Mitotic Chromosome Transmission Fidelity Mutants in Saccharomyces Cerevisiae

    PubMed Central

    Spencer, F.; Gerring, S. L.; Connelly, C.; Hieter, P.

    1990-01-01

    We have isolated 136 independent mutations in haploid yeast strains that exhibit decreased chromosome transmission fidelity in mitosis. Eighty-five percent of the mutations are recessive and 15% are partially dominant. Complementation analysis between MATa and MAT? isolates identifies 11 chromosome transmission fidelity (CTF) complementation groups, the largest of which is identical to CHL1. For 49 independent mutations, no corresponding allele has been recovered in the opposite mating type. The initial screen monitored the stability of a centromere-linked color marker on a nonessential yeast chromosome fragment; the mitotic inheritance of natural yeast chromosome III is also affected by the ctf mutations. Of the 136 isolates identified, seven were inviable at 37° and five were inviable at 11°. In all cases tested, these temperature conditional lethalities cosegregated with the chromosome instability phenotype. Five additional complementation groups (ctf12 through ctf16) have been defined by complementation analysis of the mutations causing inviability at 37°. Twenty-three of the 136 isolates exhibited growth defects at concentrations of benomyl permissive for the parent strain, and nine appeared to be tolerant of inhibitory levels of benomyl. All of the mutant strains showed normal sensitivity to ultraviolet and ?-irradiation. Further characterization of these mutant strains will describe the functions of gene products crucial to the successful execution of processes required for aspects of the chromosome cycle that are important for chromosome transmission fidelity in mitosis. PMID:2407610

  11. Breast cancer mitosis detection in histopathological images with spatial feature extraction

    NASA Astrophysics Data System (ADS)

    Albayrak, Abdülkadir; Bilgin, Gökhan

    2013-12-01

    In this work, cellular mitosis detection in histopathological images has been investigated. Mitosis detection is very expensive and time consuming process. Development of digital imaging in pathology has enabled reasonable and effective solution to this problem. Segmentation of digital images provides easier analysis of cell structures in histopathological data. To differentiate normal and mitotic cells in histopathological images, feature extraction step is very crucial step for the system accuracy. A mitotic cell has more distinctive textural dissimilarities than the other normal cells. Hence, it is important to incorporate spatial information in feature extraction or in post-processing steps. As a main part of this study, Haralick texture descriptor has been proposed with different spatial window sizes in RGB and La*b* color spaces. So, spatial dependencies of normal and mitotic cellular pixels can be evaluated within different pixel neighborhoods. Extracted features are compared with various sample sizes by Support Vector Machines using k-fold cross validation method. According to the represented results, it has been shown that separation accuracy on mitotic and non-mitotic cellular pixels gets better with the increasing size of spatial window.

  12. Online feature selection with streaming features.

    PubMed

    Wu, Xindong; Yu, Kui; Ding, Wei; Wang, Hao; Zhu, Xingquan

    2013-05-01

    We propose a new online feature selection framework for applications with streaming features where the knowledge of the full feature space is unknown in advance. We define streaming features as features that flow in one by one over time whereas the number of training examples remains fixed. This is in contrast with traditional online learning methods that only deal with sequentially added observations, with little attention being paid to streaming features. The critical challenges for Online Streaming Feature Selection (OSFS) include 1) the continuous growth of feature volumes over time, 2) a large feature space, possibly of unknown or infinite size, and 3) the unavailability of the entire feature set before learning starts. In the paper, we present a novel Online Streaming Feature Selection method to select strongly relevant and nonredundant features on the fly. An efficient Fast-OSFS algorithm is proposed to improve feature selection performance. The proposed algorithms are evaluated extensively on high-dimensional datasets and also with a real-world case study on impact crater detection. Experimental results demonstrate that the algorithms achieve better compactness and higher prediction accuracy than existing streaming feature selection algorithms. PMID:23520258

  13. Local changes of work function near rough features on Cu surfaces operated under high external electric field

    NASA Astrophysics Data System (ADS)

    Djurabekova, Flyura; Ruzibaev, Avaz; Holmström, Eero; Parviainen, Stefan; Hakala, Mikko

    2013-12-01

    Metal surfaces operated under high electric fields produce sparks even if they are held in ultra high vacuum. In spite of extensive research on the topic of vacuum arcs, the mystery of vacuum arc origin still remains unresolved. The indications that the sparking rates depend on the material motivate the research on surface response to extremely high external electric fields. In this work by means of density-functional theory calculations we analyze the redistribution of electron density on {100} Cu surfaces due to self-adatoms and in presence of high electric fields from -1 V/nm up to -2 V/nm (-1 to -2 GV/m, respectively). We also calculate the partial charge induced by the external field on a single adatom and a cluster of two adatoms in order to obtain reliable information on charge redistribution on surface atoms, which can serve as a benchmarking quantity for the assessment of the electric field effects on metal surfaces by means of molecular dynamics simulations. Furthermore, we investigate the modifications of work function around rough surface features, such as step edges and self-adatoms.

  14. Spectral features of Mini-Neptunes and EGP orbiting different stars: exploring the effect of high stellar FUV radiation

    NASA Astrophysics Data System (ADS)

    Miguel, Y.; Kaltenegger, L.

    2014-03-01

    Motivated by the growing population of hot exoplanets, we calculated an atmospheric grid for hot mini-Neptune and giant planets, that links astrophysical observable parameters - orbital distance and stellar type - with the atmospheric features expected in transmission and emission spectra. We link a 1D code that calculates the atmospheric thermal structure with a photochemical model that includes disequilibrium chemistry for planets with temperature between 2700K and 700K and explore the effect of empirical model parameters like eddy diffusion coefficients on the results (Miguel & Kaltenegger, 2013). We then use a line by line radiative transfer code to generate the observable spectra. Our models explore the detectable atmospheric features for a wide range of stellar types from F to M for distances between 0.01AU and 0.1 AU. Many main sequence M stars present strong chromospheric activity that produces high-energy radiation. That strongly affects hot exoplanet atmospheres. We use our models to reproduce results for known planets (WASP-12b, CoRoT-2b, XO-1b and HD189733b), model a new planet (HD97658b) and produce a grid for observed planets as well as to inform future observations. Our grid can be applied to current and future observations to characterize exoplanet atmospheres and serves as a reference to interpret atmospheric retrieval analysis results.

  15. The development of wing shape in Lepidoptera: mitotic density, not orientation, is the primary determinant of shape.

    PubMed

    Nijhout, H Frederik; Cinderella, Margaret; Grunert, Laura W

    2014-03-01

    The wings of butterflies and moths develop from imaginal disks whose structure is always congruent with the final adult wing. It is therefore possible to map every point on the imaginal disk to a location on the adult wing throughout ontogeny. We studied the growth patterns of the wings of two distantly related species with very different adult wing shapes, Junonia coenia and Manduca sexta. The shape of the wing disks change throughout their growth phase in a species-specific pattern. We measured mitotic densities and mitotic orientation in successive stages of wing development approximately one cell division apart. Cell proliferation was spatially patterned, and the density of mitoses was highly correlated with local growth. Unlike other systems in which the direction of mitoses has been viewed as the primary determinant of directional growth, we found that in these two species the direction of growth was only weakly correlated with the orientation of mitoses. Directional growth appears to be imposed by a constantly changing spatial pattern of cell division coupled with a weak bias in the orientation of cell division. Because growth and cell division in imaginal disk require ecdysone and insulin signaling, the changing spatial pattern of cell division may due to a changing pattern of expression of receptors or downstream elements in the signaling pathways for one or both of these hormones. Evolution of wing shape comes about by changes in the progression of spatial patterns of cell division. PMID:24617986

  16. High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance

    PubMed Central

    Qin, Huijun; Zhang, Xiaolin; Ye, Fei; Zhong, Liangwei

    2014-01-01

    High-fat diet (HFD) can induce oxidative stress. Thioredoxin (Trx) and thioredoxin reductase (TrxR) are critical antioxidant proteins but how they are affected by HFD remains unclear. Using HFD-induced insulin-resistant mouse model, we show here that liver Trx and TrxR are significantly decreased, but, remarkably, the degree of their S-acylation is increased after consuming HFD. These HFD-induced changes in Trx/TrxR may reflect abnormalities of lipid metabolism and insulin signaling transduction. HFD-driven accumulation of 4-hydroxynonenal is another potential mechanism behind inactivation and decreased expression of Trx/TrxR. Thus, we propose HFD-induced impairment of liver Trx/TrxR as major contributor to oxidative stress and as a novel feature of insulin resistance. PMID:25426412

  17. Automatic segmentation of brain MRI in high-dimensional local and non-local feature space based on sparse representation.

    PubMed

    Khalilzadeh, Mohammad Mahdi; Fatemizadeh, Emad; Behnam, Hamid

    2013-06-01

    Automatic extraction of the varying regions of magnetic resonance images is required as a prior step in a diagnostic intelligent system. The sparsest representation and high-dimensional feature are provided based on learned dictionary. The classification is done by employing the technique that computes the reconstruction error locally and non-locally of each pixel. The acquired results from the real and simulated images are superior to the best MRI segmentation method with regard to the stability advantages. In addition, it is segmented exactly through a formula taken from the distance and sparse factors. Also, it is done automatically taking sparse factor in unsupervised clustering methods whose results have been improved. PMID:23260393

  18. Human papillomavirus type 16 E7 perturbs DREAM to promote cellular proliferation and mitotic gene expression.

    PubMed

    DeCaprio, J A

    2014-07-31

    The study of the small DNA tumor viruses continues to provide valuable new insights into oncogenesis and fundamental biological processes. Although much has already been revealed about how the human papillomaviruses (HPVs) can transform cells and contribute to cervical and oropharyngeal cancer, there clearly is much more to learn. In this issue of Oncogene, Pang et al., doi:10.1038/onc.2013.426, demonstrate that the high-risk HPV16 E7 oncogene can promote cellular proliferation by interacting with the DREAM (DP, RB-like, E2F and MuvB) complex at two distinct phases of the cell cycle. Consistent with earlier work, HPV16 E7 can bind to the retinoblastoma tumor suppressor (RB) family member p130 (RBL2) protein and promote its proteasome-mediated destruction thereby disrupting the DREAM complex and can prevent exit from the cell cycle into quiescence. In addition, they demonstrate that HPV16 E7 can bind to MuvB core complex in association with BMYB and FOXM1 and activate gene expression during the G2 and M phase of the cell cycle. Thus, HPV16 E7 acts to prevent exit from the cell cycle entry and promotes mitotic proliferation and may account for the high levels of FOXM1 often observed in poor-risk cervical cancers. PMID:24166507

  19. Analogues to features and processes of a high-level radioactive waste repository proposed for Yucca Mountain, Nevada

    USGS Publications Warehouse

    Simmons, Ardyth M.; Stuckless, John S.; with a Foreword by Abraham Van Luik, U.S. Department of Energy

    2010-01-01

    Natural analogues are defined for this report as naturally occurring or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have taken place over time periods of decades to millennia and on spatial scales as much as tens of kilometers. Analogues provide an important temporal and spatial dimension that cannot be tested by laboratory or field-scale experiments. Analogues provide one of the multiple lines of evidence intended to increase confidence in the safe geologic disposal of high-level radioactive waste. Although the work in this report was completed specifically for Yucca Mountain, Nevada, as the proposed geologic repository for high-level radioactive waste under the U.S. Nuclear Waste Policy Act, the applicability of the science, analyses, and interpretations is not limited to a specific site. Natural and anthropogenic analogues have provided and can continue to provide value in understanding features and processes of importance across a wide variety of topics in addressing the challenges of geologic isolation of radioactive waste and also as a contribution to scientific investigations unrelated to waste disposal. Isolation of radioactive waste at a mined geologic repository would be through a combination of natural features and engineered barriers. In this report we examine analogues to many of the various components of the Yucca Mountain system, including the preservation of materials in unsaturated environments, flow of water through unsaturated volcanic tuff, seepage into repository drifts, repository drift stability, stability and alteration of waste forms and components of the engineered barrier system, and transport of radionuclides through unsaturated and saturated rock zones.

  20. Uncovering immobilized trypsin digestion features from large-scale proteome data generated by high-resolution mass spectrometry.

    PubMed

    Sun, Liangliang; Zhu, Guijie; Yan, Xiaojing; Mou, Si; Dovichi, Norman J

    2014-04-11

    Immobilized trypsin produces very fast protein digestion, which is attractive for application to high throughput bottom-up proteomics. While there is a rich literature on the preparation of immobilized trypsin, there are very few studies that investigate its application to complex proteomic samples. In this work, we compared solution-phase trypsin with trypsin immobilized on magnetic microspheres for digestion of two complex proteomes, Escherichia coli and the MCF7 cell line. The digests were separated by HPLC, and detected with a Q-Exactive mass spectrometer, which generated high resolution and high quality parent- and fragment-ion mass spectra. The data were analyzed using MaxQuant. We make several conclusions about the features of immobilized trypsin digestion of complex proteomes. First, both immobilized and solution-phase trypsin generate peptides that sample the same protein pool. Second, immobilized trypsin can digest complex proteomes two orders of magnitude faster than solution-phase trypsin while retaining similar numbers of protein identifications and proteome depth. Digestion using immobilized trypsin for 5-min produces a similar number of missed cleavages as solution-based trypsin digestion for 4-h; digestion using immobilized trypsin for 20-min produces a similar number of missed cleavages as solution-based trypsin digestion for 12-h. Third, immobilized trypsin produces quantitatively reproducible digestion of complex proteomes. Finally, there is small but measurable loss of peptide due to non-specific adsorption to the immobilization matrix. This adsorption generates a bias against detection of basic peptides. PMID:24636566

  1. Realizing one-dimensional quantum and high-frequency transport features in aligned single-walled carbon nanotube ropes

    SciTech Connect

    Ncube, Siphephile; Chimowa, George; Chiguvare, Zivayi; Bhattacharyya, Somnath, E-mail: Somnath.Bhattacharyya@wits.ac.za [Nano-Scale Transport Physics Laboratory, School of Physics and DST/NRF Centre of Excellence in Strong Materials, University of the Witwatersrand, Private Bag 3, WITS 2050, Johannesburg (South Africa)

    2014-07-14

    The superiority of the electronic transport properties of single-walled carbon nanotube (SWNT) ropes over SWNT mats is verified from low temperature and frequency-dependent transport. The overall change of resistance versus in nanotube mats shows that 3D variable range hopping is the dominant conduction mechanism within the 2–300?K range. The magneto-resistance (MR) is found to be predominantly negative with a parabolic nature, which can also be described by the hopping model. Although the positive upturn of the MR at low temperatures establishes the contribution from quantum interference, the inherent quantum transport in individual tubes is suppressed at elevated temperatures. Therefore, to minimize multi-channel effects from inter-tube interactions and other defects, two-terminal devices were fabricated from aligned SWNT (extracted from a mat) for low temperature transport as well as high-frequency measurements. In contrast to the mat, the aligned ropes exhibit step-like features in the differential conductance within the 80–300?K temperature range. The effects of plasmon propagation, unique to one dimension, were identified in electronic transport as a non-universal power-law dependence of the differential conductance on temperature and source-drain voltage. The complex impedance showed high power transmission capabilities up to 65?GHz as well as oscillations in the frequency range up to 30 GHz. The measurements suggest that aligned SWNT ropes have a realistic potential for high-speed device applications.

  2. Realizing one-dimensional quantum and high-frequency transport features in aligned single-walled carbon nanotube ropes

    NASA Astrophysics Data System (ADS)

    Ncube, Siphephile; Chimowa, George; Chiguvare, Zivayi; Bhattacharyya, Somnath

    2014-07-01

    The superiority of the electronic transport properties of single-walled carbon nanotube (SWNT) ropes over SWNT mats is verified from low temperature and frequency-dependent transport. The overall change of resistance versus in nanotube mats shows that 3D variable range hopping is the dominant conduction mechanism within the 2-300 K range. The magneto-resistance (MR) is found to be predominantly negative with a parabolic nature, which can also be described by the hopping model. Although the positive upturn of the MR at low temperatures establishes the contribution from quantum interference, the inherent quantum transport in individual tubes is suppressed at elevated temperatures. Therefore, to minimize multi-channel effects from inter-tube interactions and other defects, two-terminal devices were fabricated from aligned SWNT (extracted from a mat) for low temperature transport as well as high-frequency measurements. In contrast to the mat, the aligned ropes exhibit step-like features in the differential conductance within the 80-300 K temperature range. The effects of plasmon propagation, unique to one dimension, were identified in electronic transport as a non-universal power-law dependence of the differential conductance on temperature and source-drain voltage. The complex impedance showed high power transmission capabilities up to 65 GHz as well as oscillations in the frequency range up to 30 GHz. The measurements suggest that aligned SWNT ropes have a realistic potential for high-speed device applications.

  3. Volcanic Features

    NSDL National Science Digital Library

    2005-12-17

    This interactive resource adapted from the National Park Service illustrates the variety of landforms and features created by volcanoes. Featured are calderas, craters, fumaroles and other geothermal features, igneous rocks, lava flows, lava tubes, and maars.

  4. Benzo[a]pyrene-induced cell cycle arrest in HepG2 cells is associated with delayed induction of mitotic instability.

    PubMed

    Stellas, Dimitris; Souliotis, Vassilis L; Bekyrou, Margarita; Smirlis, Despina; Kirsch-Volders, Micheline; Degrassi, Francesca; Cundari, Enrico; Kyrtopoulos, Soterios A

    2014-11-01

    The environmental carcinogen benzo[a]pyrene (B[a]P) after being metabolised by cytochrome P450 enzymes forms DNA adducts. This abnormal situation induces changes in the cell cycle, DNA damage, chromosomal and mitotic aberrations, all of which may be related to carcinogenesis. In order to further investigate the mechanistic basis of these effects, HepG2 cells were treated with 3?M B[a]P for various time periods, followed by further incubation in the absence of B[a]P for up to 192h. B[a]P treatment led initially to S-phase arrest followed by recovery and subsequent induction of G2/M arrest, indicating activation of the corresponding DNA damage checkpoints. Immunofluorescence-based studies revealed accumulation of B[a]P-induced DNA adducts and chromosomal damage which persisted beyond mitosis and entry into a new cycle, thus giving rise to a new round of activation of the S-phase checkpoint. Prolonged further cultivation of the cells in the absence of B[a]P resulted in high frequencies of various abnormal mitotic events. Abrogation of the B[a]P-induced S-phase arrest by the Chk1 inhibitor UCN-01 triggered a strong apoptotic response but also dramatically decreased the frequency of mitotic abnormalities in the surviving cells, suggesting that events occurring during S-phase arrest contribute to the formation of delayed mitotic damage. Overall, our data demonstrate that, although S-phase arrest serves as a mechanism by which the cells reduce their load of genetic damage, its prolonged activation may also have a negative impact on the balance between cell death and heritable genetic damage. PMID:25771725

  5. A new E6/P63 pathway, together with a strong E7/E2F mitotic pathway, modulates the transcriptome in cervical cancer cells.

    PubMed

    Teissier, Sébastien; Ben Khalifa, Youcef; Mori, Marcella; Pautier, Patricia; Desaintes, Christian; Thierry, Françoise

    2007-09-01

    Cervical carcinoma is associated with certain types of human papillomaviruses expressing the E6 and E7 oncogenes, which are involved in carcinogenesis through their interactions with the p53 and pRB pathways, respectively. A critical event on the path to malignant transformation is often manifested by the loss of expression of the viral E2 transcription factor due to the integration into the host genome of the viral DNA. Using microarrays, we have previously shown that reintroduction of a functional E2 in the HeLa cervical carcinoma cell line activates a cluster of p53 target genes while at the same time severely repressing a group of E2F target genes. In the present study, using new high-density microarrays containing more than 22,000 human cDNA sequences, we identified a novel p63 pathway among E2-activated genes and 38 new mitotic genes repressed by E2. We then sought to determine the pathways through which these genes were modulated and used an approach that relies on small interfering RNA to demonstrate that the p63 target genes were activated through silencing of the E6/E6AP pathway while the mitotic genes were mainly repressed through E7 silencing. Importantly, a subset of the mitotic genes was shown to be significantly induced in biopsies of stage IV cervical cancers, which points to a prominent E7 pathway in cervical carcinoma. PMID:17582001

  6. Prevalence and clinical features of Thought-Perception-Sensitivity Symptoms: results from a community survey of Korean high school students.

    PubMed

    Kang, Nam-In; Park, Tae-Won; Yang, Jong-Chul; Oh, Keun-Young; Shim, Shi-Ha; Chung, Young-Chul

    2012-08-15

    Epidemiologic research indicates that psychosis and depression most frequently develop during adolescence. Hence, an efficient strategy for improving youth mental health would be to focus on detection of early-stage psychosis and depression in adolescence. In this study, 1461 high school students were surveyed using self-report scales. Students who scored equal to or above the cut-off value on any of the scales and who agreed to a further examination proceeded to a second assessment, using the Kiddie Schedule for Affective Disorders and Schizophrenia and Comprehensive Assessment of At-Risk Mental States along with self-reporting scales. The estimated prevalence of adolescents at ultra-high risk (UHR) for psychosis and of depression-spectrum disorders was 1.26 and 3.69% respectively. Compared with the normal group, experiences of bullying, suicidal ideation, and suicide attempts were significantly higher in these two groups; the subjects at UHR for psychosis were found to have significantly lower academic performance and lower ratings on SCRS; and submissive behavior was more prevalent in the depression-spectrum group. Our results reveal several clinical features of adolescents at UHR for psychosis and with depression-spectrum disorder and underscore the importance of accurate assessment of and early appropriate care for these adolescents. PMID:22475525

  7. Lip-Reading Aids Word Recognition Most in Moderate Noise: A Bayesian Explanation Using High-Dimensional Feature Space

    PubMed Central

    Ross, Lars A.; Foxe, John J.; Parra, Lucas C.

    2009-01-01

    Watching a speaker's facial movements can dramatically enhance our ability to comprehend words, especially in noisy environments. From a general doctrine of combining information from different sensory modalities (the principle of inverse effectiveness), one would expect that the visual signals would be most effective at the highest levels of auditory noise. In contrast, we find, in accord with a recent paper, that visual information improves performance more at intermediate levels of auditory noise than at the highest levels, and we show that a novel visual stimulus containing only temporal information does the same. We present a Bayesian model of optimal cue integration that can explain these conflicts. In this model, words are regarded as points in a multidimensional space and word recognition is a probabilistic inference process. When the dimensionality of the feature space is low, the Bayesian model predicts inverse effectiveness; when the dimensionality is high, the enhancement is maximal at intermediate auditory noise levels. When the auditory and visual stimuli differ slightly in high noise, the model makes a counterintuitive prediction: as sound quality increases, the proportion of reported words corresponding to the visual stimulus should first increase and then decrease. We confirm this prediction in a behavioral experiment. We conclude that auditory-visual speech perception obeys the same notion of optimality previously observed only for simple multisensory stimuli. PMID:19259259

  8. Design and operating features of the high-level waste vitrification system for the West Valley demonstration project

    SciTech Connect

    Siemens, D.H.; Beary, M.M.; Barnes, S.M.; Berger, D.N.; Brouns, R.A.; Chapman, C.C.; Jones, R.M.; Peters, R.D.; Peterson, M.E.

    1986-03-01

    A liquid-fed joule-heated ceramic melter system is the reference process for immobilization of the high-level liquid waste in the US and several foreign countries. This system has been under development for over ten years at Pacific Northwest Laboratory and other national laboratories operated for the US Department of Energy. Pacific Northwest Laboratory contributed to this research through its Nuclear Waste Treatment Program and used applicable data to design and test melters and related systems using remote handling of simulated radioactive wastes. This report describes the equipment designed in support of the high-level waste vitrification program at West Valley, New York. Pacific Northwest Laboratory worked closely with West Valley Nuclear Services Company to design a liquid-fed ceramic melter, a liquid waste preparation and feed tank and pump, an off-gas treatment scrubber, and an enclosed turntable for positioning the waste canisters. Details of these designs are presented including the rationale for the design features and the alternatives considered.

  9. Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness

    SciTech Connect

    Tran, Truong-An; Gillet, Ludovic; Roger, Sebastien; Besson, Pierre [Inserm, U921, 37000 Tours (France); Universite Francois-Rabelais, 37000 Tours (France); White, Edward [Institute of Membrane and Systems Biology, University of Leeds, LS2 9JT LEEDS (United Kingdom); Le Guennec, Jean-Yves [Inserm, U921, 37000 Tours (France); Universite Francois-Rabelais, 37000 Tours (France)], E-mail: Jean-Yves.LeGuennec@Univ-Tours.Fr

    2009-02-06

    Taxol is widely used in breast cancer chemotherapy. Its effects are primarily attributed to its anti-mitotic activity. Microtubule perturbators also exert antimetastatic activities which cannot be explained solely by the inhibition of proliferation. Voltage-dependent sodium channels (Na{sub V}) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting Na{sub V} activity with tetrodotoxin is responsible for an approximately 0.4-fold reduction of MDA-MB-231 cell invasiveness. In this study, we focused on the effect of a single, 2-h application of 10 nM taxol on the two cell lines MDA-MB-231 and MDA-MB-468. At this concentration, taxol had no effect on proliferation after 7 days and on migration in any cell line. However it led to a 40% reduction of transwell invasion of MDA-MB-231 cells. There was no additive effect when taxol and tetrodotoxin were simultaneously applied. Na{sub V} activity, as assessed by patch-clamp, indicates that it was changed by taxol pre-treatment. We conclude that taxol can exert anti-tumoral activities, in cells expressing Na{sub V}, at low doses that have no effect on cell proliferation. This effect might be due to a modulation of signalling pathways involving sodium channels.

  10. Revertant mosaicism in a human skin fragility disorder results from slipped mispairing and mitotic recombination.

    PubMed

    Kiritsi, Dimitra; He, Yinghong; Pasmooij, Anna M G; Onder, Meltem; Happle, Rudolf; Jonkman, Marcel F; Bruckner-Tuderman, Leena; Has, Cristina

    2012-05-01

    Spontaneous gene repair, also called revertant mosaicism, has been documented in several genetic disorders involving organs that undergo self-regeneration, including the skin. Genetic reversion may occur through different mechanisms, and in a single individual, the mutation can be repaired in various ways. Here we describe a disseminated pattern of revertant mosaicism observed in 6 patients with Kindler syndrome (KS), a genodermatosis caused by loss of kindlin-1 (encoded by FERMT1) and clinically characterized by patchy skin pigmentation and atrophy. All patients presented duplication mutations (c.456dupA and c.676dupC) in FERMT1, and slipped mispairing in direct nucleotide repeats was identified as the reversion mechanism in all investigated revertant skin spots. The sequence around the mutations demonstrated high propensity to mutations, favoring both microinsertions and microdeletions. Additionally, in some revertant patches, mitotic recombination generated areas with homozygous normal keratinocytes. Restoration of kindlin-1 expression led to clinically and structurally normal skin. Since loss of kindlin-1 severely impairs keratinocyte proliferation, we predict that revertant cells have a selective advantage that allows their clonal expansion and, consequently, the improvement of the skin condition. PMID:22466645

  11. Mitotic index and size of symbiotic algae in Caribbean Reef corals

    NASA Astrophysics Data System (ADS)

    Wilkerson, F. P.; Kobayashi, D.; Muscatine, L.

    1988-05-01

    Size and frequency of division were determined for zooxanthellae from nine scleractinian coral species collected in February, 1983 at Discovery Bay, Jamaica, from four depths over a 51 m bathymetric range. Mean diameters of zooxanthellae ranged from 6.4 to 12.6 ?m. Small zooxanthellae were found in Madracis mirabilis, Eusmilia fastigiata and Dendrogyra cylindrus whereas larger cells were seen in Agaricia agaricites, Porites astreoides, Montastrea cavernosa and Acropora cervicornis. Zooxanthellae division was not phased over a diel cycle. The percentage of zooxanthellae in a paired stage of cytokinesis (mitotic index or MI) was highly variable and ranged from 1.1% to 14.1%. Values measured in E. fastigiata and D. cylindrus were greater than in the other corals. MI was higher in branch tips of A. cervicornis than in branch bases. Daily average MI was negatively correlated with mean cell diameter and for a majority of the coral species increased with habitat depth. MI values were used to estimate specific growth rates and generation times for zooxanthellae in vivo for comparison with other dinoflagellates.

  12. The prognostic relevance of the mitotic activity index in axillary lymph node-negative breast cancer.

    PubMed

    Jobsen, Jan J; van der Palen, Job; Brinkhuis, Mariël; Nortier, Johan W R; Struikmans, Henk

    2015-01-01

    The aim of the present study is to look at the mitotic activity index (MAI) as a prognostic factor in a prospective population-based cohort of lymph node-negative invasive breast cancer patients. Analyses were based on 2,048 breast-conserving therapies in 1,971 patients, node-negative, and without any form of adjuvant systemic therapy with long-term follow-up. The 15-year distant metastases-free survival (DMFS) for women ?55 years was 88.3 % for low MAI values (?12) versus 73.4 % for high MAI values (>12); (HR 2.8; 95 % CI 1.8-4.4; p < 0.001). Multivariate analyses for DMFS showed significance for MAI. For MAI and Bloom-Richardson grading, by performing a likelihood ratio test, we showed the statistical significance for both. For women >55-years, the MAI was not an independent significant factor. We also confirmed the above findings for disease-specific survival. When multi-gene assays are not available, the MAI remains a robust prognostic marker in women younger than 55 years of age with early node-negative breast cancer. PMID:25526926

  13. Electro-acoustic behavior of the mitotic spindle: a semi-classical coarse-grained model.

    PubMed

    Havelka, Daniel; Ku?era, Ond?ej; Deriu, Marco A; Cifra, Michal

    2014-01-01

    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells--a strategy used in novel methods for cancer treatment. PMID:24497952

  14. Cyclin B1 Overexpression Induces Cell Death Independent of Mitotic Arrest

    PubMed Central

    Eichhorn, Joshua M.; Kothari, Anisha; Chambers, Timothy C.

    2014-01-01

    Microtubule inhibitors are widely used in cancer chemotherapy. These drugs characteristically induce mitotic arrest and cell death but the mechanisms linking the two are not firmly established. One of the problems is that cancer cells vary widely in their sensitivity to these agents, and thus comparison of data from different systems is difficult. To alleviate this problem we sought to molecularly induce mitotic death and study its mechanisms, by expressing non-degradable cyclin B (R42A) in HeLa cells. However, this approach failed to induce significant mitotic arrest, Cdk1 activation, or phosphorylation of anti-apoptotic Bcl-2 proteins, all characteristics of cells treated with microtubule inhibitors. Furthermore, cyclin B1-R42A induced rapid cell death, and when expressed in synchronized cells, cell death occurred in G1 phase. Decreasing the plasmid concentration reduced transfection efficiency but restored mitotic arrest and eliminated non-specific death. These results show that inappropriate overexpression of cyclin B1 causes non-specific cell death and suggest caution in its use for the study of mitotic events. PMID:25415322

  15. Electro-Acoustic Behavior of the Mitotic Spindle: A Semi-Classical Coarse-Grained Model

    PubMed Central

    Havelka, Daniel; Ku?era, Ond?ej; Deriu, Marco A.; Cifra, Michal

    2014-01-01

    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells—a strategy used in novel methods for cancer treatment. PMID:24497952

  16. Mitotic crossover - an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma

    PubMed Central

    Rovcanin, Branislav; Ivanovski, Ivan; Djuric, Olivera; Nikolic, Dimitrije; Petrovic, Jelena; Ivanovski, Petar

    2014-01-01

    Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors. PMID:25253953

  17. Cell fate after mitotic arrest in different tumor cells is determined by the balance between slippage and apoptotic threshold

    SciTech Connect

    Galán-Malo, Patricia; Vela, Laura; Gonzalo, Oscar; Calvo-Sanjuán, Rubén; Gracia-Fleta, Lucía; Naval, Javier; Marzo, Isabel, E-mail: imarzo@unizar.es

    2012-02-01

    Microtubule poisons and other anti-mitotic drugs induce tumor death but the molecular events linking mitotic arrest to cell death are still not fully understood. We have analyzed cell fate after mitotic arrest produced by the microtubule-destabilizing drug vincristine in a panel of human tumor cell lines showing different response to vincristine. In Jurkat, RPMI 8226 and HeLa cells, apoptosis was triggered shortly after vincristine-induced mitotic arrest. However, A549 cells, which express a great amount of Bcl-x{sub L} and undetectable amounts of Bak, underwent mitotic slippage prior to cell death. However, when Bcl-x{sub L} gene was silenced in A549 cells, vincristine induced apoptosis during mitotic arrest. Another different behavior was found in MiaPaca2 cells, where vincristine caused death by mitotic catastrophe that switched to apoptosis when cyclin B1 degradation was prevented by proteasome inhibition. Overexpression of Bcl-x{sub L} or silencing Bax and Bak expression delayed the onset of apoptosis in Jurkat and RPMI 8226 cells, enabling mitotic slippage and endoreduplication. In HeLa cells, overexpression of Bcl-x{sub L} switched cell death from apoptosis to mitotic catastrophe. Mcl-1 offered limited protection to vincristine-induced cell death and Mcl-1 degradation was not essential for vincristine-induced death. All these results, taken together, indicate that the Bcl-x{sub L}/Bak ratio and the ability to degrade cyclin B1 determine cell fate after mitotic arrest in the different tumor cell types. Highlights: ? Vincristine induces cell death by apoptosis or mitotic catastrophe. ? Apoptosis-proficient cells die by apoptosis during mitosis upon vincristine treatment. ? p53wt apoptosis-deficient cells undergo apoptosis from a G1-like tetraploid state. ? p53mt apoptosis-deficient cells can survive and divide giving rise to 8N cells.

  18. Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: diagnostic features in surepath™ cervical samples.

    PubMed

    Gupta, Nalini; Crossley, John; Dudding, Nick; Ellis, Kay; Smith, J H F

    2013-06-01

    This study was undertaken to identify the situations in which a diagnosis of "Atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H)" is offered in SurePath™ cervical samples and to identify cytological criteria helpful in predicting high-grade disease. 2,335 (3.4%) SurePath samples reported as atypical squamous cells (ASC) over a period of 2 years, including 1,112 cases with known hrHPV status were retrieved. 105/1,112 cases were categorized into ASC-H, and slides were available for review in 88/105 cases. These 88 samples were divided into two categories based on follow-up histological outcome and hrHPV status-category A: cases with CIN2+ lesions on follow-up (n = 48) and category B: cases with ?CIN1 lesions or hrHPV negative status (n = 40). 78% (82/105) cases of ASC-H tested positive for hrHPV. Overall CIN2+ lesions were found in 50.3% (53/105) cases. Of 88 cases reviewed, HCGs were noted in 56.3% (27/48) cases in category A and 75% (30/40) cases in category B. Dispersed metaplastic cells and scattered small atypical cells were seen in 37.5% (18/48) cases in category A and 12.5%(5/40) in category B. The majority of cases with dispersed atypical cells had <20 cells/sample and cases with HCGs had <10 HCGs per sample. The majority of the cases reported as ASC-H contained HCGs. Of these groups with nuclear crowding, disorganization and those with steep edges ("blocks") are likely to predict high-grade disease. The samples with only dispersed atypical cells had <20 cells/sample in majority of cases. In these, a disproportionate and especially high nuclear: cytoplasmic ratio and irregular chromatin were the most useful features in predicting high-grade disease. PMID:22807399

  19. Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase II?

    PubMed Central

    Vagnarelli, Paola; Ogawa, Hiromi; Vargiu, Giulia; Kelly, David A.; de Lima Alves, Flavia; Kerr, Alastair; Green, Lydia C.; Hudson, Damien F.; Ohta, Shinya; Cooke, Carol A.; Farr, Christine J.; Rappsilber, Juri

    2012-01-01

    Mitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic “X” shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, KIF4 and condensin were mutually dependent for their dynamic localization on the chromatid axes. Depletion of either caused sister chromatids to expand and compromised the “intrinsic structure” of the chromosomes (defined in an in vitro assay), with loss of condensin showing stronger effects. Simultaneous depletion of KIF4 and condensin caused complete loss of chromosome morphology. In these experiments, topoisomerase II? contributed to shaping mitotic chromosomes by promoting the shortening of the chromatid axes and apparently acting in opposition to the actions of KIF4 and condensins. These three proteins are major determinants in shaping the characteristic mitotic chromosome morphology. PMID:23166350

  20. A nontranscriptional role for Oct4 in the regulation of mitotic entry.

    PubMed

    Zhao, Rui; Deibler, Richard W; Lerou, Paul H; Ballabeni, Andrea; Heffner, Garrett C; Cahan, Patrick; Unternaehrer, Juli J; Kirschner, Marc W; Daley, George Q

    2014-11-01

    Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin-Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry. PMID:25324523

  1. EAM-based high-speed 100-km OFDM transmission featuring tolerant modulator operation enabled using SSII cancellation.

    PubMed

    Chen, Hsing-Yu; Wei, Chia-Chien; Lu, I-Cheng; Chen, Yu-Chao; Chu, Hsuan-Hao; Chen, Jyehong

    2014-06-16

    In this study, a technique was developed to compensate for nonlinear distortion through cancelling subcarrier-to-subcarrier intermixing interference (SSII) in an electroabsorption modulator (EAM)-based orthogonal frequency-division multiplexing (OFDM) transmission system. The nonlinear distortion to be compensated for is induced by both EAM nonlinearity and fiber dispersion. Because an OFDM signal features an inherently high peak-to-average power ratio, a trade-off exists between the optical modulation index (OMI) and modulator nonlinearity. Therefore, the nonlinear distortion limits the operational tolerance of the bias voltage and the driving power to a small region. After applying the proposed SSII cancellation, the OMI of an OFDM signal was increased yielding only a small increment of nonlinear distortion, and the tolerance region of the operational conditions was also increased. By employing the proposed scheme, this study successfully demonstrates 50-Gbps OFDM transmission over 100-km dispersion-uncompensated single-mode fiber based on a single 10-GHz EAM. PMID:24977559

  2. High-Resolution Imaging Reveals New Features of Nuclear Export of mRNA through the Nuclear Pore Complexes

    PubMed Central

    Kelich, Joseph M.; Yang, Weidong

    2014-01-01

    The nuclear envelope (NE) of eukaryotic cells provides a physical barrier for messenger RNA (mRNA) and the associated proteins (mRNPs) traveling from sites of transcription in the nucleus to locations of translation processing in the cytoplasm. Nuclear pore complexes (NPCs) embedded in the NE serve as a dominant gateway for nuclear export of mRNA. However, the fundamental characterization of export dynamics of mRNPs through the NPC has been hindered by several technical limits. First, the size of NPC that is barely below the diffraction limit of conventional light microscopy requires a super-resolution microscopy imaging approach. Next, the fast transit of mRNPs through the NPC further demands a high temporal resolution by the imaging approach. Finally, the inherent three-dimensional (3D) movements of mRNPs through the NPC demand the method to provide a 3D mapping of both transport kinetics and transport pathways of mRNPs. This review will highlight the recently developed super-resolution imaging techniques advanced from 1D to 3D for nuclear export of mRNPs and summarize the new features in the dynamic nuclear export process of mRNPs revealed from these technical advances. PMID:25141104

  3. A highly selective and sensitive fluorescent probe for quantitative detection of Hg(2+) based on aggregation-induced emission features.

    PubMed

    Wang, Aizhi; Yang, Yunxu; Yu, Feifei; Xue, Lingwei; Hu, Biwei; Fan, Weiping; Dong, Yajun

    2015-01-01

    A ?-conjugated cyanostilbene derivative of (Z)-2-(4-nitrophenyl)-3-(4-(vinyloxy)phenyl)acrylonitrile (CN-vinyl) had been designed, synthesized and confirmed by the standard spectroscopic analyses. CN-vinyl possesses an unusual high emissive aggregation-induced emission (AIE) feature in a tetrahydrofuran/water mixture (2:8, v/v). The fluorescence intensity of CN-vinyl can be quenched linearly with the addition of Hg(2+) in a range of 0-50 ?M with a correlation coefficient of R(2)=0.9957. The detection limit of Hg(2+) is 37 nM. The mechanism for Hg(2+)-mediated optical properties of CN-vinyl is due to the selective cleavage of vinyl group by Hg(2+). Accuracy of the proposed methodology was evaluated by means of the recovery study in real samples and the analyzing certified reference material of the standard solution of Hg(2+). By this novel strategy, CN-vinyl can be used for quantitative detection of Hg(2+) as well as the presence of other physiological relevant metal ions. PMID:25476389

  4. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    SciTech Connect

    Verbakel, Werner, E-mail: werner.verbakel@chem.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)] [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium); Carmeliet, Geert, E-mail: geert.carmeliet@med.kuleuven.be [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium)] [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium); Engelborghs, Yves, E-mail: yves.engelborghs@fys.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)] [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)

    2011-08-12

    Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction suggests additional functions for NuSAP, as recently identified for other nuclear spindle assembly factors with a role in gene expression or DNA damage response.

  5. Low specific nitrate uptake rate: A common feature of high-nutrient, low-chlorophyll marine ecosystems

    SciTech Connect

    Dugdale, R.C.; Wilkerson, F.P. (Univ. of Southern California, Los Angeles (United States))

    1991-12-01

    The authors have searched for common features of three high-nutrient, low-chlorophyll (HNLC) regions of interest - the Southern Ocean, the eastern equatorial Pacific, and Station P in the northeast Pacific. In each of these areas, the rates of specific NO{sub 3} uptake, whether normalized to particulate organic nitrogen (PON) or chlorophyll, are low compared to coastal upwelling systems with comparable nutrient concentrations. When maximum values of NO{sub 3} concentration and maximum values of PON-specific {sup 15}NO{sub 3} uptake, V{sup 15}NO{sub 3} track for the coastal systems, and a low V{sup 15}NO{sub 3} track for the three HNLC regions which have V{sup 15}NO{sub 3} values consistent with oligotrophic regions and so are functionally oligotrophic. These values of V{sup 15}NO{sub 3} are too low to allow biomass accumulation and the formation of blooms of diatoms. One possible reason for the lack of high V{sup 15}NO{sub 3} values in the HNLC regions is that seeding of the large, fast-growing, fast-sinking diatoms is inadequate and primarily due to the lack of a bottom or other recirculation system to assure a supply of these diatoms to the surface regions. Grazing control limits biomass development and may function to hold V{sup 15}NO{sub 3} to low values resulting in conditions certain to appear as HNLC. Comparison with model results suggests that deep mixed layers in the Southern Ocean and at Station P may limit V{sup 15}NO{sub 3} and that in much of the eastern equatorial Pacific NO{sub 3} concentrations are too low for VNO{sub 3} to develop to coastal upwelling values.

  6. Multiple phosphorylation events control mitotic degradation of the muscle transcription factor Myf5

    E-print Network

    Doucet, Christine; Gutierrez, Gustavo J; Lindon, Catherine; Lorca, Thierry; Lledo, Gwendaline; Pinset, Christian; Coux, Olivier

    2005-12-01

    , and is inhibited by Myf5 mitotic degradation is conserved in non-muscle cellsFigure 1 Myf5 mitotic degradation is conserved in non-muscle cells. HeLa-S3 cells expressing Myf5 under an inducible pro- motor (tetoff) were treated (lanes 2, 3, 4) or not (AS, lane 1... ) for 30 min at 30°C. 25 µg of each extract were resolved by 10% SDS-PAGE and immuno- blotted with anti-Myf5 antibodies. AS: asynchronous cells; * indicates a non specific band recognized by the antibodies that can be used as a loading control. Myf5 MG...

  7. Chromosome no. 1 of Crepis capillaris shows dened 3D-shapes in mitotic A. B. Houtsmuller1

    E-print Network

    Smeulders, Arnold

    Chromosome no. 1 of Crepis capillaris shows de®ned 3D-shapes in mitotic prophase A. B. Houtsmuller1, plant chromosome, prophase chromosome shape Abstract The shape of mitotic prophase chromosomes has been studied in root tip nuclei by confocal microscopy and 3D- image analysis. Crepis capillaris chromosome no

  8. A Temperature-Dependent Index of Mitotic Interval (?0) for Chromosome Manipulation in Paddlefish and Shovelnose Sturgeon

    Microsoft Academic Search

    William L. Shelton; Steven D. Mims; Julia A. Clark; Ana E. Hiott; Changzheng Wang

    1997-01-01

    A temperature-dependent measure of the mitotic interval (?0) can help standardize chromosome manipulation in fish eggs. A tau unit (?0) is the duration in minutes of one mitotic cycle during synchronous embryonic cleavage. It is measured over a range of temperatures, and the resulting relationship of ?0 to temperature can be used to anticipiate developmental events that are affected by

  9. Identification and partial characterization of mitotic centromere- associated kinesin, a kinesin-related protein that associates with centromeres during mitosis

    Microsoft Academic Search

    Linda Wordeman; Timothy J. Mitchison

    1995-01-01

    Using antipeptide antibodies to conserved regions of the kinesin motor domain, we cloned a kinesin-related protein that associates with the centro- mere region of mitotic chromosomes. We call the pro- tein MCAK, for mitotic centromere-associated kinesin. MCAK appears concentrated on centromeres at prophase and persists until telophase, after which time the localization disperses. It is found throughout the centromere region

  10. Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

    PubMed Central

    Bergman, Zane J.; Mclaurin, Justin D.; Eritano, Anthony S.; Johnson, Brittany M.; Sims, Amanda Q.; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope. PMID:25689737

  11. NAP1 Acts with Clb2 to Perform Mitotic Functions and to Suppress Polar Bud Growth in Budding Yeast

    E-print Network

    Murray, Andrew W.

    NAP1 Acts with Clb2 to Perform Mitotic Functions and to Suppress Polar Bud Growth in Budding Yeast, California 94143-0444 Abstract. NAP1 is a 60-kD protein that interacts spe- cificallywith mitotic cyclins in cells that lack NAP1. Our results demonstrate that Clb2 is unable to carry out its full range

  12. Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly

    PubMed Central

    Gorjánácz, Mátyás; Klerkx, Elke P F; Galy, Vincent; Santarella, Rachel; López-Iglesias, Carmen; Askjaer, Peter; Mattaj, Iain W

    2007-01-01

    Barrier-to-autointegration factor (BAF) is an essential, highly conserved, metazoan protein. BAF interacts with LEM (LAP2, emerin, MAN1) domain-carrying proteins of the inner nuclear membrane. We analyzed the in vivo function of BAF in Caenorhabditis elegans embryos using both RNA interference and a temperature-sensitive baf-1 gene mutation and found that BAF is directly involved in nuclear envelope (NE) formation. NE defects were observed independent of and before the chromatin organization phenotype previously reported in BAF-depleted worms and flies. We identified vaccinia-related kinase (VRK) as a regulator of BAF phosphorylation and localization. VRK localizes both to the NE and chromatin in a cell-cycle-dependent manner. Depletion of VRK results in several mitotic defects, including impaired NE formation and BAF delocalization. We propose that phosphorylation of BAF by VRK plays an essential regulatory role in the association of BAF with chromatin and nuclear membrane proteins during NE formation. PMID:17170708

  13. Induced rates of mitotic crossing over and possible mitotic gene conversion per wing anlage cell in Drosophila melanogaster by X rays and fission neutrons

    SciTech Connect

    Ayaki, T.; Fujikawa, K.; Ryo, H.; Itoh, T.; Kondo, S. (Nagasaki Univ. School of Medicine (Japan))

    1990-09-01

    As a model for chromosome aberrations, radiation-induced mitotic recombination of mwh and flr genes in Drosophila melanogaster strain (mwh +/+ flr) was quantitatively studied. Fission neutrons were five to six times more effective than X rays per unit dose in producing either crossover-mwh/flr twins and mwh singles-or flr singles, indicating that common processes are involved in the production of crossover and flr singles. The X-ray-induced rate/wing anlage cell/Gy for flr singles was 1 X 10(-5), whereas that of crossover was 2 x 10(-4); the former and the latter rate are of the same order of magnitude as those of gene conversion and crossover in yeast, respectively. Thus, we conclude that proximal-marker flr singles induced in the transheterozygote are gene convertants. Using the model based on yeast that recombination events result from repair of double-strand breaks or gaps, we propose that mitotic recombination in the fly is a secondary result of recombinational DNA repair. Evidence for recombinational misrepair in the fly is given. The relative ratio of radiation-induced mitotic crossover to spontaneous meiotic crossover is one order of magnitude higher in the fly than in yeast and humans.

  14. Low-temperature plasma etching of high aspect-ratio densely packed 15 to sub-10 nm silicon features derived from PS-PDMS block copolymer patterns

    NASA Astrophysics Data System (ADS)

    Liu, Zuwei; Gu, Xiaodan; Hwu, Justin; Sassolini, Simone; Olynick, Deirdre L.

    2014-07-01

    The combination of block copolymer (BCP) lithography and plasma etching offers a gateway to densely packed sub-10 nm features for advanced nanotechnology. Despite the advances in BCP lithography, plasma pattern transfer remains a major challenge. We use controlled and low substrate temperatures during plasma etching of a chromium hard mask and then the underlying substrate as a route to high aspect ratio sub-10 nm silicon features derived from BCP lithography. Siloxane masks were fabricated using poly(styrene-b-siloxane) (PS-PDMS) BCP to create either line-type masks or, with the addition of low molecular weight PS-OH homopolymer, dot-type masks. Temperature control was essential for preventing mask migration and controlling the etched feature’s shape. Vertical silicon wire features (15 nm with feature-to-feature spacing of 26 nm) were etched with aspect ratios up to 17 : 1; higher aspect ratios were limited by the collapse of nanoscale silicon structures. Sub-10 nm fin structures were etched with aspect ratios greater than 10 : 1. Transmission electron microscopy images of the wires reveal a crystalline silicon core with an amorphous surface layer, just slightly thicker than a native oxide.

  15. The Fisher-Markov selector: fast selecting maximally separable feature subset for multiclass classification with applications to high-dimensional data.

    PubMed

    Cheng, Qiang; Zhou, Hongbo; Cheng, Jie

    2011-06-01

    Selecting features for multiclass classification is a critically important task for pattern recognition and machine learning applications. Especially challenging is selecting an optimal subset of features from high-dimensional data, which typically have many more variables than observations and contain significant noise, missing components, or outliers. Existing methods either cannot handle high-dimensional data efficiently or scalably, or can only obtain local optimum instead of global optimum. Toward the selection of the globally optimal subset of features efficiently, we introduce a new selector--which we call the Fisher-Markov selector--to identify those features that are the most useful in describing essential differences among the possible groups. In particular, in this paper we present a way to represent essential discriminating characteristics together with the sparsity as an optimization objective. With properly identified measures for the sparseness and discriminativeness in possibly high-dimensional settings, we take a systematic approach for optimizing the measures to choose the best feature subset. We use Markov random field optimization techniques to solve the formulated objective functions for simultaneous feature selection. Our results are noncombinatorial, and they can achieve the exact global optimum of the objective function for some special kernels. The method is fast; in particular, it can be linear in the number of features and quadratic in the number of observations. We apply our procedure to a variety of real-world data, including mid--dimensional optical handwritten digit data set and high-dimensional microarray gene expression data sets. The effectiveness of our method is confirmed by experimental results. In pattern recognition and from a model selection viewpoint, our procedure says that it is possible to select the most discriminating subset of variables by solving a very simple unconstrained objective function which in fact can be obtained with an explicit expression. PMID:21493968

  16. Heat induction of a novel Rad9 variant from a cryptic translation initiation site reduces mitotic commitment.

    PubMed

    Janes, Simon; Schmidt, Ulrike; Ashour Garrido, Karim; Ney, Nadja; Concilio, Susanna; Zekri, Mohamed; Caspari, Thomas

    2012-10-01

    Exposure of human cells to heat switches the activating signal of the DNA damage checkpoint from genotoxic to temperature stress. This change reduces mitotic commitment at the expense of DNA break repair. The thermal alterations behind this switch remain elusive despite the successful use of heat to sensitise cancer cells to DNA breaks. Rad9 is a highly conserved subunit of the Rad9-Rad1-Hus1 (9-1-1) checkpoint-clamp that is loaded by Rad17 onto damaged chromatin. At the DNA, Rad9 activates the checkpoint kinases Rad3(ATR) and Chk1 to arrest cells in G2. Using Schizosaccharomyces pombe as a model eukaryote, we discovered a new variant of Rad9, Rad9-M50, whose expression is specifically induced by heat. High temperatures promote alternative translation from a cryptic initiation codon at methionine-50. This process is restricted to cycling cells and is independent of the temperature-sensing mitogen-activated protein kinase (MAPK) pathway. While full-length Rad9 delays mitosis in the presence of DNA lesions, Rad9-M50 functions in a remodelled checkpoint pathway to reduce mitotic commitment at elevated temperatures. This remodelled pathway still relies on Rad1 and Hus1, but acts independently of Rad17. Heat-induction of Rad9-M50 ensures that the kinase Chk1 remains in a hypo-phosphorylated state. Elevated temperatures specifically reverse the DNA-damage-induced modification of Chk1 in a manner dependent on Rad9-M50. Taken together, heat reprogrammes the DNA damage checkpoint at the level of Chk1 by inducing a Rad9 variant that can act outside of the canonical 9-1-1 complex. PMID:22797921

  17. P2P-R protein localizes to the nucleolus of interphase cells and the periphery of chromosomes in mitotic cells which show maximum P2P-R immunoreactivity.

    PubMed

    Gao, Sizhi; Witte, Michael M; Scott, Robert E

    2002-05-01

    P2P-R is a nuclear protein that can bind both p53 and Rb1. Its functions include roles in the control of RNA metabolism, apoptosis, and p53-dependent transcription. The expression of P2P-R also is repressed in G1 arrested terminally differentiated cells. The current studies therefore evaluated if P2P-R undergoes cell cycle-associated changes in its abundance and/or localization. Western blots show that relative to G0 quiescent cells, P2P-R protein levels are higher in populations of G2/M cells prepared by the physiological parasynchronization technique of serum deprivation followed by serum stimulation. More striking is the > 10-fold enrichment of P2P-R protein in specimens of highly purified mitotic cells prepared by the mitotic shake-select technique, or by synchrony with the mitotic spindle disruption agents nocodazole or vinblastine. These changes in P2P-R protein occur without a concomitant change in P2P-R mRNA expression suggesting that P2P-R immunoreactivity increases during mitosis. Confocal microscopy next established the localization of P2P-R to nucleoli in interphase cells and at the periphery of chromosomes in mitotic cells that lack nucleoli. The high levels of P2P-R localized to the periphery of chromosomes in mitotic cells suggest that P2P-R shares characteristics with other nucleolar proteins that associate with the periphery of chromosomes during mitosis. These include: nucleolin, B23, Ki67, and fibrillarin. PMID:12064457

  18. [Features of chronic pulmonary diseases in workers engaged in the production of high aluminum mullite refractory items].

    PubMed

    Fishman, B B

    2003-01-01

    The article represents features for differential diagnosis between pulmonary tuberculosis and dust diseases in workers engaged into mullite refractories production. The author suggests possible course of the disease as a new type of chronic pulmonary malady--mullitosis. PMID:12958876

  19. Measurement of post-eruptive volcanic deformation and depositional features using high-resolution remote sensing data

    NASA Astrophysics Data System (ADS)

    McAlpin, D. B.; Meyer, F. J.

    2011-12-01

    This proposal examines changes in volcanic geomorphology and topography using a new, multi-sensor approach to produce high-resolution digital elevation models (DEMs) and surface deformation maps that measure post-eruption volcanic changes and depositional features, including lava domes, lahars, and pyroclastic flow deposits. The advantage of this new approach is to exploit available data sets that have not previously been used systematically, or in full coordination. The use of readily available spaceborne remote sensing data is therefore maximized in a manner that is routine in method, but of sufficient quality to answer many important geophysical questions. Finally, this method provides these benefits while reducing expensive and potentially hazardous field campaigns. The multi-sensor approach involves a mix of stereoscopic optical, interferometric radar, and thermal space borne images to generate high-resolution DEMs and multi-sensor analyses of volcanic domes, as well as lower resolution analyses of deposits from other volcanic activity. The terrain of volcanic areas is subject to rapid topographic change. The time and elevation information obtained from DEMs of these areas enable us to perform accurate topographic phase correction of interferograms derived from interferometric synthetic aperture radar (InSAR) imaging and therefore facilitates the use of InSAR data for monitoring centimeter scale surface motion. It also allows us to determine quantitative volume estimates of dynamically emplaced deposits from lahars, tsunamis, and mud flows, and it provides information for emergency planners to use in risk assessments facing communities in volcanically active areas. A principal test scenario for our method is Redoubt Volcano in South-Central Alaska. During March and April, 2009, Redoubt erupted in a series of explosive eruptions that melted the Drift Glacier on its North flank, and produced lahars that inundated the adjacent Drift River Valley. Quantitative volume estimates of Redoubt's dome, as well as the lahars created by its eruption have important implications for coastal areas, commercial facilities, and populations that face volcanic geohazards. We demonstrate that the selected remote sensing data sets, if applied in full coordination, are able to produce valuable information pertaining to catastrophic coastal events of vital interest to coastal population centers. Moreover, we show that the multi-sensor approach enabled volume estimates of Redoubt's dome, revealed detailed scour patterns on the Drift River glacier, and produced accurate information on the extent of lahar inundation, as well as on post-eruptive surface deformation.

  20. Bayesian analysis of X-ray jet features of the high redshift quasar jets observed with Chandra

    NASA Astrophysics Data System (ADS)

    McKeough, Kathryn; Siemiginowska, Aneta; Kashyap, Vinay; Stein, Nathan; Cheung, Chi C.

    2015-01-01

    X-ray emission of powerful quasar jets may be a result of the inverse Compton (IC) process in which the Cosmic Microwave Background (CMB) photons gain energy by interactions with the jet's relativistic electrons. However, there is no definite evidence that IC/CMB process is responsible for the observed X-ray emission of large scale jets. A step toward understanding the X-ray emission process is to study the Radio and X-ray morphologies of the jet. Results from Chandra X-ray and multi-frequency VLA imaging observations of a sample of 11 high- redshift (z > 2) quasars with kilo-parsec scale radio jets are reported. The sample consists of a set of four z ? 3.6 flat-spectrum radio quasars, and seven intermediate redshift (z = 2.1 - 2.9) quasars comprised of four sources with integrated steep radio spectra and three with flat radio spectra.We implement a Bayesian image analysis program, Low-count Image Reconstruction and Analysis (LIRA) , to analyze jet features in the X-ray images of the high redshift quasars. Out of the 36 regions where knots are visible in the radio jets, nine showed detectable X-ray emission. Significant detections are based on the upper bound p-value test based on LIRA simulations. The X-ray and radio properties of this sample combined are examined and compared to lower-redshift samples.This work is supported in part by the National Science Foundation REU and the Department of Defense ASSURE programs under NSF Grant no.1262851 and by the Smithsonian Institution, and by NASA Contract NAS8-39073 to the Chandra X-ray Center (CXC). This research has made use of data obtained from the Chandra Data Archive and Chandra Source Catalog, and software provided by the CXC in the application packages CIAO, ChIPS, and Sherpa. Work is also supported by the Chandra grant GO4-15099X.

  1. Application of a Temperature-Dependent Mitotic Interval (?o) for Induction of Diploid Meiotic Gynogenetic Paddlefish

    Microsoft Academic Search

    Steven D. Mims; William L. Shelton; Otomar Linhart; Changzheng Wang; Boris Gomelsky; Richard J. Onders

    2005-01-01

    We tested the application of mitotic interval (tau [?o]) unit in comparison with absolute time to help standardize preshock timing for a consistent production of diploid meiotic gynogenetic paddlefish Polyodon spathula. The diploid gynogenetic larvae were produced by applying heat shock (35°C; 2 min) at different times after activation of paddlefish eggs with irradiated sperm of shovelnose sturgeon Scaphirhynchus platorynchus

  2. Formation in vitro of Sperm Pronuclei and Mitotic Chromosomes Induced by Amphibian Ooplasmic Components

    Microsoft Academic Search

    Manfred J. Lohka; Yoshio Masui

    1983-01-01

    A cell-free preparation of the cytoplasm from activated eggs of Rana pipiens induces, in demembranated sperm nuclei of Xenopus laevis, formation of a nuclear envelope, chromatin decondensation, initiation of DNA synthesis, and chromosome condensation. Both soluble and particulate cytoplasmic constituents are required to initiate these processes in vitro. The observed changes resemble processes occurring during fertilization and the mitotic cycle

  3. Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells

    PubMed Central

    Leontieva, Olga V.; Lenzo, Felicia; Demidenko, Zoya N.; Blagosklonny, Mikhail V.

    2012-01-01

    When the cell cycle is arrested, even though growth-promoting pathways such as mTOR are still active, then cells senesce. For example, induction of either p21 or p16 arrests the cell cycle without inhibiting mTOR, which, in turn, converts p21/p16-induced arrest into senescence (geroconversion). Here we show that geroconversion is accompanied by dramatic accumulation of cyclin D1 followed by cyclin E and replicative stress. When p21 was switched off, senescent cells (despite their loss of proliferative potential) progressed through S phase, and levels of cyclins D1 and E dropped. Most cells entered mitosis and then died, either during mitotic arrest or after mitotic slippage, or underwent endoreduplication. Next, we investigated whether inhibition of mTOR would prevent accumulation of cyclins and loss of mitotic competence in p21-arrested cells. Both nutlin-3, which inhibits mTOR in these cells, and rapamycin suppressed geroconversion during p21-induced arrest, decelerated accumulation of cyclins D1 and E and decreased replicative stress. When p21 was switched off, cells successfully progressed through both S phase and mitosis. Also, senescent mouse embryonic fibroblasts (MEFs) overexpressed cyclin D1. After release from cell cycle arrest, senescent MEFs entered S phase but could not undergo mitosis and did not proliferate. We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence. PMID:23187803

  4. Regulation of Mitotic Cytoskeleton Dynamics and Cytokinesis by Integrin-Linked Kinase in Retinoblastoma Cells

    PubMed Central

    Sharma, Manju; Assi, Kiran; Salh, Baljinder; Cox, Michael E.; Mills, Julia

    2014-01-01

    During cell division integrin-linked kinase (ILK) has been shown to regulate microtubule dynamics and centrosome clustering, processes involved in cell cycle progression, and malignant transformation. In this study, we examine the effects of downregulating ILK on mitotic function in human retinoblastoma cell lines. These retinal cancer cells, caused by the loss of function of two gene alleles (Rb1) that encode the retinoblastoma tumour suppressor, have elevated expression of ILK. Here we show that inhibition of ILK activity results in a concentration-dependent increase in nuclear area and multinucleated cells. Moreover, inhibition of ILK activity and expression increased the accumulation of multinucleated cells over time. In these cells, aberrant cytokinesis and karyokinesis correlate with altered mitotic spindle organization, decreased levels of cortical F-actin and centrosome de-clustering. Centrosome de-clustering, induced by ILK siRNA, was rescued in FLAG-ILK expressing Y79 cells as compared to those expressing FLAG-tag alone. Inhibition of ILK increased the proportion of cells exhibiting mitotic spindles and caused a significant G2/M arrest as early as 24 hours after exposure to QLT-0267. Live cell analysis indicate ILK downregulation causes an increase in multipolar anaphases and failed cytokinesis (bipolar and multipolar) of viable cells. These studies extend those indicating a critical function for ILK in mitotic cytoskeletal organization and describe a novel role for ILK in cytokinesis of Rb deficient cells. PMID:24911651

  5. Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling

    PubMed Central

    Han, Joo Seok; Vitre, Benjamin; Fachinetti, Daniele; Cleveland, Don W.

    2014-01-01

    The mitotic checkpoint (also known as the spindle assembly checkpoint) prevents premature anaphase onset through generation of an inhibitor of the E3 ubiquitin ligase APC/C, whose ubiquitination of cyclin B and securin targets them for degradation. Combining in vitro reconstitution and cell-based assays, we now identify dual mechanisms through which Bub3 promotes mitotic checkpoint signaling. Bub3 enhances signaling at unattached kinetochores not only by facilitating binding of BubR1 but also by enhancing Cdc20 recruitment to kinetochores mediated by BubR1’s internal Cdc20 binding site. Downstream of kinetochore-produced complexes, Bub3 promotes binding of BubR1’s conserved, amino terminal Cdc20 binding domain to a site in Cdc20 that becomes exposed by initial Mad2 binding. This latter Bub3-stimulated event generates the final mitotic checkpoint complex of Bub3–BubR1–Cdc20 that selectively inhibits ubiquitination of securin and cyclin B by APC/CCdc20. Thus, Bub3 promotes two distinct BubR1-Cdc20 interactions, involving each of the two Cdc20 binding sites of BubR1 and acting at unattached kinetochores or cytoplasmically, respectively, to facilitate production of the mitotic checkpoint inhibitor. PMID:25246557

  6. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression

    SciTech Connect

    Takahashi, Akinori [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Kikuguchi, Chisato [Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan)] [Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan); Morita, Masahiro; Shimodaira, Tetsuhiro; Tokai-Nishizumi, Noriko; Yokoyama, Kazumasa; Ohsugi, Miho; Suzuki, Toru [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan) [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer CNOT3 depletion increases the mitotic index. Black-Right-Pointing-Pointer CNOT3 inhibits the expression of MAD1. Black-Right-Pointing-Pointer CNOT3 destabilizes the MAD1 mRNA. Black-Right-Pointing-Pointer MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- Abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4-NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4-NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4-NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4-NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.

  7. MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression

    PubMed Central

    Zhu, Mei; Settele, Florian; Kotak, Sachin; Sanchez-Pulido, Luis; Ehret, Lena; Ponting, Chris P.; Gönczy, Pierre

    2013-01-01

    Precise positioning of the mitotic spindle determines the correct cell division axis and is crucial for organism development. Spindle positioning is mediated through a cortical machinery by capturing astral microtubules, thereby generating pushing/pulling forces at the cell cortex. However, the molecular link between these two structures remains elusive. Here we describe a previously uncharacterized protein, MISP (C19orf21), as a substrate of Plk1 that is required for correct mitotic spindle positioning. MISP is an actin-associated protein throughout the cell cycle. MISP depletion led to an impaired metaphase-to-anaphase transition, which depended on phosphorylation by Plk1. Loss of MISP induced mitotic defects including spindle misorientation accompanied by shortened astral microtubules. Furthermore, we find that MISP formed a complex with and regulated the cortical distribution of the +TIP binding protein p150glued, a subunit of the dynein–dynactin complex. We propose that Plk1 phosphorylates MISP, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. PMID:23509069

  8. Mitotic stability of small supernumerary marker chromosomes: a study based on 93 immortalized cell lines.

    PubMed

    Spittel, Hannes; Kubek, Florian; Kreskowski, Katharina; Ziegler, Monika; Klein, Elisabeth; Hamid, Ahmed B; Kosyakova, Nadezda; Radhakrishnan, Gopakumar; Junge, Annelore; Kozlowski, Peter; Schulze, Berndt; Martin, Thomas; Huhle, Dagmar; Mehnert, Karl; Rodríguez, Laura; Ergun, Mehmet A; Sarri, Catherine; Militaru, Mariela; Stipoljev, Fedora; Tittelbach, Hanne; Vasheghani, Faezeh; de Bello Cioffi, Marcelo; Hussein, Shaymaa S; Fan, Xiaobo; Volleth, Marianne; Liehr, Thomas

    2014-01-01

    Small supernumerary marker chromosomes (sSMC) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. However, no detailed studies have been done for the mitotic stability of sSMC so far, mainly due to the lack of a corresponding in vitro model system. Recently, we established an sSMC-cell bank (Else Kröner-Fresenius-sSMC-cellbank) with >150 cell lines. Therefore, 93 selected sSMC cases were studied here for the presence of the corresponding marker chromosomes before and after Epstein-Barr virus-induced immortalization. The obtained results showed that dicentric inverted duplicated-shaped sSMC are by far more stable in vitro than monocentric centric minute- or ring-shaped sSMC. Simultaneously, a review of the literature revealed that a comparable shape-dependent mitotic stability can be found in vivo in sSMC carriers. Additionally, a possible impact of the age of the sSMC carrier on mitotic stability was found: sSMC cell lines established from patients between 10-20 years of age were predominantly mitotically unstable. The latter finding was independent of the sSMC shape. The present study shows that in vitro models can lead to new and exciting insights into the biology of this genetically and clinically heterogeneous patient group. PMID:24714101

  9. Effects of ovariectomy on estrogen uptake capacity, mitotic index and morphology of immunocytochemically-identified gonadotropes

    SciTech Connect

    Smith, P.F.

    1985-01-01

    The primary objective of these studies was to examine the effects of ovariectomy on the pituitary gonadotrope population in the rat. Several parameters were examined including morphology, mitotic index and ability of individual cells to concentrate estrogen. Adult, female rats which had been ovariectomized 3, 14, or 50 previously, were injected with /sup 3/H-estradiol (i.v.) and killed 1 hour later. Pituitaries were excised and immediately hemisected (mid-sagittal cut). Trunk blood was collected for subsequent radioimmunoassay of serum LH levels to assess the activity of the pituitary gonadotropes. Frozen pituitaries were sectioned and processed for dry-mount autoradiography. Estrogen uptake capacity of gonadotropes increased with time after ovariectomy. This increase was not seen in male rats after castration. Hemi-pituitaries were sectioned (1 ..mu..m) and analyzed for the number of mitotic figures per mm/sup 2/ and dividing cells were characterized as to their hormonal content. Ovariectomy induced an increase in the mitotic index of the pituitary gland. Furthermore, a majority of the mitotic futures seen in the ovariectomized rat were found in cells containing LH-immunoreactivity. Electron microscopic examination of dividing gonadotropes revealed that these cells contained large amounts of vesiculated endoplasmic reticumum typical of post-castration gonadotropes.

  10. Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.

    PubMed

    Álvarez-Fernández, Mónica; Sánchez-Martínez, Ruth; Sanz-Castillo, Belén; Gan, Pei Pei; Sanz-Flores, María; Trakala, Marianna; Ruiz-Torres, Miguel; Lorca, Thierry; Castro, Anna; Malumbres, Marcos

    2013-10-22

    Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B-Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB. PMID:24101512

  11. Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals

    PubMed Central

    Álvarez-Fernández, Mónica; Sánchez-Martínez, Ruth; Sanz-Castillo, Belén; Gan, Pei Pei; Sanz-Flores, María; Trakala, Marianna; Ruiz-Torres, Miguel; Lorca, Thierry; Castro, Anna; Malumbres, Marcos

    2013-01-01

    Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B–Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB. PMID:24101512

  12. Interaction between Poly(ADP-ribose) and NuMA Contributes to Mitotic Spindle Pole Assembly

    E-print Network

    Coughlin, M.

    Poly(ADP-ribose) (pADPr), made by PARP-5a/tankyrase-1, localizes to the poles of mitotic spindles and is required for bipolar spindle assembly, but its molecular function in the spindle is poorly understood. To investigate ...

  13. Proteomic Analysis of Mitotic RNA Polymerase II Reveals Novel Interactors and Association

    E-print Network

    Babu, M. Madan

    Proteomic Analysis of Mitotic RNA Polymerase II Reveals Novel Interactors and Association-coding genes in eukaryotes and interacts with factors involved in chromatin remodeling, transcriptional and in interphase nuclei. Functional assays of transcriptional activity were performed after siRNA-mediated knock

  14. Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion

    SciTech Connect

    Totsukawa, Go; Matsuo, Ayaka; Kubota, Ayano; Taguchi, Yuya; Kondo, Hisao, E-mail: hk228@med.kyushu-u.ac.jp

    2013-04-05

    Highlights: •VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2. •Phosphorylated VCIP135 does not bind to p97ATPase. •The phosphorylation of VCIP135 inhibits p97ATPase-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.

  15. Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA).

    PubMed

    Seo, Jae Sung; Kim, Ha Na; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Ki Sa; Yoon, Hyun-Joo; Yoo, Hae Yong; Choi, Cheol Yong

    2014-01-01

    Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis. PMID:24309115

  16. RanGTP and CLASP1 cooperate to position the mitotic spindle.

    PubMed

    Bird, Stephen L; Heald, Rebecca; Weis, Karsten

    2013-08-01

    Accurate positioning of the mitotic spindle is critical to ensure proper distribution of chromosomes during cell division. The small GTPase Ran, which regulates a variety of processes throughout the cell cycle, including interphase nucleocytoplasmic transport and mitotic spindle assembly, was recently shown to also control spindle alignment. Ran is required for the correct cortical localization of LGN and nuclear-mitotic apparatus protein (NuMA), proteins that generate pulling forces on astral microtubules (MTs) through cytoplasmic dynein. Here we use importazole, a small-molecule inhibitor of RanGTP/importin-? function, to study the role of Ran in spindle positioning in human cells. We find that importazole treatment results in defects in astral MT dynamics, as well as in mislocalization of LGN and NuMA, leading to misoriented spindles. Of interest, importazole-induced spindle-centering defects can be rescued by nocodazole treatment, which depolymerizes astral MTs, or by overexpression of CLASP1, which does not restore proper LGN and NuMA localization but stabilizes astral MT interactions with the cortex. Together our data suggest a model for mitotic spindle positioning in which RanGTP and CLASP1 cooperate to align the spindle along the long axis of the dividing cell. PMID:23783028

  17. Dynamic Phosphorylation of HP1? Regulates Mitotic Progression in Human Cells

    PubMed Central

    Chakraborty, Arindam; Prasanth, Kannanganattu V.; Prasanth, Supriya G.

    2014-01-01

    Heterochromatin protein 1? (HP1?), a key player in the establishment and maintenance of higher-order chromatin regulates key cellular processes, including metaphase chromatid cohesion and centromere organization. However, how HP1? controls these processes is not well understood. Here we demonstrate that post-translational modifications of HP1? dictate its mitotic functions. HP1? is constitutively phosphorylated within its N-terminus whereas phosphorylation within the hinge domain occurs preferentially at G2/M phase of the cell cycle. The hinge-phosphorylated form of HP1? specifically localizes to kinetochores during early mitosis and this phosphorylation mediated by NDR1 kinase is required for mitotic progression and for Sgo1 binding to mitotic centromeres. Cells lacking NDR kinase show loss of mitosis-specific phosphorylation of HP1? leading to prometaphase arrest. Our results reveal that NDR kinase catalyzes the hinge-specific phosphorylation of human HP1? during G2/M in vivo and this orchestrates accurate chromosome alignment and mitotic progression. PMID:24619172

  18. Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase , Satoru Inaba1

    E-print Network

    Fang, Guowei

    Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1 Anu Gupta1 University, Stanford, CA 94305, USA The abnormal expression of breast cancer-specific gene 1 (BCSG1 that BCSG1 expression significantly stimulates proliferation, invasion, and metastasis of breast cancer

  19. WT1 Interacts with MAD2 and Regulates Mitotic Checkpoint Function

    PubMed Central

    Shandilya, Jayasha; Toska, Eneda; Richard, Derek J; Medler, Kathryn F; Roberts, Stefan GE

    2014-01-01

    SUMMARY Tumor suppressors safeguard the fidelity of the mitotic checkpoint by transcriptional regulation of genes that encode components of the mitotic checkpoint complex (MCC). Here we report a new role for the tumor suppressor and transcription factor, WT1, in the mitotic checkpoint. We show that WT1 regulates the MCC by directly interacting with the spindle assembly checkpoint protein, MAD2. WT1 colocalizes with MAD2 during mitosis and preferentially binds to the functionally active, closed-conformer, C-MAD2. Furthermore, WT1 associates with the MCC containing MAD2, BUBR1 and CDC20, resulting in prolonged inhibition of the anaphase promoting complex/cyclosome (APC/C), and delayed degradation of its substrates SECURIN and CYCLIN B1. Strikingly, RNAi-mediated depletion of WT1 leads to enhanced turnover of SECURIN, decreased lag time to anaphase, and defects in chromosome-segregation. Our findings identify WT1 as a regulator of the mitotic checkpoint and chromosomal stability. PMID:25232865

  20. Human Homolog of Fission Yeast cdc25 Mitotic Inducer is Predominantly Expressed in G_2

    Microsoft Academic Search

    Krishna Sadhu; Steven I. Reed; Helena Richardson; Paul Russell

    1990-01-01

    Entry into mitosis during the somatic cell cycle is regulated in response to signals that monitor the completion of DNA replication, the integrity of the nuclear genome, and, possibly, the increase in cellular mass during the cell cycle. It has been postulated that the operation of this cell cycle control involves the gradual accumulation of rate-limiting mitotic inducers, which trigger

  1. Supplementary Information for: Individual dimers of the mitotic kinesin motor Eg5 step

    E-print Network

    Block, Steven

    1 Supplementary Information for: Individual dimers of the mitotic kinesin motor Eg5 step profiles for Eg5 motors purified from E. coli. (a) Elution profiles monitoring intrinsic fluorescence vs or multiple step sizes, which can be generated when beads carry multiple motors. © 2006 Nature Publishing

  2. Computer simulations predict that chromosome movements and rotations accelerate mitotic spindle

    E-print Network

    Mogilner, Alex

    Computer simulations predict that chromosome movements and rotations accelerate mitotic spindle in space until chromosomes are captured, and a chromosomal pathway, in which microtubules grow from chromosomes and focus to the spindle poles. Quantitative mechanistic understanding of how spindle assembly can

  3. Separation of Linked Markers in Chinese Hamster Cell Hybrids: Mitotic Recombination Is Not Involved

    PubMed Central

    Rosenstraus, Maurice J.; Chasin, Lawrence A.

    1978-01-01

    A search for mitotic recombination was carried out using mutant subclones of cultured Chinese hamster ovary cells. Recombination events were sought between the linked loci specifying the enzymes hypoxanthine phosphoribosyl transferase and glucose-6-phosphate dehydrogenase. It was shown by fluctuation analysis that markers at these two loci co-segregate from doubly heterozygous pseudotetraploid hybrid cells more than 90% of the time. The minority class of segregants, which had lost one marker without losing the other, were genetically analyzed to distinguish between the possibilities of mitotic recombination and deletion of chromosomal material. Nine clones in which a linkage disruption had occured were studied, using further cell hybridization and segregation. In three cases, a recessive lethal loss of genetic information was indicated, suggesting the deletion mechanism. In six cases, it was demonstrated that no new linkage relationships had been established concomitant with linkage disruption. Thus, in all nine clones, the evidence indicated that mitotic recombination was not involved in the events that disrupted linkage between these two loci. If mitotic recombination takes place at all in this system, the rate must be less than about 10-6 per cell per generation. PMID:744475

  4. ADVERTISING FEATURE APPLICATION NOTES

    E-print Network

    Cai, Long

    ADVERTISING FEATURE APPLICATION NOTES NATURE METHODS MPep MALDI Chips for high-sensitivity and high- tion strategies. Matrix spots are located on an ultraphobic surface The surface surrounding the matrix

  5. A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission.

    PubMed Central

    Smith, M M; Yang, P; Santisteban, M S; Boone, P W; Goldstein, A T; Megee, P C

    1996-01-01

    The histone proteins are essential for the assembly and function of th e eukaryotic chromosome. Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The mutant requires two amino acid substitutions in histone H4: a lethal Thr-to-Ile change at position 82, which lies within one of the DNA-binding surfaces of the protein, and a substitution of Ala to Val at position 89 that is an intragenic suppressor. Genetic and biochemical evidence shows that the mutant histone H4 is temperature sensitive for function but not for synthesis, deposition, or stability. The chromatin structure of 2 micrometer circle minichromosomes is temperature sensitive in vivo, consistent with a defect in H4-DNA interactions. The mutant also has defects in transcription, displaying weak Spt- phenotypes. At the restrictive temperature, mutant cells arrest in the cell cycle at nuclear division, with a large bud, a single nucleus with 2C DNA content, and a short bipolar spindle. At semipermissive temperatures, the frequency of chromosome loss is elevated 60-fold in the mutant while DNA recombination frequencies are unaffected. High-copy CSE4, encoding an H3 variant related to the mammalian CENP-A kinetochore antigen, was found to suppress the temperature sensitivity of the mutant without suppressing the Spt- transcription defect. These genetic, biochemical, and phenotypic results indicate that this novel histone H4 mutant defines one or more chromatin-dependent steps in chromosome segregation. PMID:8622646

  6. Cutting edge: Chk1 directs senescence and mitotic catastrophe in recovery from G2 checkpoint arrest

    PubMed Central

    Poehlmann, Angela; Habold, Caroline; Walluscheck, Diana; Reissig, Kathrin; Bajbouj, Khuloud; Ullrich, Oliver; Hartig, Roland; Gali-Muhtasib, Hala; Diestel, Antje; Roessner, Albert; Schneider-Stock, Regine

    2011-01-01

    Abstract Besides the well-understood DNA damage response via establishment of G2 checkpoint arrest, novel studies focus on the recovery from arrest by checkpoint override to monitor cell cycle re-entry. The aim of this study was to investigate the role of Chk1 in the recovery from G2 checkpoint arrest in HCT116 (human colorectal cancer) wt, p53–/– and p21–/– cell lines following H2O2 treatment. Firstly, DNA damage caused G2 checkpoint activation via Chk1. Secondly, overriding G2 checkpoint led to (i) mitotic slippage, cell cycle re-entry in G1 and subsequent G1 arrest associated with senescence or (ii) premature mitotic entry in the absence of p53/p21WAF1 causing mitotic catastrophe. We revealed subtle differences in the initial Chk1-involved G2 arrest with respect to p53/p21WAF1: absence of either protein led to late G2 arrest instead of the classic G2 arrest during checkpoint initiation, and this impacted the release back into the cell cycle. Thus, G2 arrest correlated with downstream senescence, but late G2 arrest led to mitotic catastrophe, although both cell cycle re-entries were linked to upstream Chk1 signalling. Chk1 knockdown deciphered that Chk1 defines long-term DNA damage responses causing cell cycle re-entry. We propose that recovery from oxidative DNA damage-induced G2 arrest requires Chk1. It works as cutting edge and navigates cells to senescence or mitotic catastrophe. The decision, however, seems to depend on p53/p21WAF1. The general relevance of Chk1 as an important determinant of recovery from G2 checkpoint arrest was verified in HT29 colorectal cancer cells. PMID:20716119

  7. Functional Characterization of G12, a Gene Required for Mitotic Progression during Gastrulation in Zebrafish

    NASA Technical Reports Server (NTRS)

    Reinsch, Sigrid; Conway, Gregory; Dalton, Bonnie P. (Technical Monitor)

    2002-01-01

    In a differential RNA display screen we have isolated a zebrafish gene, G12, for which homologs can only be found in DNA databases for vertebrates, but not invertebrates. This suggests that this is a gene required specifically in vertebrates. G12 expression is upregulated at mid-blastula transition (MBT). Morpholino inactivation of this gene by injection into 1-cell embryos results in mitotic defects and apoptosis shortly after MBT. Nuclei in morpholino treated embryos also display segregation defects. We have characterized the localization of this gene as a GFP fusion in live and fixed embryos. Overexpression of G12-GFP is non-toxic. Animals retain GFP expression for at least 7 days with no developmental defects, Interestingly in these animals G12-GFP is never detectable in blood cells though blood is present. In the deep cells of early embryos, G 12GFP is localized to nuclei and cytoskeletal elements in interphase and to the centrosome and spindle apparatus during mitosis. In the EVL, G12-GFP shows additional localization to the cell periphery, especially in mitosis. In the yolk syncytium, G12-GFP again localizes to nuclei and strongly to cytoplasmic microtubules of migrating nuclei at the YSL margin. Morpholinc, injection specifically into the YSL after cellularization blocks epiboly and nuclei of the YSL show mitotic defects while deep cells show no mitotic defects and continue to divide. Rescue experiments in which morpholino and G12-GFP RNA are co-injected indicate partial rescue by the G12-GFP. The rescue is cell autonomous; that is, regions of the embryo with higher G12-GFP expression show fewer mitotic defects. Spot 14, the human bomolog of G12, has been shown to be amplified in aggressive breast tumors. This finding, along with our functional and morphological data suggest that G12 and spot 14 are vertebrate-specific and may function either as mitotic checkpoints or as structural components of the spindle apparatus.

  8. Cyclin B3 Is a Mitotic Cyclin that Promotes the Metaphase-Anaphase Transition.

    PubMed

    Yuan, Kai; O'Farrell, Patrick H

    2015-03-16

    The timing mechanism for mitotic progression is still poorly understood. The spindle assembly checkpoint (SAC), whose reversal upon chromosome alignment is thought to time anaphase [1-3], is functional during the rapid mitotic cycles of the Drosophila embryo; but its genetic inactivation had no consequence on the timing of the early mitoses. Mitotic cyclins-Cyclin A, Cyclin B, and Cyclin B3-influence mitotic progression and are degraded in a stereotyped sequence [4-11]. RNAi knockdown of Cyclins A and B resulted in a Cyclin B3-only mitosis in which anaphase initiated prior to chromosome alignment. Furthermore, in such a Cyclin B3-only mitosis, colchicine-induced SAC activation failed to block Cyclin B3 destruction, chromosome decondensation, or nuclear membrane re-assembly. Injection of Cyclin B proteins restored the ability of SAC to prevent Cyclin B3 destruction. Thus, SAC function depends on particular cyclin types. Changing Cyclin B3 levels showed that it accelerated progress to anaphase, even in the absence of SAC function. The impact of Cyclin B3 on anaphase initiation appeared to decline with developmental progress. Our results show that different cyclin types affect anaphase timing differently in the early embryonic divisions. The early-destroyed cyclins-Cyclins A and B-restrain anaphase-promoting complex/cyclosome (APC/C) function, whereas the late-destroyed cyclin, Cyclin B3, stimulates function. We propose that the destruction schedule of cyclin types guides mitotic exit by affecting both Cdk1 and APC/C, whose activities change as each cyclin type is lost. PMID:25754637

  9. Some features on hot forging of powder metallurgy sintered high strength 4%titanium carbide composite steel preforms under different stress state conditions

    Microsoft Academic Search

    R. Narayanasamy; V. Senthilkumar; K. S. Pandey

    2008-01-01

    In this paper, the authors propose mathematical expressions for the determination of different stress ratio parameters under plane and triaxial stress state conditions. Experiments were carried out to evaluate the hot forging features in the high strength sintered powder metallurgy 4%titanium carbide composite steel performs under different stress states, namely, plane stress and triaxial stress states. Cylindrical compacts with aspect

  10. High performance of gas identification by wavelet transform-based fast feature extraction from temperature modulated semiconductor gas sensors

    Microsoft Academic Search

    Hui Ding; Haifeng Ge; Junhua Liu

    2005-01-01

    Temperature modulation of semiconductor gas sensors is a powerful strategy to improve selectivity and stability of gas sensors in applications of identifying different gases. This paper presents a new strategy to extract features from the response of a thermally modulated semiconductor sensor for gas identification. This strategy contains two main steps. First, make the sensor work under temperature modulation and

  11. Loop L5 Assumes Three Distinct Orientations during the ATPase Cycle of the Mitotic Kinesin Eg5

    PubMed Central

    Muretta, Joseph M.; Behnke-Parks, William M.; Major, Jennifer; Petersen, Karl J.; Goulet, Adeline; Moores, Carolyn A.; Thomas, David D.; Rosenfeld, Steven S.

    2013-01-01

    Members of the kinesin superfamily of molecular motors differ in several key structural domains, which probably allows these molecular motors to serve the different physiologies required of them. One of the most variable of these is a stem-loop motif referred to as L5. This loop is longest in the mitotic kinesin Eg5, and previous structural studies have shown that it can assume different conformations in different nucleotide states. However, enzymatic domains often consist of a mixture of conformations whose distribution shifts in response to substrate binding or product release, and this information is not available from the “static” images that structural studies provide. We have addressed this issue in the case of Eg5 by attaching a fluorescent probe to L5 and examining its fluorescence, using both steady state and time-resolved methods. This reveals that L5 assumes an equilibrium mixture of three orientations that differ in their local environment and segmental mobility. Combining these studies with transient state kinetics demonstrates that there is a major shift in this distribution during transitions that interconvert weak and strong microtubule binding states. Finally, in conjunction with previous cryo-EM reconstructions of Eg5·microtubule complexes, these fluorescence studies suggest a model in which L5 regulates both nucleotide and microtubule binding through a set of reversible interactions with helix ?3. We propose that these features facilitate the production of sustained opposing force by Eg5, which underlies its role in supporting formation of a bipolar spindle in mitosis. PMID:24145034

  12. A 90nm high volume manufacturing logic technology featuring novel 45nm gate length strained silicon CMOS transistors

    Microsoft Academic Search

    T. Ghani; M. Armstrong; C. Auth; M. Bost; P. Charvat; G. Glass; T. Hoffmann; K. Johnson; C. Kenyon; J. Klaus; B. McIntyre; K. Mistry; A. Murthy; J. Sandford; M. Silberstein; S. Sivakumar; P. Smith; K. Zawadzki; S. Thompson; M. Bohr

    2003-01-01

    This paper describes the details of a novel strained transistor architecture which is incorporated into a 90nm logic technology on 300mm wafers. The unique strained PMOS transistor structure features an epitaxially grown strained SiGe film embedded in the source drain regions. Dramatic performance enhancement relative to unstrained devices are reported. These transistors have gate length of 45nm and 50nm for

  13. Analysis of Biological Features Associated with Meiotic Recombination Hot and Cold Spots in Saccharomyces cerevisiae

    PubMed Central

    Hansen, Loren; Kim, Nak-Kyeong; Marińo-Ramírez, Leonardo; Landsman, David

    2011-01-01

    Meiotic recombination is not distributed uniformly throughout the genome. There are regions of high and low recombination rates called hot and cold spots, respectively. The recombination rate parallels the frequency of DNA double-strand breaks (DSBs) that initiate meiotic recombination. The aim is to identify biological features associated with DSB frequency. We constructed vectors representing various chromatin and sequence-based features for 1179 DSB hot spots and 1028 DSB cold spots. Using a feature selection approach, we have identified five features that distinguish hot from cold spots in Saccharomyces cerevisiae with high accuracy, namely the histone marks H3K4me3, H3K14ac, H3K36me3, and H3K79me3; and GC content. Previous studies have associated H3K4me3, H3K36me3, and GC content with areas of mitotic recombination. H3K14ac and H3K79me3 are novel predictions and thus represent good candidates for further experimental study. We also show nucleosome occupancy maps produced using next generation sequencing exhibit a bias at DSB hot spots and this bias is strong enough to obscure biologically relevant information. A computational approach using feature selection can productively be used to identify promising biological associations. H3K14ac and H3K79me3 are novel predictions of chromatin marks associated with meiotic DSBs. Next generation sequencing can exhibit a bias that is strong enough to lead to incorrect conclusions. Care must be taken when interpreting high throughput sequencing data where systematic biases have been documented. PMID:22242140

  14. Subnuclear localization and mitotic phosphorylation of HIRA, the human homologue of Saccharomyces cerevisiae transcriptional regulators Hir1p/Hir2p.

    PubMed Central

    De Lucia, F; Lorain, S; Scamps, C; Galisson, F; MacHold, J; Lipinski, M

    2001-01-01

    The HIRA gene encodes a nuclear protein with histone-binding properties that have been conserved from yeast to humans. Hir1p and Hir2p, the two HIRA homologues in Saccharomyces cerevisiae, are transcriptional co-repressors whose action resides at the chromatin level and occurs in a cell-cycle-regulated fashion. In mammals, HIRA is an essential gene early during development, possibly through the control of specific gene-transcription programmes, but its exact function remains to be deciphered. Here we report on the subnuclear distribution and cell-cycle behaviour of the HIRA protein. Using both biochemical and immunofluorescence techniques, a minor fraction of HIRA was found tightly associated with the nuclear matrix, the material that remains after nuclease treatment and high-salt extraction. However, most HIRA molecules proved extractable. In non-synchronized cell populations, extraction from chromatin necessitated 300 mM NaCl whereas 150 mM was sufficient in mitotic cells. Immunofluorescence staining and microscopic examination of mitotic cells revealed HIRA as excluded from condensed chromosomes, confirming a lack of association with chromatin during mitosis. Western-blot analysis indicated that HIRA molecules were hyper-phosphorylated at this point in the cell cycle. Metabolic labelling and pulse-chase experiments characterized HIRA as a stable protein with a half-life of approx. 12 h. The mitotic phosphorylation of HIRA could provide the dividing cell with a way to retarget HIRA-containing multi-protein complexes to different chromatin regions in daughter compared with parental cells. PMID:11513744

  15. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint.

    PubMed

    Yu, Yueyang; Munger, Karl

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons. PMID:22748180

  16. Changes of G-actin localisation in the mitotic spindle region or nucleus during mitosis and after heat shock: a histochemical study of G-actin in various cell lines with fluorescent labelled vitamin D-binding protein

    Microsoft Academic Search

    Irma Meijerman; W. Marty Blom; Hans J. G. M de Bont; Gerard J Mulder; J. Fred Nagelkerke

    1999-01-01

    The presence and localisation of G-actin in various cell lines was studied using the highly G-actin specific, fluorescence-labelled vitamin D-binding protein. In various cell-types, pig kidney-derived cells (LLC-PK1), Chinese hamster ovary (CHO) cells, SV-40 transformed African green monkey kidney (COS) cells and human hepatoma (HepG2) cells, G-actin was only visible in the cytoplasm of interphase cells. However, in mitotic cells,

  17. Features | Poster

    Cancer.gov

    Skip to main content About Us Services Science For Our Staff Phonebook Poster Search form Search Main menu Home Science Publications Platinum Highlight Platinum Publications Technology Transfer Awards Health and Safety Outreach Students Features Poster

  18. Synergy between Multiple Microtubule-Generating Pathways Confers Robustness to Centrosome-Driven Mitotic Spindle Formation

    PubMed Central

    Hayward, Daniel; Metz, Jeremy; Pellacani, Claudia; Wakefield, James G.

    2014-01-01

    Summary The mitotic spindle is defined by its organized, bipolar mass of microtubules, which drive chromosome alignment and segregation. Although different cells have been shown to use different molecular pathways to generate the microtubules required for spindle formation, how these pathways are coordinated within a single cell is poorly understood. We have tested the limits within which the Drosophila embryonic spindle forms, disrupting the inherent temporal control that overlays mitotic microtubule generation, interfering with the molecular mechanism that generates new microtubules from preexisting ones, and disrupting the spatial relationship between microtubule nucleation and the usually dominant centrosome. Our work uncovers the possible routes to spindle formation in embryos and establishes the central role of Augmin in all microtubule-generating pathways. It also demonstrates that the contributions of each pathway to spindle formation are integrated, highlighting the remarkable flexibility with which cells can respond to perturbations that limit their capacity to generate microtubules. PMID:24389063

  19. Mitotic Spindle Assembly around RCC1-Coated Beads in Xenopus Egg Extracts

    PubMed Central

    Halpin, David; Kalab, Petr; Wang, Jay; Weis, Karsten; Heald, Rebecca

    2011-01-01

    During cell division the genetic material on chromosomes is distributed to daughter cells by a dynamic microtubule structure called the mitotic spindle. Here we establish a reconstitution system to assess the contribution of individual chromosome proteins to mitotic spindle formation around single 10 µm diameter porous glass beads in Xenopus egg extracts. We find that Regulator of Chromosome Condensation 1 (RCC1), the Guanine Nucleotide Exchange Factor (GEF) for the small GTPase Ran, can induce bipolar spindle formation. Remarkably, RCC1 beads oscillate within spindles from pole to pole, a behavior that could be converted to a more typical, stable association by the addition of a kinesin together with RCC1. These results identify two activities sufficient to mimic chromatin-mediated spindle assembly, and establish a foundation for future experiments to reconstitute spindle assembly entirely from purified components. PMID:22215983

  20. Spatio-temporal Model for Silencing of the Mitotic Spindle Assembly Checkpoint

    PubMed Central

    Chen, Jing; Liu, Jian

    2014-01-01

    The spindle assembly checkpoint arrests mitotic progression until each kinetochore secures a stable attachment to the spindle. Despite fluctuating noise, this checkpoint remains robust and remarkably sensitive to even a single unattached kinetochore among many attached kinetochores; moreover, the checkpoint is silenced only after the final kinetochore-spindle attachment. Experimental observations have shown that checkpoint components stream from attached kinetochores along microtubules toward spindle poles. Here, we incorporate this streaming behavior into a theoretical model that accounts for the robustness of checkpoint silencing. Poleward streams are integrated at spindle poles, but are diverted by any unattached kinetochore; consequently, accumulation of checkpoint components at spindle poles increases markedly only when every kinetochore is properly attached. This step-change robustly triggers checkpoint silencing after, and only after, the final kinetochore-spindle attachment. Our model offers a conceptual framework that highlights the role of spatiotemporal regulation in mitotic spindle checkpoint signaling and fidelity of chromosome segregation. PMID:25216458

  1. Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic tissues

    PubMed Central

    Nowak, Katarzyna; Seisenbacher, Gerhard; Hafen, Ernst; Stocker, Hugo

    2013-01-01

    How single cells in a mitotic tissue progressively acquire hallmarks of cancer is poorly understood. We exploited mitotic recombination in developing Drosophila imaginal tissues to analyze the behavior of cells devoid of the tumor suppressor PTEN, a negative regulator of PI3K signaling, under varying nutritional conditions. Cells lacking PTEN strongly overproliferated specifically in nutrient restricted larvae. Although the PTEN mutant cells were sensitive to starvation, they successfully competed with neighboring cells by autonomous and non-autonomous mechanisms distinct from cell competition. The overgrowth was strictly dependent on the activity of the downstream components Akt/PKB and TORC1, and a reduction in amino acid uptake by reducing the levels of the amino acid transporter Slimfast caused clones of PTEN mutant cells to collapse. Our findings demonstrate how limiting nutritional conditions impact on cells lacking the tumor suppressor PTEN to cause hyperplastic overgrowth. DOI: http://dx.doi.org/10.7554/eLife.00380.001 PMID:23853709

  2. GLP-1 is localized to the mitotic region of the C. elegans germ line.

    PubMed

    Crittenden, S L; Troemel, E R; Evans, T C; Kimble, J

    1994-10-01

    In C. elegans, germline mitosis depends on induction by the somatic distal tip cell (DTC) and on activity of the glp-1 gene. Using antibodies to GLP-1 protein, we have examined GLP-1 on western blots and by immunocytochemistry. GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. Furthermore, GLP-1 is localized within the germ line to the mitotic region, consistent with the model that GLP-1 acts as a membrane receptor for the distal tip cell signal. Unexpectedly, GLP-1 and the zone of mitosis extend further than the DTC processes. We present three models by which the DTC may influence GLP-1 activity and thereby determine the zone of mitosis. The spatial restriction of GLP-1 appears to be controlled at the translational level in hermaphrodites. We suggest that down-regulation of GLP-1 may be required to effect the transition from mitosis into meiosis. PMID:7607080

  3. Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A, causing mitotic arrest

    PubMed Central

    Coon, Tiffany A; Glasser, Jennifer R; Mallampalli, Rama K

    2012-01-01

    Aurora family kinases play pivotal roles in several steps during mitosis. Specifically, Aurora A kinase is an important regulator of bipolar mitotic spindle formation and chromosome segregation. Like other members of the Aurora family, Aurora A kinase is also regulated by post-translational modifications. Here, we show that a previously undescribed E3 ligase component belonging to the SCF (Skp-Cullin1-F-box protein) E3 ligase family, SCFFBXL7, impairs cell proliferation by mediating Aurora A polyubiquitination and degradation. Both Aurora A and FBXL7 co-localize within the centrosome during spindle formation. FBXL7 ectopic expression led to G2/M phase arrest in transformed epithelia, resulting in the appearance of tetraploidy and mitotic arrest with circular monopolar spindles and multipolar spindle formation. Interestingly, FBXL7 specifically interacts with Aurora A during mitosis but not in interphase, suggesting a regulatory role for FBXL7 in controlling Aurora A abundance during mitosis. PMID:22306998

  4. Sorting Nexin 9 Recruits Clathrin Heavy Chain to the Mitotic Spindle for Chromosome Alignment and Segregation

    PubMed Central

    Ma, Maggie P. C.; Robinson, Phillip J.; Chircop, Megan

    2013-01-01

    Sorting nexin 9 (SNX9) and clathrin heavy chain (CHC) each have roles in mitosis during metaphase. Since the two proteins directly interact for their other cellular function in endocytosis we investigated whether they also interact for metaphase and operate on the same pathway. We report that SNX9 and CHC functionally interact during metaphase in a specific molecular pathway that contributes to stabilization of mitotic spindle kinetochore (K)-fibres for chromosome alignment and segregation. This function is independent of their endocytic role. SNX9 residues in the clathrin-binding low complexity domain are required for CHC association and for targeting both CHC and transforming acidic coiled-coil protein 3 (TACC3) to the mitotic spindle. Mutation of these sites to serine increases the metaphase plate width, indicating inefficient chromosome congression. Therefore SNX9 and CHC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association. PMID:23861900

  5. C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis

    Microsoft Academic Search

    Kirsten A. Hagstrom; Victor F. Holmes; Nicholas R. Cozzarelli; Barbara J. Meyer

    2002-01-01

    Chromosome segregation and X-chromosome gene regulation in Caenorhabditis elegans share the component MIX-1, a mitotic protein that also represses X-linked genes during dosage compensation. MIX-1 achieves its dual roles through interactions with different protein partners. To repress gene expression, MIX-1 acts in an X-chromosome complex that resembles the mitotic condensin complex yet lacks chromosome segregation function. Here we show that

  6. Loss of CHFR in Human Mammary Epithelial Cells Causes Genomic Instability by Disrupting the Mitotic Spindle Assembly Checkpoint1

    Microsoft Academic Search

    Lisa M. Privette; Jingly Fung Weier; Ha Nam Nguyen; Xiaochun Yu; Elizabeth M. Petty

    CHFR is an E3 ubiquitin ligase and an early mitotic checkpoint protein implicated in many cancers and in the main- tenance of genomic stability. To analyze the role of CHFR in genomic stability, by siRNA, we decreased its expres- sion in genomically stable MCF10A cells. Lowered CHFR expression quickly led to increased aneuploidy due to many mitotic defects. First, we

  7. RBPJ, the Major Transcriptional Effector of Notch Signaling, Remains Associated with Chromatin throughout Mitosis, Suggesting a Role in Mitotic Bookmarking

    PubMed Central

    Choi, Inchan; Won, Kyoung-Jae; Fan, Hua-Ying

    2014-01-01

    Mechanisms that maintain transcriptional memory through cell division are important to maintain cell identity, and sequence-specific transcription factors that remain associated with mitotic chromatin are emerging as key players in transcriptional memory propagation. Here, we show that the major transcriptional effector of Notch signaling, RBPJ, is retained on mitotic chromatin, and that this mitotic chromatin association is mediated through the direct association of RBPJ with DNA. We further demonstrate that RBPJ binds directly to nucleosomal DNA in vitro, with a preference for sites close to the entry/exit position of the nucleosomal DNA. Genome-wide analysis in the murine embryonal-carcinoma cell line F9 revealed that roughly 60% of the sites occupied by RBPJ in asynchronous cells were also occupied in mitotic cells. Among them, we found that a fraction of RBPJ occupancy sites shifted between interphase and mitosis, suggesting that RBPJ can be retained on mitotic chromatin by sliding on DNA rather than disengaging from chromatin during mitotic chromatin condensation. We propose that RBPJ can function as a mitotic bookmark, marking genes for efficient transcriptional activation or repression upon mitotic exit. Strikingly, we found that sites of RBPJ occupancy were enriched for CTCF-binding motifs in addition to RBPJ-binding motifs, and that RBPJ and CTCF interact. Given that CTCF regulates transcription and bridges long-range chromatin interactions, our results raise the intriguing hypothesis that by collaborating with CTCF, RBPJ may participate in establishing chromatin domains and/or long-range chromatin interactions that could be propagated through cell division to maintain gene expression programs. PMID:24603501

  8. The SUMO protease SENP1 is required for cohesion maintenance and mitotic arrest following spindle poison treatment

    SciTech Connect

    Era, Saho [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy) [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Abe, Takuya; Arakawa, Hiroshi [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy)] [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Kobayashi, Shunsuke [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan)] [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Szakal, Barnabas [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy)] [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Yoshikawa, Yusuke; Motegi, Akira; Takeda, Shunichi [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan)] [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Branzei, Dana, E-mail: dana.branzei@ifom.eu [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy)] [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer SENP1 knockout chicken DT40 cells are hypersensitive to spindle poisons. Black-Right-Pointing-Pointer Spindle poison treatment of SENP1{sup -/-} cells leads to increased mitotic slippage. Black-Right-Pointing-Pointer Mitotic slippage in SENP1{sup -/-} cells associates with apoptosis and endoreplication. Black-Right-Pointing-Pointer SENP1 counteracts sister chromatid separation during mitotic arrest. Black-Right-Pointing-Pointer Plk1-mediated cohesion down-regulation is involved in colcemid cytotoxicity. -- Abstract: SUMO conjugation is a reversible posttranslational modification that regulates protein function. SENP1 is one of the six SUMO-specific proteases present in vertebrate cells and its altered expression is observed in several carcinomas. To characterize SENP1 role in genome integrity, we generated Senp1 knockout chicken DT40 cells. SENP1{sup -/-} cells show normal proliferation, but are sensitive to spindle poisons. This hypersensitivity correlates with increased sister chromatid separation, mitotic slippage, and apoptosis. To test whether the cohesion defect had a causal relationship with the observed mitotic events, we restored the cohesive status of sister chromatids by introducing the TOP2{alpha}{sup +/-} mutation, which leads to increased catenation, or by inhibiting Plk1 and Aurora B kinases that promote cohesin release from chromosomes during prolonged mitotic arrest. Although TOP2{alpha} is SUMOylated during mitosis, the TOP2{alpha}{sup +/-} mutation had no obvious effect. By contrast, inhibition of Plk1 or Aurora B rescued the hypersensitivity of SENP1{sup -/-} cells to colcemid. In conclusion, we identify SENP1 as a novel factor required for mitotic arrest and cohesion maintenance during prolonged mitotic arrest induced by spindle poisons.

  9. Histone modifications defining active genes persist after transcriptional and mitotic inactivation

    Microsoft Academic Search

    Antigone Kouskouti; Iannis Talianidis

    2004-01-01

    We examined various histone modifications across the promoter and the coding regions of constitutively active hepatic genes in G0\\/G1-enriched, mitotically arrested and a-amanitin-blocked cells. Gene activation correlated with localized histone hyperacetylation, H3-K4 tri- or dimethyl- ation and H3-K79 dimethylation and localized nucleosome remodeling at the promoter and the 50 portion of the coding regions. Nucleosomes at more downstream loca- tions

  10. [Antiproliferative effect of bcl-2 gene does not concern the control of mitotic events].

    PubMed

    Neliudova, A M; Brichkina, A I; Rukhlova, M P; Aksenov, N D; Pospelova, T V

    2004-01-01

    E1A + c-Ha-ras-transformants overexpressing bcl-2 oncogene are able to be arrested at the G1/S boundary of the cell cycle after DNA damage and upon serum starvation, this cell cycle blockage being accompanied by a decrease in the activity of cyclin E--Cdk2 complexes. Roscovitine-induced inhibition of cyclin-dependent kinases (Cdks) activity does not result in the G1/S arrest of E1A + c-Ha-ras + bcl-2-transformants. Roscovitine treatment causes an accumulation of G2/M cells, mainly at the expense of mitotic cells. However, the expression of Bcl-2 oncoproducts does not re-establish the regulation of mitotic events broken by introduction of E1A and c-Ha-ras oncogenes in normal cells, as revealed by the treatment of E1A + c-Ha-ras + bcl-2-transformants with nocodazole inducing mitotic arrest in normal cells. In spite of the elevated expression of antiapoptotic bcl-2 gene in transformants, nocodazole treatment results in mass apoptotic death preceded by polyploidy. Roscovitine also induces apoptosis with no polyploid cell accumulation being observed. Inhibition of Cdks activity with Roscovitine, as well as violation of microtubule depolymerization with nocodazole result in the apoptotic death in the tested cell lines sensitive (E1A + c-Ha-ras) and resistant (E1A + c-Ha-ras + bcl-2) to damaging agents. Thus, the application of Roscovitine, a specific inhibitor of Cdks, suggests that the decrease in Cdks activity in E1A + c-Ha-ras + bcl-2-transformants is not likely to be responsible for G1/S cell cycle arrest realization after damaging influences. Moreover, an antiproliferative effect of Bcl-2 in E1A + c-Ha-ras-transformants is restricted by restoration of cell cycle events at G1/S and G2/M boundaries, and does not concern the program of mitotic events regulation. PMID:15214171

  11. Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly

    Microsoft Academic Search

    M. Andrew Hoyt; Ling He; Kek Khee Loo; William S. Saunders

    1992-01-01

    Two Saccharomyces cerevisiae genes, CIN8 and KIP1 (a.k.a. CIN9), were identified by their re- quirement for normal chromosome segregation. Both genes encode polypeptides related to the heavy chain of the microtubule-based force-generating enzyme kinesin. Cin8p was found to be required for pole separation during mitotic spindle assembly at 37~ although overproduced Kiplp could substitute. At lower temperatures, the activity of

  12. Expression, regulation and activity of a B2-type cyclin in mitotic and endoreduplicating maize endosperm

    PubMed Central

    Sabelli, Paolo A.; Dante, Ricardo A.; Nguyen, Hong N.; Gordon-Kamm, William J.; Larkins, Brian A.

    2014-01-01

    Cyclin-dependent kinases, the master regulators of the eukaryotic cell cycle, are complexes comprised of a catalytic serine/threonine protein kinase and an essential regulatory cyclin. The maize genome encodes over 50 cyclins grouped in different types, but they have been little investigated. We characterized a type B2 cyclin (CYCB2;2) during maize endosperm development, which comprises a cell proliferation phase based on the standard mitotic cell cycle, followed by an endoreduplication phase in which DNA replication is reiterated in the absence of mitosis or cytokinesis. CYCB2;2 RNA was present throughout the period of endosperm development studied, but its level declined as the endosperm transitioned from a mitotic to an endoreduplication cell cycle. However, the level of CYCB2;2 protein remained relatively constant during both stages of endosperm development. CYCB2;2 was recalcitrant to degradation by the 26S proteasome in endoreduplicating endosperm extracts, which could explain its sustained accumulation during endosperm development. In addition, although CYCB2;2 was generally localized to the nucleus of endosperm cells, a lower molecular weight form of the protein accumulated specifically in the cytosol of endoreduplicating endosperm cells. In dividing cells, CYCB2;2 appeared to be localized to the phragmoplast and may be involved in cytokinesis and cell wall formation. Kinase activity was associated with CYCB2;2 in mitotic endosperm, but was absent or greatly reduced in immature ear and endoreduplicating endosperm. CYCB2;2-associated kinase phosphorylated maize E2F1 and the “pocket” domains of RBR1 and RBR3. CYCB2;2 interacted with both maize CDKA;1 and CDKA;3 in insect cells. These results suggest CYCB2;2 functions primarily during the mitotic cell cycle, and they are discussed in the context of the roles of cyclins, CDKs and proteasome activity in the regulation of the cell cycle during endosperm development. PMID:25368625

  13. Mitotic Kinesin-Like Protein 2 Binds and Colocalizes with Papillomavirus E2 during Mitosis

    Microsoft Academic Search

    Ting Yu; Yu-Cai Peng; Elliot J. Androphy

    2007-01-01

    MKlp2 is a kinesin-like motor protein of the central mitotic spindle required for completion of cytokinesis. Papillomavirus E2 is a sequence specific DNA binding protein that regulates viral transcription and replica- tion and is responsible for partitioning viral episomes into daughter cells during cell division. We demonstrate that MKlp2 specifically associates with the E2 protein during mitosis. Using chromatin immunoprecipitation,

  14. Protective effect of ethanol on X-ray-induced mitotic recombination in drosophilia melanogaster

    Microsoft Academic Search

    Ana M. Palermo; Mónica Rey; E. R. Munoz

    1994-01-01

    The effect of ethanol treatment on X-ray-induced mitotic recombination in D. melanogaster females was investigated by means of the white\\/white{sup +} w\\/w{sup +} spot test. White females inseminated by yellow males were allowed to oviposit for 8 hr on medium containing 5%, 7.5% and 10% (v\\/v) ethanol and submitted to 10 Gy of X-rays 52 hr after the beginning of

  15. Mitotic Haploidization by Treatment of Aspergillus niger Diploids with para-Fluorophenylalanine

    Microsoft Academic Search

    Pol Lhoas

    1961-01-01

    IN genetic analysis based on mitotic segregation1-4 an important step is the recovery of haploid segregants from heterozygous diploids. This has been done until recently by laborious or complicated techniques4,5. I am indebted to Dr. G. Morpurgo, of the Istituto Superiore di Sanitŕ, Rome, for informing me and permitting me to make use of his discovery that treatment with para-fluoro-phenylalanine

  16. The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint

    Microsoft Academic Search

    Eric Weiss; Mark Winey

    1996-01-01

    M-phase checkpoints inhibit cell division when mitotic spindle function is perturbed. Here we show that the Saccharomyces cerevisiae MPS1 gene product, an essential protein kinase required for spin- dle pole body (SPB) duplication (Winey et al., 1991; Lauze et al., 1995), is also required for M-phase check- point function. In cdc31-2 and mps2-1 mutants, condi- tional failure of SPB duplication

  17. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women

    Microsoft Academic Search

    Yvonne A R White; Dori C Woods; Yasushi Takai; Osamu Ishihara; Hiroyuki Seki; Jonathan L Tilly

    2012-01-01

    Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a fluorescence-activated cell sorting-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically active cells that have a gene expression profile that is

  18. Structural differentiation of the meiotic and mitotic chromosomes of the salamander, Ambystoma macrodactylum

    Microsoft Academic Search

    James Kezer; Pedro E. León

    1980-01-01

    The lampbrush chromosomes of the long-toed salamander, Ambystoma macrodactylum Baird, have been analysed and a map of the oocyte genome prepared. The location of C-bands and cold-induced-constrictions has been established in mitotic chromosomes and compared with the location of marker structures and chiasmata in several lampbrush bivalents. In the lampbrush chromosomes, C-bands are tentatively correlated with sphere-organizing loci and with

  19. Visualization of mitotic chromosomes in filamentous fungi by fluorescence staining and fluorescence in situ hybridization

    Microsoft Academic Search

    Masatoki Taga; Minoru Murata

    1994-01-01

    Mitotic chromosomes of the plant pathogenic filamentous fungi Botrytis cinerea and Alternaria alternata were observed. Chromosomes prepared by the germ tube burst method were stained with the fluorescent dye 4',6-diamidino-2-phenylindole (DAPI) to yield figures with good resolution. Using this method, component chromosomes were clearly distinguished and the chromosome number could be determined. Fluorescence in situ hybridization (FISH) was also successfully

  20. Pb-inhibited mitotic activity in onion roots involves DNA damage and disruption of oxidative metabolism.

    PubMed

    Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2014-09-01

    Plant responses to abiotic stress significantly affect the development of cells, tissues and organs. However, no studies correlating Pb-induced mitotic inhibition and DNA damage and the alterations in redox homeostasis during root division per se were found in the literature. Therefore, an experiment was conducted to evaluate the impact of Pb on mitotic activity and the associated changes in the oxidative metabolism in onion roots. The cytotoxic effect of Pb on cell division was assessed in the root meristems of Allium cepa (onion). The mitotic index (MI) was calculated and chromosomal abnormalities were sought. Pb-treatment induced a dose-dependent decrease in MI in the onion root tips and caused mitotic abnormalities such as distorted metaphase, fragments, sticky chromosomes, laggards, vagrant chromosomes and bridges. Single Cell Gel Electrophoresis was also performed to evaluate Pb induced genotoxicity. It was accompanied by altered oxidative metabolism in the onion root tips suggesting the interference of Pb with the redox homeostasis during cell division. There was a higher accumulation of malondialdehyde, conjugated dienes and hydrogen peroxide, and a significant increase in the activities of superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases in Pb-treated onion roots, whereas catalases activity exhibited a decreasing pattern upon Pb exposure. The study concludes that Pb-induced cytotoxicity and genotoxicity in the onion roots is mediated through ROS and is also tightly linked to the cell cycle. The exposure to higher concentrations arrested cell cycle leading to cell death, whereas different repair responses are generated at lower concentrations, thereby allowing the cell to complete the cell cycle. PMID:25023386

  1. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1

    Microsoft Academic Search

    F. Ralf Bischoff; Herwig Ponstingl

    1991-01-01

    THE product of the gene RCC1 (regulator of chromosome condensation) in a BHK cell line is involved in the control of mitotic events1. Homologous genes have been found in Xenopus 2, Drosophila 3 and yeast4,5. A human genomic DNA fragment and complementary DNA that complement a temperature-sensitive mutation ofRCC1 in BHK21 cells6,7 encode a protein of relative molecular mass 45,000

  2. A very high-resolution, deep-towed, multichannel seismic survey of gas, gas hydrates and gas hydrate-related features in marine sediments off Peru

    Microsoft Academic Search

    M. Breitzke; J. Bialas

    2003-01-01

    A very high-resolution, deep-towed, multichannel seismic survey was carried out in the Yaquina Basin off Peru in 2002 (RV Sonne cruise SO162) in order (1) to test the newly developed deep tow system and verify the lateral and vertical resolution of the recorded data and (2) to image small-scale features related to the occurrence of gas, gas hydrates and fluid

  3. Regulatory dephosphorylation of CDK at G2/M in plants: yeast mitotic phosphatase cdc25 induces cytokinin-like effects in transgenic tobacco morphogenesis

    PubMed Central

    Lipavská, Helena; Mašková, Petra; Vojvodová, Petra

    2011-01-01

    Background During the last three decades, the cell cycle and its control by cyclin-dependent kinases (CDKs) have been extensively studied in eukaryotes. This endeavour has produced an overall picture that basic mechanisms seem to be largely conserved among all eukaryotes. The intricate regulation of CDK activities includes, among others, CDK activation by CDC25 phosphatase at G2/M. In plants, however, studies of this regulation have lagged behind as a plant Cdc25 homologue or other unrelated phosphatase active at G2/M have not yet been identified. Scope Failure to identify a plant mitotic CDK activatory phosphatase led to characterization of the effects of alien cdc25 gene expression in plants. Tobacco, expressing the Schizosaccharomyces pombe mitotic activator gene, Spcdc25, exhibited morphological, developmental and biochemical changes when compared with wild type (WT) and, importantly, increased CDK dephosphorylation at G2/M. Besides changes in leaf shape, internode length and root development, in day-neutral tobacco there was dramatically earlier onset of flowering with a disturbed acropetal floral capacity gradient typical of WT. In vitro, de novo organ formation revealed substantially earlier and more abundant formation of shoot primordia on Spcdc25 tobacco stem segments grown on shoot-inducing media when compared with WT. Moreover, in contrast to WT, stem segments from transgenic plants formed shoots even without application of exogenous growth regulator. Spcdc25-expressing BY-2 cells exhibited a reduced mitotic cell size due to a shortening of the G2 phase together with high activity of cyclin-dependent kinase, NtCDKB1, in early S-phase, S/G2 and early M-phase. Spcdc25-expressing tobacco (‘Samsun’) cell suspension cultures showed a clustered, more circular, cell phenotype compared with chains of elongated WT cells, and increased content of starch and soluble sugars. Taken together, Spcdc25 expression had cytokinin-like effects on the characteristics studied, although determination of endogenous cytokinin levels revealed a dramatic decrease in Spcdc25 transgenics. Conclusions The data gained using the plants expressing yeast mitotic activator, Spcdc25, clearly argue for the existence and importance of activatory dephosphorylation at G2/M transition and its interaction with cytokinin signalling in plants. The observed cytokinin-like effects of Spcdc25 expression are consistent with the concept of interaction between cell cycle regulators and phytohormones during plant development. The G2/M control of the plant cell cycle, however, remains an elusive issue as doubts persist about the mode of activatory dephosphorylation, which in other eukaryotes is provided by Cdc25 phosphatase serving as a final all-or-nothing mitosis regulator. PMID:21339187

  4. GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features.

    PubMed

    Wang, Tianjiao; Feldman, Andrew L; Wada, David A; Lu, Ye; Polk, Avery; Briski, Robert; Ristow, Kay; Habermann, Thomas M; Thomas, Dafydd; Ziesmer, Steven C; Wellik, Linda E; Lanigan, Thomas M; Witzig, Thomas E; Pittelkow, Mark R; Bailey, Nathanael G; Hristov, Alexandra C; Lim, Megan S; Ansell, Stephen M; Wilcox, Ryan A

    2014-05-01

    The cell of origin and the tumor microenvironment's role remain elusive for the most common peripheral T-cell lymphomas (PTCLs). As macrophages promote the growth and survival of malignant T cells and are abundant constituents of the tumor microenvironment, their functional polarization was examined in T-cell lymphoproliferative disorders. Cytokines that are abundant within the tumor microenvironment, particularly interleukin (IL)-10, were observed to promote alternative macrophage polarization. Macrophage polarization was signal transducer and activator of transcription 3 dependent and was impaired by the Janus kinase inhibitor ruxolitinib. In conventional T cells, the production of T helper (Th)2-associated cytokines and IL-10, both of which promote alternative macrophage polarization, is regulated by the T-cell transcription factor GATA-binding protein 3 (GATA-3). Therefore, its role in the T-cell lymphomas was examined. GATA-3 expression was observed in 45% of PTCLs, not otherwise specified (PTCL, NOS) and was associated with distinct molecular features, including the production of Th2-associated cytokines. In addition, GATA-3 expression identified a subset of PTCL, NOS with distinct clinical features, including inferior progression-free and overall survival. Collectively, these data suggest that further understanding the cell of origin and lymphocyte ontogeny among the T-cell lymphomas may improve our understanding of the tumor microenvironment's pathogenic role in these aggressive lymphomas. PMID:24497534

  5. Dovitinib induces mitotic defects and activates the G2 DNA damage checkpoint.

    PubMed

    Man, Wing Yu; Mak, Joyce P Y; Poon, Randy Y C

    2014-01-01

    Dovitinib (TKI258; formerly CHIR-258) is an orally bioavailable inhibitor of multiple receptor tyrosine kinases. Interestingly, Dovitinib triggered a G2 /M arrest in cancer cell lines from diverse origins including HeLa, nasopharyngeal carcinoma, and hepatocellular carcinoma. Single-cell analysis revealed that Dovitinib promoted a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induced a G2 arrest similar to the G2 DNA damage checkpoint. In support of this, DNA damage was triggered by Dovitinib as revealed by ?-H2AX and comet assays. The mitotic kinase CDK1 was found to be inactivated by phosphorylation in the presence of Dovitinib. Furthermore, the G2 arrest could be overcome by abrogation of the G2 DNA damage checkpoint using small molecule inhibitors of CHK1 and WEE1. Finally, Dovitinib-mediated G2 cell cycle arrest and subsequent cell death could be promoted after DNA damage repair was disrupted by inhibitors of poly(ADP-ribose) polymerases. These results are consistent with the recent finding that Dovitinib can also target topoisomerases. Collectively, these results suggest additional directions for use of Dovitinib, in particular with agents that target the DNA damage checkpoint. PMID:24238094

  6. Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration

    PubMed Central

    Bernis, Cyril; Swift-Taylor, Beth; Nord, Matthew; Carmona, Sarah; Chook, Yuh Min; Forbes, Douglass J.

    2014-01-01

    The nuclear import receptors importin ? and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin ? is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin ? for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin ?, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin ? and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. PMID:24478460

  7. Drosophila FANCM helicase prevents spontaneous mitotic crossovers generated by the MUS81 and SLX1 nucleases.

    PubMed

    Kuo, H Kenny; McMahan, Susan; Rota, Christopher M; Kohl, Kathryn P; Sekelsky, Jeff

    2014-11-01

    Several helicases function during repair of double-strand breaks and handling of blocked or stalled replication forks to promote pathways that prevent formation of crossovers. Among these are the Bloom syndrome helicase BLM and the Fanconi anemia group M (FANCM) helicase. To better understand functions of these helicases, we compared phenotypes of Drosophila melanogaster Blm and Fancm mutants. As previously reported for BLM, FANCM has roles in responding to several types of DNA damage in preventing mitotic and meiotic crossovers and in promoting the synthesis-dependent strand annealing pathway for repair of a double-strand gap. In most assays, the phenotype of Fancm mutants is less severe than that of Blm mutants, and the phenotype of Blm Fancm double mutants is more severe than either single mutant, indicating both overlapping and unique functions. It is thought that mitotic crossovers arise when structure-selective nucleases cleave DNA intermediates that would normally be unwound or disassembled by these helicases. When BLM is absent, three nucleases believed to function as Holliday junction resolvases--MUS81-MMS4, MUS312-SLX1, and GEN--become essential. In contrast, no single resolvase is essential in mutants lacking FANCM, although simultaneous loss of GEN and either of the others is lethal in Fancm mutants. Since Fancm mutants can tolerate loss of a single resolvase, we were able to show that spontaneous mitotic crossovers that occur when FANCM is missing are dependent on MUS312 and either MUS81 or SLX1. PMID:25205745

  8. Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression

    PubMed Central

    Wang, Peng; Galan, Jacob A.; Normandin, Karine; Bonneil, Éric; Hickson, Gilles R.; Roux, Philippe P.; Thibault, Pierre

    2013-01-01

    Cell division requires the coordination of critical protein kinases and phosphatases. Greatwall (Gwl) kinase activity inactivates PP2A-B55 at mitotic entry to promote the phosphorylation of cyclin B–Cdk1 substrates, but how Gwl is regulated is poorly understood. We found that the subcellular localization of Gwl changed dramatically during the cell cycle in Drosophila. Gwl translocated from the nucleus to the cytoplasm in prophase. We identified two critical nuclear localization signals in the central, poorly characterized region of Gwl, which are required for its function. The Polo kinase associated with and phosphorylated Gwl in this region, promoting its binding to 14-3-3? and its localization to the cytoplasm in prophase. Our results suggest that cyclin B–Cdk1 phosphorylation of Gwl is also required for its nuclear exclusion by a distinct mechanism. We show that the nucleo-cytoplasmic regulation of Gwl is essential for its functions in vivo and propose that the spatial regulation of Gwl at mitotic entry contributes to the mitotic switch. PMID:23857770

  9. Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.

    PubMed

    Wang, Peng; Galan, Jacob A; Normandin, Karine; Bonneil, Éric; Hickson, Gilles R; Roux, Philippe P; Thibault, Pierre; Archambault, Vincent

    2013-07-22

    Cell division requires the coordination of critical protein kinases and phosphatases. Greatwall (Gwl) kinase activity inactivates PP2A-B55 at mitotic entry to promote the phosphorylation of cyclin B-Cdk1 substrates, but how Gwl is regulated is poorly understood. We found that the subcellular localization of Gwl changed dramatically during the cell cycle in Drosophila. Gwl translocated from the nucleus to the cytoplasm in prophase. We identified two critical nuclear localization signals in the central, poorly characterized region of Gwl, which are required for its function. The Polo kinase associated with and phosphorylated Gwl in this region, promoting its binding to 14-3-3? and its localization to the cytoplasm in prophase. Our results suggest that cyclin B-Cdk1 phosphorylation of Gwl is also required for its nuclear exclusion by a distinct mechanism. We show that the nucleo-cytoplasmic regulation of Gwl is essential for its functions in vivo and propose that the spatial regulation of Gwl at mitotic entry contributes to the mitotic switch. PMID:23857770

  10. Nur1 Dephosphorylation Confers Positive Feedback to Mitotic Exit Phosphatase Activation in Budding Yeast

    PubMed Central

    Godfrey, Molly; Kuilman, Thomas; Uhlmann, Frank

    2015-01-01

    Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. Initial Net1 phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14 Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN) signaling cascade maintains Cdc14 release. An important unresolved question is how Cdc14 activity can increase in early anaphase, while Cdk activity, that is required for Net1 phosphorylation, decreases and the MEN is not yet active. Here we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in early anaphase, relieving the inhibition and promoting further Cdc14 release. Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14 phosphatase activation during mitotic exit, required for faithful chromosome segregation and completion of the cell division cycle. PMID:25569132

  11. Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe

    PubMed Central

    Cornago, M; Garcia-Alberich, C; Blasco-Angulo, N; Vall-llaura, N; Nager, M; Herreros, J; Comella, J X; Sanchis, D; Llovera, M

    2014-01-01

    Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis. PMID:25275596

  12. Population dynamics of a meiotic/mitotic expansion model for the fragile X syndrome

    SciTech Connect

    Ashley, A.E.; Sherman, S.L. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1995-12-01

    A model to explain the mutational process and population dynamics of the fragile X syndrome is presented. The mutational mechanism was assumed to be a multi-pathway, multistep process. Expansion of CGG repeats was based on an underlying biological process and was assumed to occur at two time points: meiosis and early embryonic development (mitosis). Meiotic expansion was assumed to occur equally in oogenesis and spermatogenesis, while mitotic expansion was restricted to somatic, or constitutional, alleles of maternal origin. Testable hypotheses were predicted by this meiotic/mitotic model. First, parental origin of mutation is predicted to be associated with the risk of a woman to have a full-mutation child. Second, {open_quotes}contractions{close_quotes} seen in premutation male transmissions are predicted not to be true contractions in repeat size, but a consequence of the lack of mitotic expansion in paternally derived alleles. Third, a portion of full-mutation males should have full-mutation alleles in their sperm, due to the lack of complete selection against the full-mutation female. Fourth, a specific premutation-allele frequency distribution is predicted and differs from that based on models assuming only meiotic expansion. Last, it is predicted that {approximately}65 generations are required to achieve equilibrium, but this depends greatly on the expansion probabilities. 42 refs., 4 figs., 4 tabs.

  13. EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis.

    PubMed

    Bańón-Rodríguez, Inmaculada; Gálvez-Santisteban, Manuel; Vergarajauregui, Silvia; Bosch, Minerva; Borreguero-Pascual, Arantxa; Martín-Belmonte, Fernando

    2014-01-13

    Establishing the correct orientation of the mitotic spindle is an essential step in epithelial cell division in order to ensure that epithelial tubules form correctly during organ development and regeneration. While recent findings have identified some of the molecular mechanisms that underlie spindle orientation, many aspects of this process remain poorly understood. Here, we have used the 3D-MDCK model system to demonstrate a key role for a newly identified protein complex formed by IQGAP1 and the epithelial growth factor receptor (EGFR) in controlling the orientation of the mitotic spindle. IQGAP1 is a scaffolding protein that regulates many cellular pathways, from cell-cell adhesion to microtubule organization, and its localization in the basolateral membrane ensures correct spindle orientation. Through its IQ motifs, IQGAP1 binds to EGFR, which is responsible for maintaining IQGAP1 in the basolateral membrane domain. Silencing IQGAP1, or disrupting the basolateral localization of either IQGAP1 or EGFR, results in a non-polarized distribution of NuMA, mitotic spindle misorientation and defects in single lumen formation. PMID:24421325

  14. Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle

    PubMed Central

    Hochegger, Helfrid; Hégarat, Nadia; Pereira-Leal, Jose B.

    2013-01-01

    The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules. PMID:23516109

  15. Aurora B-dependent Regulation of Class IIa Histone Deacetylases by Mitotic Nuclear Localization Signal Phosphorylation*

    PubMed Central

    Guise, Amanda J.; Greco, Todd M.; Zhang, Irene Y.; Yu, Fang; Cristea, Ileana M.

    2012-01-01

    Class IIa histone deacetylases (HDACs 4/5/7/9) are transcriptional regulators with critical roles in cardiac disease and cancer. HDAC inhibitors are promising anticancer agents, and although they are known to disrupt mitotic progression, the underlying mechanisms of mitotic regulation by HDACs are not fully understood. Here we provide the first identification of histone deacetylases as substrates of Aurora B kinase (AurB). Our study identifies class IIa HDACs as a novel family of AurB targets and provides the first evidence that HDACs are temporally and spatially regulated by phosphorylation during the cell cycle. We define the precise site of AurB-mediated phosphorylation as a conserved serine within the nuclear localization signals of HDAC4, HDAC5, and HDAC9 at Ser265, Ser278, and Ser242, respectively. We establish that AurB interacts with these HDACs in vivo, and that this association increases upon disruption of 14-3-3 binding. We observe colocalization of endogenous, phosphorylated HDACs with AurB at the mitotic midzone in late anaphase and the midbody during cytokinesis, complemented by a reduction in HDAC interactions with components of the nuclear corepressor complex. We propose that AurB-dependent phosphorylation of HDACs induces sequestration within a phosphorylation gradient at the midzone, maintaining separation from re-forming nuclei and contributing to transcriptional control. PMID:22865920

  16. Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle.

    PubMed

    Hochegger, Helfrid; Hégarat, Nadia; Pereira-Leal, Jose B

    2013-03-01

    The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules. PMID:23516109

  17. Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

    NASA Technical Reports Server (NTRS)

    Baird, R. A.; Burton, M. D.; Fashena, D. S.; Naeger, R. A.

    2000-01-01

    Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

  18. Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration.

    PubMed

    Bernis, Cyril; Swift-Taylor, Beth; Nord, Matthew; Carmona, Sarah; Chook, Yuh Min; Forbes, Douglass J

    2014-04-01

    The nuclear import receptors importin ? and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin ? is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin ? for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin ?, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107-160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin ? and transportin "global positioning system"or "GPS" pathways that are mechanistically parallel. PMID:24478460

  19. The ? isoform of topoisomerase II is required for hypercompaction of mitotic chromosomes in human cells

    PubMed Central

    Farr, Christine J.; Antoniou-Kourounioti, Melissa; Mimmack, Michael L.; Volkov, Arsen; Porter, Andrew C. G.

    2014-01-01

    As proliferating cells transit from interphase into M-phase, chromatin undergoes extensive reorganization, and topoisomerase (topo) II?, the major isoform of this enzyme present in cycling vertebrate cells, plays a key role in this process. In this study, a human cell line conditional null mutant for topo II? and a derivative expressing an auxin-inducible degron (AID)-tagged version of the protein have been used to distinguish real mitotic chromosome functions of topo II? from its more general role in DNA metabolism and to investigate whether topo II? makes any contribution to mitotic chromosome formation. We show that topo II? does contribute, with endogenous levels being sufficient for the initial stages of axial shortening. However, a significant effect of topo II? depletion, seen with or without the co-depletion of topo II?, is the failure of chromosomes to hypercompact when delayed in M-phase. This requires much higher levels of topo II protein and is impaired by drugs or mutations that affect enzyme activity. A prolonged delay at the G2/M border results in hyperefficient axial shortening, a process that is topo II?-dependent. Rapid depletion of topo II? has allowed us to show that its function during late G2 and M-phase is truly required for shaping mitotic chromosomes. PMID:24476913

  20. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.

    PubMed

    Li, Wenyan; Wu, Jingfang; Yang, Jianming; Sun, Shan; Chai, Renjie; Chen, Zheng-Yi; Li, Huawei

    2015-01-01

    The activation of cochlear progenitor cells is a promising approach for hair cell (HC) regeneration and hearing recovery. The mechanisms underlying the initiation of proliferation of postnatal cochlear progenitor cells and their transdifferentiation to HCs remain to be determined. We show that Notch inhibition initiates proliferation of supporting cells (SCs) and mitotic regeneration of HCs in neonatal mouse cochlea in vivo and in vitro. Through lineage tracing, we identify that a majority of the proliferating SCs and mitotic-generated HCs induced by Notch inhibition are derived from the Wnt-responsive leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5(+)) progenitor cells. We demonstrate that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5(+) progenitor cells to mitotically generate new HCs. Our study reveals a new function of Notch signaling in limiting proliferation and regeneration potential of postnatal cochlear progenitor cells, and provides a new route to regenerate HCs from progenitor cells by interrupting the interaction between the Notch and Wnt pathways. PMID:25535395

  1. Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation.

    PubMed

    Nozawa, Ryu-Suke; Nagao, Koji; Masuda, Hiro-Taka; Iwasaki, Osamu; Hirota, Toru; Nozaki, Naohito; Kimura, Hiroshi; Obuse, Chikashi

    2010-07-01

    Heterochromatin protein 1 (HP1) has an essential role in heterochromatin formation and mitotic progression through its interaction with various proteins. We have identified a unique HP1alpha-binding protein, POGZ (pogo transposable element-derived protein with zinc finger domain), using an advanced proteomics approach. Proteins generally interact with HP1 through a PxVxL (where x is any amino-acid residue) motif; however, POGZ was found to bind to HP1alpha through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1alpha-chromatin interaction. Depletion experiments confirmed that the POGZ HP1-binding domain is essential for normal mitotic progression and dissociation of HP1alpha from mitotic chromosome arms. Furthermore, POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis. PMID:20562864

  2. PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator

    PubMed Central

    Kim, Yoosik; Lee, Jung Hyun; Park, Jong-Eun; Cho, Jun; Yi, Hyerim; Kim, V. Narry

    2014-01-01

    dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well known for its roles in immune response. Upon binding to viral dsRNA, PKR undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates translation and multiple signaling pathways in infected cells. Here, we found that PKR is activated in uninfected cells, specifically during mitosis, by binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu-containing RNAs are segregated in the cytosol and nucleus of interphase cells, respectively, they interact during mitosis when nuclear structure is disrupted. Once phosphorylated, PKR suppresses global translation by phosphorylating the ? subunit of eukaryotic initiation factor 2 (eIF2?). In addition, pPKR acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels of multiple mitotic factors such as CYCLINS A and B and POLO-LIKE KINASE 1 and phosphorylation of HISTONE H3. Disruption of PKR activation via RNAi or expression of a transdominant-negative mutant leads to misregulation of the mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our study unveils a novel function of PKR and endogenous dsRNAs as signaling molecules during the mitosis of uninfected cells. PMID:24939934

  3. Androgen receptor degradation by the E3 ligase CHIP modulates mitotic arrest in prostate cancer cells.

    PubMed

    Sarkar, S; Brautigan, D L; Parsons, S J; Larner, J M

    2014-01-01

    The androgen receptor (AR) has a vital role in the onset and progression of prostate cancer by promoting G1-S progression, possibly by functioning as a licensing factor for DNA replication. We here report that low dose 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, induces mitotic arrest in prostate cancer cells involving activation of the E3 ligase CHIP (C-terminus of Hsp70-interacting protein) and degradation of the AR. Depletion of the AR by small interfering RNA (siRNA) eliminates 2-ME-induced arrest and introducing AR into PC3-M cells confers 2-ME-induced mitotic arrest. Knockdown of CHIP or MDM2 (mouse homolog of double minute 2 protein) individually or in combination reduced AR degradation and abrogated M phase arrest induced by 2-ME. Our data link AR degradation via ubiquitination to mitotic arrest. Targeting the AR by activating E3 ligases such as CHIP represents a novel strategy for the treatment of prostate cancer. PMID:23246967

  4. Androgen receptor degradation by the E3 ligase CHIP modulates mitotic arrest in prostate cancer cells

    PubMed Central

    Sarkar, S; Brautigan, DL; Parsons, SJ; Larner, JM

    2013-01-01

    The androgen receptor (AR) has a vital role in the onset and progression of prostate cancer by promoting G1-S progression, possibly by functioning as a licensing factor for DNA replication. We here report that low dose 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, induces mitotic arrest in prostate cancer cells involving activation of the E3 ligase CHIP (C-terminus of Hsp70-interacting protein) and degradation of the AR. Depletion of the AR by small interfering RNA (siRNA) eliminates 2-ME-induced arrest and introducing AR into PC3-M cells confers 2-ME-induced mitotic arrest. Knockdown of CHIP or MDM2 (mouse homolog of double minute 2 protein) individually or in combination reduced AR degradation and abrogated M phase arrest induced by 2-ME. Our data link AR degradation via ubiquitination to mitotic arrest. Targeting the AR by activating E3 ligases such as CHIP represents a novel strategy for the treatment of prostate cancer. PMID:23246967

  5. Fragile Site Instability in Saccharomyces cerevisiae Causes Loss of Heterozygosity by Mitotic Crossovers and Break-Induced Replication

    PubMed Central

    Miller, Shaylynn D.; Casper, Anne M.

    2013-01-01

    Loss of heterozygosity (LOH) at tumor suppressor loci is a major contributor to cancer initiation and progression. Both deletions and mitotic recombination can lead to LOH. Certain chromosomal loci known as common fragile sites are susceptible to DNA lesions under replication stress, and replication stress is prevalent in early stage tumor cells. There is extensive evidence for deletions stimulated by common fragile sites in tumors, but the role of fragile sites in stimulating mitotic recombination that causes LOH is unknown. Here, we have used the yeast model system to study the relationship between fragile site instability and mitotic recombination that results in LOH. A naturally occurring fragile site, FS2, exists on the right arm of yeast chromosome III, and we have analyzed LOH on this chromosome. We report that the frequency of spontaneous mitotic BIR events resulting in LOH on the right arm of yeast chromosome III is higher than expected, and that replication stress by low levels of polymerase alpha increases mitotic recombination 12-fold. Using single-nucleotide polymorphisms between the two chromosome III homologs, we mapped the locations of recombination events and determined that FS2 is a strong hotspot for both mitotic reciprocal crossovers and break-induced replication events under conditions of replication stress. PMID:24068975

  6. Disruption of a Conserved CAP-D3 Threonine Alters Condensin Loading on Mitotic Chromosomes Leading to Chromosome Hypercondensation.

    PubMed

    Bakhrebah, Muhammed; Zhang, Tao; Mann, Jeff R; Kalitsis, Paul; Hudson, Damien F

    2015-03-01

    The condensin complex plays a key role in organizing mitotic chromosomes. In vertebrates, there are two condensin complexes that have independent and cooperative roles in folding mitotic chromosomes. In this study, we dissect the role of a putative Cdk1 site on the condensin II subunit CAP-D3 in chicken DT40 cells. This conserved site has been shown to activate condensin II during prophase in human cells, and facilitate further phosphorylation by polo-like kinase I. We examined the functional significance of this phosphorylation mark by mutating the orthologous site of CAP-D3 (CAP-D3(T1403A)) in chicken DT40 cells. We show that this mutation is a gain of function mutant in chicken cells; it disrupts prophase, results in a dramatic shortening of the mitotic chromosome axis, and leads to abnormal INCENP localization. Our results imply phosphorylation of CAP-D3 acts to limit condensin II binding onto mitotic chromosomes. We present the first in vivo example that alters the ratio of condensin I:II on mitotic chromosomes. Our results demonstrate this ratio is a critical determinant in shaping mitotic chromosomes. PMID:25605712

  7. A study of mitotic activity and the diurnal variation of the epithelial cells in wounded rectal mucous membrane.

    PubMed Central

    Reeve, D R

    1975-01-01

    Excision ulcers of the rectal mucous membrane were made in two groups of rats. One group was wounded at 09.00 hours and the second group at 21.00 hours. Mitotic counts were carried out in the glandular epithelium at the ulcer edges at 2 hour intervals over a period of 24 hours. Mitotic activity increased in 2-4 hours and thereafter showed a peak-and-trough pattern. The wounded rectal epithelial cells exhibited a diurnal variation with a peak of activity during the day and a low period of activity at night. It would seem unlikely that the adrenaline-chalone complex acts on the rectal epithelium, as this would entail maximal mitotic activity during periods of rest, when the circulating levels of adrenaline in the rat are at their lowest. The experiments clearly showed that the diurnal variation was not abolished by wounding. The increased mitotic activity occurred in the epithelial cells in the lower and mid thirds of the colonic glands; dividing cells were rarely seen in the top twenty cells or so of the glands, or in the surface epithelium. Mitotic activity was often lower in the first one or two glands at the immediate wound edge, which is difficult to explain by present theories of mitotic control. PMID:1133099

  8. Detection of subtle tectonic-geomorphic features in densely forested mountains by very high-resolution airborne LiDAR survey

    NASA Astrophysics Data System (ADS)

    Lin, Zhou; Kaneda, Heitaro; Mukoyama, Sakae; Asada, Norichika; Chiba, Tatsuro

    2013-01-01

    Despite successes elsewhere in the world, 2 m resolution DEMs from a standard airborne LiDAR survey failed to detect small tectonic-geomorphic features in densely-forested high-relief mountains of central Japan. Our new 0.5-m DEMs from an unprecedentedly high-resolution LiDAR survey along the Neodani Fault now reveal a number of previously unknown fault scarps as well as other hidden geomorphic features. The survey achieves a ground-return density of 6.2 m- 2 out of a total shot density of as much as ~ 12.7 m- 2. The main factor to gain sufficient ground returns in unfavorable conditions is a large side lap of ~ 70% between flight swaths, which means that any specific area in the target zone is scanned three or more times from different angles. Evaluation of DEMs with resolution from 0.25 to 10 m assures that a 0.5m resolution LiDAR DEM is necessary for the detection of subtle tectonic breaks. Another key factor for complete detection of small tectonic-geomorphic features is the application of a recently developed DEM visualization "Red Relief Image Map (RRIM)", which allows mapping of all the small features with various sizes, orientations and morphology, overcoming major drawbacks of classic DEM visualizations. A very high-resolution LiDAR survey aided with RRIM visualization as used in this study provides a more reliable approach for the detailed mapping of slight active fault traces hidden under dense vegetation.

  9. Same but different: 9-month-old infants at average and high risk for autism look at the same facial features but process them using different brain mechanisms.

    PubMed

    Key, Alexandra P F; Stone, Wendy L

    2012-08-01

    The study examined whether 9-month-old infants at average vs. high risk for autism spectrum disorder (ASD) process facial features (eyes, mouth) differently and whether such differences are related to infants' social and communicative skills. Eye tracking and visual event-related potentials (ERPs) were recorded in 35 infants (20 average-risk typical infants, 15 high-risk siblings of children with ASD) while they viewed photographs of a smiling unfamiliar female face. On 30% of the trials, the eyes or the mouth of that face was replaced with corresponding features from a different female. There were no group differences in the number, duration, or distribution of fixations, and all infants looked at the eyes and mouth regions equally. However, increased attention to the mouth was associated with weaker receptive communication skills and increased attention to the eyes correlated with better interpersonal skills. ERP results revealed that all infants detected eye and mouth changes but did so using different brain mechanisms. Changes in facial features were associated with changes in activity of the face perception mechanisms (N290) for the average-risk group but not for the high-risk infants. For all infants, correlations between ERP and eye-tracking measures indicated that larger and faster ERPs to feature changes were associated with fewer fixations on the irrelevant regions of stimuli. The size and latency of the ERP responses also correlated with parental reports of receptive and expressive communication skills, suggesting that differences in brain processing of human faces are associated with individual differences in social-communicative behaviors. PMID:22674669

  10. The cytologic features of sinonasal undifferentiated carcinoma and olfactory neuroblastoma.

    PubMed

    Bellizzi, Andrew M; Bourne, T David; Mills, Stacey E; Stelow, Edward B

    2008-03-01

    Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal tract. Olfactory neuroblastoma (ONB) is an uncommon neuroectodermal tumor of the superior nasal cavity. Upon examining these lesions, a broad differential diagnosis of poorly differentiated round cell tumors must be considered. The cytologic features of SNUC and ONB have been rarely reported. We searched our cytology files for cases of SNUC and ONB and assessed the following: cellularity, architecture, cytoplasm, cell size, nuclear contours, nucleoli, chromatin, anisonucleosis/anisocytosis, mitotic activity, background, and nuclear crush. Seven cases of SNUC produced hypercellular smears with a single-cell-predominant pattern. Cells were intermediate-sized with irregular nuclear contours and small nucleoli. Nuclear crush and mitotic figures were noted. The background exhibited naked nuclei and karyorrhectic debris. Of 7 cases, 6 (86%) exhibited vacuoles or extracellular lumina. The 10 cases of ONB exhibited cellularity, cellular arrangement, and chromatin similar to SNUC. In contrast, ONBs demonstrated fibrillary cytoplasm and smooth nuclear contours; mitotic figures were generally absent. Homer Wright rosettes were encountered in 9 cases (90%). We believe that in the appropriate clinical context, a specific cytologic diagnosis should be possible. PMID:18285258

  11. Multiscale analysis of geomorphological and geological features in high resolution digital elevation models using the wavelet transform

    Microsoft Academic Search

    Michael Kalbermatten; Dimitri Van De Ville; Pascal Turberg; Devis Tuia; Stéphane Joost

    At the end of the 1990s the emergence of high resolution (1m) digital elevation models (DEMs) settled the context of high precision geomorphological analysis. These new elevation models permitted to reveal structures that remained heretofore undetectable. Earth scientists henceforth benefit from a source of data with a textural detail that was never attained before. Despite its richness, this information must

  12. Design Features of a Mitotic Spindle: Balancing Tension and Compression at a Single Microtubule Kinetochore Interface in Budding Yeast

    PubMed Central

    Bouck, David C.; Joglekar, Ajit P.; Bloom, Kerry S.

    2010-01-01

    Accurate segregation of duplicated chromosomes ensures that daughter cells get one and only one copy of each chromosome. Errors in chromosome segregation result in aneuploidy and have severe consequences on human health. Incorrect chromosome number and chromosomal instability are hallmarks of tumor cells. Hence, segregation errors are thought to be a major cause of tumorigenesis. A study of the physical mechanical basis of chromosome segregation is essential to understand the processes that can lead to errors. Tremendous progress has been made in recent years in identifying the proteins necessary for chromosome movement and segregation, but the mechanism and structure of critical force generating components and the molecular basis of centromere stiffness remain poorly understood. PMID:18680435

  13. Using high resolution IKONOS imagery and feature-based classifiers to automate a classification of savanna woodlands 

    E-print Network

    Michelakis, Dimitrios

    2008-12-05

    High resolution remote sensing imagery offers one possible means to discriminate the constituent land cover components within savanna woodlands, with differing economic potential and ability to sequester carbon. Recent work on tropical savannas...

  14. The plant-specific family of DNA-binding proteins containing three HMG-box domains interacts with mitotic and meiotic chromosomes.

    PubMed

    Pedersen, Dorthe S; Coppens, Frederik; Ma, Lu; Antosch, Martin; Marktl, Barbara; Merkle, Thomas; Beemster, Gerrit T S; Houben, Andreas; Grasser, Klaus D

    2011-11-01

    • The high mobility group (HMG)-box represents a DNA-binding domain that is found in various eukaryotic DNA-interacting proteins. Proteins that contain three copies of the HMG-box domain, termed 3 × HMG-box proteins, appear to be specific to plants. The Arabidopsis genome encodes two 3 × HMG-box proteins that were studied here. • DNA interactions were examined using electrophoretic mobility shift assays, whereas expression, subcellular localization and chromosome association were mainly analysed by different types of fluorescence microscopy. • The 3 × HMG-box proteins bind structure specifically to DNA, display DNA bending activity and, in addition to the three HMG-box domains, the basic N-terminal domain contributes to DNA binding. The expression of the two Arabidopsis genes encoding 3 × HMG-box proteins is linked to cell proliferation. In synchronized cells, expression is cell cycle dependent and peaks in cells undergoing mitosis. 3 × HMG-box proteins are excluded from the nuclei of interphase cells and localize to the cytosol, but, during mitosis, they associate with condensed chromosomes. The 3 × HMG-box2 protein generally associates with mitotic chromosomes, while 3 × HMG-box1 is detected specifically at 45S rDNA loci. • In addition to mitotic chromosomes the 3 × HMG-box proteins associate with meiotic chromosomes, suggesting that they are involved in a general process of chromosome function related to cell division, such as chromosome condensation and/or segregation. PMID:21781122

  15. Quantitative in vivo analysis of chromatin binding of Polycomb and Trithorax group proteins reveals retention of ASH1 on mitotic chromatin

    PubMed Central

    Steffen, Philipp A.; Fonseca, Joăo Pedro; Gänger, Cornelia; Dworschak, Eva; Kockmann, Tobias; Beisel, Christian; Ringrose, Leonie

    2013-01-01

    The Polycomb (PcG) and Trithorax (TrxG) group proteins work antagonistically on several hundred developmentally important target genes, giving stable mitotic memory, but also allowing flexibility of gene expression states. How this is achieved in quantitative terms is poorly understood. Here, we present a quantitative kinetic analysis in living Drosophila of the PcG proteins Enhancer of Zeste, (E(Z)), Pleiohomeotic (PHO) and Polycomb (PC) and the TrxG protein absent, small or homeotic discs 1 (ASH1). Fluorescence recovery after photobleaching and fluorescence correlation spectroscopy reveal highly dynamic chromatin binding behaviour for all proteins, with exchange occurring within seconds. We show that although the PcG proteins substantially dissociate from mitotic chromatin, ASH1 remains robustly associated with chromatin throughout mitosis. Finally, we show that chromatin binding by ASH1 and PC switches from an antagonistic relationship in interphase, to a cooperative one during mitosis. These results provide quantitative insights into PcG and TrxG chromatin-binding dynamics and have implications for our understanding of the molecular nature of epigenetic memory. PMID:23580551

  16. Identification and characterization of INMAP, a novel interphase nucleus and mitotic apparatus protein that is involved in spindle formation and cell cycle progression

    SciTech Connect

    Shen, Enzhi; Lei, Yan; Liu, Qian [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China)] [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China); Zheng, Yanbo [The Institute of Medical Biotechnology (IMB) of the Chinese Academy of Medical Sciences, Beijing 100050 (China)] [The Institute of Medical Biotechnology (IMB) of the Chinese Academy of Medical Sciences, Beijing 100050 (China); Song, Chunqing [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China)] [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China); Marc, Jan [School of Biological Sciences, University of Sydney, Sydney 2006 (Australia)] [School of Biological Sciences, University of Sydney, Sydney 2006 (Australia); Wang, Yongchao [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China)] [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China); Sun, Le [AbMax Biotechnology Co., Haidian, Beijing 100085 (China)] [AbMax Biotechnology Co., Haidian, Beijing 100085 (China); Liang, Qianjin, E-mail: Liangqianjin0059@163.com [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China) [Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875 (China); College of Life Sciences, Beijing Normal University, Beijing Key Laboratory, Beijing 100875 (China)

    2009-04-15

    A novel protein that associates with interphase nucleus and mitotic apparatus (INMAP) was identified by screening HeLa cDNA expression library with an autoimmune serum followed by tandem mass spectrometry. Its complete cDNA sequence of 1.818 kb encodes 343 amino acids with predicted molecular mass of 38.2 kDa and numerous phosphorylation sites. The sequence is identical with nucleotides 1-1800 bp of an unnamed gene (GenBank accession no. (7022388)) and highly homologous with the 3'-terminal sequence of POLR3B. A monoclonal antibody against INMAP reacted with similar proteins in S. cerevisiae, Mel and HeLa cells, suggesting that it is a conserved protein. Confocal microscopy using either GFP-INMAP fusion protein or labeling with the monoclonal antibody revealed that the protein localizes as distinct dots in the interphase nucleus, but during mitosis associates closely with the spindle. Double immunolabeling using specific antibodies showed that the INMAP co-localizes with {alpha}-tubulin, {gamma}-tubulin, and NuMA. INMAP also co-immunoprecipitated with these proteins in their native state. Stable overexpression of INMAP in HeLa cell lines leads to defects in the spindle, mitotic arrest, formation of polycentrosomal and multinuclear cells, inhibition of growth, and apoptosis. We propose that INMAP is a novel protein that plays essential role in spindle formation and cell-cycle progression.

  17. The conserved histone deacetylase Rpd3 and its DNA binding subunit Ume6 control dynamic transcript architecture during mitotic growth and meiotic development

    PubMed Central

    Lardenois, Aurélie; Stuparevic, Igor; Liu, Yuchen; Law, Michael J.; Becker, Emmanuelle; Smagulova, Fatima; Waern, Karl; Guilleux, Marie-Hélčne; Horecka, Joe; Chu, Angela; Kervarrec, Christine; Strich, Randy; Snyder, Mike; Davis, Ronald W.; Steinmetz, Lars M.; Primig, Michael

    2015-01-01

    It was recently reported that the sizes of many mRNAs change when budding yeast cells exit mitosis and enter the meiotic differentiation pathway. These differences were attributed to length variations of their untranslated regions. The function of UTRs in protein translation is well established. However, the mechanism controlling the expression of distinct transcript isoforms during mitotic growth and meiotic development is unknown. In this study, we order developmentally regulated transcript isoforms according to their expression at specific stages during meiosis and gametogenesis, as compared to vegetative growth and starvation. We employ regulatory motif prediction, in vivo protein-DNA binding assays, genetic analyses and monitoring of epigenetic amino acid modification patterns to identify a novel role for Rpd3 and Ume6, two components of a histone deacetylase complex already known to repress early meiosis-specific genes in dividing cells, in mitotic repression of meiosis-specific transcript isoforms. Our findings classify developmental stage-specific early, middle and late meiotic transcript isoforms, and they point to a novel HDAC-dependent control mechanism for flexible transcript architecture during cell growth and differentiation. Since Rpd3 is highly conserved and ubiquitously expressed in many tissues, our results are likely relevant for development and disease in higher eukaryotes. PMID:25477386

  18. The Effect of Radiation Timing on Patients With High-Risk Features of Parameningeal Rhabdomyosarcoma: An Analysis of IRS-IV and D9803

    SciTech Connect

    Spalding, Aaron C., E-mail: Aaron.Spalding@nortonhealthcare.org [Kosair Children's Hospital and Brain Tumor Center, Louisville, Kentucky (United States); Hawkins, Douglas S. [Division of Hematology/Oncology, Seattle Children's Hospital, and Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Anderson, James R.; Lyden, Elizabeth [University of Nebraska Medical Center, Omaha, Nebraska (United States); Laurie, Fran [Quality Assurance Review Center, Providence, Rhode Island and Seattle, Washington (United States); Wolden, Suzanne L. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Arndt, Carola A.S. [Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2013-11-01

    Purpose: Radiation therapy remains an essential treatment for patients with parameningeal rhabdomyosarcoma (PMRMS), and early radiation therapy may improve local control for patients with intracranial extension (ICE). Methods and Materials: To address the role of radiation therapy timing in PMRMS in the current era, we reviewed the outcome from 2 recent clinical trials for intermediate-risk RMS: Intergroup Rhabdomyosarcoma Study (IRS)-IV and Children's Oncology Group (COG) D9803. The PMRMS patients on IRS-IV with any high-risk features (cranial nerve palsy [CNP], cranial base bony erosion [CBBE], or ICE) were treated immediately at day 0, and PMRMS patients without any of these 3 features received week 6-9 radiation therapy. The D9803 PMRMS patients with ICE received day 0 X-Ray Therapy (XRT) as well; however, those with either CNP or CBBE had XRT at week 12. Results: Compared with the 198 PMRMS patients from IRS-IV, the 192 PMRMS patients from D9803 had no difference (P<.05) in 5-year local failure (19% vs 19%), failure-free-survival (70% vs 67%), or overall survival (75% vs 73%) in aggregate. The 5-year local failure rates by subset did not differ when patients were classified as having no risk features (None, 15% vs 19%, P=.25), cranial nerve palsy/cranial base of skull erosion (CNP/CBBE, 15% vs 28%, P=.22), or intracranial extension (ICE, 21% vs 15%, P=.27). The D9083 patients were more likely to have received initial staging by magnetic resonance imaging (71% vs 53%). Conclusions: These data support that a delay in radiation therapy for high-risk PMRMS features of CNP/CBBE does not compromise clinical outcomes.

  19. High-strength lightweight concrete mixtures based on hollow microspheres: technological features and industrial experience of preparation

    NASA Astrophysics Data System (ADS)

    Inozemtcev, A. S.

    2015-01-01

    The research results concerning dependencies between technological parameters and physical properties of structural lightweight concrete are presented in the article. High-strength lightweight concrete has unique performance characteristics: low average density (less than 1500 kg/m3) and high compressive strength (more than 70 MPa). Hollow alumina-silicate microspheres with nanoscale modifier are used for obtaining these properties. It is shown in the article that the preparation of high-strength lightweight concrete in industrial conditions must be implemented using a turbine mixer having six paddles and engine power more than 39.2 kW. Oscillation frequency of more than 3000 rpm, vibro-compacting time less than 15 seconds, heat-humid treatment temperature approximately 60-65 °C and heat-humid treatment time 6-7 hours are optimal for production. The results of industrial mixing-test are presented.

  20. Bisubstrate inhibitor approach for targeting mitotic kinase haspin.

    PubMed

    Kestav, Katrin; Lavogina, Darja; Raidaru, Gerda; Chaikuad, Apirat; Knapp, Stefan; Uri, Asko

    2015-02-18

    During the past decade, the basophilic atypical kinase Haspin has emerged as a key player in mitosis responsible for phosphorylation of Thr3 residue of histone H3. Here, we report the construction of conjugates comprising an aromatic fragment targeted to the ATP-site of Haspin and a peptide mimicking the N-terminus of histone H3. The combination of effective solid phase synthesis procedures and a high throughput binding/displacement assay with fluorescence anisotropy readout afforded the development of inhibitors with remarkable subnanomolar affinity toward Haspin. The selectivity profiles of novel conjugates were established by affinity studies with a model basophilic kinase (catalytic subunit of cAMP-dependent protein kinase) and by a commercial 1-point inhibition assay with 43 protein kinases. PMID:25595038