53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

Science.gov (United States)

Fong, Chii Shyang; Mazo, Gregory; Das, Tuhin; Goodman, Joshua; Kim, Minhee; O'Rourke, Brian P; Izquierdo, Denisse; Tsou, Meng-Fu Bryan

2016-07-02

Mitosis occurs efficiently, but when it is disturbed or delayed, p53-dependent cell death or senescence is often triggered after mitotic exit. To characterize this process, we conducted CRISPR-mediated loss-of-function screens using a cell-based assay in which mitosis is consistently disturbed by centrosome loss. We identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo. Moreover, 53BP1 can transduce prolonged mitosis to cell cycle arrest independently of the spindle assembly checkpoint (SAC), suggesting that while SAC protects mitotic accuracy by slowing down mitosis, 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency.

Relocalization of human chromatin remodeling cofactor TIP48 in mitosis

International Nuclear Information System (INIS)

Sigala, Barbara; Edwards, Mina; Puri, Teena; Tsaneva, Irina R.

2005-01-01

TIP48 is a highly conserved eukaryotic AAA + protein which is an essential cofactor for several complexes involved in chromatin acetylation and remodeling, transcriptional and developmental regulation and nucleolar organization and trafficking. We show that TIP48 abundance in HeLa cells did not change during the cell cycle, nor did its distribution in various biochemical fractions. However, we observed distinct changes in the subcellular localization of TIP48 during M phase using immunofluorescence microscopy. Our studies demonstrate that in interphase cells TIP48 was found mainly in the nucleus and exhibited a distinct localization in the nuclear periphery. As the cells entered mitosis, TIP48 was excluded from the condensing chromosomes but showed association with the mitotic apparatus. During anaphase, some TIP48 was detected in the centrosome colocalizing with tubulin but the strongest staining appeared in the mitotic equator associated with the midzone central spindle. Accumulation of TIP48 in the midzone and the midbody was observed in late telophase and cytokinesis. This redeployment of TIP48 during anaphase and cytokinesis was independent of microtubule assembly. The relocation of endogenous TIP48 to the midzone/midbody under physiological conditions suggests a novel and distinct function for TIP48 in mitosis and possible involvement in the exit of mitosis

Polo-like kinase 1 inhibits DNA damage response during mitosis.

Science.gov (United States)

Benada, Jan; Burdová, Kamila; Lidak, Tomáš; von Morgen, Patrick; Macurek, Libor

2015-01-01

In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage response (DDR) pathway that coordinates DNA repair and progression through the cell cycle. Extensive modification of the chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are required for homologous recombination and non-homologous end joining, respectively. Whereas mechanisms of DDR are relatively well understood in interphase cells, comparatively less is known about organization of DDR during mitosis. Although ATM can be activated in mitotic cells, 53BP1 is not recruited to the chromatin until cells exit mitosis. Here we report mitotic phosphorylation of 53BP1 by Plk1 and Cdk1 that impairs the ability of 53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage. Phosphorylation of 53BP1 at S1618 occurs at kinetochores and in cytosol and is restricted to mitotic cells. Interaction between 53BP1 and Plk1 depends on the activity of Cdk1. We propose that activity of Cdk1 and Plk1 allows spatiotemporally controlled suppression of 53BP1 function during mitosis.

DeepMitosis: Mitosis detection via deep detection, verification and segmentation networks.

Science.gov (United States)

Li, Chao; Wang, Xinggang; Liu, Wenyu; Latecki, Longin Jan

2018-04-01

Mitotic count is a critical predictor of tumor aggressiveness in the breast cancer diagnosis. Nowadays mitosis counting is mainly performed by pathologists manually, which is extremely arduous and time-consuming. In this paper, we propose an accurate method for detecting the mitotic cells from histopathological slides using a novel multi-stage deep learning framework. Our method consists of a deep segmentation network for generating mitosis region when only a weak label is given (i.e., only the centroid pixel of mitosis is annotated), an elaborately designed deep detection network for localizing mitosis by using contextual region information, and a deep verification network for improving detection accuracy by removing false positives. We validate the proposed deep learning method on two widely used Mitosis Detection in Breast Cancer Histological Images (MITOSIS) datasets. Experimental results show that we can achieve the highest F-score on the MITOSIS dataset from ICPR 2012 grand challenge merely using the deep detection network. For the ICPR 2014 MITOSIS dataset that only provides the centroid location of mitosis, we employ the segmentation model to estimate the bounding box annotation for training the deep detection network. We also apply the verification model to eliminate some false positives produced from the detection model. By fusing scores of the detection and verification models, we achieve the state-of-the-art results. Moreover, our method is very fast with GPU computing, which makes it feasible for clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.

Science.gov (United States)

Douglas, Pauline; Ye, Ruiqiong; Morrice, Nicholas; Britton, Sébastien; Trinkle-Mulcahy, Laura; Lees-Miller, Susan P

2015-08-01

Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis

DEFF Research Database (Denmark)

Lukas, C; Kramer, E R; Peters, J M

2000-01-01

, in Saccharomyces cerevisiae and Drosophila spp., triggers exit from mitosis and during G(1) prevents unscheduled DNA replication. In this study we investigated the importance of periodic oscillation of the APC-Cdh1 activity for the cell cycle progression in human cells. We show that conditional interference...

Movie Mitosis

Science.gov (United States)

Bogiages, Christopher; Hitt, Austin M.

2008-01-01

Mitosis and meiosis are essential for the growth, development, and reproduction of organisms. Because these processes are essential to life, both are emphasized in biology texts, state standards, and the National Science Education Standards. In this article, the authors present their methodology for teaching mitosis by having students produce…

INPP5E Preserves Genomic Stability through Regulation of Mitosis.

Science.gov (United States)

Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

2017-03-15

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

Presenting Mitosis

Science.gov (United States)

Roche, Stephanie; Sterling, Donna R.

2005-01-01

When the topic of cell division is introduced in the classroom, students can showcase their interpretations of the stages of mitosis by creating a slide show illustrating prophase, metaphase, anaphase, and telophase (see samples in Figure 1). With the help of a computer, they can create a model of mitosis that will help them distinguish the…

Calcium and Mitosis

Science.gov (United States)

Hepler, P.

1983-01-01

Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

Phospho-Bcl-xL(Ser62) influences spindle assembly and chromosome segregation during mitosis.

Science.gov (United States)

Wang, Jianfang; Beauchemin, Myriam; Bertrand, Richard

2014-01-01

Functional analysis of a series of phosphorylation mutants reveals that Bcl-xL(Ser62Ala) influences cell entry into anaphase and mitotic exit in taxol-exposed cells compared with cells expressing wild-type Bcl-xL or a series of other phosphorylation mutants, an effect that appears to be independent of its anti-apoptotic activity. During normal mitosis progression, Bcl-xL(Ser62) is strongly phosphorylated by PLK1 and MAPK14/SAPKp38α at the prometaphase, metaphase, and the anaphase boundaries, while it is de-phosphorylated at telophase and cytokinesis. Phospho-Bcl-xL(Ser62) localizes in centrosomes with γ-tubulin and in the mitotic cytosol with some spindle-assembly checkpoint signaling components, including PLK1, BubR1, and Mad2. In taxol- and nocodazole-exposed cells, phospho-Bcl-xL(Ser62) also binds to Cdc20- Mad2-, BubR1-, and Bub3-bound complexes, while Bcl-xL(Ser62Ala) does not. Silencing Bcl-xL expression and expressing the phosphorylation mutant Bcl-xL(Ser62Ala) lead to an increased number of cells harboring mitotic spindle defects including multipolar spindle, chromosome lagging and bridging, aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h. Together, the data indicate that during mitosis, Bcl-xL(Ser62) phosphorylation impacts on spindle assembly and chromosome segregation, influencing chromosome stability. Observations of mitotic cells harboring aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h were also made with cells expressing the phosphorylation mutant Bcl-xL(Ser49Ala) and dual mutant Bcl-xL(Ser49/62Ala).

Apoptosis and mitosis as prognostic factors in pathologically staged N1 nonsmall cell lung cancer

International Nuclear Information System (INIS)

Komaki, Ritsuko; Fujii, Takashi; Perkins, Penny; Ro, Jae Y.; Allen, Pamela K.; Mason, Kathryn A.; Mountain, Clifton F.; Milas, Luka

1996-01-01

Purpose: This study aimed to establish whether spontaneous apoptosis or mitosis has prognostic value among patients with pathologically staged N1 nonsmall cell lung carcinoma (NSCLC) treated with surgical resection with or without adjuvant therapy. Methods and Materials: Material from 173 patients who had resections between 1970 and 1988 was analyzed for apoptosis and mitosis. There were 128 men and 45 women, with a median age of 61 years. There were 86 squamous cell carcinomas (SQ), 73 adenocarcinomas (AC), 3 large-cell carcinomas (LC), 6 SQ-AC, and 5 unclassified. Patients were observed from 2 to 209 months (median 27). Actuarial methods were used to assess survival and freedom from distant metastasis. Results: In NSCLC, apoptosis was found to range from 0.2% to 2.8% (median 1.0%) and mitosis from 0 to 1.8% (median 0.4%). Tumors having higher levels of apoptosis also had higher levels of mitosis (p = 0.001). The values of neither apoptosis nor mitosis depended on size, location, differentiation of tumors, age, performance status, or weight loss of patients. However, the values of apoptosis depended on tumor histology in that high values (greater than or equal to the median) were more frequent in SQ (49%) than in AC/LC (29%) (p 0.01). The overall survival for NSCLC patients, which was 33% at 5 years, did not depend on the level of either apoptosis or mitosis. The 5-year survival of patients having SQ was higher (43%) than that of patients having AC/LC (21%) (p = 0.03). Patients with high apoptosis showed significantly better 5-year overall (p = 0.008) and DMF (p = 0.0012) survivals in the SQ group compared to the AC/LC group. High mitosis compared to low mitosis was a significantly better predictor for 5-year survival (62% vs. 29%, respectively) (p = 0.035) in the SQ. However, high mitosis was a significantly worse 5-year DMF survival predictor compared to low mitosis: 13% vs. 56%, respectively (p = 0.05) in AC/LC. In the multivariate models for AC/LC, mitosis

SnapShot: Phosphoregulation of Mitosis.

Science.gov (United States)

Burgess, Andrew; Vuong, Jenny; Rogers, Samuel; Malumbres, Marcos; O'Donoghue, Seán I

2017-06-15

During mitosis, a cell divides its duplicated genome into two identical daughter cells. This process must occur without errors to prevent proliferative diseases (e.g., cancer). A key mechanism controlling mitosis is the precise timing of more than 32,000 phosphorylation and dephosphorylation events by a network of kinases and counterbalancing phosphatases. The identity, magnitude, and temporal regulation of these events have emerged recently, largely from advances in mass spectrometry. Here, we show phosphoevents currently believed to be key regulators of mitosis. For an animated version of this SnapShot, please see http://www.cell.com/cell/enhanced/odonoghue2. Copyright © 2017. Published by Elsevier Inc.

The NIMA Kinase Is Required To Execute Stage-Specific Mitotic Functions after Initiation of Mitosis

Science.gov (United States)

Govindaraghavan, Meera; Lad, Alisha A.

2014-01-01

The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events. PMID:24186954

TopBP1-mediated DNA processing during mitosis.

Science.gov (United States)

Gallina, Irene; Christiansen, Signe Korbo; Pedersen, Rune Troelsgaard; Lisby, Michael; Oestergaard, Vibe H

2016-01-01

Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells. (1) Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases.

Effects of copper on mitosis

Energy Technology Data Exchange (ETDEWEB)

Kostal, L

1971-01-01

The author deals with the effects of copper on mitosis. He found that a Cu concentration of 1 mg per liter is very toxic and strongly inhibits the course of mitosis in Vicia fabia. The effects of 0.5 mg and 0.25 mg Cu concentrations per liter were similar but a much weaker character.

The SUMO Pathway in Mitosis.

Science.gov (United States)

Mukhopadhyay, Debaditya; Dasso, Mary

2017-01-01

Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.

Inhibition of Cell Division and DNA Replication Impair Mouse-Naïve Pluripotency Exit.

Science.gov (United States)

Waisman, Ariel; Vazquez Echegaray, Camila; Solari, Claudia; Cosentino, María Soledad; Martyn, Iain; Deglincerti, Alessia; Ozair, Mohammad Zeeshan; Ruzo, Albert; Barañao, Lino; Miriuka, Santiago; Brivanlou, Ali; Guberman, Alejandra

2017-09-01

The cell cycle has gained attention as a key determinant for cell fate decisions, but the contribution of DNA replication and mitosis in stem cell differentiation has not been extensively studied. To understand if these processes act as "windows of opportunity" for changes in cell identity, we established synchronized cultures of mouse embryonic stem cells as they exit the ground state of pluripotency. We show that initial transcriptional changes in this transition do not require passage through mitosis and that conversion to primed pluripotency is linked to lineage priming in the G1 phase. Importantly, we demonstrate that impairment of DNA replication severely blocks transcriptional switch to primed pluripotency, even in the absence of p53 activity induced by the DNA damage response. Our data suggest an important role for DNA replication during mouse embryonic stem cell differentiation, which could shed light on why pluripotent cells are only receptive to differentiation signals during G1, that is, before the S phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

PLK1 regulation of PCNT cleavage ensures fidelity of centriole separation during mitotic exit.

Science.gov (United States)

Kim, Jaeyoun; Lee, Kwanwoo; Rhee, Kunsoo

2015-12-09

Centrioles are duplicated and segregated in close link to the cell cycle. During mitosis, daughter centrioles are disengaged and eventually separated from mother centrioles. New daughter centrioles may be generated only after centriole separation. Therefore, centriole separation is considered a licensing step for centriole duplication. It was previously known that separase specifically cleaves pericentrin (PCNT) during mitotic exit. Here we report that PCNT has to be phosphorylated by PLK1 to be a suitable substrate of separase. Phospho-resistant mutants of PCNT are not cleaved by separase and eventually inhibit centriole separation. Furthermore, phospho-mimetic PCNT mutants rescue centriole separation even in the presence of a PLK1 inhibitor. On the basis on these results, we propose that PLK1 phosphorylation is a priming step for separase-mediated cleavage of PCNT and eventually for centriole separation. PLK1 phosphorylation of PCNT provides an additional layer of regulatory mechanism to ensure the fidelity of centriole separation during mitotic exit.

Mitosis.

Science.gov (United States)

Henderson, Paula

Cytology is the subject that is dealt with in this autoinstructional program. The process to be understood by secondary school students who are taking biology is mitosis. The material is presented to be adequate for achievers at the middle level. Knowledge of the structure of the DNA molecule and of the parts of the cell are considered as…

Regulation of mRNA translation during mitosis.

Science.gov (United States)

Tanenbaum, Marvin E; Stern-Ginossar, Noam; Weissman, Jonathan S; Vale, Ronald D

2015-08-25

Passage through mitosis is driven by precisely-timed changes in transcriptional regulation and protein degradation. However, the importance of translational regulation during mitosis remains poorly understood. Here, using ribosome profiling, we find both a global translational repression and identified ~200 mRNAs that undergo specific translational regulation at mitotic entry. In contrast, few changes in mRNA abundance are observed, indicating that regulation of translation is the primary mechanism of modulating protein expression during mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in mitosis are translationally repressed, rather than activated. One of the most pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase promoting complex (APC) which is degraded during mitosis. We show that full APC activation requires translational repression of Emi1 in addition to its degradation. These results identify gene-specific translational repression as a means of controlling the mitotic proteome, which may complement post-translational mechanisms for inactivating protein function.

Fresh WNT into the regulation of mitosis.

Science.gov (United States)

Stolz, Ailine; Bastians, Holger

2015-01-01

Canonical Wnt signaling triggering β-catenin-dependent gene expression contributes to cell cycle progression, in particular at the G1/S transition. Recently, however, it became clear that the cell cycle can also feed back on Wnt signaling at the G2/M transition. This is illustrated by the fact that mitosis-specific cyclin-dependent kinases can phosphorylate the Wnt co-receptor LRP6 to prime the pathway for incoming Wnt signals when cells enter mitosis. In addition, there is accumulating evidence that various Wnt pathway components might exert additional, Wnt-independent functions that are important for proper regulation of mitosis. The importance of Wnt pathways during mitosis was most recently enforced by the discovery of Wnt signaling contributing to the stabilization of proteins other than β-catenin, specifically at G2/M and during mitosis. This Wnt-mediated stabilization of proteins, now referred to as Wnt/STOP, might on one hand contribute to maintaining a critical cell size required for cell division and, on the other hand, for the faithful execution of mitosis itself. In fact, most recently we have shown that Wnt/STOP is required for ensuring proper microtubule dynamics within mitotic spindles, which is pivotal for accurate chromosome segregation and for the maintenance of euploidy.

Meiosis: An Overview of Key Differences from Mitosis

Science.gov (United States)

Ohkura, Hiroyuki

2015-01-01

Meiosis is the specialized cell division that generates gametes. In contrast to mitosis, molecular mechanisms and regulation of meiosis are much less understood. Meiosis shares mechanisms and regulation with mitosis in many aspects, but also has critical differences from mitosis. This review highlights these differences between meiosis and mitosis. Recent studies using various model systems revealed differences in a surprisingly wide range of aspects, including cell-cycle regulation, recombination, postrecombination events, spindle assembly, chromosome–spindle interaction, and chromosome segregation. Although a great degree of diversity can be found among organisms, meiosis-specific processes, and regulation are generally conserved. PMID:25605710

The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis.

Science.gov (United States)

Lee, Sun Joo; Rodriguez-Bravo, Veronica; Kim, Hyunjung; Datta, Sutirtha; Foley, Emily A

2017-05-15

PP2A comprising B56 regulatory subunit isoforms (PP2A B56 ) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2A B56 both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing APC/C (APC/C Cdc20 ), which is an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/C Cdc20 inhibitor formed at unattached kinetochores through SAC signaling. In contrast to this prediction, we show that depletion of B56 subunits does not increase the amount or stability of the MCC. Rather, delays in APC/C Cdc20 activation in B56-depleted cells correlate with impaired Cdc20 binding to APC/C. Stimulation of APC/C Cdc20 assembly does not require binding between PP2A B56 and BubR1, and thus this contribution of PP2A B56 towards mitotic exit is distinct from its functions at kinetochores. PP2A B56 associates with APC/C constitutively in a BubR1-independent manner. A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2A B56 , modulates APC/C Cdc20 assembly. These results elucidate the contributions of PP2A B56 towards completion of mitosis. © 2017. Published by The Company of Biologists Ltd.

Role-Playing Mitosis.

Science.gov (United States)

Wyn, Mark A.; Stegink, Steven J.

2000-01-01

Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

Kinases Involved in Both Autophagy and Mitosis.

Science.gov (United States)

Li, Zhiyuan; Zhang, Xin

2017-08-31

Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

Kinases Involved in Both Autophagy and Mitosis

Directory of Open Access Journals (Sweden)

Zhiyuan Li

2017-08-01

Full Text Available Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases, Aurora kinases, PLK-1 (polo-like kinase 1, BUB1 (budding uninhibited by benzimidazoles 1, MAPKs (mitogen-activated protein kinases, mTORC1 (mechanistic target of rapamycin complex 1, AMPK (AMP-activated protein kinase, PI3K (phosphoinositide-3 kinase and protein kinase B (AKT. By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

Live imaging of mitosis in the developing mouse embryonic cortex.

Science.gov (United States)

Pilaz, Louis-Jan; Silver, Debra L

2014-06-04

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixed brain sections. This protocol will describe in detail an approach for live imaging of mitosis in ex vivo embryonic brain slices. We will describe the critical steps for this procedure, which include: brain extraction, brain embedding, vibratome sectioning of brain slices, staining and culturing of slices, and time-lapse imaging. We will then demonstrate and describe in detail how to perform post-acquisition analysis of mitosis. We include representative results from this assay using the vital dye Syto11, transgenic mice (histone H2B-EGFP and centrin-EGFP), and in utero electroporation (mCherry-α-tubulin). We will discuss how this procedure can be best optimized and how it can be modified for study of genetic regulation of mitosis. Live imaging of mitosis in brain slices is a flexible approach to assess the impact of age, anatomy, and genetic perturbation in a controlled environment, and to generate a large amount of data with high temporal and spatial resolution. Hence this protocol will complement existing tools for analysis of neural progenitor mitosis.

Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins.

Science.gov (United States)

Ohta, Shinya; Kimura, Michiko; Takagi, Shunsuke; Toramoto, Iyo; Ishihama, Yasushi

2016-09-02

During mitosis, phosphorylation of chromosome-associated proteins is a key regulatory mechanism. Mass spectrometry has been successfully applied to determine the complete protein composition of mitotic chromosomes, but not to identify post-translational modifications. Here, we quantitatively compared the phosphoproteome of isolated mitotic chromosomes with that of chromosomes in nonsynchronized cells. We identified 4274 total phosphorylation sites and 350 mitosis-specific phosphorylation sites in mitotic chromosome-associated proteins. Significant mitosis-specific phosphorylation in centromere/kinetochore proteins was detected, although the chromosomal association of these proteins did not change throughout the cell cycle. This mitosis-specific phosphorylation might play a key role in regulation of mitosis. Further analysis revealed strong dependency of phosphorylation dynamics on kinase consensus patterns, thus linking the identified phosphorylation sites to known key mitotic kinases. Remarkably, chromosomal axial proteins such as non-SMC subunits of condensin, TopoIIα, and Kif4A, together with the chromosomal periphery protein Ki67 involved in the establishment of the mitotic chromosomal structure, demonstrated high phosphorylation during mitosis. These findings suggest a novel mechanism for regulation of chromosome restructuring in mitosis via protein phosphorylation. Our study generated a large quantitative database on protein phosphorylation in mitotic and nonmitotic chromosomes, thus providing insights into the dynamics of chromatin protein phosphorylation at mitosis onset.

Poly(ADP-ribosyl)ation is recognized by ECT2 during mitosis.

Science.gov (United States)

Li, Mo; Bian, Chunjing; Yu, Xiaochun

2014-01-01

Poly(ADP-ribosyl)ation is an unique posttranslational modification and required for spindle assembly and function during mitosis. However, the molecular mechanism of poly(ADP-ribose) (PAR) in mitosis remains elusive. Here, we show the evidence that PAR is recognized by ECT2, a key guanine nucleotide exchange factor in mitosis. The BRCT domain of ECT2 directly binds to PAR both in vitro and in vivo. We further found that α-tubulin is PARylated during mitosis. PARylation of α-tubulin is recognized by ECT2 and recruits ECT2 to mitotic spindle for completing mitosis. Taken together, our study reveals a novel mechanism by which PAR regulates mitosis.

Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex

OpenAIRE

Pilaz, Louis-Jan; Silver, Debra L.

2014-01-01

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixe...

Imaging Mitosis in the Moss Physcomitrella patens.

Science.gov (United States)

Yamada, Moé; Miki, Tomohiro; Goshima, Gohta

2016-01-01

At first glance, mitosis in plants looks quite different from that in animals. In fact, terrestrial plants have lost the centrosome during evolution, and the mitotic spindle is assembled independently of a strong microtubule organizing center. The phragmoplast is a plant-specific mitotic apparatus formed after anaphase, which expands centrifugally towards the cell cortex. However, the extent to which plant mitosis differs from that of animals at the level of the protein repertoire is uncertain, largely because of the difficulty in the identification and in vivo characterization of mitotic genes of plants. Here, we discuss protocols for mitosis imaging that can be combined with endogenous green fluorescent protein (GFP) tagging or conditional RNA interference (RNAi) in the moss Physcomitrella patens, which is an emergent model plant for cell and developmental biology. This system has potential for use in the high-throughput study of mitosis and other intracellular processes, as is being done with various animal cell lines.

Nucleocytoplasmic protein translocation during mitosis in the social amoebozoan Dictyostelium discoideum.

Science.gov (United States)

O'Day, Danton H; Budniak, Aldona

2015-02-01

Mitosis is a fundamental and essential life process. It underlies the duplication and survival of all cells and, as a result, all eukaryotic organisms. Since uncontrolled mitosis is a dreaded component of many cancers, a full understanding of the process is critical. Evolution has led to the existence of three types of mitosis: closed, open, and semi-open. The significance of these different mitotic species, how they can lead to a full understanding of the critical events that underlie the asexual duplication of all cells, and how they may generate new insights into controlling unregulated cell division remains to be determined. The eukaryotic microbe Dictyostelium discoideum has proved to be a valuable biomedical model organism. While it appears to utilize closed mitosis, a review of the literature suggests that it possesses a form of mitosis that lies in the middle between truly open and fully closed mitosis-it utilizes a form of semi-open mitosis. Here, the nucleocytoplasmic translocation patterns of the proteins that have been studied during mitosis in the social amoebozoan D. discoideum are detailed followed by a discussion of how some of them provide support for the hypothesis of semi-open mitosis. © 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.

Science.gov (United States)

Shirazi Fard, Shahrzad; Thyselius, Malin; All-Ericsson, Charlotta; Hallböök, Finn

2014-01-01

For proper development, cells need to coordinate proliferation and cell cycle-exit. This is mediated by a cascade of proteins making sure that each phase of the cell cycle is controlled before the initiation of the next. Retinal progenitor cells divide during the process of interkinetic nuclear migration, where they undergo S-phase on the basal side, followed by mitoses on the apical side of the neuroepithelium. The final cell cycle of chicken retinal horizontal cells (HCs) is an exception to this general cell cycle behavior. Lim1 expressing (+) horizontal progenitor cells (HPCs) have a heterogenic final cell cycle, with some cells undergoing a terminal mitosis on the basal side of the retina. The results in this study show that this terminal basal mitosis of Lim1+ HPCs is not dependent on Chk1/2 for its regulation compared to retinal cells undergoing interkinetic nuclear migration. Neither activating nor blocking Chk1 had an effect on the basal mitosis of Lim1+ HPCs. Furthermore, the Lim1+ HPCs were not sensitive to cisplatin-induced DNA damage and were able to continue into mitosis in the presence of γ-H2AX without activation of caspase-3. However, Nutlin3a-induced expression of p21 did reduce the mitoses, suggesting the presence of a functional p53/p21 response in HPCs. In contrast, the apical mitoses were blocked upon activation of either Chk1/2 or p21, indicating the importance of these proteins during the process of interkinetic nuclear migration. Inhibiting Cdk1 blocked M-phase transition both for apical and basal mitoses. This confirmed that the cyclin B1-Cdk1 complex was active and functional during the basal mitosis of Lim1+ HPCs. The regulation of the final cell cycle of Lim1+ HPCs is of particular interest since it has been shown that the HCs are able to sustain persistent DNA damage, remain in the cell cycle for an extended period of time and, consequently, survive for months.

Comparing Heterosexuals' and Gay Men/Lesbians' Responses to Relationship Problems and the Effects of Internalized Homophobia on Gay Men/Lesbians' Responses to Relationship Problems in Turkey.

Science.gov (United States)

Okutan, Nur; Buyuksahin Sunal, Ayda; Sakalli Ugurlu, Nuray

2017-01-01

The purpose of the present study was twofold: (1) to investigate the effects of sexual orientation (heterosexuals and gay men/lesbians) and gender difference on responses to romantic relationship problems (Exit, Voice, Loyalty, and Neglect [EVLN] responses) and of perceived partner's EVLN responses in Turkey, and (2) to examine whether internalized homophobia was associated with EVLN responses and perceived partner's EVLN responses for gay men and lesbians. Responses to Dissatisfaction Scale-Accommodation Instrument, Internalized Homophobia, and Demographics Information were administered to 187 participants (44 lesbians, 44 gay men, 53 heterosexual women, 46 heterosexual men).The MANCOVA results showed that men reported higher loyalty than women, whereas women presented more exit responses than men. Further, the interactions between gender and sexual orientation on the participants' EVLN responses and on the perceived partner's EVLN responses were significant. With respect to heterosexual women, heterosexual men displayed more loyalty responses. Lesbians had higher scores on loyalty than did heterosexual women. Lesbians also had higher scores on perceived partner's exit response than did heterosexual women and gay men. On the contrary, heterosexual women reported more perceived partner's voice response than lesbians. In addition, lesbians reported higher perceived partner's neglect responses than heterosexual women. Compared to heterosexual women, heterosexual men reported higher perceived partner's exit response. Finally, internalized homophobia was associated with destructive responses for both lesbians and gay men.

Tradescantia cytogenetic tests (root-tip mitosis, pollen mitosis, pollen mother-cell meiosis). A report of the US Environmental Protection Agency gene-tox program

Energy Technology Data Exchange (ETDEWEB)

Ma, T H

1982-01-01

3 kinds of cytogenetic tests for screening of environmental mutagens were established for Tradescantia, namely, root-tip mitosis, pollen mitosis, and pollen mother-cell meiosis (commonly referred to as the Tradescantia-micronucleus (Trad-MCN) test). All these tests are technically simple, inexpensive, and can yield reliable results in a relatively short time (36 to 72 h). The root-tip mitosis test is suitable only for liquid agents, while pollen mitosis is suitable for both liquid and gaseous agents. Pollen tube mitotic chromosomes are extremely sensitive to mutagens; therefore, they are good materials for detecting very low concentrations of mutagens. Both root-tip mitosis and pollen mitosis tests use chromosome and/or chromatid aberrations as end points for scoring. The Trad-MCN test is suitable for both liquid and gaseous agents. In addition, it is especially suitable for in situ monitoring of water and air pollutants. Of the 12 chemicals tested, 5-fluorouracil and 1,2-dibromoethane indicate that they are very potent mutagens based on the effective dosages used to produce a positive response. Sulfur dioxide, ethyl methanesulfonate, sodium azide, Phosdrin, and Bladex rank next in potency.

Exit selection strategy in pedestrian evacuation simulation with multi-exits

International Nuclear Information System (INIS)

Yue Hao; Zhang Bin-Ya; Shao Chun-Fu; Xing Yan

2014-01-01

A mixed strategy of the exit selection in a pedestrian evacuation simulation with multi-exits is constructed by fusing the distance-based and time-based strategies through a cognitive coefficient, in order to reduce the evacuation imbalance caused by the asymmetry of exits or pedestrian layout, to find a critical density to distinguish whether the strategy of exit selection takes effect or not, and to analyze the exit selection results with different cognitive coefficients. The strategy of exit selection is embedded in the computation of the shortest estimated distance in a dynamic parameter model, in which the concept of a jam area layer and the procedure of step-by-step expending are introduced. Simulation results indicate the characteristics of evacuation time gradually varying against cognitive coefficient and the effectiveness of reducing evacuation imbalance caused by the asymmetry of pedestrian or exit layout. It is found that there is a critical density to distinguish whether a pedestrian jam occurs in the evacuation and whether an exit selection strategy is in effect. It is also shown that the strategy of exit selection has no effect on the evacuation process in the no-effect phase with a low density, and that evacuation time and exit selection are dependent on the cognitive coefficient and pedestrian initial density in the in-effect phase with a high density. (general)

Students as "Humans Chromosomes" in Role-Playing Mitosis and Meiosis

Science.gov (United States)

Chinnici, Joseph P.; Yue, Joyce W.; Torres, Kieron M.

2004-01-01

Students often find it challenging to understand mitosis and meiosis and determine their processes. To develop an easier way to understand these terms, students are asked to role-play mitosis and meiosis and students themselves act as human chromosomes, which help students to learn differences between mitosis and meiosis.

Genome accessibility is widely preserved and locally modulated during mitosis.

Science.gov (United States)

Hsiung, Chris C-S; Morrissey, Christapher S; Udugama, Maheshi; Frank, Christopher L; Keller, Cheryl A; Baek, Songjoon; Giardine, Belinda; Crawford, Gregory E; Sung, Myong-Hee; Hardison, Ross C; Blobel, Gerd A

2015-02-01

Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements. © 2015 Hsiung et al.; Published by

Promyelocytic leukemia bodies tether to early endosomes during mitosis.

Science.gov (United States)

Palibrk, Vuk; Lång, Emma; Lång, Anna; Schink, Kay Oliver; Rowe, Alexander D; Bøe, Stig Ove

2014-01-01

During mitosis the nuclear envelope breaks down, leading to potential interactions between cytoplasmic and nuclear components. PML bodies are nuclear structures with tumor suppressor and antiviral functions. Early endosomes, on the other hand, are cytoplasmic vesicles involved in transport and growth factor signaling. Here we demonstrate that PML bodies form stable interactions with early endosomes immediately following entry into mitosis. The 2 compartments remain stably associated throughout mitosis and dissociate in the cytoplasm of newly divided daughter cells. We also show that a minor subset of PML bodies becomes anchored to the mitotic spindle poles during cell division. The study demonstrates a stable mitosis-specific interaction between a cytoplasmic and a nuclear compartment.

Deciphering the evolutionary history of open and closed mitosis.

Science.gov (United States)

Sazer, Shelley; Lynch, Michael; Needleman, Daniel

2014-11-17

The origin of the nucleus at the prokaryote-to-eukaryote transition represents one of the most important events in the evolution of cellular organization. The nuclear envelope encircles the chromosomes in interphase and is a selectively permeable barrier between the nucleoplasm and cytoplasm and an organizational scaffold for the nucleus. It remains intact in the 'closed' mitosis of some yeasts, but loses its integrity in the 'open' mitosis of mammals. Instances of both types of mitosis within two evolutionary clades indicate multiple evolutionary transitions between open and closed mitosis, although the underlying genetic changes that influenced these transitions remain unknown. A survey of the diversity of mitotic nuclei that fall between these extremes is the starting point from which to determine the physiologically relevant characteristics distinguishing open from closed mitosis and to understand how they evolved and why they are retained in present-day organisms. The field is now poised to begin addressing these issues by defining and documenting patterns of mitotic nuclear variation within and among species and mapping them onto a phylogenic tree. Deciphering the evolutionary history of open and closed mitosis will complement cell biological and genetic approaches aimed at deciphering the fundamental organizational principles of the nucleus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rescue from replication stress during mitosis.

Science.gov (United States)

Fragkos, Michalis; Naim, Valeria

2017-04-03

Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

Automated mitosis detection using texture, SIFT features and HMAX biologically inspired approach.

Science.gov (United States)

Irshad, Humayun; Jalali, Sepehr; Roux, Ludovic; Racoceanu, Daniel; Hwee, Lim Joo; Naour, Gilles Le; Capron, Frédérique

2013-01-01

According to Nottingham grading system, mitosis count in breast cancer histopathology is one of three components required for cancer grading and prognosis. Manual counting of mitosis is tedious and subject to considerable inter- and intra-reader variations. The aim is to investigate the various texture features and Hierarchical Model and X (HMAX) biologically inspired approach for mitosis detection using machine-learning techniques. We propose an approach that assists pathologists in automated mitosis detection and counting. The proposed method, which is based on the most favorable texture features combination, examines the separability between different channels of color space. Blue-ratio channel provides more discriminative information for mitosis detection in histopathological images. Co-occurrence features, run-length features, and Scale-invariant feature transform (SIFT) features were extracted and used in the classification of mitosis. Finally, a classification is performed to put the candidate patch either in the mitosis class or in the non-mitosis class. Three different classifiers have been evaluated: Decision tree, linear kernel Support Vector Machine (SVM), and non-linear kernel SVM. We also evaluate the performance of the proposed framework using the modified biologically inspired model of HMAX and compare the results with other feature extraction methods such as dense SIFT. The proposed method has been tested on Mitosis detection in breast cancer histological images (MITOS) dataset provided for an International Conference on Pattern Recognition (ICPR) 2012 contest. The proposed framework achieved 76% recall, 75% precision and 76% F-measure. Different frameworks for classification have been evaluated for mitosis detection. In future work, instead of regions, we intend to compute features on the results of mitosis contour segmentation and use them to improve detection and classification rate.

Automated mitosis detection using texture, SIFT features and HMAX biologically inspired approach

Directory of Open Access Journals (Sweden)

Humayun Irshad

2013-01-01

Full Text Available Context: According to Nottingham grading system, mitosis count in breast cancer histopathology is one of three components required for cancer grading and prognosis. Manual counting of mitosis is tedious and subject to considerable inter- and intra-reader variations. Aims: The aim is to investigate the various texture features and Hierarchical Model and X (HMAX biologically inspired approach for mitosis detection using machine-learning techniques. Materials and Methods: We propose an approach that assists pathologists in automated mitosis detection and counting. The proposed method, which is based on the most favorable texture features combination, examines the separability between different channels of color space. Blue-ratio channel provides more discriminative information for mitosis detection in histopathological images. Co-occurrence features, run-length features, and Scale-invariant feature transform (SIFT features were extracted and used in the classification of mitosis. Finally, a classification is performed to put the candidate patch either in the mitosis class or in the non-mitosis class. Three different classifiers have been evaluated: Decision tree, linear kernel Support Vector Machine (SVM, and non-linear kernel SVM. We also evaluate the performance of the proposed framework using the modified biologically inspired model of HMAX and compare the results with other feature extraction methods such as dense SIFT. Results: The proposed method has been tested on Mitosis detection in breast cancer histological images (MITOS dataset provided for an International Conference on Pattern Recognition (ICPR 2012 contest. The proposed framework achieved 76% recall, 75% precision and 76% F-measure. Conclusions: Different frameworks for classification have been evaluated for mitosis detection. In future work, instead of regions, we intend to compute features on the results of mitosis contour segmentation and use them to improve detection and

Linking abnormal mitosis to the acquisition of DNA damage

Science.gov (United States)

Pellman, David

2012-01-01

Cellular defects that impair the fidelity of mitosis promote chromosome missegregation and aneuploidy. Increasing evidence reveals that errors in mitosis can also promote the direct and indirect acquisition of DNA damage and chromosome breaks. Consequently, deregulated cell division can devastate the integrity of the normal genome and unleash a variety of oncogenic stimuli that may promote transformation. Recent work has shed light on the mechanisms that link abnormal mitosis with the development of DNA damage, how cells respond to such affronts, and the potential impact on tumorigenesis. PMID:23229895

Mitosis-associated repression in development.

Science.gov (United States)

Esposito, Emilia; Lim, Bomyi; Guessous, Ghita; Falahati, Hanieh; Levine, Michael

2016-07-01

Transcriptional repression is a pervasive feature of animal development. Here, we employ live-imaging methods to visualize the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm of early Drosophila embryos. Snail target enhancers were attached to an MS2 reporter gene, permitting detection of nascent transcripts in living embryos. The transgenes exhibit initially broad patterns of transcription but are refined by repression in the mesoderm following mitosis. These observations reveal a correlation between mitotic silencing and Snail repression. We propose that mitosis and other inherent discontinuities in transcription boost the activities of sequence-specific repressors, such as Snail. © 2016 Esposito et al.; Published by Cold Spring Harbor Laboratory Press.

Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis

OpenAIRE

En-Ju Chou; Liang-Yi Hung; Chieh-Ju C. Tang; Wen-Bin Hsu; Hsin-Yi Wu; Pao-Chi Liao; Tang K. Tang

2016-01-01

CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. In...

Exit from contract

Directory of Open Access Journals (Sweden)

Oren Bar-Gill

2016-01-01

Full Text Available Objective to study the procedure of exiting the contract its costs and benefits. Methods statistical method comparative analysis. Results free exit from contract is one of the most powerful tools for the consumer rights protection. The procedure frees consumers from bad deals and keeps businesses honest. Yet consumers often choose transactions with lockin provisions trading off exit rights for other perks. This article examines the costs and benefits of free exit as compared to the lockin alternative. According to the authors the present regulation of exit penalties in the USA is poorly tailored to address concerns about lockin particularly in light of increasingly ubiquitous marketbased solutions. The article also calls regulatory attention to loyalty rewards which are shown to be as powerful as exit penalties and equally detrimental. Scientific novelty the article reveals a paradoxical state of the law exit regulations in the USA are used most where they are needed least. Termination penalties present an obvishyous target for regulatory intervention while loyalty programs seem benign not warranting any regulatory attention. Practical significance the article is of interest for the Russian juridical science and lawmaking authorities as in Russia the issue of exiting the contract is as topical as in the USA and requires solution which would impair neither the rights of consumers nor the rights of the sellers ofnbspproducts and services. nbsp

Mitosis-specific phosphorylation of PML at T409 regulates spindle checkpoint.

Science.gov (United States)

Jin, J; Liu, J

2016-08-31

During mitosis, Promyelocytic leukemia nuclear bodies (PML NBs) change dramatically in morphology and composition, but little is known about function of PML in mitosis. Here, we show that PML is phosphorylated at T409 (PML p409) in a mitosis-specific manner. More importantly, PML p409 contributes to maintain the duration of pro-metaphase and regulates spindle checkpoint. Deficient PML p409 caused a shortening of pro-metaphase and challenged the nocodazole-triggered mitotic arrest. T409A mutation led to a higher frequency of misaligned chromosomes on metaphase plate, and subsequently death in late mitosis. In addition, inhibition of PML p409 repressed growth of tumor cells, suggesting that PML p409 is a potential target for cancer therapy. Collectively, our study demonstrated an important phosphorylated site of PML, which contributed to explore the role of PML in mitosis.

Exit-strategies

DEFF Research Database (Denmark)

Mørck, Line Lerche; Palm, Anne-Mette; Sys Møller-Andersen, Camilla

different empirical sources. To develop and extend an "exit-prototype" about conditions of importance for moving beyond a gang/criminal position, we have analyzed documents (from newspapers and books), involved ex-gang members, social workers and experts as co-researchers in interviews, "gang......This paper is about exit-strategies, constructing a theoretical and empirical informed analysis of current societal conditions that influence motor cycle gangs such as Hells Angels or Bandidos and other ‘wild' youth' possibilities and limitations for moving beyond criminal activities. We especially...... focus on the involved communities in the current Danish gang-conflict, which escalated with deadly killings in 2008, and thereby became a so called "gang-war". We will start out presenting different practice notions of exit, and we will extend and discuss understandings of "exit-strategies" by analyzing...

Regulatory functional territory of PLK-1 and their substrates beyond mitosis.

Science.gov (United States)

Kumar, Shiv; Sharma, Garima; Chakraborty, Chiranjib; Sharma, Ashish Ranjan; Kim, Jaebong

2017-06-06

Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly associated with poor prognosis and cancer progression, it is one of the most extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell cycle events, such as spindle pole maturation, chromosome segregation and cytokinesis. However, studies have demonstrated that the role of PLK-1 is not only restricted to mitosis, but PLK-1 can also regulate other vital events beyond mitosis, including transcription, translation, ciliogenesis, checkpoint adaptation and recovery, apoptosis, chromosomes dynamics etc. Recent reviews have tried to define the regulatory role of PLK-1 during mitosis progression and tumorigenesis, but its' functional role beyond mitosis is still largely unexplored. PLK-1 can regulate the activity of many proteins that work outside of its conventional territory. The dysregulation of these proteins can cause diseases such as Alzheimer's disease, tumorigenesis etc. and may also lead to drug resistance. Thus, in this review, we discussed the versatile role of PLK-1 and tried to collect data to validate its' functional role in cell cycle regulation apart from mitosis.

A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition.

Science.gov (United States)

Hsiung, Chris C-S; Bartman, Caroline R; Huang, Peng; Ginart, Paul; Stonestrom, Aaron J; Keller, Cheryl A; Face, Carolyne; Jahn, Kristen S; Evans, Perry; Sankaranarayanan, Laavanya; Giardine, Belinda; Hardison, Ross C; Raj, Arjun; Blobel, Gerd A

2016-06-15

During mitosis, RNA polymerase II (Pol II) and many transcription factors dissociate from chromatin, and transcription ceases globally. Transcription is known to restart in bulk by telophase, but whether de novo transcription at the mitosis-G1 transition is in any way distinct from later in interphase remains unknown. We tracked Pol II occupancy genome-wide in mammalian cells progressing from mitosis through late G1. Unexpectedly, during the earliest rounds of transcription at the mitosis-G1 transition, ∼50% of active genes and distal enhancers exhibit a spike in transcription, exceeding levels observed later in G1 phase. Enhancer-promoter chromatin contacts are depleted during mitosis and restored rapidly upon G1 entry but do not spike. Of the chromatin-associated features examined, histone H3 Lys27 acetylation levels at individual loci in mitosis best predict the mitosis-G1 transcriptional spike. Single-molecule RNA imaging supports that the mitosis-G1 transcriptional spike can constitute the maximum transcriptional activity per DNA copy throughout the cell division cycle. The transcriptional spike occurs heterogeneously and propagates to cell-to-cell differences in mature mRNA expression. Our results raise the possibility that passage through the mitosis-G1 transition might predispose cells to diverge in gene expression states. © 2016 Hsiung et al.; Published by Cold Spring Harbor Laboratory Press.

The role of model organisms in the history of mitosis research.

Science.gov (United States)

Yanagida, Mitsuhiro

2014-09-02

Mitosis is a cell-cycle stage during which condensed chromosomes migrate to the middle of the cell and segregate into two daughter nuclei before cytokinesis (cell division) with the aid of a dynamic mitotic spindle. The history of mitosis research is quite long, commencing well before the discovery of DNA as the repository of genetic information. However, great and rapid progress has been made since the introduction of recombinant DNA technology and discovery of universal cell-cycle control. A large number of conserved eukaryotic genes required for the progression from early to late mitotic stages have been discovered, confirming that DNA replication and mitosis are the two main events in the cell-division cycle. In this article, a historical overview of mitosis is given, emphasizing the importance of diverse model organisms that have been used to solve fundamental questions about mitosis. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

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

Science.gov (United States)

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

2014-11-01

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

Action of mercury in plant mitosis II

Energy Technology Data Exchange (ETDEWEB)

Lorente, R

1972-01-01

The cytological abnormalities induced by mercurochrome on mitosis and meiosis of Allium cepa are studied and the capacity of the chemical agent to induce c-mitosis is shown. Inhibition of the cytokinetic process as well as alterations of the nucleoli and pollen-mother cells (from pachytene to division II) have also been observed. These cytological effects may be ascribed to the affinity of the mercurial compounds for the thyolic groups existing in the nucleoproteins and protoplasmic proteins, with the subsequent inhibitory effect on the enzymatic mechanisms.

Foci of cyclin A2 interact with actin and RhoA in mitosis.

Science.gov (United States)

Loukil, Abdelhalim; Izard, Fanny; Georgieva, Mariya; Mashayekhan, Shaereh; Blanchard, Jean-Marie; Parmeggiani, Andrea; Peter, Marion

2016-06-09

Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis depends primarily on the ubiquitin-proteasome system (UPS), while autophagy also contributes. However, a fraction of cyclin A2 persists beyond metaphase. In this work, we focus on cyclin A2-rich foci detected in mitosis by high resolution imaging and analyse their movements. We demonstrate that cyclin A2 interacts with actin and RhoA during mitosis, and that cyclin A2 depletion induces a dramatic decrease in active RhoA in mitosis. Our data suggest cyclin A2 participation in RhoA activation in late mitosis.

Exit Prostitution

DEFF Research Database (Denmark)

Henriksen, Theresa Dyrvig; Aslaug Kjær, Agnete; Christensen, Gunvor

2015-01-01

Dette midtvejsnotat omhandler projektet ”Exit prostitution”. Exit-projektet blev påbegyndt i april 2012 og løber til udgangen af 2015 og befinder sig i øjeblikket midtvejs i projektets afprøvningsfase. I projektet anvendes metoden Critical Time Intervention (CTI), der er en evidensbaseret...... til det. Exit-projektet er dermed en central socialpolitisk indsats overfor borgere i prostitution i det danske samfund. I dette notat belyser vi midtvejsresultater for, hvordan udviklingen er for de borgere, der er nået halvt igennem et CTI-forløb. I den afsluttende evaluering af projektet i 2015 vil...

Characterization of mitosis-specific phosphorylation of tumor-associated microtubule-associated protein.

Science.gov (United States)

Hong, Kyung Uk; Kim, Hyun-Jun; Bae, Chang-Dae; Park, Joobae

2009-11-30

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also plays an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one of the mitosis-specific phosphorylation residues (i.e., Thr-622). However, the phosphorylation events at the remaining mitotic phosphorylation sites of TMAP have not been fully characterized in detail. Here, we report on generation and characterization of phosphorylated Thr-578- and phosphorylated Thr-596-specific antibodies. Using the antibodies, we show that phosphorylation of TMAP at Thr-578 and Thr-596 indeed occurs specifically during mitosis. Immunofluorescent staining using the antibodies shows that these residues become phosphorylated starting at prophase and then become rapidly dephosphorylated soon after initiation of anaphase. Subtle differences in the kinetics of phosphorylation between Thr-578 and Thr-596 imply that they may be under different mechanisms of phosphorylation during mitosis. Unlike the phosphorylation-deficient mutant form for Thr-622, the mutant in which both Thr-578 and Thr-596 had been mutated to alanines did not induce significant delay in progression of mitosis. These results show that the majority of mitosis-specific phosphorylation of TMAP is limited to pre-anaphase stages and suggest that the multiple phosphorylation may not act in concert but serve diverse functions.

Autophagic flux is highly active in early mitosis and differentially regulated throughout the cell cycle.

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Li, Zhiyuan; Ji, Xinmiao; Wang, Dongmei; Liu, Juanjuan; Zhang, Xin

2016-06-28

Mitosis is a fast process that involves dramatic cellular remodeling and has a high energy demand. Whether autophagy is active or inactive during the early stages of mitosis in a naturally dividing cell is still debated. Here we aimed to use multiple assays to resolve this apparent discrepancy. Although the LC3 puncta number was reduced in mitosis, the four different cell lines we tested all have active autophagic flux in both interphase and mitosis. In addition, the autophagic flux was highly active in nocodazole-induced, double-thymidine synchronization released as well as naturally occurring mitosis in HeLa cells. Multiple autophagy proteins are upregulated in mitosis and the increased Beclin-1 level likely contributes to the active autophagic flux in early mitosis. It is interesting that although the autophagic flux is active throughout the cell cycle, early mitosis and S phase have relatively higher autophagic flux than G1 and late G2 phases, which might be helpful to degrade the damaged organelles and provide energy during S phase and mitosis.

The Functional Role of TopBP1 in DNA Maintenance at Mitosis

DEFF Research Database (Denmark)

Pedersen, Rune Troelsgaard

When cells traverse mitosis, genome integrity of the emerging daughter cells is dependent on replication of the entire genome during the preceding S-phase and accurate chromosome segregation in mitosis. Replication stress may cause cells to enter mitosis with underreplicated loci, consisting...... can lead to anaphase bridges that impair accurate chromosome segregation. The recent decade featured many advances in our understanding of how cells cope with underreplicated loci in mitosis. A major advance was the description of ultra-fine anaphase bridges (UFBs), a class of anaphase bridges...... established Saccharomyces cerevisiae as a model organism to study anaphase bridges, and we identified Dpb11/TopBP1 as a novel UFB-associated protein in yeast and avian DT40 cells, respectively. TopBP1 localized to confined areas on replication-stress induced UFBs. Upon onset of mitosis we observed a burst...

Aurora-A regulates MCRS1 function during mitosis.

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Meunier, Sylvain; Timón, Krystal; Vernos, Isabelle

2016-07-02

The mitotic spindle is made of microtubules (MTs) nucleated through different pathways involving the centrosomes, the chromosomes or the walls of pre-existing MTs. MCRS1 is a RanGTP target that specifically associates with the chromosome-driven MTs protecting them from MT depolymerases. MCRS1 is also needed for the control of kinetochore fiber (K-fiber) MT minus-ends dynamics in metaphase. Here, we investigated the regulation of MCRS1 activity in M-phase. We show that MCRS1 is phosphorylated by the Aurora-A kinase in mitosis on Ser35/36. Although this phosphorylation has no role on MCRS1 localization to chromosomal MTs and K-fiber minus-ends, we show that it regulates MCRS1 activity in mitosis. We conclude that Aurora-A activity is particularly important in the tuning of K-fiber minus-ends dynamics in mitosis.

Using a Case-Study Article to Effectively Introduce Mitosis

Science.gov (United States)

Van Hoewyk, Doug

2007-01-01

Community college students in a nonmajors biology class are introduced to mitosis by reading a case-study article that allows them to gauge how many times various parts of their bodies have been regenerated. The case-study article allows students to develop a conceptual framework of the cell cycle prior to a lecture on mitosis. (Contains 1 figure.)

ERK5 pathway regulates the phosphorylation of tumour suppressor hDlg during mitosis

Energy Technology Data Exchange (ETDEWEB)

Inesta-Vaquera, Francisco A. [Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia-CSIC, Campus de Cantoblanco-UAM, 28049 Madrid (Spain); Campbell, David G.; Arthur, J. Simon C. [MRC Protein Phosphorylation Unit, Sir James Black Building, School of Life Sciences, University of Dundee, Dundee DD1 5EH (United Kingdom); Cuenda, Ana, E-mail: acuenda@cnb.csic.es [Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia-CSIC, Campus de Cantoblanco-UAM, 28049 Madrid (Spain)

2010-08-13

Research highlights: {yields} hDlg is phosphorylated during mitosis in multiple residues. {yields} Prospho-hDlg is excluded from the midbody during mitosis. {yields} hDlg is not phosphorylated by p38{gamma} or JNK1/2 during mitosis. {yields} ERK5 pathway mediates hDlg phosphorylation in mitosis. -- Abstract: Human disc-large (hDlg) is a scaffold protein critical for the maintenance of cell polarity and adhesion. hDlg is thought to be a tumour suppressor that regulates the cell cycle and proliferation. However, the mechanism and pathways involved in hDlg regulation during these processes is still unclear. Here we report that hDlg is phosphorylated during mitosis, and we establish the identity of at least three residues phosphorylated in hDlg; some are previously unreported. Phosphorylation affects hDlg localisation excluding it from the contact point between the two daughter cells. Our results reveal a previously unreported pathway for hDlg phosphorylation in mitosis and show that ERK5 pathway mediates hDlg cell cycle dependent phosphorylation. This is likely to have important implications in the correct timely mitotic entry and mitosis progression.

ERK5 pathway regulates the phosphorylation of tumour suppressor hDlg during mitosis

International Nuclear Information System (INIS)

Inesta-Vaquera, Francisco A.; Campbell, David G.; Arthur, J. Simon C.; Cuenda, Ana

2010-01-01

Research highlights: → hDlg is phosphorylated during mitosis in multiple residues. → Prospho-hDlg is excluded from the midbody during mitosis. → hDlg is not phosphorylated by p38γ or JNK1/2 during mitosis. → ERK5 pathway mediates hDlg phosphorylation in mitosis. -- Abstract: Human disc-large (hDlg) is a scaffold protein critical for the maintenance of cell polarity and adhesion. hDlg is thought to be a tumour suppressor that regulates the cell cycle and proliferation. However, the mechanism and pathways involved in hDlg regulation during these processes is still unclear. Here we report that hDlg is phosphorylated during mitosis, and we establish the identity of at least three residues phosphorylated in hDlg; some are previously unreported. Phosphorylation affects hDlg localisation excluding it from the contact point between the two daughter cells. Our results reveal a previously unreported pathway for hDlg phosphorylation in mitosis and show that ERK5 pathway mediates hDlg cell cycle dependent phosphorylation. This is likely to have important implications in the correct timely mitotic entry and mitosis progression.

Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events.

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Araujo, Ana Rita; Gelens, Lendert; Sheriff, Rahuman S M; Santos, Silvia D M

2016-10-20

Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Bora and Aurora-A continue to activate Plk1 in mitosis.

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Bruinsma, Wytse; Macurek, Libor; Freire, Raimundo; Lindqvist, Arne; Medema, René H

2014-02-15

Polo-like kinase-1 (Plk1) is required for proper cell division. Activation of Plk1 requires phosphorylation on a conserved threonine in the T-loop of the kinase domain (T210). Plk1 is first phosphorylated on T210 in G2 phase by the kinase Aurora-A, in concert with its cofactor Bora. However, Bora was shown to be degraded prior to entry into mitosis, and it is currently unclear how Plk1 activity is sustained in mitosis. Here we show that the Bora-Aurora-A complex remains the major activator of Plk1 in mitosis. We show that a small amount of Aurora-A activity is sufficient to phosphorylate and activate Plk1 in mitosis. In addition, a fraction of Bora is retained in mitosis, which is essential for continued Aurora-A-dependent T210 phosphorylation of Plk1. We find that once Plk1 is activated, minimal amounts of the Bora-Aurora-A complex are sufficient to sustain Plk1 activity. Thus, the activation of Plk1 by Aurora-A may function as a bistable switch; highly sensitive to inhibition of Aurora-A in its initial activation, but refractory to fluctuations in Aurora-A activity once Plk1 is fully activated. This provides a cell with robust Plk1 activity once it has committed to mitosis.

The Biochemistry of Mitosis

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Wieser, Samuel; Pines, Jonathon

2015-01-01

In this article, we will discuss the biochemistry of mitosis in eukaryotic cells. We will focus on conserved principles that, importantly, are adapted to the biology of the organism. It is vital to bear in mind that the structural requirements for division in a rapidly dividing syncytial Drosophila embryo, for example, are markedly different from those in a unicellular yeast cell. Nevertheless, division in both systems is driven by conserved modules of antagonistic protein kinases and phosphatases, underpinned by ubiquitin-mediated proteolysis, which create molecular switches to drive each stage of division forward. These conserved control modules combine with the self-organizing properties of the subcellular architecture to meet the specific needs of the cell. Our discussion will draw on discoveries in several model systems that have been important in the long history of research on mitosis, and we will try to point out those principles that appear to apply to all cells, compared with those in which the biochemistry has been specifically adapted in a particular organism. PMID:25663668

Cancer: Mitosis Run Amok

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Science Scope, 2005

2005-01-01

Virtually every student knows someone who has battled cancer. It is a topic that is of great interest to many students because of their personal connection to the subject. Mitosis is an important topic in a middle school unit on cells and cell processes (National Science Standards, Grades 5?8: Life Sciences: Content Standard C). Studying cancer…

Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

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Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

2016-01-06

Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. Copyright © 2016 Elsevier Inc. All rights reserved.

Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

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Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

2015-03-01

Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1.

Science.gov (United States)

Lee, Seung Baek; Kim, Jung Jin; Nam, Hyun-Ja; Gao, Bowen; Yin, Ping; Qin, Bo; Yi, Sang-Yeop; Ham, Hyoungjun; Evans, Debra; Kim, Sun-Hyun; Zhang, Jun; Deng, Min; Liu, Tongzheng; Zhang, Haoxing; Billadeau, Daniel D; Wang, Liewei; Giaime, Emilie; Shen, Jie; Pang, Yuan-Ping; Jen, Jin; van Deursen, Jan M; Lou, Zhenkun

2015-10-01

Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. We demonstrate that ordered progression through mitosis is orchestrated by two distinct E3 ligases through the shared use of Cdc20 and Cdh1. Furthermore, Parkin is phosphorylated and activated by polo-like kinase 1 (Plk1) during mitosis. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. These results suggest that the Parkin-Cdc20/Cdh1 complex is an important regulator of mitosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative proteomics of mitosis and meiosis in Saccharomyces cerevisiae.

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Kumar, Ravinder; Dhali, Snigdha; Srikanth, Rapole; Ghosh, Santanu Kumar; Srivastava, Sanjeeva

2014-09-23

Precise and timely segregation of genetic material and conservation of ploidy are the two foremost requirements for survival of a eukaryotic organism. Two highly regulated cell division processes, namely mitosis and meiosis are central to achieve this objective. The modes of chromosome segregation are distinct in these two processes that generate progeny cells of equal ploidy and half the ploidy in mitosis and meiosis, respectively. Additionally, the nutritional requirement and intracellular processing of biological cue also differ in these two processes. From this, it can be envisaged that proteome of mitotic and meiotic cells will differ significantly. Therefore, identification of proteins that differ in their level of expression between mitosis and meiosis would further reveal the mechanistic detail of these processes. In the present study, we have investigated the protein expression profile of mitosis and meiosis by comparing proteome of budding yeast cultures arrested at mitotic metaphase and metaphase-I of meiosis using proteomic approach. Approximately 1000 and 2000 protein spots were visualized on 2-DE and 2D-DIGE gels respectively, out of which 14 protein spots were significant in 2-DE and 22 in 2D-DIGE (pmitosis, an up-regulation of actin cytoskeleton and its negative regulator occurs in meiosis. Mitosis and meiosis are two different types of cell division cycles with entirely different outcomes with definite biological implication for almost all eukaryotic species. In this work, we investigated, for the first time, the differential proteomic profile of Saccharomyces cerevisiae culture arrested at mitotic metaphase (M) and metaphase-I (MI) of meiosis using 2-DE and 2D-DIGE. Our findings of up-regulation of actin and its negative regulator cofilin during meiosis suggest that the rate of actin cytoskeleton turnover is more in meiosis and actin cytoskeleton may play more crucial role during meiosis compared to mitosis. Present study also suggests that actin

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

Science.gov (United States)

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

2017-01-01

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

Maximized Inter-Class Weighted Mean for Fast and Accurate Mitosis Cells Detection in Breast Cancer Histopathology Images.

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Nateghi, Ramin; Danyali, Habibollah; Helfroush, Mohammad Sadegh

2017-08-14

Based on the Nottingham criteria, the number of mitosis cells in histopathological slides is an important factor in diagnosis and grading of breast cancer. For manual grading of mitosis cells, histopathology slides of the tissue are examined by pathologists at 40× magnification for each patient. This task is very difficult and time-consuming even for experts. In this paper, a fully automated method is presented for accurate detection of mitosis cells in histopathology slide images. First a method based on maximum-likelihood is employed for segmentation and extraction of mitosis cell. Then a novel Maximized Inter-class Weighted Mean (MIWM) method is proposed that aims at reducing the number of extracted non-mitosis candidates that results in reducing the false positive mitosis detection rate. Finally, segmented candidates are classified into mitosis and non-mitosis classes by using a support vector machine (SVM) classifier. Experimental results demonstrate a significant improvement in accuracy of mitosis cells detection in different grades of breast cancer histopathological images.

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

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Wang, Yi-Long; Chen, Hui; Zhan, Yi-Qun; Yin, Rong-Hua; Li, Chang-Yan; Ge, Chang-Hui; Yu, Miao; Yang, Xiao-Ming

2016-08-17

EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

Resumption of mitosis in frozen-thawed embryos is not related to the chromosomal constitution

DEFF Research Database (Denmark)

Agerholm, Inge E; Kølvrå, Steen; Crüger, Dorthe G

2007-01-01

OBJECTIVE: To study the relation between the resumption of mitosis after thaw and chromosomal constitution in frozen-thawed embryos. In addition, to evaluate the correlation among the three parameters of resumption of mitosis after thaw, postthaw blastomere loss, and multinucleation. DESIGN: Frozen......(S): Forty IVF and/or intracytoplasmic sperm injection patients. INTERVENTION(S): Embryo thawing, morphological evaluation, and fluorescence in situ hybridization analysis for aneuploidy screening. MAIN OUTCOME MEASURE(S): Resumption of mitosis, blastomere loss, multinucleation, and chromosome enumeration....... RESULT(S): No difference was observed in the chromosomal constitution of embryos with and without resumption of mitosis. Neither was the postthaw blastomere loss connected to the chromosomal constitution. The resumption of mitosis was not associated with postthaw loss of blastomeres...

Phosphorylation of p37 is important for Golgi disassembly at mitosis

International Nuclear Information System (INIS)

Kaneko, Yayoi; Tamura, Kaori; Totsukawa, Go; Kondo, Hisao

2010-01-01

Research highlights: → p37 is phosphorylated on Serine-56 and Threonine-59 by Cdc2 at mitosis. → Phosphorylated p37 does not bind to Golgi membranes. → p37 phosphorylation inhibits p97/p37-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled at 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 by Cdc2 results in mitotic inhibition of the p97/p47 pathway . In this study, we demonstrate that p37 is phosphorylated on Serine-56 and Threonine-59 by Cdc2 at mitosis, and this phosphorylated p37 does not bind to Golgi membranes. Using an in vitro Golgi reassembly assay, we show that mutated p37(S56D, T59D), which mimics mitotic phosphorylation, does not cause any cisternal regrowth, indicating that p37 phosphorylation inhibits the p97/p37 pathway. Our results demonstrate that p37 phosphorylation on Serine-56 and Threonine-59 is important for Golgi disassembly at mitosis.

Monitoring the elasticity changes of HeLa cells during mitosis by atomic force microscopy

Science.gov (United States)

Jiang, Ningcheng; Wang, Yuhua; Zeng, Jinshu; Ding, Xuemei; Xie, Shusen; Yang, Hongqin

2016-10-01

Cell mitosis plays a crucial role in cell life activity, which is one of the important phases in cell division cycle. During the mitosis, the cytoskeleton micro-structure of the cell changed and the biomechanical properties of the cell may vary depending upon different mitosis stages. In this study, the elasticity property of HeLa cells during mitosis was monitored by atomic force microscopy. Also, the actin filaments in different mitosis stages of the cells were observed by confocal imaging. Our results show that the cell in anaphase is stiffer than that in metaphase and telophase. Furthermore, lots of actin filaments gathered in cells' center area in anaphase, which contributes to the rigidity of the cell in this phase. Our findings demonstrate that the nano-biomechanics of living cells could provide a new index for characterizing cell physiological states.

Pathologic mitoses and pathology of mitosis in tumorigenesis

Directory of Open Access Journals (Sweden)

RG Steinbeck

2009-12-01

Full Text Available The gist of my hypothesis (.. is a certain abnormal chromatin constitution. Each process, which brings about this chromatin constitution, would result in the origin of a malignant tumour. Certainly, I consider irregularities with mitosis as the normal mode of the origin of an incorrectly assembled nucleus. This statement by Boveri (1914 has considered earlier observations of asymmetric divisions in human cancers (Hansemann, 1890. The hypothesis is based on the understanding of mitosis as an equational bipartition of the hereditary substance (Flemming, 1879; Roux, 1883. Latest since it was known that genes are located on chromosomes (Sturtevant, 1913, their balanced transport in anaphase appeared as a condition of correct somatic proliferation. True mitoses guarantee the constancy of terminally differentiated tissues. Politzer (1934 has performed X-ray experiments to investigate abnormal karyokinesis with regard to anomalous chromatin condensation, chromosome breakage, spindle malformation, and failure in cytokinesis. On the basis of light microscopy, further significant progress in understanding the pathology of mitosis was not possible. Tumour cases with reduced chromosome numbers seduced to the idea that mitotic activity is rather under cytoplasmic than under nuclear control (Koller, 1947.

29 CFR 1917.122 - Employee exits.

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2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Employee exits. 1917.122 Section 1917.122 Labor Regulations...) MARINE TERMINALS Terminal Facilities § 1917.122 Employee exits. (a) Employee exits shall be clearly marked. (b) If an employee exit is not visible from employees' work stations, directional signs...

p53 Dependent Centrosome Clustering Prevents Multipolar Mitosis in Tetraploid Cells

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Yi, Qiyi; Zhao, Xiaoyu; Huang, Yun; Ma, Tieliang; Zhang, Yingyin; Hou, Heli; Cooke, Howard J.; Yang, Da-Qing; Wu, Mian; Shi, Qinghua

2011-01-01

Background p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. Principal Findings Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2∼ 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53-/- tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53-/- tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53+/+ tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. Conclusions p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway. PMID:22076149

Mitosis Counting in Breast Cancer: Object-Level Interobserver Agreement and Comparison to an Automatic Method.

Science.gov (United States)

Veta, Mitko; van Diest, Paul J; Jiwa, Mehdi; Al-Janabi, Shaimaa; Pluim, Josien P W

2016-01-01

Tumor proliferation speed, most commonly assessed by counting of mitotic figures in histological slide preparations, is an important biomarker for breast cancer. Although mitosis counting is routinely performed by pathologists, it is a tedious and subjective task with poor reproducibility, particularly among non-experts. Inter- and intraobserver reproducibility of mitosis counting can be improved when a strict protocol is defined and followed. Previous studies have examined only the agreement in terms of the mitotic count or the mitotic activity score. Studies of the observer agreement at the level of individual objects, which can provide more insight into the procedure, have not been performed thus far. The development of automatic mitosis detection methods has received large interest in recent years. Automatic image analysis is viewed as a solution for the problem of subjectivity of mitosis counting by pathologists. In this paper we describe the results from an interobserver agreement study between three human observers and an automatic method, and make two unique contributions. For the first time, we present an analysis of the object-level interobserver agreement on mitosis counting. Furthermore, we train an automatic mitosis detection method that is robust with respect to staining appearance variability and compare it with the performance of expert observers on an "external" dataset, i.e. on histopathology images that originate from pathology labs other than the pathology lab that provided the training data for the automatic method. The object-level interobserver study revealed that pathologists often do not agree on individual objects, even if this is not reflected in the mitotic count. The disagreement is larger for objects from smaller size, which suggests that adding a size constraint in the mitosis counting protocol can improve reproducibility. The automatic mitosis detection method can perform mitosis counting in an unbiased way, with substantial

Testing of mitosis and meiosis in female and male gametes

Directory of Open Access Journals (Sweden)

L. F. Kurilo

2016-01-01

Full Text Available Method of quantitative evaluation of the immature germ cells, their pathology in mitosis and meiosis (in semen, embryo and fetal ovaries, of gonad biopsies or fragments of sectioned material is informative method and should be introduced into the clinical practice in andrology and gynecology and fundamental research. Quantitative analysis of mitosis and female meiosis development was initiated on experimental animals and fetal gonads from spontaneous or therapeutic abortions.

Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis

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En-Ju Chou

2016-03-01

Full Text Available CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. Interestingly, the dispersal of the PCM was effectively rescued by ectopic expression of wild-type CPAP or a phospho-mimic CPAP-S467D mutant, but not a non-phosphorylated CPAP-S467A mutant. Finally, we found that CPAP-S467D has a low affinity for microtubule binding but a high affinity for PCM proteins. Together, our results support a model wherein CPAP is required for proper mitotic progression, and phosphorylation of CPAP by Aurora-A is essential for maintaining spindle pole integrity.

A nutrient dependant switch explains mutually exclusive existence of meiosis and mitosis initiation in budding yeast.

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Wannige, C T; Kulasiri, D; Samarasinghe, S

2014-01-21

Nutrients from living environment are vital for the survival and growth of any organism. Budding yeast diploid cells decide to grow by mitosis type cell division or decide to create unique, stress resistant spores by meiosis type cell division depending on the available nutrient conditions. To gain a molecular systems level understanding of the nutrient dependant switching between meiosis and mitosis initiation in diploid cells of budding yeast, we develop a theoretical model based on ordinary differential equations (ODEs) including the mitosis initiator and its relations to budding yeast meiosis initiation network. Our model accurately and qualitatively predicts the experimentally revealed temporal variations of related proteins under different nutrient conditions as well as the diverse mutant studies related to meiosis and mitosis initiation. Using this model, we show how the meiosis and mitosis initiators form an all-or-none type bistable switch in response to available nutrient level (mainly nitrogen). The transitions to and from meiosis or mitosis initiation states occur via saddle node bifurcation. This bidirectional switch helps the optimal usage of available nutrients and explains the mutually exclusive existence of meiosis and mitosis pathways. © 2013 Elsevier Ltd. All rights reserved.

Quantitative comparison of a human cancer cell surface proteome between interphase and mitosis.

Science.gov (United States)

Özlü, Nurhan; Qureshi, Mohammad H; Toyoda, Yusuke; Renard, Bernhard Y; Mollaoglu, Gürkan; Özkan, Nazlı E; Bulbul, Selda; Poser, Ina; Timm, Wiebke; Hyman, Anthony A; Mitchison, Timothy J; Steen, Judith A

2015-01-13

The cell surface is the cellular compartment responsible for communication with the environment. The interior of mammalian cells undergoes dramatic reorganization when cells enter mitosis. These changes are triggered by activation of the CDK1 kinase and have been studied extensively. In contrast, very little is known of the cell surface changes during cell division. We undertook a quantitative proteomic comparison of cell surface-exposed proteins in human cancer cells that were tightly synchronized in mitosis or interphase. Six hundred and twenty-eight surface and surface-associated proteins in HeLa cells were identified; of these, 27 were significantly enriched at the cell surface in mitosis and 37 in interphase. Using imaging techniques, we confirmed the mitosis-selective cell surface localization of protocadherin PCDH7, a member of a family with anti-adhesive roles in embryos. We show that PCDH7 is required for development of full mitotic rounding pressure at the onset of mitosis. Our analysis provided basic information on how cell cycle progression affects the cell surface. It also provides potential pharmacodynamic biomarkers for anti-mitotic cancer chemotherapy. © 2014 The Authors.

How protein kinases co-ordinate mitosis in animal cells.

Science.gov (United States)

Ma, Hoi Tang; Poon, Randy Y C

2011-04-01

Mitosis is associated with profound changes in cell physiology and a spectacular surge in protein phosphorylation. To accomplish these, a remarkably large portion of the kinome is involved in the process. In the present review, we will focus on classic mitotic kinases, such as cyclin-dependent kinases, Polo-like kinases and Aurora kinases, as well as more recently characterized players such as NIMA (never in mitosis in Aspergillus nidulans)-related kinases, Greatwall and Haspin. Together, these kinases co-ordinate the proper timing and fidelity of processes including centrosomal functions, spindle assembly and microtubule-kinetochore attachment, as well as sister chromatid separation and cytokinesis. A recurrent theme of the mitotic kinase network is the prevalence of elaborated feedback loops that ensure bistable conditions. Sequential phosphorylation and priming phosphorylation on substrates are also frequently employed. Another important concept is the role of scaffolds, such as centrosomes for protein kinases during mitosis. Elucidating the entire repertoire of mitotic kinases, their functions, regulation and interactions is critical for our understanding of normal cell growth and in diseases such as cancers.

Mathematical imaging methods for mitosis analysis in live-cell phase contrast microscopy.

Science.gov (United States)

Grah, Joana Sarah; Harrington, Jennifer Alison; Koh, Siang Boon; Pike, Jeremy Andrew; Schreiner, Alexander; Burger, Martin; Schönlieb, Carola-Bibiane; Reichelt, Stefanie

2017-02-15

In this paper we propose a workflow to detect and track mitotic cells in time-lapse microscopy image sequences. In order to avoid the requirement for cell lines expressing fluorescent markers and the associated phototoxicity, phase contrast microscopy is often preferred over fluorescence microscopy in live-cell imaging. However, common specific image characteristics complicate image processing and impede use of standard methods. Nevertheless, automated analysis is desirable due to manual analysis being subjective, biased and extremely time-consuming for large data sets. Here, we present the following workflow based on mathematical imaging methods. In the first step, mitosis detection is performed by means of the circular Hough transform. The obtained circular contour subsequently serves as an initialisation for the tracking algorithm based on variational methods. It is sub-divided into two parts: in order to determine the beginning of the whole mitosis cycle, a backwards tracking procedure is performed. After that, the cell is tracked forwards in time until the end of mitosis. As a result, the average of mitosis duration and ratios of different cell fates (cell death, no division, division into two or more daughter cells) can be measured and statistics on cell morphologies can be obtained. All of the tools are featured in the user-friendly MATLAB®Graphical User Interface MitosisAnalyser. Copyright © 2017. Published by Elsevier Inc.

Exit Polls and Voter Turnout

DEFF Research Database (Denmark)

Andersen, Asger Lau; Jensen, Thomas

2014-01-01

After the 2009 referendum on a proposed change to the Danish Law of Succession, it was widely claimed that the early publication of exit poll results changed the rate of turnout and eventually the outcome. We investigate this claim and contribute to the wider debate on the implications of exit...... polls by setting up and analyzing a formal model. We find that the introduction of an exit poll influences the incentive to vote both before and after the poll is published, but the signs of the effects are generally ambiguous. The observation that exit polls influence the incentive to vote even before...

A minimal number of MELT repeats supports all functions of KNL1 in chromosome segregation

DEFF Research Database (Denmark)

Zhang, Gang; Lischetti, Tiziana; Nilsson, Jakob

2013-01-01

The Bub1-Bub3 and BubR1-Bub3 checkpoint complexes, or the Bubs, contribute to the accurate segregation of chromosomes during mitosis by promoting chromosome bi-orientation and halting exit from mitosis if this fails. The complexes associate with kinetochores during mitosis, which is required...

Tripolar mitosis in human cells and embryos: occurrence, pathophysiology and medical implications.

Science.gov (United States)

Kalatova, Beata; Jesenska, Renata; Hlinka, Daniel; Dudas, Marek

2015-01-01

Tripolar mitosis is a specific case of cell division driven by typical molecular mechanisms of mitosis, but resulting in three daughter cells instead of the usual count of two. Other variants of multipolar mitosis show even more mitotic poles and are relatively rare. In nature, this phenomenon was frequently observed or suspected in multiple common cancers, infected cells, the placenta, and in early human embryos with impaired pregnancy-yielding potential. Artificial causes include radiation and various toxins. Here we combine several pieces of the most recent evidence for the existence of different types of multipolar mitosis in preimplantation embryos together with a detailed review of the literature. The related molecular and cellular mechanisms are discussed, including the regulation of centriole duplication, mitotic spindle biology, centromere functions, cell cycle checkpoints, mitotic autocorrection mechanisms, and the related complicating factors in healthy and affected cells, including post-mitotic cell-cell fusion often associated with multipolar cell division. Clinical relevance for oncology and embryo selection in assisted reproduction is also briefly discussed in this context. Copyright © 2014 Elsevier GmbH. All rights reserved.

Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis.

Science.gov (United States)

Chou, En-Ju; Hung, Liang-Yi; Tang, Chieh-Ju C; Hsu, Wen-Bin; Wu, Hsin-Yi; Liao, Pao-Chi; Tang, Tang K

2016-03-29

CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. Interestingly, the dispersal of the PCM was effectively rescued by ectopic expression of wild-type CPAP or a phospho-mimic CPAP-S467D mutant, but not a non-phosphorylated CPAP-S467A mutant. Finally, we found that CPAP-S467D has a low affinity for microtubule binding but a high affinity for PCM proteins. Together, our results support a model wherein CPAP is required for proper mitotic progression, and phosphorylation of CPAP by Aurora-A is essential for maintaining spindle pole integrity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Characterization of mitosis-specific phosphorylation of tumor-associated microtubule-associated protein

OpenAIRE

Hong, Kyung Uk; Kim, Hyun-Jun; Bae, Chang-Dae; Park, Joobae

2009-01-01

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also plays an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one o...

EGF stimulates the activation of EGF receptors and the selective activation of major signaling pathways during mitosis.

Science.gov (United States)

Wee, Ping; Shi, Huaiping; Jiang, Jennifer; Wang, Yuluan; Wang, Zhixiang

2015-03-01

Mitosis and epidermal growth factor (EGF) receptor (EGFR) are both targets for cancer therapy. The role of EGFR signaling in mitosis has been rarely studied and poorly understood. The limited studies indicate that the activation of EGFR and downstream signaling pathways is mostly inhibited during mitosis. However, we recently showed that EGFR is phosphorylated in response to EGF stimulation in mitosis. Here we studied EGF-induced EGFR activation and the activation of major signaling pathways downstream of EGFR during mitosis. We showed that EGFR was strongly activated by EGF during mitosis as all the five major tyrosine residues including Y992, Y1045, Y1068, Y1086, and Y1173 were phosphorylated to a level similar to that in the interphase. We further showed that the activated EGFR is able to selectively activate some downstream signaling pathways while avoiding others. Activated EGFR is able to activate PI3K and AKT2, but not AKT1, which may be responsible for the observed effects of EGF against nocodazole-induced cell death. Activated EGFR is also able to activate c-Src, c-Cbl and PLC-γ1 during mitosis. However, activated EGFR is unable to activate ERK1/2 and their downstream substrates RSK and Elk-1. While it activated Ras, EGFR failed to fully activate Raf-1 in mitosis due to the lack of phosphorylation at Y341 and the lack of dephosphorylation at pS259. We conclude that contrary to the dogma, EGFR is activated by EGF during mitosis. Moreover, EGFR-mediated cell signaling is regulated differently from the interphase to specifically serve the needs of the cell in mitosis. Copyright © 2015 Elsevier Inc. All rights reserved.

The duration of mitosis and daughter cell size are modulated by nutrients in budding yeast.

Science.gov (United States)

Leitao, Ricardo M; Kellogg, Douglas R

2017-11-06

The size of nearly all cells is modulated by nutrients. Thus, cells growing in poor nutrients can be nearly half the size of cells in rich nutrients. In budding yeast, cell size is thought to be controlled almost entirely by a mechanism that delays cell cycle entry until sufficient growth has occurred in G1 phase. Here, we show that most growth of a new daughter cell occurs in mitosis. When the rate of growth is slowed by poor nutrients, the duration of mitosis is increased, which suggests that cells compensate for slow growth in mitosis by increasing the duration of growth. The amount of growth required to complete mitosis is reduced in poor nutrients, leading to a large reduction in cell size. Together, these observations suggest that mechanisms that control the extent of growth in mitosis play a major role in cell size control in budding yeast. © 2017 Leitao and Kellogg.

A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation.

Science.gov (United States)

Kabeche, Lilian; Nguyen, Hai Dang; Buisson, Rémi; Zou, Lee

2018-01-05

The ataxia telangiectasia mutated and Rad3-related (ATR) kinase is crucial for DNA damage and replication stress responses. Here, we describe an unexpected role of ATR in mitosis. Acute inhibition or degradation of ATR in mitosis induces whole-chromosome missegregation. The effect of ATR ablation is not due to altered cyclin-dependent kinase 1 (CDK1) activity, DNA damage responses, or unscheduled DNA synthesis but to loss of an ATR function at centromeres. In mitosis, ATR localizes to centromeres through Aurora A-regulated association with centromere protein F (CENP-F), allowing ATR to engage replication protein A (RPA)-coated centromeric R loops. As ATR is activated at centromeres, it stimulates Aurora B through Chk1, preventing formation of lagging chromosomes. Thus, a mitosis-specific and R loop-driven ATR pathway acts at centromeres to promote faithful chromosome segregation, revealing functions of R loops and ATR in suppressing chromosome instability. Copyright © 2018, American Association for the Advancement of Science.

The labor of a lifetime?: health and occupation type as predictors of workforce exit among older Australians.

Science.gov (United States)

McPhedran, Samara

2012-03-01

The structural aging of the population and withdrawal of older people from the labor force have become common themes within Western social policy discourse and have particular relevance to policy development around health and aging. The current study examines whether particular occupation types are associated with both poor health and an increased likelihood of labor force exit. Longitudinal data are used to examine workforce participation among older Australians (aged between 55 and 64, in 2002). Older workers in trades, labor, and production occupations, the majority of whom are men, have poorer general health than their counterparts in other occupations and are also the most likely to exit the workforce. These findings suggest that a number of older men in Australia (and, indeed, elsewhere) may face both poor health and limited employment opportunities in areas that match their abilities and experience. These individuals may experience a number of years out of the labor force, highlighting a role for targeted policies and programs.

Association of rheumatic diseases with early exit from paid employment in Portugal.

Science.gov (United States)

Laires, Pedro A; Gouveia, Miguel

2014-04-01

To examine the association between rheumatic diseases (RD) and other chronic morbidity with early exit from paid employment in the Portuguese population. The study population consisted of all people between 50 and 64 years of age (3,762 men and 4,241 women) who participated in the Portuguese National Health Survey, conducted in 2005/2006. Data were collected on demographics, ill-health, lifestyle, and socioeconomic factors. Logistic regression was used to estimate the isolated effect of rheumatic diseases and other chronic diseases on the likelihood of exit from paid employment. At the time of the survey, 45.1 % of the Portuguese population with ages between 50 and 64 years old were not employed. In the nonemployed population, 31.6 % self-reported "poor" to "very poor" health, whereas 16.4 % did so in the employed population. A larger average number of major chronic diseases per capita were also found in those not employed (1.9 vs. 1.4, p paid employment. In particular, rheumatic diseases were more prevalent (43.4 vs. 32.1 %) and associated with early exit from work (OR 1.31; CI 1.12-1.52, p = 0.001). This study suggests an association between RD and other major chronic diseases with early exit from paid employment in Portugal. Thus, health and social protection policies should target these chronic disorders in order to better address sustainability issues and social protection effectiveness.

Firm Exit, Technological Progress and Trade

DEFF Research Database (Denmark)

Schröder, Philipp; Sørensen, Allan

The dynamics of export market exit and firm closure have found limited attention in the new heterogeneous-firms trade literature. In fact, several of the predictions on firm survival and exit stemming from this new class of models are at odds with the stylized facts. Empirically, higher productiv......The dynamics of export market exit and firm closure have found limited attention in the new heterogeneous-firms trade literature. In fact, several of the predictions on firm survival and exit stemming from this new class of models are at odds with the stylized facts. Empirically, higher...... productivity firms survive longer, most firm closures are young firms, higher productivity exporters are more likely to continue to export compared to less productive exporters and market exits as well as firm closures are typically preceded by periods of contracting market shares. The present paper shows...... liberalization on export market exit and firm closure....

How unfinished business from S-phase affects mitosis and beyond

DEFF Research Database (Denmark)

Mankouri, H.W.; Huttner, D.; Hickson, I.D.

2013-01-01

The eukaryotic cell cycle is conventionally viewed as comprising several discrete steps, each of which must be completed before the next one is initiated. However, emerging evidence suggests that incompletely replicated, or unresolved, chromosomes from S-phase can persist into mitosis, where...... they present a potential threat to the faithful segregation of sister chromatids. In this review, we provide an overview of the different classes of loci where this 'unfinished S-phase business' can lead to a variety of cytogenetically distinct DNA structures throughout the various steps of mitosis...

Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells.

Science.gov (United States)

Kuffer, Christian; Kuznetsova, Anastasia Yurievna; Storchová, Zuzana

2013-08-01

Erroneously arising tetraploid mammalian cells are chromosomally instable and may facilitate cell transformation. An increasing body of evidence shows that the propagation of mammalian tetraploid cells is limited by a p53-dependent arrest. The trigger of this arrest has not been identified so far. Here we show by live cell imaging of tetraploid cells generated by an induced cytokinesis failure that most tetraploids arrest and die in a p53-dependent manner after the first tetraploid mitosis. Furthermore, we found that the main trigger is a mitotic defect, in particular, chromosome missegregation during bipolar mitosis or spindle multipolarity. Both a transient multipolar spindle followed by efficient clustering in anaphase as well as a multipolar spindle followed by multipolar mitosis inhibited subsequent proliferation to a similar degree. We found that the tetraploid cells did not accumulate double-strand breaks that could cause the cell cycle arrest after tetraploid mitosis. In contrast, tetraploid cells showed increased levels of oxidative DNA damage coinciding with the p53 activation. To further elucidate the pathways involved in the proliferation control of tetraploid cells, we knocked down specific kinases that had been previously linked to the cell cycle arrest and p53 phosphorylation. Our results suggest that the checkpoint kinase ATM phosphorylates p53 in tetraploid cells after abnormal mitosis and thus contributes to proliferation control of human aberrantly arising tetraploids.

Promoting Exit from Violent Extremism

DEFF Research Database (Denmark)

Dalgaard-Nielsen, Anja

2013-01-01

A number of Western countries are currently adding exit programs targeting militant Islamists to their counterterrorism efforts. Drawing on research into voluntary exit from violent extremism, this article identifies themes and issues that seem to cause doubt, leading to exit. It then provides a ...... the influence attempt as subtle as possible, use narratives and self-affirmatory strategies to reduce resistance to persuasion, and consider the possibility to promote attitudinal change via behavioral change as an alternative to seek to influence beliefs directly....

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.

Science.gov (United States)

Skansing, Daniel Bräuner; Londero, Stefano Christian; Asschenfeldt, Pia; Larsen, Stine Rosenkilde; Godballe, Christian

2017-06-01

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

Excess free histone H3 localizes to centrosomes for proteasome-mediated degradation during mitosis in metazoans.

Science.gov (United States)

Wike, Candice L; Graves, Hillary K; Wason, Arpit; Hawkins, Reva; Gopalakrishnan, Jay; Schumacher, Jill; Tyler, Jessica K

2016-08-17

The cell tightly controls histone protein levels in order to achieve proper packaging of the genome into chromatin, while avoiding the deleterious consequences of excess free histones. Our accompanying study has shown that a histone modification that loosens the intrinsic structure of the nucleosome, phosphorylation of histone H3 on threonine 118 (H3 T118ph), exists on centromeres and chromosome arms during mitosis. Here, we show that H3 T118ph localizes to centrosomes in humans, flies, and worms during all stages of mitosis. H3 abundance at the centrosome increased upon proteasome inhibition, suggesting that excess free histone H3 localizes to centrosomes for degradation during mitosis. In agreement, we find ubiquitinated H3 specifically during mitosis and within purified centrosomes. These results suggest that targeting of histone H3 to the centrosome for proteasome-mediated degradation is a novel pathway for controlling histone supply, specifically during mitosis.

Mitosis, double strand break repair, and telomeres: a view from the end: how telomeres and the DNA damage response cooperate during mitosis to maintain genome stability.

Science.gov (United States)

Cesare, Anthony J

2014-11-01

Double strand break (DSB) repair is suppressed during mitosis because RNF8 and downstream DNA damage response (DDR) factors, including 53BP1, do not localize to mitotic chromatin. Discovery of the mitotic kinase-dependent mechanism that inhibits DSB repair during cell division was recently reported. It was shown that restoring mitotic DSB repair was detrimental, resulting in repair dependent genome instability and covalent telomere fusions. The telomere DDR that occurs naturally during cellular aging and in cancer is known to be refractory to G2/M checkpoint activation. Such DDR-positive telomeres, and those that occur as part of the telomere-dependent prolonged mitotic arrest checkpoint, normally pass through mitosis without covalent ligation, but result in cell growth arrest in G1 phase. The discovery that suppressing DSB repair during mitosis may function primarily to protect DDR-positive telomeres from fusing during cell division reinforces the unique cooperation between telomeres and the DDR to mediate tumor suppression. © 2014 The Author. Bioessays published by WILEY Periodicals, Inc.

Apoptosis and mitosis in the small intestine at radiation injury

International Nuclear Information System (INIS)

Hashiguchi, Junichiro; Ito, Masahiro; Onizuka, Shinya; Sekine, Ichiro; Uchida, Shinji

1990-01-01

A single whole body irradiation was given at a dose rate of 0.298 Gy/min in 6-week-old male mice. Intestinal crypt apoptosis and mitosis cells were determined by delivering radiation doses of 0.4, 0.6, 1.0, 1.5, 2.0, 5.0, 10.0, and 20.0 Gy. The incidence of apoptosis was linearly increased in a dose-dependent manner up to 5.0 Gy, and thereafter, it was gradually decreased. There was a decreased tendency for mitosis with delivering higher radiation doses. The incidence of apoptosis rapidly increased 2 hours after irradiation with either 0.6 Gy or 2.0 Gy, and reached to the peak 4 hours later. It brought about a 18-fold and 28-fold increase for 0.6 Gy and 2.0 Gy, respectively, relative to that before irradiation. Mitosis cells decreased by half one hour after irradiation with 0.6 Gy, and then returned to the pre-irradiation value through synchronization 24 hours later. The number of cells positive to BrdU was 776 in the group of mice without irradiation and 479 in the group of mice irradiated with 2.0 Gy. (N.K.)

Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.

Science.gov (United States)

Takemoto, Ai; Kawashima, Shigehiro A; Li, Juan-Juan; Jeffery, Linda; Yamatsugu, Kenzo; Elemento, Olivier; Nurse, Paul

2016-03-15

Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation. © 2016. Published by The Company of Biologists Ltd.

PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

DEFF Research Database (Denmark)

Nielsen, Christian Thomas Friberg; Huttner, Diana; Bizard, Anna H

2015-01-01

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural......-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis....

Evolutionary consequences of polyploidy in prokaryotes and the origin of mitosis and meiosis.

Science.gov (United States)

Markov, Alexander V; Kaznacheev, Ilya S

2016-06-08

The origin of eukaryote-specific traits such as mitosis and sexual reproduction remains disputable. There is growing evidence that both mitosis and eukaryotic sex (i.e., the alternation of syngamy and meiosis) may have already existed in the basal eukaryotes. The mating system of the halophilic archaeon Haloferax volcanii probably represents an intermediate stage between typical prokaryotic and eukaryotic sex. H. volcanii is highly polyploid, as well as many other Archaea. Here, we use computer simulation to explore genetic and evolutionary outcomes of polyploidy in amitotic prokaryotes and its possible role in the origin of mitosis, meiosis and eukaryotic sex. Modeling suggests that polyploidy can confer strong short-term evolutionary advantage to amitotic prokaryotes. However, it also promotes the accumulation of recessive deleterious mutations and the risk of extinction in the long term, especially in highly mutagenic environment. There are several possible strategies that amitotic polyploids can use in order to reduce the genetic costs of polyploidy while retaining its benefits. Interestingly, most of these strategies resemble different components or aspects of eukaryotic sex. They include asexual ploidy cycles, equalization of genome copies by gene conversion, high-frequency lateral gene transfer between relatives, chromosome exchange coupled with homologous recombination, and the evolution of more accurate chromosome distribution during cell division (mitosis). Acquisition of mitosis by an amitotic polyploid results in chromosome diversification and specialization. Ultimately, it transforms a polyploid cell into a functionally monoploid one with multiple unique, highly redundant chromosomes. Specialization of chromosomes makes the previously evolved modes of promiscuous chromosome shuffling deleterious. This can result in selective pressure to develop accurate mechanisms of homolog pairing, and, ultimately, meiosis. Emergence of mitosis and the first

Spoiled Onions: Exposing Malicious Tor Exit Relays

OpenAIRE

Winter, Philipp; Lindskog, Stefan

2014-01-01

Several hundred Tor exit relays together push more than 1 GiB/s of network traffic. However, it is easy for exit relays to snoop and tamper with anonymised network traffic and as all relays are run by independent volunteers, not all of them are innocuous. In this paper, we seek to expose malicious exit relays and document their actions. First, we monitored the Tor network after developing a fast and modular exit relay scanner. We implemented several scanning modules for detecting common attac...

VISUALIZACIÓN DE LA MITOSIS CON EL MICROSCOPIO DE FUERZA ATÓMICA

Directory of Open Access Journals (Sweden)

María de Lourdes Segura-Valdez

2008-01-01

Full Text Available En eucariontes, la división celular generalmente ocurre por medio de la mitosis. En estudios previos hemos documentado la posibilidad de estudiar la estructura celular in situ con el microscopio de fuerza atómica, con énfasis en la estructura nuclear en interfase. En este trabajo mostramos que las diferentes etapas de la mitosis pueden ser visualizadas con este instrumento, lo que abre la posibilidad de estudiar este fenómeno en el rango nanométrico.

Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.

Science.gov (United States)

Liang, Kaiwei; Woodfin, Ashley R; Slaughter, Brian D; Unruh, Jay R; Box, Andrew C; Rickels, Ryan A; Gao, Xin; Haug, Jeffrey S; Jaspersen, Sue L; Shilatifard, Ali

2015-11-05

Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division. Copyright © 2015 Elsevier Inc. All rights reserved.

Understanding international exit from a non-economic and emotional perspective: the case of Taiwanese entrepreneurs exit China

OpenAIRE

Lin, Yangpei

2015-01-01

I investigate why Taiwanese entrepreneurs who have invested in China exit. Viewed from the non-economic perspective, there are three main themes in this thesis. Theme A focuses on the non-economic variables in international exit. Theme B examines how incident-generated emotions shape entrepreneur’s actions in internationalization. Theme C presents an overview of the decision-making of international exit, summarizing the finding in Theme A and Theme B and revisiting the theor...

14 CFR 25.809 - Emergency exit arrangement.

Science.gov (United States)

2010-01-01

... moveable door or hatch in the external walls of the fuselage, allowing an unobstructed opening to the... event of failure of the primary system. Manual operation of the exit (after failure of the primary... during flight. (i) Each emergency exit must have a means to retain the exit in the open position, once...

Regulation of nuclear envelope dynamics via APC/C is necessary for the progression of semi-open mitosis in Schizosaccharomyces japonicus.

Science.gov (United States)

Aoki, Keita; Shiwa, Yuh; Takada, Hiraku; Yoshikawa, Hirofumi; Niki, Hironori

2013-09-01

Three types of mitosis, which are open, closed or semi-open mitosis, function in eukaryotic cells, respectively. The open mitosis involves breakage of the nuclear envelope before nuclear division, whereas the closed mitosis proceeds with an intact nuclear envelope. To understand the mechanism and significance of three types of mitotic division in eukaryotes, we investigated the process of semi-open mitosis, in which the nuclear envelope is only partially broken, in the fission yeast Schizosaccharomyces japonicus. In anaphase-promoting complex/cyclosome (APC/C) mutants of Sz. japonicus, the nuclear envelope remained relatively intact during anaphase, resulting in impaired semi-open mitosis. As a suppressor of apc2 mutant, a mutation of Oar2, which was a 3-oxoacyl-[acyl carrier protein] reductase, was obtained. The level of the Oar2, which had two destruction-box motifs recognized by APC/C, was increased in APC/C mutants. Furthermore, the defective semi-open mitosis observed in an apc2 mutant was restored by mutated oar2+. Based on these findings, we propose that APC/C regulates the dynamics of the nuclear envelope through degradation of Oar2 dependent on APC/C during the metaphase-to-anaphase transition of semi-open mitosis in Sz. japonicus. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Direct evidence that radiation induced micronuclei of early embryos require a mitosis for expression

International Nuclear Information System (INIS)

Mueller, W.U.; Schlusen, I.; Streffer, C.

1991-01-01

The naturally synchronous development of early mouse embryos was exploited to address the question, whether micronuclei require a mitosis for expression or whether they can be expressed in the same cell cycle, in which exposure to X-rays or caffeine took place. Experiments with 2-cell and with 4-cell embryos showed that micronulcei are expressed only if a mitosis is completed. There was no indication, even after doses up to 20 Gy, that micronuclei can be expressed before the mitosis was reached, which followed exposure. Furthermore, no nuclear fragmentation pointing to apoptosis could be detected in the cycle, in which cells were exposed. The same results were obtained when caffeine (5 mM) was used as micronucleus inducing agent. (orig.)

The mitosis-regulating and protein-protein interaction activities of astrin are controlled by aurora-A-induced phosphorylation.

Science.gov (United States)

Chiu, Shao-Chih; Chen, Jo-Mei Maureen; Wei, Tong-You Wade; Cheng, Tai-Shan; Wang, Ya-Hui Candice; Ku, Chia-Feng; Lian, Chiao-Hsuan; Liu, Chun-Chih Jared; Kuo, Yi-Chun; Yu, Chang-Tze Ricky

2014-09-01

Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser(115). The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis. Copyright © 2014 the American Physiological Society.

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

Science.gov (United States)

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

2013-01-07

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.

Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival

Science.gov (United States)

Elsing, Alexandra N.; Aspelin, Camilla; Björk, Johanna K.; Bergman, Heidi A.; Himanen, Samu V.; Kallio, Marko J.; Roos-Mattjus, Pia

2014-01-01

Unless mitigated, external and physiological stresses are detrimental for cells, especially in mitosis, resulting in chromosomal missegregation, aneuploidy, or apoptosis. Heat shock proteins (Hsps) maintain protein homeostasis and promote cell survival. Hsps are transcriptionally regulated by heat shock factors (HSFs). Of these, HSF1 is the master regulator and HSF2 modulates Hsp expression by interacting with HSF1. Due to global inhibition of transcription in mitosis, including HSF1-mediated expression of Hsps, mitotic cells are highly vulnerable to stress. Here, we show that cells can counteract transcriptional silencing and protect themselves against proteotoxicity in mitosis. We found that the condensed chromatin of HSF2-deficient cells is accessible for HSF1 and RNA polymerase II, allowing stress-inducible Hsp expression. Consequently, HSF2-deficient cells exposed to acute stress display diminished mitotic errors and have a survival advantage. We also show that HSF2 expression declines during mitosis in several but not all human cell lines, which corresponds to the Hsp70 induction and protection against stress-induced mitotic abnormalities and apoptosis. PMID:25202032

Towards A Model of Identity and Role Exit

Directory of Open Access Journals (Sweden)

Jason S. Milne

2011-11-01

Full Text Available Explanations of role exit often focus on how factors associated with a specific role that affect whether the individual will exit a role or not. Other research explains how identities affect our performance in a role. However, no one has yet to demonstrate the connection between role-set factors and identities, and role exit. Using data from a survey of 940 current and former soccer referees, this paper provides a model of role exit that involves a complex of processes that include role-set factors (structural and cultural factors associated with a specific role and identity processes. Specifically, this paper demonstrates that, other than role conflict, identity processes explain the relationship between role-set factors and role exit. The model provides a beginning method for understanding the connection between identities and role exit.

Zelfstandig ondernemerschap in Nederland: determinanten van de instroom en de uitstroom [Self-employment in the Netherlands: determinants of entry and exit

NARCIS (Netherlands)

Blumberg, B.F.; Graaf, P.M. de

2004-01-01

In this article we investigate (a) recent developments in Dutch self-employment rates and (b) individual determinants of entry into self-employment and exit from self-employment. Labor market surveys show that in the Netherlands the proportion of self-employed men and women has increased strongly

Duck hepatitis B virus covalently closed circular DNA appears to survive hepatocyte mitosis in the growing liver

International Nuclear Information System (INIS)

Reaiche-Miller, Georget Y.; Thorpe, Michael; Low, Huey Chi; Qiao, Qiao; Scougall, Catherine A.; Mason, William S.; Litwin, Samuel; Jilbert, Allison R.

2013-01-01

Nucleos(t)ide analogues that inhibit hepatitis B virus (HBV) DNA replication are typically used as monotherapy for chronically infected patients. Treatment with a nucleos(t)ide analogue eliminates most HBV DNA replication intermediates and produces a gradual decline in levels of covalently closed circular DNA (cccDNA), the template for viral RNA synthesis. It remains uncertain if levels of cccDNA decline primarily through hepatocyte death, or if loss also occurs during hepatocyte mitosis. To determine if cccDNA survives mitosis, growing ducklings infected with duck hepatitis B virus (DHBV) were treated with the nucleoside analogue, Entecavir. Viremia was suppressed at least 10 5 -fold, during a period when average liver mass increased 23-fold. Analysis of the data suggested that if cccDNA synthesis was completely inhibited, at least 49% of cccDNA survived hepatocyte mitosis. However, there was a large duck-to-duck variation in cccDNA levels, suggesting that low level cccDNA synthesis may contribute to this apparent survival through mitosis. - Highlights: • The hepatitis B virus nuclear template is covalently closed circular DNA (cccDNA). • cccDNA was studied during liver growth in duck hepatitis B virus infected ducks. • Virus DNA replication and new cccDNA synthesis were inhibited with Entecavir. • At least 49% of cccDNA appeared to survive hepatocyte mitosis. • Low level virus DNA synthesis may contribute to survival of cccDNA through mitosis

Duck hepatitis B virus covalently closed circular DNA appears to survive hepatocyte mitosis in the growing liver

Energy Technology Data Exchange (ETDEWEB)

Reaiche-Miller, Georget Y.; Thorpe, Michael; Low, Huey Chi; Qiao, Qiao; Scougall, Catherine A. [School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Mason, William S.; Litwin, Samuel [Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111 (United States); Jilbert, Allison R., E-mail: allison.jilbert@adelaide.edu.au [School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia)

2013-11-15

Nucleos(t)ide analogues that inhibit hepatitis B virus (HBV) DNA replication are typically used as monotherapy for chronically infected patients. Treatment with a nucleos(t)ide analogue eliminates most HBV DNA replication intermediates and produces a gradual decline in levels of covalently closed circular DNA (cccDNA), the template for viral RNA synthesis. It remains uncertain if levels of cccDNA decline primarily through hepatocyte death, or if loss also occurs during hepatocyte mitosis. To determine if cccDNA survives mitosis, growing ducklings infected with duck hepatitis B virus (DHBV) were treated with the nucleoside analogue, Entecavir. Viremia was suppressed at least 10{sup 5}-fold, during a period when average liver mass increased 23-fold. Analysis of the data suggested that if cccDNA synthesis was completely inhibited, at least 49% of cccDNA survived hepatocyte mitosis. However, there was a large duck-to-duck variation in cccDNA levels, suggesting that low level cccDNA synthesis may contribute to this apparent survival through mitosis. - Highlights: • The hepatitis B virus nuclear template is covalently closed circular DNA (cccDNA). • cccDNA was studied during liver growth in duck hepatitis B virus infected ducks. • Virus DNA replication and new cccDNA synthesis were inhibited with Entecavir. • At least 49% of cccDNA appeared to survive hepatocyte mitosis. • Low level virus DNA synthesis may contribute to survival of cccDNA through mitosis.

Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis

DEFF Research Database (Denmark)

Lukas, C; Kramer, E R; Peters, J M

2000-01-01

Ubiquitin-proteasome-mediated destruction of rate-limiting proteins is required for timely progression through the main cell cycle transitions. The anaphase-promoting complex (APC), periodically activated by the Cdh1 subunit, represents one of the major cellular ubiquitin ligases which, in Saccha......Ubiquitin-proteasome-mediated destruction of rate-limiting proteins is required for timely progression through the main cell cycle transitions. The anaphase-promoting complex (APC), periodically activated by the Cdh1 subunit, represents one of the major cellular ubiquitin ligases which......, in Saccharomyces cerevisiae and Drosophila spp., triggers exit from mitosis and during G(1) prevents unscheduled DNA replication. In this study we investigated the importance of periodic oscillation of the APC-Cdh1 activity for the cell cycle progression in human cells. We show that conditional interference...... transition and lowered the rate of DNA synthesis during S phase, some of the activities essential for DNA replication became markedly amplified, mainly due to a progressive increase of E2F-dependent cyclin E transcription and a rapid turnover of the p27(Kip1) cyclin-dependent kinase inhibitor. Consequently...

A new theory of the origin of cancer: quantum coherent entanglement, centrioles, mitosis, and differentiation.

Science.gov (United States)

Hameroff, Stuart R

2004-11-01

Malignant cells are characterized by abnormal segregation of chromosomes during mitosis ("aneuploidy"), generally considered a result of malignancy originating in genetic mutations. However, recent evidence supports a century-old concept that maldistribution of chromosomes (and resultant genomic instability) due to abnormalities in mitosis itself is the primary cause of malignancy rather than a mere byproduct. In normal mitosis chromosomes replicate into sister chromatids which are then precisely separated and transported into mirror-like sets by structural protein assemblies called mitotic spindles and centrioles, both composed of microtubules. The elegant yet poorly understood ballet-like movements and geometric organization occurring in mitosis have suggested guidance by some type of organizing field, however neither electromagnetic nor chemical gradient fields have been demonstrated or shown to be sufficient. It is proposed here that normal mirror-like mitosis is organized by quantum coherence and quantum entanglement among microtubule-based centrioles and mitotic spindles which ensure precise, complementary duplication of daughter cell genomes and recognition of daughter cell boundaries. Evidence and theory supporting organized quantum states in cytoplasm/nucleoplasm (and quantum optical properties of centrioles in particular) at physiological temperature are presented. Impairment of quantum coherence and/or entanglement among microtubule-based mitotic spindles and centrioles can result in abnormal distribution of chromosomes, abnormal differentiation and uncontrolled growth, and account for all aspects of malignancy. New approaches to cancer therapy and stem cell production are suggested via non-thermal laser-mediated effects aimed at quantum optical states of centrioles.

Systematic Analysis of the Crosstalk between Mitosis and DNA Damage by a Live Cell siRNA Screen

DEFF Research Database (Denmark)

Pedersen, Ronni Sølvhøi

Recent research has shown, that the biological processes of DNA replication, DNA damage, cell cycle and mitosis cannot be considered as isolated cellular functions but are mechanistically linked in many ways. For instance, when cells are exposed to replication stress and enter mitosis...... propose that this strong p53 response, which often occurs without detectable increase in DNA damage, is caused by the acute increase in chromosomal aneuploidy. Finally, our systematic approach to the DNA damage-mitosis crosstalk reveals widespread cell death in response to mitotic pertubations, showing...

Cycling with BRCA2 from DNA repair to mitosis

International Nuclear Information System (INIS)

Lee, Hyunsook

2014-01-01

Genetic integrity in proliferating cells is guaranteed by the harmony of DNA replication, appropriate DNA repair, and segregation of the duplicated genome. Breast cancer susceptibility gene BRCA2 is a unique tumor suppressor that is involved in all three processes. Hence, it is critical in genome maintenance. The functions of BRCA2 in DNA repair and homology-directed recombination (HDR) have been reviewed numerous times. Here, I will briefly go through the functions of BRCA2 in HDR and focus on the emerging roles of BRCA2 in telomere homeostasis and mitosis, then discuss how BRCA2 exerts distinct functions in a cell-cycle specific manner in the maintenance of genomic integrity. - Highlights: • BRCA2 is a multifaceted tumor suppressor and is crucial in genetic integrity. • BRCA2 exerts distinct functions in cell cycle-specific manner. • Mitotic kinases regulate diverse functions of BRCA2 in mitosis and cytokinesis

Cycling with BRCA2 from DNA repair to mitosis

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyunsook, E-mail: HL212@snu.ac.kr

2014-11-15

Genetic integrity in proliferating cells is guaranteed by the harmony of DNA replication, appropriate DNA repair, and segregation of the duplicated genome. Breast cancer susceptibility gene BRCA2 is a unique tumor suppressor that is involved in all three processes. Hence, it is critical in genome maintenance. The functions of BRCA2 in DNA repair and homology-directed recombination (HDR) have been reviewed numerous times. Here, I will briefly go through the functions of BRCA2 in HDR and focus on the emerging roles of BRCA2 in telomere homeostasis and mitosis, then discuss how BRCA2 exerts distinct functions in a cell-cycle specific manner in the maintenance of genomic integrity. - Highlights: • BRCA2 is a multifaceted tumor suppressor and is crucial in genetic integrity. • BRCA2 exerts distinct functions in cell cycle-specific manner. • Mitotic kinases regulate diverse functions of BRCA2 in mitosis and cytokinesis.

Exit or revival?

International Nuclear Information System (INIS)

Anon.

2001-01-01

The answer given by the international representative at the colloquium:'nuclear: exit or revival? ' was tending towards the revival. The international, democratic, ecological and of energy policy stakes are tackled. (N.C.)

Mitosis, diffusible crosslinkers, and the ideal gas law.

Science.gov (United States)

Odde, David J

2015-03-12

During mitosis, molecular motors hydrolyze ATP to generate sliding forces between adjacent microtubules and form the bipolar mitotic spindle. Lansky et al. now show that the diffusible microtubule crosslinker Ase1p can generate sliding forces between adjacent microtubules, and it does so without ATP hydrolysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Seasonal temperature variations influence tapetum mitosis patterns associated with reproductive fitness.

Science.gov (United States)

Lavania, Umesh C; Basu, Surochita; Kushwaha, Jyotsana Singh; Lavania, Seshu

2014-09-01

Environmental stress in plants impacts many biological processes, including male gametogenesis, and affects several cytological mechanisms that are strongly interrelated. To understand the likely impact of rising temperature on reproductive fitness in the climate change regime, a study of tapetal mitosis and its accompanying meiosis over seasons was made to elucidate the influence of temperature change on the cytological events occurring during microsporogenesis. For this we used two species of an environmentally sensitive plant system, i.e., genus Cymbopogon Sprengel (Poaceae), namely Cymbopogon nardus (L.) Rendle var. confertiflorus (Steud.) Bor (2n = 20) and Cymbopogon jwaruncusha (Jones) Schult. (2n = 20). Both species flower profusely during extreme summer (48 °C) and mild winter (15 °C) but support low and high seed fertility, respectively, in the two seasons. We have shown that tapetal mitotic patterns over seasons entail differential behavior for tapetal mitosis. During the process of tapetum development there are episodes of endomitosis that form either (i) an endopolyploid genomically imbalanced uninucleate and multinucleate tapetum, and (or) (ii) an acytokinetic multinucleate genomically balanced tapetum, with the progression of meiosis in the accompanying sporogenous tissue. The relative frequency of occurrence of the two types of tapetum mitosis patterns is significantly different in the two seasons, and it is found to be correlated with the temperature conditions. Whereas, the former (genomically imbalanced tapetum) are prevalent during the hot summer, the latter (genomically balanced tapetum) are frequent under optimal conditions. Such a differential behaviour in tapetal mitosis vis-à-vis temperature change is also correspondingly accompanied by substantial disturbances or regularity in meiotic anaphase disjunction. Both species show similar patterns. The study underpins that tapetal mitotic behaviour per se could be a reasonable indicator to

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis.

Science.gov (United States)

Zhang, Xu Rui; Liu, Yong Ai; Sun, Fang; Li, He; Lei, Su Wen; Wang, Ju Fang

2016-07-01

To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker. Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Exit from Synchrony in Joint Improvised Motion.

Directory of Open Access Journals (Sweden)

Assi Dahan

Full Text Available Motion synchrony correlates with effective and well-rated human interaction. However, people do not remain locked in synchrony; Instead, they repeatedly enter and exit synchrony. In many important interactions, such as therapy, marriage and parent-infant communication, it is the ability to exit and then re-enter synchrony that is thought to build strong relationship. The phenomenon of entry into zero-phase synchrony is well-studied experimentally and in terms of mathematical modeling. In contrast, exit-from-synchrony is under-studied. Here, we focus on human motion coordination, and examine the exit-from-synchrony phenomenon using experimental data from the mirror game paradigm, in which people perform joint improvised motion, and from human tracking of computer-generated stimuli. We present a mathematical mechanism that captures aspects of exit-from-synchrony in human motion. The mechanism adds a random motion component when the accumulated velocity error between the players is small. We introduce this mechanism to several models for human coordinated motion, including the widely studied HKB model, and the predictor-corrector model of Noy, Dekel and Alon. In all models, the new mechanism produces realistic simulated behavior when compared to experimental data from the mirror game and from tracking of computer generated stimuli, including repeated entry and exit from zero-phase synchrony that generates a complexity of motion similar to that of human players. We hope that these results can inform future research on exit-from-synchrony, to better understand the dynamics of coordinated action of people and to enhance human-computer and human-robot interaction.

Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2

Science.gov (United States)

Andersen, Joshua L; Johnson, Carrie E; Freel, Christopher D; Parrish, Amanda B; Day, Jennifer L; Buchakjian, Marisa R; Nutt, Leta K; Thompson, J Will; Moseley, M Arthur; Kornbluth, Sally

2009-01-01

The apoptotic initiator caspase-2 has been implicated in oocyte death, in DNA damage- and heat shock-induced death, and in mitotic catastrophe. We show here that the mitosis-promoting kinase, cdk1–cyclin B1, suppresses apoptosis upstream of mitochondrial cytochrome c release by phosphorylating caspase-2 within an evolutionarily conserved sequence at Ser 340. Phosphorylation of this residue, situated in the caspase-2 interdomain, prevents caspase-2 activation. S340 was susceptible to phosphatase 1 dephosphorylation, and an interaction between phosphatase 1 and caspase-2 detected during interphase was lost in mitosis. Expression of S340A non-phosphorylatable caspase-2 abrogated mitotic suppression of caspase-2 and apoptosis in various settings, including oocytes induced to undergo cdk1-dependent maturation. Moreover, U2OS cells treated with nocodazole were found to undergo mitotic catastrophe more readily when endogenous caspase-2 was replaced with the S340A mutant to lift mitotic inhibition. These data demonstrate that for apoptotic stimuli transduced by caspase-2, cell death is prevented during mitosis through the inhibitory phosphorylation of caspase-2 and suggest that under conditions of mitotic arrest, cdk1–cyclin B1 activity must be overcome for apoptosis to occur. PMID:19730412

Assessment of exit block following pulmonary vein isolation: far-field capture masquerading as entrance without exit block.

Science.gov (United States)

Vijayaraman, Pugazhendhi; Dandamudi, Gopi; Naperkowski, Angela; Oren, Jess; Storm, Randle; Ellenbogen, Kenneth A

2012-10-01

Complete electrical isolation of pulmonary veins (PVs) remains the cornerstone of ablation therapy for atrial fibrillation. Entrance block without exit block has been reported to occur in 40% of the patients. Far-field capture (FFC) can occur during pacing from the superior PVs to assess exit block, and this may appear as persistent conduction from PV to left atrium (LA). To facilitate accurate assessment of exit block. Twenty consecutive patients with symptomatic atrial fibrillation referred for ablation were included in the study. Once PV isolation (entrance block) was confirmed, pacing from all the bipoles on the Lasso catheter was used to assess exit block by using a pacing stimulus of 10 mA at 2 ms. Evidence for PV capture without conduction to LA was necessary to prove exit block. If conduction to LA was noticed, pacing output was decreased until there was PV capture without conduction to LA or no PV capture was noted to assess for far-field capture in both the upper PVs. All 20 patients underwent successful isolation (entrance block) of all 76 (4 left common PV) veins: mean age 58 ± 9 years; paroxysmal atrial fibrillation 40%; hypertension 70%, diabetes mellitus 30%, coronary artery disease 15%; left ventricular ejection fraction 55% ± 10%; LA size 42 ± 11 mm. Despite entrance block, exit block was absent in only 16% of the PVs, suggesting persistent PV to LA conduction. FFC of LA appendage was noted in 38% of the left superior PVs. FFC of the superior vena cava was noted in 30% of the right superior PVs. The mean pacing threshold for FFC was 7 ± 4 mA. Decreasing pacing output until only PV capture (loss of FFC) is noted was essential to confirm true exit block. FFC of LA appendage or superior vena cava can masquerade as persistent PV to LA conduction. A careful assessment for PV capture at decreasing pacing output is essential to exclude FFC. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Tritium in Exit Signs | RadTown USA | US EPA

Science.gov (United States)

2017-08-07

Many exit signs contain tritium to light the sign without batteries or electricity. Using tritium in exit signs allows the sign to remain lit if the power goes out. Tritium is most dangerous when it is inhaled or swallowed. Never tamper with a tritium exit sign. If a tritium exit sign is broken, leave the area immediately and notify the building maintenance staff.

Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis

Science.gov (United States)

Macurek, Libor; Benada, Jan; Müllers, Erik; Halim, Vincentius A.; Krejčíková, Kateřina; Burdová, Kamila; Pecháčková, Sona; Hodný, Zdeněk; Lindqvist, Arne; Medema, René H.; Bartek, Jiri

2013-01-01

Cells are constantly challenged by DNA damage and protect their genome integrity by activation of an evolutionary conserved DNA damage response pathway (DDR). A central core of DDR is composed of a spatiotemporally ordered net of post-translational modifications, among which protein phosphorylation plays a major role. Activation of checkpoint kinases ATM/ATR and Chk1/2 leads to a temporal arrest in cell cycle progression (checkpoint) and allows time for DNA repair. Following DNA repair, cells re-enter the cell cycle by checkpoint recovery. Wip1 phosphatase (also called PPM1D) dephosphorylates multiple proteins involved in DDR and is essential for timely termination of the DDR. Here we have investigated how Wip1 is regulated in the context of the cell cycle. We found that Wip1 activity is downregulated by several mechanisms during mitosis. Wip1 protein abundance increases from G1 phase to G2 and declines in mitosis. Decreased abundance of Wip1 during mitosis is caused by proteasomal degradation. In addition, Wip1 is phosphorylated at multiple residues during mitosis, and this leads to inhibition of its enzymatic activity. Importantly, ectopic expression of Wip1 reduced γH2AX staining in mitotic cells and decreased the number of 53BP1 nuclear bodies in G1 cells. We propose that the combined decrease and inhibition of Wip1 in mitosis decreases the threshold necessary for DDR activation and enables cells to react adequately even to modest levels of DNA damage encountered during unperturbed mitotic progression. PMID:23255129

Relationship between Amount of Exited Blood During Wet-cupping with Patient’s Individual Conditions and the Time of Doing it

Directory of Open Access Journals (Sweden)

Ghazanfari M

2017-12-01

Full Text Available Aims Wet-cupping as a therapeutic method has been recommended to be done on certain days based on authentic sources of traditional medicine in Iran. The purpose of this study was to determine the relationship between amount of exited blood during wet-cupping with patient’s individual conditions and the time it was performed. Instruments & Methods In this descriptive cross-sectional study, 391 men who were referred to a cupping center in Saveh city in the spring of 2016, were selected by simple sampling and wet-cupping in the position between the two scapula was performed. The research instrument was a questionnaire including demographic characteristics, date of reference (day, month and year, age, height, weight and amount of exited blood during the wet-cupping in gram. Data were analyzed by SPSS 16 software and using chi-square test, paired t test and one-way analysis of variance. Findings The means of age, weight and body mass index were significantly related to the mean of amount of exited blood during wet-cupping (p0.05, but the amount of exited blood was higher in people with previous history of wet-cupping than those without previous history (p<0.001. Also, in people with hypertension, the amount of exited blood was higher than other treatment groups (p<0.05. Conclusion Individual characteristics such as age, weight, body mass index, cause of referral and previous history of wet-cupping affect the amount of exited blood during wet-cupping, but the time of wet-cupping (day and month does not affect the amount of exited blood.

Entry and Exit Dynamics of Nascent Business Owners

DEFF Research Database (Denmark)

Rocha, Vera; Carneiro, Anabela; Varum, Celeste

2015-01-01

results suggest that different exit modes can be predicted by business owners’ entry route. Furthermore, different exit modes exhibit different duration dependence patterns according to the entry mode. Additionally, the paper shows that businesses started after a displacement episode are not necessarily......This paper reports a comprehensive study on the dynamics of nascent business owners using a unique longitudinal matched employer–employee dataset. We follow over 157,000 individuals who leave paid employment and become business owners during the period 1992–2007. The contributions of this paper...... are twofold. First, we analyze both entry and exit, identifying and characterizing different profiles of individuals leaving paid employment to become business owners, and distinguishing exits by dissolution from exits by ownership transfer. Second, we provide new evidence on how particular experiences...

Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident

NARCIS (Netherlands)

Korver, W.; Schilham, M. W.; Moerer, P.; van den Hoff, M. J.; Dam, K.; Lamers, W. H.; Medema, R. H.; Clevers, H.

1998-01-01

In order to maintain a stable karyotype, the eukaryotic cell cycle is coordinated such that only one round of S phase precedes each mitosis, and mitosis is not initiated until DNA replication is completed. Several checkpoints and regulatory proteins have been defined in lower eukaryotes that govern

Polo-like kinase-1 is a target of the DNA damage checkpoint

NARCIS (Netherlands)

Smits, V.A.J.; Klompmaker, R.; Arnaud, L.; Rijksen, G.; Nigg, E.A.; Medema, R.H.

2000-01-01

Polo-like kinases (PLKs) have an important role in several stages of mitosis. They contribute to the activation of cyclin B/Cdc2 and are involved in centrosome maturation and bipolar spindle formation at the onset of mitosis1, 2. PLKs also control mitotic exit by regulating the anaphase-promoting

Unsuccessful mitosis in multicellular tumour spheroids.

Science.gov (United States)

Molla, Annie; Couvet, Morgane; Coll, Jean-Luc

2017-04-25

Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere. Moreover aurora kinases are fully active and histone H3 is phosphorylated on Ser 10. Consequently, the mitotic spindle checkpoint is satisfied and, anaphase proceeds as illustrated by the transfer of survivin on the spindle and by the segregation of the two lots of chromosomes. However, the segregation plane is not well defined and oscillations of the dividing cells are observed. Finally, cytokinesis fails and the absence of separation of the two daughter cells gives rise to binucleated cells.Division orientation is specified during interphase and persists throughout mitosis. Our data indicate that the cancer cells, in multicellular spheroids, lose their ability to regulate their orientation, a feature commonly encountered in tumours.Moreover, multicellular spheroid expansion is still sensitive to mitotic drugs as pactlitaxel and aurora kinase inhibitors. The spheroids thus represent a highly relevant model for studying drug efficiency in tumours.

PLK1 Activation in Late G2 Sets Up Commitment to Mitosis.

Science.gov (United States)

Gheghiani, Lilia; Loew, Damarys; Lombard, Bérangère; Mansfeld, Jörg; Gavet, Olivier

2017-06-06

Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation before mitotic entry. Plk1-dependent Cdc25C1 phosphosites are sufficient to promote mitotic entry, even when Plk1 activity is inhibited. Furthermore, we find that activation of Plk1 during G2 relies on CyclinA2-Cdk activity levels. Our findings thus elucidate a critical role for Plk1 in CyclinB1-Cdk1 activation and mitotic entry and outline how CyclinA2-Cdk, an S-promoting factor, poises cells for commitment to mitosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Real-time fluorescence imaging of the DNA damage repair response during mitosis.

Science.gov (United States)

Miwa, Shinji; Yano, Shuya; Yamamoto, Mako; Matsumoto, Yasunori; Uehara, Fuminari; Hiroshima, Yukihiko; Toneri, Makoto; Murakami, Takashi; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Efimova, Elena V; Tsuchiya, Hiroyuki; Hoffman, Robert M

2015-04-01

The response to DNA damage during mitosis was visualized using real-time fluorescence imaging of focus formation by the DNA-damage repair (DDR) response protein 53BP1 linked to green fluorescent protein (GFP) (53BP1-GFP) in the MiaPaCa-2(Tet-On) pancreatic cancer cell line. To observe 53BP1-GFP foci during mitosis, MiaPaCa-2(Tet-On) 53BP1-GFP cells were imaged every 30 min by confocal microscopy. Time-lapse imaging demonstrated that 11.4 ± 2.1% of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells had increased focus formation over time. Non-mitotic cells did not have an increase in 53BP1-GFP focus formation over time. Some of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells with focus formation became apoptotic. The results of the present report suggest that DNA strand breaks occur during mitosis and undergo repair, which may cause some of the mitotic cells to enter apoptosis in a phenomenon possibly related to mitotic catastrophe. © 2014 Wiley Periodicals, Inc.

Hearing loss and disability exit: Measurement issues and coping strategies.

Science.gov (United States)

Christensen, Vibeke Tornhøj; Datta Gupta, Nabanita

2017-02-01

Hearing loss is one of the most common conditions related to aging, and previous descriptive evidence links it to early exit from the labor market. These studies are usually based on self-reported hearing difficulties, which are potentially endogenous to labor supply. We use unique representative data collected in the spring of 2005 through in-home interviews. The data contains self-reported functional and clinically-measured hearing ability for a representative sample of the Danish population aged 50-64. We estimate the causal effect of hearing loss on early retirement via disability benefits, taking into account the endogeneity of functional hearing. Our identification strategy involves the simultaneous estimation of labor supply, functional hearing, and coping strategies (i.e. accessing assistive devices at work or informing one's employer about the problem). We use hearing aids as an instrument for functional hearing. Our main empirical findings are that endogeneity bias is more severe for men than women and that functional hearing problems significantly increase the likelihood of receiving disability benefits for both men and women. However, relative to the baseline the effect is larger for men (47% vs. 20%, respectively). Availability of assistive devices in the workplace decreases the likelihood of receiving disability benefits, whereas informing an employer about hearing problems increases this likelihood. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring the Reasons and Ways to Exit: The Entrepreneur Perspective

NARCIS (Netherlands)

Parastuty, Zulaicha; Breitenecker, Robert J.; Schwarz, Erich J.; Harms, Rainer; Bögenhold, Dieter; Bonnet, Jean; Dejardin, Marcus; Garcia Perez de Lema, Domingo

2016-01-01

Research on entrepreneurial exit has received growing attention recently, attributing to the importance of exit in the entrepreneurial process. Yet, the complex phenomena of exit render the research scattered in the field. This research is aimed at understanding entrepreneurial exit at the

The Political Economy of Early Exit

DEFF Research Database (Denmark)

Schmitt, Carina; Starke, Peter

2016-01-01

Large-scale exit from the labour market began in the 1970s in many OECD countries. The literature indicates that individual early retirement decisions are facilitated by generous and accessible ‘pathways’ into retirement in the public pension system, unemployment insurance or disability benefits....... in the tradable sector, against a more traditional class-based logic of welfare state policy-making. Quantitative analysis of employment outcomes in 21 countries shows that the political economy of early exit clearly rests on the sectoral politics of cost-shifting.......Large-scale exit from the labour market began in the 1970s in many OECD countries. The literature indicates that individual early retirement decisions are facilitated by generous and accessible ‘pathways’ into retirement in the public pension system, unemployment insurance or disability benefits....... It is unclear, however, why early exit became so much more prevalent in some countries than in others and why such differences remain, despite a recent shift back towards higher employment rates and ‘active ageing’. We test a logic of sectoral cost-shifting politics involving cross-class alliances...

Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis.

Science.gov (United States)

DiGiuseppe, Stephen; Luszczek, Wioleta; Keiffer, Timothy R; Bienkowska-Haba, Malgorzata; Guion, Lucile G M; Sapp, Martin J

2016-05-31

During the entry process, the human papillomavirus (HPV) capsid is trafficked to the trans-Golgi network (TGN), whereupon it enters the nucleus during mitosis. We previously demonstrated that the minor capsid protein L2 assumes a transmembranous conformation in the TGN. Here we provide evidence that the incoming viral genome dissociates from the TGN and associates with microtubules after the onset of mitosis. Deposition onto mitotic chromosomes is L2-mediated. Using differential staining of an incoming viral genome by small molecular dyes in selectively permeabilized cells, nuclease protection, and flotation assays, we found that HPV resides in a membrane-bound vesicle until mitosis is completed and the nuclear envelope has reformed. As a result, expression of the incoming viral genome is delayed. Taken together, these data provide evidence that HPV has evolved a unique strategy for delivering the viral genome to the nucleus of dividing cells. Furthermore, it is unlikely that nuclear vesicles are unique to HPV, and thus we may have uncovered a hitherto unrecognized cellular pathway that may be of interest for future cell biological studies.

Cdc15 Phosphorylates the C-terminal Domain of RNA Polymerase II for Transcription during Mitosis.

Science.gov (United States)

Singh, Amit Kumar; Rastogi, Shivangi; Shukla, Harish; Asalam, Mohd; Rath, Srikanta Kumar; Akhtar, Md Sohail

2017-03-31

In eukaryotes, the basal transcription in interphase is orchestrated through the regulation by kinases (Kin28, Bur1, and Ctk1) and phosphatases (Ssu72, Rtr1, and Fcp1), which act through the post-translational modification of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. The CTD comprises the repeated Tyr-Ser-Pro-Thr-Ser-Pro-Ser motif with potential epigenetic modification sites. Despite the observation of transcription and periodic expression of genes during mitosis with entailing CTD phosphorylation and dephosphorylation, the associated CTD specific kinase(s) and its role in transcription remains unknown. Here we have identified Cdc15 as a potential kinase phosphorylating Ser-2 and Ser-5 of CTD for transcription during mitosis in the budding yeast. The phosphorylation of CTD by Cdc15 is independent of any prior Ser phosphorylation(s). The inactivation of Cdc15 causes reduction of global CTD phosphorylation during mitosis and affects the expression of genes whose transcript levels peak during mitosis. Cdc15 also influences the complete transcription of clb2 gene and phosphorylates Ser-5 at the promoter and Ser-2 toward the 3' end of the gene. The observation that Cdc15 could phosphorylate Ser-5, as well as Ser-2, during transcription in mitosis is in contrast to the phosphorylation marks put by the kinases in interphase (G 1 , S, and G 2 ), where Cdck7/Kin28 phosphorylates Ser-5 at promoter and Bur1/Ctk1 phosphorylates Ser-2 at the 3' end of the genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

29 CFR 1910.36 - Design and construction requirements for exit routes.

Science.gov (United States)

2010-07-01

... construction requirements for exit routes. (a) Basic requirements. Exit routes must meet the following design... your workplace, consult NFPA 101-2000, Life Safety Code. (c) Exit discharge. (1) Each exit discharge... route must be adequate. (1) Exit routes must support the maximum permitted occupant load for each floor...

Ase1p Organizes Antiparallel Microtubule Arrays during Interphase and Mitosis in Fission YeastV⃞

OpenAIRE

Loïodice, Isabelle; Staub, Jayme; Setty, Thanuja Gangi; Nguyen, Nam-Phuong T.; Paoletti, Anne; Tran, P. T.

2005-01-01

Proper microtubule organization is essential for cellular processes such as organelle positioning during interphase and spindle formation during mitosis. The fission yeast Schizosaccharomyces pombe presents a good model for understanding microtubule organization. We identify fission yeast ase1p, a member of the conserved ASE1/PRC1/MAP65 family of microtubule bundling proteins, which functions in organizing the spindle midzone during mitosis. Using fluorescence live cell imaging, we show that ...

Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis.

Science.gov (United States)

Douglas, Pauline; Ye, Ruiqiong; Trinkle-Mulcahy, Laura; Neal, Jessica A; De Wever, Veerle; Morrice, Nick A; Meek, Katheryn; Lees-Miller, Susan P

2014-06-25

The protein kinase activity of the DNA-PKcs (DNA-dependent protein kinase catalytic subunit) and its autophosphorylation are critical for DBS (DNA double-strand break) repair via NHEJ (non-homologous end-joining). Recent studies have shown that depletion or inactivation of DNA-PKcs kinase activity also results in mitotic defects. DNA-PKcs is autophosphorylated on Ser2056, Thr2647 and Thr2609 in mitosis and phosphorylated DNA-PKcs localize to centrosomes, mitotic spindles and the midbody. DNA-PKcs also interacts with PP6 (protein phosphatase 6), and PP6 has been shown to dephosphorylate Aurora A kinase in mitosis. Here we report that DNA-PKcs is phosphorylated on Ser3205 and Thr3950 in mitosis. Phosphorylation of Thr3950 is DNA-PK-dependent, whereas phosphorylation of Ser3205 requires PLK1 (polo-like kinase 1). Moreover, PLK1 phosphorylates DNA-PKcs on Ser3205 in vitro and interacts with DNA-PKcs in mitosis. In addition, PP6 dephosphorylates DNA-PKcs at Ser3205 in mitosis and after IR (ionizing radiation). DNA-PKcs also phosphorylates Chk2 on Thr68 in mitosis and both phosphorylation of Chk2 and autophosphorylation of DNA-PKcs in mitosis occur in the apparent absence of Ku and DNA damage. Our findings provide mechanistic insight into the roles of DNA-PKcs and PP6 in mitosis and suggest that DNA-PKcs' role in mitosis may be mechanistically distinct from its well-established role in NHEJ.

Effects of tyrosine kinase and phosphatase inhibitors on mitosis progression in synchronized tobacco BY-2 cells.

Science.gov (United States)

Sheremet, Ya A; Yemets, A I; Azmi, A; Vissenberg, K; Verbelen, J P; Blume, Ya B

2012-01-01

To test whether reversible tubulin phosphorylation plays any role in the process of plant mitosis the effects of inhibitors of tyrosine kinases, herbimycin A, genistein and tyrphostin AG 18, and of an inhibitor of tyrosine phosphatases, sodium orthovanadate, on microtubule organization and mitosis progression in a synchronized BY-2 culture has been investigated. It was found that treatment with inhibitors of tyrosine kinases of BY-2 cells at the G2/M transition did not lead to visible disturbances of mitotic microtubule structures, while it did reduce the frequency of their appearance. We assume that a decreased tyrosine phosphorylation level could alter the microtubule dynamic instability parameters during interphase/prophase transition. All types of tyrosine kinase inhibitors used caused a prophase delay: herbimycin A and genistein for 2 h, and tyrphostin AG18 for 1 h. Thereafter the peak of mitosis was displaced for 1 h by herbimycin A or genistein exposure, but after tyrphostin AG18 treatment the timing of the mitosis-peak was comparable to that in control cells. Enhancement of tyrosine phosphorylation induced by the tyrosine phosphatase inhibitor resulted in the opposite effect on BY-2 mitosis transition. Culture treatment with sodium orthovanadate during 1 h resulted in an accelerated start of the prophase and did not lead to the alteration in time of the mitotic index peak formation, as compared to control cells. We suppose that the reversible tyrosine phosphorylation can be involved in the regulation of interphase to M phase transition possibly through regulation of microtubule dynamics in plant cells.

TMBP200, a XMAP215 homologue of tobacco BY-2 cells, has an essential role in plant mitosis.

Science.gov (United States)

Yasuhara, Hiroki; Oe, Yuki

2011-07-01

TMBP200 from tobacco BY-2 cells is a member of the highly conserved family of microtubule-associated proteins that includes Xenopus XMAP215, human TOGp, and Arabidopsis MOR1/GEM1. XMAP215 homologues have an essential role in spindle assembly and function in animals and yeast, but their role in plant mitosis is not fully clarified. Here, we show by immunoblot analysis that TMBP200 levels in synchronously cultured BY-2 cells increased when the cells entered mitosis, thus indicating that TMBP200 plays an important role in mitosis in tobacco. To investigate the role of TMBP200 in mitosis, we employed inducible RNA interference to silence TMBP200 expression in BY-2 cells. The resulting depletion of TMBP200 caused severe defects in bipolar spindle formation and resulted in the appearance of multinucleated cells with variable-sized nuclei. This finding indicates that TMBP200 has an essential role in bipolar spindle formation and function.

The Cell Cycle Timing of Centromeric Chromatin Assembly in Drosophila Meiosis Is Distinct from Mitosis Yet Requires CAL1 and CENP-C

Science.gov (United States)

Gorgescu, Walter; Tang, Jonathan; Costes, Sylvain V.; Karpen, Gary H.

2012-01-01

CENP-A (CID in flies) is the histone H3 variant essential for centromere specification, kinetochore formation, and chromosome segregation during cell division. Recent studies have elucidated major cell cycle mechanisms and factors critical for CENP-A incorporation in mitosis, predominantly in cultured cells. However, we do not understand the roles, regulation, and cell cycle timing of CENP-A assembly in somatic tissues in multicellular organisms and in meiosis, the specialized cell division cycle that gives rise to haploid gametes. Here we investigate the timing and requirements for CID assembly in mitotic tissues and male and female meiosis in Drosophila melanogaster, using fixed and live imaging combined with genetic approaches. We find that CID assembly initiates at late telophase and continues during G1 phase in somatic tissues in the organism, later than the metaphase assembly observed in cultured cells. Furthermore, CID assembly occurs at two distinct cell cycle phases during male meiosis: prophase of meiosis I and after exit from meiosis II, in spermatids. CID assembly in prophase I is also conserved in female meiosis. Interestingly, we observe a novel decrease in CID levels after the end of meiosis I and before meiosis II, which correlates temporally with changes in kinetochore organization and orientation. We also demonstrate that CID is retained on mature sperm despite the gross chromatin remodeling that occurs during protamine exchange. Finally, we show that the centromere proteins CAL1 and CENP-C are both required for CID assembly in meiosis and normal progression through spermatogenesis. We conclude that the cell cycle timing of CID assembly in meiosis is different from mitosis and that the efficient propagation of CID through meiotic divisions and on sperm is likely to be important for centromere specification in the developing zygote. PMID:23300382

Transcriptional intermediary factor 1γ binds to the anaphase-promoting complex/cyclosome and promotes mitosis

DEFF Research Database (Denmark)

Sedgwick, G.G.; Townsend, K.; Martin, A.

2013-01-01

The anaphase-promoting complex/cyclosome (APC/C) is an ubiquitin ligase that functions during mitosis. Here we identify the transcriptional regulator, transcriptional intermediary factor 1γ, TIF1γ, as an APC/C-interacting protein that regulates APC/C function. TIF1γ is not a substrate for APC....../C-dependent ubiquitylation but instead, associates specifically with the APC/C holoenzyme and Cdc20 to affect APC/C activity and progression through mitosis. RNA interference studies indicate that TIF1γ knockdown results in a specific reduction in APC/C ubiquitin ligase activity, the stabilization of APC/C substrates......, and an increase in the time taken for cells to progress through mitosis from nuclear envelope breakdown to anaphase. TIF1γ knockdown cells are also characterized by the inappropriate presence of cyclin A at metaphase, and an increase in the number of cells that fail to undergo metaphase-to-anaphase transition...

Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

Science.gov (United States)

Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

2014-12-01

Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Specific primary sequence requirements for Aurora B kinase-mediated phosphorylation and subcellular localization of TMAP during mitosis.

Science.gov (United States)

Kim, Hyun-Jun; Kwon, Hye-Rim; Bae, Chang-Dae; Park, Joobae; Hong, Kyung U

2010-05-15

During mitosis, regulation of protein structures and functions by phosphorylation plays critical roles in orchestrating a series of complex events essential for the cell division process. Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton-associated protein 2 (CKAP2), is a novel player in spindle assembly and chromosome segregation. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis. However, the mechanisms and functional importance of phosphorylation at most of the sites identified are currently unknown. Here, we report that TMAP is a novel substrate of the Aurora B kinase. Ser627 of TMAP was specifically phosphorylated by Aurora B both in vitro and in vivo. Ser627 and neighboring conserved residues were strictly required for efficient phosphorylation of TMAP by Aurora B, as even minor amino acid substitutions of the phosphorylation motif significantly diminished the efficiency of the substrate phosphorylation. Nearly all mutations at the phosphorylation motif had dramatic effects on the subcellular localization of TMAP. Instead of being localized to the chromosome region during late mitosis, the mutants remained associated with microtubules and centrosomes throughout mitosis. However, the changes in the subcellular localization of these mutants could not be completely explained by the phosphorylation status on Ser627. Our findings suggest that the motif surrounding Ser627 ((625) RRSRRL (630)) is a critical part of a functionally important sequence motif which not only governs the kinase-substrate recognition, but also regulates the subcellular localization of TMAP during mitosis.

Differential Regulation of Smad3 and of the Type II Transforming Growth Factor-β Receptor in Mitosis: Implications for Signaling

Science.gov (United States)

Hirschhorn, Tal; Barizilay, Lior; Smorodinsky, Nechama I.; Ehrlich, Marcelo

2012-01-01

The response to transforming growth factor-β (TGF-β) depends on cellular context. This context is changed in mitosis through selective inhibition of vesicle trafficking, reduction in cell volume and the activation of mitotic kinases. We hypothesized that these alterations in cell context may induce a differential regulation of Smads and TGF-β receptors. We tested this hypothesis in mesenchymal-like ovarian cancer cells, arrested (or not) in mitosis with 2-methoxyestradiol (2ME2). In mitosis, without TGF-β stimulation, Smad3 was phosphorylated at the C-terminus and linker regions and localized to the mitotic spindle. Phosphorylated Smad3 interacted with the negative regulators of Smad signaling, Smurf2 and Ski, and failed to induce a transcriptional response. Moreover, in cells arrested in mitosis, Smad3 levels were progressively reduced. These phosphorylations and reduction in the levels of Smad3 depended on ERK activation and Mps1 kinase activity, and were abrogated by increasing the volume of cells arrested in mitosis with hypotonic medium. Furthermore, an Mps1-dependent phosphorylation of GFP-Smad3 was also observed upon its over-expression in interphase cells, suggesting a mechanism of negative regulation which counters increases in Smad3 concentration. Arrest in mitosis also induced a block in the clathrin-mediated endocytosis of the type II TGF-β receptor (TβRII). Moreover, following the stimulation of mitotic cells with TGF-β, the proteasome-mediated attenuation of TGF-β receptor activity, the degradation and clearance of TβRII from the plasma membrane, and the clearance of the TGF-β ligand from the medium were compromised, and the C-terminus phosphorylation of Smad3 was prolonged. We propose that the reduction in Smad3 levels, its linker phosphorylation, and its association with negative regulators (observed in mitosis prior to ligand stimulation) represent a signal attenuating mechanism. This mechanism is balanced by the retention of active TGF

Dissuasive exit signage for building fire evacuation.

Science.gov (United States)

Olander, Joakim; Ronchi, Enrico; Lovreglio, Ruggiero; Nilsson, Daniel

2017-03-01

This work presents the result of a questionnaire study which investigates the design of dissuasive emergency signage, i.e. signage conveying a message of not utilizing a specific exit door. The work analyses and tests a set of key features of dissuasive emergency signage using the Theory of Affordances. The variables having the largest impact on observer preference, interpretation and noticeability of the signage have been identified. Results show that features which clearly negate the exit-message of the original positive exit signage are most effective, for instance a red X-marking placed across the entirety of the exit signage conveys a clear dissuasive message. Other features of note are red flashing lights and alternation of colour. The sense of urgency conveyed by the sign is largely affected by sensory inputs such as red flashing lights or other features which cause the signs to break the tendencies of normalcy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-01-01

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

Anther-preferential expressing gene PMR is essential for the mitosis of pollen development in rice.

Science.gov (United States)

Liu, Yaqin; Xu, Ya; Ling, Sheng; Liu, Shasha; Yao, Jialing

2017-06-01

Phenotype identification, expression examination, and function prediction declared that the anther-preferential expressing gene PMR may participate in regulation of male gametophyte development in rice. Male germline development in flowering plants produces the pair of sperm cells for double fertilization and the pollen mitosis is a key process of it. Although the structural features of male gametophyte have been defined, the molecular mechanisms regulating the mitotic cell cycle are not well elucidated in rice. Here, we reported an anther-preferential expressing gene in rice, PMR (Pollen Mitosis Relative), playing an essential role in male gametogenesis. When PMR gene was suppressed via RNAi, the mitosis of microspore was severely damaged, and the plants formed unmatured pollens containing only one or two nucleuses at the anthesis, ultimately leading to serious reduction of pollen fertility and seed-setting. The CRISPR mutants, pmr-1 and pmr-2, both showed the similar defects as the PMR-RNAi lines. Further analysis revealed that PMR together with its co-expressing genes were liable to participate in the regulation of DNA metabolism in the nucleus, and affected the activities of some enzymes related to the cell cycle. We finally discussed that unknown protein PMR contained the PHD, SWIB and Plus-3 domains and they might have coordinating functions in regulation pathway of the pollen mitosis in rice.

Phosphorylation by CK2 regulates MUS81/EME1 in mitosis and after replication stress.

Science.gov (United States)

Palma, Anita; Pugliese, Giusj Monia; Murfuni, Ivana; Marabitti, Veronica; Malacaria, Eva; Rinalducci, Sara; Minoprio, Anna; Sanchez, Massimo; Mazzei, Filomena; Zolla, Lello; Franchitto, Annapaola; Pichierri, Pietro

2018-06-01

The MUS81 complex is crucial for preserving genome stability through the resolution of branched DNA intermediates in mitosis. However, untimely activation of the MUS81 complex in S-phase is dangerous. Little is known about the regulation of the human MUS81 complex and how deregulated activation affects chromosome integrity. Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex. In line with a role in mitosis, phosphorylation at Serine 87 is suppressed in S-phase and is mainly detected in the MUS81 molecules associated with EME1. Loss of CK2-dependent MUS81 phosphorylation contributes modestly to chromosome integrity, however, expression of the phosphomimic form induces DSBs accumulation in S-phase, because of unscheduled targeting of HJ-like DNA intermediates, and generates a wide chromosome instability phenotype. Collectively, our findings describe a novel regulatory mechanism controlling the MUS81 complex function in human cells. Furthermore, they indicate that, genome stability depends mainly on the ability of cells to counteract targeting of branched intermediates by the MUS81/EME1 complex in S-phase, rather than on a correct MUS81 function in mitosis.

Use of unstable chromosome aberrations for biological dosimetry after the first postirradiation mitosis

International Nuclear Information System (INIS)

Doloy, M.T.; Malarbet, J.L.; Guedeney, G.; Bourguignon, M.; Leroy, A.; Reillaudou, M.; Masse, R.

1991-01-01

The loss of unstable chromosome aberrations after the first postirradiation mitosis makes their use difficult in radiation dosimetry. We describe here a method which, in a cell population observed at this stage, allows retrospective estimation of the frequencies of the unstable aberrations induced at the time of irradiation, and their use as a dosimeter. The laws controlling the behavior of unstable aberrations during mitosis were defined from a large-scale experiment on irradiated human lymphocytes. For cells undergoing the first, second, or third mitosis after irradiation, relationships were determined between the frequency, at irradiation time, of acentric fragments not arising from formation of dicentrics or rings, and the ratio of dicentrics and centric rings appearing without acentric fragments to the total number of dicentrics plus rings. On the basis of this ratio, the method described here provides an assessment of the postirradiation mitotic activity in a cell population. This assessment permitted estimation of the cell distribution and frequency of dicentrics plus centric rings, and of the frequency of acentric fragments at the time of irradiation. The use of this method for retrospective dosimetry after whole-body irradiation under various conditions of exposure is illustrated

JMJD5 (Jumonji Domain-containing 5) Associates with Spindle Microtubules and Is Required for Proper Mitosis.

Science.gov (United States)

He, Zhimin; Wu, Junyu; Su, Xiaonan; Zhang, Ye; Pan, Lixia; Wei, Huimin; Fang, Qiang; Li, Haitao; Wang, Da-Liang; Sun, Fang-Lin

2016-02-26

Precise mitotic spindle assembly is a guarantee of proper chromosome segregation during mitosis. Chromosome instability caused by disturbed mitosis is one of the major features of various types of cancer. JMJD5 has been reported to be involved in epigenetic regulation of gene expression in the nucleus, but little is known about its function in mitotic process. Here we report the unexpected localization and function of JMJD5 in mitotic progression. JMJD5 partially accumulates on mitotic spindles during mitosis, and depletion of JMJD5 results in significant mitotic arrest, spindle assembly defects, and sustained activation of the spindle assembly checkpoint (SAC). Inactivating SAC can efficiently reverse the mitotic arrest caused by JMJD5 depletion. Moreover, JMJD5 is found to interact with tubulin proteins and associate with microtubules during mitosis. JMJD5-depleted cells show a significant reduction of α-tubulin acetylation level on mitotic spindles and fail to generate enough interkinetochore tension to satisfy the SAC. Further, JMJD5 depletion also increases the susceptibility of HeLa cells to the antimicrotubule agent. Taken together, these results suggest that JMJD5 plays an important role in regulating mitotic progression, probably by modulating the stability of spindle microtubules. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Exit interviews to reduce turnover amongst healthcare professionals.

Science.gov (United States)

Webster, Joan; Flint, Anndrea

2014-08-19

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going studies. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no studies that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new studies. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Exit examinations, peer academic climate, and adolescents' developmental outcomes.

Science.gov (United States)

Benner, Aprile D

2013-02-01

Implications of high school exit examination performance were examined with a sample of 672 racial/ethnic minority students. Exit examination failure in the 10th grade was negatively linked to subsequent grade point average, school engagement, and school belonging one year later, controlling for outcomes prior to taking the examination. Academically incongruent students-those who failed the exit examination but were in schools where their same-race/ethnicity peers were performing well academically-seemed to be at particular risk for struggling grades and poorer socioemotional well-being (e.g., experiencing greater depressive symptoms and loneliness). Findings contribute to the limited research base on exit examinations and highlight the links between exit examination performance and developmental outcomes beyond the oft-studied academic domain. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Remodeling of bovine oviductal epithelium by mitosis of secretory cells.

Science.gov (United States)

Ito, Sayaka; Kobayashi, Yoshihiko; Yamamoto, Yuki; Kimura, Koji; Okuda, Kiyoshi

2016-11-01

Two types of oviductal epithelial cells, secretory and ciliated, play crucial roles in the first days after fertilization in mammals. Secretory cells produce various molecules promoting embryo development, while ciliated cells facilitate transport of oocytes and zygotes by ciliary beating. The proportions of the two cell types change during the estrous cycle. The proportion of ciliated cells on the oviductal luminal surface is abundant at the follicular phase, whereas the proportion of secretory cells gradually increases with the formation of the corpus luteum. In the present study, we hypothesize that the proportions of ciliated and secretory epithelial cells are regulated by mitosis. The proportion of the cells being positive for FOXJ1 (a ciliated cell marker) or Ki67 (a mitosis marker) in epithelial cells during the estrous cycle were immunohistochemically examined. Ki67 and FOXJ1 or PAX8 (a secretory cell marker), were double-stained to clarify which types of epithelial cells undergo mitosis. In the ampulla, the percentage of FOXJ1-positive cells was highest at the day of ovulation (Day 0) and decreased by about 50 % by Days 8-12, while in the isthmus it did not change during the estrous cycle. The proportion of Ki67-positive cells was highest at around the time of ovulation in both the ampulla and isthmus. All the Ki67-positive cells were PAX8-positive and FOXJ1-negative in both the ampulla and isthmus. These findings suggest that epithelial remodeling, which is regulated by differentiation and/or proliferation of secretory cells of the oviduct, provides the optimal environment for gamete transport, fertilization and embryonic development.

TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

DEFF Research Database (Denmark)

Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

2015-01-01

mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise...... temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin...

Requirements of cyclin a for mitosis are independent of its subcellular localization.

Science.gov (United States)

Dienemann, Axel; Sprenger, Frank

2004-06-22

Cyclin A (CycA), the only essential mitotic cyclin in Drosophila, is cytoplasmic during interphase and accumulates in the nucleus during prophase. We show that interphase localization is mediated by Leptomycin B (LMB)-sensitive nuclear export. This is a feature shared with human CyclinB1, and it is assumed that nuclear accumulation is necessary for mitotic entry. Here, we tested if the unique mitotic function of CycA requires nuclear accumulation. We fused subcellular localization signals to CycA and tested their mitotic capability. Surprisingly, nuclear accumulation was not required, and even a membrane-tethered form of CycA was able to induce mitosis. We noted that Cyclin B (CycB) protein disappears prematurely in CycA mutants, reminiscent of rca1 mutants. Rca1 is an inhibitor of Fizzy-related-APC/C activity, and in rca1 mutants, mitotic cyclins are degraded in G2 of the 16(th) embryonic cell cycle. Overexpression of Rca1 can restore mitosis in CycA mutants, indicating that the mitotic failure of CycA mutants is caused by premature activation of the APC/C. The essential mitotic function of CycA is therefore not the activation of numerous mitotic substrates by Cdk1-dependent phosphorylation. Rather, CycA-dependent kinase activity is required to inhibit one inhibitor of mitosis, the Fzr protein.

Possible mechanisms of chromosomal aberrations: VII. Comparative dynamics of sister chromatid disjunction and realization of radiation-induced chromosomal aberrations during mitosis

International Nuclear Information System (INIS)

Lebedeva, L.I.; Akhmamet'eva, E.M.

1994-01-01

An increase in radiation-induced chromosomal aberrations during c-metaphase sister chromatid disjunction was demonstrated in murine bone marrow cells exposed to a total γ-irradiation at 0.5 Gy. Caffeine (Cf) treatment during mitosis partially suppressed the chromatid disjunction rate and increased the number of radiation-induced aberrations in this mitosis. Nalidixic acid (NA) treatment of c-metaphase cells completely suppressed chromatid disjunction and the realization of induced aberrations. Topoisomerase 2 was assumed to be involved during mitosis in both processes

Is the publication of exit poll results morally permissible?

DEFF Research Database (Denmark)

Sønderholm, Jørn

2016-01-01

This article is about exit polls. It addresses the question of whether or not it is morally permissible to publish exit poll results. The conclusion of the article is that an affirmative answer should be given to this question. In section 2, the master argument in favor of the moral permissibility...... of the publication of exit poll results is introduced. This is a strong argument. It is, however, argued that it might be the case that the conclusion of this argument should be rejected if there are other, and weightier, arguments against the idea that the publication of exit poll results is morally permissible....... In section 3, the strongest arguments against the moral permissibility of the publication of exit poll results are outlined and discussed. The conclusion of this section is that all these arguments fail in their intended purpose. The conclusion of the article is therefore justified....

Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.

Science.gov (United States)

Reinecke, James B; Katafiasz, Dawn; Naslavsky, Naava; Caplan, Steve

2015-01-01

During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IPO as an Exit startegy in Management Buyouts

OpenAIRE

Sheth, Vidhi Chetan

2008-01-01

The basic subject to this research project is,IPO as an exit strategy in management buyouts. The paper provides with an understanding of the various characteristics and factors that have an impact on a buyout exit through an IPO. Discussions on the issues like the IPO versus other exit strategies, performance of a company's pre-IPO as well as post-IPO, the trends in the buyout and the IPO market, etc are done. For a better understanding and an in-depth knowledge about the topic, we have analy...

Exit by Afghanisation

DEFF Research Database (Denmark)

Holmberg, Hasse

USA’s exit-strategi fra Afghanistan har båret præg af et italesat hovedmål om overdragelse af ansvar til de nationale myndigheder i landet. Exit-strategien udmærker sig ved sin lighed med USA’s afvikling af sit engagement i Vietnam for snart et halvt århundrede siden, hvor begrebet Vietnamisation...... om national selvbestemmelse. Den amerikanske opinion spillede en afgørende rolle og afslutningen af engagementet i Vietnam kan i lige så høj grad ses som en reaktion på den massive folkelige modstand mod krigen. Omtrent 40 år efter kan Obama-administrationen notere sig en lignende negativ trend i...... Kissinger vidste, at krigen i Vietnam var tabt. Vietnamisation havde i høj grad til formål at slutte USA’s engagement på en måde, der tog hensyn til USA’s internationale renomme. Spørgsmålet er så om de mange strategiske ligheder kan overføres til samme konklusion: krigen er tabt. Briefet har til hensigt...

Experimental study of mutagenous and mitosis modifying activity of silver nanoparticles

Directory of Open Access Journals (Sweden)

B. S. Kirbik

2015-01-01

Full Text Available Mutagenous and mitosis modifying impact of silver nanoparticles has been studied on outbred mice. Nanoparticles were of round shape with dimensions of 5-50 nm, size of generated organic shell of 2-5 nm, the quantity in 1 mcm3 makes 120-270. Metaphasic analysis of mice bone marrow cells was used as a testing technique. The frequency of chromosome aberrations and mitotic index of preparations were accounted. During single intraperitoneal administration of the agent in the dose of 250 mcg/kg the silver nanoparticles demonstrated mitosis stimulating activity. No mutagenous effect of silver nanoparticles by daily administration for 4 days of 25 mcg/kg and single administration in the dose of 250 mcg/kg has been registered, but there is statistically insignificant tendency of aberrant metaphases increase. Consequently silver nanoparticles in the investigated doses demonstrated no mutagenous activity and can be considered safe for mammalian cells.

Kindlin1 regulates microtubule function to ensure normal mitosis.

Science.gov (United States)

Patel, Hitesh; Stavrou, Ifigeneia; Shrestha, Roshan L; Draviam, Viji; Frame, Margaret C; Brunton, Valerie G

2016-08-01

Loss of Kindlin 1 (Kin1) results in the skin blistering disorder Kindler Syndrome (KS), whose symptoms also include skin atrophy and reduced keratinocyte proliferation. Kin1 binds to integrins to modulate their activation and more recently it has been shown to regulate mitotic spindles and cell survival in a Plk1-dependent manner. Here we report that short-term Kin1 deletion in mouse skin results in impaired mitosis, which is associated with reduced acetylated tubulin (ac-tub) levels and cell proliferation. In cells, impaired mitosis and reduced ac-tub levels are also accompanied by reduced microtubule stability, all of which are rescued by HDAC6 inhibition. The ability of Kin1 to regulate HDAC6-dependent cellular ac-tub levels is dependent on its phosphorylation by Plk1. Taken together, these data define a novel role for Kin1 in microtubule acetylation and stability and offer a mechanistic insight into how certain KS phenotypes, such as skin atrophy and reduced cell proliferation, arise. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis

DEFF Research Database (Denmark)

Ballabeni, Andrea; Melixetian, Marina; Zamponi, Raffaella

2004-01-01

-mediated degradation by inhibiting its ubiquitination. In particular, Geminin ensures basal levels of CDT1 during S phase and its accumulation during mitosis. Consistently, inhibition of Geminin synthesis during M phase leads to impairment of pre-RC formation and DNA replication during the following cell cycle....... Moreover, we show that inhibition of CDK1 during mitosis, and not Geminin depletion, is sufficient for premature formation of pre-RCs, indicating that CDK activity is the major mitotic inhibitor of licensing in human cells. Taken together with recent data from our laboratory, our results demonstrate...

The roles of cohesins in mitosis, meiosis, and human health and disease

Science.gov (United States)

Brooker, Amanda S.; Berkowitz, Karen M.

2015-01-01

Summary Mitosis and meiosis are essential processes that occur during development. Throughout these processes, cohesion is required to keep the sister chromatids together until their separation at anaphase. Cohesion is created by multi-protein subunit complexes called cohesins. Although the subunits differ slightly in mitosis and meiosis, the canonical cohesin complex is composed of four subunits that are quite diverse. The cohesin complexes are also important for DNA repair, gene expression, development, and genome integrity. Here we provide an overview of the roles of cohesins during these different events, as well as their roles in human health and disease, including the cohesinopathies. Although the exact roles and mechanisms of these proteins are still being elucidated, this review will serve as a guide for the current knowledge of cohesins. PMID:24906316

Entry and exit decisions under uncertainty

DEFF Research Database (Denmark)

Kongsted, Hans Christian

1996-01-01

This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result......This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result...

Jet Exit Rig Six Component Force Balance

Science.gov (United States)

Castner, Raymond; Wolter, John; Woike, Mark; Booth, Dennis

2012-01-01

A new six axis air balance was delivered to the NASA Glenn Research Center. This air balance has an axial force capability of 800 pounds, primary airflow of 10 pounds per second, and a secondary airflow of 3 pounds per second. Its primary use was for the NASA Glenn Jet Exit Rig, a wind tunnel model used to test both low-speed, and high-speed nozzle concepts in a wind tunnel. This report outlines the installation of the balance in the Jet Exit Rig, and the results from an ASME calibration nozzle with an exit area of 8 square-inches. The results demonstrated the stability of the force balance for axial measurements and the repeatability of measurements better than 0.20 percent.

Centrosomes split in the presence of impaired DNA integrity during mitosis

NARCIS (Netherlands)

Hut, HMJ; Lemstra, W; Blaauw, EH; van Cappellen, GWA; Kampinga, HH; Sibon, OCM

A well-established function of centrosomes is their role in accomplishing a successful mitosis that gives rise to a pair of identical daughter cells. We recently showed that DNA replication defects and DNA damage in Drosophila embryos trigger centrosomal changes, but it remained unclear whether

Assessment of algorithms for mitosis detection in breast cancer histopathology images

NARCIS (Netherlands)

Veta, M.; Diest, van P.J.; Willems, S.M.; Wang, Haibo; Madabhushi, A. (Anant); Cruz-Roa, A. (Angel); González, F.; Larsen, A.B.L. (Anders); Vestergaard, J.S. (Jacob); Dahl, A.B. (Anders); Ciresan, D.C. (Dan); Schmidhuber, J.; Giusti, A. (Alessandro); Gambardella, L.M. (Luca); Tek, F. Boray; Walter, Th. (Thomas); Wang, Ching-Wei; Kondo, Satoshi; Matuszewski, B.J. (Bogdan); Precioso, F. (Frederic); Snell, V. (Violet); Kittler, Josef; de Campos, Teofilo E.; Khan, Adnan M.; Rajpoot, Nasir M.; Arkoumani, Evdokia; Lacle, Miangela M.; Viergever, M.A.; Pluim, J.P.W.

2015-01-01

The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from low

Assessment of algorithms for mitosis detection in breast cancer histopathology images

DEFF Research Database (Denmark)

Veta, Mitko; van Diest, Paul J.; Willems, Stefan M.

2014-01-01

The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from lo...

Role of substrate concentration in mitosis and hyphal extension of Aspergillus

DEFF Research Database (Denmark)

Müller, Christian; Spohr, Anders Bendsen; Nielsen, Jens

2000-01-01

The filamentous fungi Aspergillus oryzae and A. niger grow by apical extension of multinucleate hyphae that are subdivided into compartments by cross-walls called septa. Submerged cultivation, image analysis, and fluorescence microscopy were used to study the role of the carbon source on mitosis...

Clathrin is spindle-associated but not essential for mitosis.

Directory of Open Access Journals (Sweden)

Joana Borlido

Full Text Available Clathrin is a multimeric protein involved in vesicle coat assembly. Recently clathrin distribution was reported to change during the cell cycle and was found to associate with the mitotic spindle. Here we test whether the recruitment of clathrin to the spindle is indicative of a critical functional contribution to mitosis.Previously a chicken pre-B lymphoma cell line (DKO-R was developed in which the endogenous clathrin heavy chain alleles were replaced with the human clathrin heavy chain under the control of a tetracycline-regulatable promoter. Receptor-mediated and fluid-phase endocytosis were significantly inhibited in this line following clathrin knockout, and we used this to explore the significance of clathrin heavy chain expression for cell cycle progression. We confirmed using confocal microscopy that clathrin colocalised with tubulin at mitotic spindles. Using a propidium iodide flow cytometric assay we found no statistical difference in the cell cycle distribution of the knockout cells versus the wild-type. Additionally, we showed that the ploidy and the recovery kinetics following cell cycle arrest with nocodazole were unchanged by repressing clathrin heavy chain expression.We conclude that the association of clathrin with the mitotic spindle and the contribution of clathrin to endocytosis are evolutionarily conserved. However we find that the contribution of clathrin to mitosis is less robust and dependent on cellular context. In other cell-lines silencing RNA has been used by others to knockdown clathrin expression resulting in an increase in the mitotic index of the cells. We show an effect on the G2/M phase population of clathrin knockdown in HEK293 cells but show that repressing clathrin expression in the DKO-R cell-line has no effect on the size of this population. Consequently this work highlights the need for a more detailed molecular understanding of the recruitment and function of clathrin at the spindle, since the

Criticality safety analysis of a calciner exit chute

International Nuclear Information System (INIS)

Haught, C.F.; Basoglu, B.; Brewer, R.W.; Hollenback, D.F.; Wilkinson, A.D.; Dodds, H.L.

1994-01-01

Calcination of uranyl nitrate into uranium oxide is part of normal operations of some enrichment plants. Typically, a calciner discharges uranium oxide powder (U 3 O 8 ) into an exit chute that directs the powder into a receiving can located in a glove box. One possible scenario for a criticality accident is the exit chute becoming blocked with powder near its discharge. The blockage restricts the flow of powder causing the exit chute to become filled with the powder. If blockage does occur, the height of the powder could reach a level that would not be safe from a criticality point of view. In this analysis, the subcritical height limit is examined for 98% enriched U 3 O 8 in the exit chute with full water reflection and optimal water moderation. The height limit for ensuring criticality safety during such an accumulation is 28.2 cm above the top of the discharge pipe at the bottom of the chute. Chute design variations are also evaluated with full water reflection and optimal water moderation. Subcritical configurations for the exit chute variation are developed, but the configurations are not safe when combined with the calciner. To ensure criticality safety, modifications must be made to the calciner tube or safety measures must be implemented if these designs are to be utilized with 98% enriched material. A geometrically safe configuration for the exit chute is developed for a blockage of 20% enriched powder with full water reflection and optimal water moderation, and this configuration is safe when combined with the existing calciner

The FEAR protein Slk19 restricts Cdc14 phosphatase to the nucleus until the end of anaphase, regulating its participation in mitotic exit in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Ann Marie E Faust

Full Text Available In Saccharomyces cerevisiae mitosis, the protein Slk19 plays an important role in the initial release of Cdc14 phosphatase from the nucleolus to the nucleus in early anaphase, an event that is critical for proper anaphase progression. A role for Slk19 in later mitotic stages of Cdc14 regulation, however, has not been demonstrated. While investigating the role of Slk19 post-translational modification on Cdc14 regulation, we found that a triple point mutant of SLK19, slk19(3R (three lysine-to-arginine mutations, strongly affects Cdc14 localization during late anaphase and mitotic exit. Using fluorescence live-cell microscopy, we found that, similar to slk19Δ cells, slk19(3R cells exhibit no defect in spindle stability and only a mild defect in spindle elongation dynamics. Unlike slk19Δcells, however, slk19(3R cells exhibit no defect in Cdc14 release from the nucleolus to the nucleus. Instead, slk19(3R cells are defective in the timing of Cdc14 movement from the nucleus to the cytoplasm at the end of anaphase. This mutant has a novel phenotype: slk19(3R causes premature Cdc14 movement to the cytoplasm prior to, rather than concomitant with, spindle disassembly. One consequence of this premature Cdc14 movement is the inappropriate activation of the mitotic exit network, made evident by the fact that slk19(3R partially rescues a mutant of the mitotic exit network kinase Cdc15. In conclusion, in addition to its role in regulating Cdc14 release from the nucleolus to the nucleus, we found that Slk19 is also important for regulating Cdc14 movement from the nucleus to the cytoplasm at the end of anaphase.

Dysregulation of the mitosis-meiosis switch in testicular carcinoma in situ

DEFF Research Database (Denmark)

Jørgensen, Anne; Nielsen, John E; Almstrup, Kristian

2013-01-01

, except in spermatocytic seminoma (not derived from CIS). In conclusion, this study indicates that meiosis signalling is dysregulated in CIS cells and that a key regulator of the mitosis-meiosis switch, DMRT1, is expressed in 'early-stage' CIS cells but is down-regulated with further invasive...

LOX is a novel mitotic spindle-associated protein essential for mitosis.

Science.gov (United States)

Boufraqech, Myriem; Wei, Darmood; Weyemi, Urbain; Zhang, Lisa; Quezado, Martha; Kalab, Petr; Kebebew, Electron

2016-05-17

LOX regulates cancer progression in a variety of human malignancies. It is overexpressed in aggressive cancers and higher expression of LOX is associated with higher cancer mortality. Here, we report a new function of LOX in mitosis. We show that LOX co-localizes to mitotic spindles from metaphase to telophase, and p-H3(Ser10)-positive cells harbor strong LOX staining. Further, purification of mitotic spindles from synchronized cells show that LOX fails to bind to microtubules in the presence of nocodazole, whereas paclitaxel treated samples showed enrichment in LOX expression, suggesting that LOX binds to stabilized microtubules. LOX knockdown leads to G2/M phase arrest; reduced p-H3(Ser10), cyclin B1, CDK1, and Aurora B. Moreover, LOX knockdown significantly increased sensitivity of cancer cells to chemotherapeutic agents that target microtubules. Our findings suggest that LOX has a role in cancer cell mitosis and may be targeted to enhance the activity of microtubule inhibitors for cancer therapy.

24 CFR 3280.106 - Exit facilities; egress windows and devices.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Exit facilities; egress windows and... § 3280.106 Exit facilities; egress windows and devices. (a) Every room designed expressly for sleeping purposes, unless it has an exit door (see § 3280.105), shall have at least one outside window or approved...

An Identity Theory of Role Exit among Soccer Referees

OpenAIRE

Milne, Jason Syme

2006-01-01

This study examines how identity processes affect role exit. I test a model of role exit that situates the identity processes of cognitive processes (reflected appraisals and social comparisons), rewards and costs related to the role, commitment to the role, and identity centrality as mediating factors between role-set and social characteristic background factors, and role exit. Using a sample of 940 current and former soccer referees in Virginia and the District of Columbia, the results s...

Regularity of mitosis in different varieties of winter bread wheat under the action of herbicides

Directory of Open Access Journals (Sweden)

Tatyana Eugenivna KOPYTCHUK

2012-05-01

Full Text Available The influence of the most widespread herbicides on winter wheat in Ukraine was studied by anaphase test. Treatment with herbicides reduced the germination of the seeds and disturbed the regularity of mitosis in all varieties of wheat. The range of violations of mitosis was demonstrated by the formation of chromosomal aberrations and dysfunctions of cell cytoskeleton which occurred while processing herbicides. Varietal differences between investigated wheat by sensitivity to herbicides were discovered. The most resistant to herbicides was variety Fantasya Odesskaya, and the most sensitive – Nikoniya, while the most harmful herbicide for wheat was Napalm.

Elimination of radiation-induced chromosome damages in human peripheral blood lymphocyte cultures. 2. The frequency of aberrations in the first-fifth post-irradiation mitosis

International Nuclear Information System (INIS)

Pyatkin, E.K.; Pokrovskaya, V.N.; Nugis, V.Yu.

1982-01-01

The number of chromosome aberrations in 1.-5. mitoses cultivated from lymphocyte PHA of peripheric man blood after gamma irradiation in vitro in 1e5; 3 and 6 Gy has been determined. For all the doses, as the cells passed 1. and successive postradiation divisiops, observed was the decrease in the number of aberrant metaphases and all the aberrations of the chromosomal typee at that their elimination rate increases with the dose increase. No considerable differences in the frequency of pair fragments in 1.-4. mitosis after irradiation in 1,5 Gy dose, in 1.-3. mitoses after irradiation in 3 Gy dose and in 1.-2. mitoses after irradiation in 6 Gy dose were found. In lymphocyte cultures irradiated in 3 and 6 Gy doses the number of dicentries in 2. mitosis was approximately 2 times smaller than in 1. mitosis and in 3. mitosis two times smaller than in 2. mitosis. In 1. mitosis almost all the dicentrics have accompanying pair fragments in 2. and 3. mitoses a share of the dicentrics without fragments constituted about 30-70 %, and in 4.-5. mitoses amounted to 95-100 %. The reduction of the number of irregular chromosomes in the process of cell passing of 1. and successive postradiation mitosis was noted only during lymphocyte investigation irradiated in 6 Gy. At 1,5 and 3 Gy doses these aberration frequency in 1.-5. and 1.-4. mitoses were nearly the same

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1

NARCIS (Netherlands)

Lee, S.B.; Kim, J.J.; Nam, H.J.; Gao, B.; Yin, P.; Qin, B.; Yi, S.Y.; Ham, H.; Evans, D.; Kim, S.H.; Zhang, J.; Deng, M.; Liu, T.; Zhang, H.; Billadeau, D.D.; Wang, L.; Giaime, E.; Shen, J.; Pang, Y.P.; Jen, J.; Deursen, J.M.A. van; Lou, Z.

2015-01-01

Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate

Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death.

Science.gov (United States)

Bougé, Anne-Laure; Parmentier, Marie-Laure

2016-03-01

In neurodegenerative diseases such as Alzheimer's disease (AD), cell cycle defects and associated aneuploidy have been described. However, the importance of these defects in the physiopathology of AD and the underlying mechanistic processes are largely unknown, in particular with respect to the microtubule (MT)-binding protein Tau, which is found in excess in the brain and cerebrospinal fluid of affected individuals. Although it has long been known that Tau is phosphorylated during mitosis to generate a lower affinity for MTs, there is, to our knowledge, no indication that an excess of this protein could affect mitosis. Here, we studied the effect of an excess of human Tau (hTau) protein on cell mitosis in vivo. Using the Drosophila developing wing disc epithelium as a model, we show that an excess of hTau induces a mitotic arrest, with the presence of monopolar spindles. This mitotic defect leads to aneuploidy and apoptotic cell death. We studied the mechanism of action of hTau and found that the MT-binding domain of hTau is responsible for these defects. We also demonstrate that the effects of hTau occur via the inhibition of the function of the kinesin Klp61F, the Drosophila homologue of kinesin-5 (also called Eg5 or KIF11). We finally show that this deleterious effect of hTau is also found in other Drosophila cell types (neuroblasts) and tissues (the developing eye disc), as well as in human HeLa cells. By demonstrating that MT-bound Tau inhibits the Eg5 kinesin and cell mitosis, our work provides a new framework to consider the role of Tau in neurodegenerative diseases. © 2016. Published by The Company of Biologists Ltd.

Shape Transformation of the Nuclear Envelope during Closed Mitosis.

Science.gov (United States)

Zhu, Qian; Zheng, Fan; Liu, Allen P; Qian, Jin; Fu, Chuanhai; Lin, Yuan

2016-11-15

The nuclear envelope (NE) in lower eukaryotes such as Schizosaccharomyces pombe undergoes large morphology changes during closed mitosis. However, which physical parameters are important in governing the shape evolution of the NE, and how defects in the dividing chromosomes/microtubules are reflected in those parameters, are fundamental questions that remain unresolved. In this study, we show that improper separation of chromosomes in genetically deficient cells leads to membrane tethering or asymmetric division in contrast to the formation of two equal-sized daughter nuclei in wild-type cells. We hypothesize that the poleward force is transmitted to the nuclear membrane through its physical contact with the separated sister chromatids at the two spindle poles. A theoretical model is developed to predict the morphology evolution of the NE where key factors such as the work done by the poleward force and bending and surface energies stored in the membrane have been taken into account. Interestingly, the predicted phase diagram, summarizing the dependence of nuclear shape on the size of the load transmission regions, and the pole-to-pole distance versus surface area relationship all quantitatively agree well with our experimental observations, suggesting that this model captures the essential physics involved in closed mitosis. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Aurora A's functions during mitotic exit: the Guess Who game

Directory of Open Access Journals (Sweden)

David eReboutier

2015-12-01

Full Text Available Until recently, the knowledge of Aurora A kinase functions during mitosis was limited to pre-metaphase events, particularly centrosome maturation, G2/M transition, and mitotic spindle assembly. However, an involvement of Aurora A in post-metaphase events was also suspected, but not clearly demonstrated due to the technical difficulty to perform the appropriate experiments. Recent developments of both an analog specific version of Aurora A, and of small molecule inhibitors have led to the first demonstration that Aurora A is required for the early steps of cytokinesis. As in pre-metaphase, Aurora A plays diverse functions during anaphase, essentially participating in astral microtubules dynamics and central spindle assembly and functioning. The present review describes the experimental systems used to decipher new functions of Aurora A during late mitosis and situate these functions into the context of cytokinesis mechanisms.

Automatic Detection of Mitosis and Nuclei from Cytogenetic Images by CellProfiler Software for Mitotic Index Estimation

International Nuclear Information System (INIS)

Gonzalez, Jorge Ernesto; Romero, Ivonne; Garcia, Omar; Radl, Analia; Di Giorgio, Marina; Barquinero, Joan Francesc

2016-01-01

Mitotic Index (MI) estimation expressed as percentage of mitosis plays an important role as quality control endpoint. To this end, MI is applied to check the lot of media and reagents to be used throughout the assay and also to check cellular viability after blood sample shipping, indicating satisfactory/unsatisfactory conditions for the progression of cell culture. The objective of this paper was to apply the CellProfiler open-source software for automatic detection of mitotic and nuclei figures from digitized images of cultured human lymphocytes for MI assessment, and to compare its performance to that performed through semi-automatic and visual detection. Lymphocytes were irradiated and cultured for mitosis detection. Sets of images from cultures were analyzed visually and findings were compared with those using CellProfiler software. The CellProfiler pipeline includes the detection of nuclei and mitosis with 80% sensitivity and more than 99% specificity. We conclude that CellProfiler is a reliable tool for counting mitosis and nuclei from cytogenetic images, saves considerable time compared to manual operation and reduces the variability derived from the scoring criteria of different scorers. The CellProfiler automated pipeline achieves good agreement with visual counting workflow, i.e. it allows fully automated mitotic and nuclei scoring in cytogenetic images yielding reliable information with minimal user intervention. (authors)

Elimination of radiation-induced chromosomal damages in numan peripheral blood lymphocyte cultures. 1. The frequency of aberrations in the first and second mitosis

International Nuclear Information System (INIS)

Pyatkin, E.K.; Nugis, V.Yu.

1981-01-01

A comparative analysis of chromosomal aberrations in the first and second mitosis of cultivated human peripheral blood lymphocytes after gamma irradiation in vitro at 1-5 Gy doses has been made. Irradiated blood lymphocytes were incubated for 58 to 66 h at 37 deg with PGA and BDU (20 μg /ml). The first, second and third postradiation mitosises were identified using the distinguishing staining of sister chromatids. The share of the cells in the first mitosis fluctuated from 32 to 77 %, in the second - from 23 to 68 %, and the third - from 0 to 9 %. At all radiation doses significant differences in the frequency of the aberration cells passing the first and second mitosises were revealed as well as in the total number of chromosomal aberrations in all the cells. The frequency of pair fragments and dicentrics chromosomes in the first mitosis was on the average 1.6 and 2 times as high as in the second one, respectively. In the first mitosis almost all dicentric chromosomes occurred with accompanying pair fragments, and in the second mitosis the share of dicentric chromosomes without accompanying fragments was 25 to 50 %. The distribution of the dicentric chromosomes in the cells in the first and second mitosis did not differ from Poison distribution for the 2 to 5 Gy dose range

Exit channels of autoionization resonances in atoms

International Nuclear Information System (INIS)

Krause, M.O.

1985-01-01

In many-electron atoms with open shells strong autoionization resonances occur when an electron from an inner, weakly bound subshell is excited. Usually, the resonance state lies above several ionization thresholds and, hence, will decay into more than one exit or continuum channel. Several cases are discussed in which the resonance state is induced by synchrotron radiation, and the exit channels are differentiated and characterized by the analysis of the ejected electrons

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

Science.gov (United States)

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

Continuation of mitosis after selective laser microbeam destruction of the centriolar region

Energy Technology Data Exchange (ETDEWEB)

Berns, N.W.; Richardson, S.M.

1977-12-01

The centriole regions of prophase PTK2 cells were irradiated with a laser microbeam. Cells continued through mitosis normally. Ultrastructural analysis revealed either an absence of centrioles or severely damaged centrioles at the irradiated poles. Microtubules appeared to focus into pericentriolar cloud material.

Continuation of mitosis after selective laser microbeam destruction of the centriolar region

International Nuclear Information System (INIS)

Berns, N.W.; Richardson, S.M.

1977-01-01

The centriole regions of prophase PTK2 cells were irradiated with a laser microbeam. Cells continued through mitosis normally. Ultrastructural analysis revealed either an absence of centrioles or severely damaged centrioles at the irradiated poles. Microtubules appeared to focus into pericentriolar cloud material

The G2/M DNA damage checkpoint inhibits mitosis through Tyr15 phosphorylation of p34cdc2 in Aspergillus nidulans.

Science.gov (United States)

Ye, X S; Fincher, R R; Tang, A; Osmani, S A

1997-01-02

It is possible to cause G2 arrest in Aspergillus nidulans by inactivating either p34cdc2 or NIMA. We therefore investigated the negative control of these two mitosis-promoting kinases after DNA damage. DNA damage caused rapid Tyr15 phosphorylation of p34cdc2 and transient cell cycle arrest but had little effect on the activity of NIMA. Dividing cells deficient in Tyr15 phosphorylation of p34cdc2 were sensitive to both MMS and UV irradiation and entered lethal premature mitosis with damaged DNA. However, non-dividing quiescent conidiospores of the Tyr15 mutant strain were not sensitive to DNA damage. The UV and MMS sensitivity of cells unable to tyrosine phosphorylate p34cdc2 is therefore caused by defects in DNA damage checkpoint regulation over mitosis. Both the nimA5 and nimT23 temperature-sensitive mutations cause an arrest in G2 at 42 degrees C. Addition of MMS to nimT23 G2-arrested cells caused a marked delay in their entry into mitosis upon downshift to 32 degrees C and this delay was correlated with a long delay in the dephosphorylation and activation of p34cdc2. Addition of MMS to nimA5 G2-arrested cells caused inactivation of the H1 kinase activity of p34cdc2 due to an increase in its Tyr15 phosphorylation level and delayed entry into mitosis upon return to 32 degrees C. However, if Tyr15 phosphorylation of p34cdc2 was prevented then its H1 kinase activity was not inactivated upon MMS addition to nimA5 G2-arrested cells and they rapidly progressed into a lethal mitosis upon release to 32 degrees C. Thus, Tyr15 phosphorylation of p34cdc2 in G2 arrests initiation of mitosis after DNA damage in A. nidulans.

Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its dissociation from centrosomes in mitosis.

Science.gov (United States)

Mori, Yusuke; Inoue, Yoko; Taniyama, Yuki; Tanaka, Sayori; Terada, Yasuhiko

2015-12-25

Cep169 is a centrosomal protein conserved among vertebrates. In our previous reports, we showed that mammalian Cep169 interacts and collaborates with CDK5RAP2 to regulate microtubule (MT) dynamics and stabilization. Although Cep169 is required for MT regulation, its precise cellular function remains largely elusive. Here we show that Cep169 associates with centrosomes during interphase, but dissociates from these structures from the onset of mitosis, although CDK5RAP2 (Cep215) is continuously located at the centrosomes throughout cell cycle. Interestingly, treatment with purvalanol A, a Cdk1 inhibitor, nearly completely blocked the dissociation of Cep169 from centrosomes during mitosis. In addition, mass spectrometry analyses identified 7 phosphorylated residues of Cep169 corresponding to consensus phosphorylation sequence for Cdk1. These data suggest that the dissociation of Cep169 from centrosomes is controlled by Cdk1/Cyclin B during mitosis, and that Cep169 might regulate MT dynamics of mitotic spindle. Copyright © 2015 Elsevier Inc. All rights reserved.

Turbine-missile casing exit tests

International Nuclear Information System (INIS)

Yoshimura, H.R.; Sliter, G.E.

1978-01-01

Nuclear power plant designers are required to provide safety-related components with adequate protection against hypothetical turbine-missile impacts. In plants with a ''peninsula'' arrangement, protection is provided by installing the turbine axis radially from the reactor building, so that potential missile trajectories are not in line with the plant. In plants with a ''non-peninsula'' arrangement (turbine axis perpendicular to a radius), designers rely on the low probability of a missile strike and on the protection provided by reinforced concrete walls in order to demonstrate an adequate level of protection USNRC Regulatory Guide 1.115). One of the critical first steps in demonstrating adequacy is the determination of the energy and spin of the turbine segments as they exit the turbine casing. The spin increases the probability that a subsequent impact with a protective barrier will be off-normal and therefore less severe than the normal impact assumed in plant designs. Two full-scale turbine-missile casing exit tests which were conducted by Sandia Laboratories at their rocket-sled facility in Albuquerque, New Mexico, are described. Because of wide variations in turbine design details, postulated failure conditions, and missile exit scenarios, the conditions for the two tests were carefully selected to be as prototypical as possible, while still maintaining the well-controlled and well-characterized test conditions needed for generating benchmark data

Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

Science.gov (United States)

Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

2015-04-20

During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Entry and Exit.

Science.gov (United States)

1987-03-01

1. Introduction R Analyses of industrial competition have attained a new vigor with the application of game -theoretic methods. The process of... competition is represented in models that reflect genuine struggles for entry, market power, and continuing survival. Dynamics and informational effects are...presents a few of the models developed recently to study competitive processes that affect a firm’s entry into a market , and the decision to exit. The

Exiting and Returning to the Parental Home for Boomerang Kids.

Science.gov (United States)

Sandberg-Thoma, Sara E; Snyder, Anastasia R; Jang, Bohyun Joy

2015-06-01

Young adults commonly exit from and return to the parental home, yet few studies have examined the motivation behind these exits and returns using a life course framework. Using data from the National Longitudinal Survey of Youth 1997, the authors examined associations between mental health problems and economic characteristics and exits from (n = 8,162), and returns to (n = 6,530), the parental home during the transition to adulthood. The average age of the respondents was 24 years. The authors found evidence that mental health and economic characteristics were related to home leaving and returning. Emotional distress was associated with earlier exits from, and returns to, the parental home; alcohol problems were associated with earlier returns to the parental home. The findings regarding economic resources were unexpectedly mixed. Greater economic resources were linked to delayed exits from, and earlier returns to, the parental home. The implications of these findings for young adults are discussed.

Shored gunshot wound of exit. A phenomenon with identity crisis.

Science.gov (United States)

Aguilar, J C

1983-09-01

Shored gunshot wound of exit is produced when the outstretched skin is impaled, sandwiched, and crushed between the outgoing bullet and the unyielding object over the exit site, thus leaving an abrasion collar on the wound margin. Proper coaptation of the wound margin is impossible because of the loss of skin just like those observed in entrance wounds. In contrast to the entrance wound, the supported exit wound shows a scalloped or punched-out abrasion collar and sharply contoured skin in between the radiating skin lacerations marginating the abrasion (Fig. 1). Should gunpowder be observed around the exit site, it is often unevenly distributed, and is not associated with searing, gunpowder stippled abrasion, tatooing, and deposition of soot.

Dance of the Chromosomes: A Kinetic Learning Approach to Mitosis and Meiosis

Science.gov (United States)

Kreiser, Brian; Hairston, Rosalina

2007-01-01

Understanding mitosis and meiosis is fundamental to understanding the basics of Mendelian inheritance, yet many students find these concepts challenging or confusing. Here we present a visually and physically stimulating activity using minimal supplies to supplement traditional instruction in order to engage the students and facilitate…

Induction of mitosis in the cultured rabbit lens initiated by the addition of insulin to medium KEI-4

Energy Technology Data Exchange (ETDEWEB)

Reddan, J R; Unakar, N J; Harding, C V; Bagchi, M; Saldana, G

1975-01-01

The epithelium of lenses cultured in KEI-4, a completely defined medium formulated with specific reference to the biochemistry and physiology of the rabbit lens, exhibits a pattern of cell division similar to that noted for the organ in situ. Initial fluctuations in mitotic activity occurred in the area of the germinative zone during the first 24 hr of culture. Mitosis decreased at 1 hr, was extremely low at 3 hr and returned to values comparable for lens in vivo by 22 hr. The precipitous drop in mitosis noted at 3 hr is in part attributable to the isolation of the lens from adjoining tissue. The addition of insulin to KEI-4 triggers a parasynchronous burst of DNA synthesis throughout the central lens epithelium. The activation requires the intact hormone; neither proinsulin nor the A and/or B chains of insulin, nor glucagon nor zinc chloride can initiate mitosis. The gamma-globulin-rich fraction of rabbit serum can also stimulate mitosis. The addition of dibutyryl adenosine 3':5' cyclic monophosphate (DBeAMP) plus theophylline to KEI-4-insulin inhibits mitosis and prevents the cells from entering the synthetic phase of the cell cycle. Theophylline alone or DBeAMP alone brings about a 90 percent reduction in the insulin-induced mitotic responses. Lenses exposed to insulin show a marked increase in RNA synthesis and also exhibit an increased binding of tritiated actinomycin D at 1 and 3 hr of culture relative to KEI-4 controls. The hormone apparently activates the genome including those genes governing cell division. The system is amenable for long-term culture of the mammalian lens and since the constituents of the medium are known it should be possible to determine the factor(s) in the medium which, in conjunction with insulin, are needed for the induction of cell division.

Exit and Voice: Organizational Loyalty and Dispute Resolution Strategies

Science.gov (United States)

Hoffmann, Elizabeth A.

2006-01-01

This study compares workplace dispute resolution strategies (exit, voice and toleration) in matched pairs of conventional and worker-owned cooperative organizations operating in three industries--coal mining, taxicab driving and organic food distribution. Building on Hirschman's classic exit, voice and loyalty thesis, this research demonstrates…

Automatic Detection of Mitosis and Nuclei From Cytogenetic Images by CellProfiler Software for Mitotic Index Estimation.

Science.gov (United States)

González, Jorge Ernesto; Radl, Analía; Romero, Ivonne; Barquinero, Joan Francesc; García, Omar; Di Giorgio, Marina

2016-12-01

Mitotic Index (MI) estimation expressed as percentage of mitosis plays an important role as quality control endpoint. To this end, MI is applied to check the lot of media and reagents to be used throughout the assay and also to check cellular viability after blood sample shipping, indicating satisfactory/unsatisfactory conditions for the progression of cell culture. The objective of this paper was to apply the CellProfiler open-source software for automatic detection of mitotic and nuclei figures from digitized images of cultured human lymphocytes for MI assessment, and to compare its performance to that performed through semi-automatic and visual detection. Lymphocytes were irradiated and cultured for mitosis detection. Sets of images from cultures were analyzed visually and findings were compared with those using CellProfiler software. The CellProfiler pipeline includes the detection of nuclei and mitosis with 80% sensitivity and more than 99% specificity. We conclude that CellProfiler is a reliable tool for counting mitosis and nuclei from cytogenetic images, saves considerable time compared to manual operation and reduces the variability derived from the scoring criteria of different scorers. The CellProfiler automated pipeline achieves good agreement with visual counting workflow, i.e. it allows fully automated mitotic and nuclei scoring in cytogenetic images yielding reliable information with minimal user intervention. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lingering illness or sudden death? Pre-exit employment developments in German establishments

OpenAIRE

Fackler, Daniel; Schnabel, Claus; Wagner, Joachim

2012-01-01

Using a large administrative dataset for Germany, this paper compares employment developments in exiting and surviving establishments. For both West and East Germany we find a clear 'shadow of death' effect reflecting lingering illness: establishments shrink dramatically already several years before closure, employment growth rates differ strongly between exiting and surviving establishments, and this difference becomes stronger as exit approaches. We further show that prior to exit the workf...

The importance of G1/S-border and mitosis in the fixation

International Nuclear Information System (INIS)

Iliakis, G.; Nuesse, M.

1983-01-01

The ability of synchronized Ehrlich ascites tumour cells to repair PLD was measured by introducing delays in their progression through the cell cycle either in the same phase as that where the irradiation was given or in a subsequent phase. Cells were incubated for this purpose either in balanced salt solution which nonspecifically delayed progression in all cell cycle phases or with 0.5 μg/ml aphidicolin which delayed cells in S-phase. Cells which had been delayed in their progression through the cell cycle were able to repair PLD irrespective of the phase at which they were held. In cases where the delay in the progression through the cell cycle was introduced in a phase subsequent to that of the exposure to irradiation, repair of PLD was observed only if the cells had not passed the G1/S-border or mitosis. Based on these results, the importance of G1/S-border and mitosis in the fixation of PLD is suggested. (orig.)

Analysis of unexpected exits using the Fokker - Planck equation

NARCIS (Netherlands)

Herwaarden, van O.A.

1996-01-01

In this thesis exit problems are considered for stochastic dynamical systems with small random fluctuations. We study exit from a domain in the state space through a boundary, or a specified part of the boundary, that is unattainable in the underlying deterministic system. We analyze

Cdk1-cyclin B1-mediated phosphorylation of tumor-associated microtubule-associated protein/cytoskeleton-associated protein 2 in mitosis.

Science.gov (United States)

Hong, Kyung Uk; Kim, Hyun-Jun; Kim, Hyo-Sil; Seong, Yeon-Sun; Hong, Kyeong-Man; Bae, Chang-Dae; Park, Joobae

2009-06-12

During mitosis, establishment of structurally and functionally sound bipolar spindles is necessary for maintaining the fidelity of chromosome segregation. Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton-associated protein 2 (CKAP2), is a mitotic spindle-associated protein whose level is frequently up-regulated in various malignancies. Previous reports have suggested that TMAP is a potential regulator of mitotic spindle assembly and dynamics and that it is required for chromosome segregation to occur properly. So far, there have been no reports on how its mitosis-related functions are regulated. Here, we report that TMAP is hyper-phosphorylated at the C terminus specifically during mitosis. At least four different residues (Thr-578, Thr-596, Thr-622, and Ser-627) were responsible for the mitosis-specific phosphorylation of TMAP. Among these, Thr-622 was specifically phosphorylated by Cdk1-cyclin B1 both in vitro and in vivo. Interestingly, compared with the wild type, a phosphorylation-deficient mutant form of TMAP, in which Thr-622 had been replaced with an alanine (T622A), induced a significant increase in the frequency of metaphase cells with abnormal bipolar spindles, which often displayed disorganized, asymmetrical, or narrow and elongated morphologies. Formation of these abnormal bipolar spindles subsequently resulted in misalignment of metaphase chromosomes and ultimately caused a delay in the entry into anaphase. Moreover, such defects resulting from the T622A mutation were associated with a decrease in the rate of protein turnover at spindle microtubules. These findings suggest that Cdk1-cyclin B1-mediated phosphorylation of TMAP is important for and contributes to proper regulation of microtubule dynamics and establishment of functional bipolar spindles during mitosis.

Cdk1-Cyclin B1-mediated Phosphorylation of Tumor-associated Microtubule-associated Protein/Cytoskeleton-associated Protein 2 in Mitosis*

Science.gov (United States)

Uk Hong, Kyung; Kim, Hyun-Jun; Kim, Hyo-Sil; Seong, Yeon-Sun; Hong, Kyeong-Man; Bae, Chang-Dae; Park, Joobae

2009-01-01

During mitosis, establishment of structurally and functionally sound bipolar spindles is necessary for maintaining the fidelity of chromosome segregation. Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton-associated protein 2 (CKAP2), is a mitotic spindle-associated protein whose level is frequently up-regulated in various malignancies. Previous reports have suggested that TMAP is a potential regulator of mitotic spindle assembly and dynamics and that it is required for chromosome segregation to occur properly. So far, there have been no reports on how its mitosis-related functions are regulated. Here, we report that TMAP is hyper-phosphorylated at the C terminus specifically during mitosis. At least four different residues (Thr-578, Thr-596, Thr-622, and Ser-627) were responsible for the mitosis-specific phosphorylation of TMAP. Among these, Thr-622 was specifically phosphorylated by Cdk1-cyclin B1 both in vitro and in vivo. Interestingly, compared with the wild type, a phosphorylation-deficient mutant form of TMAP, in which Thr-622 had been replaced with an alanine (T622A), induced a significant increase in the frequency of metaphase cells with abnormal bipolar spindles, which often displayed disorganized, asymmetrical, or narrow and elongated morphologies. Formation of these abnormal bipolar spindles subsequently resulted in misalignment of metaphase chromosomes and ultimately caused a delay in the entry into anaphase. Moreover, such defects resulting from the T622A mutation were associated with a decrease in the rate of protein turnover at spindle microtubules. These findings suggest that Cdk1-cyclin B1-mediated phosphorylation of TMAP is important for and contributes to proper regulation of microtubule dynamics and establishment of functional bipolar spindles during mitosis. PMID:19369249

Proteomic analysis of polyribosomes identifies splicing factors as potential regulators of translation during mitosis.

Science.gov (United States)

Aviner, Ranen; Hofmann, Sarah; Elman, Tamar; Shenoy, Anjana; Geiger, Tamar; Elkon, Ran; Ehrlich, Marcelo; Elroy-Stein, Orna

2017-06-02

Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis. Then, using a combination of pulsed SILAC, metabolic labeling and ribosome profiling, we showed that knockdown of hnRNP C affects both global and transcript-specific translation rates and found that hnRNP C is specifically important for translation of mRNAs that encode ribosomal proteins and translation factors. Taken together, our results demonstrate how proteomic analysis of polysomes can provide insight into translation regulation under various cellular conditions of interest and suggest that hnRNP C facilitates production of translation machinery components during mitosis to provide daughter cells with the ability to efficiently synthesize proteins as they enter G1 phase. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Going, Going, Gone. Innovation and Exit in Manufacturing Firms

NARCIS (Netherlands)

E. Cefis (Elena); O. Marsili (Orietta)

2007-01-01

textabstractThis paper examines the effect of innovation on the risk of exit of a firm, distinguishing between different modes of exits. Innovation represents a resource and a capability that helps a firm to build competitive advantage and remain in the market. At the same time, the resources and

Comparison of sources of exit fluence variation for IMRT

International Nuclear Information System (INIS)

Gardner, Joseph K; Gordon, J James; Wang Song; Siebers, Jeffrey V; Clews, Luke; Greer, Peter B

2009-01-01

The fluence exiting a patient during beam delivery can be used as treatment delivery quality assurance, either by direct comparison with expected exit fluences or by backprojection to reconstruct the patient dose. Multiple possible sources of measured exit fluence deviations exist, including changes in the beam delivery and changes in the patient anatomy. The purpose of this work is to compare the deviations caused by these sources. Machine delivery-related variability is measured by acquiring multiple dosimetric portal images (DPIs) of several test fields without a patient/phantom in the field over a time period of 2 months. Patient anatomy-related sources of fluence variability are simulated by computing transmission DPIs for a prostate patient using the same incident fluence for 11 different computed tomography (CT) images of the patient anatomy. The standard deviation (SD) and maximum deviation of the exit fluence, averaged over 5 mm x 5 mm square areas, is calculated for each test set. Machine delivery fluence SDs as large as 1% are observed for a sample patient field and as large as 2.5% for a picket-fence dMLC test field. Simulations indicate that day-to-day patient anatomy variations induce exit fluence SDs as large as 3.5%. The largest observed machine delivery deviations are 4% for the sample patient field and 7% for the picket-fence field, while the largest difference for the patient anatomy-related source is 8.5%. Since daily changes in patient anatomy can result in substantial exit fluence deviations, care should be taken when applying fluence back-projection to ensure that such deviations are properly attributed to their source. (note)

Asymmetrical distribution of the transcriptionally competent NORs in mitosis

Czech Academy of Sciences Publication Activity Database

Kalmárová, Markéta; Kováčik, Lubomír; Popov, Alexey; Testillano, P. S.; Smirnov, Evgeny

2008-01-01

Roč. 163, č. 1 (2008), s. 40-44 ISSN 1047-8477 R&D Projects: GA ČR(CZ) GA304/06/1691 Grant - others:Wellcome Trust(XE) 075834/04/Z; GA MŠk(CZ) LC535; GA ČR(CZ) GA304/06/1662; C.S.I.C.(ES) CS-ES2007-8/16 Program:LC Institutional research plan: CEZ:AV0Z50110509 Keywords : mitosis * NORs * asymmetry Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.059, year: 2008

Heterologous expression of mammalian Plk1 in Drosophila reveals divergence from Polo during late mitosis

International Nuclear Information System (INIS)

Pearson, John; Godinho, Susana A.; Tavares, Alvaro; Glover, David M.

2006-01-01

Drosophila Polo kinase is the founder member of a conserved kinase family required for multiple stages of mitosis. We assessed the ability of mouse Polo-like kinase 1 (Plk1) to perform the multiple mitotic functions of Polo kinase, by expressing a Plk1-GFP fusion in Drosophila. Consistent with the previously reported localization of Polo kinase, Plk1-GFP was strongly localized to centrosomes and recruited to the centromeric regions of condensing chromosomes during early mitosis. However, in contrast to a functional Polo-GFP fusion, Plk1-GFP failed to localize to the central spindle midzone in both syncytial embryo mitosis and the conventional mitoses of cellularized embryos and S2 cells. Moreover, unlike endogenous Polo kinase and Polo-GFP, Plk1-GFP failed to associate with the contractile ring. Expression of Plk1-GFP enhanced the lethality of hypomorphic polo mutants and disrupted the organization of the actinomyosin cytoskeleton in a dominant-negative manner. Taken together, our results suggest that endogenous Polo kinase has specific roles in regulating actinomyosin rearrangements during Drosophila mitoses that its mammalian counterpart, Plk1, cannot fulfill. Consistent with this hypothesis, we observed defects in the cortical recruitment of myosin and myosin regulatory light chain in Polo deficient cells

INDEKS MITOSIS UJUNG AKAR KECAMBAH CABE BESAR (Capsicum annuum L. SETELAH PERLAKUAN SUSPENSI Trichoderma sp.

Directory of Open Access Journals (Sweden)

PetroneLa Deno Raja

2016-06-01

Full Text Available Penelitian ini bertujuan untuk mengetahui indeks mitosis ujung akar kecambah cabe besar (Capsicum annuum L. setelah perlakuan suspensi Trichoderma sp. Penelitian ini dilakukan di laboratorium Struktur Perkembangan Tumbuhan Jurusan Biologi FMIPA, Universitas Udayana dari Oktober 2013-November 2013. Metode yang digunakan adalah metode squash, biji cabe untuk kontrol direndam dalam air ± 6 jam, untuk perlakuan biji setelah direndam air, direndam lagi dalam suspensi Trichoderma sp. 10-7 selama ± 6 jam, selanjutnya dikecambahkan. Ujung akar kecambah 2 mm dipotong, difiksasi dalam larutan farmer ± 2-24 jam, dihidrolisis dalam larutan 3N HCL ± 2-5 menit dan kemudian pewarnaan dengan aceto orcein ± 5 menit. Pengamatan dilakukan dengan mikroskop binokuler, data pembelahan tiap fase mitosis dihitung (%, dicatat dan difoto, dan dianalisis dengan menggunakan uji paired T tes.Hasil penelitian menunjukkan bahwa Trichoderma sp. berpengaruh terhadap indeks mitosis sel ujung akar Capsicum annuum L.,  pada fase metafase berbeda nyata antara kontrol dan perlakuan, sedangkan pada fase profase, anafase dan telofase berbeda tidak nyata.  Pada perlakuan persentase fase profase, metafase, anafase dan telofase (77,14%; 12,96 %; 5,88 % dan 5,23 % lebih tinggi dari kontrol (66,40 %; 5,44 %; 4,96 % dan 4,66 %.

Using an electronic portal imaging device for exit dose measurements in radiotherapy

International Nuclear Information System (INIS)

Ganowicz, M.; Wozniak, B.; Bekman, A.; Maniakowski, Z.

2003-01-01

To present a method of determining the exit dose with the use of an electronic portal imaging device (EPID). The device used was the Portal Vision LC250 (Varian). The EPID signals on the central beam axis have been related to the exit dose. The exit dose measurements were performed with the ionisation chamber in the slab phantom at the distance of dose maximum from the exit surface of the phantom. EPID reading was investigated as a function of field size, phantom thickness and source-detector distance. The relation between dose rate and the EPID reading is described with empirical functions applicable to the obtained data. The exit dose is calculated from the EPID reading as a product of the calibration factor and appropriate correction factors. The determination of the exit dose rate from the EPID signal requires the knowledge of many parameters and earlier determination of essential characteristics. (author)

Mitosis detection in breast cancer histological images An ICPR 2012 contest

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Ludovic Roux

2013-01-01

Full Text Available Introduction: In the framework of the Cognitive Microscope (MICO project, we have set up a contest about mitosis detection in images of H and E stained slides of breast cancer for the conference ICPR 2012. Mitotic count is an important parameter for the prognosis of breast cancer. However, mitosis detection in digital histopathology is a challenging problem that needs a deeper study. Indeed, mitosis detection is difficult because mitosis are small objects with a large variety of shapes, and they can thus be easily confused with some other objects or artefacts present in the image. We added a further dimension to the contest by using two different slide scanners having different resolutions and producing red-green-blue (RGB images, and a multi-spectral microscope producing images in 10 different spectral bands and 17 layers Z-stack. 17 teams participated in the study and the best team achieved a recall rate of 0.7 and precision of 0.89. Context: Several studies on automatic tools to process digitized slides have been reported focusing mainly on nuclei or tubule detection. Mitosis detection is a challenging problem that has not yet been addressed well in the literature. Aims: Mitotic count is an important parameter in breast cancer grading as it gives an evaluation of the aggressiveness of the tumor. However, consistency, reproducibility and agreement on mitotic count for the same slide can vary largely among pathologists. An automatic tool for this task may help for reaching a better consistency, and at the same time reducing the burden of this demanding task for the pathologists. Subjects and Methods: Professor Frιdιrique Capron team of the pathology department at Pitiι-Salpκtriθre Hospital in Paris, France, has selected a set of five slides of breast cancer. The slides are stained with H and E. They have been scanned by three different equipments: Aperio ScanScope XT slide scanner, Hamamatsu NanoZoomer 2.0-HT slide scanner and 10 bands

The determinants of firm exit in the French food industries

OpenAIRE

Blanchard, Pierre; Mathieu, Claude

2012-01-01

A semi-parametric approach is used to estimate firm propensity to exit. The unobserved individual productivity of a firm is first estimated using the Ackerberg et al. (2006) approach and then introduced as a determinant of firm exit in conjunction with other variables that may serve as barriers to exit, including the firm’s level of sunk costs and the industry concentration. Using an unbalanced panel of data for 5,849 firms in French food industries from 1996 to 2002, we find a signifi...

Bora and Aurora-A continue to activate Plk1 in mitosis

Czech Academy of Sciences Publication Activity Database

Bruinsma, W.; Macůrek, Libor; Freire, R.; Lindqvist, A.; Medema, R.H.

2014-01-01

Roč. 127, č. 4 (2014), s. 801-811 ISSN 0021-9533 R&D Projects: GA ČR GA13-18392S Grant - others:Ministerio de Economía y Competitividad(ES) SAF2010-22357; CONSOLIDER-Ingenio(NL) CDS2007-0015 Keywords : Aurora-A * Bora * Mitosis * Plk1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.432, year: 2014

Congenital Cervical Teratoma: Anaesthetic Management (The EXIT Procedure

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Ferruh Bilgin

2009-01-01

Full Text Available Ex utero intrapartum treatment (EXIT is a procedure performed during caesarean section with preservation of fetal-placental circulation, which allows the safe handling of fetal airways with risk of airways obstruction. This report aimed at describing a case of anaesthesia for EXIT in a fetus with cervical teratoma. A 30-year-old woman, 70 kg, 160 cm, gravida 2, para 1, was followed because of polyhydramniosis diagnosed at 24 weeks′ gestation. During a routine ultrasonographic examination at 35 weeks′ gestation, it was noticed that the fetus had a tumoral mass on the anterior neck, the mass had cystic and calcified components and with a size of was 10 x 6 x5 cm. The patient with physical status ASA I, was submitted to caesarean section under general anaesthesia with mechanically controlled ventilation for exutero intrapartum treatment (EXIT. Anaesthesia was induced in rapid sequence with fentanyl, propofol and rocuronium and was maintained with isoflurane in 2.5 at 3 % in O 2 and N 2 O (50%. After hysterotomy, fetus was partially released assuring uterus-placental circulation, followed by fetal laryngoscopy and tracheal intuba-tion. The infant was intubated with an uncuffed, size 2.5 endotracheal tube. Excision of the mass was performed under general anaesthesia. After surgical intervention, on the fourth postoperative day, the infant was extubated and the newborn was discharged to the pediatric neonatal unit and on the seventh day postoperatively to home without complications. Major recommendations for EXIT are maternal-fetal safety, uterine relaxation to maintain uterine volume and uterus-placental circulation, and fetal immobility to help airway handling. We report one case of cervical teratoma managed successfully with EXIT procedure.

The Effect of Exit Strategy on Optimal Portfolio Selection with Birandom Returns

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Guohua Cao

2013-01-01

Full Text Available The aims of this paper are to use a birandom variable to denote the stock return selected by some recurring technical patterns and to study the effect of exit strategy on optimal portfolio selection with birandom returns. Firstly, we propose a new method to estimate the stock return and use birandom distribution to denote the final stock return which can reflect the features of technical patterns and investors' heterogeneity simultaneously; secondly, we build a birandom safety-first model and design a hybrid intelligent algorithm to help investors make decisions; finally, we innovatively study the effect of exit strategy on the given birandom safety-first model. The results indicate that (1 the exit strategy affects the proportion of portfolio, (2 the performance of taking the exit strategy is better than when the exit strategy is not taken, if the stop-loss point and the stop-profit point are appropriately set, and (3 the investor using the exit strategy become conservative.

3D analysis of mitosis distribution highlights the longitudinal zonation and diarch symmetry in proliferation activity of the Arabidopsis thaliana root meristem.

Science.gov (United States)

Lavrekha, Viktoriya V; Pasternak, Taras; Ivanov, Victor B; Palme, Klaus; Mironova, Victoria V

2017-12-01

To date CYCB1;1 marker and cortex cell lengths have been conventionally used to determine the proliferation activity of the Arabidopsis root meristem. By creating a 3D map of mitosis distribution we showed that these markers overlooked that stele and endodermis save their potency to divide longer than the cortex and epidermis. Cessation of cell divisions is not a random process, so that mitotic activity within the endodermis and stele shows a diarch pattern. Mitotic activity of all root tissues peaked at the same distance from the quiescent center (QC); however, different tissues stopped dividing at different distances, with cells of the protophloem exiting the cell cycle first and the procambial cells being the last. The robust profile of mitotic activity in the root tip defines the longitudinal zonation in the meristem with the proliferation domain, where all cells are able to divide; and the transition domain, where the cell files cease to divide. 3D analysis of cytokinin deficient and cytokinin signaling mutants showed that their proliferation domain is similar to that of the wild type, but the transition domain is much longer. Our data suggest a strong inhibitory effect of cytokinin on anticlinal cell divisions in the stele. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Thrombopoietin-induced Polyploidization of Bone Marrow Megakaryocytes Is Due to a Unique Regulatory Mechanism in Late Mitosis

Science.gov (United States)

Nagata, Yuka; Muro, Yoshinao; Todokoro, Kazuo

1997-01-01

Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. However, the mechanism underlying this polyploidization remains totally unknown. It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication. We carried out immunohistochemical studies on mouse bone marrow megakaryocytes during thrombopoietin- induced polyploidization and found that during this process megakaryocytes indeed enter mitosis and progress through normal prophase, prometaphase, metaphase, and up to anaphase A, but not to anaphase B, telophase, or cytokinesis. It was clearly observed that multiple spindle poles were formed as the polyploid megakaryocytes entered mitosis; the nuclear membrane broke down during prophase; the sister chromatids were aligned on a multifaced plate, and the centrosomes were symmetrically located on either side of each face of the plate at metaphase; and a set of sister chromatids moved into the multiple centrosomes during anaphase A. We further noted that the pair of spindle poles in anaphase were located in close proximity to each other, probably because of the lack of outward movement of spindle poles during anaphase B. Thus, the reassembling nuclear envelope may enclose all the sister chromatids in a single nucleus at anaphase and then skip telophase and cytokinesis. These observations clearly indicate that polyploidization of megakaryocytes is not simply due to a skipping of mitosis, and that the megakaryocytes must have a unique regulatory mechanism in anaphase, e.g., factors regulating anaphase such as microtubule motor proteins might be involved in this polyploidization process. PMID:9334347

30 CFR 56.4530 - Exits.

Science.gov (United States)

2010-07-01

... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control... a sufficient number of exits to permit prompt escape in case of fire. ...

STIMULATION METHODS IMPROVEMENT OF EXIT ROUTE ON RAILWAY TRANSPORT

Directory of Open Access Journals (Sweden)

A. I. Verlan

2014-01-01

Full Text Available Purpose. The purpose of the article is to assess the costs, which are redistributed in the system «shipper−railroad−consignee» during routing of rail transportation and the development of tariff simulation methods of shippers to the exit routes formation. Methodology. Using economic and mathematical analysis the distribution of costs among the various participants of transportation process during the exit routes formation is investigated in the article. Findings. For implementation of the tariff simulation methods of exit routes and retention of the existing tariff structure it is proposed to provide in the «Tariff catalogue for freight transportation by railway transport of Ukraine» the discount, differentiated from haulage distance. A new method for determining the fees amount for cars supply and removal on approach tracks by train locomotives was also offered. Originality. As a result of the research a new method for determination of the exit rout efficiency that, unlike the existing one, takes into account the various interests of the individual participants in the transportation process was proposed. The dependence of the correction factors to the tariff for freight transportation in their own cars by direct exit routes from distance haulage was obtained. Implementation of these coefficients provides an approximation of railway tariffs to the traffic handling costs. A method for determination the rate of fees for cars supply and removal on approach tracks by train locomotives was offered. Practical value. InUkraine creation of the tariff discounts system for freight transportation by exit routes consistent with international practice and allows bringing the tariff to the real traffic handling cost. This change on the one hand will provide stimulation for private capital investments in infrastructure development and shunting means of approach tracks, on the other – it will fix the shippers to the railroads and stop their outflow

Creating a Double-Spring Model to Teach Chromosome Movement during Mitosis & Meiosis

Science.gov (United States)

Luo, Peigao

2012-01-01

The comprehension of chromosome movement during mitosis and meiosis is essential for understanding genetic transmission, but students often find this process difficult to grasp in a classroom setting. I propose a "double-spring model" that incorporates a physical demonstration and can be used as a teaching tool to help students understand this…

The Set1/COMPASS histone H3 methyltransferase helps regulate mitosis with the CDK1 and NIMA mitotic kinases in Aspergillus nidulans.

Science.gov (United States)

Govindaraghavan, Meera; Anglin, Sarah Lea; Osmani, Aysha H; Osmani, Stephen A

2014-08-01

Mitosis is promoted and regulated by reversible protein phosphorylation catalyzed by the essential NIMA and CDK1 kinases in the model filamentous fungus Aspergillus nidulans. Protein methylation mediated by the Set1/COMPASS methyltransferase complex has also been shown to regulate mitosis in budding yeast with the Aurora mitotic kinase. We uncover a genetic interaction between An-swd1, which encodes a subunit of the Set1 protein methyltransferase complex, with NIMA as partial inactivation of nimA is poorly tolerated in the absence of swd1. This genetic interaction is additionally seen without the Set1 methyltransferase catalytic subunit. Importantly partial inactivation of NIMT, a mitotic activator of the CDK1 kinase, also causes lethality in the absence of Set1 function, revealing a functional relationship between the Set1 complex and two pivotal mitotic kinases. The main target for Set1-mediated methylation is histone H3K4. Mutational analysis of histone H3 revealed that modifying the H3K4 target residue of Set1 methyltransferase activity phenocopied the lethality seen when either NIMA or CDK1 are partially functional. We probed the mechanistic basis of these genetic interactions and find that the Set1 complex performs functions with CDK1 for initiating mitosis and with NIMA during progression through mitosis. The studies uncover a joint requirement for the Set1 methyltransferase complex with the CDK1 and NIMA kinases for successful mitosis. The findings extend the roles of the Set1 complex to include the initiation of mitosis with CDK1 and mitotic progression with NIMA in addition to its previously identified interactions with Aurora and type 1 phosphatase in budding yeast. Copyright © 2014 by the Genetics Society of America.

Accuracy synthesis of T-shaped exit fixed mechanism in a double-crystal monochromator

International Nuclear Information System (INIS)

Wang Fengqin; Cao Chongzhen; Wang Jidai; Li Yushan; Gao Xueguan

2007-01-01

It is a key performance requirement for a double-crystal monochromator that the exit is fixed, and in order to improve the height accuracy of the exit in T-shaped exit fixed mechanism, the expression between the height of the exit and various original errors was put forward using geometrical analysis method. According to the independent action principle of original errors, accuracy synthesis of T-shaped exit fixed mechanism was studied by using the equal accuracy method, and the tolerance ranges of original errors were obtained. How to calculate the tolerance ranges of original errors was explained by giving an example. (authors)

Breast cancer mitosis detection in histopathological images with spatial feature extraction

Science.gov (United States)

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.

Technological Progress, Exit and Trade

DEFF Research Database (Denmark)

Schröder, Philipp; Sørensen, Allan

productivity exporters are more likely to continue to export, and market exit is typically preceded by periods of contracting market shares. We show that the simple inclusion of exogenous economy wide technological progress into the standard Melitz (2003) model generates a tractable dynamic framework...

Do spouses coordinate their work exits? A combined survey and register analysis from Norway.

Science.gov (United States)

Syse, Astri; Solem, Per Erik; Ugreninov, Elisabeth; Mykletun, Reidar; Furunes, Trude

2014-09-01

Research on spouses' joint work exits is scarce, although household factors such as spouses' work status, marital quality, and caregiving burdens are likely to affect seniors' work engagement. We therefore examine whether the work exit probability of one spouse affects that of the other. Discrete-time hazard regression analyses of survey data linked to later registry information including all gainfully employed married respondents aged 50-74 with a working spouse (N = 1,764) were used to assess subsequent work exits. A spouse's work exit is a strong predictor of a respondent's work exit (hazard ratio 3.1, 95% confidence interval [2.5, 4.0]). Educational attainment, poor marital quality, and spouses' health and care needs do not predict work exits. Surprisingly, no gender differences are observed. Research on larger survey samples to distinguish different work exit routes and reasons for spouses' joint work exits appears warranted. To account for cultural and welfare state characteristics, cross-national studies ought to be undertaken. © The Author(s) 2013.

Experiment of cavitation erosion at the exit of a long orifice

Energy Technology Data Exchange (ETDEWEB)

Yagi, Yoshinori; Murase, Michio [Inst. of Nuclear Safety System Inc., Mihama, Fukui (Japan)

2002-09-01

We performed experiments to clarify mechanism of cavitation erosion and to predict cavitation erosion rate at the exit of a long orifice equipped at the chemical and volume control system in a pressurized water reactor (PWR). In order to find this mechanism, we used a high speed video camera. As the result, we observed bubble collapses near the exit of the orifice when flow condition was oscillating. So the bubble collapses due to the oscillation might cause the first stage erosion at the exit of the orifice. Using the orifice which had the cone-shaped exit, we observed that bubbles collapsed near the exit and then they collapsed at the upstream like a chain reaction. So this bubble collapse mechanism could be explained as follows: shock wave was generated by the bubble collapse near the exit, then it propagated upwards, consequently it caused the bubble collapse at the upstream. And we predicted erosion rate by evaluating the effect of the velocity and comparing the erosion resistance between the test speciment (aluminum) and the plant material (stainless steel) by means of vibratory tests. We compared the predicted erosion rate with that of the average value estimated from plant investigation, then we examined the applicability of these method to the plant evaluations. (author)

Effects of radiation and porphyrin on mitosis and chromosomes in human hematopoietic cell lines

International Nuclear Information System (INIS)

Tan, J.C.; Huang, C.C.; Fiel, R.J.

1976-01-01

The effect on mitosis of a human hematopoietic cell line RPMI-1788 treated with a metal chelate (Zn ++ ) of meso-tetra (p-carboxyphenyl) porphine (Zn-TCPP) alone at various concentrations or in combination with gamma-irradiation at various doses were studied. The results showed that both Zn-TCPP and radiation were effective in interfering with normal mitosis and that the effect of radiation was relatively more effective. Data also suggest interacting effects between Zn-TCPP and gamma-irradiation. At low doses of radiation, Zn-TCPP potentiated the effect of radiation. The reverse seemed to be true at a high dose of radiation. The effects of two porphyrins (Zn-TCPP and hematoporphyrin) and radiation on chromosomes were also studied. Chromosomal aberrations characteristic of radiation were observed. The porphyrins were found not to be effective chromosome-breaking agents under the experimental conditions tested

Mto2 multisite phosphorylation inactivates non-spindle microtubule nucleation complexes during mitosis

Science.gov (United States)

Borek, Weronika E.; Groocock, Lynda M.; Samejima, Itaru; Zou, Juan; de Lima Alves, Flavia; Rappsilber, Juri; Sawin, Kenneth E.

2015-01-01

Microtubule nucleation is highly regulated during the eukaryotic cell cycle, but the underlying molecular mechanisms are largely unknown. During mitosis in fission yeast Schizosaccharomyces pombe, cytoplasmic microtubule nucleation ceases simultaneously with intranuclear mitotic spindle assembly. Cytoplasmic nucleation depends on the Mto1/2 complex, which binds and activates the γ-tubulin complex and also recruits the γ-tubulin complex to both centrosomal (spindle pole body) and non-centrosomal sites. Here we show that the Mto1/2 complex disassembles during mitosis, coincident with hyperphosphorylation of Mto2 protein. By mapping and mutating multiple Mto2 phosphorylation sites, we generate mto2-phosphomutant strains with enhanced Mto1/2 complex stability, interaction with the γ-tubulin complex and microtubule nucleation activity. A mutant with 24 phosphorylation sites mutated to alanine, mto2[24A], retains interphase-like behaviour even in mitotic cells. This provides a molecular-level understanding of how phosphorylation ‘switches off' microtubule nucleation complexes during the cell cycle and, more broadly, illuminates mechanisms regulating non-centrosomal microtubule nucleation. PMID:26243668

“Understanding exit from the founder’s business in family firms”

OpenAIRE

C. Salvato; F. Chirico; P. Sharma

2010-01-01

In this chapter we investigate the role of family-specific factors in facilitating or constraining business exit in family firms. Family business literature seems to have an implicit bias towards continuity and persistence in the founder’s business. This is explained by heavy emotional involvement and development of path-dependent core competences over generations. However, several long-lived family firms were able to successfully exit the founder’s business. Exit allowed them to free signifi...

Sumoylation promotes optimal APC/C Activation and Timely Anaphase.

Science.gov (United States)

Lee, Christine C; Li, Bing; Yu, Hongtao; Matunis, Michael J

2018-03-08

The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin E3 ligase that functions as the gatekeeper to mitotic exit. APC/C activity is controlled by an interplay of multiple pathways during mitosis, including the spindle assembly checkpoint (SAC), that are not yet fully understood. Here, we show that sumoylation of the APC4 subunit of the APC/C peaks during mitosis and is critical for timely APC/C activation and anaphase onset. We have also identified a functionally important SUMO interacting motif in the cullin-homology domain of APC2 located near the APC4 sumoylation sites and APC/C catalytic core. Our findings provide evidence of an important regulatory role for SUMO modification and binding in affecting APC/C activation and mitotic exit. © 2018, Lee et al.

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells.

Science.gov (United States)

Lin, Shu; Yuan, Zuo-Fei; Han, Yumiao; Marchione, Dylan M; Garcia, Benjamin A

2016-07-15

How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di- and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di- or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells*

Science.gov (United States)

Lin, Shu; Yuan, Zuo-Fei; Han, Yumiao; Marchione, Dylan M.; Garcia, Benjamin A.

2016-01-01

How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di- and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di- or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2. PMID:27226594

Water-Exit Process Modeling and Added-Mass Calculation of the Submarine-Launched Missile

Directory of Open Access Journals (Sweden)

Yang Jian

2017-11-01

Full Text Available In the process that the submarine-launched missile exits the water, there is the complex fluid solid coupling phenomenon. Therefore, it is difficult to establish the accurate water-exit dynamic model. In the paper, according to the characteristics of the water-exit motion, based on the traditional method of added mass, considering the added mass changing rate, the water-exit dynamic model is established. And with help of the CFX fluid simulation software, a new calculation method of the added mass that is suit for submarine-launched missile is proposed, which can effectively solve the problem of fluid solid coupling in modeling process. Then by the new calculation method, the change law of the added mass in water-exit process of the missile is obtained. In simulated analysis, for the water-exit process of the missile, by comparing the results of the numerical simulation and the calculation of theoretical model, the effectiveness of the new added mass calculation method and the accuracy of the water-exit dynamic model that considers the added mass changing rate are verified.

Analysis of structural and numerical chromosomal aberrations at the first and second mitosis after X irradiation of two-cell mouse embryos

International Nuclear Information System (INIS)

Weissenborn, U.; Streffer, C.

1989-01-01

Two-cell mouse embryos were X-irradiated in the late G2 phase in vivo. The first and second postradiation mitoses were analyzed for chromosomal anomalies. The majority of structural aberrations visible at the first mitosis after irradiation were chromatid breaks and chromatid gaps; only a few interchanges and dicentrics were observed. The aberration frequency resulted in a dose-effect relationship which was well described by a linear model. At the second mitosis 29% of the structural aberrations of the first mitosis were counted; the aberration quality changed only slightly. It is discussed whether these aberrations are to be considered new, derived, or unchanged transmitted aberrations. Contrary to the results obtained after irradiation of one-cell embryos, little chromosome loss was induced by radiation in two-cell embryos

Collective behavior of mice passing through an exit under panic

Science.gov (United States)

Zhang, Teng; Zhang, Xuelin; Huang, Shenshi; Li, Changhai; Lu, Shouxiang

2018-04-01

Collective movement of animal in emergency condition has attracted growing attentions among researchers. However, many rules still need to be confirmed with adequate explanation. Study of collective behavior of mice can improve our understanding about the dynamics of pedestrian movement. However, its rules still need to be confirmed with adequate explanation. In this paper, collective behavior of mice passing through an exit under panic was investigated. The results showed that the total evacuation time decreased with exit width increasing in a certain range. Based on the different tendency of the curve in temporal evolution, the process of mice flow was divided into three stages. The density of mice near the exit peaks at a certain horizontal offset and starts to decrease over time. With the increase of the exit width, the duration of the higher density state decreased. We found that the frequency of time intervals obeyed a lognormal distribution or an exponential decay for different exit widths. In addition, the relationship between the group size and the group flow rate in different scenarios was analyzed. The phenomena found in our experiments show the collective behavioral characteristic of mice under panic. Our analysis in this paper will deepen our understanding of crowd dynamics in emergency condition.

The spatio-temporal dynamics of PKA activity profile during mitosis and its correlation to chromosome segregation

Science.gov (United States)

Vandame, Pauline; Spriet, Corentin; Trinel, Dave; Gelaude, Armance; Caillau, Katia; Bompard, Coralie; Biondi, Emanuele; Bodart, Jean-François

2014-01-01

The cyclic adenosine monophosphate dependent kinase protein (PKA) controls a variety of cellular processes including cell cycle regulation. Here, we took advantages of genetically encoded FRET-based biosensors, using an AKAR-derived biosensor to characterize PKA activity during mitosis in living HeLa cells using a single-cell approach. We measured PKA activity changes during mitosis. HeLa cells exhibit a substantial increase during mitosis, which ends with telophase. An AKAREV T>A inactive form of the biosensor and H89 inhibitor were used to ascertain for the specificity of the PKA activity measured. On a spatial point of view, high levels of activity near to chromosomal plate during metaphase and anaphase were detected. By using the PKA inhibitor H89, we assessed the role of PKA in the maintenance of a proper division phenotype. While this treatment in our hands did not impaired cell cycle progression in a drastic manner, inhibition of PKA leads to a dramatic increase in chromososme misalignement on the spindle during metaphase that could result in aneuploidies. Our study emphasizes the insights that can be gained with genetically encoded FRET-based biosensors, which enable to overcome the shortcomings of classical methologies and unveil in vivo PKA spatiotemporal profiles in HeLa cells. PMID:25485503

The spatio-temporal dynamics of PKA activity profile during mitosis and its correlation to chromosome segregation.

Science.gov (United States)

Vandame, Pauline; Spriet, Corentin; Trinel, Dave; Gelaude, Armance; Caillau, Katia; Bompard, Coralie; Biondi, Emanuele; Bodart, Jean-François

2014-01-01

The cyclic adenosine monophosphate dependent kinase protein (PKA) controls a variety of cellular processes including cell cycle regulation. Here, we took advantages of genetically encoded FRET-based biosensors, using an AKAR-derived biosensor to characterize PKA activity during mitosis in living HeLa cells using a single-cell approach. We measured PKA activity changes during mitosis. HeLa cells exhibit a substantial increase during mitosis, which ends with telophase. An AKAREV T>A inactive form of the biosensor and H89 inhibitor were used to ascertain for the specificity of the PKA activity measured. On a spatial point of view, high levels of activity near to chromosomal plate during metaphase and anaphase were detected. By using the PKA inhibitor H89, we assessed the role of PKA in the maintenance of a proper division phenotype. While this treatment in our hands did not impaired cell cycle progression in a drastic manner, inhibition of PKA leads to a dramatic increase in chromososme misalignement on the spindle during metaphase that could result in aneuploidies. Our study emphasizes the insights that can be gained with genetically encoded FRET-based biosensors, which enable to overcome the shortcomings of classical methologies and unveil in vivo PKA spatiotemporal profiles in HeLa cells.

TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

Science.gov (United States)

Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

2015-01-01

Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. PMID:26283799

30 CFR 57.4530 - Exits for surface buildings and structures.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Exits for surface buildings and structures. 57... Fire Prevention and Control Installation/construction/maintenance § 57.4530 Exits for surface buildings and structures. Surface buildings or structures in which persons work shall have a sufficient number...

Exit, punishment and rewards in commons dilemmas: an experimental study.

Directory of Open Access Journals (Sweden)

Giangiacomo Bravo

Full Text Available Commons dilemmas are interaction situations where a common good is provided or exploited by a group of individuals so that optimal collective outcomes clash with private interests. Although in these situations, social norms and institutions exist that might help individuals to cooperate, little is known about the interaction effects between positive and negative incentives and exit options by individuals. We performed a modified public good game experiment to examine the effect of exit, rewards and punishment, as well as the interplay between exit and rewards and punishment. We found that punishment had a stronger effect than rewards on cooperation if considered by itself, whereas rewards had a stronger effect when combined with voluntary participation. This can be explained in terms of the 'framing effect', i.e., as the combination of exit and rewards might induce people to attach higher expected payoffs to cooperative strategies and expect better behaviour from others.

Critical heat flux and exit film flow rate in a flow boiling system

International Nuclear Information System (INIS)

Ueda, Tatsuhiro; Isayama, Yasushi

1981-01-01

The critical heat flux in a flowing boiling system is an important problem in the evaporating tubes with high thermal load such as nuclear reactors and boilers, and gives the practical design limit. When the heat flux in uniformly heated evaporating tubes is gradually raised, the tube exit quality increases, and soon, the critical heat flux condition arises, and the wall temperature near tube exit rises rapidly. In the region of low exit quality, the critical heat flux condition is caused by the transition from nucleating boiling, and in the region of high exit quality, it is caused by dry-out. But the demarcation of both regions is not clear. In this study, for the purpose of obtaining the knowledge concerning the critical heat flux condition in a flowing boiling system, the relation between the critical heat flux and exit liquid film flow rate was examined. For the experiment, a uniformly heated vertical tube supplying R 113 liquid was used, and the measurement in the range of higher heating flux and mass velocity than the experiment by Ueda and Kin was carried out. The experimental setup and experimental method, the critical heat flux and exit quality, the liquid film flow rate at heating zone exit, and the relation between the critical heat flux and the liquid film flow rate at exit are described. (Kako, I.)

First Degree Pacemaker Exit Block

Directory of Open Access Journals (Sweden)

Johnson Francis

2016-10-01

Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

Exit Planning At Joost El

DEFF Research Database (Denmark)

Nellemann, Camilla

2017-01-01

This is a Danish version. This case focuses on an owner-manager's considerations regarding his exit. Carsten Joost established Joost El in 2005. It currently employs 10 people. He has two sons but no intention to hand over the business to them. Rather, he hopes that his key employee eventually...

Effects of injection nozzle exit width on rotating detonation engine

Science.gov (United States)

Sun, Jian; Zhou, Jin; Liu, Shijie; Lin, Zhiyong; Cai, Jianhua

2017-11-01

A series of numerical simulations of RDE modeling real injection nozzles with different exit widths are performed in this paper. The effects of nozzle exit width on chamber inlet state, plenum flowfield and detonation propagation are analyzed. The results are compared with that using an ideal injection model. Although the ideal injection model is a good approximation method to model RDE inlet, the two-dimensional effects of real nozzles are ignored in the ideal injection model so that some complicated phenomena such as the reflected waves caused by the nozzle walls and the reversed flow into the nozzles can not be modeled accurately. Additionally, the ideal injection model overpredicts the block ratio. In all the cases that stabilize at one-wave mode, the block ratio increases as the nozzle exit width gets smaller. The dual-wave mode case also has a relatively high block ratio. A pressure oscillation in the plenum with the same main frequency with the rotating detonation wave is observed. A parameter σ is applied to describe the non-uniformity in the plenum. σ increases as the nozzle exit width gets larger. Under some condition, the heat release on the interface of fresh premixed gas layer and detonation products can be strong enough to induce a new detonation wave. A spontaneous mode-transition process is observed for the smallest exit width case. Due to the detonation products existing in the premixed gas layer before the detonation wave, the detonation wave will propagate through reactants and products alternately, and therefore its strength will vary with time, especially near the chamber inlet. This tendency gets weaker as the injection nozzle exit width increases.

Revisit the faster-is-slower effect for an exit at a corner

Science.gov (United States)

Chen, Jun Min; Lin, Peng; Wu, Fan Yu; Li Gao, Dong; Wang, Guo Yuan

2018-02-01

The faster-is-slower effect (FIS), which means that crowd at a high enough velocity could significantly increase the evacuation time to escape through an exit, is an interesting phenomenon in pedestrian dynamics. Such phenomenon had been studied widely and has been experimentally verified in different systems of discrete particles flowing through a centre exit. To experimentally validate this phenomenon by using people under high pressure is difficult due to ethical issues. A mouse, similar to a human, is a kind of self-driven and soft body creature with competitive behaviour under stressed conditions. Therefore, mice are used to escape through an exit at a corner. A number of repeated tests are conducted and the average escape time per mouse at different levels of stimulus are analysed. The escape times do not increase obviously with the level of stimulus for the corner exit, which is contrary to the experiment with the center exit. The experimental results show that the FIS effect is not necessary a universal law for any discrete system. The observation could help the design of buildings by relocating their exits to the corner in rooms to avoid the formation of FIS effect.

Application of an entry-exit tariff model to the gas transport system in Spain

International Nuclear Information System (INIS)

Alonso, Alejandro; Serrano, Miguel; Olmos, Luis

2010-01-01

Under an entry-exit gas tariff system, reservation of capacity is split into entry capacity, to transport gas from the injection points to a virtual balancing point, and exit capacity, to transport gas from the balancing point to the exit points in the system. Entry-exit tariff for gas transport systems have been recommended by the 3rd EU Energy Package, since they are cost reflective, facilitate gas trade and can provide signals for the location of gas injections or off-takes. The advisability of applying an entry-exit tariff system is discussed in this paper. Apart from this, authors propose an entry-exit tariff model and apply it to compute charges for the Spanish gas transport system in 2009. Results produced by the model are presented as coefficients which should multiply the current postal transport tariff. The paper concludes that entry-exit tariffs would be useful location signals which would result in a better use of the gas transport system in Spain. In those cases where demand exceeds available capacity, as it occurs at the congested connection with France, entry-exit tariffs could be supplemented by capacity charges at entry points resulting from auctions. (author)

RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis

DEFF Research Database (Denmark)

Di Marco, Stefano; Hasanova, Zdenka; Kanagaraj, Radhakrishnan

2017-01-01

The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent...... on its Ser727 phosphorylation by CDK1. Upon replication stress, RECQ5 associates with CFSs in early mitosis through its physical interaction with MUS81 and promotes MUS81-dependent mitotic DNA synthesis. RECQ5 depletion or mutational inactivation of its ATP-binding site, RAD51-interacting domain...

The use of the exit interview to reduce turnover amongst healthcare professionals.

Science.gov (United States)

Flint, Anndrea; Webster, Joan

2011-01-19

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We used a comprehensive search strategy including an electronic search of the following databases: DARE, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC (search date: 7 September 2010) and EPOC Specialised Register (search date: 30 September 2009). We also screened the reference lists of included studies and relevant reviews. Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The search identified 1560 citations of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment. They were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

How-to-Do-It: Hands-on Activity for Mitosis, Meiosis and the Fundamentals of Heredity.

Science.gov (United States)

Taylor, Mark F.

1988-01-01

Described is an exercise which uses inexpensive and easy-to-make materials to demonstrate the basic fundamentals of heredity. Discusses two approaches using a hypothetical insert to demonstrate inheritance, mitosis, meiosis, and genotypic and phenotypic frequencies. (CW)

Population control of resident and immigrant microglia by mitosis and apoptosis.

Science.gov (United States)

Wirenfeldt, Martin; Dissing-Olesen, Lasse; Anne Babcock, Alicia; Nielsen, Marianne; Meldgaard, Michael; Zimmer, Jens; Azcoitia, Iñigo; Leslie, Robert Graham Quinton; Dagnaes-Hansen, Frederik; Finsen, Bente

2007-08-01

Microglial population expansion occurs in response to neural damage via processes that involve mitosis and immigration of bone marrow-derived cells. However, little is known of the mechanisms that regulate clearance of reactive microglia, when microgliosis diminishes days to weeks later. We have investigated the mechanisms of microglial population control in a well-defined model of reactive microgliosis in the mouse dentate gyrus after perforant pathway axonal lesion. Unbiased stereological methods and flow cytometry demonstrate significant lesion-induced increases in microglial numbers. Reactive microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations.

Exploring the Relationship of Exit Flow and Jam Density in Panic Scenarios Using Animal Dynamics

NARCIS (Netherlands)

Sobhani, A.; Sarvi, M.; Duives, D.C.; Ejtemai, O.; Aghabayk, K.; Hoogendoorn, S.P.

2014-01-01

There are few studies investigating crowd dynamics in panic situations. They used measures such as exit flow rate to explore the exit performance in evacuation scenarios. However, there is limited research exploring the relationship of exit flow rate and density behind the exit for panic scenarios.

Localization of spindle checkpoint proteins in cells undergoing mitosis with unreplicated genomes.

Science.gov (United States)

Johnson, Mary Kathrine; Cooksey, Amanda M; Wise, Dwayne A

2008-11-01

CHO cells can be arrested with hydoxyurea at the beginning of the DNA synthesis phase of the cell cycle. Subsequent treatment with the xanthine, caffeine, induces cells to bypass the S-phase checkpoint and enter unscheduled mitosis [Schlegel and Pardee,1986, Science 232:1264-1266]. These treated cells build a normal spindle and distribute kinetochores, unattached to chromosomes, to their daughter cells [Brinkley et al.,1988, Nature 336:251-254; Zinkowski et al.,1991, J Cell Biol 113:1091-1110; Wise and Brinkley,1997, Cell Motil Cytoskeleton 36:291-302; Balczon et al.,2003, Chromosoma 112:96-102]. To investigate how these cells distribute kinetochores to daughter cells, we analyzed the spindle checkpoint components, Mad2, CENP-E, and the 3F3 phosphoepitope, using immunofluorescence and digital microscopy. Even though the kinetochores were unpaired and DNA was fragmented, the tension, alignment, and motor components of the checkpoint were found to be present and localized as predicted in prometaphase and metaphase. This unusual mitosis proves that a cell can successfully localize checkpoint proteins and divide even when kinetochores are unpaired and fragmented. (c) 2008 Wiley-Liss, Inc.

Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis.

Science.gov (United States)

Shan, Lingjuan; Wu, Chan; Chen, Di; Hou, Lei; Li, Xin; Wang, Lixia; Chu, Xiao; Hou, Yifeng; Wang, Zhaohui

2017-02-20

In the sexually reproductive organisms, gametes are produced by meiosis following a limited mitotic amplification. However, the intrinsic program switching cells from mitotic to meiotic cycle is unclear. Alternative polyadenylation (APA) is a highly conserved means of gene regulation and is achieved by the RNA 3'-processing machinery to generate diverse 3'UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 3'UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 3'UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 3'-processing factors disrupted germline's progression to meiosis, indicative of APA's active role in this transition. An RNA-binding protein (RBP) Tut could directly bind 3'UTRs of 3'-processing factors whose expressions were repressed in the presence of Tut-containing complex. Further, we demonstrated that this RBP complex could execute the repression post-transcriptionally by recruiting CCR4/Twin of deadenylation complex. Thus, we propose that an RBP complex regulates the dynamic APA profile to promote the mitosis-to-meiosis transition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

International Competition and Small-Firm Exit in US Manufacturing

OpenAIRE

Robert M Feinberg

2013-01-01

This study analyzes both the determinants of small firm exit rates in US manufacturing over the 1989–2004 period, especially the reaction of domestic firms to the nature of foreign competition as measured by industry-specific real exchange rate movements (interacted with import penetration by industry). These international pressures seem to lead to increased rates of smallest-firm exit in manufacturing, though the magnitudes of these effects are smaller than sometimes discussed. However, high...

Water droplet excess free energy determined by cluster mitosis using guided molecular dynamics

Science.gov (United States)

Lau, Gabriel V.; Hunt, Patricia A.; Müller, Erich A.; Jackson, George; Ford, Ian J.

2015-12-01

Atmospheric aerosols play a vital role in affecting climate by influencing the properties and lifetimes of clouds and precipitation. Understanding the underlying microscopic mechanisms involved in the nucleation of aerosol droplets from the vapour phase is therefore of great interest. One key thermodynamic quantity in nucleation is the excess free energy of cluster formation relative to that of the saturated vapour. In our current study, the excess free energy is extracted for clusters of pure water modelled with the TIP4P/2005 intermolecular potential using a method based on nonequilibrium molecular dynamics and the Jarzynski relation. The change in free energy associated with the "mitosis" or division of a cluster of N water molecules into two N/2 sub-clusters is evaluated. This methodology is an extension of the disassembly procedure used recently to calculate the excess free energy of argon clusters [H. Y. Tang and I. J. Ford, Phys. Rev. E 91, 023308 (2015)]. Our findings are compared to the corresponding excess free energies obtained from classical nucleation theory (CNT) as well as internally consistent classical theory (ICCT). The values of the excess free energy that we obtain with the mitosis method are consistent with CNT for large cluster sizes but for the smallest clusters, the results tend towards ICCT; for intermediate sized clusters, we obtain values between the ICCT and CNT predictions. Furthermore, the curvature-dependent surface tension which can be obtained by regarding the clusters as spherical droplets of bulk density is found to be a monotonically increasing function of cluster size for the studied range. The data are compared to other values reported in the literature, agreeing qualitatively with some but disagreeing with the values determined by Joswiak et al. [J. Phys. Chem. Lett. 4, 4267 (2013)] using a biased mitosis approach; an assessment of the differences is the main motivation for our current study.

Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells.

Science.gov (United States)

Nakagawa, Tadashi; Zhang, Teng; Kushi, Ryo; Nakano, Seiji; Endo, Takahiro; Nakagawa, Makiko; Yanagihara, Noriko; Zarkower, David; Nakayama, Keiko

2017-11-15

The mitosis-meiosis transition is essential for spermatogenesis. Specific and timely downregulation of the transcription factor DMRT1, and consequent induction of Stra8 expression, is required for this process in mammals, but the molecular mechanism has remained unclear. Here, we show that β-TrCP, the substrate recognition component of an E3 ubiquitin ligase complex, targets DMRT1 for degradation and thereby controls the mitosis-meiosis transition in mouse male germ cells. Conditional inactivation of β-TrCP2 in male germ cells of β-TrCP1 knockout mice resulted in sterility due to a lack of mature sperm. The β-TrCP-deficient male germ cells did not enter meiosis, but instead underwent apoptosis. The induction of Stra8 expression was also attenuated in association with the accumulation of DMRT1 at the Stra8 promoter in β-TrCP-deficient testes. DMRT1 contains a consensus β-TrCP degron sequence that was found to bind β-TrCP. Overexpression of β-TrCP induced the ubiquitylation and degradation of DMRT1. Heterozygous deletion of Dmrt1 in β-TrCP-deficient spermatogonia increased meiotic cells with a concomitant reduction of apoptosis. Collectively, our data indicate that β-TrCP regulates the transition from mitosis to meiosis in male germ cells by targeting DMRT1 for degradation. © 2017. Published by The Company of Biologists Ltd.

Improved social force model based on exit selection for microscopic pedestrian simulation in subway station

Institute of Scientific and Technical Information of China (English)

郑勋; 李海鹰; 孟令云; 许心越; 陈旭

2015-01-01

An improved social force model based on exit selection is proposed to simulate pedestrians’ microscopic behaviors in subway station. The modification lies in considering three factors of spatial distance, occupant density and exit width. In addition, the problem of pedestrians selecting exit frequently is solved as follows: not changing to other exits in the affected area of one exit, using the probability of remaining preceding exit and invoking function of exit selection after several simulation steps. Pedestrians in subway station have some special characteristics, such as explicit destinations, different familiarities with subway station. Finally, Beijing Zoo Subway Station is taken as an example and the feasibility of the model results is verified through the comparison of the actual data and simulation data. The simulation results show that the improved model can depict the microscopic behaviors of pedestrians in subway station.

Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

Science.gov (United States)

Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

2013-01-01

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

Does Business Cycle Have an Impact on Entrants and Exits?

Directory of Open Access Journals (Sweden)

Nikolay Sterev

2017-03-01

Full Text Available Purpose: The role of entrants and exits has enlarged indisputably over recent years. The basic explanation is connected to the deepening of innovation's influence on industrial growth. Furthermore, new businesses have to be more effective, and based on products, technological or organizational innovations, and exits have to be ineffective (respectively unprofitable, based on denoted products or technology. Design/methodology/approach: According to the above-mentioned prerequisites, policymakers need to manage the role (respectively the impact that entrants (new start-up companies and exits play in industrial growth. Nevertheless, this impact is not a cornerstone of the Bulgarian National Strategy, or the Europe 2020 Strategy. Findings: The paper tries to answer the following two questions: 1 Do new start-up companies and exits have any role and influence on economic growth in Bulgaria? and 2 Does the role (respectively the impact of entrants and exits in industrial growth change according to economic cycle? Research limitations/implications: In addition, according to the Lisbon Strategy, as well as the European Union's (EU Strategy 2020, the current economic policy supports entrepreneurship and innovations. Thus, the establishment of innovative companies, as well as the development of innovative, incumbent business are core issues of EU economic policy for the past decade. Originality/value: The paper builds on the industrial dynamic methodology and on the understanding of how business decisions (entrepreneurship, innovations, and R&D on micro level correspond to macro level (GDP growth and innovation policy.

Mitosis counting in breast cancer : object-level interobserver agreement and comparison to an automatic method

NARCIS (Netherlands)

Veta, M.; van Diest, P.J.; Jiwa, M.; Al-Janabi, S.; Pluim, J.P.W.

2016-01-01

BACKGROUND: Tumor proliferation speed, most commonly assessed by counting of mitotic figures in histological slide preparations, is an important biomarker for breast cancer. Although mitosis counting is routinely performed by pathologists, it is a tedious and subjective task with poor

Mitosis Counting in Breast Cancer : Object-Level Interobserver Agreement and Comparison to an Automatic Method

NARCIS (Netherlands)

Veta, Mitko; van Diest, Paul J; Jiwa, Mehdi; Al-Janabi, Shaimaa; Pluim, JPW

2016-01-01

BACKGROUND: Tumor proliferation speed, most commonly assessed by counting of mitotic figures in histological slide preparations, is an important biomarker for breast cancer. Although mitosis counting is routinely performed by pathologists, it is a tedious and subjective task with poor

The comparison of exit-site care with normal saline and povidone-iodine in preventing exit-site infection and peritonitis in children on chronic peritoneal dialysis treatment

Directory of Open Access Journals (Sweden)

Onder Yavascan

2011-01-01

Full Text Available Peritonitis and catheter exit- site infections (ESI are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis (CPD. The frequency of infection can be reduced by scrupulous exit- site care with or without topical antiseptics. There are no studies showing any benefit in the use of povidone-iodine or normal saline for care of exit- sites in long- term CPD patients. In this study, we aimed to determine the potential effectiveness of the application of povidone-iodine or normal saline at the catheter exit- site in preventing ESI and peritonitis in children on CPD. A total of 98 patients treated with either povidone-iodine or normal saline were included in this study. Group I (34 patients used povidone-iodine and group II (64 patients simply cleansed the exit- site with normal saline (0.9% NaCl. Dressings were changed 2 to 3 times in a week. The total cumulative follow- up time was 3233 patient- months. ESIs occurred in 10 (29.4% of 34 patients using povidone-iodine and in 10 (15.6% of 64 patients using normal saline. The frequency of ESI was significantly high in group I (povidone-iodine patients. The mean rate of ESI was 1 episode/60.8 patient- months for group I versus 1 episode/144 patient- months for group II (P 0.05. In conclusion, exit- site care with normal saline is an effective strategy in reducing the incidence of ESI in children on CPD. It can thus significantly reduce morbidity, catheter loss, and the need to transfer patients on peritoneal dialysis to hemodialysis.

Influence of drill helical direction on exit damage development in drilling carbon fiber reinforced plastic

Science.gov (United States)

Bai, Y.; Jia, Z. Y.; Wang, F. J.; Fu, R.; Guo, H. B.; Cheng, D.; Zhang, B. Y.

2017-06-01

Drilling is inevitable for CFRP components’ assembling process in the aviation industry. The exit damage frequently occurs and affects the load carrying capacity of components. Consequently, it is of great urgency to enhance drilling exit quality on CFRP components. The article aims to guide the reasonable choice of drill helical direction and effectively reduce exit damage. Exit observation experiments are carried out with left-hand helical, right-hand helical and straight one-shot drill drilling T800S CFRP laminates separately. The development rules of exit damage and delamination factor curves are obtained. Combined with loading conditions and fracture modes of push-out burrs, and thrust force curves, the influence of drill helical direction on exit damage development is derived. It is found that the main fracture modes for left-hand helical, right-hand helical, and straight one-shot drill are mode I, extrusive fracture, mode III respectively. Among them, mode III has the least effect on exit damage development. Meanwhile, the changing rate of thrust force is relative slow for right-hand helical and straight one-shot drill in the thrust force increasing phase of stage II, which is disadvantaged for exit damage development. Therefore, straight one-shot drill’s exit quality is the best.

Effects of Generational Competition and Substitution on Late Labour Participation and Labour Market Exit from a Multilevel Perspective

Directory of Open Access Journals (Sweden)

Henriette Engelhardt

2013-12-01

-term unemployment and the share of highly-educated older men. While our analyses reveal some evidence of intragenerational competition, we do not find evidence of intergenerational competition forcing early exit or decreasing participation.

A thermodynamic approach to the 'mitosis/apoptosis' ratio in cancer

Science.gov (United States)

Lucia, Umberto; Ponzetto, Antonio; Deisboeck, Thomas S.

2015-10-01

Cancer can be considered as an open, complex, (bio-thermo)dynamic and self-organizing system. Consequently, an entropy generation approach has been employed to analyze its mitosis/apoptosis ratio. Specifically, a novel thermodynamic anticancer strategy is suggested, based on the variation of entropy generation caused by the application of external fields, for example electro-magnetic fields, for therapeutic purposes. Eventually, this innovative approach could support conventional therapies, particularly for inoperable tumors or advanced stages of cancer, when larger tumor burden is diagnosed, and therapeutic options are often limited.

Epigenetics as a First Exit Problem

Science.gov (United States)

Aurell, E.; Sneppen, K.

2002-01-01

We develop a framework to discuss the stability of epigenetic states as first exit problems in dynamical systems with noise. We consider in particular the stability of the lysogenic state of the λ prophage. The formalism defines a quantitative measure of robustness of inherited states.

Evaluation of six TPS algorithms in computing entrance and exit doses

Science.gov (United States)

Metwaly, Mohamed; Glegg, Martin; Baggarley, Shaun P.; Elliott, Alex

2014-01-01

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%‐3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.N‐, 87.53.Bn PMID:24892349

After exit: Academic achievement patterns of former English language learners.

Directory of Open Access Journals (Sweden)

Ester J. de Jong

2004-09-01

Full Text Available With few exceptions, accountability systems for programs for English language learners (ELLs have focused on the achievement patterns of ELLs who are still considered “limited English proficient” and program evaluations have been unable to answer the question whether ELLs actually catch up with English proficient peers after attending a bilingual or English as a Second Language (ESL program. Disaggregating data for former ELLs can therefore provide important information for long-term district and program accountability. The study was concerned with the achievement patterns in English language arts, Math, and Science of former ELLs who attended a bilingual and a English as a Second Language (ESL program. It also explored whether length of program participation and grade level exited played a significant role in predicting academic achievement patterns for these exited students. Results indicate that 4th grade students more closely paralleled non- ELL students’ achievement patterns than 8th grade students, particularly for the BE students. While length of program participation is not a significant predictor of former ELLs’ academic success, exit grade does emerge as an important variable to take into consideration in setting exit guidelines.

Drink Specials and the Intoxication Levels of Patrons Exiting College Bars

Science.gov (United States)

Thombs, Dennis L.; Dodd, Virginia; Porkorny, Steven B.; Omli, Morrow R.; O'Mara, Ryan; Webb, Monica C.; Lacaci, Diana M.; Werch, Chad

2008-01-01

Objectives: To determine whether drink specials independently increase patrons' risk of achieving a high level of intoxication upon exiting drinking establishments. Methods: In a campus community, data were collected from exiting patrons (N=291) via sidewalk interviews and breath tests on 6 nights of 2 consecutive semesters. Results: A…

Plant WEE1 kinase is cell cycle regulated and removed at mitosis via the 26S proteasome machinery

Science.gov (United States)

Cook, Gemma S.; Grønlund, Anne Lentz; Siciliano, Ilario; Spadafora, Natasha; Amini, Maryam; Herbert, Robert J.; Bitonti, M. Beatrice; Graumann, Katja; Francis, Dennis; Rogers, Hilary J.

2013-01-01

In yeasts and animals, premature entry into mitosis is prevented by the inhibitory phosphorylation of cyclin-dependent kinase (CDK) by WEE1 kinase, and, at mitosis, WEE1 protein is removed through the action of the 26S proteasome. Although in higher plants WEE1 function has been confirmed in the DNA replication checkpoint, Arabidopsis wee1 insertion mutants grow normally, and a role for the protein in the G2/M transition during an unperturbed plant cell cycle is yet to be confirmed. Here data are presented showing that the inhibitory effect of WEE1 on CDK activity in tobacco BY-2 cell cultures is cell cycle regulated independently of the DNA replication checkpoint: it is high during S-phase but drops as cells traverse G2 and enter mitosis. To investigate this mechanism further, a yeast two-hybrid screen was undertaken to identify proteins interacting with Arabidopsis WEE1. Three F-box proteins and a subunit of the proteasome complex were identified, and bimolecular fluorescence complementation confirmed an interaction between AtWEE1 and the F-box protein SKP1 INTERACTING PARTNER 1 (SKIP1). Furthermore, the AtWEE1–green fluorescent protein (GFP) signal in Arabidopsis primary roots treated with the proteasome inhibitor MG132 was significantly increased compared with mock-treated controls. Expression of AtWEE1–YFPC (C-terminal portion of yellow fluorescent protein) or AtWEE1 per se in tobacco BY-2 cells resulted in a premature increase in the mitotic index compared with controls, whereas co-expression of AtSKIP1–YFPN negated this effect. These data support a role for WEE1 in a normal plant cell cycle and its removal at mitosis via the 26S proteasome. PMID:23536609

14 CFR 135.129 - Exit seating.

Science.gov (United States)

2010-01-01

... emergency evacuation provided by the certificate holder in printed or graphic form or the ability to... accordance with this section. (d) Each certificate holder shall include on passenger information cards.... (e) Each certificate holder shall include on passenger information cards, at each exit seat— (1) In...

"Do I stay or do I go?"--job change and labor market exit intentions of employees providing informal care to older adults.

Science.gov (United States)

Schneider, Ulrike; Trukeschitz, Birgit; Mühlmann, Richard; Ponocny, Ivo

2013-10-01

This article examines whether providing informal eldercare to an older dependent person predicts employees' intentions to change jobs or exit the labor market and, if so, which particular aspects of both caregiving (e.g. time demands, physical/cognitive care burden) and their current work environment shape these intentions. We used data from a sample of 471 caring and 431 noncaring employees in Austria and split the analyses by gender. We found different aspects of informal caregiving to be associated with the intention to change jobs and with the anticipated labor market withdrawal of male and female workers. A time-based conflict between informal eldercare and paid work was significantly and positively related to the intended job change of female workers but not of their male counterparts. Flexible work arrangements were found to facilitate the attachment of female workers to their jobs and the labor market. Intentions to exit the labor market of male workers appeared to be triggered by a physical care burden rather than time demands. We studied the effects of providing informal eldercare on the turnover intention of men and women in a group of workers who were also the main carers providing support to a dependent older person with substantial care needs. The intention of male and female workers to change jobs and exit the labor market is shaped by the different characteristics of informal caregiving. Time-based conflicts between informal care and paid work are associated with a higher relative risk of anticipating job changes for female workers. Flextime facilitates the job and labor market attachment of female workers with eldercare responsibilities. The intensity of personal care provided to an older relative is significantly positively related to male workers' relative risk of anticipated labor market exit. Care to an older person in need of supervision makes the labor market exit of female workers less likely, lending thus support to the idea of the respite

Door locking and exit security measures on acute psychiatric admission wards

NARCIS (Netherlands)

Nijman, H.L.I.; Bowers, L.; Haglund, K.; Muir-Cochrane, E.; Simpson, A.; Merwe, M. van der

2011-01-01

Locking the exit doors of psychiatric wards is believed to reduce the risk of patients absconding. The aims of the study were to investigate both the prevalence of door locking and other exit security measures on UK admission wards, as well as whether door locking appears to be effective in keeping

EXIT Chart Analysis of Binary Message-Passing Decoders

DEFF Research Database (Denmark)

Lechner, Gottfried; Pedersen, Troels; Kramer, Gerhard

2007-01-01

Binary message-passing decoders for LDPC codes are analyzed using EXIT charts. For the analysis, the variable node decoder performs all computations in the L-value domain. For the special case of a hard decision channel, this leads to the well know Gallager B algorithm, while the analysis can...... be extended to channels with larger output alphabets. By increasing the output alphabet from hard decisions to four symbols, a gain of more than 1.0 dB is achieved using optimized codes. For this code optimization, the mixing property of EXIT functions has to be modified to the case of binary message......-passing decoders....

Nucleolus disassembly in mitosis and apoptosis: dynamic redistribution of phosphorylated-c-Myc, fibrillarin and Ki-67

Directory of Open Access Journals (Sweden)

C Soldani

2009-06-01

Full Text Available The nucleolus may undergo disassembly either reversibly during mitosis, or irreversibly in apoptosis, thus allowing the redistribution of the nucleolar proteins.We investigated here by immunocytochemistry the fate of three representative proteins, namely phosphorylated c-Myc, fibrillarin and Ki-67, and found that they behave independently in both processes: they relocate in distinct compartments during mitosis, whereas during apoptosis they may either be cleaved (Ki-67 or be extruded into the cytoplasm with a different kinetics and following an ordered, non chaotic program. The separation of these nucleolar proteins which occurs in early apoptotic nuclei continues also in the cytoplasm, and culminates in the final formation of apoptotic blebs containing different nucleolar proteins: this evidence confirms that the apoptotic bodies may be variable in size, content and surface reactivity, and include heterogeneous aggregates of nuclear proteins and/or nucleic acids.

Predicting The Exit Time Of Employees In An Organization Using Statistical Model

Directory of Open Access Journals (Sweden)

Ahmed Al Kuwaiti

2015-08-01

Full Text Available Employees are considered as an asset to any organization and each organization provide a better and flexible working environment to retain its best and resourceful workforce. As such continuous efforts are being taken to avoid or extend the exitwithdrawal of employees from the organization. Human resource managers are facing a challenge to predict the exit time of employees and there is no precise model existing at present in the literature. This study has been conducted to predict the probability of exit of an employee in an organization using appropriate statistical model. Accordingly authors designed a model using Additive Weibull distribution to predict the expected exit time of employee in an organization. In addition a Shock model approach is also executed to check how well the Additive Weibull distribution suits in an organization. The analytical results showed that when the inter-arrival time increases the expected time for the employees to exit also increases. This study concluded that Additive Weibull distribution can be considered as an alternative in the place of Shock model approach to predict the exit time of employee in an organization.

14 CFR 121.585 - Exit seating.

Science.gov (United States)

2010-01-01

... section and related to emergency evacuation provided by the certificate holder in printed or graphic form... include on passenger information cards, presented in the language in which briefings and oral commands are... passenger information cards, at each exit seat— (1) In the primary language in which emergency commands are...

Control of mitosis in Physarum polycephalum. The effect of lowering the DNA: mass ratio by uv irradiation

International Nuclear Information System (INIS)

Sudbery, P.E.; Grant, W.D.

1975-01-01

A model for the control of mitosis is presented and, along with four other models described previously, is tested by the response of Physarum polycephalum to uv irradiation. Plasmodia were irradiated following the second mitosis (M II) after fusion of microplasmodia. As shown by other authors, the onset of the next mitosis (M III) was delayed but the period M III-M IV was shortened relative to control plasmodia. It is shown that the period M III-M IV cannot be shortened beyond a minimum of 6 h despite increasing doses of uv. This minimum length is shown to be relatively independent of growth rate. If conditions were such that the length of M III-M IV was shortened to this minimum value the length of M IV-M V was also shorter than the corresponding control period. If the period M II-M IV was longer than the minimum following irradiation then the length of M IV-M V was not shortened. It is argued that only the latter situation allows models to be tested and it is shown how the observed result is consistent with only two of the five models considered. A further test compared the length of M III-M IV under these conditions with that predicted from the amount of DNA destroyed by the uv. This result was consistent only with the same two models

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application

Science.gov (United States)

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.; Mundy, Michael B.

2015-07-21

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application, including: identifying a subset of compute nodes in the parallel computer to execute the parallel application; selecting one compute node in the subset of compute nodes in the parallel computer as a job leader compute node; initiating execution of the parallel application on the subset of compute nodes; receiving an exit status from each compute node in the subset of compute nodes, where the exit status for each compute node includes information describing execution of some portion of the parallel application by the compute node; aggregating each exit status from each compute node in the subset of compute nodes; and sending an aggregated exit status for the subset of compute nodes in the parallel computer.

Comparison of exit time moment spectra for extrinsic metric balls

DEFF Research Database (Denmark)

Hurtado, Ana; Markvorsen, Steen; Palmer, Vicente

2012-01-01

We prove explicit upper and lower bounds for the $L^1$-moment spectra for the Brownian motion exit time from extrinsic metric balls of submanifolds $P^m$ in ambient Riemannian spaces $N^n$. We assume that $P$ and $N$ both have controlled radial curvatures (mean curvature and sectional curvature...... obtain new intrinsic comparison results for the exit time spectra for metric balls in the ambient manifolds $N^n$ themselves....

Formal procedures of the exit from a community for a university social media agency

OpenAIRE

Peleschyshyn, Andriy; Peleschyshyn, Oksana; Korzh, Roman

2016-01-01

The aim of the paper is to consider the process of exiting of a university from an online community. The importance of performing the task of exiting in a proper way is proved. Preconditions and risks of the process are investigated. All the stages of the suggested algorithm for exiting from online community are scrutinized.

Efficiency, Leverage and Exit: The Role of Information Asymmetry in Concentrated Industries

DEFF Research Database (Denmark)

Siyahhan, Baran

2011-01-01

This paper develops a real options model of imperfect competition with asymmetric information that analyzes firms’ exit decisions. Optimal exit decision is linked to firm characteristics such as financial leverage and efficiency. The model shows that informational asymmetries can lead more...

Efficiency, Leverage and Exit: The Role of Information Asymmetry in Concentrated Industries

DEFF Research Database (Denmark)

Siyahhan, Baran

This paper develops a real options model of imperfect competition with asymmetric information that analyzes firms’ exit decisions. Optimal exit decision is linked to firm characteristics such as financial leverage and efficiency. The model shows that informational asymmetries can lead more...

MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis.

Science.gov (United States)

Wang, Yingmei; Wen, Jing; Zhang, Wei

2011-02-01

The migration and invasion inhibitory protein (MIIP) was initially discovered in a yeast two-hybrid screen for proteins that interact and inhibit the migration and invasion-promoting protein insulin-like growth factor binding protein 2 (IGFBP2). Recent studies have shown that MIIP not only modulates IGFBP2 but also regulates microtubule by binding to and inhibiting HDAC6, a class 2 histone deacetylase that deacetylates α-tubulin, heat-shock protein 90 (HSP90), and cortactin. In addition, MIIP also regulates the mitosis checkpoint, another microtubule-associated process. The location of the MIIP gene in chromosomal region 1p36, a commonly deleted region in a broad spectrum of human cancers, and the observation that MIIP attenuates tumorigenesis in a mouse model suggest that it functions as a tumor-suppressor gene. This review summarizes the recent progress in characterizing this novel protein, which regulates cell migration and mitosis, two processes that rely on the highly coordinated dynamics of the microtubule and cytoskeleton systems.

PGRMC1 participates in late events of bovine granulosa cells mitosis and oocyte meiosis.

Science.gov (United States)

Terzaghi, L; Tessaro, I; Raucci, F; Merico, V; Mazzini, G; Garagna, S; Zuccotti, M; Franciosi, F; Lodde, V

2016-08-02

Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in both oocyte and ovarian somatic cells, where it is found in multiple cellular sub-compartments including the mitotic spindle apparatus. PGRMC1 localization in the maturing bovine oocytes mirrors its localization in mitotic cells, suggesting a possible common action in mitosis and meiosis. To test the hypothesis that altering PGRMC1 activity leads to similar defects in mitosis and meiosis, PGRMC1 function was perturbed in cultured bovine granulosa cells (bGC) and maturing oocytes and the effect on mitotic and meiotic progression assessed. RNA interference-mediated PGRMC1 silencing in bGC significantly reduced cell proliferation, with a concomitant increase in the percentage of cells arrested at G2/M phase, which is consistent with an arrested or prolonged M-phase. This observation was confirmed by time-lapse imaging that revealed defects in late karyokinesis. In agreement with a role during late mitotic events, a direct interaction between PGRMC1 and Aurora Kinase B (AURKB) was observed in the central spindle at of dividing cells. Similarly, treatment with the PGRMC1 inhibitor AG205 or PGRMC1 silencing in the oocyte impaired completion of meiosis I. Specifically the ability of the oocyte to extrude the first polar body was significantly impaired while meiotic figures aberration and chromatin scattering within the ooplasm increased. Finally, analysis of PGRMC1 and AURKB localization in AG205-treated oocytes confirmed an altered localization of both proteins when meiotic errors occur. The present findings demonstrate that PGRMC1 participates in late events of both mammalian mitosis and oocyte meiosis, consistent with PGRMC1's localization at the mid-zone and mid-body of the mitotic and meiotic spindle.

Arrest of irradiated G1, S, or G2 cells at mitosis using nocodazole promotes repair of potentially lethal damage

International Nuclear Information System (INIS)

Iliakis, G.; Nuesse, M.

1984-01-01

The ability of synchronized Ehrlich ascites tumor cells, irradiated in G1, S, and G2 phases, to repair potentially lethal damage when arrested at mitosis by using 0.4 μg/ml nocodazole, a specific inhibitor of microtubule polymerization, has been studied. Cells irradiated in these phases were found to repair potentially lethal damage at mitosis. The extent of this repair was similar to that observed for cells irradiated at the same stages in the cell cycle but allowed to repair potentially lethal damage by incubating in balanced salt solution for 6 hr after X irradiation

Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation

International Nuclear Information System (INIS)

Fernandez, Carlos; Lobo, Maria del Val T.; Gomez-Coronado, Diego; Lasuncion, Miguel A.

2004-01-01

As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, geranylgeraniol, and dolichol. The aim of the present study was to elucidate the role of cholesterol in mitosis. For this, human leukemia cells (HL-60) were incubated in a cholesterol-free medium and treated with SKF 104976, which inhibits cholesterol biosynthesis by blocking sterol 14α-demethylase, and the expression of relevant cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged cholesterol starvation induced the inhibition of cytokinesis and the formation of polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with cholesterol completely abolished these effects, demonstrating they were specifically due to cholesterol deficiency. This is the first evidence that cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher DNA ploidy (tetraploidy), and then progressed through S (rereplication) into G2, generating polyploid cells

The G2/M DNA damage checkpoint inhibits mitosis through Tyr15 phosphorylation of p34cdc2 in Aspergillus nidulans.

OpenAIRE

Ye, X S; Fincher, R R; Tang, A; Osmani, S A

1997-01-01

It is possible to cause G2 arrest in Aspergillus nidulans by inactivating either p34cdc2 or NIMA. We therefore investigated the negative control of these two mitosis-promoting kinases after DNA damage. DNA damage caused rapid Tyr15 phosphorylation of p34cdc2 and transient cell cycle arrest but had little effect on the activity of NIMA. Dividing cells deficient in Tyr15 phosphorylation of p34cdc2 were sensitive to both MMS and UV irradiation and entered lethal premature mitosis with damaged DN...

Toward 3D structural information from quantitative electron exit wave analysis

International Nuclear Information System (INIS)

Borisenko, Konstantin B; Moldovan, Grigore; Kirkland, Angus I; Wang, Amy; Van Dyck, Dirk; Chen, Fu-Rong

2012-01-01

Simulations show that using a new direct imaging detector and accurate exit wave restoration algorithms allows nearly quantitative restoration of electron exit wave phase, which can be regarded as only qualitative for conventional indirect imaging cameras. This opens up a possibility of extracting accurate information on 3D atomic structure of the sample even from a single projection.

Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)

Energy Technology Data Exchange (ETDEWEB)

Seo, Jae Sung; Kim, Ha Na; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Ki Sa [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Yoon, Hyun-Joo [TissueGene Inc. 9605 Medical Center Dr., Rockville, MD 20850 (United States); Yoo, Hae Yong [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of); Choi, Cheol Yong, E-mail: choicy@skku.ac.kr [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2014-01-03

Highlights: •NuMA is modified by SUMO-1 in a cell cycle-dependent manner. •NuMA lysine 1766 is the primary target site for SUMOylation. •SUMOylation-deficient NuMA induces multiple spindle poles during mitosis. •SUMOylated NuMA induces microtubule bundling. -- Abstract: 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.

Replication stress activates DNA repair synthesis in mitosis

DEFF Research Database (Denmark)

Minocherhomji, Sheroy; Ying, Songmin; Bjerregaard, Victoria A

2015-01-01

Oncogene-induced DNA replication stress has been implicated as a driver of tumorigenesis. Many chromosomal rearrangements characteristic of human cancers originate from specific regions of the genome called common fragile sites (CFSs). CFSs are difficult-to-replicate loci that manifest as gaps...... into mitotic prophase triggers the recruitment of MUS81 to CFSs. The nuclease activity of MUS81 then promotes POLD3-dependent DNA synthesis at CFSs, which serves to minimize chromosome mis-segregation and non-disjunction. We propose that the attempted condensation of incompletely duplicated loci in early...... mitosis serves as the trigger for completion of DNA replication at CFS loci in human cells. Given that this POLD3-dependent mitotic DNA synthesis is enhanced in aneuploid cancer cells that exhibit intrinsically high levels of chromosomal instability (CIN(+)) and replicative stress, we suggest...

Association Between Health Plan Exit From Medicaid Managed Care and Quality of Care, 2006-2014.

Science.gov (United States)

Ndumele, Chima D; Schpero, William L; Schlesinger, Mark J; Trivedi, Amal N

2017-06-27

State Medicaid programs have increasingly contracted with insurers to provide medical care services for enrollees (Medicaid managed care plans). Insurers that provide these plans can exit Medicaid programs each year, with unclear effects on quality of care and health care experiences. To determine the frequency and interstate variation of health plan exit from Medicaid managed care and evaluate the relationship between health plan exit and market-level quality. Retrospective cohort of all comprehensive Medicaid managed care plans (N = 390) during the interval 2006-2014. Plan exit, defined as the withdrawal of a managed care plan from a state's Medicaid program. Eight measures from the Healthcare Effectiveness Data and Information Set were used to construct 3 composite indicators of quality (preventive care, chronic disease care management, and maternity care). Four measures from the Consumer Assessment of Healthcare Providers and Systems were combined into a composite indicator of patient experience, reflecting the proportion of beneficiaries rating experiences as 8 or above on a 0-to-10-point scale. Outcome data were available for 248 plans (68% of plans operating prior to 2014, representing 78% of beneficiaries). Of the 366 comprehensive Medicaid managed care plans operating prior to 2014, 106 exited Medicaid. These exiting plans enrolled 4 848 310 Medicaid beneficiaries, with a mean of 606 039 beneficiaries affected by plan exits annually. Six states had a mean of greater than 10% of Medicaid managed care recipients enrolled in plans that exited, whereas 10 states experienced no plan exits. Plans that exited from a state's Medicaid market performed significantly worse prior to exiting than those that remained in terms of preventive care (57.5% vs 60.4%; difference, 2.9% [95% CI, 0.3% to 5.5%]), maternity care (69.7% vs 73.6%; difference, 3.8% [95% CI, 1.7% to 6.0%]), and patient experience (73.5% vs 74.8%; difference, 1.3% [95% CI, 0.6% to 1

Stor forskel på kommuners bande-exit

DEFF Research Database (Denmark)

Mørck, Line Lerche

2015-01-01

DEBAT: Kommunerne har meget forskellige exit-tilbud til bande- og rockermedlemmer. Der er brug for mere indgående forskning, så vi ved, hvad der virker bedst, skriver Line Lerche Mørck, lektor i pædagogisk psykologi....

iDermatoPath - a novel software tool for mitosis detection in H&E-stained tissue sections of malignant melanoma.

Science.gov (United States)

Andres, C; Andres-Belloni, B; Hein, R; Biedermann, T; Schäpe, A; Brieu, N; Schönmeyer, R; Yigitsoy, M; Ring, J; Schmidt, G; Harder, N

2017-07-01

Malignant Melanoma (MM) is characterized by a growing incidence and a high malignant potential. Besides well-defined prognostic factors such as tumour thickness and ulceration, the Mitotic Rate (MR) was included in the AJCC recommendations for diagnosis and treatment of MM. In daily routine, the identification of a single mitosis can be difficult on haematoxylin and eosin slides alone. Several studies showed a big inter- and intra-individual variability in detecting the MR in MM even by very experienced investigators, thus raising the question for a computer-assisted method. The objective was to develop a software system for mitosis detection in MM on H&E slides based on machine learning for diagnostic support. We developed a computer-aided staging support system based on image analysis and machine learning on the basis of 59 MM specimens. Our approach automatically detects tumour regions, identifies mitotic nuclei and classifies them with respect to their diagnostic relevance. A convenient user interface enables the investigator to browse through the proposed mitoses for fast and efficient diagnosing. A quantitative evaluation on manually labelled ground truth data revealed that the tumour region detection yields a medium spatial overlap index (dice coefficient) of 0.72. For the mitosis detection, we obtained high accuracies of above 83%. On the technical side, the developed iDermatoPath software tool provides a novel approach for mitosis detection in MM, which can be further improved using more training data such as dermatopathologist annotations. On the practical side, a first evaluation of the clinical utility was positive, albeit this approach provides most benefit for difficult cases in a research setting. Assuming all slides to be digitally processed and reported in the near future, this method could become a helpful additional tool for the pathologist. © 2017 European Academy of Dermatology and Venereology.

Cdc20 control of cell fate during prolonged mitotic arrest

DEFF Research Database (Denmark)

Nilsson, Jakob

2011-01-01

The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations...

Blocking Internalization of Phosphatidylethanolamine at Cleavage Furrow of Mitosis as a Novel Mechanism of Anti-Breast Cancer Strategy

National Research Council Canada - National Science Library

Cui, Zhen

2002-01-01

During the formation of cleavage furrow of mitosis, phosphatidylethanolamine (PE) flips from inner leaflet of the plasma membrane to the outer leaflet specifically in the furrow region near the contractile ring...

Blocking Internalization of Phosphatidylethanolamine at Cleavage Furrow of Mitosis as a Novel Mechanism of Anti-Breast-Cancer Strategy

National Research Council Canada - National Science Library

Cui, Zheng

2003-01-01

During the formation of cleavage furrow of mitosis, phosphatidylethanolamine (PE) flips from inner leaflet of the plasma membrane to the outer leaflet specifically in the furrow region near the contractile ring...

PCTAIRE1 phosphorylates p27 and regulates mitosis in cancer cells.

Science.gov (United States)

Yanagi, Teruki; Krajewska, Maryla; Matsuzawa, Shu-ichi; Reed, John C

2014-10-15

PCTAIRE1 is distant relative of the cyclin-dependent kinase family that has been implicated in spermatogenesis and neuronal development, but it has not been studied in cancer. Here, we report that PCTAIRE1 is expressed in prostate, breast, and cervical cancer cells, where its RNAi-mediated silencing causes growth inhibition with aberrant mitosis due to defects in centrosome dynamics. PCTAIRE1 was not similarly involved in proliferation of nontransformed cells, including diploid human IMR-90 fibroblasts. Through yeast two-hybrid screening, we identified tumor suppressor p27 as a PCTAIRE1 interactor. In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells. In a mouse xenograft model of PPC1 prostate cancer, conditional silencing of PCTAIRE1 restored p27 protein expression and suppressed tumor growth. Mechanistic studies in HeLa cells showed that PCTAIRE1 phosphorylates p27 during the S and M phases of the cell cycle. Notably, p27 silencing was sufficient to rescue cells from mitotic arrest caused by PCTAIRE1 silencing. Clinically, PCTAIRE1 was highly expressed in primary breast and prostate tumors compared with adjacent normal epithelial tissues. Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. ©2014 American Association for Cancer Research.

14 CFR 23.805 - Flightcrew emergency exits.

Science.gov (United States)

2010-01-01

... emergency exit must be located to allow rapid evacuation of the crew and have a size and shape of at least a... than six feet from the ground, an assisting means must be provided. The assisting means may be a rope...

Exit Polling in an Emergent Democracy: The Complex Case of Ukraine

Directory of Open Access Journals (Sweden)

Natalya Nikolaevna Kharchenko

2010-05-01

Full Text Available This report considers the methodological specifics of conducting exit polls to verify election returns, mainly using an example of election campaigns in Ukraine from 2002-2007. The deepest public resonance was aroused by exit polls conducted after the second round of Ukrainian presidential elections in 2004. These polls were one of the factors, which led to massive demonstrations (the so-called "Orange Revolution" and the revocation of election results. The authors show that in the environment of administrative pressure on voters, governmental control of mass media, and severe political struggle, inaccuracy increases. Thus, to acquire reliable and valid information, the polling methods used must be modified. The recommendations given for the methodology of conducting exit polls may be useful for emergent democratic countries.

Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis.

Science.gov (United States)

Princz, Lissa N; Wild, Philipp; Bittmann, Julia; Aguado, F Javier; Blanco, Miguel G; Matos, Joao; Pfander, Boris

2017-03-01

DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner. Moreover, DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81-Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Centrioles: active players or passengers during mitosis?

Science.gov (United States)

Debec, Alain; Sullivan, William; Bettencourt-Dias, Monica

2010-07-01

Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as "the organ for cell division". However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues.

A Diversity Exit Interview/Survey for the Military

National Research Council Canada - National Science Library

Knouse, Stephen

2001-01-01

The exit interview and survey are means for identifying organizational problems, including diversity issues, through individuals separating from the organization, who are in a unique position to supply candid feedback...

Symmetry associated with symmetry break: Revisiting ants and humans escaping from multiple-exit rooms

Science.gov (United States)

Ji, Q.; Xin, C.; Tang, S. X.; Huang, J. P.

2018-02-01

Crowd panic has incurred massive injuries or deaths throughout the world, and thus understanding it is particularly important. It is now a common knowledge that crowd panic induces "symmetry break" in which some exits are jammed while others are underutilized. Amazingly, here we show, by experiment, simulation and theory, that a class of symmetry patterns come to appear for ants and humans escaping from multiple-exit rooms while the symmetry break exists. Our symmetry pattern is described by the fact that the ratio between the ensemble-averaging numbers of ants or humans escaping from different exits is equal to the ratio between the widths of the exits. The mechanism lies in the effect of heterogeneous preferences of agents with limited information for achieving the Nash equilibrium. This work offers new insights into how to improve public safety because large public areas are always equipped with multiple exits, and it also brings an ensemble-averaging method for seeking symmetry associated with symmetry breaking.

Mitosis delay in cells of the root meristem of pea seedlings in S and G2-phases when irradiated with gamma-rays

International Nuclear Information System (INIS)

Gudkov, I.N.; Zezina, N.V.

1976-01-01

Irradiation (800 rads) of pea seedlings, synchronized by a 24-hr treatment with 0.03% hydroxyurea, at the stage of G 1 →S, induced a 12-hr delay of mitosis peak; an 8-hr delay, in the early S-phase; a 4-hr delay, in the middle of S-phase; a 10-hr delay in the late S- and a 14-16-hr delay, in G 2 -phase. The number of cells having chromosome aberrations at the mitosis peak was similar in all the phases under study

Exits from Temporary Jobs in Europe: A Competing Risks Analysis

DEFF Research Database (Denmark)

D'Addio, Anna Christina; Rosholm, Michael

2005-01-01

We study transitions out of temporary jobs using the waves 1994-1999 of the European Community Household Panel applying a discrete time duration model. Specifically, we use a multinomial logitmodel distinguishing between exits into permanent employment and non-employment. Two different specificat......We study transitions out of temporary jobs using the waves 1994-1999 of the European Community Household Panel applying a discrete time duration model. Specifically, we use a multinomial logitmodel distinguishing between exits into permanent employment and non-employment. Two different...

O-Linked N-Acetylglucosamine Transiently Elevates in HeLa Cells during Mitosis

Directory of Open Access Journals (Sweden)

Viktória Fisi

2018-05-01

Full Text Available O-linked N-acetylglucosamine (O-GlcNAc is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins. O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation. Multiple studies also showed that cell cycle might be modulated by O-GlcNAc. Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial. In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block. O-GlcNAc levels in G1, S, G2 and M phase were measured. We observed that O-GlcNAc levels are significantly increased during mitosis in comparison to the other cell cycle phases. However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G2/M fraction of the synchronized cells. Our data verify that O-GlcNAc is elevated during mitosis, but also emphasize that O-GlcNAc levels can significantly change in a short period of time. Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.

Adolescents Exiting Homelessness over Two Years: The Risk Amplification and Abatement Model

Science.gov (United States)

Milburn, Norweeta G.; Rice, Eric; Rotheram-Borus, Mary Jane; Mallett, Shelley; Rosenthal, Doreen; Batterham, Phillip; May, Susanne J.; Witkin, Andrea; Duan, Naihua

2009-01-01

The Risk Amplification and Abatement Model (RAAM) demonstrates that negative contact with socializing agents amplify risk, while positive contact abates risk for homeless adolescents. To test this model, the likelihood of exiting homelessness and returning to familial housing at 2 years and stably exiting over time are examined with longitudinal…

Achieving HIV risk reduction through HealthMpowerment.org, a user-driven eHealth intervention for young Black men who have sex with men and transgender women who have sex with men.

Science.gov (United States)

Muessig, Kathryn E; Baltierra, Nina B; Pike, Emily C; LeGrand, Sara; Hightow-Weidman, Lisa B

Young, Black men who have sex with men and transgender women who have sex with men (YBMSM/TW) are at disproportionate risk for HIV and other sexually transmitted infections (HIV/STI). HealthMpowerment.org (HMP) is a mobile phone optimised online intervention that utilises behaviour change and gaming theories to reduce risky sexual behaviours and build community among HIV-positive and negative YBMSM/TW. The intervention is user-driven, provides social support, and utilises a point reward system. A four-week pilot trial was conducted with a diverse group of 15 YBMSM/TW. During exit interviews, participants described how HMP components led to behaviour changes such as asking partners' sexual history, increased condom use, and HIV/STI testing. The user-driven structure, interactivity, and rewards appeared to facilitate sustained user engagement and the mobile platform provided relevant information in real-time. Participants described the reward elements of exceeding their previous scores and earning points toward prizes as highly motivating. HMP showed promise for being able to deliver a sufficient intervention dose and we found a trend toward higher dose received and more advanced stages of behaviour change. In this pilot trial, HMP was well accepted and demonstrates promise for translating virtual intervention engagement into actual behaviour change to reduce HIV risk behaviours.

Centriole distribution during tripolar mitosis in Chinese hamster ovary cells

Science.gov (United States)

1984-01-01

During bipolar mitosis a pair of centrioles is distributed to each cell but the activities of the two centrioles within the pair are not equivalent. The parent is normally surrounded by a cloud of pericentriolar material that serves as a microtubule-organizing center. The daughter does not become associated with pericentriolar material until it becomes a parent in the next cell cycle (Rieder, C.L., and G. G. Borisy , 1982, Biol. Cell., 44:117-132). We asked whether the microtubule-organizing activity associated with a centriole was dependent on its becoming a parent. We induced multipolar mitosis in Chinese hamster ovary cells by treatment with 0.04 micrograms/ml colcemid for 4 h. After recovery from this colcemid block, the majority of cells divided into two, but 40% divided into three and 2% divided into four. The tripolar mitotic cells were examined by antitubulin immunofluorescence and by high voltage electron microscopy of serial thick (0.25-micron) sections. The electron microscope analysis showed that centriole number was conserved and that the centrioles were distributed among the three spindle poles, generally in a 2:1:1 or 2:2:0 pattern. The first pattern shows that centriole parenting is not prerequisite for association with pole function; the second pattern indicates that centrioles per se are not required at all. However, the frequency of midbody formation and successful division was higher when centrioles were present in the 2:1:1 pattern. We suggest that the centrioles may help the proper distribution and organization of the pericentriolar cloud, which is needed for the formation of a functional spindle pole. PMID:6373793

Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16/FoxO exit dauer.

Directory of Open Access Journals (Sweden)

Verena Gelmedin

Full Text Available Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3 in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370;daf-16(mu86 mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.

Two-dimensional exit dosimetry using a liquid-filled electronic portal imaging device and a convolution model

International Nuclear Information System (INIS)

Boellaard, Ronald; Herk, Marcel van; Uiterwaal, Hans; Mijnheer, Ben

1997-01-01

Background and purpose: To determine the accuracy of two-dimensional exit dose measurements with an electronic portal imaging device, EPID, using a convolution model for a variety of clinically relevant situations. Materials and methods: Exit doses were derived from portal dose images, obtained with a liquid-filled EPID at distances of 50 cm or more behind the patient, by using a convolution model. The resulting on- and off-axis exit dose values were first compared with ionization chamber exit dose measurements for homogeneous and inhomogeneous phantoms in open and wedged 4,8 and 18 MV photon beams. The accuracy of the EPID exit dose measurements was then determined for a number of anthropomorphic phantoms (lung and larynx) irradiated under clinical conditions and for a few patients treated in an 8 MV beam. The latter results were compared with in vivo exit dose measurements using diodes. Results: The exit dose can be determined from portal images with an accuracy of 1.2% (1 SD) compared with ionization chamber measurements for open beams and homogeneous phantoms at all tested beam qualities. In the presence of wedges and for inhomogeneous phantoms the average relative accuracy slightly deteriorated to 1.7% (1 SD). For lung phantoms in a 4 MV beam a similar accuracy was obtained after refinement of our convolution model, which requires knowledge of the patient contour. Differences between diode and EPID exit dose measurements for an anthropomorphic lung phantom in an 8 MV beam were 2.5% at most, with an average agreement within 1% (1 SD). For larynx phantoms in a 4 MV beam exit doses obtained with an ionization chamber and EPID agreed within 1.5% (1 SD). Finally, exit doses in a few patients irradiated in an 8 MV beam could be determined with the EPID with an accuracy of 1.1% (1 SD) relative to exit dose measurements using diodes. Conclusions: Portal images, obtained with our EPID and analyzed with our convolution model, can be used to determine the exit dose

From equator to pole: splitting chromosomes in mitosis and meiosis

Science.gov (United States)

Duro, Eris

2015-01-01

During eukaryotic cell division, chromosomes must be precisely partitioned to daughter cells. This relies on a mechanism to move chromosomes in defined directions within the parental cell. While sister chromatids are segregated from one another in mitosis and meiosis II, specific adaptations enable the segregation of homologous chromosomes during meiosis I to reduce ploidy for gamete production. Many of the factors that drive these directed chromosome movements are known, and their molecular mechanism has started to be uncovered. Here we review the mechanisms of eukaryotic chromosome segregation, with a particular emphasis on the modifications that ensure the segregation of homologous chromosomes during meiosis I. PMID:25593304

Explaining discrepancies in reproductive health indicators from population-based surveys and exit surveys: a case from Rwanda.

Science.gov (United States)

Meekers, D; Ogada, E A

2001-06-01

Reproductive health programmes often need exit surveys and population-based surveys for monitoring and evaluation. This study investigates why such studies produce discrepant estimates of condom use, sexual behaviour and condom brand knowledge, and discusses the implications for future use of exit surveys for programme monitoring. Logistic regression is used to explain differences between a household survey of 1295 persons and an exit survey among a random sample of 2550 consumers at retail outlets in RWANDA: Discrepancies in ever use of condoms and risky sexual behaviours are due to differences in socioeconomic status of the two samples. After controls, exit surveys at most outlet types have the same results as the household survey. Only exit surveys at bars, nightclubs and hotels yield significantly different estimates. However, the above-average knowledge of Prudence Plus condoms in the exit interviews is not attributable to socioeconomic or demographic variables, most likely because respondents have seen the product at the outlets. Information about condom use and sexual behaviour obtained from exit surveys appears as accurate as that obtained through household surveys. Nevertheless, exit surveys must be used cautiously. Because exit surveys may include wealthier and better-educated respondents, they are not representative of the general population. The composition of exit survey samples should be validated through existing household surveys. Comparisons across survey types are generally unadvisable, unless they control for sample differences. When generalizing to the population at large is not needed (e.g. for studies aimed at identifying the characteristics and behaviour of users of particular products or services), exit surveys can provide an appropriate alternative to household surveys.

Ethnic variations in immigrant poverty exit and female employment: the missing link.

Science.gov (United States)

Kaida, Lisa

2015-04-01

Despite widespread interest in poverty among recent immigrants and female immigrant employment, research on the link between the two is limited. This study evaluates the effect of recently arrived immigrant women's employment on the exit from family poverty and considers the implications for ethnic differences in poverty exit. It uses the bivariate probit model and the Fairlie decomposition technique to analyze data from the Longitudinal Survey of Immigrants to Canada (LSIC), a nationally representative survey of immigrants arriving in Canada, 2000-2001. Results show that the employment of recently arrived immigrant women makes a notable contribution to lifting families out of poverty. Moreover, the wide ethnic variations in the probability of exit from poverty between European and non-European groups are partially explained by the lower employment rates among non-European women. The results suggest that the equal earner/female breadwinner model applies to low-income recent immigrant families in general, but the male breadwinner model explains the low probability of poverty exit among select non-European groups whose female employment rates are notably low.

Regulatory Control of the Resolution of DNA Recombination Intermediates during Meiosis and Mitosis

OpenAIRE

Matos, Joao; Blanco, Miguel G.; Maslen, Sarah; Skehel, J. Mark; West, Stephen C.

2011-01-01

The efficient and timely resolution of DNA recombination intermediates is essential for bipolar chromosome segregation. Here, we show that the specialized chromosome segregation patterns of meiosis and mitosis, which require the coordination of recombination with cell-cycle progression, are achieved by regulating the timing of activation of two crossover-promoting endonucleases. In yeast meiosis, Mus81-Mms4 and Yen1 are controlled by phosphorylation events that lead to their sequential activa...

Mean-Variance portfolio optimization when each asset has individual uncertain exit-time

Directory of Open Access Journals (Sweden)

Reza Keykhaei

2016-12-01

Full Text Available The standard Markowitz Mean-Variance optimization model is a single-period portfolio selection approach where the exit-time (or the time-horizon is deterministic. ‎In this paper we study the Mean-Variance portfolio selection problem ‎with ‎uncertain ‎exit-time ‎when ‎each ‎has ‎individual uncertain ‎xit-time‎, ‎which generalizes the Markowitz's model‎. ‎‎‎‎‎‎We provide some conditions under which the optimal portfolio of the generalized problem is independent of the exit-times distributions. Also, ‎‎it is shown that under some general circumstances, the sets of optimal portfolios‎ ‎in the generalized model and the standard model are the same‎.

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

Science.gov (United States)

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

2016-06-01

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

Tunneling time, exit time and exit momentum in strong field tunnel ionization

International Nuclear Information System (INIS)

Teeny, Nicolas

2016-01-01

Tunnel ionization belongs to the fundamental processes of atomic physics. It is still an open question when does the electron tunnel ionize and how long is the duration of tunneling. In this work we solve the time-dependent Schroedinger equation in one and two dimensions and use ab initio quantum calculations in order to answer these questions. Additionally, we determine the exit momentum of the tunnel ionized electron from first principles. We find out results that are different from the assumptions of the commonly employed two-step model, which assumes that the electron ionizes at the instant of electric field maximum with a zero momentum. After determining the quantum final momentum distribution of tunnel ionized electrons we show that the two-step model fails to predict the correct final momentum. Accordingly we suggest how to correct the two-step model. Furthermore, we determine the instant at which tunnel ionization starts, which turns out to be different from the instant usually assumed. From determining the instant at which it is most probable for the electron to enter the tunneling barrier and the instant at which it exits we determine the most probable time spent under the barrier. Moreover, we apply a quantum clock approach in order to determine the duration of tunnel ionization. From the quantum clock we determine an average tunneling time which is different in magnitude and origin with respect to the most probable tunneling time. By defining a probability distribution of tunneling times using virtual detectors we relate both methods and explain the apparent discrepancy. The results found have in general an effect on the interpretation of experiments that measure the spectra of tunnel ionized electrons, and specifically on the calibration of the so called attoclock experiments, because models with imprecise assumptions are usually employed in order to interpret experimental results.

Tunneling time, exit time and exit momentum in strong field tunnel ionization

Energy Technology Data Exchange (ETDEWEB)

Teeny, Nicolas

2016-10-18

Tunnel ionization belongs to the fundamental processes of atomic physics. It is still an open question when does the electron tunnel ionize and how long is the duration of tunneling. In this work we solve the time-dependent Schroedinger equation in one and two dimensions and use ab initio quantum calculations in order to answer these questions. Additionally, we determine the exit momentum of the tunnel ionized electron from first principles. We find out results that are different from the assumptions of the commonly employed two-step model, which assumes that the electron ionizes at the instant of electric field maximum with a zero momentum. After determining the quantum final momentum distribution of tunnel ionized electrons we show that the two-step model fails to predict the correct final momentum. Accordingly we suggest how to correct the two-step model. Furthermore, we determine the instant at which tunnel ionization starts, which turns out to be different from the instant usually assumed. From determining the instant at which it is most probable for the electron to enter the tunneling barrier and the instant at which it exits we determine the most probable time spent under the barrier. Moreover, we apply a quantum clock approach in order to determine the duration of tunnel ionization. From the quantum clock we determine an average tunneling time which is different in magnitude and origin with respect to the most probable tunneling time. By defining a probability distribution of tunneling times using virtual detectors we relate both methods and explain the apparent discrepancy. The results found have in general an effect on the interpretation of experiments that measure the spectra of tunnel ionized electrons, and specifically on the calibration of the so called attoclock experiments, because models with imprecise assumptions are usually employed in order to interpret experimental results.

Ecologies of ideologies : Explaining party entry and exit in European parliaments, 1945-2013

NARCIS (Netherlands)

van de Wardt, Marc; Berkhout, Joost; Vermeulen, Floris

This study introduces a population-ecological approach to the entry and exit of political parties. A primary proposition of population ecology is that organizational entry and exit depends on the number of organizations already present: that is, density. We propose that political parties mainly

Market entry and exit by biotech and device companies funded by venture capital.

Science.gov (United States)

Burns, Lawton R; Housman, Michael G; Robinson, Charles A

2009-01-01

Start-up companies in the biotechnology and medical device sectors are important sources of health care innovation. This paper describes the role of venture capital in supporting these companies and charts the growth in venture capital financial support. The paper then uses longitudinal data to describe market entry and exit by these companies. Similar factors are associated with entry and exit in the two sectors. Entries and exits in one sector also appear to influence entry in the other. These findings have important implications for developing innovative technologies and ensuring competitive markets in the life sciences.

Novel functions of plant cyclin-dependent kinase inhibitors, ICK1/KRP1, can act non-cell-autonomously and inhibit entry into mitosis

DEFF Research Database (Denmark)

Weinl, Christina; Marquardt, Sebastian; Kuijt, Suzanne J H

2005-01-01

numbers of cells consistent with a function of CKIs in blocking the G1-S cell cycle transition. Here, we demonstrate that at least one inhibitor from Arabidopsis, ICK1/KRP1, can also block entry into mitosis but allows S-phase progression causing endoreplication. Our data suggest that plant CKIs act...... independently from ICK1/KRP1-induced endoreplication. Strikingly, we found that endoreplicated cells were able to reenter mitosis, emphasizing the high degree of flexibility of plant cells during development. Moreover, we show that in contrast with animal CDK inhibitors, ICK1/KRP1 can move between cells...

CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid‐specific cancer cell death through autophagy induction

DEFF Research Database (Denmark)

Lee, Alvin J. X.; Roylance, Rebecca; Sander, Jil

2012-01-01

cell microscopy analysis revealed that CERT depletion induces LAMP2‐dependent death of polyploid cells following exit from mitosis in the presence of paclitaxel. We find that CERT is relatively over‐expressed in HER2+ breast cancer and CERT protein expression acts as an independent prognostic variable...

Sequence Classification: 890890 [

Lifescience Database Archive (English)

Full Text Available lar protein of unknown function, positive regulator of exit from mitosis; involved in regulating the release of Cdc14p from the nucle...olus in early anaphase; proposed to play similar role in meiosis; Spo12p || http://www.ncbi.nlm.nih.gov/protein/6321946 ...

Przebieg mitozy w korzeniach siewek pszenicy pod wpływem rubidu [Course of mitosis in root seedlings of Triticum aestivum L. under the influence of rubidium

Directory of Open Access Journals (Sweden)

Kazimierz Olech

2015-06-01

Full Text Available The depresion of mitosis as a result of rubidium action illustrated by the lower frequency of mitosis was found in an investigation made on roots of wheat seedlings grown on a nutrient medium which the total amount of potassium or a half of it was replaced by rubidium. The lower mitotic activity was caused by limited number of nuclei beginning prophase and by a prolonged duration of metaphase.

Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

Science.gov (United States)

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

Wives' Relative Wages, Husbands' Paid Work Hours, and Wives' Labor-Force Exit

Science.gov (United States)

Shafer, Emily Fitzgibbons

2011-01-01

Economic theories predict that women are more likely to exit the labor force if their partners' earnings are higher and if their own wage rate is lower. In this article, I use the National Longitudinal Survey of Youth (N = 2,254) and discrete-time event-history analysis to show that wives' relative wages are more predictive of their exit than are…

First exit times of harmonically trapped particles: a didactic review

International Nuclear Information System (INIS)

Grebenkov, Denis S

2015-01-01

We revise the classical problem of characterizing first exit times of a harmonically trapped particle whose motion is described by a one- or multidimensional Ornstein–Uhlenbeck process. We start by recalling the main derivation steps of a propagator using Langevin and Fokker–Planck equations. The mean exit time, the moment-generating function and the survival probability are then expressed through confluent hypergeometric functions and thoroughly analyzed. We also present a rapidly converging series representation of confluent hypergeometric functions that is particularly well suited for numerical computation of eigenvalues and eigenfunctions of the governing Fokker–Planck operator. We discuss several applications of first exit times, such as the detection of time intervals during which motor proteins exert a constant force onto a tracer in optical tweezers single-particle tracking experiments; adhesion bond dissociation under mechanical stress; characterization of active periods of trend-following and mean-reverting strategies in algorithmic trading on stock markets; relation to the distribution of first crossing times of a moving boundary by Brownian motion. Some extensions are described, including diffusion under quadratic double-well potential and anomalous diffusion. (topical review)

Visual Barriers to Prevent Ambulatory ALzheimer's Patients from Exiting through an Emergency Door.

Science.gov (United States)

Namazi, Kevan H.; And Others

1989-01-01

Conducted study on Alzheimer's unit to test seven different visual barrier conditions for reducing patient exits. Findings indicated that exiting was eliminated under two conditions. Results suggest visual agnosia, the inability to interpret what the eye sees, may be used as tool in managing wandering behavior of Alzheimer's patients. (Author/NB)

Mitosis can drive cell cannibalism through entosis

Science.gov (United States)

Durgan, Joanne; Tseng, Yun-Yu; Hamann, Jens C; Domart, Marie-Charlotte; Collinson, Lucy; Overholtzer, Michael; Florey, Oliver

2017-01-01

Entosis is a form of epithelial cell cannibalism that is prevalent in human cancer, typically triggered by loss of matrix adhesion. Here, we report an alternative mechanism for entosis in human epithelial cells, driven by mitosis. Mitotic entosis is regulated by Cdc42, which controls mitotic morphology. Cdc42 depletion enhances mitotic deadhesion and rounding, and these biophysical changes, which depend on RhoA activation and are phenocopied by Rap1 inhibition, permit subsequent entosis. Mitotic entosis occurs constitutively in some human cancer cell lines and mitotic index correlates with cell cannibalism in primary human breast tumours. Adherent, wild-type cells can act efficiently as entotic hosts, suggesting that normal epithelia may engulf and kill aberrantly dividing neighbours. Finally, we report that Paclitaxel/taxol promotes mitotic rounding and subsequent entosis, revealing an unconventional activity of this drug. Together, our data uncover an intriguing link between cell division and cannibalism, of significance to both cancer and chemotherapy. DOI: http://dx.doi.org/10.7554/eLife.27134.001 PMID:28693721

Entrance, exit, and reentrance of one shot with a shotgun

DEFF Research Database (Denmark)

Gulmann, C; Hougen, H P

1999-01-01

The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region, and ther......The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region...

Formation Mechanisms for Entry and Exit Defects in Bobbin Friction Stir Welding

Directory of Open Access Journals (Sweden)

Abbas Tamadon

2018-01-01

Full Text Available Bobbin friction stir welding (BFSW is an innovative variant for the solid state welding process whereby a rotating symmetrical tool causes a fully penetrated bond. Despite the process development, there are still unknown variables in the characterization of the process parameters which can cause uncontrolled weld defects. The entry zone and the exit zone consist of two discontinuity-defects and removing them is one of the current challenges for improving the weld quality. In the present research, the characteristic features of the entry and exit defects in the weld structure and formation mechanism of them during the BFSW processing was investigated. Using stacked layers of multi-colour plasticine the material flow, analogous to metal flow, can be visualised. By using different colours as the path markers of the analogue model, the streamline flow can be easily delineated in the discontinuity defects compared with the metal welds. AA6082-T6 aluminium plates and multi-layered plasticine slabs were employed to replicate the entry-exit defects in the metal weld and analogue samples. The fixed-bobbin tool utilized for this research was optimized by adding a thread feature and tri-flat geometry to the pin and closed-end spiral scrolls on both shoulder surfaces. Samples were processed at different rotating and longitudinal speeds to show the degree of dependency on the welding parameters for the defects. The analogue models showed that the entry zone and the exit zone of the BFSW are affected by the inhomogeneity of the material flow regime which causes the ejection or disruption of the plastic flow in the gap between the bobbin shoulders. The trial aluminium welds showed that the elimination of entry-exit defects in the weld body is not completely possible but the size of the defects can be minimized by modification of the welding parameters. For the entry zone, the flow pattern evolution suggested formation mechanisms for a sprayed tail, island zone

The impact of ill health on exit from paid employment in Europe among older workers.

Science.gov (United States)

van den Berg, Tilja; Schuring, Merel; Avendano, Mauricio; Mackenbach, Johan; Burdorf, Alex

2010-12-01

To determine the impact of ill health on exit from paid employment in Europe among older workers. Participants of the Survey on Health and Ageing in Europe (SHARE) in 11 European countries in 2004 and 2006 were selected when 50-63 years old and in paid employment at baseline (n=4611). Data were collected on self-rated health, chronic diseases, mobility limitations, obesity, smoking, alcohol use, physical activity and work characteristics. Participants were classified into employed, retired, unemployed and disabled at the end of the 2-year follow-up. Multinomial logistic regression was used to estimate the effect of different measures of ill health on exit from paid employment. During the 2-year follow-up, 17% of employed workers left paid employment, mainly because of early retirement. Controlling for individual and work related characteristics, poor self-perceived health was strongly associated with exit from paid employment due to retirement, unemployment or disability (ORs from 1.32 to 4.24). Adjustment for working conditions and lifestyle reduced the significant associations between ill health and exit from paid employment by 0-18.7%. Low education, obesity, low job control and effort-reward imbalance were associated with measures of ill health, but also risk factors for exit from paid employment after adjustment for ill health. Poor self-perceived health was strongly associated with exit from paid employment among European workers aged 50-63 years. This study suggests that the influence of ill health on exit from paid employment could be lessened by measures targeting obesity, problematic alcohol use, job control and effort-reward balance.

49 CFR 238.113 - Emergency window exits.

Science.gov (United States)

2010-10-01

..., electrical locker, or kitchen); and (B) There are no more than eight seats in the seating area. (4) Cars with...), a bathroom, kitchen, or locomotive cab is not considered a “compartment.” (b) Ease of operability. On or after November 8, 1999, each emergency window exit shall be designed to permit rapid and easy...

Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

DEFF Research Database (Denmark)

Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore

2005-01-01

of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi...

Golgi twins in late mitosis revealed by genetically encoded tags for live cell imaging and correlated electron microscopy

NARCIS (Netherlands)

Gaietta, Guido M; Giepmans, Ben N G; Deerinck, Thomas J; Smith, W Bryan; Ngan, Lucy; Llopis, Juan; Adams, Stephen R; Tsien, Roger Y; Ellisman, Mark H

2006-01-01

Combinations of molecular tags visible in light and electron microscopes become particularly advantageous in the analysis of dynamic cellular components like the Golgi apparatus. This organelle disassembles at the onset of mitosis and, after a sequence of poorly understood events, reassembles after

NAD+ Is a Food Component That Promotes Exit from Dauer Diapause in Caenorhabditis elegans.

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Mykola Mylenko

Full Text Available The free-living soil nematode Caenorhabditis elegans adapts its development to the availability of food. When food is scarce and population density is high, worms enter a developmentally arrested non-feeding diapause stage specialized for long-term survival called the dauer larva. When food becomes available, they exit from the dauer stage, resume growth and reproduction. It has been postulated that compound(s present in food, referred to as the "food signal", promote exit from the dauer stage. In this study, we have identified NAD+ as a component of bacterial extract that promotes dauer exit. NAD+, when dissolved in alkaline medium, causes opening of the mouth and ingestion of food. We also show that to initiate exit from the dauer stage in response to NAD+ worms require production of serotonin. Thus, C. elegans can use redox cofactors produced by dietary organisms to sense food.

Exit, voice, and loyalty in the Italian public health service: macroeconomic and corporate implications.

Science.gov (United States)

Ippolito, Adelaide; Impagliazzo, Cira; Zoccoli, Paola

2013-01-01

The paper analyses how customers of public health organizations can express their dissatisfaction for the services offered to them. The main aim is to evaluate the effects that possible dissatisfaction of Italian public health service customers can have on public health organizations. We adopted the methodological scheme developed by Hirschman with exit, voice, and loyalty, considering the macroeconomic and corporate implications that it causes for Italian public health organizations. The study investigated the effects developed by exit of the patients on the system of financing of local health authorities considering both the corporate level of analysis and the macroeconomic level. As a result, local health authority management is encouraged to pay greater attention to the exit phenomena through the adoption of tools that promote loyalty, such as the promotion of voice, even if exit is not promoting, at a macroeconomic level, considerable attention to this phenomenon.

Exit, Voice, and Loyalty in the Italian Public Health Service: Macroeconomic and Corporate Implications

Science.gov (United States)

Impagliazzo, Cira; Zoccoli, Paola

2013-01-01

The paper analyses how customers of public health organizations can express their dissatisfaction for the services offered to them. The main aim is to evaluate the effects that possible dissatisfaction of Italian public health service customers can have on public health organizations. We adopted the methodological scheme developed by Hirschman with exit, voice, and loyalty, considering the macroeconomic and corporate implications that it causes for Italian public health organizations. The study investigated the effects developed by exit of the patients on the system of financing of local health authorities considering both the corporate level of analysis and the macroeconomic level. As a result, local health authority management is encouraged to pay greater attention to the exit phenomena through the adoption of tools that promote loyalty, such as the promotion of voice, even if exit is not promoting, at a macroeconomic level, considerable attention to this phenomenon. PMID:24348148

Mitotic accumulation of dimethylated lysine 79 of histone H3 is important for maintaining genome integrity during mitosis in human cells.

Science.gov (United States)

Guppy, Brent J; McManus, Kirk J

2015-02-01

The loss of genome stability is an early event that drives the development and progression of virtually all tumor types. Recent studies have revealed that certain histone post-translational modifications exhibit dynamic and global increases in abundance that coincide with mitosis and exhibit essential roles in maintaining genomic stability. Histone H2B ubiquitination at lysine 120 (H2Bub1) is regulated by RNF20, an E3 ubiquitin ligase that is altered in many tumor types. Through an evolutionarily conserved trans-histone pathway, H2Bub1 is an essential prerequisite for subsequent downstream dimethylation events at lysines 4 (H3K4me2) and 79 (H3K79me2) of histone H3. Although the role that RNF20 plays in tumorigenesis has garnered much attention, the downstream components of the trans-histone pathway, H3K4me2 and H3K79me2, and their potential contributions to genome stability remain largely overlooked. In this study, we employ single-cell imaging and biochemical approaches to investigate the spatial and temporal patterning of RNF20, H2Bub1, H3K4me2, and H3K79me2 throughout the cell cycle, with a particular focus on mitosis. We show that H2Bub1, H3K4me2, and H3K79me2 exhibit distinct temporal progression patterns throughout the cell cycle. Most notably, we demonstrate that H3K79me2 is a highly dynamic histone post-translational modification that reaches maximal abundance during mitosis in an H2Bub1-independent manner. Using RNAi and chemical genetic approaches, we identify DOT1L as a histone methyltransferase required for the mitotic-associated increases in H3K79me2. We also demonstrate that the loss of mitotic H3K79me2 levels correlates with increases in chromosome numbers and increases in mitotic defects. Collectively, these data suggest that H3K79me2 dynamics during mitosis are normally required to maintain genome stability and further implicate the loss of H3K79me2 during mitosis as a pathogenic event that contributes to the development and progression of tumors

Ecologies of Ideologies : Explaining Party Entry and Exit in West-European Parliaments, 1945-2013

NARCIS (Netherlands)

van de Wardt, M.; Berkhout, J.; Vermeulen, F.

2017-01-01

This study introduces a population-ecological approach to the entry and exit of political parties. A primary proposition of population ecology is that organizational entry and exit depends on the number of organizations already present: that is, density. We propose that political parties mainly

Marines, medics, and machismo: lack of fit with masculine occupational stereotypes discourages men's participation.

Science.gov (United States)

Peters, Kim; Ryan, Michelle K; Haslam, S Alexander

2015-11-01

Women have made substantial inroads into some traditionally masculine occupations (e.g., accounting, journalism) but not into others (e.g., military, surgery). Evidence suggests the latter group of occupations is characterized by hyper-masculine 'macho' stereotypes that are especially disadvantageous to women. Here, we explore whether such macho occupational stereotypes may be especially tenacious, not just because of their impact on women, but also because of their impact on men. We examined whether macho stereotypes associated with marine commandos and surgeons discourage men who feel that they are 'not man enough'. Study 1 demonstrates that male new recruits' (N = 218) perceived lack of fit with masculine commandos was associated with reduced occupational identification and motivation. Study 2 demonstrates that male surgical trainees' (N = 117) perceived lack of fit with masculine surgeons was associated with reduced identification and increased psychological exit a year later. Together, this suggests that macho occupational stereotypes may discourage the very men who may challenge them. © 2014 The British Psychological Society.

Sampling for Patient Exit Interviews: Assessment of Methods Using Mathematical Derivation and Computer Simulations.

Science.gov (United States)

Geldsetzer, Pascal; Fink, Günther; Vaikath, Maria; Bärnighausen, Till

2018-02-01

(1) To evaluate the operational efficiency of various sampling methods for patient exit interviews; (2) to discuss under what circumstances each method yields an unbiased sample; and (3) to propose a new, operationally efficient, and unbiased sampling method. Literature review, mathematical derivation, and Monte Carlo simulations. Our simulations show that in patient exit interviews it is most operationally efficient if the interviewer, after completing an interview, selects the next patient exiting the clinical consultation. We demonstrate mathematically that this method yields a biased sample: patients who spend a longer time with the clinician are overrepresented. This bias can be removed by selecting the next patient who enters, rather than exits, the consultation room. We show that this sampling method is operationally more efficient than alternative methods (systematic and simple random sampling) in most primary health care settings. Under the assumption that the order in which patients enter the consultation room is unrelated to the length of time spent with the clinician and the interviewer, selecting the next patient entering the consultation room tends to be the operationally most efficient unbiased sampling method for patient exit interviews. © 2016 The Authors. Health Services Research published by Wiley Periodicals, Inc. on behalf of Health Research and Educational Trust.

The exit-time problem for a Markov jump process

Science.gov (United States)

Burch, N.; D'Elia, M.; Lehoucq, R. B.

2014-12-01

The purpose of this paper is to consider the exit-time problem for a finite-range Markov jump process, i.e, the distance the particle can jump is bounded independent of its location. Such jump diffusions are expedient models for anomalous transport exhibiting super-diffusion or nonstandard normal diffusion. We refer to the associated deterministic equation as a volume-constrained nonlocal diffusion equation. The volume constraint is the nonlocal analogue of a boundary condition necessary to demonstrate that the nonlocal diffusion equation is well-posed and is consistent with the jump process. A critical aspect of the analysis is a variational formulation and a recently developed nonlocal vector calculus. This calculus allows us to pose nonlocal backward and forward Kolmogorov equations, the former equation granting the various moments of the exit-time distribution.

Progesterone Receptor Membrane Component 1 (PGRMC1 in cell division: its role in bovine granulosa cells mitosis

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Laura Terzaghi

2015-07-01

Full Text Available The present studies were aimed to assess Progesterone Receptor Membrane Component-1 (PGRMC1 role in regulating bovine granulosa cells (bGC mitosis. First, we performed immunofluorescence studies on in vitro cultured bGC collected from antral follicles, which showed that PGRMC1 localizes to the spindle apparatus in mitotic cells. Then, to evaluate PGRMC1 effect on cell proliferation we silenced its expression with RNA interference technique (RNAi. Quantitative RT-PCR and immunoblotting confirmed down-regulation of PGRMC1 expression, when compared to CTRL-RNAi treated bGC (p<0.05. After 72h of culture, PGRMC1 silencing determined a lower growth rate (p<0.05 and a higher percentage of cells arrested at G2/M phase as assessed by flowcytometry (p<0.05. Accordingly, live imaging studies revealed more aberrant mitosis and a delayed M-phase in PGRMC1-RNAi treated cells compared to CTRL-RNAi group (p<0.05. These data confirmed that PGRMC1 is directly involved in bGC mitosis and ongoing preliminary studies are aimed to elucidate its putative mechanisms of action. Since PGRMC1 is a membrane protein, we hypothesize its possible involvement in vesicular trafficking and endocytosis, which is in turn an important process to assure proper cell division. To assess this hypothesis, we have preliminarily conducted immunofluorescence and in situ proximity ligation assay experiments that showed PGRMC1 co-localization and direct interaction with clathrin. This is important since clathrin is an essential protein for both endosomes formation, and cell division acting directly on the spindle apparatus. Thus our studies set the stage for analysis aimed to further characterize PGRMC1’s mechanism of action in mitotic cell.

Probability evolution method for exit location distribution

Science.gov (United States)

Zhu, Jinjie; Chen, Zhen; Liu, Xianbin

2018-03-01

The exit problem in the framework of the large deviation theory has been a hot topic in the past few decades. The most probable escape path in the weak-noise limit has been clarified by the Freidlin-Wentzell action functional. However, noise in real physical systems cannot be arbitrarily small while noise with finite strength may induce nontrivial phenomena, such as noise-induced shift and noise-induced saddle-point avoidance. Traditional Monte Carlo simulation of noise-induced escape will take exponentially large time as noise approaches zero. The majority of the time is wasted on the uninteresting wandering around the attractors. In this paper, a new method is proposed to decrease the escape simulation time by an exponentially large factor by introducing a series of interfaces and by applying the reinjection on them. This method can be used to calculate the exit location distribution. It is verified by examining two classical examples and is compared with theoretical predictions. The results show that the method performs well for weak noise while may induce certain deviations for large noise. Finally, some possible ways to improve our method are discussed.

Histopathological detection of entry and exit holes in human skin wounds caused by firearms.

Science.gov (United States)

Baptista, Marcus Vinícius; d'Ávila, Solange C G P; d'Ávila, Antônio Miguel M P

2014-07-01

The judiciary needs forensic medicine to determine the difference between an entry hole and an exit hole in human skin caused by firearms for civilian use. This important information would be most useful if a practical and accurate method could be done with low-cost and minimal technological resources. Both macroscopic and microscopic analyses were performed on skin lesions caused by firearm projectiles, to establish histological features of 14 entry holes and 14 exit holes. Microscopically, in the abrasion area macroscopically observed, there were signs of burns (sub-epidermal cracks and keratinocyte necrosis) in the entrance holes in all cases. These signs were not found in three exit holes which showed an abrasion collar, nor in other exit holes. Some other microscopic features not found in every case were limited either to entry holes, such as cotton fibres, grease deposits, or tattooing in the dermis, or to exit holes, such as adipose tissue, bone or muscle tissue in the dermis. Coagulative necrosis of keratinocytes and sub-epidermal cracks are characteristic of entry holes. Despite the small sample size, it can be safely inferred that this is an important microscopic finding, among others less consistently found, to define an entry hole in questionable cases. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Exit and Failure of Credit Unions in Brazil: A Risk Analysis

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Flávio Leonel de Carvalho

2015-04-01

Full Text Available This study aims to investigate the factors that affect the market exit of Brazilian singular credit unions from 1995 to 2009; it also identifies and lists the determinants of various types of market exits and analyzes whether profitability is a significant factor for credit union survival. This study was conducted with accounting data provided by the Central Bank of Brazil, which derives only from individual cooperatives, i.e. singular credit unions. Quarterly financial statements from these credit unions that were active from 1995 to the second quarter of 2009 were employed, totaling 71,325 observations for 1,929 credit unions. Based on survival and the model of competing risks (such as the Cox, Exponential, Weibull, Gompertz, and Competing Risk models, the results show that there is no statistical evidence to ensure a correlation between profitability and credit union survival. The results also suggest that the size of credit unions plays a key role in their survival and longevity and that their funding and investment management are related to their survival and risk of market exit. In conclusion, the results confirm the initial idea that the duality inherent to credit unions - cooperative principles versus economic efficiency - might influence the stability, survival, and longevity of these institutions. Such results may also imply that a credit union embracing the rationale of a private bank will become more estranged from its members, something which will hinder its future operations and increase the likelihood of its exit from the market.

Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

Science.gov (United States)

Calton, Christine M; Bronnimann, Matthew P; Manson, Ariana R; Li, Shuaizhi; Chapman, Janice A; Suarez-Berumen, Marcela; Williamson, Tatum R; Molugu, Sudheer K; Bernal, Ricardo A; Campos, Samuel K

2017-05-01

The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.

Regulation of mitosis by the NIMA kinase involves TINA and its newly discovered partner, An-WDR8, at spindle pole bodies

Science.gov (United States)

Shen, Kuo-Fang; Osmani, Stephen A.

2013-01-01

The NIMA kinase is required for mitotic nuclear pore complex disassembly and potentially controls other mitotic-specific events. To investigate this possibility, we imaged NIMA–green fluorescent protein (GFP) using four-dimensional spinning disk confocal microscopy. At mitosis NIMA-GFP locates to spindle pole bodies (SPBs), which contain Cdk1/cyclin B, followed by Aurora, TINA, and the BimC kinesin. NIMA promotes NPC disassembly in a spatially regulated manner starting near SPBs. NIMA is also required for TINA, a NIMA-interacting protein, to locate to SPBs during initiation of mitosis, and TINA is then necessary for locating NIMA back to SPBs during mitotic progression. To help expand the NIMA-TINA pathway, we affinity purified TINA and found it to uniquely copurify with An-WDR8, a WD40-domain protein conserved from humans to plants. Like TINA, An-WDR8 accumulates within nuclei during G2 but disperses from nuclei before locating to mitotic SPBs. Without An-WDR8, TINA levels are greatly reduced, whereas TINA is necessary for mitotic targeting of An-WDR8. Finally, we show that TINA is required to anchor mitotic microtubules to SPBs and, in combination with An-WDR8, for successful mitosis. The findings provide new insights into SPB targeting and indicate that the mitotic microtubule-anchoring system at SPBs involves WDR8 in complex with TINA. PMID:24152731

Population control of resident and immigrant microglia by mitosis and apoptosis

DEFF Research Database (Denmark)

Wirenfeldt, Martin; Dissing-Olesen, Lasse; Babcock, Alicia

2007-01-01

microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate...... in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced...... in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations....

Fast Water Transport in CNTs: length dependence and entrane/exit effects

DEFF Research Database (Denmark)

Walther, Jens Honore; Koumoutsakos, Petros

Superfast water transport in carbon nanotube (CNT) membranes has been reported in experimental studies. We use Molecular Dynamics simulations to elucidate the mechanisms of water entry, exit and transport in 2nm-diameter hydrophobic CNTs embedded in a hydrophilic membrane matrix. We demonstrate......, for the first time, that under imposed pressures of the order of 1 bar, water entry into the CNT cavity and exit from the CNT end, can occur only on pre-wetted membranes. We conduct large scale simulations for up to 500nm long CNTs and observe a previously unseen dependence of the flow enhancement rates...

Forthcoming EU Rules on Exit Taxes for Companies

NARCIS (Netherlands)

van de Streek, J.

2015-01-01

Rules on exit taxation for the EU as a whole are under construction at European Council level. Formally, the work on this piece of EU tax legislation is part of the controversial Common Consolidated Corporate Tax Base (CCCTB). But it is also thinkable that even without a CCCTB being established in

Customer Protest: Exit, Voice or Negative Word of Mouth

Directory of Open Access Journals (Sweden)

Solvang, B. K.

2008-01-01

Full Text Available Of the three forms of protest the propensity of word of mouth (WOM seems to be the most common, and the most exclusive form of protest seems to be exit. The propensity for voice lies in between. The costs linked to voice influence the propensity for WOM. The customers seem to do an evaluation between the three forms of protest, yet the rational picture of the customers should be moderated.Leaders should improve their treatment of the customers making complaints. The more they can treat customer complaints in an orderly and nice way the less informal negative word of mouth activity they will experience and they will reduce the exit propensity and lead the customers to the complain organisation. They should also ensure that their customers feel they get equal treatment by the staff.

The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Jennifer L Bandura

Full Text Available The coordination of cell proliferation and differentiation is crucial for proper development. In particular, robust mechanisms exist to ensure that cells permanently exit the cell cycle upon terminal differentiation, and these include restraining the activities of both the E2F/DP transcription factor and Cyclin/Cdk kinases. However, the full complement of mechanisms necessary to restrain E2F/DP and Cyclin/Cdk activities in differentiating cells are not known. Here, we have performed a genetic screen in Drosophila melanogaster, designed to identify genes required for cell cycle exit. This screen utilized a PCNA-miniwhite(+ reporter that is highly E2F-responsive and results in a darker red eye color when crossed into genetic backgrounds that delay cell cycle exit. Mutation of Hsp83, the Drosophila homolog of mammalian Hsp90, results in increased E2F-dependent transcription and ectopic cell proliferation in pupal tissues at a time when neighboring wild-type cells are postmitotic. Further, these Hsp83 mutant cells have increased Cyclin/Cdk activity and accumulate proteins normally targeted for proteolysis by the anaphase-promoting complex/cyclosome (APC/C, suggesting that APC/C function is inhibited. Indeed, reducing the gene dosage of an inhibitor of Cdh1/Fzr, an activating subunit of the APC/C that is required for timely cell cycle exit, can genetically suppress the Hsp83 cell cycle exit phenotype. Based on these data, we propose that Cdh1/Fzr is a client protein of Hsp83. Our results reveal that Hsp83 plays a heretofore unappreciated role in promoting APC/C function during cell cycle exit and suggest a mechanism by which Hsp90 inhibition could promote genomic instability and carcinogenesis.

The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila melanogaster.

Science.gov (United States)

Bandura, Jennifer L; Jiang, Huaqi; Nickerson, Derek W; Edgar, Bruce A

2013-01-01

The coordination of cell proliferation and differentiation is crucial for proper development. In particular, robust mechanisms exist to ensure that cells permanently exit the cell cycle upon terminal differentiation, and these include restraining the activities of both the E2F/DP transcription factor and Cyclin/Cdk kinases. However, the full complement of mechanisms necessary to restrain E2F/DP and Cyclin/Cdk activities in differentiating cells are not known. Here, we have performed a genetic screen in Drosophila melanogaster, designed to identify genes required for cell cycle exit. This screen utilized a PCNA-miniwhite(+) reporter that is highly E2F-responsive and results in a darker red eye color when crossed into genetic backgrounds that delay cell cycle exit. Mutation of Hsp83, the Drosophila homolog of mammalian Hsp90, results in increased E2F-dependent transcription and ectopic cell proliferation in pupal tissues at a time when neighboring wild-type cells are postmitotic. Further, these Hsp83 mutant cells have increased Cyclin/Cdk activity and accumulate proteins normally targeted for proteolysis by the anaphase-promoting complex/cyclosome (APC/C), suggesting that APC/C function is inhibited. Indeed, reducing the gene dosage of an inhibitor of Cdh1/Fzr, an activating subunit of the APC/C that is required for timely cell cycle exit, can genetically suppress the Hsp83 cell cycle exit phenotype. Based on these data, we propose that Cdh1/Fzr is a client protein of Hsp83. Our results reveal that Hsp83 plays a heretofore unappreciated role in promoting APC/C function during cell cycle exit and suggest a mechanism by which Hsp90 inhibition could promote genomic instability and carcinogenesis.

Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis

DEFF Research Database (Denmark)

Hein, Jamin B; Hertz, Emil P T; Garvanska, Dimitriya H

2017-01-01

Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains ...

45 CFR 670.34 - Entry and exit ports.

Science.gov (United States)

2010-10-01

... ANTARCTIC ANIMALS AND PLANTS Import Into and Export From the United States § 670.34 Entry and exit ports. (a) Any native mammal, native bird, or native plants taken within Antarctica that are imported into or... Orleans, Louisiana. (7) New York, New York. (8) Seattle, Washington. (9) Dallas/Fort Worth, Texas. (10...

A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application

International Nuclear Information System (INIS)

Banjade, D.P.; Shukri, A.; Tajuddin, A.A.; Shrestha, S.L.; Bhat, M.

2002-01-01

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within ±3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at d max ). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice. Copyright (2002) Australasian College of Physical Scientists and Engineers in Medicine

Airport exit and entry screening for Ebola--August-November 10, 2014.

Science.gov (United States)

Brown, Clive M; Aranas, Aaron E; Benenson, Gabrielle A; Brunette, Gary; Cetron, Marty; Chen, Tai-Ho; Cohen, Nicole J; Diaz, Pam; Haber, Yonat; Hale, Christa R; Holton, Kelly; Kohl, Katrin; Le, Amanda W; Palumbo, Gabriel J; Pearson, Kate; Phares, Christina R; Alvarado-Ramy, Francisco; Roohi, Shah; Rotz, Lisa D; Tappero, Jordan; Washburn, Faith M; Watkins, James; Pesik, Nicki

2014-12-12

In response to the largest recognized Ebola virus disease epidemic now occurring in West Africa, the governments of affected countries, CDC, the World Health Organization (WHO), and other international organizations have collaborated to implement strategies to control spread of the virus. One strategy recommended by WHO calls for countries with Ebola transmission to screen all persons exiting the country for "unexplained febrile illness consistent with potential Ebola infection." Exit screening at points of departure is intended to reduce the likelihood of international spread of the virus. To initiate this strategy, CDC, WHO, and other global partners were invited by the ministries of health of Guinea, Liberia, and Sierra Leone to assist them in developing and implementing exit screening procedures. Since the program began in August 2014, an estimated 80,000 travelers, of whom approximately 12,000 were en route to the United States, have departed by air from the three countries with Ebola transmission. Procedures were implemented to deny boarding to ill travelers and persons who reported a high risk for exposure to Ebola; no international air traveler from these countries has been reported as symptomatic with Ebola during travel since these procedures were implemented.

Toward electron exit wave tomography of amorphous materials at atomic resolution

Energy Technology Data Exchange (ETDEWEB)

Borisenko, Konstantin B., E-mail: konstantin.borisenko@materials.ox.ac.uk [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Moldovan, Grigore [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Kirkland, Angus I., E-mail: angus.kirkland@materials.ox.ac.uk [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Van Dyck, Dirk [Department of Physics, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Tang, Hsin-Yu; Chen, Fu-Rong [Department of Engineering and System Science, National Tsing Hua University, Kuang-Fu Road, 300 Hsinchu, Taiwan (China)

2012-09-25

Highlights: Black-Right-Pointing-Pointer We suggest a novel electron exit wave tomography approach to obtain three dimensional atomic structures of amorphous materials. Black-Right-Pointing-Pointer Theoretical tests using a model of amorphous Si doped with Au show that it is feasible to reconstruct both Si and Au atoms positions. Black-Right-Pointing-Pointer Reconstructions of the strongly scattering Au atoms positions appear to be insensitive to typical experimental errors. - Abstract: We suggest to use electron exit wave phase for tomographic reconstruction of structure of Au-doped amorphous Si with atomic resolution. In the present theoretical investigation into the approach it is found that the number of projections and the accuracy of defocus in the focal series restoration are the main factors that contribute to the final resolution. Although resolution is ultimately limited by these factors, phase shifts in the exit wave are sufficient to identify the position of Au atoms in an amorphous Si needle model, even when only 19 projections with defocus error of 4 nm are used. Electron beam damage will probably further limit the resolution of such tomographic reconstructions, however beam damage can be mitigated using lower accelerating voltages.

A balance of FGF and BMP signals regulates cell cycle exit and Equarin expression in lens cells

Science.gov (United States)

Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena

2012-01-01

In embryonic and adult lenses, a balance of cell proliferation, cell cycle exit, and differentiation is necessary to maintain physical function. The molecular mechanisms regulating the transition of proliferating lens epithelial cells to differentiated primary lens fiber cells are poorly characterized. To investigate this question, we used gain- and loss-of-function analyses to modulate fibroblast growth factor (FGF) and/or bone morphogenetic protein (BMP) signals in chick lens/retina explants. Here we show that FGF activity plays a key role for proliferation independent of BMP signals. Moreover, a balance of FGF and BMP signals regulates cell cycle exit and the expression of Ccdc80 (also called Equarin), which is expressed at sites where differentiation of lens fiber cells occurs. BMP activity promotes cell cycle exit and induces Equarin expression in an FGF-dependent manner. In contrast, FGF activity is required but not sufficient to induce cell cycle exit or Equarin expression. Furthermore, our results show that in the absence of BMP activity, lens cells have increased cell cycle length or are arrested in the cell cycle, which leads to decreased cell cycle exit. Taken together, these findings suggest that proliferation, cell cycle exit, and early differentiation of primary lens fiber cells are regulated by counterbalancing BMP and FGF signals. PMID:22718906

Determination of the availability of core exit thermocouples during severe accident situations

International Nuclear Information System (INIS)

Edson, J.L.

1985-04-01

This report presents the findings and recommendations of the Nuclear Power Plant Instrumentation Evaluation (NPPIE) program concerning signal validation methods to determine the on-line availability of core exit thermocouples during accident situations. Methods of selecting appropriate signal validation techniques are discussed and sources of error identified. This report shows that through the use of these techniques the existence of high-temperature-caused errors may be detected as they occur. Specific recommendations for application of selected signal validation techniques to core exit thermocouples and other measurement systems are made. 23 refs., 22 figs., 3 tabs

Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal

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Pfeifer Aleksandra

2009-06-01

Full Text Available Abstract Background The molecular mechanisms of cell cycle exit are poorly understood. Studies on lymphocytes at cell cycle exit after growth factor deprivation have predominantly focused on the initiation of apoptosis. We aimed to study gene expression profile of primary and immortalised IL-2-dependent human T cells forced to exit the cell cycle by growth factor withdrawal, before apoptosis could be evidenced. Results By the Affymetrix microarrays HG-U133 2.0 Plus, 53 genes were distinguished as differentially expressed before and soon after IL-2 deprivation. Among those, PIM1, BCL2, IL-8, HBEGF, DUSP6, OSM, CISH, SOCS2, SOCS3, LIF and IL13 were down-regulated and RPS24, SQSTM1, TMEM1, LRRC8D, ECOP, YY1AP1, C1orf63, ASAH1, SLC25A46 and MIA3 were up-regulated. Genes linked to transcription, cell cycle, cell growth, proliferation and differentiation, cell adhesion, and immune functions were found to be overrepresented within the set of the differentially expressed genes. Conclusion Cell cycle exit of the growth factor-deprived T lymphocytes is characterised by a signature of differentially expressed genes. A coordinate repression of a set of genes known to be induced during T cell activation is observed. However, growth arrest following exit from the cell cycle is actively controlled by several up-regulated genes that enforce the non-dividing state. The identification of genes involved in cell cycle exit and quiescence provides new hints for further studies on the molecular mechanisms regulating the non-dividing state of a cell, the mechanisms closely related to cancer development and to many biological processes.

The Effect of Exit-Site Antibacterial Honey Versus Nasal Mupirocin Prophylaxis on the Microbiology and Outcomes of Peritoneal Dialysis-Associated Peritonitis and Exit-Site Infections: A Sub-Study of the Honeypot Trial.

Science.gov (United States)

Zhang, Lei; Badve, Sunil V; Pascoe, Elaine M; Beller, Elaine; Cass, Alan; Clark, Carolyn; de Zoysa, Janak; Isbel, Nicole M; McTaggart, Steven; Morrish, Alicia T; Playford, E Geoffrey; Scaria, Anish; Snelling, Paul; Vergara, Liza A; Hawley, Carmel M; Johnson, David W

2015-12-01

♦ The HONEYPOT study recently reported that daily exit-site application of antibacterial honey was not superior to nasal mupirocin prophylaxis for preventing overall peritoneal dialysis (PD)-related infection. This paper reports a secondary outcome analysis of the HONEYPOT study with respect to exit-site infection (ESI) and peritonitis microbiology, infectious hospitalization and technique failure. ♦ A total of 371 PD patients were randomized to daily exit-site application of antibacterial honey plus usual exit-site care (N = 186) or intranasal mupirocin prophylaxis (in nasal Staphylococcus aureus carriers only) plus usual exit-site care (control, N = 185). Groups were compared on rates of organism-specific ESI and peritonitis, peritonitis- and infection-associated hospitalization, and technique failure (PD withdrawal). ♦ The mean peritonitis rates in the honey and control groups were 0.41 (95% confidence interval [CI] 0.32 - 0.50) and 0.41 (95% CI 0.33 - 0.49) episodes per patient-year, respectively (incidence rate ratio [IRR] 1.01, 95% CI 0.75 - 1.35). When specific causative organisms were examined, no differences were observed between the groups for gram-positive (IRR 0.99, 95% CI 0.66 - 1.49), gram-negative (IRR 0.71, 95% CI 0.39 - 1.29), culture-negative (IRR 2.01, 95% CI 0.91 - 4.42), or polymicrobial peritonitis (IRR 1.08, 95% CI 0.36 - 3.20). Exit-site infection rates were 0.37 (95% CI 0.28 - 0.45) and 0.33 (95% CI 0.26 - 0.40) episodes per patient-year for the honey and control groups, respectively (IRR 1.12, 95% CI 0.81 - 1.53). No significant differences were observed between the groups for gram-positive (IRR 1.10, 95% CI 0.70 - 1.72), gram-negative (IRR: 0.85, 95% CI 0.46 - 1.58), culture-negative (IRR 1.88, 95% CI 0.67 - 5.29), or polymicrobial ESI (IRR 1.00, 95% CI 0.40 - 2.54). Times to first peritonitis-associated and first infection-associated hospitalization were similar in the honey and control groups. The rates of technique failure (PD

EFFECT OF REVENUE INSURANCE ON ENTRY AND EXIT DECISIONS IN TABLE GRAPE PRODUCTION: A REAL OPTION APPROACH

OpenAIRE

Seo, Sangtaek; Salin, Victoria; Mitchell, Paul D.; Leatham, David J.

2004-01-01

This study determines the entry and exit thresholds of table grape farming with irreversible investment under uncertainty. Real option approach is adopted to consider the investment and management flexibility. Also revenue insurance is introduced to consider the effect of the risk management programs on the entry and exit thresholds. Results show that revenue insurance increases the entry and exit thresholds by 1% and 4%, respectively, thus discouraging new investment and current farming, as ...

Phospho-H1 Decorates the Inter-chromatid Axis and Is Evicted along with Shugoshin by SET during Mitosis.

Science.gov (United States)

Krishnan, Swathi; Smits, Arne H; Vermeulen, Michiel; Reinberg, Danny

2017-08-17

Precise control of sister chromatid separation during mitosis is pivotal to maintaining genomic integrity. Yet, the regulatory mechanisms involved are not well understood. Remarkably, we discovered that linker histone H1 phosphorylated at S/T18 decorated the inter-chromatid axial DNA on mitotic chromosomes. Sister chromatid resolution during mitosis required the eviction of such H1S/T18ph by the chaperone SET, with this process being independent of and most likely downstream of arm-cohesin dissociation. SET also directed the disassembly of Shugoshins in a polo-like kinase 1-augmented manner, aiding centromere resolution. SET ablation compromised mitotic fidelity as evidenced by unresolved sister chromatids with marked accumulation of H1S/T18ph and centromeric Shugoshin. Thus, chaperone-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. Our findings also elucidate the functional implications of the decades-old observation of mitotic linker histone phosphorylation, serving as a paradigm to explore the role of linker histones in bio-signaling processes. Copyright © 2017 Elsevier Inc. All rights reserved.

The Exit Gradient As a Measure of Groundwater Dependency of Watershed Ecosystem Services

Science.gov (United States)

Faulkner, B. R.; Canfield, T. J.; Justin, G. F.

2014-12-01

Flux of groundwater to surface water is often of great interest for the determination of the groundwater dependency of ecosystem services, such as maintenance of wetlands and of baseflow as a contributor to stream channel storage. It is difficult to measure. Most methods are based on coarse mass balance estimates or seepage meters. One drawback of these methods is they are not entirely spatially explicit. The exit gradient is commonly used in engineering studies of hydraulic structures affected by groundwater flow. It can be simply defined in the groundwater modeling context as the ratio of the difference between the computed head and the land surface elevation, for each computational cell, to the thickness of the cell, as it varies in space. When combined with calibrated groundwater flow models, it also has the potential to be useful in watershed scale evaluations of groundwater dependency in a spatially explicit way. We have taken advantage of calibrated models for the Calapooia watershed, Oregon, to map exit gradients for the watershed. Streams in the Calapooia are hydraulically well connected with groundwater. Not surprisingly, we found large variations in exit gradients between wet and dry season model runs, supporting the notion of stream expansion, as observed in the field, which may have a substantial influence on water quality. We have mapped the exit gradients in the wet and dry seasons, and compared them to regions which have been mapped in wetland surveys. Those classified as Palustrine types fell largest in the area of contribution from groundwater. In many cases, substantially high exit gradients, even on average, did not correspond to mapped wetland areas, yet nutrient retention ecosystem services may still be playing a role in these areas. The results also reinforce the notion of the importance of baseflow to maintenance of stream flow, even in the dry summer season in this Temperate/Mediterranean climate. Exit gradient mapping is a simple, yet

CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

Science.gov (United States)

Převorovský, Martin; Oravcová, Martina; Zach, Róbert; Jordáková, Anna; Bähler, Jürg; Půta, František; Folk, Petr

2016-11-16

For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.

Hydroelastic slamming of flexible wedges: Modeling and experiments from water entry to exit

Science.gov (United States)

Shams, Adel; Zhao, Sam; Porfiri, Maurizio

2017-03-01

Fluid-structure interactions during hull slamming are of great interest for the design of aircraft and marine vessels. The main objective of this paper is to establish a semi-analytical model to investigate the entire hydroelastic slamming of a wedge, from the entry to the exit phase. The structural dynamics is described through Euler-Bernoulli beam theory and the hydrodynamic loading is estimated using potential flow theory. A Galerkin method is used to obtain a reduced order modal model in closed-form, and a Newmark-type integration scheme is utilized to find an approximate solution. To benchmark the proposed semi-analytical solution, we experimentally investigate fluid-structure interactions through particle image velocimetry (PIV). PIV is used to estimate the velocity field, and the pressure is reconstructed by solving the incompressible Navier-Stokes equations from PIV data. Experimental results confirm that the flow physics and free-surface elevation during water exit are different from water entry. While water entry is characterized by positive values of the pressure field, with respect to the atmospheric pressure, the pressure field during water exit may be less than atmospheric. Experimental observations indicate that the location where the maximum pressure in the fluid is attained moves from the pile-up region to the keel, as the wedge reverses its motion from the entry to the exit stage. Comparing experimental results with semi-analytical findings, we observe that the model is successful in predicting the free-surface elevation and the overall distribution of the hydrodynamic loading on the wedge. These integrated experimental and theoretical analyses of water exit problems are expected to aid in the design of lightweight structures, which experience repeated slamming events during their operation.

Exit interviews administered to patients participating in the COSTOP placebo controlled randomised trial in Uganda

Directory of Open Access Journals (Sweden)

Andrew Nunn

2016-08-01

Discussion: The exit interview demonstrated that there was some evidence of open label drug being taken by the participants. However, the results from the interview do not suggest that the trial results would have been seriously compromised. We would recommend the exit interview as a valuable way of assessing adherence to trial procedures.

Self-organization of intracellular gradients during mitosis

Directory of Open Access Journals (Sweden)

Fuller Brian G

2010-01-01

Full Text Available Abstract Gradients are used in a number of biological systems to transmit spatial information over a range of distances. The best studied are morphogen gradients where information is transmitted over many cell lengths. Smaller mitotic gradients reflect the need to organize several distinct events along the length of the mitotic spindle. The intracellular gradients that characterize mitosis are emerging as important regulatory paradigms. Intracellular gradients utilize intrinsic auto-regulatory feedback loops and diffusion to establish stable regions of activity within the mitotic cytosol. We review three recently described intracellular mitotic gradients. The Ran GTP gradient with its elaborate cascade of nuclear transport receptors and cargoes is the best characterized, yet the dynamics underlying the robust gradient of Ran-GTP have received little attention. Gradients of phosphorylation have been observed on Aurora B kinase substrates both before and after anaphase onset. In both instances the phosphorylation gradient appears to result from a soluble gradient of Aurora B kinase activity. Regulatory properties that support gradient formation are highlighted. Intracellular activity gradients that regulate localized mitotic events bare several hallmarks of self-organizing biologic systems that designate spatial information during pattern formation. Intracellular pattern formation represents a new paradigm in mitotic regulation.

New approach of a traditional analysis for predicting near-exit jet liquid instabilities

Science.gov (United States)

Jaramillo, Guillermo; Collicott, Steven

2015-11-01

Traditional linear instability theory for round liquid jets requires an exit-plane velocity profile be assumed so as to derive the characteristic growth rates and wavelengths of instabilities. This requires solving an eigenvalue problem for the Rayleigh Equation. In this new approach, a hyperbolic tangent velocity profile is assumed at the exit-plane of a round jet and a comparison is made with a hyperbolic secant profile. Temporal and Spatial Stability Analysis (TSA and SSA respectively) are the employed analytical tools to compare results of predicted most-unstable wavelengths from the given analytical velocity profiles and from previous experimental work. The local relevance of the velocity profile in the near-exit region of a liquid jet and the validity of an inviscid formulation through the Rayleigh equation are discussed as well. A comparison of numerical accuracy is made between two different mathematical approaches for the hyperbolic tangent profile with and without the Ricatti transformation. Reynolds number based on the momentum thickness of the boundary layer at the exit plane non-dimensionalizes the problem and, the Re range, based on measurements by Portillo in 2011, is 185 to 600. Wavelength measurements are taken from Portillo's experiment. School of Mechanical Engineering at Universidad del Valle, supported by a grant from Fulbright and Colciencias. Ph.D. student at the School of Aeronautics and Astronautics Purdue University.

Ecologies of ideologies: Explaining party entry and exit in West-European parliaments, 1945-2013.

Science.gov (United States)

van de Wardt, Marc; Berkhout, Joost; Vermeulen, Floris

2017-06-01

This study introduces a population-ecological approach to the entry and exit of political parties. A primary proposition of population ecology is that organizational entry and exit depends on the number of organizations already present: that is, density. We propose that political parties mainly experience competition from parties in the same ideological niche (left, centre, right). Pooled time-series analyses of 410 parties, 263 elections and 18 West-European countries largely support our expectations. We find that political parties are more likely to exit when density within their niche increases. Also there is competition between adjacent ideological niches, i.e. between centrist and right-wing niches. In contrast to our expectations, neither density nor institutional rules impact party entry. This raises important questions about the rationale of prospective entrants.

Prediction of midline dose from entrance ad exit dose using OSLD measurements for total irradiation

Energy Technology Data Exchange (ETDEWEB)

Choi, Chang Heon; Park, Jong Min; Park, So Yeon; Chun, Min Soo; Han, Ji Hye; Cho, Jin Dong; Kim, Jung In [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of)

2017-06-15

This study aims to predict the midline dose based on the entrance and exit doses from optically stimulated luminescence detector (OSLD) measurements for total body irradiation (TBI). For TBI treatment, beam data sets were measured for 6 MV and 15 MV beams. To evaluate the tissue lateral effect of various thicknesses, the midline dose and peak dose were measured using a solid water phantom (SWP) and ion chamber. The entrance and exit doses were measured using OSLDs. OSLDs were attached onto the central beam axis at the entrance and exit surfaces of the phantom. The predicted midline dose was evaluated as the sum of the entrance and exit doses by OSLD measurement. The ratio of the entrance dose to the exit dose was evaluated at various thicknesses. The ratio of the peak dose to the midline dose was 1.12 for a 30 cm thick SWP at both energies. When the patient thickness is greater than 30 cm, the 15 MV should be used to ensure dose homogeneity. The ratio of the entrance dose to the exit dose was less than 1.0 for thicknesses of less than 30 cm and 40 cm at 6 MV and 15 MV, respectively. Therefore, the predicted midline dose can be underestimated for thinner body. At 15 MV, the ratios were approximately 1.06 for a thickness of 50 cm. In cases where adult patients are treated with the 15 MV photon beam, it is possible for the predicted midline dose to be overestimated for parts of the body with a thickness of 50 cm or greater. The predicted midline dose and OSLD-measured midline dose depend on the phantom thickness. For in-vivo dosimetry of TBI, the measurement dose should be corrected in order to accurately predict the midline dose.

The use of an electronic portal imaging device for exit dosimetry and quality control measurements

International Nuclear Information System (INIS)

Kirby, Michael C.; Williams, Peter C.

1995-01-01

Purpose: To determine ways in which electronic portal imaging devices (EPIDs) could be used to (a) measure exit doses for external beam radiotherapy and (b) perform quality control checks on linear accelerators. Methods and Materials: When imaging, our fluoroscopic EPID adjusts the gain, offset, and frame acquisition time of the charge coupled device (CCD) camera automatically, to allow for the range of photon transmissions through the patient, and to optimize the signal-to-noise ratio. However, our EPID can be programmed to act as an integrating dosemeter. EPID dosemeter measurements were made for 20 MV photons, for different field sizes and thicknesses of unit density phantom material placed at varying exit surface to detector distances. These were compared with simultaneous Silicon diode exit dose measurements. Our exit dosimetry technique was verified using an anthropomorphic type phantom, and some initial measurements have been made for patients treated with irregularly shaped 20 MV x-ray fields. In this dosimetry mode, our EPID was also used to measure certain quality control parameters, x-ray field flatness, and the verification of segmented intensity modulated field prescriptions. Results: Configured for dosimetry, our EPID exhibited a highly linear response, capable of resolving individual monitor units. Exit doses could be measured to within about 3% of that measured using Silicon diodes. Field flatness was determined to within 1.5% of Farmer dosemeter measurements. Segmented intensity modulated fields can be easily verified. Conclusions: Our EPID has the versatility to assess a range of parameters pertinent to the delivery of high quality, high precision radiotherapy. When configured appropriately, it can measure exit doses in vivo, with reasonable accuracy, perform certain quick quality control checks, and analyze segmented intensity modulated treatment fields

Exit, voice and loyalty in Kenya's French bean industry: What ...

African Journals Online (AJOL)

response affected their continued participation in the supermarket business. It applies Hirschman's concept of exit, voice and loyalty to assess the strategies used by ... This strategy of compliance with IFSS has since become the model in

On a mean field game optimal control approach modeling fast exit scenarios in human crowds

KAUST Repository

Burger, Martin; Di Francesco, Marco; Markowich, Peter A.; Wolfram, Marie Therese

2013-01-01

The understanding of fast exit and evacuation situations in crowd motion research has received a lot of scientific interest in the last decades. Security issues in larger facilities, like shopping malls, sports centers, or festivals necessitate a better understanding of the major driving forces in crowd dynamics. In this paper we present an optimal control approach modeling fast exit scenarios in pedestrian crowds. The model is formulated in the framework of mean field games and based on a parabolic optimal control problem. We consider the case of a large human crowd trying to exit a room as fast as possible. The motion of every pedestrian is determined by minimizing a cost functional, which depends on his/her position and velocity, the overall density of people, and the time to exit. This microscopic setup leads in a mean-field formulation to a nonlinear macroscopic optimal control problem, which raises challenging questions for the analysis and numerical simulations.We discuss different aspects of the mathematical modeling and illustrate them with various computational results. ©2013 IEEE.

On a mean field game optimal control approach modeling fast exit scenarios in human crowds

KAUST Repository

Burger, Martin

2013-12-01

The understanding of fast exit and evacuation situations in crowd motion research has received a lot of scientific interest in the last decades. Security issues in larger facilities, like shopping malls, sports centers, or festivals necessitate a better understanding of the major driving forces in crowd dynamics. In this paper we present an optimal control approach modeling fast exit scenarios in pedestrian crowds. The model is formulated in the framework of mean field games and based on a parabolic optimal control problem. We consider the case of a large human crowd trying to exit a room as fast as possible. The motion of every pedestrian is determined by minimizing a cost functional, which depends on his/her position and velocity, the overall density of people, and the time to exit. This microscopic setup leads in a mean-field formulation to a nonlinear macroscopic optimal control problem, which raises challenging questions for the analysis and numerical simulations.We discuss different aspects of the mathematical modeling and illustrate them with various computational results. ©2013 IEEE.

Drivers' Visual Characteristics when Merging onto or Exiting an Urban Expressway.

Directory of Open Access Journals (Sweden)

Ying Cheng

Full Text Available The aim of this study is to examine drivers' visual and driving behavior while merging onto or exiting an urban expressway with low and high traffic densities. The analysis was conducted according to three periods (approaching, merging or exiting, and accelerating or decelerating. A total of 10 subjects (8 males and 2 females with ages ranging from 25 to 52 years old (M = 30.0 years old participated in the study. The research was conducted in a natural driving situation, and the drivers' eye movements were monitored and recorded using an eye tracking system. The results show that the influence of traffic density on the glance duration and scan duration is more significant when merging than when exiting. The results also demonstrate that the number of glances and the mean glance duration are mainly related to the driving task (e.g., the merging period. Therefore, drivers' visual search strategies mainly depend on the current driving task. With regard to driving behavior, the variation tendencies of the duration and the velocity of each period are similar. These results support building an automated driving assistant system that can automatically identify gaps and accelerate or decelerate the car accordingly or provide suggestions to the driver to do so.

High resolution electron exit wave reconstruction from a diffraction pattern using Gaussian basis decomposition

International Nuclear Information System (INIS)

Borisenko, Konstantin B; Kirkland, Angus I

2014-01-01

We describe an algorithm to reconstruct the electron exit wave of a weak-phase object from single diffraction pattern. The algorithm uses analytic formulations describing the diffraction intensities through a representation of the object exit wave in a Gaussian basis. The reconstruction is achieved by solving an overdetermined system of non-linear equations using an easily parallelisable global multi-start search with Levenberg-Marquard optimisation and analytic derivatives

Hedgehog signaling acts with the temporal cascade to promote neuroblast cell cycle exit.

Directory of Open Access Journals (Sweden)

Phing Chian Chai

Full Text Available In Drosophila postembryonic neuroblasts, transition in gene expression programs of a cascade of transcription factors (also known as the temporal series acts together with the asymmetric division machinery to generate diverse neurons with distinct identities and regulate the end of neuroblast proliferation. However, the underlying mechanism of how this "temporal series" acts during development remains unclear. Here, we show that Hh signaling in the postembryonic brain is temporally regulated; excess (earlier onset of Hh signaling causes premature neuroblast cell cycle exit and under-proliferation, whereas loss of Hh signaling causes delayed cell cycle exit and excess proliferation. Moreover, the Hh pathway functions downstream of Castor but upstream of Grainyhead, two components of the temporal series, to schedule neuroblast cell cycle exit. Interestingly, hh is likely a target of Castor. Hence, Hh signaling provides a link between the temporal series and the asymmetric division machinery in scheduling the end of neurogenesis.

Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest

Directory of Open Access Journals (Sweden)

Dina Dikovskaya

2015-09-01

Full Text Available Oncogene-induced senescence (OIS is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells.

Condensate subcooling near tube exit during horizontal in-tube condensation

International Nuclear Information System (INIS)

Hashizume, K.; Abe, N.; Ozeki, T.

1992-01-01

In-tube condensation is encountered in various applications for heat exchangers, such as domestic air-conditioning equipment, industrial air-cooled condensers, and moisture separator reheaters (MSRs) for nuclear power pants. Numerous research work has been conducted to predict the condensation heat transfer coefficient, and we have now enough information for thermal design of heat exchangers with horizontal in-tube condensation. Most of the research is analytical and/or experimental work in the annular or stratified flow regime, or experimental work on bulk condensation, i.e., from saturated vapor to complete condensation. On the other hand, there exist few data about the heat transfer phenomena in the very lower-quality region near the tube exit. The purpose of this paper is to clarify the condensation heat transfer phenomena near the tube exit experimentally and analytically, and to predict the degree of condensate subcooling

The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis

Energy Technology Data Exchange (ETDEWEB)

Marchetti, Francesco; Venkatachalam, Sundaresan

2009-06-19

Aneuploidy, any deviation from an exact multiple of the haploid number of chromosomes, is a common occurrence in cancer and represents the most frequent chromosomal disorder in newborns. Eukaryotes have evolved mechanisms to assure the fidelity of chromosome segregation during cell division that include a multiplicity of checks and controls. One of the main cell division control mechanisms is the spindle assembly checkpoint (SAC) that monitors the proper attachment of chromosomes to spindle fibers and prevents anaphase until all kinetochores are properly attached. The mammalian SAC is composed by at least 14 evolutionary-conserved proteins that work in a coordinated fashion to monitor the establishment of amphitelic attachment of all chromosomes before allowing cell division to occur. Among the SAC proteins, the budding uninhibited by benzimidazole protein 1 (Bub1), is a highly conserved protein of prominent importance for the proper functioning of the SAC. Studies have revealed many roles for Bub1 in both mitosis and meiosis, including the localization of other SAC proteins to the kinetochore, SAC signaling, metaphase congression and the protection of the sister chromatid cohesion. Recent data show striking sex specific differences in the response to alterations in Bub1 activity. Proper Bub1 functioning is particularly important during oogenesis in preventing the generation of aneuploid gametes that can have detrimental effects on the health status of the fetus and the newborn. These data suggest that Bub1 is a master regulator of SAC and chromosomal segregation in both mitosis and meiosis. Elucidating its many essential functions in regulating proper chromosome segregation can have important consequences for preventing tumorigenesis and developmental abnormalities.

Atypical growth, abonormal mitosis and polyploidy induced by ethyl-mercury-chloride

Energy Technology Data Exchange (ETDEWEB)

Kostoff, D

1940-01-01

Experiments were performed to study the effect of ethyl mercury chloride upon the atypical growths of plants. Seeds of peas, flax, rye, and wheat were treated with 2% ethyl mercury chloride. The fungicide suppressed the development of the seedlings. Cytological studies revealed that the fungicide had also significantly affected the procedure of mitosis in most of the treated seedlings. The chromosomes did not become arranged into a proper equatorial plate when the nucleus membrane and the nucleolei disappeared, but occupied a position similar to that which they had during the prophase. The chromosomes split, then the centromeres divided so that from each one chromosome, two chromosomes originated, situated side by side without polar separation, chiefly due to the absence of normal achromatic figures. Thus, chromosome division without cell division takes place.

Adhesion of axolemmal fragments to Schwann cells: a signal- and target-specific process closely linked to axolemmal induction of Schwann cell mitosis

International Nuclear Information System (INIS)

Sobue, G.; Pleasure, D.

1985-01-01

Radioiodinated rat CNS axolemmal fragments adhered to cultured rat Schwann cells by a time-, temperature-, and concentration-dependent process independent of extracellular ionized calcium. Adhesion showed target and signal specificity; axolemmal fragments adhered to endoneurial or dermal fibroblasts to a much lesser extent than to Schwann cells, and plasma membrane fragments from skeletal muscle, erythrocytes, or PNS myelin adhered to Schwann cells to a lesser extent than did axolemmal fragments. Brief trypsinization removed 94 to 97% of bound radioactivity from Schwann cells previously incubated with 125 I-axolemmal fragments for up to 24 hr, indicating that adhesion was largely a surface phenomenon rather than the result of rapid internalization of axolemmal fragments by the Schwann cells. When adhesion was compared to the axolemmal mitogenic response of Schwann cells, the concentration of axolemmal fragments yielding half-maximal adhesion was the same as the concentration producing half-maximal stimulation of Schwann cell mitosis. Trypsin digestion, homogenization, or heating of axolemmal fragments before application to cultured Schwann cells diminished adhesion and axolemmal fragment-induced stimulation of Schwann cell mitosis in a parallel fashion. Whereas adhesion of axolemmal fragments to the surfaces of the cultured Schwann cells reached completion within 4 hr in this assay system, induction of Schwann cell mitosis by the fragments required contact with Schwann cells for a minimum of 6 to 8 hr and reached a maximum when the axolemmal fragments had adhered to the Schwann cells for 24 hr or more

Expression of progesterone receptor membrane component-2 within the immature rat ovary and its role in regulating mitosis and apoptosis of spontaneously immortalized granulosa cells.

Science.gov (United States)

Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K; Peluso, John J

2014-08-01

Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular (3)H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development. © 2014 by the Society for the Study of Reproduction, Inc.

Ecologies of Ideologies: Explaining Party Entry and Exit in West-European Parliaments, 1945-2013

OpenAIRE

van de Wardt, M.; Berkhout, J.; Vermeulen, F.

2017-01-01

This study introduces a population-ecological approach to the entry and exit of political parties. A primary proposition of population ecology is that organizational entry and exit depends on the number of organizations already present: that is, density. We propose that political parties mainly experience competition from parties in the same ideological niche (left, centre, right). Pooled time-series analyses of 410 parties, 263 elections and 18 West-European countries largely support our exp...

An integrated overview of spatiotemporal organization and regulation in mitosis in terms of the proteins in the functional supercomplexes

Directory of Open Access Journals (Sweden)

Yueyuan eZheng

2014-10-01

Full Text Available Eukaryotic cells may divide via the critical cellular process of cell division/mitosis, resulting in two daughter cells with the same genetic information. A large number of dedicated proteins are involved in this process and spatiotemporally assembled into three distinct super-complex structures/organelles, including the centrosome/spindle pole body, kinetochore/centromere and cleavage furrow/midbody/bud neck, so as to precisely modulate the cell division/mitosis events of chromosome alignment, chromosome segregation and cytokinesis in an orderly fashion. In recent years, many efforts have been made to identify the protein components and architecture of these subcellular organelles, aiming to uncover the organelle assembly pathways, determine the molecular mechanisms underlying the organelle functions, and thereby provide new therapeutic strategies for a variety of diseases. However, the organelles are highly dynamic structures, making it difficult to identify the entire components. Here, we review the current knowledge of the identified protein components governing the organization and functioning of organelles, especially in human and yeast cells, and discuss the multi-localized protein components mediating the communication between organelles during cell division.

Spanish exit polls. Sampling error or nonresponse bias?

Directory of Open Access Journals (Sweden)

Pavía, Jose M.

2016-09-01

Full Text Available Countless examples of misleading forecasts on behalf of both pre-election and exit polls can be found all over the world. Non-representative samples due to differential nonresponse have been claimed as being the main reason for inaccurate exit-poll projections. In real inference problems, it is seldom possible to compare estimates and true values. Electoral forecasts are an exception. Comparisons between estimates and final outcomes can be carried out once votes have been tallied. In this paper, we examine the raw data collected in seven exit polls conducted in Spain and test the likelihood that the data collected in each sampled voting location can be considered as a random sample of actual results. Knowing the answer to this is relevant for both electoral analysts and forecasters as, if the hypothesis is rejected, the shortcomings of the collected data would need amending. Analysts could improve the quality of their computations by implementing local correction strategies. We find strong evidence of nonsampling error in Spanish exit polls and evidence that the political context matters. Nonresponse bias is larger in polarized elections and in a climate of fearExiste un gran número de ejemplos de predicciones inexactas obtenidas a partir tanto de encuestas pre-electorales como de encuestas a pie de urna a lo largo del mundo. La presencia de tasas de no-respuesta diferencial entre distintos tipos de electores ha sido la principal razón esgrimida para justificar las proyecciones erróneas en las encuestas a pie de urna. En problemas de inferencia rara vez es posible comparar estimaciones y valores reales. Las predicciones electorales son una excepción. La comparación entre estimaciones y resultados finales puede realizarse una vez los votos han sido contabilizados. En este trabajo, examinamos los datos brutos recogidos en siete encuestas a pie de urna realizadas en España y testamos la hipótesis de que los datos recolectados en cada punto

Repressive histone methylation regulates cardiac myocyte cell cycle exit.

Science.gov (United States)

El-Nachef, Danny; Oyama, Kyohei; Wu, Yun-Yu; Freeman, Miles; Zhang, Yiqiang; Robb MacLellan, W

2018-05-22

Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D. Although H3K9me3 is found across the genome, its loss in CMs preferentially disrupts cell cycle gene silencing. KDM4D binds directly to cell cycle genes and reduces H3K9me3 levels at these promotors. Loss of H3K9me3 preferentially leads to increased cell cycle gene expression resulting in enhanced CM cycling. Heart mass was increased in KDM4D overexpressing mice by postnatal day 14 (P14) and continued to increase until 9-weeks of age. ACM number, but not size, was significantly increased in KDM4D expressing hearts, suggesting CM hyperplasia accounts for the increased heart mass. Inducing KDM4D after normal development specifically in ACMs resulted in increased cell cycle gene expression and cycling. We demonstrated that H3K9me3 is required for CM cell cycle exit and terminal differentiation in ACMs. Depletion of H3K9me3 in adult hearts prevents and reverses permanent cell cycle exit and allows hyperplastic growth in adult hearts in vivo. Copyright © 2017. Published by Elsevier Ltd.

The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities.

Science.gov (United States)

Naim, Valeria; Rosselli, Filippo

2009-06-01

Loss-of-function of caretaker genes characterizes a group of cancer predisposition diseases that feature cellular hypersensitivity to DNA damage and chromosome fragility; this group includes Fanconi anaemia and Bloom syndrome. The products of the 13 FANC genes (mutated in Fanconi anaemia), which constitute the 'FANC' pathway, and BLM (the RecQ helicase mutated in Bloom syndrome) are thought to collaborate during the S phase of the cell cycle, preventing chromosome instability. Recently, BLM has been implicated in the completion of sister chromatid separation during mitosis, a complex process in which precise regulation and execution is crucial to preserve genomic stability. Here we show for the first time a role for the FANC pathway in chromosome segregation during mitotic cell division. FANCD2, a key component of the pathway, localizes to discrete spots on mitotic chromosomes. FANCD2 chromosomal localization is responsive to replicative stress and specifically targets aphidicolin (APH)-induced chromatid gaps and breaks. Our data indicate that the FANC pathway is involved in rescuing abnormal anaphase and telophase (ana-telophase) cells, limiting aneuploidy and reducing chromosome instability in daughter cells. We further address a cooperative role for the FANC pathway and BLM in preventing micronucleation, through FANC-dependent targeting of BLM to non-centromeric abnormal structures induced by replicative stress. We reveal new crosstalk between FANC and BLM proteins, extending their interaction beyond the S-phase rescue of damaged DNA to the safeguarding of chromosome stability during mitosis.

The Right of Exit in the Context of Multiculturalism

Directory of Open Access Journals (Sweden)

Ana Maria D'Ávila Lopes

2015-12-01

Full Text Available http://dx.doi.org/10.5007/2177-7055.2015v36n71p155 The terrorist attack on the Twin Towers in the United States provoked heated discussions about the need to limit and control the performance of some cultural minorities, as well as to create mechanisms to protect members of these minorities against the decisions taken by the group. In this context, this paper aims to analyze the possibilities and limits of the right of exit in the context of Multiculturalism. To this end, a literature research was performed in national and foreign doctrine. After analyzing the data, it was found that the right to exit is a valuable mechanism for protecting members of cultural minorities, however, there are situations, especially in cases where the values of the group are internalized by the members, in which this right is insufficient and should be supplemented by other human rights.

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

Science.gov (United States)

Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

2018-04-10

Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Organized medicine and Scandinavian professional unionism: hospital policies and exit options in Denmark and Sweden.

Science.gov (United States)

Heidenheimer, A J; Johansen, L N

1985-01-01

Strikes by junior hospital doctors over the issue of on-call remuneration in Denmark and Sweden in 1981 are analyzed to clarify the impact of public-sector cost-control policies on intra- and interprofessional solidarity within the Scandinavian professional peak associations. The junior doctors' grievances could find expression either through increased "voice" within the medical negotiating machinery, or by pursuing the exit option in having the medical associations quit the peak associations. The article explains why the "exit" option was selected in Denmark, while in Sweden the granting of additional voice helped persuade the medical association to withdraw its exit threat and to remain within the peak association. The two cases are interpreted as presaging a divergence in the paths being taken by the various Scandinavian welfare states.

Ecologies of ideologies: Explaining party entry and exit in West-European parliaments, 1945–2013

Science.gov (United States)

Berkhout, Joost; Vermeulen, Floris

2016-01-01

This study introduces a population-ecological approach to the entry and exit of political parties. A primary proposition of population ecology is that organizational entry and exit depends on the number of organizations already present: that is, density. We propose that political parties mainly experience competition from parties in the same ideological niche (left, centre, right). Pooled time-series analyses of 410 parties, 263 elections and 18 West-European countries largely support our expectations. We find that political parties are more likely to exit when density within their niche increases. Also there is competition between adjacent ideological niches, i.e. between centrist and right-wing niches. In contrast to our expectations, neither density nor institutional rules impact party entry. This raises important questions about the rationale of prospective entrants. PMID:29046613

Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis.

Science.gov (United States)

Traynard, Pauline; Feillet, Céline; Soliman, Sylvain; Delaunay, Franck; Fages, François

2016-11-01

Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the culture medium is enriched with growth factors, and the absence of such acceleration in confluent cells. In order to explain these observations, we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective activation of RevErb-α or the selective inhibition of Bmal1 transcription during the mitosis phase, allow us to fit the experimental data on both period and phase, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on the arguments favoring the RevErb-α up-regulation hypothesis and on some further predictions of the model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A smooth exit from eternal inflation?

Science.gov (United States)

Hawking, S. W.; Hertog, Thomas

2018-04-01

The usual theory of inflation breaks down in eternal inflation. We derive a dual description of eternal inflation in terms of a deformed Euclidean CFT located at the threshold of eternal inflation. The partition function gives the amplitude of different geometries of the threshold surface in the no-boundary state. Its local and global behavior in dual toy models shows that the amplitude is low for surfaces which are not nearly conformal to the round three-sphere and essentially zero for surfaces with negative curvature. Based on this we conjecture that the exit from eternal inflation does not produce an infinite fractal-like multiverse, but is finite and reasonably smooth.

Factors influencing the stay-exit intention of small livestock farmers

NARCIS (Netherlands)

Carter-Leal, Luis M.; Oude-Lansink, Alfons; Saatkamp, Helmut

2018-01-01

This study analyses the factors driving the stay-exit intention of small livestock farmers located in southern Chile. Technical, economic, and social characteristics from 212 farmers were included in this study. Through an empirical probit model we identified the variables that should be considered

Exit From the High Street

DEFF Research Database (Denmark)

Bly, Sarah; Gwozdz, Wencke; Reisch, Lucia

2015-01-01

by focusing on a previously under-researched group of consumers – ‘sustainable fashion consumption pioneers’ who actively engage and shape their own discourse around the notion of sustainable fashion consumption. These pioneers actively create and communicate strategies for sustainable fashion behaviour...... of sustainable fashion including such key behaviours as purchasing fewer garments of higher quality, exiting the retail market, purchasing only second-hand fashion goods and sewing or upgrading their own clothing. Central to much of these behaviours is the notion that personal style, rather than fashion, can...... bridge the potential disconnect between sustainability and fashion while also facilitating a sense of well-being not found in traditional fashion consumption. As such, our research suggests that for these consumers sustainability is as much about reducing measurable environmental or social impacts...

OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM.

Science.gov (United States)

Cromer, Laurence; Heyman, Jefri; Touati, Sandra; Harashima, Hirofumi; Araou, Emilie; Girard, Chloe; Horlow, Christine; Wassmann, Katja; Schnittger, Arp; De Veylder, Lieven; Mercier, Raphael

2012-01-01

Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especially required for exit from mitosis. We have shown previously that OSD1 is involved in entry into both meiosis I and meiosis II in Arabidopsis thaliana; however, the molecular mechanism by which OSD1 controls these transitions has remained unclear. Here we show that OSD1 promotes meiotic progression through APC/C inhibition. Next, we explored the functional relationships between OSD1 and the genes known to control meiotic cell cycle transitions in Arabidopsis. Like osd1, cyca1;2/tam mutation leads to a premature exit from meiosis after the first division, while tdm mutants perform an aberrant third meiotic division after normal meiosis I and II. Remarkably, while tdm is epistatic to tam, osd1 is epistatic to tdm. We further show that the expression of a non-destructible CYCA1;2/TAM provokes, like tdm, the entry into a third meiotic division. Finally, we show that CYCA1;2/TAM forms an active complex with CDKA;1 that can phosphorylate OSD1 in vitro. We thus propose that a functional network composed of OSD1, CYCA1;2/TAM, and TDM controls three key steps of meiotic progression, in which OSD1 is a meiotic APC/C inhibitor.

Film techniques in radiotherapy for treatment verification, determination of patient exit dose, and detection of localization error

International Nuclear Information System (INIS)

Haus, A.G.; Marks, J.E.

1974-01-01

In patient radiation therapy, it is important to know that the diseased area is included in the treatment field and that normal anatomy is properly shielded or excluded. Since 1969, a film technique developed for imaging of the complete patient radiation exposure has been applied for treatment verification and for the detection and evaluation of localization errors that may occur during treatment. The technique basically consists of placing a film under the patient during the entire radiation exposure. This film should have proper sensitivity and contrast in the exit dose exposure range encountered in radiotherapy. In this communication, we describe how various exit doses fit the characteristic curve of the film; examples of films exposed to various exit doses; the technique for using the film to determine the spatial distribution of the absorbed exit dose; and types of errors commonly detected. Results are presented illustrating that, as the frequency of use of this film technique is increased, localization error is reduced significantly

Water droplet excess free energy determined by cluster mitosis using guided molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Lau, Gabriel V.; Müller, Erich A.; Jackson, George [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom); Hunt, Patricia A. [Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom); Ford, Ian J. [Department of Physics and Astronomy and London Centre for Nanotechnology, University College London, Gower Street, London WC1E 6BT (United Kingdom)

2015-12-28

Atmospheric aerosols play a vital role in affecting climate by influencing the properties and lifetimes of clouds and precipitation. Understanding the underlying microscopic mechanisms involved in the nucleation of aerosol droplets from the vapour phase is therefore of great interest. One key thermodynamic quantity in nucleation is the excess free energy of cluster formation relative to that of the saturated vapour. In our current study, the excess free energy is extracted for clusters of pure water modelled with the TIP4P/2005 intermolecular potential using a method based on nonequilibrium molecular dynamics and the Jarzynski relation. The change in free energy associated with the “mitosis” or division of a cluster of N water molecules into two N/2 sub-clusters is evaluated. This methodology is an extension of the disassembly procedure used recently to calculate the excess free energy of argon clusters [H. Y. Tang and I. J. Ford, Phys. Rev. E 91, 023308 (2015)]. Our findings are compared to the corresponding excess free energies obtained from classical nucleation theory (CNT) as well as internally consistent classical theory (ICCT). The values of the excess free energy that we obtain with the mitosis method are consistent with CNT for large cluster sizes but for the smallest clusters, the results tend towards ICCT; for intermediate sized clusters, we obtain values between the ICCT and CNT predictions. Furthermore, the curvature-dependent surface tension which can be obtained by regarding the clusters as spherical droplets of bulk density is found to be a monotonically increasing function of cluster size for the studied range. The data are compared to other values reported in the literature, agreeing qualitatively with some but disagreeing with the values determined by Joswiak et al. [J. Phys. Chem. Lett. 4, 4267 (2013)] using a biased mitosis approach; an assessment of the differences is the main motivation for our current study.

Exit points, on plasma, of lost fast ions during NBI in TJ-II

International Nuclear Information System (INIS)

Guasp, J.

1995-09-01

The distribution of the exit points, on plasma border, for the lost fast ions during tangential balanced NBI in TJ-II helical axis Stellarator is theoretically analysed, as well for direct as for delayed losses. The link between the position of those exit points and the corresponding at birth, orbits and drifts is analysed also, it is shown that such relation is rather independent of beam energy and plasma density and is mainly related to the magnetic configuration characteristics. This study is a needed intermediate step to the analysis of impacts of those ions on the vacuum vessel of TJ-II

Monetary Policy of the Federal Reserve System from the Perspective of Exit Strategies

Directory of Open Access Journals (Sweden)

Aleksandra Nocoń

2015-07-01

Full Text Available Central banks, after the experience of the global financial crisis, are now starting the implementation of the exit strategies, which are the process of normalization of monetary policy. The pace of monetary policy normalization process depends on the market reaction to central bank's decisions and macroeconomic conditions, in which they will be implemented. The main aim of the study is to present the principles of the exit strategy of the Federal Reserve System (Fed, on the background of the changes that have occurred in the United States within the monetary policy during the global financial crisis.

SEC16 in COPII coat dynamics at ER exit sites

NARCIS (Netherlands)

Sprangers, Joep; Rabouille, Catherine

Protein export from the endoplasmic reticulum (ER), the first step in protein transport through the secretory pathway, is mediated by coatomer protein II (COPII)-coated vesicles at ER exit sites. COPII coat assembly on the ER is well understood and the conserved large hydrophilic protein Sec16

Explicit solutions for exit-only radioactive decay chains

International Nuclear Information System (INIS)

Yuan, Ding; Kernan, Warnick

2007-01-01

In this study, we extended Bateman's [Proc. Cambridge Philos. Soc. 15, 423 (1910)] original work for solving radioactive decay chains and explicitly derived analytic solutions for generic exit-only radioactive decay problems under given initial conditions. Instead of using the conventional Laplace transform for solving Bateman's equations, we used a much simpler algebraic approach. Finally, we discuss methods of breaking down certain classes of large decay chains into collections of simpler chains for easy handling

Nuclear energy - no thanks. The long way to the exit

International Nuclear Information System (INIS)

Sternstein, Wolfgang

2013-01-01

The anti-nuclear movement is one of the most successful social movements of the recent history of Germany and firmly anchored in huge parts of the population. After a struggle lasting more than forty years it has nearly reached its aims: The exit from nuclear energy and a rethinking in direction of alternative energy concepts. Decisive for the nuclear exit of the Federal government were thereby less the nuclear accidents of Harrisburg (1979), Chernobyl (1986), and Fukushima (2011) but rather the decades-long, stubborn commitment of numerous citizens as well as of citizen's initiatives. ''Nuclear energy - no thanks.'' is the analysis of the citizen's movement from Wyhl until Gorleben. The nonviolent activist and peace researcher Sternstein was there from the beginning and reports about anger and indignation that has been condensed to the social movement with political objectives. Extremely helpful are thereby the methods and strategies of nonviolent actions described by him.

10 CFR 431.204 - Uniform test method for the measurement of energy consumption of illuminated exit signs.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Uniform test method for the measurement of energy consumption of illuminated exit signs. 431.204 Section 431.204 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION... Procedures § 431.204 Uniform test method for the measurement of energy consumption of illuminated exit signs...

Ramp Metering Influence on Freeway Operational Safety near On-ramp Exits

Directory of Open Access Journals (Sweden)

Chiu Liu, PhD, PE, PTOE

2013-06-01

Full Text Available Ramp metering has been widely installed in urban areas where congestion on a freeway or an expressway may occur recurrently during weekday peak periods to enhance mainline throughput and reduce system-wide delay. These operational benefits may also help reduce vehicular emissions and improve air quality in urban areas. However, the impact on traffic safety due to ramp metering hasn't been explored in details before. Supported by physical understanding and arguments, we characterize the ramp metering influence on freeway safety by examining vehicular collisions near on-ramp exits within the ramp meter operating hours before and after the activation of the ramp metering. Collisions for a sample of 19 operating ramp meters along several freeways in northern California were collected and organized to show that ramp metering can help reduce freeway collisions at the vicinity of on-ramp exits. It was found that the average reductions on freeway collisions in the vicinity of an on-ramp exit are around 36%. Although most of the reduced collisions belong to the property damage only category, a 36% reduction shows the significant safety benefit of ramp metering. The traffic congestion induced by each collision, especially during peak hours when ramp metering is in operation, could last for an hour or two. Consequently, ramp metering must be contributing to the reduction of non-recurrent congestion in addition to mitigating recurrent congestion, which is better documented. This study strongly supports the implementation of ramp metering in California.

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

Science.gov (United States)

2007-07-01

axoneme, or with two axonemes, were found. Also, cytoplasmic fragmentation together with condensed cytoplasmic remnants and gigantic cytoplasmic... Endocrine - Related Cancer 2001; 8: 249-258. 33. Faivre S, Kroemer G and Raymond E. Current development of mTOR inhibitors as anticancer agents

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

Science.gov (United States)

2008-07-01

chrysosporium --- http://genome.jgi-p Aspergillus flavus --- http://www.tigr.or Arabidopsis thaliana --- http://www.tigr.or Oryza sativa --- http...distinguish colon and ovarian adenocarcinomas: identi- fication, genomic, proteomic , and tissue array profiling. Cancer Res 2003;63:5243–50. 108

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

National Research Council Canada - National Science Library

Chang, Long-Sheng

2008-01-01

... determination of dorsal/ventral compartment border during wing imaginal disc development. We show that the Merlin protein is dynamically redistributed during meiosis and demonstrate, for the first time, Merlin immunoreactivity in mitochondria...

MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis.

Science.gov (United States)

Ali, Aamir; Veeranki, Sailaja Naga; Chinchole, Akash; Tyagi, Shweta

2017-06-19

Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis. We have identified a conserved WDR5 interaction (Win) motif, so far unique to the MLL family, in Kif2A. The Win motif of Kif2A engages in direct interactions with WDR5 for its spindle localization. Our findings highlight a non-canonical mitotic function of MLL complex, which may have a direct impact on chromosomal stability, frequently compromised in cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

TomoTherapy MLC verification using exit detector data

Energy Technology Data Exchange (ETDEWEB)

Chen Quan; Westerly, David; Fang Zhenyu; Sheng, Ke; Chen Yu [TomoTherapy Inc., 1240 Deming Way, Madison, Wisconsin 53717 (United States); Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado 80045 (United States); Xinghua Cancer Hospital, Xinghua, Jiangsu 225700 (China); Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, California 90095 (United States); TomoTherapy Inc., 1240 Deming Way, Madison, Wisconsin 53717 (United States)

2012-01-15

Purpose: Treatment delivery verification (DV) is important in the field of intensity modulated radiation therapy (IMRT). While IMRT and image guided radiation therapy (IGRT), allow us to create more conformal plans and enables the use of tighter margins, an erroneously executed plan can have detrimental effects on the treatment outcome. The purpose of this study is to develop a DV technique to verify TomoTherapy's multileaf collimator (MLC) using the onboard mega-voltage CT detectors. Methods: The proposed DV method uses temporal changes in the MVCT detector signal to predict actual leaf open times delivered on the treatment machine. Penumbra and scattered radiation effects may produce confounding results when determining leaf open times from the raw detector data. To reduce the impact of the effects, an iterative, Richardson-Lucy (R-L) deconvolution algorithm is applied. Optical sensors installed on each MLC leaf are used to verify the accuracy of the DV technique. The robustness of the DV technique is examined by introducing different attenuation materials in the beam. Additionally, the DV technique has been used to investigate several clinical plans which failed to pass delivery quality assurance (DQA) and was successful in identifying MLC timing discrepancies as the root cause. Results: The leaf open time extracted from the exit detector showed good agreement with the optical sensors under a variety of conditions. Detector-measured leaf open times agreed with optical sensor data to within 0.2 ms, and 99% of the results agreed within 8.5 ms. These results changed little when attenuation was added in the beam. For the clinical plans failing DQA, the dose calculated from reconstructed leaf open times played an instrumental role in discovering the root-cause of the problem. Throughout the retrospective study, it is found that the reconstructed dose always agrees with measured doses to within 1%. Conclusions: The exit detectors in the TomoTherapy treatment

TomoTherapy MLC verification using exit detector data

International Nuclear Information System (INIS)

Chen Quan; Westerly, David; Fang Zhenyu; Sheng, Ke; Chen Yu

2012-01-01

Purpose: Treatment delivery verification (DV) is important in the field of intensity modulated radiation therapy (IMRT). While IMRT and image guided radiation therapy (IGRT), allow us to create more conformal plans and enables the use of tighter margins, an erroneously executed plan can have detrimental effects on the treatment outcome. The purpose of this study is to develop a DV technique to verify TomoTherapy's multileaf collimator (MLC) using the onboard mega-voltage CT detectors. Methods: The proposed DV method uses temporal changes in the MVCT detector signal to predict actual leaf open times delivered on the treatment machine. Penumbra and scattered radiation effects may produce confounding results when determining leaf open times from the raw detector data. To reduce the impact of the effects, an iterative, Richardson-Lucy (R-L) deconvolution algorithm is applied. Optical sensors installed on each MLC leaf are used to verify the accuracy of the DV technique. The robustness of the DV technique is examined by introducing different attenuation materials in the beam. Additionally, the DV technique has been used to investigate several clinical plans which failed to pass delivery quality assurance (DQA) and was successful in identifying MLC timing discrepancies as the root cause. Results: The leaf open time extracted from the exit detector showed good agreement with the optical sensors under a variety of conditions. Detector-measured leaf open times agreed with optical sensor data to within 0.2 ms, and 99% of the results agreed within 8.5 ms. These results changed little when attenuation was added in the beam. For the clinical plans failing DQA, the dose calculated from reconstructed leaf open times played an instrumental role in discovering the root-cause of the problem. Throughout the retrospective study, it is found that the reconstructed dose always agrees with measured doses to within 1%. Conclusions: The exit detectors in the TomoTherapy treatment systems

A study on the impulse wave discharged from the exit of a right-angle pipe bend

International Nuclear Information System (INIS)

Lee, D. H.; Hur, S. C.; Kweon, Y. H.; Kim, H. D.

2001-01-01

The current study addresses experimental and computational work of impulse wave discharged from the exit of two kinds of right-angle pipe bends, which are attached to the open end of a simple shock tube. The weak normal shock wave with its magnitude of Mach number from 1.02 to 1.20 is employed to obtain the impulse wave propagating outside the exit of the pipe bends. A Schlieren optical system visualizes the impulse wave discharged from the exit of the pipe bends at an instant. The experimental data of the magnitude of the impulse wave and its propagating directivity are analyzed to characterize the impulse waves discharged from the exit of the pipe bends and compared with those discharged from a straight pipe. Computational results well predict the experimented dynamic behaviors of the impulse wave. The results obtained show that a right-angle miter bend considerably reduces the magnitude of the impulse wave and its directivity toward to the pipe axis, compared with the straight pipe and right-angle smooth bend. It is believed that the right-angle miter bend pipe can play a role of a passive control against the impulse wave

An Eclectic Approach to Loyalty-Promoting Instruments in Corporate Law: Revisiting Hirschman's Model of Exit, Voice, and Loyalty

NARCIS (Netherlands)

A.A. Bootsma (Bart)

2013-01-01

markdownabstract__Abstract__ This essay analyses the shareholder role in corporate governance in terms of Albert Hirschman's Exit, Voice, and Loyalty. The term 'exit' is embedded in a law & economics framework, while 'voice' relates to a corporate constitutional framework. The essay takes an

The roles of BDNF, pCREB and Wnt3a in the latent period preceding activation of progenitor cell mitosis in the adult dentate gyrus by fluoxetine.

Directory of Open Access Journals (Sweden)

Scarlett B Pinnock

2010-10-01

Full Text Available The formation of new neurons continues into adult life in the dentate gyrus of the rat hippocampus, as in many other species. Neurogenesis itself turns out to be highly labile, and is regulated by a number of factors. One of these is the serotoninergic system: treatment with drugs (such as the SSRI fluoxetine markedly stimulates mitosis in the progenitor cells of the dentate gyrus. But this process has one remarkable feature: it takes at least 14 days of continuous treatment to be effective. This is despite the fact that the pharmacological action of fluoxetine occurs within an hour or so of first administration. This paper explores the role of BDNF in this process, using the effect of a Trk antagonist (K252a on the labelling of progenitor cells with the mitosis marker Ki67 and the associated expression of pCREB and Wnt3a. These experiments show that (i Fluoxetine increased Ki67 counts, as well as pCREB and Wnt3a expression in the dentate gyrus. The action of fluoxetine on the progenitor cells and on pCREB (but not Wnt3a depends upon Trk receptor activation, since it was prevented by icv infusion of K252a. (ii These receptors are required for both the first 7 days of fluoxetine action, during which no apparent change in progenitor mitosis occurs, as well as the second 7 days. Increased pCREB was always associated with progenitor cell mitosis, but Wnt3a expression may be necessary but not sufficient for increased progenitor cell proliferation. These results shed new light on the action of fluoxetine on neurogenesis in the adult dentate gyrus, and have both clinical and experimental interest.

Exit points, on plasma, of lost fast ions during NBI in TJ-II

International Nuclear Information System (INIS)

Guasp, J.

1995-01-01

The distribution of the exit points, on plasma border, for the lost fast ions during tangential balanced NBI in TJ-II helical axis Stellarator is theoretically analysed, as well for direct as for delayed losses. The link between, the position of those exit points and the corresponding at birth, orbits and drifts is analysed also. It is shown that such relation is rather independent of beam energy and plasma density and is mainly related to the magnetic configuration characteristics. This study is a needed intermediate step to the analysis of impacts of those ions on the vacuum vessel of TJ-II. (Author) 2 refs

A Study on the Design of PM Exited Transverse Flux Linear Motor for Ropeless Elevator

Energy Technology Data Exchange (ETDEWEB)

Kang, Do Hyun; Bang, Deok Je; Kim, Jong Moo; Jeong, Yeon Ho [Korea Electrotechnology Research Institute (Korea); Kim, Moon Hwan [Silla University (Korea)

2000-03-01

The topological investigations regarding magnetic circuit geometry and winding form of the transverse flux machine have brought up a variety of constructable arrangements with different features for several types of application[1, 2]. Here with, a novel PM-exited linear motor with inner mover, based on the transverse flux configuration leads to a considerable increase in power density for moving part. In this study we designed PM-exited transverse flux linear motor for ropeless elevator, whose output power density is higher and weight is lighter than conventional linear synchronous motors, When the designed motor in this study is applied to ropeless elevator, it is possible to increase power density more than 400% comparing with PM exited linear synchronous motor. The result of this study can be utilized for ropeless elevator or gearless direct linear moving system with high output[3]. (author). 8 refs., 9 figs., 4 tabs.

Educational Inequalities in Exit from Paid Employment among Dutch Workers: The Influence of Health, Lifestyle and Work.

Science.gov (United States)

Robroek, Suzan J W; Rongen, Anne; Arts, Coos H; Otten, Ferdy W H; Burdorf, Alex; Schuring, Merel

2015-01-01

Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle-related factors and work characteristics on educational differences in exit from paid employment. 14,708 Dutch employees participated in a ten-year follow-up study during 1999-2008. At baseline, education, self-perceived health, lifestyle (smoking, alcohol, sports, BMI) and psychosocial (demands, control, rewards) and physical work characteristics were measured by questionnaire. Employment status was ascertained monthly based on tax records. The relation between education, health, lifestyle, work-characteristics and exit from paid employment through disability benefits, unemployment, early retirement and economic inactivity was investigated by competing risks regression analyses. The mediating effects of these factors on educational differences in exit from paid employment were tested using a stepwise approach. Lower educated workers were more likely to exit paid employment through disability benefits (SHR:1.84), unemployment (SHR:1.74), and economic inactivity (SHR:1.53) but not due to early retirement (SHR:0.92). Poor or moderate health, an unhealthy lifestyle, and unfavourable work characteristics were associated with disability benefits and unemployment, and an unhealthy lifestyle with economic inactivity. Educational differences in disability benefits were explained for 40% by health, 31% by lifestyle, and 12% by work characteristics. For economic inactivity and unemployment, up to 14% and 21% of the educational differences could be explained, particularly by lifestyle-related factors. There are educational differences in exit from paid employment, which are partly mediated by health, lifestyle and work

Construction of an easy-to-use CRISPR-Cas9 system by patching a newly designed EXIT circuit.

Science.gov (United States)

Tang, Qiang; Lou, Chunbo; Liu, Shuang-Jiang

2017-01-01

Plasmid-borne genetic editing tools, including the widely used CRISPR-Cas9 system, have greatly facilitated bacterial programming to obtain novel functionalities. However, the lack of effective post-editing plasmid elimination methods impedes follow-up genetic manipulation or application. Conventional strategies including exposure to physical and chemical treatments, or exploiting temperature-sensitive replication origins have several drawbacks (e.g., they are limited for efficiency and are time-consuming). Therefore, the demand is apparent for easy and rapid elimination of the tool plasmids from their bacterial hosts after genetic manipulation. To bridge this gap, we designed a novel EXIT circuit with the homing endonuclease, which can be exploited for rapid and efficient elimination of various plasmids with diverse replication origins. As a proof of concept, we validated the EXIT circuit in Escherichia coli by harnessing homing endonuclease I- Sce I and its cleavage site. When integrated into multiple plasmids with different origins, the EXIT circuit allowed them to be eliminated from the host cells, simultaneously. By combining the widely used plasmid-borne CRISPR-Cas9 system and the EXIT circuit, we constructed an easy-to-use CRISPR-Cas9 system that eliminated the Cas9- and the single-guide RNA (sgRNA)-encoding plasmids in one-step. Within 3 days, we successfully constructed an atrazine-degrading E. coli strain, thus further demonstrating the advantage of this new CRISPR-Cas9 system for bacterial genome editing. Our novel EXIT circuit, which exploits the homing endonuclease I- Sce I, enables plasmid(s) with different replication origins to be eliminated from their host cells rapidly and efficiently. We also developed an easy-to-use CRISPR-Cas9 system with the EXIT circuit, and this new system can be widely applied to bacterial genome editing.

Embracing the Exit: Assessment, Trust, and the Teaching of Writing

Science.gov (United States)

Eng, Joseph

2006-01-01

Historically, the Composition Program at Eastern Washington University (EWU), a comprehensive university in Cheney, WA, required a single essay sample from each composition student as the final exit exam; in practice, a student passed or failed the course based on an in-class argumentative essay, written in three consecutive class periods. Such a…

Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

Science.gov (United States)

Satory, P R

2012-03-01

This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient.

An optimization method for the distance between exits of buildings considering uncertainties based on arbitrary polynomial chaos expansion

NARCIS (Netherlands)

Xie, Qimiao; Wang, Jinhui; Lu, Shouxiang; Hensen, J.L.M.

2016-01-01

The distance between exits is an important design parameter in fire safety design of buildings. In order to find the optimal distance between exits under uncertainties with a low computational cost, the surrogate model (i.e. approximation model) of evacuation time is constructed by the arbitrary

An entry and exit model on the energy-saving investment strategy with real options

International Nuclear Information System (INIS)

Lin, Tyrone T.; Huang, S.-L.

2010-01-01

This paper presents an improved decision model based on the real options approach presented by for the firms that have not yet established energy-saving equipment under the entry and exit strategies. Furthermore, the proposed model takes account of the inevitable equipment renewal and the occurrence of unexpected events under the Poisson jump process. The timing for terminating an investment when continuous operations of that business are unprofitable is also explored to realize the optimal timing of implementing the energy-saving strategy. The future discounted benefit B follows the geometric Brownian motion with the Poisson jump process and the replacement of investment equipment. A numerical analysis is followed by a sensitivity study of various parameters to better realize their impacts on the entry and exit thresholds. The results show that for the jump case, the higher probability of occurrence of unfavorable events will result in a higher entry threshold and lower exit threshold. Investors are forced to request higher benefit thresholds to cover the higher probability of losses brought by unfavorable events.

Which consequences for the USA of its exit from the Paris agreement? An economic, commercial and geopolitical view

International Nuclear Information System (INIS)

Hache, Emmanuel; Bourcet, Clemence; Palle, Angelique

2017-06-01

The authors discuss economic impacts which its exit from the Paris agreement may have on the US at the medium and long terms, and also the possible geopolitical reconfigurations which may result from this exit at the international level. Possible economic impacts are discussed in terms of loss of competitiveness, of image and of leadership in the international innovation dynamics. The authors also notice and comment that this exit process has already started in January 2017 with the exit form the Transpacific Partnership Treaty. They question the possible emergence of new leaders for international climatic issues, and discuss the consequences of this loss of political and moral influence of the US, and of China be this leader. The authors comment the domestic situation for the US in terms of political debate between Democrats and Republicans, but also by considering the fact that the environment policy is a power issue between local and federal authorities in the US

Timely Endocytosis of Cytokinetic Enzymes Prevents Premature Spindle Breakage during Mitotic Exit.

Directory of Open Access Journals (Sweden)

Cheen Fei Chin

2016-07-01

Full Text Available Cytokinesis requires the spatio-temporal coordination of membrane deposition and primary septum (PS formation at the division site to drive acto-myosin ring (AMR constriction. It has been demonstrated that AMR constriction invariably occurs only after the mitotic spindle disassembly. It has also been established that Chitin Synthase II (Chs2p neck localization precedes mitotic spindle disassembly during mitotic exit. As AMR constriction depends upon PS formation, the question arises as to how chitin deposition is regulated so as to prevent premature AMR constriction and mitotic spindle breakage. In this study, we propose that cells regulate the coordination between spindle disassembly and AMR constriction via timely endocytosis of cytokinetic enzymes, Chs2p, Chs3p, and Fks1p. Inhibition of endocytosis leads to over accumulation of cytokinetic enzymes during mitotic exit, which accelerates the constriction of the AMR, and causes spindle breakage that eventually could contribute to monopolar spindle formation in the subsequent round of cell division. Intriguingly, the mitotic spindle breakage observed in endocytosis mutants can be rescued either by deleting or inhibiting the activities of, CHS2, CHS3 and FKS1, which are involved in septum formation. The findings from our study highlight the importance of timely endocytosis of cytokinetic enzymes at the division site in safeguarding mitotic spindle integrity during mitotic exit.

Formation of vortex pairs with hinged rigid flaps at the nozzle exit

Science.gov (United States)

Das, Prashant; Govardhan, Raghuraman; Arakeri, Jaywant

2013-11-01

Biological flows related to aquatic propulsion using pulsed jets, or flow through the valves in a human heart, have received considerable attention in the last two decades. Both these flows are associated with starting jets that occur through biological tissue/membranes that are flexible. Motivated by these flows, we explore in the present work, the effect of passive flexibility of the nozzle exit on vortex generation from a starting jet. The starting jet is generated using a two-dimensional piston cylinder mechanism, the cross-section of the cylinder being rectangular with large aspect ratio. The fluid is pushed out of this cylinder or channel using a computer controlled piston. We introduce flexibility at the channel exit by hinging rigid flaps, which are initially parallel to the channel. The hinge used is such that it provides negligible stiffness or damping, thus allowing for the maximum opening of the flaps due to fluid forces. Using this system, we study both the flap kinematics and the vorticity dynamics downstream of the channel exit. Visualizations show large flap motions as the piston starts and this dramatically changes the vorticity distribution downstream of the flaps, with the formation of up to three different kinds of vortex pairs. This idealized configuration opens new opportunities to look at the effect of flexibility in such biological flows.

Exit Options in Corporate Finance: Liquidity versus Incentives

OpenAIRE

Aghion, Philippe; Bolton, P.; Tirole, J.

2004-01-01

This paper provides a first study of the optimal design of active monitors' exit options in a problem involving a demand for liquidity and costly monitoring of the issuer. Optimal incentives to monitor the issuer may involve restricting the monitor's right to sell her claims on the firm's cash-flow early. But the monitor will then require a liquidity premium for holding such an illiquid claim. In general, therefore, there will be a trade off between incentives and liquidity. The paper highlig...

Water Entry and Exit of Horizontal Cylinder in Free Surface Flow

International Nuclear Information System (INIS)

Hafsia, Zouhaier; Maalel, Khlifa; Mnasri, Chokri; Mohamed, Omri

2009-01-01

This paper describes two-dimensional numerical simulations of the water entry and exit of horizontal circular cylinder at constant velocity. The deformation of free surface is described by Navier-Stokes (N S) equations of incompressible and viscous fluid with additional transport equation of the volume-of-fluid (VOF). The motion of the cylinder is modeled by the associated momentum source term implemented in the Phoenicis (Parabolic Hyperbolic Or Elliptic Numerical Integration Code Series) code. The domain is discretized by a fixed Cartesian grid using a finite volume method and the cylinder is represented and cut cell method. The simulated results are compared with the numerical results of Lin (2007). This comparison shows good agreement in terms of free surface evolution for water exit and sinking. However, for water entry, the jet flow simulated by Lin is not reproduced. The free surface deformation around the cylinder in downward direction is accurately predicted

Some Features of Aerodynamics of Cyclonic Chamber with Free Exit

Directory of Open Access Journals (Sweden)

A. N. Orekhov

2007-01-01

Full Text Available The paper cites results of an experimental research in aerodynamics of a cyclonic chamber with a free exit that has a large relative length. Distributions of aerodynamic stream characteristics depending on geometry of working volume of the cyclonic chamber are given in the paper. Calculative dependences are proposed in the paper.

Diving, Jumping and Drinking: instabilities during water entry and exit

Science.gov (United States)

Jung, Sunghwan

2017-11-01

All organisms interact with fluids in one way or another, and some have presumably adapted their behaviors or features in response to fluid-mechanical forces. Particularly, fluid forces are of great importance when organisms or their body parts move in and out of water. In this talk, I will discuss three problems in which fluid mechanics principles affect form and function of animals. The first problem is how several seabirds (e.g. Gannets and Boobies) dive into water at up to 24 m/s without any injuries. This study examines the effects of their beak shape and dense feathers during water entry to reduce or spread the impact force on the body. The second problem is how animals jump out of water, from plankton to whales. Some aquatic animals generate enough force to exit the water surface as an effective method of capturing prey or escaping from predators. Finally, I will discuss about lapping animals (e.g. dog and cat) as a combined water entry and exit. During the tongue-lapping, associated fluid forces and pinch-off instability will be discussed.

Steam exit flow design for aft cavities of an airfoil

Science.gov (United States)

Storey, James Michael; Tesh, Stephen William

2002-01-01

Turbine stator vane segments have inner and outer walls with vanes extending therebetween. The inner and outer walls have impingement plates. Steam flowing into the outer wall passes through the impingement plate for impingement cooling of the outer wall surface. The spent impingement steam flows into cavities of the vane having inserts for impingement cooling the walls of the vane. The steam passes into the inner wall and through the impingement plate for impingement cooling of the inner wall surface and for return through return cavities having inserts for impingement cooling of the vane surfaces. A skirt or flange structure is provided for shielding the steam cooling impingement holes adjacent the inner wall aerofoil fillet region of the nozzle from the steam flow exiting the aft nozzle cavities. Moreover, the gap between the flash rib boss and the cavity insert is controlled to minimize the flow of post impingement cooling media therebetween. This substantially confines outflow to that exiting via the return channels, thus furthermore minimizing flow in the vicinity of the aerofoil fillet region that may adversely affect impingement cooling thereof.

Relationship of core exit-temperature noise to thermal-hydraulic conditions in PWRs

International Nuclear Information System (INIS)

Sweeney, F.J.; Upadhyaya, B.R.

1983-01-01

Core exit thermocouple temperature noise and neutron detector noise measurements were performed at the Loss of Fluid Test Facility (LOFT) reactor and a Westinghouse, 1148 MW(e) PWR to relate temperature noise to core thermal-hydraulic conditions. The noise analysis results show that the RMS of the temperature noise increases linearly with increasing core δT at LOFT and the commercial PWR. Out-of-core test loop temperature noise has shown similar behavior. The phase angle between core exit temperature noise and in-core or ex-core neutron noise is directly related to the core coolant flow velocity. However, if the thermocouple response time is slow, compared to the coolant transit time between the sensors, velocities inferred from the phase angle are lower than measured coolant flow velocities

The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel

DEFF Research Database (Denmark)

Wekselman, Itai; Zimmerman, Ella; Davidovich, Chen

2017-01-01

Erythromycin is a clinically useful antibiotic that binds to an rRNA pocket in the ribosomal exit tunnel. Commonly, resistance to erythromycin is acquired by alterations of rRNA nucleotides that interact with the drug. Mutations in the β hairpin of ribosomal protein uL22, which is rather distal...... of the β hairpin of the mutated uL22 toward the interior of the exit tunnel, triggering a cascade of structural alterations of rRNA nucleotides that propagate to the erythromycin binding pocket. Our findings support recent studies showing that the interactions between uL22 and specific sequences within...

S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

Science.gov (United States)

Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

2018-05-04

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

Association between keeping home records of catheter exit-site and incidence of peritoneal dialysis-related infections.

Science.gov (United States)

Iida, Hidekazu; Kurita, Noriaki; Fujimoto, Shino; Kamijo, Yuka; Ishibashi, Yoshitaka; Fukuma, Shingo; Fukuhara, Shunichi

2018-04-01

To prevent peritoneal dialysis (PD)-related infection, components of self-catheter care have been emphasized. However, studies on the effectiveness of home recording for the prevention of PD-related infections are limited. This study aimed to examine the association between keeping home records of catheter exit site and incidence of PD-related infections. Home record books were submitted by patients undergoing PD. The proportion of days on which exit-site home recording was carried out for 120 days (0-100%) was obtained. The patients were divided into the frequent home recording group (≥ 40.5%; median value) and the infrequent home recording group (home recording groups for PD-related infection were 1.58 (95% confidence interval [CI], 0.72-3.46) in the univariate analysis and 1.49 (95% CI, 0.65-3.42) in the multivariate analysis. The IRRs of the frequent versus infrequent home recording groups for composite of surgery to create a new exit site and removal of PD catheter were 0.55 (95% CI, 0.78-3.88) and 0.35 (95% CI, 0.06-1.99), respectively. This study could not prove that keeping home records of patients' catheter exit site is associated with a lower incidence of PD-related infections.

Cdk1-Cyclin B1-mediated Phosphorylation of Tumor-associated Microtubule-associated Protein/Cytoskeleton-associated Protein 2 in Mitosis*

OpenAIRE

Uk Hong, Kyung; Kim, Hyun-Jun; Kim, Hyo-Sil; Seong, Yeon-Sun; Hong, Kyeong-Man; Bae, Chang-Dae; Park, Joobae

2009-01-01

During mitosis, establishment of structurally and functionally sound bipolar spindles is necessary for maintaining the fidelity of chromosome segregation. Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton-associated protein 2 (CKAP2), is a mitotic spindle-associated protein whose level is frequently up-regulated in various malignancies. Previous reports have suggested that TMAP is a potential regulator of mitotic spindle assembly and dynamics and that it is re...

All rights reserved and www.bioline.org.br/ja Estimation of exit ...

African Journals Online (AJOL)

ADOWIE PERE

and www.bioline.org.br/ja. Estimation of exit temperatures in the isentropic compression of real gases. 1 ..... other thermodynamic properties can be calculated within the framework of ... of negative compressibility) has no physical significance.

Estimation of exit temperatures in the isentropic compression of real ...

African Journals Online (AJOL)

This paper presents the estimation of exit temperatures in the isentropic compression of real gases based on the Peng-Robinson equation of state and entropy balance method. The methods were applied to Ar, N2, CH4, CO2, C2H4 and C2H6. Data obtained revealed that isentropic exponent method provides useful results ...

Helping Survivors of Human Trafficking: A Systematic Review of Exit and Postexit Interventions.

Science.gov (United States)

Dell, Nathaniel A; Maynard, Brandy R; Born, Kara R; Wagner, Elizabeth; Atkins, Bonnie; House, Whitney

2017-01-01

Human trafficking is a global problem and results in deleterious psychological, social, and physical effects on the lives of those who are trafficked; however, it is not clear how to best intervene with survivors. The purpose of this review was to synthesize the evidence of exit and postexit intervention programs for survivors of human trafficking to inform practice and research. Systematic review methods were used to search, select, and extract data from published and unpublished experimental, quasi-experimental, and preexperimental studies that assessed the effects of any exit or postexit interventions for victims of human trafficking. The authors searched eight databases, reviewed bibliographies, and conducted forward citation searches from relevant reports and prior reviews to find studies authored between 2005 and 2015. The search yielded six eligible studies that included 155 female and 6 male survivors from four countries. Interventions were diverse, with three using a trauma-informed approach. Authors measured a myriad of outcomes, including mental health, social network, community reintegration, and employment; however, the quality of most studies was poor. Evidence of effects of exit and postexit interventions is sparse, and much of the research is poorly designed and executed; however, the needs of trafficking survivors are complex and effective interventions are desperately needed. Implications for practice and research are discussed.

The duration of G1, S, G2, and mitosis at four different temperatures in Zea mays L. as measured with 3H-thymidine

International Nuclear Information System (INIS)

Verma, R.S.

1980-01-01

The effect of different temperatures on the duration of nuclear cycle in Zea mays (single cross hybrid 'Seneca 60') root meristem cells, was studied with autoradiographic techniques and it was shown that all component phases of the nuclear cycle are shortened by an increase in temperature from 20 to 35 0 C. The durations of total nuclear cycle at 20, 25, 30, and 35 0 C were 16.5, 9.9, 7.0, and 4.4 hours respectively while the durations of mitosis were 2.68, 1.10, 0.83, and 0.43 hours respectively. 85 - 90 percent of the nuclear cycle is required for interphase, while the remaining 10 - 15 percent of the cycle is occupied by mitosis. The mean mitotic indices at 20, 25, 30, and 35 0 C were 9.8, 9.1, 5.3, and 4.9 percent respectively. (author)

Radiation degradation of aromatic pollutants exit in wastewater and ph dependence

CERN Document Server

Takriti, S

2002-01-01

The effect of gamma radiation on the degradation of phenol (hydroxybenzene), resorcinol (1,3 dihydroxybenzen) and hydroquinone (1,4 dihydroxybenzen) exit in waste water was investigated. The concentrations of these pollutants as well as the irradiated solution ph were studied. The results showed that the phenol is very resistance against the radiation doses comparing the other phenol compounds. Phenol was also a product of radiolysis of resorcinol and hydroquinone. On the other hand, the acid phase of the irradiation sample increased the degradation rate of pollutants. Spectrophotometer (UV-VIS) and chromatography (HPLC) were used to monitor the analysis of the radiation product solution. The results illustrated the existing of many substances such as organic alcohol, aldehyde, ketone and acidic functional groups as a final radiation products. The degradation of benzene, monochlorobenzene (CB) and 1,2 dichlorobenzene (1,2 DCB) exit in waste water by gamma irradiation was investigated. The effect of the irradi...

Role of endothelial permeability hotspots and endothelial mitosis in determining age-related patterns of macromolecule uptake by the rabbit aortic wall near branch points.

Science.gov (United States)

Chooi, K Yean; Comerford, Andrew; Cremers, Stephanie J; Weinberg, Peter D

2016-07-01

Transport of macromolecules between plasma and the arterial wall plays a key role in atherogenesis. Scattered hotspots of elevated endothelial permeability to macromolecules occur in the aorta; a fraction of them are associated with dividing cells. Hotspots occur particularly frequently downstream of branch points, where lesions develop in young rabbits and children. However, the pattern of lesions varies with age, and can be explained by similar variation in the pattern of macromolecule uptake. We investigated whether patterns of hotspots and mitosis also change with age. Evans' Blue dye-labeled albumin was injected intravenously into immature or mature rabbits and its subsequent distribution in the aortic wall around intercostal branch ostia examined by confocal microscopy and automated image analysis. Mitosis was detected by immunofluorescence after adding 5-bromo-2-deoxiuridine to drinking water. Hotspots were most frequent downstream of branches in immature rabbits, but a novel distribution was observed in mature rabbits. Neither pattern was explained by mitosis. Hotspot uptake correlated spatially with the much greater non-hotspot uptake (p hotspots were considered. The pattern of hotspots changes with age. The data are consistent with there being a continuum of local permeabilities rather than two distinct mechanisms. The distribution of the dye, which binds to elastin and collagen, was similar to that of non-binding tracers and to lesions apart from a paucity at the lateral margins of branches that can be explained by lower levels of fibrous proteins in those regions. Copyright © 2016. Published by Elsevier Ireland Ltd.

Functional importance of the anaphase-promoting complex-Cdh1-mediated degradation of TMAP/CKAP2 in regulation of spindle function and cytokinesis.

Science.gov (United States)

Hong, Kyung Uk; Park, Young Soo; Seong, Yeon-Sun; Kang, Dongmin; Bae, Chang-Dae; Park, Joobae

2007-05-01

Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein (TMAP), is a novel microtubule-associated protein that is frequently upregulated in various malignances. However, its cellular functions remain unknown. A previous study has shown that its protein level begins to increase during G(1)/S and peaks at G(2)/M, after which it decreases abruptly. Ectopic overexpression of TMAP/CKAP2 induced microtubule bundling related to increased microtubule stability. TMAP/CKAP2 overexpression also resulted in cell cycle arrest during mitosis due to a defect in centrosome separation and subsequent formation of a monopolar spindle. We also show that degradation of TMAP/CKAP2 during mitotic exit is mediated by the anaphase-promoting complex bound to Cdh1 and that the KEN box motif near the N terminus is necessary for its destruction. Compared to the wild type, expression of a nondegradable mutant of TMAP/CKAP2 significantly increased the occurrence of spindle defects and cytokinesis failure. These results suggest that TMAP/CKAP2 plays a role in the assembly and maintenance of mitotic spindles, presumably by regulating microtubule dynamics, and its destruction during mitotic exit serves an important role in the completion of cytokinesis and in the maintenance of spindle bipolarity in the next mitosis.

Functional Importance of the Anaphase-Promoting Complex-Cdh1-Mediated Degradation of TMAP/CKAP2 in Regulation of Spindle Function and Cytokinesis▿ †

Science.gov (United States)

Hong, Kyung Uk; Park, Young Soo; Seong, Yeon-Sun; Kang, Dongmin; Bae, Chang-Dae; Park, Joobae

2007-01-01

Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein (TMAP), is a novel microtubule-associated protein that is frequently upregulated in various malignances. However, its cellular functions remain unknown. A previous study has shown that its protein level begins to increase during G1/S and peaks at G2/M, after which it decreases abruptly. Ectopic overexpression of TMAP/CKAP2 induced microtubule bundling related to increased microtubule stability. TMAP/CKAP2 overexpression also resulted in cell cycle arrest during mitosis due to a defect in centrosome separation and subsequent formation of a monopolar spindle. We also show that degradation of TMAP/CKAP2 during mitotic exit is mediated by the anaphase-promoting complex bound to Cdh1 and that the KEN box motif near the N terminus is necessary for its destruction. Compared to the wild type, expression of a nondegradable mutant of TMAP/CKAP2 significantly increased the occurrence of spindle defects and cytokinesis failure. These results suggest that TMAP/CKAP2 plays a role in the assembly and maintenance of mitotic spindles, presumably by regulating microtubule dynamics, and its destruction during mitotic exit serves an important role in the completion of cytokinesis and in the maintenance of spindle bipolarity in the next mitosis. PMID:17339342

In vivo dosimetry with thermoluminescent dosimeters in radiotherapy: entrance and exit doses

International Nuclear Information System (INIS)

Alves, C.; Lopes, M.C.

2000-01-01

In vivo dosimetry, by entrance and exit dose measurements, is a vital part of a radiotherapy quality assurance program. The uncertainty associated with dose delivery is internationally accepted to be within 5% or inferior depending on the tumor pathology. Thermoluminescent dosimetry is one of the dosimetric techniques used to verify the agreement between delivered and prescribed doses. Nevertheless, it requires a very accurate calibration methodology. We have used LiF chips (4.5 mm diameter and 0.8 mm thick) calibrated towards a PTW ionization chamber of 0.3 cc, in three photon energies: Co-60, 4 and 6 MeV. The TLD reader used was a Rialto 688 from NE Technology and the annealing oven the Eurotherm type 815. The calibration methodology relies on the experimental determination of individual correction factors and on a correction factor derived from a control group of dosimeters. The exit and entrance dose measurements are performed in quite different situations. To be able to achieve those two quantities with TLD, these should be independently calibrated according to the measurement conditions. Alternatively, we can use a single calibration, in entrance dose, and convert the result to the exit dose value by introducing some correction factors. These corrections are related to the different measurement depths and to the different backscattering contributions. We have proved that within an acceptable error we can perform a single calibration and adopt the correction factors which are energy and field size dependent. (author)

Effects of inlet distortion on gas turbine combustion chamber exit temperature profiles

Science.gov (United States)

Maqsood, Omar Shahzada

Damage to a nozzle guide vane or blade, caused by non-uniform temperature distributions at the combustion chamber exit, is deleterious to turbine performance and can lead to expensive and time consuming overhaul and repair. A test rig was designed and constructed for the Allison 250-C20B combustion chamber to investigate the effects of inlet air distortion on the combustion chamber's exit temperature fields. The rig made use of the engine's diffuser tubes, combustion case, combustion liner, and first stage nozzle guide vane shield. Rig operating conditions simulated engine cruise conditions, matching the quasi-non-dimensional Mach number, equivalence ratio and Sauter mean diameter. The combustion chamber was tested with an even distribution of inlet air and a 4% difference in airflow at either side. An even distribution of inlet air to the combustion chamber did not create a uniform temperature profile and varying the inlet distribution of air exacerbated the profile's non-uniformity. The design of the combustion liner promoted the formation of an oval-shaped toroidal vortex inside the chamber, creating localized hot and cool sections separated by 90° that appeared in the exhaust. Uneven inlet air distributions skewed the oval vortex, increasing the temperature of the hot section nearest the side with the most mass flow rate and decreasing the temperature of the hot section on the opposite side. Keywords: Allison 250, Combustion, Dual-Entry, Exit Temperature Profile, Gas Turbine, Pattern Factor, Reverse Flow.

Firm Size and Short-Term Dynamics in Aggregate Entry and Exit

NARCIS (Netherlands)

Manjon, M.C.

2004-01-01

Much of the research on industry dynamics focuses on the interdependence between the sectorial rates of entry and exit.This paper argues that the size of firms and the reaction-adjustment period are important conditions missed in this literature.I illustrate the effects of this omission using data

Numerical identification of blade exit angle effect on the performance for a multistage centrifugal pump impeller

Directory of Open Access Journals (Sweden)

Babayigit Osman

2015-01-01

Full Text Available Nowadays, single and multistage centrifugal pumps are widely used in industrial and mining enterprises. One of the most important components of a centrifugal pump is the impeller. The performance characteristics are related to the pump comprising the head and the overall efficiency rely a great deal on the impeller geometry. In this work, effects of blade exit angle change on hydraulic efficiency of a multi stage pump impeller are investigated via Ansys-Fluent computational fluid dynamics software for constant width impeller entrance and exit gates, blade numbers and blade thickness. Firstly, the flow volume of a centrifugal pump impeller is generated and then mesh structure is formed for the full impeller flow volume. Secondly, rotational periodic flow model are adopted in order to examine the effect of periodic flow assumption on the performance predictions. Corresponding to the available experimental data, inlet mass flow rate, outlet static pressure and rotation of impeller are taken as 0.02m3s-1, 450 kPa and 2950 rpm, respectively for the water fluid. No slip boundary condition is exposed to all solid of surface in the flow volume. The continuity and Navier-Stokes equations with the k-ε turbulence model and the standard wall functions are used. During the study, numerical analyses are conducted for the blade exit angle values of 18°, 20°, 25°, 30° and 35°. In consequence of the performed analyses, it is determined that hydraulic efficiency of the pump impeller value is changed between 81.0-84.6%. The most convenient blade exit angle that yields 84.6% hydraulic efficiency at is 18°. The obtained results show that the blade exit angle range has an impact on the centrifugal pump performance describing the pump head and the hydraulic efficiency.

Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes

International Nuclear Information System (INIS)

Bassuk, J.A.; Tsichlis, P.N.; Sorof, S.

1987-01-01

Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene). The level of immunohistochemically detected p14 was low when growth activity of hepatocytes was low, was markedly elevated during mitosis in normal and regenerating livers, but was very high throughout interphase during proliferation of hyperplastic and malignant hepatocytes induced in rat liver by a carcinogen (N-2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene). The authors report here that p14 is the liver fatty acid binding protein. The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage λgt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein. Furthermore, the two proteins shared the following properties: size of mRNA, amino acid composition, molecular size according to NaDodSO 4 gel electrophoresis, and electrophoretic mobilities in a Triton X-100/acetic acid/urea gel. The two polypeptides bound oleic acid similarly. Finally, identical elevations of cytoplasmic immunostain were detected specifically in mitotic hepatocytes with either antiserum. The collected findings are suggestive that liver fatty acid binding protein may carry ligands that promote hepatocyte division and may transport certain activated chemical carcinogens

Environmental regulations and plant exit: A logit analysis based on established panel data

Energy Technology Data Exchange (ETDEWEB)

Bioern, E; Golombek, R; Raknerud, A

1995-12-01

This publication uses a model to study the relationship between environmental regulations and plant exit. It has the main characteristics of a multinomial qualitative response model of the logit type, but also has elements of a Markov chain model. The model uses Norwegian panel data for establishments in three manufacturing sectors with high shares of units which have been under strict environmental regulations. In two of the sectors, the exit probability of non-regulated establishments is about three times higher than for regulated ones. It is also found that the probability of changing regulation status from non-regulated to regulated depends significantly on economic factors. In particular, establishments with weak profitability are the most likely to become subject to environmental regulation. 12 refs., 2 figs., 6 tabs.

Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution.

Science.gov (United States)

Cavalier-Smith, Thomas

2010-02-04

The transition from prokaryotes to eukaryotes was the most radical change in cell organisation since life began, with the largest ever burst of gene duplication and novelty. According to the coevolutionary theory of eukaryote origins, the fundamental innovations were the concerted origins of the endomembrane system and cytoskeleton, subsequently recruited to form the cell nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic novelties inevitable consequences of this compartmentation and novel DNA segregation mechanism. Physical and mutational mechanisms of origin of the nucleus are seldom considered beyond the long-standing assumption that it involved wrapping pre-existing endomembranes around chromatin. Discussions on the origin of sex typically overlook its association with protozoan entry into dormant walled cysts and the likely simultaneous coevolutionary, not sequential, origin of mitosis and meiosis. I elucidate nuclear and mitotic coevolution, explaining the origins of dicer and small centromeric RNAs for positionally controlling centromeric heterochromatin, and how 27 major features of the cell nucleus evolved in four logical stages, making both mechanisms and selective advantages explicit: two initial stages (origin of 30 nm chromatin fibres, enabling DNA compaction; and firmer attachment of endomembranes to heterochromatin) protected DNA and nascent RNA from shearing by novel molecular motors mediating vesicle transport, division, and cytoplasmic motility. Then octagonal nuclear pore complexes (NPCs) arguably evolved from COPII coated vesicle proteins trapped in clumps by Ran GTPase-mediated cisternal fusion that generated the fenestrated nuclear envelope, preventing lethal complete cisternal fusion, and allowing passive protein and RNA exchange. Finally, plugging NPC lumens by an FG-nucleoporin meshwork and adopting karyopherins for nucleocytoplasmic exchange conferred compartmentation advantages. These successive changes took place

Retrospectively assessed physical work environment during working life and risk of sickness absence and labour market exit among older workers

DEFF Research Database (Denmark)

Sundstrup, Emil; Hansen, Åse Marie; Mortensen, Erik Lykke

2018-01-01

OBJECTIVE: To determine the prospective association between retrospectively assessed physical work environment during working life and prospectively assessed sickness absence and labour market exit among older workers. METHODS: Using Cox regression analyses we estimated the 4-year to 6-year...... and exposure to several factors in the physical work environment, especially heavy lifting, were important for labour market exit and sickness absence. This study underscores the importance of reducing physical work exposures throughout the working life course for preventing sickness absence and premature exit...... from the labour market....

Quantifying groundwater dependency of riparian surface hydrologic features using the exit gradient

Science.gov (United States)

This study examines groundwater exit gradients as a way to quantify groundwater interactions with surface water. We calibrated high resolution groundwater models for the basin fill sediments in the lower Calapooia watershed, Oregon, using data collected between 1928--2000. The e...

The relationship between substance use and exit security on psychiatric wards

NARCIS (Netherlands)

Simpson, A.; Bowers, L.; Allan, T.; Haglund, K.; Muir-Cochrane, E.; Nijman, H.L.I.; Merwe, M. van der

2011-01-01

Aim.  In this paper we report on the rates of drug/alcohol use on acute psychiatric wards in relation to levels and intensity of exit security measures. Background.  Many inpatient wards have become permanently locked, with staff concerned about the risk of patients leaving the ward and harming

Estimates of the first Dirichlet eigenvalue from exit time moment spectra

DEFF Research Database (Denmark)

Hurtado, Ana; Markvorsen, Steen; Palmer, Vicente

2013-01-01

We compute the first Dirichlet eigenvalue of a geodesic ball in a rotationally symmetric model space in terms of the moment spectrum for the Brownian motion exit times from the ball. This expression implies an estimate as exact as you want for the first Dirichlet eigenvalue of a geodesic ball...

Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli

OpenAIRE

Sullivan, Gareth J.; Bridger, Joanna M.; Cuthbert, Andrew P.; Newbold, Robert F.; Bickmore, Wendy A.; McStay, Brian

2001-01-01

Human ribosomal gene repeats are distributed among five nucleolar organizer regions (NORs) on the p arms of acrocentric chromosomes. On exit from mitosis, nucleoli form around individual active NORs. As cells progress through the cycle, these mini-nucleoli fuse to form large nucleoli incorporating multiple NORs. It is generally assumed that nucleolar incorporation of individual NORs is dependent on ribosomal gene transcription. To test this assumption, we determined the nuclear location of in...

Cellular Tug-of-War: Forces at Work and DNA Stretching in Mitosis

Science.gov (United States)

Griffin, Brian; Kilfoil, Maria L.

2013-03-01

In the microscopic world of the cell dominated by thermal noise, a cell must be able to successfully segregate its DNA with high fidelity in order to pass its genetic information on to its progeny. In this process of mitosis in eukaryotes, driving forces act on the cytoskeleton-based architecture called the mitotic spindle to promote this division. Our preliminary data demonstrates that the dynamics of this process in yeast cells is universal. Moreover, the dynamics suggest an increasing load as the chromosomes are pulled apart. To investigate this, we use three-dimensional imaging to track the dynamics of the poles of this architecture and the points of attachment to chromosomes simultaneously and with high spatial resolution. We analyze the relative motions of chromosomes as they are organized before segregation and as they are pulled apart, using this data to investigate the force-response behavior of this cytoskeleton-chromosome polymer system.