Human ASPM participates in spindle organisation, spindle orientation and cytokinesis

Directory of Open Access Journals (Sweden)

Woods C Geoffrey

2010-11-01

Full Text Available Abstract Background Mutations in the Abnormal Spindle Microcephaly related gene (ASPM are the commonest cause of autosomal recessive primary microcephaly (MCPH a disorder characterised by a small brain and associated mental retardation. ASPM encodes a mitotic spindle pole associated protein. It is suggested that the MCPH phenotype arises from proliferation defects in neural progenitor cells (NPC. Results We show that ASPM is a microtubule minus end-associated protein that is recruited in a microtubule-dependent manner to the pericentriolar matrix (PCM at the spindle poles during mitosis. ASPM siRNA reduces ASPM protein at the spindle poles in cultured U2OS cells and severely perturbs a number of aspects of mitosis, including the orientation of the mitotic spindle, the main determinant of developmental asymmetrical cell division. The majority of ASPM depleted mitotic cells fail to complete cytokinesis. In MCPH patient fibroblasts we show that a pathogenic ASPM splice site mutation results in the expression of a novel variant protein lacking a tripeptide motif, a minimal alteration that correlates with a dramatic decrease in ASPM spindle pole localisation. Moreover, expression of dominant-negative ASPM C-terminal fragments cause severe spindle assembly defects and cytokinesis failure in cultured cells. Conclusions These observations indicate that ASPM participates in spindle organisation, spindle positioning and cytokinesis in all dividing cells and that the extreme C-terminus of the protein is required for ASPM localisation and function. Our data supports the hypothesis that the MCPH phenotype caused by ASPM mutation is a consequence of mitotic aberrations during neurogenesis. We propose the effects of ASPM mutation are tolerated in somatic cells but have profound consequences for the symmetrical division of NPCs, due to the unusual morphology of these cells. This antagonises the early expansion of the progenitor pool that underpins cortical

The Physics of the Metaphase Spindle.

Science.gov (United States)

Oriola, David; Needleman, Daniel J; Brugués, Jan

2018-05-20

The assembly of the mitotic spindle and the subsequent segregation of sister chromatids are based on the self-organized action of microtubule filaments, motor proteins, and other microtubule-associated proteins, which constitute the fundamental force-generating elements in the system. Many of the components in the spindle have been identified, but until recently it remained unclear how their collective behaviors resulted in such a robust bipolar structure. Here, we review the current understanding of the physics of the metaphase spindle that is only now starting to emerge.

Spindle formation in the mouse embryo requires Plk4 in the absence of centrioles.

Science.gov (United States)

Coelho, Paula A; Bury, Leah; Sharif, Bedra; Riparbelli, Maria G; Fu, Jingyan; Callaini, Giuliano; Glover, David M; Zernicka-Goetz, Magdalena

2013-12-09

During the first five rounds of cell division in the mouse embryo, spindles assemble in the absence of centrioles. Spindle formation initiates around chromosomes, but the microtubule nucleating process remains unclear. Here we demonstrate that Plk4, a protein kinase known as a master regulator of centriole formation, is also essential for spindle assembly in the absence of centrioles. Depletion of maternal Plk4 prevents nucleation and growth of microtubules and results in monopolar spindle formation. This leads to cytokinesis failure and, consequently, developmental arrest. We show that Plk4 function depends on its kinase activity and its partner protein, Cep152. Moreover, tethering Cep152 to cellular membranes sequesters Plk4 and is sufficient to trigger spindle assembly from ectopic membranous sites. Thus, the Plk4-Cep152 complex has an unexpected role in promoting microtubule nucleation in the vicinity of chromosomes to mediate bipolar spindle formation in the absence of centrioles. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Direct kinetochore–spindle pole connections are not required for chromosome segregation

Science.gov (United States)

Sikirzhytski, Vitali; Magidson, Valentin; Steinman, Jonathan B.; He, Jie; Le Berre, Maël; Tikhonenko, Irina; Ault, Jeffrey G.; McEwen, Bruce F.; Chen, James K.; Sui, Haixin; Piel, Matthieu; Kapoor, Tarun M.

2014-01-01

Segregation of genetic material occurs when chromosomes move to opposite spindle poles during mitosis. This movement depends on K-fibers, specialized microtubule (MT) bundles attached to the chromosomes′ kinetochores. A long-standing assumption is that continuous K-fibers connect every kinetochore to a spindle pole and the force for chromosome movement is produced at the kinetochore and coupled with MT depolymerization. However, we found that chromosomes still maintained their position at the spindle equator during metaphase and segregated properly during anaphase when one of their K-fibers was severed near the kinetochore with a laser microbeam. We also found that, in normal fully assembled spindles, K-fibers of some chromosomes did not extend to the spindle pole. These K-fibers connected to adjacent K-fibers and/or nonkinetochore MTs. Poleward movement of chromosomes with short K-fibers was uncoupled from MT depolymerization at the kinetochore. Instead, these chromosomes moved by dynein-mediated transport of the entire K-fiber/kinetochore assembly. Thus, at least two distinct parallel mechanisms drive chromosome segregation in mammalian cells. PMID:25023516

Direct kinetochore-spindle pole connections are not required for chromosome segregation.

Science.gov (United States)

Sikirzhytski, Vitali; Magidson, Valentin; Steinman, Jonathan B; He, Jie; Le Berre, Maël; Tikhonenko, Irina; Ault, Jeffrey G; McEwen, Bruce F; Chen, James K; Sui, Haixin; Piel, Matthieu; Kapoor, Tarun M; Khodjakov, Alexey

2014-07-21

Segregation of genetic material occurs when chromosomes move to opposite spindle poles during mitosis. This movement depends on K-fibers, specialized microtubule (MT) bundles attached to the chromosomes' kinetochores. A long-standing assumption is that continuous K-fibers connect every kinetochore to a spindle pole and the force for chromosome movement is produced at the kinetochore and coupled with MT depolymerization. However, we found that chromosomes still maintained their position at the spindle equator during metaphase and segregated properly during anaphase when one of their K-fibers was severed near the kinetochore with a laser microbeam. We also found that, in normal fully assembled spindles, K-fibers of some chromosomes did not extend to the spindle pole. These K-fibers connected to adjacent K-fibers and/or nonkinetochore MTs. Poleward movement of chromosomes with short K-fibers was uncoupled from MT depolymerization at the kinetochore. Instead, these chromosomes moved by dynein-mediated transport of the entire K-fiber/kinetochore assembly. Thus, at least two distinct parallel mechanisms drive chromosome segregation in mammalian cells.

Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

Energy Technology Data Exchange (ETDEWEB)

Yu, Yueyang [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

2012-10-10

The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

Science.gov (United States)

Gisselsson, David; Håkanson, Ulf; Stoller, Patrick; Marti, Dominik; Jin, Yuesheng; Rosengren, Anders H; Stewénius, Ylva; Kahl, Fredrik; Panagopoulos, Ioannis

2008-04-02

Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally. Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells. The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient generator of genetically diverse minority clones in transformed cell

When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

Directory of Open Access Journals (Sweden)

David Gisselsson

Full Text Available BACKGROUND: Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally. PRINCIPAL FINDINGS: Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells. CONCLUSION: The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient

Inscuteable Regulates the Pins-Mud Spindle Orientation Pathway

Science.gov (United States)

Mauser, Jonathon F.; Prehoda, Kenneth E.

2012-01-01

During asymmetric cell division, alignment of the mitotic spindle with the cell polarity axis ensures that the cleavage furrow separates fate determinants into distinct daughter cells. The protein Inscuteable (Insc) is thought to link cell polarity and spindle positioning in diverse systems by binding the polarity protein Bazooka (Baz; aka Par-3) and the spindle orienting protein Partner of Inscuteable (Pins; mPins or LGN in mammals). Here we investigate the mechanism of spindle orientation by the Insc-Pins complex. Previously, we defined two Pins spindle orientation pathways: a complex with Mushroom body defect (Mud; NuMA in mammals) is required for full activity, whereas binding to Discs large (Dlg) is sufficient for partial activity. In the current study, we have examined the role of Inscuteable in mediating downstream Pins-mediated spindle orientation pathways. We find that the Insc-Pins complex requires Gαi for partial activity and that the complex specifically recruits Dlg but not Mud. In vitro competition experiments revealed that Insc and Mud compete for binding to the Pins TPR motifs, while Dlg can form a ternary complex with Insc-Pins. Our results suggest that Insc does not passively couple polarity and spindle orientation but preferentially inhibits the Mud pathway, while allowing the Dlg pathway to remain active. Insc-regulated complex assembly may ensure that the spindle is attached to the cortex (via Dlg) before activation of spindle pulling forces by Dynein/Dynactin (via Mud). PMID:22253744

Measuring mitotic spindle dynamics in budding yeast

Science.gov (United States)

Plumb, Kemp

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

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.

Inhibition of CDK7 bypasses spindle assembly checkpoint via premature cyclin B degradation during oocyte meiosis.

Science.gov (United States)

Wang, HaiYang; Jo, Yu-Jin; Sun, Tian-Yi; Namgoong, Suk; Cui, Xiang-Shun; Oh, Jeong Su; Kim, Nam-Hyung

2016-12-01

To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) delays anaphase onset by preventing the premature activation of anaphase-promoting complex/cyclosome (APC/C) until all kinetochores are attached to the spindle. Although an escape from mitosis in the presence of unsatisfied SAC has been shown in several cancer cells, it has not been reported in oocyte meiosis. Here, we show that CDK7 activity is required to prevent a bypass of SAC during meiosis I in mouse oocytes. Inhibition of CDK7 using THZ1 accelerated the first meiosis, leading to chromosome misalignment, lag of chromosomes during chromosome segregation, and a high incidence of aneuploidy. Notably, this acceleration occurred in the presence of SAC proteins including Mad2 and Bub3 at the kinetochores. However, inhibition of APC/C-mediated cyclin B degradation blocked the THZ1-induced premature polar body extrusion. Moreover, chromosomal defects mediated by THZ1 were rescued when anaphase onset was delayed. Collectively, our results show that CDK7 activity is required to prevent premature anaphase onset by suppressing the bypass of SAC, thus ensuring chromosome alignment and proper segregation. These findings reveal new roles of CDK7 in the regulation of meiosis in mammalian oocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer.

LENUS (Irish Health Repository)

McGrogan, Barbara

2014-07-01

Ovarian carcinoma (OC) is the most lethal of the gynecological malignancies, often presenting at an advanced stage. Treatment is hampered by high levels of drug resistance. The taxanes are microtubule stabilizing agents, used as first-line agents in the treatment of OC that exert their apoptotic effects through the spindle assembly checkpoint. BUB1-related protein kinase (BUBR1) and mitotic arrest deficient 2 (MAD2), essential spindle assembly checkpoint components, play a key role in response to taxanes. BUBR1, MAD2, and Ki-67 were assessed on an OC tissue microarray platform representing 72 OC tumors of varying histologic subtypes. Sixty-one of these patients received paclitaxel and platinum agents combined; 11 received platinum alone. Overall survival was available for all 72 patients, whereas recurrence-free survival (RFS) was available for 66 patients. Increased BUBR1 expression was seen in serous carcinomas, compared with other histologies (P = .03). Increased BUBR1 was significantly associated with tumors of advanced stage (P = .05). Increased MAD2 and BUBR1 expression also correlated with increased cellular proliferation (P < .0002 and P = .02, respectively). Reduced MAD2 nuclear intensity was associated with a shorter RFS (P = .03), in ovarian tumors of differing histologic subtype (n = 66). In this subgroup, for those women who received paclitaxel and platinum agents combined (n = 57), reduced MAD2 intensity also identified women with a shorter RFS (P < .007). For the entire cohort of patients, irrespective of histologic subtype or treatment, MAD2 nuclear intensity retained independent significance in a multivariate model, with tumors showing reduced nuclear MAD2 intensity identifying patients with a poorer RFS (P = .05).

Sleep spindles and intelligence: evidence for a sexual dimorphism.

Science.gov (United States)

Ujma, Péter P; Konrad, Boris Nikolai; Genzel, Lisa; Bleifuss, Annabell; Simor, Péter; Pótári, Adrián; Körmendi, János; Gombos, Ferenc; Steiger, Axel; Bódizs, Róbert; Dresler, Martin

2014-12-03

Sleep spindles are thalamocortical oscillations in nonrapid eye movement sleep, which play an important role in sleep-related neuroplasticity and offline information processing. Sleep spindle features are stable within and vary between individuals, with, for example, females having a higher number of spindles and higher spindle density than males. Sleep spindles have been associated with learning potential and intelligence; however, the details of this relationship have not been fully clarified yet. In a sample of 160 adult human subjects with a broad IQ range, we investigated the relationship between sleep spindle parameters and intelligence. In females, we found a positive age-corrected association between intelligence and fast sleep spindle amplitude in central and frontal derivations and a positive association between intelligence and slow sleep spindle duration in all except one derivation. In males, a negative association between intelligence and fast spindle density in posterior regions was found. Effects were continuous over the entire IQ range. Our results demonstrate that, although there is an association between sleep spindle parameters and intellectual performance, these effects are more modest than previously reported and mainly present in females. This supports the view that intelligence does not rely on a single neural framework, and stronger neural connectivity manifesting in increased thalamocortical oscillations in sleep is one particular mechanism typical for females but not males. Copyright © 2014 the authors 0270-6474/14/3416358-11$15.00/0.

CENP-W plays a role in maintaining bipolar spindle structure.

Directory of Open Access Journals (Sweden)

Agnieszka Kaczmarczyk

Full Text Available The CENP-W/T complex was previously reported to be required for mitosis. HeLa cells depleted of CENP-W displayed profound mitotic defects, with mitotic timing delay, disorganized prometaphases and multipolar spindles as major phenotypic consequences. In this study, we examined the process of multipolar spindle formation induced by CENP-W depletion. Depletion of CENP-W in HeLa cells labeled with histone H2B and tubulin fluorescent proteins induced rapid fragmentation of originally bipolar spindles in a high proportion of cells. CENP-W depletion was associated with depletion of Hec1 at kinetochores. The possibility of promiscuous centrosomal duplication was ruled out by immunofluorescent examination of centrioles. However, centrioles were frequently observed to be abnormally split. In addition, a large proportion of the supernumerary poles lacked centrioles, but were positively stained with different centrosomal markers. These observations suggested that perturbation in spindle force distribution caused by defective kinetochores could contribute to a mechanical mechanism for spindle pole disruption. 'Spindle free' nocodazole arrested cells did not exhibit pole fragmentation after CENP-W depletion, showing that pole fragmentation is microtubule dependent. Inhibition of centrosome separation by monastrol reduced the incidence of spindle pole fragmentation, indicating that Eg5 plays a role in spindle pole disruption. Surprisingly, CENP-W depletion rescued the monopolar spindle phenotype of monastrol treatment, with an increased frequency of bipolar spindles observed after CENP-W RNAi. We overexpressed the microtubule cross-linking protein TPX2 to create spindle poles stabilized by the microtubule cross-linking activity of TPX2. Spindle pole fragmentation was suppressed in a TPX2-dependent fashion. We propose that CENP-W, by influencing proper kinetochore assembly, particularly microtubule docking sites, can confer spindle pole resistance to traction

CENP-W Plays a Role in Maintaining Bipolar Spindle Structure

Science.gov (United States)

Kaczmarczyk, Agnieszka; Sullivan, Kevin F.

2014-01-01

The CENP-W/T complex was previously reported to be required for mitosis. HeLa cells depleted of CENP-W displayed profound mitotic defects, with mitotic timing delay, disorganized prometaphases and multipolar spindles as major phenotypic consequences. In this study, we examined the process of multipolar spindle formation induced by CENP-W depletion. Depletion of CENP-W in HeLa cells labeled with histone H2B and tubulin fluorescent proteins induced rapid fragmentation of originally bipolar spindles in a high proportion of cells. CENP-W depletion was associated with depletion of Hec1 at kinetochores. The possibility of promiscuous centrosomal duplication was ruled out by immunofluorescent examination of centrioles. However, centrioles were frequently observed to be abnormally split. In addition, a large proportion of the supernumerary poles lacked centrioles, but were positively stained with different centrosomal markers. These observations suggested that perturbation in spindle force distribution caused by defective kinetochores could contribute to a mechanical mechanism for spindle pole disruption. ‘Spindle free’ nocodazole arrested cells did not exhibit pole fragmentation after CENP-W depletion, showing that pole fragmentation is microtubule dependent. Inhibition of centrosome separation by monastrol reduced the incidence of spindle pole fragmentation, indicating that Eg5 plays a role in spindle pole disruption. Surprisingly, CENP-W depletion rescued the monopolar spindle phenotype of monastrol treatment, with an increased frequency of bipolar spindles observed after CENP-W RNAi. We overexpressed the microtubule cross-linking protein TPX2 to create spindle poles stabilized by the microtubule cross-linking activity of TPX2. Spindle pole fragmentation was suppressed in a TPX2-dependent fashion. We propose that CENP-W, by influencing proper kinetochore assembly, particularly microtubule docking sites, can confer spindle pole resistance to traction forces exerted

Dgp71WD is required for the assembly of the acentrosomal Meiosis I spindle, and is not a general targeting factor for the γ-TuRC

Directory of Open Access Journals (Sweden)

Richard F. Reschen

2012-03-01

Dgp71WD/Nedd1 proteins are essential for mitotic spindle formation. In human cells, Nedd1 targets γ-tubulin to both centrosomes and spindles, but in other organisms the function of Dgp71WD/Nedd1 is less clear. In Drosophila cells, Dgp71WD plays a major part in targeting γ-tubulin to spindles, but not centrosomes, while in Xenopus egg extracts, Nedd1 acts as a more general microtubule (MT organiser that can function independently of γ-tubulin. The interpretation of these studies, however, is complicated by the fact that some residual Dgp71WD/Nedd1 is likely present in the cells/extracts analysed. Here we generate a Dgp71WD null mutant lacking all but the last 12 nucleotides of coding sequence. The complete loss of Dgp71WD has no quantifiable effect on γ-tubulin or Centrosomin recruitment to the centrosome in larval brain cells. The recruitment of γ-tubulin to spindle MTs, however, is severely impaired, and spindle MT density is reduced in a manner that is indistinguishable from cells lacking Augmin or γ-TuRC function. In contrast, the absence of Dgp71WD leads to defects in the assembly of the acentrosomal female Meiosis I spindle that are more severe than those seen in Augmin or γ-TuRC mutants, indicating that Dgp71WD has additional functions that are independent of these complexes in oocytes. Moreover, the localisation of bicoid RNA during oogenesis, which requires γ-TuRC function, is unperturbed in Dgp71WD120 mutants. Thus, Dgp71WD is not simply a general cofactor required for γ-TuRC and/or Augmin targeting, and it appears to have a crucial role independent of these complexes in the acentrosomal Meiosis I spindle.

The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation.

Science.gov (United States)

Yokoyama, Hideki; Koch, Birgit; Walczak, Rudolf; Ciray-Duygu, Fulya; González-Sánchez, Juan Carlos; Devos, Damien P; Mattaj, Iain W; Gruss, Oliver J

2014-01-01

The GTP-bound form of the Ran GTPase (RanGTP), produced around chromosomes, drives nuclear envelope and nuclear pore complex (NPC) re-assembly after mitosis. The nucleoporin MEL-28/ELYS binds chromatin in a RanGTP-regulated manner and acts to seed NPC assembly. Here we show that, upon mitotic NPC disassembly, MEL-28 dissociates from chromatin and re-localizes to spindle microtubules and kinetochores. MEL-28 directly binds microtubules in a RanGTP-regulated way via its C-terminal chromatin-binding domain. Using Xenopus egg extracts, we demonstrate that MEL-28 is essential for RanGTP-dependent microtubule nucleation and spindle assembly, independent of its function in NPC assembly. Specifically, MEL-28 interacts with the γ-tubulin ring complex and recruits it to microtubule nucleation sites. Our data identify MEL-28 as a RanGTP target that functions throughout the cell cycle. Its cell cycle-dependent binding to chromatin or microtubules discriminates MEL-28 functions in interphase and mitosis, and ensures that spindle assembly occurs only after NPC breakdown.

Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint.

Directory of Open Access Journals (Sweden)

M Kasim Diril

2016-09-01

Full Text Available The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC maintenance since the duration of mitotic arrest caused by microtubule poisons in MastlNULL MEFs is shortened, which correlates with premature disappearance of the essential SAC protein Mad1 at the kinetochores. Notably, MastlNULL MEFs display reduced phosphorylation of a number of proteins in mitosis, which include the essential SAC kinase MPS1. We further demonstrate that Mastl is required for multi-site phosphorylation of MPS1 as well as robust MPS1 kinase activity in mitosis. In contrast, treatment of MastlNULL cells with the phosphatase inhibitor okadaic acid (OKA rescues the defects in MPS1 kinase activity, mislocalization of phospho-MPS1 as well as Mad1 at the kinetochore, and premature SAC silencing. Moreover, using in vitro dephosphorylation assays, we demonstrate that Mastl promotes persistent MPS1 phosphorylation by inhibiting PP2A/B55-mediated MPS1 dephosphorylation rather than affecting Cdk1 kinase activity. Our findings establish a key regulatory function of the Greatwall kinase/Mastl->PP2A/B55 pathway in preventing premature SAC silencing.

Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint.

Science.gov (United States)

Diril, M Kasim; Bisteau, Xavier; Kitagawa, Mayumi; Caldez, Matias J; Wee, Sheena; Gunaratne, Jayantha; Lee, Sang Hyun; Kaldis, Philipp

2016-09-01

The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL) MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC) maintenance since the duration of mitotic arrest caused by microtubule poisons in MastlNULL MEFs is shortened, which correlates with premature disappearance of the essential SAC protein Mad1 at the kinetochores. Notably, MastlNULL MEFs display reduced phosphorylation of a number of proteins in mitosis, which include the essential SAC kinase MPS1. We further demonstrate that Mastl is required for multi-site phosphorylation of MPS1 as well as robust MPS1 kinase activity in mitosis. In contrast, treatment of MastlNULL cells with the phosphatase inhibitor okadaic acid (OKA) rescues the defects in MPS1 kinase activity, mislocalization of phospho-MPS1 as well as Mad1 at the kinetochore, and premature SAC silencing. Moreover, using in vitro dephosphorylation assays, we demonstrate that Mastl promotes persistent MPS1 phosphorylation by inhibiting PP2A/B55-mediated MPS1 dephosphorylation rather than affecting Cdk1 kinase activity. Our findings establish a key regulatory function of the Greatwall kinase/Mastl->PP2A/B55 pathway in preventing premature SAC silencing.

The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

DEFF Research Database (Denmark)

Zhang, Gang; Beati, Hamze; Nilsson, Jakob

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been...

Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.

Directory of Open Access Journals (Sweden)

Zhong Rong Zhang

Full Text Available Andrographolide (Andro suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC, alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.

Taxifolin Enhances Andrographolide-Induced Mitotic Arrest and Apoptosis in Human Prostate Cancer Cells via Spindle Assembly Checkpoint Activation

Science.gov (United States)

Wong, Matthew Man-Kin; Chiu, Sung-Kay; Cheung, Hon-Yeung

2013-01-01

Andrographolide (Andro) suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi) has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose) polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC), alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC. PMID:23382917

Spindle assembly checkpoint acquisition at the mid-blastula transition.

Directory of Open Access Journals (Sweden)

Maomao Zhang

Full Text Available The spindle assembly checkpoint (SAC maintains the fidelity of chromosome segregation during mitosis. Nonpathogenic cells lacking the SAC are typically only found in cleavage stage metazoan embryos, which do not acquire functional checkpoints until the mid-blastula transition (MBT. It is unclear how proper SAC function is acquired at the MBT, though several models exist. First, SAC acquisition could rely on transcriptional activity, which increases dramatically at the MBT. Embryogenesis prior to the MBT relies primarily on maternally loaded transcripts, and if SAC signaling components are not maternally supplied, the SAC would depend on zygotic transcription at the MBT. Second, checkpoint acquisition could depend on the Chk1 kinase, which is activated at the MBT to elongate cell cycles and is required for the SAC in somatic cells. Third, SAC function could depend on a threshold nuclear to cytoplasmic (N:C ratio, which increases during pre-MBT cleavage cycles and dictates several MBT events like zygotic transcription and cell cycle remodeling. Finally, the SAC could by regulated by a timer mechanism that coincides with other MBT events but is independent of them. Using zebrafish embryos we show that SAC acquisition at the MBT is independent of zygotic transcription, indicating that the checkpoint program is maternally supplied. Additionally, by precociously lengthening cleavage cycles with exogenous Chk1 activity, we show that cell cycle lengthening and Chk1 activity are not sufficient for SAC acquisition. Furthermore, we find that SAC acquisition can be uncoupled from the N:C ratio. Together, our findings indicate that SAC acquisition is regulated by a maternally programmed developmental timer.

On the Free Vibration Modeling of Spindle Systems: A Calibrated Dynamic Stiffness Matrix

Directory of Open Access Journals (Sweden)

Omar Gaber

2014-01-01

Full Text Available The effect of bearings on the vibrational behavior of machine tool spindles is investigated. This is done through the development of a calibrated dynamic stiffness matrix (CDSM method, where the bearings flexibility is represented by massless linear spring elements with tuneable stiffness. A dedicated MATLAB code is written to develop and to assemble the element stiffness matrices for the system’s multiple components and to apply the boundary conditions. The developed method is applied to an illustrative example of spindle system. When the spindle bearings are modeled as simply supported boundary conditions, the DSM model results in a fundamental frequency much higher than the system’s nominal value. The simply supported boundary conditions are then replaced by linear spring elements, and the spring constants are adjusted such that the resulting calibrated CDSM model leads to the nominal fundamental frequency of the spindle system. The spindle frequency results are also validated against the experimental data. The proposed method can be effectively applied to predict the vibration characteristics of spindle systems supported by bearings.

Experimental muscle pain produces central modulation of proprioceptive signals arising from jaw muscle spindles.

Science.gov (United States)

Capra, N F; Ro, J Y

2000-05-01

The aim of the present study was to investigate the effects of intramuscular injection with hypertonic saline, a well-established experimental model for muscle pain, on central processing of proprioceptive input from jaw muscle spindle afferents. Fifty-seven cells were recorded from the medial edge of the subnucleus interpolaris (Vi) and the adjacent parvicellular reticular formation from 11 adult cats. These cells were characterized as central units receiving jaw muscle spindle input based on their responses to electrical stimulation of the masseter nerve, muscle palpation and jaw stretch. Forty-five cells, which were successfully tested with 5% hypertonic saline, were categorized as either dynamic-static (DS) (n=25) or static (S) (n=20) neurons based on their responses to different speeds and amplitudes of jaw movement. Seventy-six percent of the cells tested with an ipsilateral injection of hypertonic saline showed a significant modulation of mean firing rates (MFRs) during opening and/or holding phases. The most remarkable saline-induced change was a significant reduction of MFR during the hold phase in S units (100%, 18/18 modulated). Sixty-nine percent of the DS units (11/16 modulated) also showed significant changes in MFRs limited to the hold phase. However, in the DS neurons, the MFRs increased in seven units and decreased in four units. Finally, five DS neurons showed significant changes of MFRs during both opening and holding phases. Injections of isotonic saline into the ipsilateral masseter muscle had little effect, but hypertonic saline injections made into the contralateral masseter muscle produced similar results to ipsilateral injections with hypertonic saline. These results unequivocally demonstrate that intramuscular injection with an algesic substance, sufficient to produce muscle pain, produces significant changes in the proprioceptive properties of the jaw movement-related neurons. Potential mechanisms involved in saline-induced changes in the

The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

Science.gov (United States)

Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs. PMID:23593258

The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

Directory of Open Access Journals (Sweden)

Gang Zhang

Full Text Available Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs.

The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

Science.gov (United States)

Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs.

DNA damage response and spindle assembly checkpoint function throughout the cell cycle to ensure genomic integrity.

Directory of Open Access Journals (Sweden)

Katherine S Lawrence

2015-04-01

Full Text Available Errors in replication or segregation lead to DNA damage, mutations, and aneuploidies. Consequently, cells monitor these events and delay progression through the cell cycle so repair precedes division. The DNA damage response (DDR, which monitors DNA integrity, and the spindle assembly checkpoint (SAC, which responds to defects in spindle attachment/tension during metaphase of mitosis and meiosis, are critical for preventing genome instability. Here we show that the DDR and SAC function together throughout the cell cycle to ensure genome integrity in C. elegans germ cells. Metaphase defects result in enrichment of SAC and DDR components to chromatin, and both SAC and DDR are required for metaphase delays. During persistent metaphase arrest following establishment of bi-oriented chromosomes, stability of the metaphase plate is compromised in the absence of DDR kinases ATR or CHK1 or SAC components, MAD1/MAD2, suggesting SAC functions in metaphase beyond its interactions with APC activator CDC20. In response to DNA damage, MAD2 and the histone variant CENPA become enriched at the nuclear periphery in a DDR-dependent manner. Further, depletion of either MAD1 or CENPA results in loss of peripherally associated damaged DNA. In contrast to a SAC-insensitive CDC20 mutant, germ cells deficient for SAC or CENPA cannot efficiently repair DNA damage, suggesting that SAC mediates DNA repair through CENPA interactions with the nuclear periphery. We also show that replication perturbations result in relocalization of MAD1/MAD2 in human cells, suggesting that the role of SAC in DNA repair is conserved.

Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

Science.gov (United States)

Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

2013-01-01

Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.

Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis.

Science.gov (United States)

Bosveld, Floris; Ainslie, Anna; Bellaïche, Yohanns

2017-10-15

Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known about the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in Drosophila ) is best known for its role in spindle orientation. Here, we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in Drosophila epithelial cells. We found that Dynein and Mud mainly initiate centrosome-spindle coupling prior to nuclear envelope breakdown (NEB) by promoting correct centrosome positioning or separation, while Asp acts largely independently of Dynein and Mud to maintain centrosome-spindle coupling. Failure in the centrosome-spindle coupling leads to mis-segregation of the two centrosomes into one daughter cell, resulting in cells with supernumerary centrosomes during subsequent divisions. Altogether, we propose that Dynein, Mud and Asp operate sequentially during the cell cycle to ensure efficient centrosome-spindle coupling in mitosis, thereby preventing centrosome mis-segregation to maintain centrosome number. © 2017. Published by The Company of Biologists Ltd.

Interplay between microtubule bundling and sorting factors ensures acentriolar spindle stability during C. elegans oocyte meiosis.

Directory of Open Access Journals (Sweden)

Timothy J Mullen

2017-09-01

Full Text Available In many species, oocyte meiosis is carried out in the absence of centrioles. As a result, microtubule organization, spindle assembly, and chromosome segregation proceed by unique mechanisms. Here, we report insights into the principles underlying this specialized form of cell division, through studies of C. elegans KLP-15 and KLP-16, two highly homologous members of the kinesin-14 family of minus-end-directed kinesins. These proteins localize to the acentriolar oocyte spindle and promote microtubule bundling during spindle assembly; following KLP-15/16 depletion, microtubule bundles form but then collapse into a disorganized array. Surprisingly, despite this defect we found that during anaphase, microtubules are able to reorganize into a bundled array that facilitates chromosome segregation. This phenotype therefore enabled us to identify factors promoting microtubule organization during anaphase, whose contributions are normally undetectable in wild-type worms; we found that SPD-1 (PRC1 bundles microtubules and KLP-18 (kinesin-12 likely sorts those bundles into a functional orientation capable of mediating chromosome segregation. Therefore, our studies have revealed an interplay between distinct mechanisms that together promote spindle formation and chromosome segregation in the absence of structural cues such as centrioles.

Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Shimada, Midori [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Yamamoto, Ayumu [Department of Chemistry, Shizuoka University, 836 Ohya, Suruga-ku, Sizuoka 422-8529 (Japan); Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aiba, Hirofumi [Laboratory of Molecular Microbiology, School of Agriculture, Nagoya University, Chikusa-ku, Nagoya 464-8601 (Japan); Murakami, Hiroshi, E-mail: hmura@med.nagoya-cu.ac.jp [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

2009-10-23

The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2{sup +}. The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

International Nuclear Information System (INIS)

Shimada, Midori; Yamamoto, Ayumu; Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi; Aiba, Hirofumi; Murakami, Hiroshi

2009-01-01

The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2 + . The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

The RanGTP pathway: from nucleo-cytoplasmic transport to spindle assembly and beyond

Directory of Open Access Journals (Sweden)

Tommaso eCavazza

2016-01-01

Full Text Available The small GTPase Ran regulates the interaction of transport receptors with a number of cellular cargo proteins. The high affinity binding of the GTP-bound form of Ran to import receptors promotes cargo release, whereas its binding to export receptors stabilizes their interaction with the cargo. This basic mechanism linked to the asymmetric distribution of the two nucleotide-bound forms of Ran between the nucleus and the cytoplasm generates a switch like mechanism controlling nucleo-cytoplasmic transport. Since 1999, we have known that after nuclear envelope breakdown (NEBD Ran and the above transport receptors also provide a local control over the activity of factors driving spindle assembly and regulating other aspects of cell division. The identification and functional characterization of RanGTP mitotic targets is providing novel insights into mechanisms essential for cell division. Here we review our current knowledge on the RanGTP system and its regulation and we focus on the recent advances made through the characterization of its mitotic targets. We then briefly review the novel functions of the pathway that were recently described. Altogether, the RanGTP system has moonlighting functions exerting a spatial control over protein interactions that drive specific functions depending on the cellular context.

Sleep spindling and fluid intelligence across adolescent development: sex matters

Directory of Open Access Journals (Sweden)

Róbert eBódizs

2014-11-01

Full Text Available Evidence supports the intricate relationship between sleep electroencephalogram (EEG spindling and cognitive abilities in children and adults. Although sleep EEG changes during adolescence index fundamental brain reorganization, a detailed analysis of sleep spindling and the spindle-intelligence relationship was not yet provided for adolescents. Therefore, adolescent development of sleep spindle oscillations were studied in a home polysomnographic study focusing on the effects of chronological age and developmentally acquired overall mental efficiency (fluid IQ with sex as a potential modulating factor. Subjects were 24 healthy adolescents (12 males with an age range of 15–22 years (mean: 18 years and fluid IQ of 91-126 (mean: 104.12, Raven Progressive Matrices Test. Slow spindles (SSs and fast spindles (FSs were analyzed in 21 EEG derivations by using the individual adjustment method. A significant age-dependent increase in average FS density (r = .57; p = .005 was found. Moreover, fluid IQ correlated with FS density (r = .43; p = .04 and amplitude (r = .41; p = .049. The latter effects were entirely driven by particularly reliable FS-IQ correlations in females [r = .80 (p = .002 and r = .67 (p = .012, for density and amplitude, respectively]. Region-specific analyses revealed that these correlations peak in the fronto-central regions. The control of the age-dependence of FS measures and IQ scores did not considerably reduce the spindle-IQ correlations with respect to FS density. The only positive spindle-index of fluid IQ in males turned out to be the frequency of FSs (r = .60, p = .04. Increases in FS density during adolescence may index reshaped structural connectivity related to white matter maturation in the late developing human brain. The continued development over this age range of cognitive functions is indexed by specific measures of sleep spindling unravelling gender differences in adolescent brain maturation and perhaps cognitive

Nap sleep spindle correlates of intelligence.

Science.gov (United States)

Ujma, Péter P; Bódizs, Róbert; Gombos, Ferenc; Stintzing, Johannes; Konrad, Boris N; Genzel, Lisa; Steiger, Axel; Dresler, Martin

2015-11-26

Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fluid intelligence scores, however more recently it has been shown that only few sleep spindle measures correlate with intelligence in females, and none in males. Sleep spindle regulation underlies a circadian rhythm, however the association between spindles and intelligence has not been investigated in daytime nap sleep so far. In a sample of 86 healthy male human subjects, we investigated the correlation between fluid intelligence and sleep spindle parameters in an afternoon nap of 100 minutes. Mean sleep spindle length, amplitude and density were computed for each subject and for each derivation for both slow and fast spindles. A positive association was found between intelligence and slow spindle duration, but not any other sleep spindle parameter. As a positive correlation between intelligence and slow sleep spindle duration in full-night polysomnography has only been reported in females but not males, our results suggest that the association between intelligence and sleep spindles is more complex than previously assumed.

The Effect of the Rotor Static Eccentricity on the Electro-Mechanical Coupled Characteristics of the Motorized Spindle

Directory of Open Access Journals (Sweden)

Wu Zaixin

2016-01-01

Full Text Available High-speed motorized spindle is a multi-variable, non-linear and strong coupling system. The rotor static eccentricity is inevitable because of machining or assembling error. The rotor static eccentricities have an important effect on the electromechanical coupled characteristics of the motorized spindle. In this paper, the electromechanical coupled mathematical model of the motorized spindle was set up. The mathematical model includes mechanical and electrical equation. The mechanical and electrical equation is built up by the variational principle. Furthermore, the inductance parameters without the rotor static eccentricity and the inductance parameters with rotor static eccentricity have been calculated by the winding function method and the high speed motorized spindle was simulated. The result show that the rotor static eccentricity can delay the starting process of the motorized spindle, and at steady state, the rotor circuit currents are still large because of the rotor static eccentricity.

Dissecting the function and assembly of acentriolar microtubule organizing centers in Drosophila cells in vivo.

Directory of Open Access Journals (Sweden)

Janina Baumbach

2015-05-01

Full Text Available Acentriolar microtubule organizing centers (aMTOCs are formed during meiosis and mitosis in several cell types, but their function and assembly mechanism is unclear. Importantly, aMTOCs can be overactive in cancer cells, enhancing multipolar spindle formation, merotelic kinetochore attachment and aneuploidy. Here we show that aMTOCs can form in acentriolar Drosophila somatic cells in vivo via an assembly pathway that depends on Asl, Cnn and, to a lesser extent, Spd-2--the same proteins that appear to drive mitotic centrosome assembly in flies. This finding enabled us to ablate aMTOC formation in acentriolar cells, and so perform a detailed genetic analysis of the contribution of aMTOCs to acentriolar mitotic spindle formation. Here we show that although aMTOCs can nucleate microtubules, they do not detectably increase the efficiency of acentriolar spindle assembly in somatic fly cells. We find that they are required, however, for robust microtubule array assembly in cells without centrioles that also lack microtubule nucleation from around the chromatin. Importantly, aMTOCs are also essential for dynein-dependent acentriolar spindle pole focusing and for robust cell proliferation in the absence of centrioles and HSET/Ncd (a kinesin essential for acentriolar spindle pole focusing in many systems. We propose an updated model for acentriolar spindle pole coalescence by the molecular motors Ncd/HSET and dynein in conjunction with aMTOCs.

Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

Science.gov (United States)

Ro, J Y; Capra, N F

2001-05-01

Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

Sleep spindling and fluid intelligence across adolescent development: sex matters.

Science.gov (United States)

Bódizs, Róbert; Gombos, Ferenc; Ujma, Péter P; Kovács, Ilona

2014-01-01

Evidence supports the intricate relationship between sleep electroencephalogram (EEG) spindling and cognitive abilities in children and adults. Although sleep EEG changes during adolescence index fundamental brain reorganization, a detailed analysis of sleep spindling and the spindle-intelligence relationship was not yet provided for adolescents. Therefore, adolescent development of sleep spindle oscillations were studied in a home polysomnographic study focusing on the effects of chronological age and developmentally acquired overall mental efficiency (fluid IQ) with sex as a potential modulating factor. Subjects were 24 healthy adolescents (12 males) with an age range of 15-22 years (mean: 18 years) and fluid IQ of 91-126 (mean: 104.12, Raven Progressive Matrices Test). Slow spindles (SSs) and fast spindles (FSs) were analyzed in 21 EEG derivations by using the individual adjustment method (IAM). A significant age-dependent increase in average FS density (r = 0.57; p = 0.005) was found. Moreover, fluid IQ correlated with FS density (r = 0.43; p = 0.04) and amplitude (r = 0.41; p = 0.049). The latter effects were entirely driven by particularly reliable FS-IQ correlations in females [r = 0.80 (p = 0.002) and r = 0.67 (p = 0.012), for density and amplitude, respectively]. Region-specific analyses revealed that these correlations peak in the fronto-central regions. The control of the age-dependence of FS measures and IQ scores did not considerably reduce the spindle-IQ correlations with respect to FS density. The only positive spindle-index of fluid IQ in males turned out to be the frequency of FSs (r = 0.60, p = 0.04). Increases in FS density during adolescence may index reshaped structural connectivity related to white matter maturation in the late developing human brain. The continued development over this age range of cognitive functions is indexed by specific measures of sleep spindling unraveling gender differences in adolescent brain maturation and perhaps

Wind turbine/generator set having a stator cooling system located between stator frame and active coils

Science.gov (United States)

Bevington, Christopher M.; Bywaters, Garrett L.; Coleman, Clint C.; Costin, Daniel P.; Danforth, William L.; Lynch, Jonathan A.; Rolland, Robert H.

2012-11-13

A wind turbine comprising an electrical generator that includes a rotor assembly. A wind rotor that includes a wind rotor hub is directly coupled to the rotor assembly via a simplified connection. The wind rotor and generator rotor assembly are rotatably mounted on a central spindle via a bearing assembly. The wind rotor hub includes an opening having a diameter larger than the outside diameter of the central spindle adjacent the bearing assembly so as to allow access to the bearing assembly from a cavity inside the wind rotor hub. The spindle is attached to a turret supported by a tower. Each of the spindle, turret and tower has an interior cavity that permits personnel to traverse therethrough to the cavity of the wind rotor hub. The wind turbine further includes a frictional braking system for slowing, stopping or keeping stopped the rotation of the wind rotor and rotor assembly.

Wind turbine/generator set and method of making same

Science.gov (United States)

Bevington, Christopher M.; Bywaters, Garrett L.; Coleman, Clint C.; Costin, Daniel P.; Danforth, William L.; Lynch, Jonathan A.; Rolland, Robert H.

2013-06-04

A wind turbine comprising an electrical generator that includes a rotor assembly. A wind rotor that includes a wind rotor hub is directly coupled to the rotor assembly via a simplified connection. The wind rotor and generator rotor assembly are rotatably mounted on a central spindle via a bearing assembly. The wind rotor hub includes an opening having a diameter larger than the outside diameter of the central spindle adjacent the bearing assembly so as to allow access to the bearing assembly from a cavity inside the wind rotor hub. The spindle is attached to a turret supported by a tower. Each of the spindle, turret and tower has an interior cavity that permits personnel to traverse therethrough to the cavity of the wind rotor hub. The wind turbine further includes a frictional braking system for slowing, stopping or keeping stopped the rotation of the wind rotor and rotor assembly.

Sleep spindle alterations in patients with Parkinson's disease

DEFF Research Database (Denmark)

Christensen, Julie Anja Engelhard; Nikolic, Miki; Warby, Simon C.

2015-01-01

The aim of this study was to identify changes of sleep spindles (SS) in the EEG of patients with Parkinson's disease (PD). Five sleep experts manually identified SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched control subjects. Each SS was given a confidence score...

Wind turbine having a direct-drive drivetrain

Science.gov (United States)

Bevington, Christopher M.; Bywaters, Garrett L.; Coleman, Clint C.; Costin, Daniel P.; Danforth, William L.; Lynch, Jonathan A.; Rolland, Robert H.

2008-10-07

A wind turbine (100) comprising an electrical generator (108) that includes a rotor assembly (112). A wind rotor (104) that includes a wind rotor hub (124) is directly coupled to the rotor assembly via a simplified connection. The wind rotor and generator rotor assembly are rotatably mounted on a central spindle (160) via a bearing assembly (180). The wind rotor hub includes an opening (244) having a diameter larger than the outside diameter of the central spindle adjacent the bearing assembly so as to allow access to the bearing assembly from a cavity (380) inside the wind rotor hub. The spindle is attached to a turret (140) supported by a tower (136). Each of the spindle, turret and tower has an interior cavity (172, 176, 368) that permits personnel to traverse therethrough to the cavity of the wind rotor hub. The wind turbine further includes a frictional braking system (276) for slowing, stopping or keeping stopped the rotation of the wind rotor and rotor assembly.

The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing

DEFF Research Database (Denmark)

Lischetti, Tiziana; Zhang, Gang; Sedgwick, Garry G

2014-01-01

Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, Mad2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of Cdc20 kinetochore localization...... in the SAC, we delineate the molecular details of its interaction with kinetochores. We find that BubR1 recruits the bulk of Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). We show that preventing Cdc20 kinetochore localization by removal of the IC20BD has a limited effect...... on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signalling and SAC...

The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity

DEFF Research Database (Denmark)

Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo

2016-01-01

The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin......-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D...... depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC...

The structure of the mitotic spindle and nucleolus during mitosis in the amebo-flagellate Naegleria.

Science.gov (United States)

Walsh, Charles J

2012-01-01

Mitosis in the amebo-flagellate Naegleria pringsheimi is acentrosomal and closed (the nuclear membrane does not break down). The large central nucleolus, which occupies about 20% of the nuclear volume, persists throughout the cell cycle. At mitosis, the nucleolus divides and moves to the poles in association with the chromosomes. The structure of the mitotic spindle and its relationship to the nucleolus are unknown. To identify the origin and structure of the mitotic spindle, its relationship to the nucleolus and to further understand the influence of persistent nucleoli on cellular division in acentriolar organisms like Naegleria, three-dimensional reconstructions of the mitotic spindle and nucleolus were carried out using confocal microscopy. Monoclonal antibodies against three different nucleolar regions and α-tubulin were used to image the nucleolus and mitotic spindle. Microtubules were restricted to the nucleolus beginning with the earliest prophase spindle microtubules. Early spindle microtubules were seen as short rods on the surface of the nucleolus. Elongation of the spindle microtubules resulted in a rough cage of microtubules surrounding the nucleolus. At metaphase, the mitotic spindle formed a broad band completely embedded within the nucleolus. The nucleolus separated into two discreet masses connected by a dense band of microtubules as the spindle elongated. At telophase, the distal ends of the mitotic spindle were still completely embedded within the daughter nucleoli. Pixel by pixel comparison of tubulin and nucleolar protein fluorescence showed 70% or more of tubulin co-localized with nucleolar proteins by early prophase. These observations suggest a model in which specific nucleolar binding sites for microtubules allow mitotic spindle formation and attachment. The fact that a significant mass of nucleolar material precedes the chromosomes as the mitotic spindle elongates suggests that spindle elongation drives nucleolar division.

Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

DEFF Research Database (Denmark)

Xia, Jingjing; Swiercz, Jakub M.; Bañón-Rodríguez, Inmaculada

2015-01-01

Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we...... show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading...... to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central...

Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis.

Science.gov (United States)

Woo Seo, Dong; Yeop You, Seung; Chung, Woo-Jae; Cho, Dong-Hyung; Kim, Jae-Sung; Su Oh, Jeong

2015-10-21

The key step for faithful chromosome segregation during meiosis is kinetochore assembly. Defects in this process result in aneuploidy, leading to miscarriages, infertility and various birth defects. However, the roles of kinetochores in homologous chromosome segregation during meiosis are ill-defined. Here we found that Zwint-1 is required for homologous chromosome segregation during meiosis. Knockdown of Zwint-1 accelerated the first meiosis by abrogating the kinetochore recruitment of Mad2, leading to chromosome misalignment and a high incidence of aneuploidy. Although Zwint-1 knockdown did not affect Aurora C kinase activity, the meiotic defects following Zwint-1 knockdown were similar to those observed with ZM447439 treatment. Importantly, the chromosome misalignment following Aurora C kinase inhibition was not restored after removing the inhibitor in Zwint-1-knockdown oocytes, whereas the defect was rescued after the inhibitor washout in the control oocytes. These results suggest that Aurora C kinase-mediated correction of erroneous kinetochore-microtubule attachment is primarily regulated by Zwint-1. Our results provide the first evidence that Zwint-1 is required to correct erroneous kinetochore-microtubule attachment and regulate spindle checkpoint function during meiosis.

Accuracy of Spindle Units with Hydrostatic Bearings

Directory of Open Access Journals (Sweden)

Fedorynenko Dmytro

2016-06-01

Full Text Available The work is devoted to the research of precision regularities in a spindle unit by the trajectory of the spindle installed on hydrostatic bearings. The mathematical model of trajectories spindle with lumped parameters that allows to define the position of the spindle with regard the simultaneous influence of design parameters, geometrical deviations ofform, temperature deformation bearing surfaces, the random nature of operational parameters and technical loads of hydrostatic bearings has been developed. Based on the results of numerical modeling the influence of shape errors of bearing surface of hydrostatic bearing on the statistical characteristics of the radius vector trajectories of the spindle by varying the values rotational speed of the spindle and oil pressure in front hydrostatic bearing has been developed. The obtained statistical regularities of precision spindle unit have been confirmed experimentally. It has been shown that an effective way to increase the precision of spindle units is to regulate the size of the gap in hydrostatic spindle bearings. The new design of an adjustable hydrostatic bearing, which can improve the accuracy of regulation size gap has been proposed.

Cenp-meta is required for sustained spindle checkpoint

Directory of Open Access Journals (Sweden)

Thomas Rubin

2014-05-01

Full Text Available Cenp-E is a kinesin-like motor protein required for efficient end-on attachment of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus mitotic extracts results in the loss of mitotic arrest and massive chromosome missegregation, whereas its depletion in mammalian cells leads to chromosome segregation defects despite the presence of a functional spindle assembly checkpoint (SAC. Cenp-meta has previously been reported to be the Drosophila homolog of vertebrate Cenp-E. In this study, we show that cenp-metaΔ mutant neuroblasts arrest in mitosis when treated with colchicine. cenp-metaΔ mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that cenp-metaΔ mutant cells display a slow but continuous degradation of cyclin B, which eventually triggers the mitotic exit observed. Thus, our data provide evidence for a role of Cenp-meta in sustaining the SAC response.

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

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.

Mechanical design principles of a mitotic spindle.

Science.gov (United States)

Ward, Jonathan J; Roque, Hélio; Antony, Claude; Nédélec, François

2014-12-18

An organised spindle is crucial to the fidelity of chromosome segregation, but the relationship between spindle structure and function is not well understood in any cell type. The anaphase B spindle in fission yeast has a slender morphology and must elongate against compressive forces. This 'pushing' mode of chromosome transport renders the spindle susceptible to breakage, as observed in cells with a variety of defects. Here we perform electron tomographic analyses of the spindle, which suggest that it organises a limited supply of structural components to increase its compressive strength. Structural integrity is maintained throughout the spindle's fourfold elongation by organising microtubules into a rigid transverse array, preserving correct microtubule number and dynamically rescaling microtubule length.

Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

Science.gov (United States)

Brunetti, Orazio; Della Torre, Giovannella; Lucchi, Maria Luisa; Chiocchetti, Roberto; Bortolami, Ruggero; Pettorossi, Vito Enrico

2003-09-01

The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through

Analysis of coolant flow in central tube of WWER-440 fuel assemblies

International Nuclear Information System (INIS)

Zsiros, G.; Toth, S.; Attila Aszodi, A.

2011-01-01

Three dimensional computational fluid dynamics model has been built to investigate the coolant flow in the central tube of the WWER-440 fuel assemblies. The model was verified based on measured data of the Kurchatov Institute. With the model calculations were performed for two fuel assemblies used in PAKS NPP. One of them has symmetrical and another has inclined pin power profile. Ratios of the outlet mass fluxes of the central tube to the inlet mass fluxes of the rod bundle were determined. Heat up ratios of the tube and rod bundle flows were calculated too. Sensitivity of the results on the assembly power distribution, inlet temperature and mass flow rate was investigated. The results of these simulations can be used as boundary conditions of central tube in studies of coolant mixing in fuel assembly heads. (Authors)

The Spindle Cell Neoplasms of the Oral Cavity.

Science.gov (United States)

Shamim, Thorakkal

2015-01-01

Spindle cell neoplasms are defined as neoplasms that consist of spindle-shaped cells in the histopathology. Spindle cell neoplasms can affect the oral cavity. In the oral cavity, the origin of the spindle cell neoplasms may be traced to epithelial, mesenchymal and odontogenic components. This article aims to review the spindle cell neoplasms of the oral cavity with emphasis on histopathology.

PLK1 regulates spindle formation kinetics and APC/C activation in mouse zygote

Czech Academy of Sciences Publication Activity Database

Baran, V.; Brzáková, Adéla; Rehák, P.; Kovaříková, V.; Šolc, Petr

2016-01-01

Roč. 24, č. 3 (2016), s. 338-345 ISSN 0967-1994 R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk LH12057 Institutional support: RVO:67985904 Keywords : APC/C * BI2536 * live cell imaging * mouse zygote * PLK1 * securin * spindle assembly Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.053, year: 2016

Sleep Spindles in the Right Hemisphere Support Awareness of Regularities and Reflect Pre-Sleep Activations.

Science.gov (United States)

Yordanova, Juliana; Kolev, Vasil; Bruns, Eike; Kirov, Roumen; Verleger, Rolf

2017-11-01

The present study explored the sleep mechanisms which may support awareness of hidden regularities. Before sleep, 53 participants learned implicitly a lateralized variant of the serial response-time task in order to localize sensorimotor encoding either in the left or right hemisphere and induce implicit regularity representations. Electroencephalographic (EEG) activity was recorded at multiple electrodes during both task performance and sleep, searching for lateralized traces of the preceding activity during learning. Sleep EEG analysis focused on region-specific slow (9-12 Hz) and fast (13-16 Hz) sleep spindles during nonrapid eye movement sleep. Fast spindle activity at those motor regions that were activated during learning increased with the amount of postsleep awareness. Independently of side of learning, spindle activity at right frontal and fronto-central regions was involved: there, fast spindles increased with the transformation of sequence knowledge from implicit before sleep to explicit after sleep, and slow spindles correlated with individual abilities of gaining awareness. These local modulations of sleep spindles corresponded to regions with greater presleep activation in participants with postsleep explicit knowledge. Sleep spindle mechanisms are related to explicit awareness (1) by tracing the activation of motor cortical and right-hemisphere regions which had stronger involvement already during learning and (2) by recruitment of individually consolidated processing modules in the right hemisphere. The integration of different sleep spindle mechanisms with functional states during wake collectively supports the gain of awareness of previously experienced regularities, with a special role for the right hemisphere. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

Directory of Open Access Journals (Sweden)

Veronica eKrenn

2015-10-01

Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity.

Science.gov (United States)

Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo; Schou, Julie; Nilsson, Jakob; Choudhary, Chunaram

2016-03-01

The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Relations between ultrastructure of mitotic spindle and chromosome translocation

Directory of Open Access Journals (Sweden)

Jadwiga A. Tarkowska

2014-01-01

Full Text Available Dividing endosperm cells of Haemanthus katherinae Bak. treated with an 0.25 per cent mixture of water-soluble glycosides from Nerium oleander were insepected in a light microscope (LM and severe disturbances were found in all phases of mitosis. The same cells were observed in the electron microscope (EM and relations were noted and analysed between the chromosome arrangement and the submicroscopic structure of the mitotuc spindle. The successive steps in the disintegration of the formed spindle are described: fragmentatiun of all microtubules (MTs starting from the poles, disappearance of non-kinetachore MTs and further the external MTs of the kineto,chore bundle. The central (internal parallel ones remain the longest at the kinerf,ochares. Oleander glycosides cause disintegration of the existing MTs and prevent formation of new ones. The causes of restitution transformations in the successive phases of mitosis are discussed.

A defect-driven diagnostic method for machine tool spindles.

Science.gov (United States)

Vogl, Gregory W; Donmez, M Alkan

2015-01-01

Simple vibration-based metrics are, in many cases, insufficient to diagnose machine tool spindle condition. These metrics couple defect-based motion with spindle dynamics; diagnostics should be defect-driven. A new method and spindle condition estimation device (SCED) were developed to acquire data and to separate system dynamics from defect geometry. Based on this method, a spindle condition metric relying only on defect geometry is proposed. Application of the SCED on various milling and turning spindles shows that the new approach is robust for diagnosing the machine tool spindle condition.

Measuring and modeling polymer concentration profiles near spindle boundaries argues that spindle microtubules regulate their own nucleation

Science.gov (United States)

Kaye, Bryan; Stiehl, Olivia; Foster, Peter J.; Shelley, Michael J.; Needleman, Daniel J.; Fürthauer, Sebastian

2018-05-01

Spindles are self-organized microtubule-based structures that segregate chromosomes during cell division. The mass of the spindle is controlled by the balance between microtubule turnover and nucleation. The mechanisms that control the spatial regulation of microtubule nucleation remain poorly understood. While previous work found that microtubule nucleators bind to pre-existing microtubules in the spindle, it is still unclear whether this binding regulates the activity of those nucleators. Here we use a combination of experiments and mathematical modeling to investigate this issue. We measured the concentration of microtubules and soluble tubulin in and around the spindle. We found a very sharp decay in the concentration of microtubules at the spindle interface. This is inconsistent with a model in which the activity of nucleators is independent of their association with microtubules but consistent with a model in which microtubule nucleators are only active when bound to pre-existing microtubules. This argues that the activity of microtubule nucleators is greatly enhanced when bound to pre-existing microtubules. Thus, microtubule nucleators are both localized and activated by the microtubules they generate.

Analytical modeling for thermal errors of motorized spindle unit

OpenAIRE

Liu, Teng; Gao, Weiguo; Zhang, Dawei; Zhang, Yifan; Chang, Wenfen; Liang, Cunman; Tian, Yanling

2017-01-01

Modeling method investigation about spindle thermal errors is significant for spindle thermal optimization in design phase. To accurately analyze the thermal errors of motorized spindle unit, this paper assumes approximately that 1) spindle linear thermal error on axial direction is ascribed to shaft thermal elongation for its heat transfer from bearings, and 2) spindle linear thermal errors on radial directions and angular thermal errors are attributed to thermal variations of bearing relati...

Valve assembly having remotely replaceable bearings

International Nuclear Information System (INIS)

Johnson, E.R.; Tanner, D.E.

1980-01-01

A valve assembly having remotely replaceable bearings is disclosed wherein a valve disc is supported within a flow duct for rotation about a pair of axially aligned bearings, one of which is carried by a spindle received within a diametral bore in the valve disc, and the other of which is carried by a bearing support block releasably mounted on the duct circumferentially of an annular collar on the valve disc coaxial with its diametrical bore. The spindle and bearing support block are adapted for remote removal to facilitate servicing or replacement of the valve disc support bearings

Mitotic spindle proteomics in Chinese hamster ovary cells.

Directory of Open Access Journals (Sweden)

Mary Kate Bonner

Full Text Available Mitosis is a fundamental process in the development of all organisms. The mitotic spindle guides the cell through mitosis as it mediates the segregation of chromosomes, the orientation of the cleavage furrow, and the progression of cell division. Birth defects and tissue-specific cancers often result from abnormalities in mitotic events. Here, we report a proteomic study of the mitotic spindle from Chinese Hamster Ovary (CHO cells. Four different isolations of metaphase spindles were subjected to Multi-dimensional Protein Identification Technology (MudPIT analysis and tandem mass spectrometry. We identified 1155 proteins and used Gene Ontology (GO analysis to categorize proteins into cellular component groups. We then compared our data to the previously published CHO midbody proteome and identified proteins that are unique to the CHO spindle. Our data represent the first mitotic spindle proteome in CHO cells, which augments the list of mitotic spindle components from mammalian cells.

Method for Vibration Response Simulation and Sensor Placement Optimization of a Machine Tool Spindle System with a Bearing Defect

Science.gov (United States)

Cao, Hongrui; Niu, Linkai; He, Zhengjia

2012-01-01

Bearing defects are one of the most important mechanical sources for vibration and noise generation in machine tool spindles. In this study, an integrated finite element (FE) model is proposed to predict the vibration responses of a spindle bearing system with localized bearing defects and then the sensor placement for better detection of bearing faults is optimized. A nonlinear bearing model is developed based on Jones' bearing theory, while the drawbar, shaft and housing are modeled as Timoshenko's beam. The bearing model is then integrated into the FE model of drawbar/shaft/housing by assembling equations of motion. The Newmark time integration method is used to solve the vibration responses numerically. The FE model of the spindle-bearing system was verified by conducting dynamic tests. Then, the localized bearing defects were modeled and vibration responses generated by the outer ring defect were simulated as an illustration. The optimization scheme of the sensor placement was carried out on the test spindle. The results proved that, the optimal sensor placement depends on the vibration modes under different boundary conditions and the transfer path between the excitation and the response. PMID:23012514

Analysis and topology optimization design of high-speed driving spindle

Science.gov (United States)

Wang, Zhilin; Yang, Hai

2018-04-01

The three-dimensional model of high-speed driving spindle is established by using SOLIDWORKS. The model is imported through the interface of ABAQUS, A finite element analysis model of high-speed driving spindle was established by using spring element to simulate bearing boundary condition. High-speed driving spindle for the static analysis, the spindle of the stress, strain and displacement nephogram, and on the basis of the results of the analysis on spindle for topology optimization, completed the lightweight design of high-speed driving spindle. The design scheme provides guidance for the design of axial parts of similar structures.

Characterization of a putative spindle assembly checkpoint kinase Mps1, suggests its involvement in cell division, morphogenesis and oxidative stress tolerance in Candida albicans.

Directory of Open Access Journals (Sweden)

Mohan Kamthan

Full Text Available In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1 mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1 and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus.

Sme4 coiled-coil protein mediates synaptonemal complex assembly, recombinosome relocalization, and spindle pole body morphogenesis.

Science.gov (United States)

Espagne, Eric; Vasnier, Christelle; Storlazzi, Aurora; Kleckner, Nancy E; Silar, Philippe; Zickler, Denise; Malagnac, Fabienne

2011-06-28

We identify a large coiled-coil protein, Sme4/PaMe4, that is highly conserved among the large group of Sordariales and plays central roles in two temporally and functionally distinct aspects of the fungal sexual cycle: first as a component of the meiotic synaptonemal complex (SC) and then, after disappearing and reappearing, as a component of the spindle pole body (SPB). In both cases, the protein mediates spatial juxtaposition of two major structures: linkage of homolog axes through the SC and a change in the SPB from a planar to a bent conformation. Corresponding mutants exhibit defects, respectively, in SC and SPB morphogenesis, with downstream consequences for recombination and astral-microtubule nucleation plus postmeiotic nuclear migration. Sme4 is also required for reorganization of recombination complexes in which Rad51, Mer3, and Msh4 foci relocalize from an on-axis position to a between-axis (on-SC) position concomitant with SC installation. Because involved recombinosome foci represent total recombinational interactions, these dynamics are irrespective of their designation for maturation into cross-overs or noncross-overs. The defined dual roles for Sme4 in two different structures that function at distinct phases of the sexual cycle also provide more functional links and evolutionary dynamics among the nuclear envelope, SPB, and SC.

Akap350 Recruits Eb1 to The Spindle Poles, Ensuring Proper Spindle Orientation and Lumen Formation in 3d Epithelial Cell Cultures.

Science.gov (United States)

Almada, Evangelina; Tonucci, Facundo M; Hidalgo, Florencia; Ferretti, Anabela; Ibarra, Solange; Pariani, Alejandro; Vena, Rodrigo; Favre, Cristián; Girardini, Javier; Kierbel, Arlinet; Larocca, M Cecilia

2017-11-02

The organization of epithelial cells to form hollow organs with a single lumen requires the accurate three-dimensional arrangement of cell divisions. Mitotic spindle orientation is defined by signaling pathways that provide molecular links between specific spots at the cell cortex and astral microtubules, which have not been fully elucidated. AKAP350 is a centrosomal/Golgi scaffold protein, implicated in the regulation of microtubule dynamics. Using 3D epithelial cell cultures, we found that cells with decreased AKAP350 expression (AKAP350KD) formed polarized cysts with abnormal lumen morphology. Analysis of mitotic cells in AKAP350KD cysts indicated defective spindle alignment. We established that AKAP350 interacts with EB1, a microtubule associated protein that regulates spindle orientation, at the spindle poles. Decrease of AKAP350 expression lead to a significant reduction of EB1 levels at spindle poles and astral microtubules. Conversely, overexpression of EB1 rescued the defective spindle orientation induced by deficient AKAP350 expression. The specific delocalization of the AKAP350/EB1complex from the centrosome decreased EB1 levels at astral microtubules and lead to the formation of 3D-organotypic structures which resembled AKAP350KD cysts. We conclude that AKAP350 recruits EB1 to the spindle poles, ensuring EB1 presence at astral microtubules and proper spindle orientation during epithelial morphogenesis.

Combination spindle-drive system for high precision machining

Science.gov (United States)

Gerth, Howard L.

1977-07-26

A combination spindle-drive is provided for fabrication of optical quality surface finishes. Both the spindle-and-drive utilize the spindle bearings for support, thereby removing the conventional drive-means bearings as a source of vibration. An airbearing spindle is modified to carry at the drive end a highly conductive cup-shaped rotor which is aligned with a stationary stator to produce torque in the cup-shaped rotor through the reaction of eddy currents induced in the rotor. This arrangement eliminates magnetic attraction forces and all force is in the form of torque on the cup-shaped rotor.

Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint

Directory of Open Access Journals (Sweden)

Aisling O'Connor

2016-01-01

Full Text Available During mitotic arrest induced by microtubule targeting drugs, the weakening of the spindle assembly checkpoint (SAC allows cells to progress through the cell cycle without chromosome segregation occurring. PLK1 kinase plays a major role in mitosis and emerging evidence indicates that PLK1 is also involved in establishing the checkpoint and maintaining SAC signalling. However, mechanistically, the role of PLK1 in the SAC is not fully understood, with several recent reports indicating that it can cooperate with either one of the major checkpoint kinases, Aurora B or MPS1. In this study, we assess the role of PLK1 in SAC maintenance. We find that in nocodazole-arrested U2OS cells, PLK1 activity is continuously required for maintaining Aurora B protein localisation and activity at kinetochores. Consistent with published data we find that upon PLK1 inhibition, phosphoThr3-H3, a marker of Haspin activity, is reduced. Intriguingly, Aurora B inhibition causes PLK1 to relocalise from kinetochores into fewer and much larger foci, possibly due to incomplete recruitment of outer kinetochore proteins. Importantly, PLK1 inhibition, together with partial inhibition of Aurora B, allows efficient SAC override to occur. This phenotype is more pronounced than the phenotype observed by combining the same PLK1 inhibitors with partial MPS1 inhibition. We also find that PLK1 inhibition does not obviously cooperate with Haspin inhibition to promote SAC override. These results indicate that PLK1 is directly involved in maintaining efficient SAC signalling, possibly by cooperating in a positive feedback loop with Aurora B, and that partially redundant mechanisms exist which reinforce the SAC.

Sleep spindles predict stress-related increases in sleep disturbances

Directory of Open Access Journals (Sweden)

Thien Thanh eDang-Vu

2015-02-01

Full Text Available Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. Methods: 12 healthy students had a polysomnography (PSG recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the Insomnia Severity Index (ISI. They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration and frequency, as well as sigma power were computed from C4-O2 electroencephalography (EEG derivation during stages N2-N3 of non-rapid-eye-movement (NREM sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester.Results: Spindle density (as well as spindle amplitude and sigma power, particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05. Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

Monitoring Method of Cutting Force by Using Additional Spindle Sensors

Science.gov (United States)

Sarhan, Ahmed Aly Diaa; Matsubara, Atsushi; Sugihara, Motoyuki; Saraie, Hidenori; Ibaraki, Soichi; Kakino, Yoshiaki

This paper describes a monitoring method of cutting forces for end milling process by using displacement sensors. Four eddy-current displacement sensors are installed on the spindle housing of a machining center so that they can detect the radial motion of the rotating spindle. Thermocouples are also attached to the spindle structure in order to examine the thermal effect in the displacement sensing. The change in the spindle stiffness due to the spindle temperature and the speed is investigated as well. Finally, the estimation performance of cutting forces using the spindle displacement sensors is experimentally investigated by machining tests on carbon steel in end milling operations under different cutting conditions. It is found that the monitoring errors are attributable to the thermal displacement of the spindle, the time lag of the sensing system, and the modeling error of the spindle stiffness. It is also shown that the root mean square errors between estimated and measured amplitudes of cutting forces are reduced to be less than 20N with proper selection of the linear stiffness.

Optimal design of high-speed loading spindle based on ABAQUS

Science.gov (United States)

Yang, Xudong; Dong, Yu; Ge, Qingkuan; Yang, Hai

2017-12-01

The three-dimensional model of high-speed loading spindle is established by using ABAQUS’s modeling module. A finite element analysis model of high-speed loading spindle was established by using spring element to simulate bearing boundary condition. The static and dynamic performance of the spindle structure with different specifications of the rectangular spline and the different diameter neck of axle are studied in depth, and the influence of different spindle span on the static and dynamic performance of the high-speed loading spindle is studied. Finally, the optimal structure of the high-speed loading spindle is obtained. The results provide a theoretical basis for improving the overall performance of the test-bed

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

Spatial signals link exit from mitosis to spindle position.

Science.gov (United States)

Falk, Jill Elaine; Tsuchiya, Dai; Verdaasdonk, Jolien; Lacefield, Soni; Bloom, Kerry; Amon, Angelika

2016-05-11

In budding yeast, if the spindle becomes mispositioned, cells prevent exit from mitosis by inhibiting the mitotic exit network (MEN). The MEN is a signaling cascade that localizes to spindle pole bodies (SPBs) and activates the phosphatase Cdc14. There are two competing models that explain MEN regulation by spindle position. In the 'zone model', exit from mitosis occurs when a MEN-bearing SPB enters the bud. The 'cMT-bud neck model' posits that cytoplasmic microtubule (cMT)-bud neck interactions prevent MEN activity. Here we find that 1) eliminating cMT- bud neck interactions does not trigger exit from mitosis and 2) loss of these interactions does not precede Cdc14 activation. Furthermore, using binucleate cells, we show that exit from mitosis occurs when one SPB enters the bud despite the presence of a mispositioned spindle. We conclude that exit from mitosis is triggered by a correctly positioned spindle rather than inhibited by improper spindle position.

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning.

Science.gov (United States)

Howard, Jonathon; Garzon-Coral, Carlos

2017-11-01

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against- the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. © 2017 The Authors. BioEssays published by Wiley Periodicals, Inc.

Inter-expert and intra-expert reliability in sleep spindle scoring

DEFF Research Database (Denmark)

Wendt, Sabrina Lyngbye; Welinder, Peter; Sørensen, Helge Bjarup Dissing

2015-01-01

Objectives To measure the inter-expert and intra-expert agreement in sleep spindle scoring, and to quantify how many experts are needed to build a reliable dataset of sleep spindle scorings. Methods The EEG dataset was comprised of 400 randomly selected 115 s segments of stage 2 sleep from 110...... with higher reliability than the estimation of spindle duration. Reliability of sleep spindle scoring can be improved by using qualitative confidence scores, rather than a dichotomous yes/no scoring system. Conclusions We estimate that 2–3 experts are needed to build a spindle scoring dataset...... with ‘substantial’ reliability (κ: 0.61–0.8), and 4 or more experts are needed to build a dataset with ‘almost perfect’ reliability (κ: 0.81–1). Significance Spindle scoring is a critical part of sleep staging, and spindles are believed to play an important role in development, aging, and diseases of the nervous...

Fission yeast cells undergo nuclear division in the absence of spindle microtubules.

Directory of Open Access Journals (Sweden)

Stefania Castagnetti

2010-10-01

Full Text Available Mitosis in eukaryotic cells employs spindle microtubules to drive accurate chromosome segregation at cell division. Cells lacking spindle microtubules arrest in mitosis due to a spindle checkpoint that delays mitotic progression until all chromosomes have achieved stable bipolar attachment to spindle microtubules. In fission yeast, mitosis occurs within an intact nuclear membrane with the mitotic spindle elongating between the spindle pole bodies. We show here that in fission yeast interference with mitotic spindle formation delays mitosis only briefly and cells proceed to an unusual nuclear division process we term nuclear fission, during which cells perform some chromosome segregation and efficiently enter S-phase of the next cell cycle. Nuclear fission is blocked if spindle pole body maturation or sister chromatid separation cannot take place or if actin polymerization is inhibited. We suggest that this process exhibits vestiges of a primitive nuclear division process independent of spindle microtubules, possibly reflecting an evolutionary intermediate state between bacterial and Archeal chromosome segregation where the nucleoid divides without a spindle and a microtubule spindle-based eukaryotic mitosis.

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

Directory of Open Access Journals (Sweden)

William T Silkworth

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

Dynamic Parameter Identification of Tool-Spindle Interface Based on RCSA and Particle Swarm Optimization

Directory of Open Access Journals (Sweden)

Erhua Wang

2013-01-01

Full Text Available In order to ensure the stability of machining processes, the tool point frequency response functions (FRFs should be obtained initially. By the receptance coupling substructure analysis (RCSA, the tool point FRFs can be generated quickly for any combination of holder and tool without the need of repeated measurements. A major difficulty in the sub-structuring analysis is to determine the connection parameters at the tool-holder interface. This study proposed an identification method to recognize the connection parameters at the tool-holder interface by using RCSA and particle swarm optimization (PSO. In this paper, the XHK machining center is divided into two components, which are the tool and the spindle assembly firstly. After that, the end point FRFs of the tool are achieved by mode superposition method. The end receptances of the spindle assembly with complicated structure are obtained by impacting test method. Through translational and rotational springs and dampers, the tool point FRF of the machining center is obtained by coupling the two components. Finally, PSO is adopted to identify the connection parameters at the tool-holder interface by minimizing the difference between the predicted and the measured tool point FRFs. Comparison results between the predicted and measured tool point FRFs show a good agreement and demonstrate that the identification method is valid in the identification of connection parameters at the tool-holder interface.

The fission yeast spindle orientation checkpoint: a model that generates tension?

Science.gov (United States)

Gachet, Yannick; Reyes, Céline; Goldstone, Sherilyn; Tournier, Sylvie

2006-10-15

In all eukaryotes, the alignment of the mitotic spindle with the axis of cell polarity is essential for accurate chromosome segregation as well as for the establishment of cell fate, and thus morphogenesis, during development. Studies in invertebrates, higher eukaryotes and yeast suggest that astral microtubules interact with the cell cortex to position the spindle. These microtubules are thought to impose pushing or pulling forces on the spindle poles to affect the rotation or movement of the spindle. In the fission yeast model, where cell division is symmetrical, spindle rotation is dependent on the interaction of astral microtubules with the cortical actin cytoskeleton. In these cells, a bub1-dependent mitotic checkpoint, the spindle orientation checkpoint (SOC), is activated when the spindles fail to align with the cell polarity axis. In this paper we review the mechanism that orientates the spindle during mitosis in fission yeast, and discuss the consequences of misorientation on metaphase progression. Copyright 2006 John Wiley & Sons, Ltd.

Measurement of Spindle Rigidity by using a Magnet Loader

Science.gov (United States)

Yamazaki, Taku; Matsubara, Atsushi; Fujita, Tomoya; Muraki, Toshiyuki; Asano, Kohei; Kawashima, Kazuyuki

The static rigidity of a rotating spindle in the radial direction is investigated in this research. A magnetic loading device (magnet loader) has been developed for the measurement. The magnet loader, which has coils and iron cores, generates the electromagnetic force and attracts a dummy tool attached to the spindle. However, the eddy current is generated in the dummy tool with the spindle rotation and reduces the attractive force at high spindle speed. In order to understand the magnetic flux and eddy current in the dummy tool, the electromagnetic field analysis by FEM was carried out. Grooves on the attraction surface of the dummy tool were designed to cut the eddy current flow. The dimension of the groove were decided based on the FEM analysis, and the designed tool were manufactured and tested. The test result shows that the designed tool successfully reduces the eddy current and recovers the attractive force. By using the magnet loader and the grooved tool, the spindle rigidity can be measured when the spindle rotates with a speed up to 10,000 min-1.

Developmental Changes in Sleep Spindle Characteristics and Sigma Power across Early Childhood

Directory of Open Access Journals (Sweden)

Ian J. McClain

2016-01-01

Full Text Available Sleep spindles, a prominent feature of the non-rapid eye movement (NREM sleep electroencephalogram (EEG, are linked to cognitive abilities. Early childhood is a time of rapid cognitive and neurophysiological maturation; however, little is known about developmental changes in sleep spindles. In this study, we longitudinally examined trajectories of multiple sleep spindle characteristics (i.e., spindle duration, frequency, integrated spindle amplitude, and density and power in the sigma frequency range (10–16 Hz across ages 2, 3, and 5 years (n=8; 3 males. At each time point, nocturnal sleep EEG was recorded in-home after 13-h of prior wakefulness. Spindle duration, integrated spindle amplitude, and sigma power increased with age across all EEG derivations (C3A2, C4A1, O2A1, and O1A2; all ps < 0.05. We also found a developmental decrease in mean spindle frequency (p<0.05 but no change in spindle density with increasing age. Thus, sleep spindles increased in duration and amplitude but decreased in frequency across early childhood. Our data characterize early developmental changes in sleep spindles, which may advance understanding of thalamocortical brain connectivity and associated lifelong disease processes. These findings also provide unique insights into spindle ontogenesis in early childhood and may help identify electrophysiological features related to healthy and aberrant brain maturation.

Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells.

Science.gov (United States)

Taniguchi, Kiichiro; Kokuryo, Akihiko; Imano, Takao; Minami, Ryunosuke; Nakagoshi, Hideki; Adachi-Yamada, Takashi

2014-12-20

In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform Mud(PBD) and the two newly characterized isoforms Mud(L) and Mud(S) regulated them differently: Mud(L) repressed cell rounding, Mud(PBD) and Mud(S) oriented the spindle along the apico-basal axis, and Mud(S) and Mud(L) repressed central spindle assembly. Importantly, overexpression of Mud(S) induced binucleation even in standard proliferating cells such as those in imaginal discs. We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate

Free Vibration Analysis of a Spinning Flexible DISK-SPINDLE System Supported by Ball Bearing and Flexible Shaft Using the Finite Element Method and Substructure Synthesis

Science.gov (United States)

JANG, G. H.; LEE, S. H.; JUNG, M. S.

2002-03-01

Free vibration of a spinning flexible disk-spindle system supported by ball bearing and flexible shaft is analyzed by using Hamilton's principle, FEM and substructure synthesis. The spinning disk is described by using the Kirchhoff plate theory and von Karman non-linear strain. The rotating spindle and stationary shaft are modelled by Rayleigh beam and Euler beam respectively. Using Hamilton's principle and including the rigid body translation and tilting motion, partial differential equations of motion of the spinning flexible disk and spindle are derived consistently to satisfy the geometric compatibility in the internal boundary between substructures. FEM is used to discretize the derived governing equations, and substructure synthesis is introduced to assemble each component of the disk-spindle-bearing-shaft system. The developed method is applied to the spindle system of a computer hard disk drive with three disks, and modal testing is performed to verify the simulation results. The simulation result agrees very well with the experimental one. This research investigates critical design parameters in an HDD spindle system, i.e., the non-linearity of a spinning disk and the flexibility and boundary condition of a stationary shaft, to predict the free vibration characteristics accurately. The proposed method may be effectively applied to predict the vibration characteristics of a spinning flexible disk-spindle system supported by ball bearing and flexible shaft in the various forms of computer storage device, i.e., FDD, CD, HDD and DVD.

Spinal spindle cell haemangioma: an atypical location.

Science.gov (United States)

Talan-Hranilović, J; Vucić, M; Sajko, T; Bedek, D; Tomić, K; Lupret, V

2007-03-01

We present a case of the 31-year-old male patient who complained of weakness in both legs and progressed slowly. Neuroimagine of the thoracic spine showed an intraspinal, extradural mass lesion, measuring 5.3 x 1.2 cm at the Th1-Th3 level. Histologically the lesion was a spindle cell haemangioma composed of dilated vascular spaces and a proliferation of bland appearing interspersed spindle cells. Immunohistochemical analysis was diffusely positive for VIM, SMA and focally for CD34. This lesion is uncommon and shows a predilection for distal extremities. Spindle cell haemangioma within the spine has not been previously reported in the literature.

Local sleep spindle modulations in relation to specific memory cues

NARCIS (Netherlands)

Cox, R.; Hofman, W.F.; de Boer, M.; Talamini, L.M.

2014-01-01

Sleep spindles have been connected to memory processes in various ways. In addition, spindles appear to be modulated at the local cortical network level. We investigated whether cueing specific memories during sleep leads to localized spindle modulations in humans. During learning of word-location

Dual mechanism controls asymmetric spindle position in ascidian germ cell precursors.

Science.gov (United States)

Prodon, François; Chenevert, Janet; Hébras, Céline; Dumollard, Rémi; Faure, Emmanuel; Gonzalez-Garcia, Jose; Nishida, Hiroki; Sardet, Christian; McDougall, Alex

2010-06-01

Mitotic spindle orientation with respect to cortical polarity cues generates molecularly distinct daughter cells during asymmetric cell division (ACD). However, during ACD it remains unknown how the orientation of the mitotic spindle is regulated by cortical polarity cues until furrowing begins. In ascidians, the cortical centrosome-attracting body (CAB) generates three successive unequal cleavages and the asymmetric segregation of 40 localized postplasmic/PEM RNAs in germ cell precursors from the 8-64 cell stage. By combining fast 4D confocal fluorescence imaging with gene-silencing and classical blastomere isolation experiments, we show that spindle repositioning mechanisms are active from prometaphase until anaphase, when furrowing is initiated in B5.2 cells. We show that the vegetal-most spindle pole/centrosome is attracted towards the CAB during prometaphase, causing the spindle to position asymmetrically near the cortex. Next, during anaphase, the opposite spindle pole/centrosome is attracted towards the border with neighbouring B5.1 blastomeres, causing the spindle to rotate (10 degrees /minute) and migrate (3 microm/minute). Dynamic 4D fluorescence imaging of filamentous actin and plasma membrane shows that precise orientation of the cleavage furrow is determined by this second phase of rotational spindle displacement. Furthermore, in pairs of isolated B5.2 blastomeres, the second phase of rotational spindle displacement was lost. Finally, knockdown of PEM1, a protein localized in the CAB and required for unequal cleavage in B5.2 cells, completely randomizes spindle orientation. Together these data show that two separate mechanisms active during mitosis are responsible for spindle positioning, leading to precise orientation of the cleavage furrow during ACD in the cells that give rise to the germ lineage in ascidians.

Modal analysis of spindle of grinder machine based on ANSYS

OpenAIRE

HE Chaocong; LIU Peipei; YAN Chunfei; WANG Muhuan; LIN Jun

2015-01-01

The object of research is to a certain type grinding wheel spindle for which a 3D model of the spindle is established by SolidWorks software and ANSYS software is imported for model analysis.Natural frequency,vibration type and critical speed of the spindle model are obtained and the resulting data are scientifically analyzed.The results show that the spindle structure is reasonable,the machining accuracy can be ensured and the position where the most severe deformation and the main shaft fat...

Sleep spindles and intelligence in early childhood-developmental and trait-dependent aspects.

Science.gov (United States)

Ujma, Péter P; Sándor, Piroska; Szakadát, Sára; Gombos, Ferenc; Bódizs, Róbert

2016-12-01

Sleep spindles act as a powerful marker of individual differences in cognitive ability. Sleep spindle parameters correlate with both age-related changes in cognitive abilities and with the age-independent concept of IQ. While some studies have specifically demonstrated the relationship between sleep spindles and intelligence in young children, our previous work in older subjects revealed sex differences in the sleep spindle correlates of IQ, which was never investigated in small children before. We investigated the relationship between age, Raven Colored Progressive Matrices (CPM) scores and sleep spindles in 28 young children (age 4-8 years, 15 girls). We specifically investigated sex differences in the psychometric correlates of sleep spindles. We also aimed to separate the correlates of sleep spindles that are because of age-related maturation from other effects that reflect an age-independent relationship between sleep spindles and general intelligence. Our results revealed a modest positive correlation between fast spindle amplitude and age. Raven CPM scores positively correlated with both slow and fast spindle amplitude, but this effect remained a tendency in males and vanished after correcting for the effects of age. Age-corrected correlations between Raven CPM scores and both slow and fast spindle amplitude were only significant in females. Overall, our results show that in male children sleep spindles are a maturational marker, but in female children they indicate trait-like intelligence, in line with previous studies in adolescent and adult subjects. Thalamocortical white matter connectivity may be the underlying mechanism behind both higher spindle amplitude and higher intelligence in female, but not male subjects. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Sleep Spindles as an Electrographic Element: Description and Automatic Detection Methods

Directory of Open Access Journals (Sweden)

Dorothée Coppieters ’t Wallant

2016-01-01

Full Text Available Sleep spindle is a peculiar oscillatory brain pattern which has been associated with a number of sleep (isolation from exteroceptive stimuli, memory consolidation and individual characteristics (intellectual quotient. Oddly enough, the definition of a spindle is both incomplete and restrictive. In consequence, there is no consensus about how to detect spindles. Visual scoring is cumbersome and user dependent. To analyze spindle activity in a more robust way, automatic sleep spindle detection methods are essential. Various algorithms were developed, depending on individual research interest, which hampers direct comparisons and meta-analyses. In this review, sleep spindle is first defined physically and topographically. From this general description, we tentatively extract the main characteristics to be detected and analyzed. A nonexhaustive list of automatic spindle detection methods is provided along with a description of their main processing principles. Finally, we propose a technique to assess the detection methods in a robust and comparable way.

Muscle Spindles and Locomotor Control-An Unrecognized Falls Determinant?

OpenAIRE

Marks Ray

2015-01-01

BACKGROUND: Historically, evidence muscle spindles might be involved in locomotion was provided by their presence in tetrapod antigravity muscles associated with posture and locomotion. Later, Brodal (1962) noted muscle spindles in all muscles of locomotion. To unravel the complexity of the muscle spindle and its role in human locomotor control many investigators have since conducted lesion and/or anaesthesia studies in subhuman species and human contexts. QUESTIONS: How ...

Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site

DEFF Research Database (Denmark)

Bolanos-Garcia, Victor M; Lischetti, Tiziana; Matak-Vinković, Dijana

2011-01-01

The maintenance of genomic stability relies on the spindle assembly checkpoint (SAC), which ensures accurate chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bioriented and attached to the mitotic spindle. BUB1 and BUBR1 kinases are central for this proc...

Xenopus laevis Kif18A is a highly processive kinesin required for meiotic spindle integrity

Directory of Open Access Journals (Sweden)

Martin M. Möckel

2017-04-01

Full Text Available The assembly and functionality of the mitotic spindle depends on the coordinated activities of microtubule-associated motor proteins of the dynein and kinesin superfamily. Our current understanding of the function of motor proteins is significantly shaped by studies using Xenopus laevis egg extract as its open structure allows complex experimental manipulations hardly feasible in other model systems. Yet, the Kinesin-8 orthologue of human Kif18A has not been described in Xenopus laevis so far. Here, we report the cloning and characterization of Xenopus laevis (Xl Kif18A. Xenopus Kif18A is expressed during oocyte maturation and its depletion from meiotic egg extract results in severe spindle defects. These defects can be rescued by wild-type Kif18A, but not Kif18A lacking motor activity or the C-terminus. Single-molecule microscopy assays revealed that Xl_Kif18A possesses high processivity, which depends on an additional C-terminal microtubule-binding site. Human tissue culture cells depleted of endogenous Kif18A display mitotic defects, which can be rescued by wild-type, but not tail-less Xl_Kif18A. Thus, Xl_Kif18A is the functional orthologue of human Kif18A whose activity is essential for the correct function of meiotic spindles in Xenopus oocytes.

Thermal Characteristic Analysis and Experimental Study of a Spindle-Bearing System

Directory of Open Access Journals (Sweden)

Li Wu

2016-07-01

Full Text Available In this paper, a thermo-mechanical coupling analysis model of the spindle-bearing system based on Hertz’s contact theory and a point contact non-Newtonian thermal elastohydrodynamic lubrication (EHL theory are developed. In this model, the effect of preload, centrifugal force, the gyroscopic moment, and the lubrication state of the spindle-bearing system are considered. According to the heat transfer theory, the mathematical model for the temperature field of the spindle system is developed and the effect of the spindle cooling system on the spindle temperature distribution is analyzed. The theoretical simulations and the experimental results indicate that the bearing preload has great effect on the frictional heat generation; the cooling fluid has great effect on the heat balance of the spindle system. If a steady-state heat balance between the friction heat generation and the cooling system cannot be reached, thermally-induced preload will lead to a further increase of the frictional heat generation and then cause the thermal failure of the spindle.

Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase.

Science.gov (United States)

Moss, David K; Wilde, Andrew; Lane, Jon D

2009-03-01

During apoptosis, the interphase microtubule network is dismantled then later replaced by a novel, non-centrosomal microtubule array. These microtubules assist in the peripheral redistribution of nuclear fragments in the apoptotic cell; however, the regulation of apoptotic microtubule assembly is not understood. Here, we demonstrate that microtubule assembly depends upon the release of nuclear RanGTP into the apoptotic cytoplasm because this process is blocked in apoptotic cells overexpressing dominant-negative GDP-locked Ran (T24N). Actin-myosin-II contractility provides the impetus for Ran release and, consequently, microtubule assembly is blocked in blebbistatin- and Y27632-treated apoptotic cells. Importantly, the spindle-assembly factor TPX2 (targeting protein for Xklp2), colocalises with apoptotic microtubules, and siRNA silencing of TPX2, but not of the microtubule motors Mklp1 and Kid, abrogates apoptotic microtubule assembly. These data provide a molecular explanation for the assembly of the apoptotic microtubule network, and suggest important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation.

Downregulation of Protein 4.1R impairs centrosome function,bipolar spindle organization and anaphase

Energy Technology Data Exchange (ETDEWEB)

Spence, Jeffrey R.; Go, Minjoung M.; Bahmanyar, S.; Barth,A.I.M.; Krauss, Sharon Wald

2006-03-17

Centrosomes nucleate and organize interphase MTs and areinstrumental in the assembly of the mitotic bipolar spindle. Here wereport that two members of the multifunctional protein 4.1 family havedistinct distributions at centrosomes. Protein 4.1R localizes to maturecentrioles whereas 4.1G is a component of the pericentriolar matrixsurrounding centrioles. To selectively probe 4.1R function, we used RNAinterference-mediated depletion of 4.1R without decreasing 4.1Gexpression. 4.1R downregulation reduces MT anchoring and organization atinterphase and impairs centrosome separation during prometaphase.Metaphase chromosomes fail to properly condense/align and spindleorganization is aberrant. Notably 4.1R depletion causes mislocalizationof its binding partner NuMA (Nuclear Mitotic Apparatus Protein),essential for spindle pole focusing, and disrupts ninein. Duringanaphase/telophase, 4.1R-depleted cells have lagging chromosomes andaberrant MT bridges. Our data provide functional evidence that 4.1R makescrucial contributions to centrosome integrity and to mitotic spindlestructure enabling mitosis and anaphase to proceed with the coordinatedprecision required to avoid pathological events.

Live imaging of spindle pole disorganization in docetaxel-treated multicolor cells

International Nuclear Information System (INIS)

Sakaushi, Shinji; Nishida, Kumi; Minamikawa, Harumi; Fukada, Takashi; Oka, Shigenori; Sugimoto, Kenji

2007-01-01

Treatment of cells with docetaxel at low concentrations induces aberrant bipolar spindles of which two centrosomes stay at only one pole, and also induces multipolar spindles. To gain insight into the relations between centrosome impairment and structural defects of the spindle, live-cell imaging was performed on a human MDA Auro/imp/H3 cell line in which centrosomes/mitotic spindles, nuclear membrane and chromatin were simultaneously visualized by fluorescent proteins. In the presence of docetaxel at IC 50 concentration, the centrosomes did not segregate, and multiple aster-like structures ectopically arose around the disappearing nuclear membrane. Those ectopic structures formed an acentrosomal pole opposing to the two-centrosomes-containing pole. In late metaphase, one pole often fragmented into multiple spindle poles, leading multipolar division. These results suggest that spindle pole fragility may be induced by centrosome impairment, and collapse of the pole may contribute to induction of aneuploid daughter cells

Magnetic suspension motorized spindle-cutting system dynamics analysis and vibration control review

Directory of Open Access Journals (Sweden)

Xiaoli QIAO

2016-10-01

Full Text Available The performance of high-speed spindle directly determines the development of high-end machine tools. The cutting system's dynamic characteristics and vibration control effect are inseparable with the performance of the spindle,which influence each other, synergistic effect together the cutting efficiency, the surface quality of the workpiece and tool life in machining process. So, the review status on magnetic suspension motorized spindle, magnetic suspension bearing-flexible rotor system dynamics modeling theory and status of active control technology of flexible magnetic suspension motorized spindle rotor vibration are studied, and the problems which present in the magnetic suspension flexible motorized spindle rotor systems are refined, and the development trend of magnetic levitation motorized spindle and the application prospect is forecasted.

Using Micromanipulation to Analyze Control of Vertebrate Meiotic Spindle Size

Directory of Open Access Journals (Sweden)

Jun Takagi

2013-10-01

Full Text Available The polymerization/depolymerization dynamics of microtubules (MTs have been reported to contribute to control of the size and shape of spindles, but quantitative analysis of how the size and shape correlate with the amount and density of MTs in the spindle remains incomplete. Here, we measured these parameters using 3D microscopy of meiotic spindles that self-organized in Xenopus egg extracts and presented a simple equation describing the relationship among these parameters. To examine the validity of the equation, we cut the spindle into two fragments along the pole-to-pole axis by micromanipulation techniques that rapidly decrease the amount of MTs. The spheroidal shape spontaneously recovered within 5 min, but the size of each fragment remained small. The equation we obtained quantitatively describes how the spindle size correlates with the amount of MTs while maintaining the shape and the MT density.

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.

Modal analysis of spindle of grinder machine based on ANSYS

Directory of Open Access Journals (Sweden)

HE Chaocong

2015-10-01

Full Text Available The object of research is to a certain type grinding wheel spindle for which a 3D model of the spindle is established by SolidWorks software and ANSYS software is imported for model analysis.Natural frequency,vibration type and critical speed of the spindle model are obtained and the resulting data are scientifically analyzed.The results show that the spindle structure is reasonable,the machining accuracy can be ensured and the position where the most severe deformation and the main shaft fatigue fracture may occur can be found out,which also provide the theoretical basis for further optimization design and precision control.

Parietal Fast Sleep Spindle Density Decrease in Alzheimer's Disease and Amnesic Mild Cognitive Impairment

Science.gov (United States)

Gorgoni, Maurizio; Lauri, Giulia; Truglia, Ilaria; Cordone, Susanna; Sarasso, Simone; Scarpelli, Serena; Mangiaruga, Anastasia; D'Atri, Aurora; Tempesta, Daniela; Ferrara, Michele; Marra, Camillo; Rossini, Paolo Maria; De Gennaro, Luigi

2016-01-01

Several studies have identified two types of sleep spindles: fast (13–15 Hz) centroparietal and slow (11–13 Hz) frontal spindles. Alterations in spindle activity have been observed in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). Only few studies have separately assessed fast and slow spindles in these patients showing a reduction of fast spindle count, but the possible local specificity of this phenomenon and its relation to cognitive decline severity are not clear. Moreover, fast and slow spindle density have never been assessed in AD/MCI. We have assessed fast and slow spindles in 15 AD patients, 15 amnesic MCI patients, and 15 healthy elderly controls (HC). Participants underwent baseline polysomnographic recording (19 cortical derivations). Spindles during nonrapid eye movements sleep were automatically detected, and spindle densities of the three groups were compared in the derivations where fast and slow spindles exhibited their maximum expression (parietal and frontal, resp.). AD and MCI patients showed a significant parietal fast spindle density decrease, positively correlated with Minimental State Examination scores. Our results suggest that AD-related changes in spindle density are specific for frequency and location, are related to cognitive decline severity, and may have an early onset in the pathology development. PMID:27066274

Hybrid Prediction Model of the Temperature Field of a Motorized Spindle

Directory of Open Access Journals (Sweden)

Lixiu Zhang

2017-10-01

Full Text Available The thermal characteristics of a motorized spindle are the main determinants of its performance, and influence the machining accuracy of computer numerical control machine tools. It is important to accurately predict the thermal field of a motorized spindle during its operation to improve its thermal characteristics. This paper proposes a model to predict the temperature field of a high-speed and high-precision motorized spindle under different working conditions using a finite element model and test data. The finite element model considers the influence of the parameters of the cooling system and the lubrication system, and that of environmental conditions on the coefficient of heat transfer based on test data for the surface temperature of the motorized spindle. A genetic algorithm is used to optimize the coefficient of heat transfer of the spindle, and its temperature field is predicted using a three-dimensional model that employs this optimal coefficient. A prediction model of the 170MD30 temperature field of the motorized spindle is created and simulation data for the temperature field are compared with the test data. The results show that when the speed of the spindle is 10,000 rpm, the relative mean prediction error is 1.5%, and when its speed is 15,000 rpm, the prediction error is 3.6%. Therefore, the proposed prediction model can predict the temperature field of the motorized spindle with high accuracy.

Characteristics of motorized spindle supported by active magnetic bearings

Directory of Open Access Journals (Sweden)

Xie Zhenyu

2014-12-01

Full Text Available A motorized spindle supported by active magnetic bearings (AMBs is generally used for ultra-high-speed machining. Iron loss of radial AMB is very great owing to high rotation speed, and it will cause severe thermal deformation. The problem is particularly serious on the occasion of large power application, such as all electric aero-engine. In this study, a prototype motorized spindle supported by five degree-of-freedom AMBs is developed. Homopolar and heteropolar AMBs are independently adopted as radial bearings. The influences of the two types of radial AMBs on the dynamic characteristics of the motorized spindle are comparatively investigated by theoretical analysis, test modal analysis and actual operation of the system. The iron loss of the two types of radial AMBs is analyzed by finite element software and verified through run-down experiments of the system. The results show that the structures of AMB have less influence on the dynamic characteristics of the motorized spindle. However, the homopolar structure can effectively reduce the iron loss of the radial AMB and it is useful for improving the overall performance of the motorized spindle.

Dynamics Analysis of Unbalanced Motorized Spindles Supported on Ball Bearings

Directory of Open Access Journals (Sweden)

Junfeng Liu

2016-01-01

Full Text Available This paper presents an improved dynamic model for unbalanced high speed motorized spindles. The proposed model includes a Hertz contact force model which takes into the internal clearance and an unbalanced electromagnetic force model based on the energy of the air magnetic field. The nonlinear characteristic of the model is analysed by Lyapunov stability theory and numerical analysis to study the dynamic properties of the spindle system. Finally, a dynamic operating test is carried out on a DX100A-24000/20-type motorized spindle. The good agreement between the numerical solutions and the experimental data indicates that the proposed model is capable of accurately predicting the dynamic properties of motorized spindles. The influence of the unbalanced magnetic force on the system is studied, and the sensitivities of the system parameters to the critical speed of the system are obtained. These conclusions are useful for the dynamic design of high speed motorized spindles.

Noninvasive three-dimensional live imaging methodology for the spindles at meiosis and mitosis

Science.gov (United States)

Zheng, Jing-gao; Huo, Tiancheng; Tian, Ning; Chen, Tianyuan; Wang, Chengming; Zhang, Ning; Zhao, Fengying; Lu, Danyu; Chen, Dieyan; Ma, Wanyun; Sun, Jia-lin; Xue, Ping

2013-05-01

The spindle plays a crucial role in normal chromosome alignment and segregation during meiosis and mitosis. Studying spindles in living cells noninvasively is of great value in assisted reproduction technology (ART). Here, we present a novel spindle imaging methodology, full-field optical coherence tomography (FF-OCT). Without any dye labeling and fixation, we demonstrate the first successful application of FF-OCT to noninvasive three-dimensional (3-D) live imaging of the meiotic spindles within the mouse living oocytes at metaphase II as well as the mitotic spindles in the living zygotes at metaphase and telophase. By post-processing of the 3-D dataset obtained with FF-OCT, the important morphological and spatial parameters of the spindles, such as short and long axes, spatial localization, and the angle of meiotic spindle deviation from the first polar body in the oocyte were precisely measured with the spatial resolution of 0.7 μm. Our results reveal the potential of FF-OCT as an imaging tool capable of noninvasive 3-D live morphological analysis for spindles, which might be useful to ART related procedures and many other spindle related studies.

TFG-MET fusion in an infantile spindle cell sarcoma with neural features

NARCIS (Netherlands)

Flucke, U.E.; Noesel, M.M. van; Wijnen, M.; Zhang, L.; Chen, C.L.; Sung, Y.S.; Antonescu, C.R.

2017-01-01

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell

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

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.

Fast and slow spindles during the sleep slow oscillation: disparate coalescence and engagement in memory processing.

Science.gov (United States)

Mölle, Matthias; Bergmann, Til O; Marshall, Lisa; Born, Jan

2011-10-01

Thalamo-cortical spindles driven by the up-state of neocortical slow (memory consolidation during sleep. We examined interactions between SOs and spindles in human slow wave sleep, focusing on the presumed existence of 2 kinds of spindles, i.e., slow frontocortical and fast centro-parietal spindles. Two experiments were performed in healthy humans (24.5 ± 0.9 y) investigating undisturbed sleep (Experiment I) and the effects of prior learning (word paired associates) vs. non-learning (Experiment II) on multichannel EEG recordings during sleep. Only fast spindles (12-15 Hz) were synchronized to the depolarizing SO up-state. Slow spindles (9-12 Hz) occurred preferentially at the transition into the SO down-state, i.e., during waning depolarization. Slow spindles also revealed a higher probability to follow rather than precede fast spindles. For sequences of individual SOs, fast spindle activity was largest for "initial" SOs, whereas SO amplitude and slow spindle activity were largest for succeeding SOs. Prior learning enhanced this pattern. The finding that fast and slow spindles occur at different times of the SO cycle points to disparate generating mechanisms for the 2 kinds of spindles. The reported temporal relationships during SO sequences suggest that fast spindles, driven by the SO up-state feed back to enhance the likelihood of succeeding SOs together with slow spindles. By enforcing such SO-spindle cycles, particularly after prior learning, fast spindles possibly play a key role in sleep-dependent memory processing.

Force encoding in muscle spindles during stretch of passive muscle.

Directory of Open Access Journals (Sweden)

Kyle P Blum

2017-09-01

Full Text Available Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle

Force encoding in muscle spindles during stretch of passive muscle.

Science.gov (United States)

Blum, Kyle P; Lamotte D'Incamps, Boris; Zytnicki, Daniel; Ting, Lena H

2017-09-01

Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs) of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt) predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening) of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle lengthening conditions

A New Approach to Spindle Radial Error Evaluation Using a Machine Vision System

Directory of Open Access Journals (Sweden)

Kavitha C.

2017-03-01

Full Text Available The spindle rotational accuracy is one of the important issues in a machine tool which affects the surface topography and dimensional accuracy of a workpiece. This paper presents a machine-vision-based approach to radial error measurement of a lathe spindle using a CMOS camera and a PC-based image processing system. In the present work, a precisely machined cylindrical master is mounted on the spindle as a datum surface and variations of its position are captured using the camera for evaluating runout of the spindle. The Circular Hough Transform (CHT is used to detect variations of the centre position of the master cylinder during spindle rotation at subpixel level from a sequence of images. Radial error values of the spindle are evaluated using the Fourier series analysis of the centre position of the master cylinder calculated with the least squares curve fitting technique. The experiments have been carried out on a lathe at different operating speeds and the spindle radial error estimation results are presented. The proposed method provides a simpler approach to on-machine estimation of the spindle radial error in machine tools.

Automatic Sleep Spindle Detection and Genetic Influence Estimation Using Continuous Wavelet Transform

NARCIS (Netherlands)

Adamczyk, M.; Genzel, L.K.E.; Dresler, M.; Steiger, A.; Friess, E.

2015-01-01

Mounting evidence for the role of sleep spindles in neuroplasticity has led to an increased interest in these non-rapid eye movement (NREM) sleep oscillations. It has been hypothesized that fast and slow spindles might play a different role in memory processing. Here, we present a new sleep spindle

Spindle neurons of the human anterior cingulate cortex

Science.gov (United States)

Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

1995-01-01

The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

Intercentrosomal angular separation during mitosis plays a crucial role for maintaining spindle stability

Science.gov (United States)

Sutradhar, S.; Basu, S.; Paul, R.

2015-10-01

Cell division through proper spindle formation is one of the key puzzles in cell biology. In most mammalian cells, chromosomes spontaneously arrange to achieve a stable bipolar spindle during metaphase which eventually ensures proper segregation of the DNA into the daughter cells. In this paper, we present a robust three-dimensional mechanistic model to investigate the formation and maintenance of a bipolar mitotic spindle in mammalian cells under different physiological constraints. Using realistic parameters, we test spindle viability by measuring the spindle length and studying the chromosomal configuration. The model strikingly predicts a feature of the spindle instability arising from the insufficient intercentrosomal angular separation and impaired sliding of the interpolar microtubules. In addition, our model successfully reproduces chromosomal patterns observed in mammalian cells, when activity of different motor proteins is perturbed.

Relationship between focal penicillin spikes and cortical spindles in the cerveau isolé cat.

Science.gov (United States)

McLachlan, R S; Kaibara, M; Girvin, J P

1983-01-01

Using the unanesthetized, cerveau isolé preparation in the cat, the association between artificially induced penicillin (PCN) spikes and spontaneously occurring electrocorticographic (ECoG) spindles was investigated. Spikes were elicited by surface application of small pledgets of PCN. After the application of PCN, there was a decrease in spindle amplitude but no change in frequency, duration, or spindle wave frequency in the area of the focus. Examination of the times of occurrence of the spikes and spindles disclosed that in the majority of cases, within a few minutes of the initiation of the foci, there was very high simultaneity, usually 100% between the occurrences of these two events. Examination of the times of occurrence of the spikes within the ECoG spindles failed to disclose any compelling evidence which would favor either the hypothesis that spikes "trigger" spindles or the hypothesis that spindles predispose to focal spikes. Thus, whether spikes trigger spindles, or spikes simply occur in a nonspecific manner during the occurrence of the spindle, or whether it is a combination of both these explanations, must remain an open question on the basis of the data available.

Sleep Spindles and Intelligence in Early Childhood--Developmental and Trait-Dependent Aspects

Science.gov (United States)

Ujma, Péter P.; Sándor, Piroska; Szakadát, Sára; Gombos, Ferenc; Bódizs, Róbert

2016-01-01

Sleep spindles act as a powerful marker of individual differences in cognitive ability. Sleep spindle parameters correlate with both age-related changes in cognitive abilities and with the age-independent concept of IQ. While some studies have specifically demonstrated the relationship between sleep spindles and intelligence in young children, our…

Spindle-shaped Microstructures: Potential Models for Planktonic Life Forms on Other Worlds

Science.gov (United States)

Oehler, Dorothy Z.; Walsh, Maud M.; Sugitani, Kenichiro; House, Christopher H.

2014-01-01

Spindle-shaped, organic microstructures ("spindles") are now known from Archean cherts in three localities (Figs. 1-4): The 3 Ga Farrel Quartzite from the Pilbara of Australia [1]; the older, 3.3-3.4 Ga Strelley Pool Formation, also from the Pilbara of Australia [2]; and the 3.4 Ga Kromberg Formation of the Barberton Mountain Land of South Africa [3]. Though the spindles were previously speculated to be pseudofossils or epigenetic organic contaminants, a growing body of data suggests that these structures are bona fide microfossils and further, that they are syngenetic with the Archean cherts in which they occur [1-2, 4-10]. As such, the spindles are among some of the oldest-known organically preserved microfossils on Earth. Moreover, recent delta C-13 study of individual spindles from the Farrel Quartzite (using Secondary Ion Mass Spectrometry [SIMS]) suggests that the spindles may have been planktonic (living in open water), as opposed to benthic (living as bottom dwellers in contact with muds or sediments) [9]. Since most Precambrian microbiotas have been described from benthic, matforming communities, a planktonic lifestyle for the spindles suggests that these structures could represent a segment of the Archean biosphere that is poorly known. Here we synthesize the recent work on the spindles, and we add new observations regarding their geographic distribution, robustness, planktonic habit, and long-lived success. We then discuss their potential evolutionary and astrobiological significance.

Phyllanthus emblica Fruit Extract Activates Spindle Assembly Checkpoint, Prevents Mitotic Aberrations and Genomic Instability in Human Colon Epithelial NCM460 Cells

Directory of Open Access Journals (Sweden)

Xihan Guo

2016-09-01

Full Text Available The fruit of Phyllanthus emblica Linn. (PE has been widely consumed as a functional food and folk medicine in Southeast Asia due to its remarkable nutritional and pharmacological effects. Previous research showed PE delays mitotic progress and increases genomic instability (GIN in human colorectal cancer cells. This study aimed to investigate the similar effects of PE by the biomarkers related to spindle assembly checkpoint (SAC, mitotic aberrations and GIN in human NCM460 normal colon epithelial cells. Cells were treated with PE and harvested differently according to the biomarkers observed. Frequencies of micronuclei (MN, nucleoplasmic bridge (NPB and nuclear bud (NB in cytokinesis-block micronucleus assay were used as indicators of GIN. Mitotic aberrations were assessed by the biomarkers of chromosome misalignment, multipolar division, chromosome lagging and chromatin bridge. SAC activity was determined by anaphase-to- metaphase ratio (AMR and the expression of core SAC gene budding uninhibited by benzimidazoles related 1 (BubR1. Compared with the control, PE-treated cells showed (1 decreased incidences of MN, NPB and NB (p < 0.01; (2 decreased frequencies of all mitotic aberration biomarkers (p < 0.01; and (3 decreased AMR (p < 0.01 and increased BubR1 expression (p < 0.001. The results revealed PE has the potential to protect human normal colon epithelial cells from mitotic and genomic damages partially by enhancing the function of SAC.

Frequency Response Studies using Receptance Coupling Approach in High Speed Spindles

Science.gov (United States)

Shaik, Jakeer Hussain; Ramakotaiah, K.; Srinivas, J.

2018-01-01

In order to assess the stability of high speed machining, estimate the frequency response at the end of tool tip is of great importance. Evaluating dynamic response of several combinations of integrated spindle-tool holder-tool will consume a lot of time. This paper presents coupled field dynamic response at tool tip for the entire integrated spindle tool unit. The spindle unit is assumed to be relying over the front and rear bearings and investigated using the Timoshenko beam theory to arrive the receptances at different locations of the spindle-tool unit. The responses are further validated with conventional finite element model as well as with the experiments. This approach permits quick outputs without losing accuracy of solution and further these methods are utilized to analyze the various design variables on system dynamics. The results obtained through this analysis are needed to design the better spindle unit in an attempt to reduce the frequency amplitudes at the tool tip to improvise the milling stability during cutting process.

Sleep Spindle Detection and Prediction Using a Mixture of Time Series and Chaotic Features

Directory of Open Access Journals (Sweden)

Amin Hekmatmanesh

2017-01-01

Full Text Available It is well established that sleep spindles (bursts of oscillatory brain electrical activity are significant indicators of learning, memory and some disease states. Therefore, many attempts have been made to detect these hallmark patterns automatically. In this pilot investigation, we paid special attention to nonlinear chaotic features of EEG signals (in combination with linear features to investigate the detection and prediction of sleep spindles. These nonlinear features included: Higuchi's, Katz's and Sevcik's Fractal Dimensions, as well as the Largest Lyapunov Exponent and Kolmogorov's Entropy. It was shown that the intensity map of various nonlinear features derived from the constructive interference of spindle signals could improve the detection of the sleep spindles. It was also observed that the prediction of sleep spindles could be facilitated by means of the analysis of these maps. Two well-known classifiers, namely the Multi-Layer Perceptron (MLP and the K-Nearest Neighbor (KNN were used to distinguish between spindle and non-spindle patterns. The MLP classifier produced a~high discriminative capacity (accuracy = 94.93%, sensitivity = 94.31% and specificity = 95.28% with significant robustness (accuracy ranging from 91.33% to 94.93%, sensitivity varying from 91.20% to 94.31%, and specificity extending from 89.79% to 95.28% in separating spindles from non-spindles. This classifier also generated the best results in predicting sleep spindles based on chaotic features. In addition, the MLP was used to find out the best time window for predicting the sleep spindles, with the experimental results reaching 97.96% accuracy.

Characterization of the Spindle Morphology Nanomicelles Assembled from Sericin and Gelatin

Directory of Open Access Journals (Sweden)

Xiaozhou Su

2017-01-01

Full Text Available Complex nanomicelles were prepared by sericin and type A gelatin with molecular weight of 5789 Da and 128664 Da separately. The assembling conditions were as follows: mass ratio (sericin/gelatin was 1 : 1, protein concentration was 0.5%, temperature was 35°C, and assembling time was 18 hours. Scanning electron microscopy (SEM, atomic force microscopy (AFM, transmission electron microscopy (TEM, Fourier transform infrared (FT-IR spectroscopy, differential scanning calorimetry (DSC, and dynamic light scattering (DLS were conducted to observe and characterize the complex nanomicelles. Results showed that the complex sericin/gelatin micelles was a kind of nanospindle micelles. The micelles had high electrochemical stability, thermal stability, antidilution stability, and storage stability.

ITER central solenoid model coil heat treatment complete and assembly started

International Nuclear Information System (INIS)

Thome, R.J.; Okuno, K.

1998-01-01

A major R and D task in the ITER program is to fabricate a Superconducting Model Coil for the Central Solenoid to establish the design and fabrication methods for ITER size coils and to demonstrate conductor performance. Completion of its components is expected in 1998, to be followed by assembly with structural components and testing in a facility at JAERI

Measurement Research of Motorized Spindle Dynamic Stiffness under High Speed Rotating

Directory of Open Access Journals (Sweden)

Xiaopeng Wang

2015-01-01

Full Text Available High speed motorized spindle has become a key functional unit of high speed machine tools and effectively promotes the development of machine tool technology. The development of higher speed and more power puts forward the stricter requirement for the performance of motorized spindle, especially the dynamic performance which affects the machining accuracy, reliability, and production efficiency. To overcome the problems of ineffective loading and dynamic performance measurement of motorized spindle, a noncontact electromagnetic loading device is developed. The cutting load can be simulated by using electromagnetic force. A new method of measuring force by force sensors is presented, and the steady and transient loading force could be measured exactly. After the high speed machine spindle is tested, the frequency response curves of the spindle relative to machine table are collected at 0~12000 rpm; then the relationships between stiffness and speeds as well as between damping ratio and speeds are obtained. The result shows that not only the static and dynamic stiffness but also the damping ratio declined with the increase of speed.

A comparison of two sleep spindle detection methods based on all night averages: individually adjusted versus fixed frequencies

Directory of Open Access Journals (Sweden)

Péter Przemyslaw Ujma

2015-02-01

Full Text Available Sleep spindles are frequently studied for their relationship with state and trait cognitive variables, and they are thought to play an important role in sleep-related memory consolidation. Due to their frequent occurrence in NREM sleep, the detection of sleep spindles is only feasible using automatic algorithms, of which a large number is available. We compared subject averages of the spindle parameters computed by a fixed frequency (11-13 Hz for slow spindles, 13-15 Hz for fast spindles automatic detection algorithm and the individual adjustment method (IAM, which uses individual frequency bands for sleep spindle detection. Fast spindle duration and amplitude are strongly correlated in the two algorithms, but there is little overlap in fast spindle density and slow spindle parameters in general. The agreement between fixed and manually determined sleep spindle frequencies is limited, especially in case of slow spindles. This is the most likely reason for the poor agreement between the two detection methods in case of slow spindle parameters. Our results suggest that while various algorithms may reliably detect fast spindles, a more sophisticated algorithm primed to individual spindle frequencies is necessary for the detection of slow spindles as well as individual variations in the number of spindles in general.

Simplified Dynamic Analysis of Grinders Spindle Node

Science.gov (United States)

Demec, Peter

2014-12-01

The contribution deals with the simplified dynamic analysis of surface grinding machine spindle node. Dynamic analysis is based on the use of the transfer matrix method, which is essentially a matrix form of method of initial parameters. The advantage of the described method, despite the seemingly complex mathematical apparatus, is primarily, that it does not require for solve the problem of costly commercial software using finite element method. All calculations can be made for example in MS Excel, which is advantageous especially in the initial stages of constructing of spindle node for the rapid assessment of the suitability its design. After detailing the entire structure of spindle node is then also necessary to perform the refined dynamic analysis in the environment of FEM, which it requires the necessary skills and experience and it is therefore economically difficult. This work was developed within grant project KEGA No. 023TUKE-4/2012 Creation of a comprehensive educational - teaching material for the article Production technique using a combination of traditional and modern information technology and e-learning.

Material Choice for spindle of machine tools

Science.gov (United States)

Gouasmi, S.; Merzoug, B.; Abba, G.; Kherredine, L.

2012-02-01

The requirements of contemporary industry and the flashing development of modern sciences impose restrictions on the majority of the elements of machines; the resulting financial constraints can be satisfied by a better output of the production equipment. As for those concerning the design, the resistance and the correct operation of the product, these require the development of increasingly precise parts, therefore the use of increasingly powerful tools [5]. The precision of machining and the output of the machine tools are generally determined by the precision of rotation of the spindle, indeed, more this one is large more the dimensions to obtain are in the zone of tolerance and the defects of shape are minimized. During the development of the machine tool, the spindle which by definition is a rotating shaft receiving and transmitting to the work piece or the cutting tool the rotational movement, must be designed according to certain optimal parameters to be able to ensure the precision required. This study will be devoted to the choice of the material of the spindle fulfilling the imposed requirements of precision.

Material Choice for spindle of machine tools

International Nuclear Information System (INIS)

Gouasmi, S; Merzoug, B; Kherredine, L; Abba, G

2012-01-01

The requirements of contemporary industry and the flashing development of modern sciences impose restrictions on the majority of the elements of machines; the resulting financial constraints can be satisfied by a better output of the production equipment. As for those concerning the design, the resistance and the correct operation of the product, these require the development of increasingly precise parts, therefore the use of increasingly powerful tools [5]. The precision of machining and the output of the machine tools are generally determined by the precision of rotation of the spindle, indeed, more this one is large more the dimensions to obtain are in the zone of tolerance and the defects of shape are minimized. During the development of the machine tool, the spindle which by definition is a rotating shaft receiving and transmitting to the work piece or the cutting tool the rotational movement, must be designed according to certain optimal parameters to be able to ensure the precision required. This study will be devoted to the choice of the material of the spindle fulfilling the imposed requirements of precision.

Pituitary spindle cell oncocytoma

Directory of Open Access Journals (Sweden)

Soledad Sosa

2018-01-01

Full Text Available Spindle cell oncocytoma is an infrequent benign non-endocrine sellar neoplasm. Due to its similar morphology to pituitary adenomas, consideration of this differential diagnosis would conduce to a more careful surgical approach in order to avoid intraoperative bleeding and aiming to a complete resection, on which depends long-term outcomes. We present the case of a 60-year-old male who complained about visual abnormalities, with computerized visual field confirmation. On biochemistry, a panhypopituitarism was detected. The brain magnetic resonance images showed a sellar mass. A non-functioning pituitary macroadenoma was presumptively diagnosed and due to the visual impairment, surgical transesphenoidal treatment was indicated. The histological diagnosis was spindle cell oncocytoma. Five months after surgery, the control image demonstrated a lesion that was considered as remnant tumor, hence radiosurgery was performed. During the follow-up, the tumor reduced its size and four years after initial treatment, the sellar resonance imaging showed disappearance of the residual tumor. Communication of new cases of this rare entity will enlarge the existing evidence and will help to determinate the most effective treatment and prognosis.

Proprioceptive Feedback through a Neuromorphic Muscle Spindle Model

Directory of Open Access Journals (Sweden)

Lorenzo Vannucci

2017-06-01

Full Text Available Connecting biologically inspired neural simulations to physical or simulated embodiments can be useful both in robotics, for the development of a new kind of bio-inspired controllers, and in neuroscience, to test detailed brain models in complete action-perception loops. The aim of this work is to develop a fully spike-based, biologically inspired mechanism for the translation of proprioceptive feedback. The translation is achieved by implementing a computational model of neural activity of type Ia and type II afferent fibers of muscle spindles, the primary source of proprioceptive information, which, in mammals is regulated through fusimotor activation and provides necessary adjustments during voluntary muscle contractions. As such, both static and dynamic γ-motoneurons activities are taken into account in the proposed model. Information from the actual proprioceptive sensors (i.e., motor encoders is then used to simulate the spindle contraction and relaxation, and therefore drive the neural activity. To assess the feasibility of this approach, the model is implemented on the NEST spiking neural network simulator and on the SpiNNaker neuromorphic hardware platform and tested on simulated and physical robotic platforms. The results demonstrate that the model can be used in both simulated and real-time robotic applications to translate encoder values into a biologically plausible neural activity. Thus, this model provides a completely spike-based building block, suitable for neuromorphic platforms, that will enable the development of sensory-motor closed loops which could include neural simulations of areas of the central nervous system or of low-level reflexes.

Sleep Spindles as Biomarker for Early Detection of Neurodegenerative Disorders

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to the use of sleep spindles as a novel biomarker for early diagnosis of synucleinopathies, in particular Parkinson's disease (PD). The method is based on automatic detection of sleep spindles. The method may be combined with measurements of one or more further...

Automatic sleep spindle detection: Benchmarking with fine temporal resolution using open science tools

Directory of Open Access Journals (Sweden)

Christian eO'Reilly

2015-06-01

Full Text Available Sleep spindle properties index cognitive faculties such as memory consolidation and diseases such as major depression. For this reason, scoring sleep spindle properties in polysomnographic recordings has become an important activity in both research and clinical settings. The tediousness of this manual task has motivated efforts for its automation. Although some progress has been made, increasing the temporal accuracy of spindle scoring and improving the performance assessment methodology are two aspects needing more attention. In this paper, four open-access automated spindle detectors with fine temporal resolution are proposed and tested against expert scoring of two proprietary and two open-access databases. Results highlight several findings: 1 that expert scoring and polysomnographic databases are important confounders when comparing the performance of spindle detectors tested using different databases or scorings; 2 because spindles are sparse events, specificity estimates are potentially misleading for assessing automated detector performance; 3 reporting the performance of spindle detectors exclusively with sensitivity and specificity estimates, as is often seen in the literature, is insufficient; including sensitivity, precision and a more comprehensive statistic such as Matthew’s correlation coefficient, F1-score, or Cohen’s κ is necessary for adequate evaluation; 4 reporting statistics for some reasonable range of decision thresholds provides a much more complete and useful benchmarking; 5 performance differences between tested automated detectors were found to be similar to those between available expert scorings; 6 much more development is needed to effectively compare the performance of spindle detectors developed by different research teams. Finally, this work clarifies a long-standing but only seldom posed question regarding whether expert scoring truly is a reliable gold standard for sleep spindle assessment.

SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

Energy Technology Data Exchange (ETDEWEB)

Verbakel, Werner, E-mail: werner.verbakel@chem.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium); Carmeliet, Geert, E-mail: geert.carmeliet@med.kuleuven.be [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium); Engelborghs, Yves, E-mail: yves.engelborghs@fys.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)

2011-08-12

Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase Nu

SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

International Nuclear Information System (INIS)

Verbakel, Werner; Carmeliet, Geert; Engelborghs, Yves

2011-01-01

Highlights: → The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. → This SAP-like domain is essential for chromosome loading during early mitosis. → NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. → The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction

Sleep spindles may predict response to cognitive-behavioral therapy for chronic insomnia.

Science.gov (United States)

Dang-Vu, Thien Thanh; Hatch, Benjamin; Salimi, Ali; Mograss, Melodee; Boucetta, Soufiane; O'Byrne, Jordan; Brandewinder, Marie; Berthomier, Christian; Gouin, Jean-Philippe

2017-11-01

While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed to determine whether pre-treatment sleep spindle density predicts treatment response to cognitive-behavioral therapy for insomnia. Twenty-four participants with chronic primary insomnia participated in a 6-week cognitive-behavioral therapy for insomnia performed in groups of 4-6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment, and at 3- and 12-months' follow-up assessments. Secondary outcome measures were extracted from sleep diaries over 7 days and overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stage N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive-behavioral therapy. After adjusting for age, sex, and education level, lower spindle density at pre-treatment predicted poorer response over the 12-month follow-up, as reflected by a smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive-behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to

Spindle-cell carcinoma of esophagus: a case report

International Nuclear Information System (INIS)

Kim, Ji Chang; Lee, Jae Mun; Jung, Seung Eun; Lee, Kyo Young; Hahn, Seong Tai; Kim, Man Deuk

2001-01-01

Spindle-cell carcinoma of the esophagus is a rare malignant tumor composed of both carcinomatous and sarcomatous elements, and has generated many terminology problems. It is characterized by a bulky polypoid intraluminal mass with a lobulated surface located in the middle third of the esophagus. Local expansion of this organ is observed. The lesion may be pedunculated but despite its bulk, causes little obstruction. We report the imaging findings of a case of spindle-cell carcinoma arising in the upper esophagus

Dynamic distribution of spindlin in nucleoli, nucleoplasm and spindle from primary oocytes to mature eggs and its critical function for oocyte-to-embryo transition in gibel carp.

Science.gov (United States)

Sun, Min; Li, Zhi; Gui, Jian-Fang

2010-10-01

Spindlin (Spin) was thought as a maternal-effect factor associated with meiotic spindle. Its role for the oocyte-to-embryo transition was suggested in mouse, but its direct evidence for the function had been not obtained in other vertebrates. In this study, we used the CagSpin-specific antibody to investigate CagSpin expression pattern and distribution during oogenesis of gibel carp (Carassius auratus gibelio). First, the oocyte-specific expression pattern and dynamic distribution was revealed in nucleoli, nucleoplasm, and spindle from primary oocytes to mature eggs by immunofluorescence localization. In primary oocytes and growth stage oocytes, CagSpin accumulates in nucleoli in increasing numbers along with the oocyte growth, and its disassembly occurs in vitellogenic oocytes, which implicates that CagSpin may be a major component of a large number of nucleoli in fish growth oocytes. Then, co-localization of CagSpin and β-tubulin was revealed in meiotic spindle of mature egg, indicating that CagSpin is one spindle-associated factor. Moreover, microinjection of CagSpin-specific antibody into the fertilized eggs blocked the first cleavage, and found that the CagSpin depletion resulted in spindle assembly disturbance. Thereby, our study provided the first direct evidence for the critical oocyte-to-embryo transition function of Spin in vertebrates, and confirmed that Spin is one important maternal-effect factor that participates in oocyte growth, oocyte maturation, and oocyte-to-embryo transition.

Topographic and sex-related differences in sleep spindles in major depressive disorder: a high-density EEG investigation.

Science.gov (United States)

Plante, D T; Goldstein, M R; Landsness, E C; Peterson, M J; Riedner, B A; Ferrarelli, F; Wanger, T; Guokas, J J; Tononi, G; Benca, R M

2013-03-20

Sleep spindles are believed to mediate several sleep-related functions including maintaining disconnection from the external environment during sleep, cortical development, and sleep-dependent memory consolidation. Prior studies that have examined sleep spindles in major depressive disorder (MDD) have not demonstrated consistent differences relative to control subjects, which may be due to sex-related variation and limited spatial resolution of spindle detection. Thus, this study sought to characterize sleep spindles in MDD using high-density electroencephalography (hdEEG) to examine the topography of sleep spindles across the cortex in MDD, as well as sex-related variation in spindle topography in the disorder. All-night hdEEG recordings were collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched controls. Topography of sleep spindle density, amplitude, duration, and integrated spindle activity (ISA) were assessed to determine group differences. Spindle parameters were compared between MDD and controls, including analysis stratified by sex. As a group, MDD subjects demonstrated significant increases in frontal and parietal spindle density and ISA compared to controls. When stratified by sex, MDD women demonstrated increases in frontal and parietal spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated either no differences or decreases in spindle parameters. Given the number of male subjects, this study may be underpowered to detect differences in spindle parameters in male MDD participants. This study demonstrates topographic and sex-related differences in sleep spindles in MDD. Further research is warranted to investigate the role of sleep spindles and sex in the pathophysiology of MDD. Copyright © 2012 Elsevier B.V. All rights reserved.

Fuel assemblies

International Nuclear Information System (INIS)

Nagano, Mamoru; Yoshioka, Ritsuo

1983-01-01

Purpose: To effectively utilize nuclear fuels by increasing the reactivity of a fuel assembly and reduce the concentration at the central region thereof upon completion of the burning. Constitution: A fuel assembly is bisected into a central region and a peripheral region by disposing an inner channel box within a channel box. The flow rate of coolants passing through the central region is made greater than that in the peripheral region. The concentration of uranium 235 of the fuel rods in the central region is made higher. In such a structure, since the moderating effect in the central region is improved, the reactivity of the fuel assembly is increased and the uranium concentration in the central region upon completion of the burning can be reduced, fuel economy and effective utilization of uranium can be attained. (Kamimura, M.)

Breast spindle cell tumours: about eight cases

Directory of Open Access Journals (Sweden)

Abd El All Howayda S

2006-07-01

Full Text Available Abstract Background Breast spindle cell tumours (BSCTs, although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC, histopathology and immunohistochemistry (IHC in differentiating BSCTs. Methods FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. Results FNAC defined the tumors as benign (n = 4, suspicious (n = 2 and malignant (n = 3, based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5 and malignant (n = 3. In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma. For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma. In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. Conclusion FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.

Comparison of a Four-Section Spindle and Stomacher for Efficacy of Detaching Microorganisms from Fresh Vegetables.

Science.gov (United States)

Kim, Do-Kyun; Kim, Soo-Ji; Kang, Dong-Hyun

2015-07-01

This study was undertaken to compare the effect of the spindle and stomacher for detaching microorganisms from fresh vegetables. The spindle is an apparatus for detaching microorganisms from food surfaces, which was developed in our laboratory. When processed with the spindle, food samples were barely disrupted, the original shape was maintained, and the diluent was clear, facilitating further detection analysis more easily than with stomacher treatment. The four-section spindle consists of four sample bag containers (A, B, C, and D) to economize time and effort by simultaneously processing four samples. The aerobic plate counts (APC) of 50 fresh vegetable samples were measured following spindle and stomacher treatment. Correlations between the two methods for each section of the spindle and stomacher were very high (R(2) = 0.9828 [spindle compartment A; Sp A], 0.9855 [Sp B], 0.9848 [Sp C], and 0.9851 [Sp D]). One-tenth milliliter of foodborne pathogens suspensions was inoculated onto surfaces of food samples, and ratios of spindle-to-stomacher enumerations were close to 1.00 log CFU/g between every section of the spindle and stomacher. One of the greatest features of the spindle is that it can treat large-sized samples that exceed 200 g. Uncut whole apples, green peppers, potatoes, and tomatoes were processed by the spindle and by hand massaging by 2 min. Large-sized samples were also assayed for aerobic plate count and recovery of the three foodborne pathogens, and the difference between each section of the spindle and hand massaging was not significant (P > 0.05). This study demonstrated that the spindle apparatus can be an alternative device for detaching microorganisms from all fresh vegetable samples for microbiological analysis by the food processing industry.

Age-related Changes In Sleep Spindles Characteristics During Daytime Recovery Following a 25-Hour Sleep Deprivation

Directory of Open Access Journals (Sweden)

Thaïna eRosinvil

2015-06-01

Full Text Available Objectives: The mechanisms underlying sleep spindles (~11-15Hz; >0.5s help to protect sleep. With age, it becomes increasingly difficult to maintain sleep at a challenging time (e.g. daytime, even after sleep loss. This study compared spindle characteristics during daytime recovery and nocturnal sleep in young and middle-aged adults. In addition, we explored whether spindles characteristics in baseline nocturnal sleep were associated with the ability to maintain sleep during daytime recovery periods in both age groups.Methods: Twenty-nine young (15 women and 14 men; 27.3 ± 5.0 and 31 middle-aged (19 women and 13 men; 51.6 y ± 5.1 healthy subjects participated in a baseline nocturnal sleep and a daytime recovery sleep after 25 hours of sleep deprivation. Spindles were detected on artefact-free NREM sleep epochs. Spindle density (nb/min, amplitude (μV, frequency (Hz and duration (s were analyzed on parasagittal (linked-ears derivations. Results: In young subjects, spindle frequency increased during daytime recovery sleep as compared to baseline nocturnal sleep in all derivations, whereas middle-aged subjects showed spindle frequency enhancement only in the prefrontal derivation. No other significant interaction between age group and sleep condition was observed. Spindle density for all derivations and centro-occipital spindle amplitude decreased whereas prefrontal spindle amplitude increased from baseline to daytime recovery sleep in both age groups. Finally, no significant correlation was found between spindle characteristics during baseline nocturnal sleep and the marked reduction in sleep efficiency during daytime recovery sleep in both young and middle-aged subjects.Conclusion: These results suggest that the interaction between homeostatic and circadian pressure module spindle frequency differently in aging. Spindle characteristics do not seem to be linked with the ability to maintain daytime recovery sleep.

Vibration sensitivity of human muscle spindles and Golgi tendon organs.

Science.gov (United States)

Fallon, James B; Macefield, Vaughan G

2007-07-01

The responses of the various muscle receptors to vibration are more complicated than a naïve categorization into stretch (muscle spindle primary ending), length (muscle spindle secondary endings), and tension (Golgi tendon organs) receptors. To emphasize the similarity of responses to small length changes, we recorded from 58 individual muscle afferents subserving receptors in the ankle or toe dorsiflexors of awake human subjects (32 primary endings, 20 secondary endings, and six Golgi tendon organs). Transverse sinusoidal vibration was applied to the distal tendon of the receptor-bearing muscle, while subjects either remained completely relaxed or maintained a weak isometric contraction of the appropriate muscle. In relaxed muscle, few units responded in a 1:1 manner to vibration, and there was no evidence of a preferred frequency of activation. In active muscle the response profiles of all three receptor types overlapped, with no significant difference in threshold between receptor types. These results emphasize that when intramuscular tension increases during a voluntary contraction, Golgi tendon organs and muscle spindle secondary endings, not just muscle spindle primary endings, can effectively encode small imposed length changes.

REM sleep behaviour disorder is associated with lower fast and higher slow sleep spindle densities.

Science.gov (United States)

O'Reilly, Christian; Godin, Isabelle; Montplaisir, Jacques; Nielsen, Tore

2015-12-01

To investigate differences in sleep spindle properties and scalp topography between patients with rapid eye movement sleep behaviour disorder (RBD) and healthy controls, whole-night polysomnograms of 35 patients diagnosed with RBD and 35 healthy control subjects matched for age and sex were compared. Recordings included a 19-lead 10-20 electroencephalogram montage and standard electromyogram, electrooculogram, electrocardiogram and respiratory leads. Sleep spindles were automatically detected using a standard algorithm, and their characteristics (amplitude, duration, density, frequency and frequency slope) compared between groups. Topological analyses of group-discriminative features were conducted. Sleep spindles occurred at a significantly (e.g. t34 = -4.49; P = 0.00008 for C3) lower density (spindles ∙ min(-1) ) for RBD (mean ± SD: 1.61 ± 0.56 for C3) than for control (2.19 ± 0.61 for C3) participants. However, when distinguishing slow and fast spindles using thresholds individually adapted to the electroencephalogram spectrum of each participant, densities smaller (31-96%) for fast but larger (20-120%) for slow spindles were observed in RBD in all derivations. Maximal differences were in more posterior regions for slow spindles, but over the entire scalp for fast spindles. Results suggest that the density of sleep spindles is altered in patients with RBD and should therefore be investigated as a potential marker of future neurodegeneration in these patients. © 2015 European Sleep Research Society.

Expert and crowd-sourced validation of an individualized sleep spindle detection method employing complex demodulation and individualized normalization

Directory of Open Access Journals (Sweden)

Laura eRay

2015-09-01

Full Text Available A spindle detection method was developed that: 1 extracts the signal of interest (i.e., spindle-related phasic changes in sigma relative to ongoing background sigma activity using complex demodulation, 2 accounts for variations of spindle characteristics across the night, scalp derivations and between individuals, and 3 employs a minimum number of sometimes arbitrary, user-defined parameters. Complex demodulation was used to extract instantaneous power in the spindle band. To account for intra- and inter-individual differences, the signal was z-score transformed using a 60s sliding window, per channel, over the course of the recording. Spindle events were detected with a z-score threshold corresponding to a low probability (e.g., 99th percentile. Spindle characteristics, such as amplitude, duration and oscillatory frequency, were derived for each individual spindle following detection, which permits spindles to be subsequently and flexibly categorized as slow or fast spindles from a single detection pass. Spindles were automatically detected in 15 young healthy subjects. Two experts manually identified spindles from C3 during Stage 2 sleep, from each recording; one employing conventional guidelines, and the other, identifying spindles with the aid of a sigma (11-16 Hz filtered channel. These spindles were then compared between raters and to the automated detection to identify the presence of true positives, true negatives, false positives and false negatives. This method of automated spindle detection resolves or avoids many of the limitations that complicate automated spindle detection, and performs well compared to a group of non-experts, and importantly, has good external validity with respect to the extant literature in terms of the characteristics of automatically detected spindles.

Different maturational changes of fast and slow sleep spindles in the first four years of life.

Science.gov (United States)

D'Atri, Aurora; Novelli, Luana; Ferrara, Michele; Bruni, Oliviero; De Gennaro, Luigi

2018-02-01

Massive changes in brain morphology and function in the first years of life reveal a postero-anterior trajectory of cortical maturation accompanied by regional modifications of NREM sleep. One of the most sensible marker of this maturation process is represented by electroencephalographic (EEG) activity within the frequency range of sleep spindles. However, direct evidence that these changes actually reflect maturational modifications of fast and slow spindles still lacks. Our study aimed at answering the following questions: 1. Do cortical changes at 11.50 Hz frequency correspond to slow spindles? 2. Do fast and slow spindles show different age trajectories and different topographical distributions? 3. Do changes in peak frequency explain age changes of slow and fast spindles? We measured the antero-posterior changes of slow and fast spindles in the first 60 min of nightly sleep of 39 infants and children (0-48 mo.). We found that (A) changes of slow spindles from birth to childhood mostly affect frontal areas (B) variations of fast and slow spindles across age groups go in opposite direction, the latter progressively increasing across ages; (C) this process is not merely reducible to changes of spindle frequency. As a main finding, our cross-sectional study shows that the first form of mature spindle (i.e., corresponding to the adult phasic event of NREM sleep) is marked by the emergence of slow spindles on anterior regions around the age of 12 months. Copyright © 2017 Elsevier B.V. All rights reserved.

Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

Directory of Open Access Journals (Sweden)

Nishida M

2016-01-01

Full Text Available Masaki Nishida,1 Yusaku Nakashima,2 Toru Nishikawa11Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, 2Medical Technology Research Laboratory, Research and Development Division, Medical Business Unit, Sony Corporation, Tokyo, JapanIntroduction: Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process.Methods: Healthy control participants (n=17 and patients medicated for major depressive disorder (n=11 were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement. Participants' brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs. Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz and slow-frequency spindle activity (10.5–12.5 Hz.Result: Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups.Conclusion: Because the changes in slow

Valve spindle gland

International Nuclear Information System (INIS)

Burda, Z.; Harazim, A.; Kerlin, K.

1979-01-01

A gland is proposed of the valve spindle designed for radioactive or otherwise harmful media, such as in nuclear power plant primary circuits. The gland is installed in the valve cover and consists of a primary and a secondary part and of a gland case partitioning the gland space into two chambers. The bottom face of the gland case is provided with a double-sided collar for controlling the elements of the bottom primary gland while the top face is provided with a removable flange. (M.S.)

On the Dynamics of Rocking Motion of the Hard-Disk Drive Spindle Motor System

Science.gov (United States)

Wang, Joseph

Excessive rocking motion of the spindle motor system can cause track misregistration resulting in poor throughput or even drive failure. The chance of excessive disk stack rocking increases as a result of decreasing torsional stiffness of spindle motor bearing system due to the market demand for low profile hard drives. As the track density increases and the vibration specification becomes increasingly stringent, rocking motion of a spindle motor system deserves even more attention and has become a primary challenge for a spindle motor system designer. Lack of understanding of the rocking phenomenon combined with misleading paradox has presented a great difficulty in the effort of avoiding the rocking motion in the hard-disk drive industry. This paper aims to provide fundamental understanding of the rocking phenomenon of a rotating spindle motor system, to clarify the paradox in disk-drive industry and to provide a design guide to an optimized spindle system. This paper, theoretically and experimentally, covers a few important areas of industrial interest including the prediction of rocking natural frequencies and mode shape of a rotating spindle, free vibration, and frequency response under common forcing functions such as rotating and fixed-plane forcing functions. The theory presented here meets with agreeable experimental observation.

A Bipolar Spindle of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation

DEFF Research Database (Denmark)

Gayathri, P; Fujii, T; Møller-Jensen, Jakob

2012-01-01

the spindle between ParRC complexes on sister plasmids. Using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture...... of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles....

Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast

Science.gov (United States)

Gergely, Zachary R.; Crapo, Ammon; Hough, Loren E.; McIntosh, J. Richard; Betterton, Meredith D.

2016-01-01

Kinesin-8 motor proteins destabilize microtubules. Their absence during cell division is associated with disorganized mitotic chromosome movements and chromosome loss. Despite recent work studying effects of kinesin-8s on microtubule dynamics, it remains unclear whether the kinesin-8 mitotic phenotypes are consequences of their effect on microtubule dynamics, their well-established motor activity, or additional, unknown functions. To better understand the role of kinesin-8 proteins in mitosis, we studied the effects of deletion of the fission yeast kinesin-8 proteins Klp5 and Klp6 on chromosome movements and spindle length dynamics. Aberrant microtubule-driven kinetochore pushing movements and tripolar mitotic spindles occurred in cells lacking Klp5 but not Klp6. Kinesin-8–deletion strains showed large fluctuations in metaphase spindle length, suggesting a disruption of spindle length stabilization. Comparison of our results from light microscopy with a mathematical model suggests that kinesin-8–induced effects on microtubule dynamics, kinetochore attachment stability, and sliding force in the spindle can explain the aberrant chromosome movements and spindle length fluctuations seen. PMID:27146110

Adaptive Spindle Balancing Using Magnetically Levitated Bearings

International Nuclear Information System (INIS)

BARNEY, PATRICK S.; LAUFFER, JAMES P.; PETTEYS, REBECCA; REDMOND, JAMES M.; SULLIVAN, WILLIAM N.

1999-01-01

A technological break through for supporting rotating shafts is the active magnetic bearing (AMB). Active magnetic bearings offer some important advantages over conventional ball, roller or journal bearings such as reduced frictional drag, no physical contact in the bearing, no need for lubricants, compatibility with high vacuum and ultra-clean environments, and ability to control shaft position within the bearing. The disadvantages of the AMB system are the increased cost and complexity, reduced bearing stiffness and the need for a controller. Still, there are certain applications, such as high speed machining, biomedical devices, and gyroscopes, where the additional cost of an AMB system can be justified. The inherent actuator capabilities of the AMB offer the potential for active balancing of spindles and micro-shaping capabilities for machine tools, The work presented in this paper concentrates on an AMB test program that utilizes the actuator capability to dynamically balance a spindle. In this study, an unbalanced AMB spindle system was enhanced with an LMS (Least Mean Squares) algorithm combined with an existing PID (proportional, integral, differential) control. This enhanced controller significantly improved the concentricity of an intentionally unbalanced shaft. The study included dynamic system analysis, test validation, control design and simulation, as well as experimental implementation using a digital LMS controller

Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

Science.gov (United States)

Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger

2015-10-01

We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

Science.gov (United States)

Wise, Merrill S.

2016-01-01

Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population. PMID:27478646

Spindle Cell Carcinoma of the hypopharynx: a case report

Directory of Open Access Journals (Sweden)

Dillu Ram Kandel

2018-03-01

Full Text Available Spindle cell carcinoma of hpopharynx is a rare pathology. It is a poorly differentiated variant of squamous cell carcinoma and morphologically resembles sarcoma. This is a disease of old age. It is usually associated with smoking and alcohol abuse. When it is associated with radiation exposure history it behaves more aggressively. Surgery is considered as the main modality of treatment and adjuvant radiotherapy if necessary. Here we present a case of 79 year old male with spindle cell carcinomaof right piriform fossa with 2-month history of progressive dysphasia and hoarseness that has been affecting his ability to speak and swallow with history of weight loss and past history of radiotherapy. So possibility of spindle cell carcinoma of the hypopharynx should beconsidered in an old patient with rapidly developing swelling of the hypopharynx with past history of radiation exposure. As it is a highly aggressive disease it should be treated timely and more aggressively to prolong the survival of the patient.   

Mounting arrangement for the drive system of an air-bearing spindle on a machine tool

Science.gov (United States)

Lunsford, J.S.; Crisp, D.W.; Petrowski, P.L.

1987-12-07

The present invention is directed to a mounting arrangement for the drive system of an air-bearing spindle utilized on a machine tool such as a lathe. The mounting arrangement of the present invention comprises a housing which is secured to the casing of the air bearing in such a manner that the housing position can be selectively adjusted to provide alignment of the air-bearing drive shaft supported by the housing and the air-bearing spindle. Once this alignment is achieved the air between spindle and the drive arrangement is maintained in permanent alignment so as to overcome misalignment problems encountered in the operation of the machine tool between the air-bearing spindle and the shaft utilized for driving the air-bearing spindle.

Evaluating and Improving Automatic Sleep Spindle Detection by Using Multi-Objective Evolutionary Algorithms

Directory of Open Access Journals (Sweden)

Min-Yin Liu

2017-05-01

Full Text Available Sleep spindles are brief bursts of brain activity in the sigma frequency range (11–16 Hz measured by electroencephalography (EEG mostly during non-rapid eye movement (NREM stage 2 sleep. These oscillations are of great biological and clinical interests because they potentially play an important role in identifying and characterizing the processes of various neurological disorders. Conventionally, sleep spindles are identified by expert sleep clinicians via visual inspection of EEG signals. The process is laborious and the results are inconsistent among different experts. To resolve the problem, numerous computerized methods have been developed to automate the process of sleep spindle identification. Still, the performance of these automated sleep spindle detection methods varies inconsistently from study to study. There are two reasons: (1 the lack of common benchmark databases, and (2 the lack of commonly accepted evaluation metrics. In this study, we focus on tackling the second problem by proposing to evaluate the performance of a spindle detector in a multi-objective optimization context and hypothesize that using the resultant Pareto fronts for deriving evaluation metrics will improve automatic sleep spindle detection. We use a popular multi-objective evolutionary algorithm (MOEA, the Strength Pareto Evolutionary Algorithm (SPEA2, to optimize six existing frequency-based sleep spindle detection algorithms. They include three Fourier, one continuous wavelet transform (CWT, and two Hilbert-Huang transform (HHT based algorithms. We also explore three hybrid approaches. Trained and tested on open-access DREAMS and MASS databases, two new hybrid methods of combining Fourier with HHT algorithms show significant performance improvement with F1-scores of 0.726–0.737.

Automated high-throughput quantification of mitotic spindle positioning from DIC movies of Caenorhabditis embryos.

Directory of Open Access Journals (Sweden)

David Cluet

Full Text Available The mitotic spindle is a microtubule-based structure that elongates to accurately segregate chromosomes during anaphase. Its position within the cell also dictates the future cell cleavage plan, thereby determining daughter cell orientation within a tissue or cell fate adoption for polarized cells. Therefore, the mitotic spindle ensures at the same time proper cell division and developmental precision. Consequently, spindle dynamics is the matter of intensive research. Among the different cellular models that have been explored, the one-cell stage C. elegans embryo has been an essential and powerful system to dissect the molecular and biophysical basis of spindle elongation and positioning. Indeed, in this large and transparent cell, spindle poles (or centrosomes can be easily detected from simple DIC microscopy by human eyes. To perform quantitative and high-throughput analysis of spindle motion, we developed a computer program ACT for Automated-Centrosome-Tracking from DIC movies of C. elegans embryos. We therefore offer an alternative to the image acquisition and processing of transgenic lines expressing fluorescent spindle markers. Consequently, experiments on large sets of cells can be performed with a simple setup using inexpensive microscopes. Moreover, analysis of any mutant or wild-type backgrounds is accessible because laborious rounds of crosses with transgenic lines become unnecessary. Last, our program allows spindle detection in other nematode species, offering the same quality of DIC images but for which techniques of transgenesis are not accessible. Thus, our program also opens the way towards a quantitative evolutionary approach of spindle dynamics. Overall, our computer program is a unique macro for the image- and movie-processing platform ImageJ. It is user-friendly and freely available under an open-source licence. ACT allows batch-wise analysis of large sets of mitosis events. Within 2 minutes, a single movie is processed

Experimental study on bearing preload optimum of machine tool spindle

International Nuclear Information System (INIS)

Xu Tao; Xu Guanghua; Zhang Qin; Hua Cheng; Zhang Hu; Jiang Kuosheng

2012-01-01

An experimental study is conducted to investigate the possibility and the effect of temperature rise and vibration level of bearing by adjusting axial preloads and radial loads in spindle bearing test rig. The shaft of the test rig is driven by a motorized high speed spindle at the range of 0∼20000 rpm. The axial preloads and radial loads on bearings are controlled by using hydraulic pressure which can be adjusted automatically. Temperature rise and radial vibration of test bearings are measured by thermocouples and Polytec portable laser vibrometer PDV100. Experiment shows that the temperature rise of bearings is nonlinear varying with the increase of radial loads, but temperature rise almost increases linearly with the increase of axial preload and rotating speed. In this paper, an alternate axial preload is used for bearings. When the rotating speed passes through the critical speed of the shaft, axial preload of bearings will have a remarkable effect. The low preload could reduce bearing vibration and temperature rise for bearings as well. At the others speed, the high preload could improve the vibration performance of high speed spindle and the bearing temperature was lower than that of the constant pressure preload spindle.

Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles.

Science.gov (United States)

Decker, Franziska; Oriola, David; Dalton, Benjamin; Brugués, Jan

2018-01-11

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting. © 2018, Decker et al.

A SUMOylation Motif in Aurora-A: Implications for Spindle Dynamics and Oncogenesis

Energy Technology Data Exchange (ETDEWEB)

Pérez de Castro, Ignacio; Aguirre-Portolés, Cristina [Molecular Oncology Programme, Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid (Spain); Martin, Benedicte [CNRS-UMR 6061, Institut de Génétique et Développement de Rennes, IFR 140 GFAS, Faculté de Médecine, Université Rennes 1, Rennes (France); Fernández-Miranda, Gonzalo [Molecular Oncology Programme, Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid (Spain); Klotzbucher, Andrea; Kubbutat, Michael H. G. [ProQinase GmBH, Freiburg (Germany); Megías, Diego [Confocal Microscopy Core Unit, Centro Nacional de Investigaciones Oncológicas, Madrid (Spain); Arlot-Bonnemains, Yannick [CNRS-UMR 6061, Institut de Génétique et Développement de Rennes, IFR 140 GFAS, Faculté de Médecine, Université Rennes 1, Rennes (France); Malumbres, Marcos, E-mail: mmm@cnio.es, E-mail: iperez@cnio.es [Molecular Oncology Programme, Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid (Spain)

2011-12-14

Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics, and chromosome orientation and it is frequently over-expressed in human cancers. In this work, we show that Aurora-A interacts with the SUMO-conjugating enzyme UBC9 and co-localizes with SUMO1 in mitotic cells. Aurora-A can be SUMOylated in vitro and in vivo. Mutation of the highly conserved SUMOylation residue lysine 249 significantly disrupts Aurora-A SUMOylation and mitotic defects characterized by defective and multipolar spindles ensue. The Aurora-A{sup K249R} mutant has normal kinase activity but displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-A{sup K249R} mutant results in a significant increase in susceptibility to malignant transformation induced by the Ras oncogene. These data suggest that modification by SUMO residues may control Aurora-A function at the spindle and that deficiency of SUMOylation of this kinase may have important implications for tumor development.

Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

Science.gov (United States)

Seibt, Julie; Richard, Clément J; Sigl-Glöckner, Johanna; Takahashi, Naoya; Kaplan, David I; Doron, Guy; de Limoges, Denis; Bocklisch, Christina; Larkum, Matthew E

2017-09-25

How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.

Warts phosphorylates mud to promote pins-mediated mitotic spindle orientation in Drosophila, independent of Yorkie.

Science.gov (United States)

Dewey, Evan B; Sanchez, Desiree; Johnston, Christopher A

2015-11-02

Multicellular animals have evolved conserved signaling pathways that translate cell polarity cues into mitotic spindle positioning to control the orientation of cell division within complex tissue structures. These oriented cell divisions are essential for the development of cell diversity and the maintenance of tissue homeostasis. Despite intense efforts, the molecular mechanisms that control spindle orientation remain incompletely defined. Here, we describe a role for the Hippo (Hpo) kinase complex in promoting Partner of Inscuteable (Pins)-mediated spindle orientation. Knockdown of Hpo, Salvador (Sav), or Warts (Wts) each result in a partial loss of spindle orientation, a phenotype previously described following loss of the Pins-binding protein Mushroom body defect (Mud). Similar to orthologs spanning yeast to mammals, Wts kinase localizes to mitotic spindle poles, a prominent site of Mud localization. Wts directly phosphorylates Mud in vitro within its C-terminal coiled-coil domain. This Mud coiled-coil domain directly binds the adjacent Pins-binding domain to dampen the Pins/Mud interaction, and Wts-mediated phosphorylation uncouples this intramolecular Mud interaction. Loss of Wts prevents cortical Pins/Mud association without affecting Mud accumulation at spindle poles, suggesting phosphorylation acts as a molecular switch to specifically activate cortical Mud function. Finally, loss of Wts in Drosophila imaginal disc epithelial cells results in diminished cortical Mud and defective planar spindle orientation. Our results provide new insights into the molecular basis for dynamic regulation of the cortical Pins/Mud spindle positioning complex and highlight a novel link with an essential, evolutionarily conserved cell proliferation pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of a novel automatic sleep spindle detector with high performance during sleep in middle aged subjects

DEFF Research Database (Denmark)

Wendt, Sabrina Lyngbye; Christensen, Julie A. E.; Kempfner, Jacob

2012-01-01

Many of the automatic sleep spindle detectors currently used to analyze sleep EEG are either validated on young subjects or not validated thoroughly. The purpose of this study is to develop and validate a fast and reliable sleep spindle detector with high performance in middle aged subjects....... An automatic sleep spindle detector using a bandpass filtering approach and a time varying threshold was developed. The validation was done on sleep epochs from EEG recordings with manually scored sleep spindles from 13 healthy subjects with a mean age of 57.9 ± 9.7 years. The sleep spindle detector reached...

Spindle frequency activity in the sleep EEG: individual differences and topographic distribution.

Science.gov (United States)

Werth, E; Achermann, P; Dijk, D J; Borbély, A A

1997-11-01

The brain topography of EEG power spectra in the frequency range of sleep spindles was investigated in 34 sleep recordings from 20 healthy young men. Referential (F3-A2, C3-A2, P3-A2 and O1-A2) and bipolar derivations (F3-C3, C3-P3 and P3-O1) along the anteroposterior axis were used. Sleep spindles gave rise to a distinct peak in the EEG power spectrum. The distribution of the peak frequencies pooled over subjects and derivations showed a bimodal pattern with modes at 11.5 and 13.0 Hz, and a trough at 12.25 Hz. The large inter-subject variation in peak frequency (range: 1.25 Hz) contrasted with the small intra-subject variation between derivations, non-REM sleep episodes and different nights. In some individuals and/or some derivations, only a single spindle peak was present. The topographic distributions from referential and bipolar recordings showed differences. The power showed a declining trend over consecutive non-REM sleep episodes in the low range of spindle frequency activity and a rising trend in the high range. The functional and topographic heterogeneity of sleep spindles in conjunction with the intra-subject stability of their frequency are important characteristics for the analysis of sleep regulation on the basis of the EEG.

The approximate thermal-model-testing method for non-stationary temperature fields in central zones of fast reactor assemblies

International Nuclear Information System (INIS)

Mikhin, V.I.; Matukhin, N.M.

2000-01-01

The approach to generalization of the non-stationary heat exchange data for the central zones of the nuclear reactor fuel assemblies and the approximate thermal-model-testing criteria are proposed. The fuel assemblies of fast and water-cooled reactors with different fuel compositions have been investigated. The reason of the non-stationary heat exchange is the fuel-energy-release time dependence. (author)

Left atrial spindle cell sarcoma – Case report

Directory of Open Access Journals (Sweden)

Nihar Mehta

2012-07-01

Full Text Available Primary spindle cell sarcoma of the left atrium is an extremely rare tumour. Surgical excision is the mainstay of treatment since it responds poorly to chemotherapy or radiotherapy. In spite of all the treatment, the prognosis remains poor due to inadvertent delay in diagnosis, few therapeutic options and propensity to metastasize. We present a 47-year-old male who underwent a surgical excision of a left atrial mass in February 2010. It was proved to be a high-grade spindle cell sarcoma on histopathology. He presented again in October 2010 with recurrence of the tumour for which he was re-operated. However, the tumour recurred again within one month, to which the patient succumbed.

Sleep-spindle detection: crowdsourcing and evaluating performance of experts, non-experts and automated methods

DEFF Research Database (Denmark)

Warby, Simon C.; Wendt, Sabrina Lyngbye; Welinder, Peter

2014-01-01

to crowdsource spindle identification by human experts and non-experts, and we compared their performance with that of automated detection algorithms in data from middle- to older-aged subjects from the general population. We also refined methods for forming group consensus and evaluating the performance...... of event detectors in physiological data such as electroencephalographic recordings from polysomnography. Compared to the expert group consensus gold standard, the highest performance was by individual experts and the non-expert group consensus, followed by automated spindle detectors. This analysis showed...... that crowdsourcing the scoring of sleep data is an efficient method to collect large data sets, even for difficult tasks such as spindle identification. Further refinements to spindle detection algorithms are needed for middle- to older-aged subjects....

Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle

Directory of Open Access Journals (Sweden)

Jack W. C. Chen

2017-05-01

Full Text Available The hetero-octameric protein complex, Augmin, recruits γ-Tubulin ring complex (γ-TuRC to pre-existing microtubules (MTs to generate branched MTs during mitosis, facilitating robust spindle assembly. However, despite a recent partial reconstitution of the human Augmin complex in vitro, the molecular basis of this recruitment remains unclear. Here, we used immuno-affinity purification of in vivo Augmin from Drosophila and cross-linking/mass spectrometry to identify distance restraints between residues within the eight Augmin subunits in the absence of any other structural information. The results allowed us to predict potential interfaces between Augmin and γ-TuRC. We tested these predictions biochemically and in the Drosophila embryo, demonstrating that specific regions of the Augmin subunits, Dgt3, Dgt5 and Dgt6 all directly bind the γ-TuRC protein, Dgp71WD, and are required for the accumulation of γ-TuRC, but not Augmin, to the mitotic spindle. This study therefore substantially increases our understanding of the molecular mechanisms underpinning MT-dependent MT nucleation.

Stage-independent, single lead EEG sleep spindle detection using the continuous wavelet transform and local weighted smoothing.

Science.gov (United States)

Tsanas, Athanasios; Clifford, Gari D

2015-01-01

Sleep spindles are critical in characterizing sleep and have been associated with cognitive function and pathophysiological assessment. Typically, their detection relies on the subjective and time-consuming visual examination of electroencephalogram (EEG) signal(s) by experts, and has led to large inter-rater variability as a result of poor definition of sleep spindle characteristics. Hitherto, many algorithmic spindle detectors inherently make signal stationarity assumptions (e.g., Fourier transform-based approaches) which are inappropriate for EEG signals, and frequently rely on additional information which may not be readily available in many practical settings (e.g., more than one EEG channels, or prior hypnogram assessment). This study proposes a novel signal processing methodology relying solely on a single EEG channel, and provides objective, accurate means toward probabilistically assessing the presence of sleep spindles in EEG signals. We use the intuitively appealing continuous wavelet transform (CWT) with a Morlet basis function, identifying regions of interest where the power of the CWT coefficients corresponding to the frequencies of spindles (11-16 Hz) is large. The potential for assessing the signal segment as a spindle is refined using local weighted smoothing techniques. We evaluate our findings on two databases: the MASS database comprising 19 healthy controls and the DREAMS sleep spindle database comprising eight participants diagnosed with various sleep pathologies. We demonstrate that we can replicate the experts' sleep spindles assessment accurately in both databases (MASS database: sensitivity: 84%, specificity: 90%, false discovery rate 83%, DREAMS database: sensitivity: 76%, specificity: 92%, false discovery rate: 67%), outperforming six competing automatic sleep spindle detection algorithms in terms of correctly replicating the experts' assessment of detected spindles.

Stage-independent, single lead EEG sleep spindle detection using the continuous wavelet transform and local weighted smoothing

Directory of Open Access Journals (Sweden)

Athanasios eTsanas

2015-04-01

Full Text Available Sleep spindles are critical in characterizing sleep and have been associated with cognitive function and pathophysiological assessment. Typically, their detection relies on the subjective and time-consuming visual examination of electroencephalogram (EEG signal(s by experts, and has led to large inter-rater variability as a result of poor definition of sleep spindle characteristics. Hitherto, many algorithmic spindle detectors inherently make signal stationarity assumptions (e.g. Fourier transform-based approaches which are inappropriate for EEG signals, and frequently rely on additional information which may not be readily available in many practical settings (e.g. more than one EEG channels, or prior hypnogram assessment. This study proposes a novel signal processing methodology relying solely on a single EEG channel, and provides objective, accurate means towards probabilistically assessing the presence of sleep spindles in EEG signals. We use the intuitively appealing continuous wavelet transform (CWT with a Morlet basis function, identifying regions of interest where the power of the CWT coefficients corresponding to the frequencies of spindles (11-16 Hz is large. The potential for assessing the signal segment as a spindle is refined using local weighted smoothing techniques. We evaluate our findings on two databases: the MASS database comprising 19 healthy controls and the DREAMS sleep spindle database comprising eight participants diagnosed with various sleep pathologies. We demonstrate that we can replicate the experts’ sleep spindles assessment accurately in both databases (MASS database: sensitivity: 84%, specificity: 90%, false discovery rate 83%, DREAMS database: sensitivity: 76%, specificity: 92%, false discovery rate: 67%, outperforming six competing automatic sleep spindle detection algorithms in terms of correctly replicating the experts’ assessment of detected spindles.

Xanthium strumarium extract inhibits mammalian cell proliferation through mitotic spindle disruption mediated by xanthatin.

Science.gov (United States)

Sánchez-Lamar, Angel; Piloto-Ferrer, Janet; Fiore, Mario; Stano, Pasquale; Cozzi, Renata; Tofani, Daniela; Cundari, Enrico; Francisco, Marbelis; Romero, Aylema; González, Maria L; Degrassi, Francesca

2016-12-24

Xanthium strumarium L. is a member of the Asteraceae family popularly used with multiple therapeutic purposes. Whole extracts of this plant have shown anti-mitotic activity in vitro suggesting that some components could induce mitotic arrest in proliferating cells. Aim of the present work was to characterize the anti-mitotic properties of the X. strumarium whole extract and to isolate and purify active molecule(s). The capacity of the whole extract to inhibit mitotic progression in mammalian cultured cells was investigated to identify its anti-mitotic activity. Isolation of active component(s) was performed using a bioassay-guided multistep separation procedure in which whole extract was submitted to a progressive process of fractionation and fractions were challenged for their anti-mitotic activity. Our results show for the first time that X. strumarium whole extract inhibits assembly of the mitotic spindle and spindle-pole separation, thereby heavily affecting mitosis, impairing the metaphase to anaphase transition and inducing apoptosis. The purification procedure led to a fraction with an anti-mitotic activity comparable to that of the whole extract. Chemical analysis of this fraction showed that its major component was xanthatin. The present work shows a new activity of X. strumarium extract, i.e. the alteration of the mitotic apparatus in cultured cells that may be responsible for the anti-proliferative activity of the extract. Anti-mitotic activity is shown to be mainly exerted by xanthatin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synthesis and surface modification of spindle-type magnetic nanoparticles: gold coating and PEG functionalization

OpenAIRE

Mendez-Garza , Juan; Wang , Biran; Madeira , Alexandra; Di-Giorgio , Christophe; Bossis , Georges

2013-01-01

International audience; In this paper, we describe the synthesis of gold coated spindle-type iron nanoparticles and its surface modification by a thiolated fluorescently-labelled polyethylene glycol (PEG) polymer. A forced hydrolysis of ferric salts in the presence of phosphate ions was used to produce α-Fe2O3 spindle-type particles. The oxide powders were first reduced to α-iron under high temperature and controlled dihydrogen atmosphere. Then, the resulting magnetic spindle-type particles w...

White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation.

Science.gov (United States)

Mander, Bryce A; Zhu, Alyssa H; Lindquist, John R; Villeneuve, Sylvia; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Ancoli-Israel, Sonia; Jagust, William J; Walker, Matthew P

2017-11-29

Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical-cortical propagation of sleep spindles and their related memory benefits. SIGNIFICANCE STATEMENT Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of

Higher efficiency by direct driven spindles with sensorless controlled engine speed in multi-axial machine tools for the timber industry; Verbesserte Energieeffizienz durch direktangetriebene winkelgeberlose drehzahlgeregelte Spindeln bei Mehrachsbohrkoepfen fuer die holzverarbeitende Industrie

Energy Technology Data Exchange (ETDEWEB)

Teisch, Arthur; Obernolte, Urs; Borcherding, Holger [Hochschule Ostwestfalen Lippe, Lemgo (Germany)

2009-07-01

The multi-axial machine tools work mainly with spindles, who are powered by a central motor with a gearbox. These drives have a relative little power efficiency. Due to the progress of the magnetic material it was possible to change the central motor with gear box by small direct driven spindles. Cause of the very high efficiency of the permanentmagnet synchronous machine (PMSM), it is the best option for the new application. With the option of the sensorless control of the rotor speed the costs for an encoder are saved too. With the good efficiency of the PMSM the overall degree of efficiency could be raised by about 70%. Because of the reduced investment, service and energy costs the new systems are more economical to operate. (orig.)

The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles.

Science.gov (United States)

Fan, Denggui; Liao, Fucheng; Wang, Qingyun

2017-07-01

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE→TC→Cortex. Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 →TC 1 →Cortex 1 and Cortex 1 →Cortex 2 →Cortex 3

The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles

Science.gov (United States)

Fan, Denggui; Liao, Fucheng; Wang, Qingyun

2017-07-01

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE → TC → Cortex . Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 → TC 1 → Cortex 1 and Cortex 1 → Cortex 2 �

Online Dynamic Balance Technology for High Speed Spindle Based on Gain Parameter Adaption and Scheduling Control

Directory of Open Access Journals (Sweden)

Shihai Zhang

2018-06-01

Full Text Available Unbalance vibration is one of the main vibration forms of a high speed machine tool spindle. The overlarge unbalance vibration will have some adverse effects on the working life of the spindle system and the surface quality of the work-piece. In order to reduce the unbalance of a high speed spindle system, a pneumatic online dynamic balance device and its control system are presented in the paper. To improve the balance accuracy and adaptation of the balance system, the gain parameter adaption and scheduling control method are proposed first, and then the different balance effects of the influence coefficient method and the gain scheduling control method are compared through many dynamic balance experiments of the high speed spindle. The experimental results indicate that the gain parameters can be changed timely according to the transformation of the speed and kinetic parameters of the spindle system. The balance accuracy can be improved for a high speed spindle with time-varying characteristics, based on the adaptive gain scheduling control method.

The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized placebo-controlled trial.

Science.gov (United States)

Wamsley, Erin J; Shinn, Ann K; Tucker, Matthew A; Ono, Kim E; McKinley, Sophia K; Ely, Alice V; Goff, Donald C; Stickgold, Robert; Manoach, Dara S

2013-09-01

In schizophrenia there is a dramatic reduction of sleep spindles that predicts deficient sleep-dependent memory consolidation. Eszopiclone (Lunesta), a non-benzodiazepine hypnotic, acts on γ-aminobutyric acid (GABA) neurons in the thalamic reticular nucleus where spindles are generated. We investigated whether eszopiclone could increase spindles and thereby improve memory consolidation in schizophrenia. In a double-blind design, patients were randomly assigned to receive either placebo or 3 mg of eszopiclone. Patients completed Baseline and Treatment visits, each consisting of two consecutive nights of polysomnography. On the second night of each visit, patients were trained on the motor sequence task (MST) at bedtime and tested the following morning. Academic research center. Twenty-one chronic, medicated schizophrenia outpatients. We compared the effects of two nights of eszopiclone vs. placebo on stage 2 sleep spindles and overnight changes in MST performance. Eszopiclone increased the number and density of spindles over baseline levels significantly more than placebo, but did not significantly enhance overnight MST improvement. In the combined eszopiclone and placebo groups, spindle number and density predicted overnight MST improvement. Eszopiclone significantly increased sleep spindles, which correlated with overnight motor sequence task improvement. These findings provide partial support for the hypothesis that the spindle deficit in schizophrenia impairs sleep-dependent memory consolidation and may be ameliorated by eszopiclone. Larger samples may be needed to detect a significant effect on memory. Given the general role of sleep spindles in cognition, they offer a promising novel potential target for treating cognitive deficits in schizophrenia.

CD30+ lymphoproliferative disorder with spindle-cell morphology.

Science.gov (United States)

Martires, Kathryn J; Cohen, Brandon E; Cassarino, David S

2016-11-01

Lymphomatoid papulosis (LyP) is classified as a CD30+ primary cutaneous lymphoproliferative disease. The phenotypic variability along the spectrum of CD30+ lymphoproliferative diseases is highlighted by the distinct histologic subtypes of LyP types A, B, C, and the more recently described types D, E, and F. We report the case of an elderly woman with a clinical presentation and histopathologic findings consistent with LyP, whose atypical CD30+ infiltrate uniquely demonstrated a spindle-cell morphology. To our knowledge, this is the first reported case of LyP characterized by CD30+ spindle-shaped cells, and may represent a new and distinct histologic variant of LyP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chromatin compaction by condensin I, intra-kinetochore stretch and tension, and anaphase onset, in collective spindle assembly checkpoint interaction

International Nuclear Information System (INIS)

Matsson, Leif

2014-01-01

The control mechanism in mitosis and meiosis by which cells decide to inhibit or allow segregation, the so-called spindle assembly checkpoint (SAC), increases the fidelity of chromosome segregation. It acts like a clockwork mechanism which measures time in units of stable attachments of microtubules (MTs) to kinetochores (the order parameter). Stable MT–kinetochore attachments mediate poleward forces and ‘unstable’ attachments, acting alone or together with motor proteins on kinetochores via chromosomes, antipoleward forces. Stable and unstable attachments could be separated, and the non-equilibrium integrated MT mediated force acting on stably attached kinetochores was derived in a collective interaction (Matsson 2009 J. Phys.: Condens. Matter 21 502101), in which kinetochores were treated as rigid protein complexes. As forces and tension in that model became equally distributed in all bioriented sister chromatid (SC) pairs, segregation was inhibited without need of a ‘wait-anaphase’ signal. In this generalization, the kinetochore is divided into an inner chromatin proximal complex and an outer MT proximal complex, and the integrated MT mediated force is divided into an integrated poleward and an integrated antipoleward force. The model also describes the collective interaction of condensin I with chromatin, which together with the MT mediated dynamics yields the putative in vivo tension in kinetochores and centromeric and pericentromeric chromatin, as a non-linear function of the order parameter. Supported by the compaction force and an increased stiffness in chromatin towards the end of metaphase, the two opposing integrated MT mediated poleward forces, together with metaphase oscillations, induce a swift and synchronized anaphase onset by first increasing the intra-kinetochore stretch. This increase lowers the SAC energy threshold, making a cleavage by separase of all cohesin tethering SC pairs in anaphase energetically possible, thereby reducing the

Spindle Cell Metaplastic Breast Cancer: Case Report

Directory of Open Access Journals (Sweden)

Dursun Ozgur Karakas

2013-08-01

Conclusion: Spindle cell metaplastic breast cancer must be considered in differential diagnosis of breast cancers, and preoperative immunohistochemical examination, including cytokeratin and vimentin, must be added to pathological examination in intervening cases. [Arch Clin Exp Surg 2013; 2(4.000: 259-262

Direct kinetochore?spindle pole connections are not required for chromosome segregation

OpenAIRE

Sikirzhytski, Vitali; Magidson, Valentin; Steinman, Jonathan B.; He, Jie; Le Berre, Ma?l; Tikhonenko, Irina; Ault, Jeffrey G.; McEwen, Bruce F.; Chen, James K.; Sui, Haixin; Piel, Matthieu; Kapoor, Tarun M.; Khodjakov, Alexey

2014-01-01

Segregation of genetic material occurs when chromosomes move to opposite spindle poles during mitosis. This movement depends on K-fibers, specialized microtubule (MT) bundles attached to the chromosomes? kinetochores. A long-standing assumption is that continuous K-fibers connect every kinetochore to a spindle pole and the force for chromosome movement is produced at the kinetochore and coupled with MT depolymerization. However, we found that chromosomes still maintained their position at the...

Thermal Error Modelling of the Spindle Using Data Transformation and Adaptive Neurofuzzy Inference System

Directory of Open Access Journals (Sweden)

Yanlei Li

2015-01-01

Full Text Available This paper proposes a new method for predicting spindle deformation based on temperature data. The method introduces the adaptive neurofuzzy inference system (ANFIS, which is a neurofuzzy modeling approach that integrates the kernel and geometrical transformations. By utilizing data transformation, the number of ANFIS rules can be effectively reduced and the predictive model structure can be simplified. To build the predictive model, we first map the original temperature data to a feature space with Gaussian kernels. We then process the mapped data with the geometrical transformation and make the data gather in the square region. Finally, the transformed data are used as input to train the ANFIS. A verification experiment is conducted to evaluate the performance of the proposed method. Six Pt100 thermal resistances are used to monitor the spindle temperature, and a laser displacement sensor is used to detect the spindle deformation. Experimental results show that the proposed method can precisely predict the spindle deformation and greatly improve the thermal performance of the spindle. Compared with back propagation (BP networks, the proposed method is more suitable for complex working conditions in practical applications.

Cytokeratin: a Shortcut to Diagnose Spindle Cell Carcinoma

Directory of Open Access Journals (Sweden)

Dehghani Nazhvani A

2017-09-01

Full Text Available A relatively rare subtype of squamous cell carcinoma (SCC is spindle cell carcinoma (SPCC. It is composed of epithelium-derived spindle cells arranged in sheets with mesenchymal properties and small, hard-ly detectable regions of SCC, challenging its definite diagnosis. We encountered five cases of SPCC. In case one, chronic inflammation and subepithelial blister with leukoplakia was found 5 years before our examination. And later, exophytic features, keratotic papules and scar with elevated margins was seen on lateral border of the tongue. In case two, three and four, an abnormal soft tissue elevations were examined, and in the fifth case we examined the soft and bony speci-men from the posterior aspect of maxillary ridge. We evaluated all of them histologically and immunohistochemically for cytokeratin to reach final diagnosis.

Declarative memory performance is associated with the number of sleep spindles in elderly women.

Science.gov (United States)

Seeck-Hirschner, Mareen; Baier, Paul Christian; Weinhold, Sara Lena; Dittmar, Manuela; Heiermann, Steffanie; Aldenhoff, Josef B; Göder, Robert

2012-09-01

Recent evidence suggests that the sleep-dependent consolidation of declarative memory relies on the nonrapid eye movement rather than the rapid eye movement phase of sleep. In addition, it is known that aging is accompanied by changes in sleep and memory processes. Hence, the purpose of this study was to investigate the overnight consolidation of declarative memory in healthy elderly women. Sleep laboratory of University. Nineteen healthy elderly women (age range: 61-74 years). We used laboratory-based measures of sleep. To test declarative memory, the Rey-Osterrieth Complex Figure Test was performed. Declarative memory performance in elderly women was associated with Stage 2 sleep spindle density. Women characterized by high memory performance exhibited significantly higher numbers of sleep spindles and higher spindle density compared with women with generally low memory performance. The data strongly support theories suggesting a link between sleep spindle activity and declarative memory consolidation.

Radiation-induced spindle cell sarcoma: A rare case report

Directory of Open Access Journals (Sweden)

Khan Mubeen

2009-01-01

Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

Method for automated building of spindle thermal model with use of CAE system

Science.gov (United States)

Kamenev, S. V.

2018-03-01

The spindle is one of the most important units of the metal-cutting machine tool. Its performance is critical to minimize the machining error, especially the thermal error. Various methods are applied to improve the thermal behaviour of spindle units. One of the most important methods is mathematical modelling based on the finite element analysis. The most common approach for its realization is the use of CAE systems. This approach, however, is not capable to address the number of important effects that need to be taken into consideration for proper simulation. In the present article, the authors propose the solution to overcome these disadvantages using automated thermal model building for the spindle unit utilizing the CAE system ANSYS.

Design of Accelerated Reliability Test for CNC Motorized Spindle Based on Vibration Signal

Directory of Open Access Journals (Sweden)

Chen Chao

2016-01-01

Full Text Available Motorized spindle is the key functional component of CNC machining centers which is a mechatronics system with long life and high reliability. The reliability test cycle of motorized spindle is too long and infeasible. This paper proposes a new accelerated test for reliability evaluation of motorized spindle. By field reliability test, authors collect and calculate the load data including rotational speed, cutting force and torque. Load spectrum distribution law is analyzed. And authors design a test platform to apply the load spectrum. A new method to define the fuzzy acceleration factor based on the vibration signal is proposed. Then the whole test plan of accelerated reliability test is done.

Spindles and active vortices in a model of confined filament-motor mixtures.

Science.gov (United States)

Head, David A; Briels, Wj; Gompper, Gerhard

2011-11-16

Robust self-organization of subcellular structures is a key principle governing the dynamics and evolution of cellular life. In fission yeast cells undergoing division, the mitotic spindle spontaneously emerges from the interaction of microtubules, motor proteins and the confining cell walls, and asters and vortices have been observed to self-assemble in quasi-two dimensional microtubule-kinesin assays. There is no clear microscopic picture of the role of the active motors driving this pattern formation, and the relevance of continuum modeling to filament-scale structures remains uncertain. Here we present results of numerical simulations of a discrete filament-motor protein model confined to a pressurised cylindrical box. Stable spindles, nematic configurations, asters and high-density semi-asters spontaneously emerge, the latter pair having also been observed in cytosol confined within emulsion droplets. State diagrams are presented delineating each stationary state as the pressure, motor speed and motor density are varied. We further highlight a parameter regime where vortices form exhibiting collective rotation of all filaments, but have a finite life-time before contracting to a semi-aster. Quantifying the distribution of life-times suggests this contraction is a Poisson process. Equivalent systems with fixed volume exhibit persistent vortices with stochastic switching in the direction of rotation, with switching times obeying similar statistics to contraction times in pressurised systems. Furthermore, we show that increasing the detachment rate of motors from filament plus-ends can both destroy vortices and turn some asters into vortices. We have shown that discrete filament-motor protein models provide new insights into the stationary and dynamical behavior of active gels and subcellular structures, because many phenomena occur on the length-scale of single filaments. Based on our findings, we argue the need for a deeper understanding of the microscopic

Combining time-frequency and spatial information for the detection of sleep spindles

Directory of Open Access Journals (Sweden)

Christian eO'Reilly

2015-02-01

Full Text Available EEG sleep spindles are short (0.5-2.0 s bursts of activity in the 11-16 Hz band occurring during non-rapid eye movement (NREM sleep. This sporadic activity is thought to play a role in memory consolidation, brain plasticity, and protection of sleep integrity. Many automatic detectors have been proposed to assist or replace experts for sleep spindle scoring. However, these algorithms usually detect too many events making it difficult to achieve a good tradeoff between sensitivity (Se and false detection rate (FDr. In this work, we propose a semi-automatic detector comprising a sensitivity phase based on well-established criteria followed by a specificity phase using spatial and spectral criteria.In the sensitivity phase, selected events are those which amplitude in the 10 – 16 Hz band and spectral ratio characteristics both reject a null hypothesis (p <0.1 stating that the considered event is not a spindle. This null hypothesis is constructed from events occurring during rapid eye movement (REM sleep epochs. In the specificity phase, a hierarchical clustering of the selected candidates is done based on events’ frequency and spatial position along the anterior-posterior axis. Only events from the classes grouping most (at least 80% spindles scored by an expert are kept. We obtain Se = 93.2% and FDr = 93.0% in the first phase and Se = 85.4% and FDr = 86.2% in the second phase. For these two phases, Matthew’s correlation coefficients are respectively 0.228 and 0.324. Results suggest that spindles are defined by specific spatio-spectral properties and that automatic detection methods can be improved by considering these features.

Sleep Spindle Density Predicts the Effect of Prior Knowledge on Memory Consolidation

Science.gov (United States)

Lambon Ralph, Matthew A.; Kempkes, Marleen; Cousins, James N.; Lewis, Penelope A.

2016-01-01

Information that relates to a prior knowledge schema is remembered better and consolidates more rapidly than information that does not. Another factor that influences memory consolidation is sleep and growing evidence suggests that sleep-related processing is important for integration with existing knowledge. Here, we perform an examination of how sleep-related mechanisms interact with schema-dependent memory advantage. Participants first established a schema over 2 weeks. Next, they encoded new facts, which were either related to the schema or completely unrelated. After a 24 h retention interval, including a night of sleep, which we monitored with polysomnography, participants encoded a second set of facts. Finally, memory for all facts was tested in a functional magnetic resonance imaging scanner. Behaviorally, sleep spindle density predicted an increase of the schema benefit to memory across the retention interval. Higher spindle densities were associated with reduced decay of schema-related memories. Functionally, spindle density predicted increased disengagement of the hippocampus across 24 h for schema-related memories only. Together, these results suggest that sleep spindle activity is associated with the effect of prior knowledge on memory consolidation. SIGNIFICANCE STATEMENT Episodic memories are gradually assimilated into long-term memory and this process is strongly influenced by sleep. The consolidation of new information is also influenced by its relationship to existing knowledge structures, or schemas, but the role of sleep in such schema-related consolidation is unknown. We show that sleep spindle density predicts the extent to which schemas influence the consolidation of related facts. This is the first evidence that sleep is associated with the interaction between prior knowledge and long-term memory formation. PMID:27030764

Experimental Analysis and Full Prediction Model of a 5-DOF Motorized Spindle

Directory of Open Access Journals (Sweden)

Weiyu Zhang

2017-01-01

Full Text Available The cost and power consumption of DC power amplifiers are much greater than that of AC power converters. Compared to a motorized spindle supported with DC magnetic bearings, a motorized spindle supported with AC magnetic bearings is inexpensive and more efficient. This paper studies a five-degrees-of-freedom (5-DOF motorized spindle supported with AC hybrid magnetic bearings (HMBs. Most models of suspension forces, except a “switching model”, are quite accurate, but only in a particular operating area and not in regional coverage. If a “switching model” is applied to a 5-DOF motorized spindle, the real-time performance of the control system can be significantly decreased due to the large amount of data processing for both displacement and current. In order to solve this defect, experiments based on the “switching model” are performed, and the resulting data are analyzed. Using the data analysis results, a “full prediction model” based on the operating state is proposed to improve real-time performance and precision. Finally, comparative, verification and stiffness tests are conducted to verify the improvement of the proposed model. Results of the tests indicate that the rotor has excellent characteristics, such as good real-time performance, superior anti-interference performance with load and the accuracy of the model in full zone. The satisfactory experimental results demonstrate the effectiveness of the “full prediction model” applied to the control system under different operating stages. Therefore, the results of the experimental analysis and the proposed full prediction model can provide a control system of a 5-DOF motorized spindle with the most suitable mathematical models of the suspension force.

Error Correction of Radial Displacement in Grinding Machine Tool Spindle by Optimizing Shape and Bearing Tuning

OpenAIRE

Khairul Jauhari; Achmad Widodo; Ismoyo Haryanto

2015-01-01

In this article, the radial displacement error correction capability of a high precision spindle grinding caused by unbalance force was investigated. The spindle shaft is considered as a flexible rotor mounted on two sets of angular contact ball bearing. Finite element methods (FEM) have been adopted for obtaining the equation of motion of the spindle. In this paper, firstly, natural frequencies, critical frequencies, and amplitude of the unbalance response caused by resi...

The function of the sleep spindle: a physiological index of intelligence and a mechanism for sleep-dependent memory consolidation.

Science.gov (United States)

Fogel, Stuart M; Smith, Carlyle T

2011-04-01

Until recently, the electrophysiological mechanisms involved in strengthening new memories into a more permanent form during sleep have been largely unknown. The sleep spindle is an event in the electroencephalogram (EEG) characterizing Stage 2 sleep. Sleep spindles may reflect, at the electrophysiological level, an ideal mechanism for inducing long-term synaptic changes in the neocortex. Recent evidence suggests the spindle is highly correlated with tests of intellectual ability (e.g.; IQ tests) and may serve as a physiological index of intelligence. Further, spindles increase in number and duration in sleep following new learning and are correlated with performance improvements. Spindle density and sigma (14-16Hz) spectral power have been found to be positively correlated with performance following a daytime nap, and animal studies suggest the spindle is involved in a hippocampal-neocortical dialogue necessary for memory consolidation. The findings reviewed here collectively provide a compelling body of evidence that the function of the sleep spindle is related to intellectual ability and memory consolidation. Copyright © 2010 Elsevier Ltd. All rights reserved.

TFG-MET fusion in an infantile spindle cell sarcoma with neural features.

Science.gov (United States)

Flucke, Uta; van Noesel, Max M; Wijnen, Marc; Zhang, Lei; Chen, Chun-Liang; Sung, Yun-Shao; Antonescu, Cristina R

2017-09-01

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials. © 2017 Wiley Periodicals, Inc.

Time-frequency dynamics during sleep spindles on the EEG in rodents with a genetic predisposition to absence epilepsy (WAG/Rij rats)

Science.gov (United States)

Hramov, Alexander E.; Sitnikova, Evgenija Y.; Pavlov, Alexey N.; Grubov, Vadim V.; Koronovskii, Alexey A.; Khramova, Marina V.

2015-03-01

Sleep spindles are known to appear spontaneously in the thalamocortical neuronal network of the brain during slow-wave sleep; pathological processes in the thalamocortical network may be the reason of the absence epilepsy. The aim of the present work is to study developed changes in the time-frequency structure of sleep spindles during the progressive development of the absence epilepsy in WAG/Rij rats. EEG recordings were made at age 7 and 9 months. Automatic recognition and subsequent analysis of sleep spindles on the EEG were performed using the continuous wavelet transform. The duration of epileptic discharges and the total duration of epileptic activity were found to increase with age, while the duration of sleep spindles, conversely, decreased. In terms of the mean frequency, sleep spindles could be divided into three classes: `slow' (mean frequency 9.3Hz), `medium' (11.4Hz), and `fast' (13.5Hz). Slow and medium (transitional) spindles in five-month-old animals showed increased frequency from the beginning to the end of the spindle. The more intense the epilepsy is, the shorter are the durations of spindles of all types. The mean frequencies of `medium' and `fast' spindles were higher in rats with more intense signs of epilepsy. Overall, high epileptic activity in WAG/Rij rats was linked with significant changes in spindles of the transitional type, with less marked changes in the two traditionally identified types of spindle, slow and fast.

Sleep spindles are related to schizotypal personality traits and thalamic glutamine/glutamate in healthy subjects.

Science.gov (United States)

Lustenberger, Caroline; O'Gorman, Ruth L; Pugin, Fiona; Tüshaus, Laura; Wehrle, Flavia; Achermann, Peter; Huber, Reto

2015-03-01

Schizophrenia is a severe mental disorder affecting approximately 1% of the worldwide population. Yet, schizophrenia-like experiences (schizotypy) are very common in the healthy population, indicating a continuum between normal mental functioning and the psychosis found in schizophrenic patients. A continuum between schizotypy and schizophrenia would be supported if they share the same neurobiological origin. Two such neurobiological markers of schizophrenia are: (1) a reduction of sleep spindles (12-15 Hz oscillations during nonrapid eye movement sleep), likely reflecting deficits in thalamo-cortical circuits and (2) increased glutamine and glutamate (Glx) levels in the thalamus. Thus, this study aimed to investigate whether sleep spindles and Glx levels are related to schizotypal personality traits in healthy subjects. Twenty young male subjects underwent 2 all-night sleep electroencephalography recordings (128 electrodes). Sleep spindles were detected automatically. After those 2 nights, thalamic Glx levels were measured by magnetic resonance spectroscopy. Subjects completed a magical ideation scale to assess schizotypy. Sleep spindle density was negatively correlated with magical ideation (r = -.64, P .1). The common relationship of sleep spindle density with schizotypy and thalamic Glx levels indicates a neurobiological overlap between nonclinical schizotypy and schizophrenia. Thus, sleep spindle density and magical ideation may reflect the anatomy and efficiency of the thalamo-cortical system that shows pronounced impairment in patients with schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Analysis of radial runout for symmetric and asymmetric HDD spindle motors with rotor eccentricity

International Nuclear Information System (INIS)

Kim, T.-J.; Kim, K.-T.; Hwang, S.-M.; Lee, S.-B.; Park, N.-G.

2001-01-01

Radial runout of disk drive spindle is one of the major limiting factors in achieving higher track densities in hard disk drives. Mechanical, magnetic and their coupled origins, such as unbalanced mass, reaction forces and magnetic forces, introduce radial runout of spindle motors. In this paper, radial magnetic forces are calculated with respect to the various rotor eccentricities using analytic method. Based on the results of the radial magnetic forces, the radial runout of the spindle motor is analyzed using finite element and transfer matrices. Results show that an asymmetric motor has a worse performance on unbalanced magnetic forces and radial runout when mechanical and magnetic coupling exists

Muscle spindle autogenetic inhibition in the extraocular muscles of lamb.

Science.gov (United States)

Pettorossi, V E; Filippi, G M

1981-09-01

The role of extraocular muscle (EOM) proprioceptors on eye motility has been investigated in lambs on "encéphale isolé", by evaluating the tension of EOMs at various lengths and velocities of stretch before and after proprioceptive blocks. The EOM tension, in the absence of proprioceptive input, was higher than in normal conditions. Such an effect occurred at lengthening values greater than 3 mm of stretch from resting muscle length, corresponding to 18 degrees of eye deviation and was dependent on the velocity of the stretch, being more effective at high velocity. The muscle receptors responsible for this effect was determined by comparing the sensitivity to vibratory stimulation of spindles and tendon organs to the amount of inhibition provoked by the same stimulation on an EOM electromyographic activity. The tension inhibition appeared to be correlated to muscle spindle activation. Thus, the presence of muscle spindles can determine a reduction of the tension within the stretched muscles. This result suggests that the EOM length and velocity signals operate moment to moment reduction on the stiffness of the muscle which antagonizes eye displacement, thus facilitating the ocular movements.

Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

Directory of Open Access Journals (Sweden)

Brand Andrea H

2007-01-01

Full Text Available Abstract Background The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. Results Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. Conclusion We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

Sleep spindle activity in double cortex syndrome: a case report.

Science.gov (United States)

Sforza, Emilia; Marcoz, Jean-Pierre; Foletti, Giovanni

2010-09-01

Cortical dysgenesis is increasingly recognised as a cause of epilepsy. We report a case with double cortex heterotopia and secondarily generalized seizures with a generalised spike wave pattern. During the course of the disease, the child developed electrical status epilepticus in slow wave sleep. From the first examination, sleep pattern revealed increased frequency and amplitude of spindle activity, more evident in anterior areas. The role of the thalamocortical pathway in increased sleep spindle activity is discussed with emphasis on the possible role of altered thalamocortical pathways in abnormal cortical migration. A strong suspicion of cortical dysgenesis may therefore be based on specific EEG sleep patterns.

Dishevelled binds the Discs large 'Hook' domain to activate GukHolder-dependent spindle positioning in Drosophila.

Directory of Open Access Journals (Sweden)

Joshua D Garcia

Full Text Available Communication between cortical cell polarity cues and the mitotic spindle ensures proper orientation of cell divisions within complex tissues. Defects in mitotic spindle positioning have been linked to various developmental disorders and have recently emerged as a potential contributor to tumorigenesis. Despite the importance of this process to human health, the molecular mechanisms that regulate spindle orientation are not fully understood. Moreover, it remains unclear how diverse cortical polarity complexes might cooperate to influence spindle positioning. We and others have demonstrated spindle orientation roles for Dishevelled (Dsh, a key regulator of planar cell polarity, and Discs large (Dlg, a conserved apico-basal cell polarity regulator, effects which were previously thought to operate within distinct molecular pathways. Here we identify a novel direct interaction between the Dsh-PDZ domain and the alternatively spliced "I3-insert" of the Dlg-Hook domain, thus establishing a potential convergent Dsh/Dlg pathway. Furthermore, we identify a Dlg sequence motif necessary for the Dsh interaction that shares homology to the site of Dsh binding in the Frizzled receptor. Expression of Dsh enhanced Dlg-mediated spindle positioning similar to deletion of the Hook domain. This Dsh-mediated activation was dependent on the Dlg-binding partner, GukHolder (GukH. These results suggest that Dsh binding may regulate core interdomain conformational dynamics previously described for Dlg. Together, our results identify Dlg as an effector of Dsh signaling and demonstrate a Dsh-mediated mechanism for the activation of Dlg/GukH-dependent spindle positioning. Cooperation between these two evolutionarily-conserved cell polarity pathways could have important implications to both the development and maintenance of tissue homeostasis in animals.

The role of p53 in the response to mitotic spindle damage

International Nuclear Information System (INIS)

Meek, D.W.

2000-01-01

The p53 tumour suppressor protein has defined roles in G1/S and G2/M cell cycle checkpoint in response to a range of cellular stresses including DNA damage, dominant oncogene expression, hypoxia, metabolic changes and viral infection. In addition to these responses, p53 can also be activated when damage occurs to the mitotic spindle. Initially, spindle damage activates a p53-independent checkpoint which functions at the metaphase-anaphase transition and prevents cells from progressing through mitosis until the completion of spindle formation. Cells eventually escape from this block (a process termed 'mitotic slippage'), and an aberrant mitosis ensues in which sister chromatids fail to segregate properly. After a delay period, p53 responds to this mitotic failure by instituting a G1-like growth arrest, with an intact nucleus containing 4N DNA, but without the cells undergoing division. Cells lacking wild-type p53 are still able to arrest transiently at mitosis, and also fail to undergo division, underscoring that the delay in mitosis is p53-independent. However, these cells are not prevented from re-entering the cell cycle and can reduplicate their DNA unchecked, leading to polyploidy. Additionally, p53-null cells which experience spindle failure often show the appearance of micronuclei arising from poorly segregated chromosomes which have de-condensed and been enclosed in a nuclear envelope. The ability of p53 to prevent their formation suggests an additional G2 involvement which prevents nuclear breakdown prior to mitosis. The molecular mechanism by which p53 is able to sense mitotic failure is still unknown, but may be linked to the ability of p53 to regulate duplication of the centrosome, the organelle which nucleates spindle formation. (authors)

The Making of SPINdle

Science.gov (United States)

Lam, Ho-Pun; Governatori, Guido

We present the design and implementation of SPINdle - an open source Java based defeasible logic reasoner capable to perform efficient and scalable reasoning on defeasible logic theories (including theories with over 1 million rules). The implementation covers both the standard and modal extensions to defeasible logics. It can be used as a standalone theory prover and can be embedded into any applications as a defeasible logic rule engine. It allows users or agents to issues queries, on a given knowledge base or a theory generated on the fly by other applications, and automatically produces the conclusions of its consequences. The theory can also be represented using XML.

Muscle spindle thixotropy affects force perception through afferent-induced facilitation of the motor pathways as revealed by the Kohnstamm effect.

Science.gov (United States)

Monjo, Florian; Forestier, Nicolas

2018-04-01

This study was designed to explore the effects of intrafusal thixotropy, a property affecting muscle spindle sensitivity, on the sense of force. For this purpose, psychophysical measurements of force perception were performed using an isometric force matching paradigm of elbow flexors consisting of matching different force magnitudes (5, 10 and 20% of subjects' maximal voluntary force). We investigated participants' capacity to match these forces after their indicator arm had undergone voluntary isometric conditioning contractions known to alter spindle thixotropy, i.e., contractions performed at long ('hold long') or short muscle lengths ('hold short'). In parallel, their reference arm was conditioned at the intermediate muscle length ('hold-test') at which the matchings were performed. The thixotropy hypothesis predicts that estimation errors should only be observed at low force levels (up to 10% of the maximal voluntary force) with overestimation of the forces produced following 'hold short' conditioning and underestimation following 'hold long' conditioning. We found the complete opposite, especially following 'hold-short' conditioning where subjects underestimated the force they generated with similar relative error magnitudes across force levels. In a second experiment, we tested the hypothesis that estimation errors depended on the degree of afferent-induced facilitation using the Kohnstamm phenomenon as a probe of motor pathway excitability. Because the stronger post-effects were observed following 'hold-short' conditioning, it appears that the conditioning-induced excitation of spindle afferents leads to force misjudgments by introducing a decoupling between the central effort and the cortical motor outputs.

Abnormal spindles in second meiosis in canola (Brassica napus and Brassica campestris

Directory of Open Access Journals (Sweden)

Alice Maria de Souza

1999-01-01

Full Text Available Studies were carried out on the occurrence of abnormal spindles in the second meiotic division in some canola cultivars recently introduced in Brazil. Fusion of spindles was observed in metaphase II rejoining the two sets of chromosomes segregated in anaphase I and also sequential and tripolar spindles were discovered rejoining two sets of chromatids segregated in anaphase II. The frequency of cells with abnormal spindles ranged from 3.18 to 8.10%. The results suggested that this abnormality was caused by environmental stress that affected the plants during the blooming period.O presente estudo descreve a ocorrência de fusos anormais na segunda divisão meiótica em algumas cultivares da canola recentemente introduzidas no Brasil. Fusão de fusos foi observada em metáfase II reunindo os dois conjuntos cromossômicos segregados na anáfase I; fusos sequenciais e tripolares reunindo cromátides segregadas na anáfase II também foram observados. A frequência de células com fusos anormais variou de 3,18 a 8,10% entre as variedades. Os resultados sugerem que estas anormalidades foram causadas por condições climáticas adversas que afetaram as plantas no período de florescimento. As implicações genéticas destas anormalidades são descritas.

Discrimination between micronuclei induced by spindle poisons and ...

African Journals Online (AJOL)

Discrimination between micronuclei induced by spindle poisons and clastogens by using toad bone marrow polychromatic erythrocytes. ... Egyptian Journal of Biology ... The used chemicals induced high percentages of micronuclei with variable sizes, which clarify the sensitivity of bone marrow cells of Bufo regularis to ...

TBCD links centriologenesis, spindle microtubule dynamics, and midbody abscission in human cells.

Directory of Open Access Journals (Sweden)

Mónica López Fanarraga

2010-01-01

Full Text Available Microtubule-organizing centers recruit alpha- and beta-tubulin polypeptides for microtubule nucleation. Tubulin synthesis is complex, requiring five specific cofactors, designated tubulin cofactors (TBCs A-E, which contribute to various aspects of microtubule dynamics in vivo. Here, we show that tubulin cofactor D (TBCD is concentrated at the centrosome and midbody, where it participates in centriologenesis, spindle organization, and cell abscission. TBCD exhibits a cell-cycle-specific pattern, localizing on the daughter centriole at G1 and on procentrioles by S, and disappearing from older centrioles at telophase as the protein is recruited to the midbody. Our data show that TBCD overexpression results in microtubule release from the centrosome and G1 arrest, whereas its depletion produces mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis. TBCD is recruited to the centriole replication site at the onset of the centrosome duplication cycle. A role in centriologenesis is further supported in differentiating ciliated cells, where TBCD is organized into "centriolar rosettes". These data suggest that TBCD participates in both canonical and de novo centriolar assembly pathways.

A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition

Science.gov (United States)

Moutinho-Santos, Tatiana

2013-01-01

Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor. PMID:23609535

Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical spindle (10-16-Hz) oscillations in the rat.

Science.gov (United States)

Zheng, Thomas W; O'Brien, Terence J; Kulikova, Sofya P; Reid, Christopher A; Morris, Margaret J; Pinault, Didier

2014-03-01

A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single systemic injection of CBZ (20 mg/kg) induced a significant increase in the power of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves. This hybrid sequence occurred during a slow hyperpolarizing trough, and was at least 10 times more frequent under the CBZ condition than under the control condition. The hyperpolarizing waves reversed at approximately -70 mV, and became depolarizing when recorded with KCl-filled intracellular micropipettes, indicating that they were GABAA receptor-mediated potentials. In neurons of the GABAergic thalamic reticular nucleus, the principal source of TC GABAergic inputs, CBZ augmented both the number and the duration of sequences of rhythmic spindle-frequency bursts of action potentials. This indicates that these GABAergic neurons are responsible for the generation of at least the spindle-frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT 5-9-Hz waves can trigger TC spindles. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3 complex-driven cytoplasmic streaming in mouse oocytes

Science.gov (United States)

Yi, Kexi; Unruh, Jay R.; Deng, Manqi; Slaughter, Brian D.; Rubinstein, Boris; Li, Rong

2012-01-01

Mature mammalian oocytes are poised for the completion of second polar body extrusion upon fertilization by positioning the metaphase spindle in close proximity to an actomyosin-rich cortical cap. Loss of this spindle position asymmetry is often associated with poor oocyte quality and infertility 1–3. Here, we report a novel role for the Arp2/3 actin nucleation complex in the maintenance of asymmetric spindle position in mature mouse oocytes. The Arp2/3 complex localizes to the cortical cap in a Ran GTPase-dependent manner and accounts for the nucleation of the majority of actin filaments in both the cortical cap and a cytoplasmic actin network. Inhibition of Arp2/3 complex activity or localization leads to rapid dissociation of the spindle from the cortex. High resolution live imaging and spatiotemporal image correlation spectroscopy (STICS) analysis reveal that in normal oocytes actin filaments flow continuously away from the Arp2/3-rich cortex, generating a cytoplamic streaming that results in a net pushing force on the spindle toward the actomyosin cap. Arp2/3 inhibition not only diminishes this actin flow and cytoplamic streaming but also enables a reverse streaming driven by myosin-II-based cortical contraction, leading to spindle movement away from the cortex. We conclude that the Arp2/3 complex maintains asymmetric meiotic spindle position by generating an actin polymerization-driven cytoplamic streaming and by suppressing a counteracting force from myosin-II-based contractility. PMID:21874009

Central myofibroma of the maxilla

Directory of Open Access Journals (Sweden)

Paramjeet Kaur

2016-01-01

Full Text Available Myofibroma is a rare benign localized or generalized proliferation of myofibroblastic tissue occurring mostly in infants or children. In the oral region, most lesions occur in the mandible, lip, buccal mucosa, and tongue; however, the lesions arising in the maxilla are very rare. Myofibroma has an aggressive clinical presentation and is often treated aggressively because of an inappropriate diagnosis. A unique feature of central myofibroma of the jaws is the potential for teeth and other odontogenic structures to be involved by tumor. We report a case of myofibroma arising in the left side of the maxilla of a 12-year-old girl and describe the differential diagnosis from other spindle cell lesions of neural and smooth muscle origin. We treated the case using surgical excision under general anesthesia. Immunohistochemical staining was done for establishing the diagnosis since histopathological diagnosis with conventional staining could not distinguish myofibroma from spindle cell tumors.

Spindle disturbances in human-hamster hybrid (AL) cells induced by mobile communication frequency range signals.

Science.gov (United States)

Schrader, Thorsten; Münter, Klaus; Kleine-Ostmann, Thomas; Schmid, Ernst

2008-12-01

The production of spindle disturbances in FC2 cells, a human-hamster hybrid (A(L)) cell line, by non-ionizing radiation was studied using an electromagnetic field with a field strength of 90 V/m at a frequency of 835 MHz. Due to the given experimental conditions slide flask cultures were exposed at room temperature in a microTEM (transversal electromagnetic field) cell, which allows optimal experimental conditions for small samples of biological material. Numerical calculations suggest that specific absorption rates of up to 60 mW/kg are reached for maximum field exposure. All exposure field parameters--either measured or calculable--are precisely defined and, for the first time, traceable to the standards of the SI system of physical units. Compared with co-incident negative controls, the results of two independently performed experiments suggest that exposure periods of time from 0.5 to 2 h with an electric field strength of 90 V/m are spindle acting agents as predominately indicated by the appearance of spindle disturbances at the ana- and telophase stages (especially lagging and non-disjunction of single chromosomes) of cell divisions. The spindle disturbances do not change the fraction of mitotic cells with increasing exposure time up to 2 h. Due to the applied experimental conditions an influence of temperature as a confounder parameter for spindle disturbances can be excluded.

SPINDLE: A 2-Stage Nuclear-Powered Cryobot for Ocean World Exploration

Science.gov (United States)

Stone, W.; Hogan, B.; Siegel, V. L.; Howe, T.; Howe, S.; Harman, J.; Richmond, K.; Flesher, C.; Clark, E.; Lelievre, S.; Moor, J.; Rothhammer, B.

2016-12-01

SPINDLE (Sub-glacial Polar Ice Navigation, Descent, and Lake Exploration) is a 2-stage autonomous vehicle system consisting of a robotic ice-penetrating carrier vehicle (cryobot) and a marsupial, hovering autonomous underwater vehicle (HAUV). The cryobot will descend through an ice body into a sub-ice aqueous environment and deploy the HAUV to conduct long range reconnaissance, life search, and sample collection. The HAUV will return to, and auto-dock with, the cryobot at the conclusion of the mission for subsequent data uplink and sample return to the surface. The SPINDLE cryobot has been currently designed for a 1.5 kilometer penetration through a terrestrial ice sheet and the HAUV has been designed for persistent exploration and science presence in for deployments up to a kilometer radius from the cryobot. Importantly, the cryobot is bi-directional and vertically controllable both in an ice sheet as well as following breakthrough into a subglacial water cavity / ocean. The vehicle has been designed for long-duration persistent science in subglacial cavities and to allow for subsequent return-to-surface at a much later date or subsequent season. Engineering designs for the current SPINDLE cryobot will be presented in addition to current designs for autonomous rendezvous, docking, and storing of the HAUV system into the cryobot for subsequent recovery of the entire system to the surface. Taken to completion in a three-phase program, SPINDLE will deliver an integrated and field-tested system that will be directly transferable into a Flagship-class mission to either the hypothesized shallow lakes of Europa, the sub-surface ocean of Ganymede, or the geyser/plume sources on both Europa and Enceladus. We present the results of several parallel laboratory investigations into advanced power transmission systems (laser, high voltage) as well as onboard systems that enable the SPINDLE vehicle to access any subglacial lake on earth while using non-nuclear surrogate, surface

Nuclear targeting by fragmentation of the Potato spindle tuber viroid genome

International Nuclear Information System (INIS)

Abraitiene, Asta; Zhao Yan; Hammond, Rosemarie

2008-01-01

Transient expression of engineered reporter RNAs encoding an intron-containing green fluorescent protein (GFP) from a Potato virus X-based expression vector previously demonstrated the nuclear targeting capability of the 359 nucleotide Potato spindle tuber viroid (PSTVd) RNA genome. To further delimit the putative nuclear-targeting signal, PSTVd subgenomic fragments were embedded within the intron, and recombinant reporter RNAs were inoculated onto Nicotiana benthamiana plants. Appearance of green fluorescence in leaf tissue inoculated with PSTVd-fragment-containing constructs indicated shuttling of the RNA into the nucleus by fragments as short as 80 nucleotides in length. Plant-to-plant variation in the timing of intron removal and subsequent GFP fluorescence was observed; however, earliest and most abundant GFP expression was obtained with constructs containing the conserved hairpin I palindrome structure and embedded upper central conserved region. Our results suggest that this conserved sequence and/or the stem-loop structure it forms is sufficient for import of PSTVd into the nucleus

ATLAS Tile Calorimeter central barrel assembly and installation.

CERN Multimedia

nikolai topilin

2009-01-01

These photos belong to the self-published book by Nikolai Topilin "ATLAS Hadron Calorimeter Assembly". The book is a collection of souvenirs from the years of assembly and installation of the Tile Hadron Calorimeter, which extended from November 2002 until May 2006.

Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska complex to kinetochores

Directory of Open Access Journals (Sweden)

Sushama Sivakumar

2017-11-01

Full Text Available Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The spindle- and kinetochore-associated (Ska complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1 to kinetochores. Here we show that PP1 and protein phosphatase 2A (PP2A both promote accumulation of Ska at kinetochores. Depletion of PP1 or PP2A by siRNA reduces Ska binding at kinetochores, impairs alignment of chromosomes to the spindle midplane, and causes metaphase delay or arrest, phenotypes that are also seen after depletion of Ska. Artificial tethering of PP1 to the outer kinetochore protein Nuf2 promotes Ska recruitment to kinetochores, and it reduces but does not fully rescue chromosome alignment and metaphase arrest defects seen after Ska depletion. We propose that Ska has multiple functions in promoting mitotic progression and that kinetochore-associated phosphatases function in a positive feedback cycle to reinforce Ska complex accumulation at kinetochores.

Spindles and active vortices in a model of confined filament-motor mixtures

Directory of Open Access Journals (Sweden)

Head David A

2011-11-01

Full Text Available Abstract Background Robust self-organization of subcellular structures is a key principle governing the dynamics and evolution of cellular life. In fission yeast cells undergoing division, the mitotic spindle spontaneously emerges from the interaction of microtubules, motor proteins and the confining cell walls, and asters and vortices have been observed to self-assemble in quasi-two dimensional microtubule-kinesin assays. There is no clear microscopic picture of the role of the active motors driving this pattern formation, and the relevance of continuum modeling to filament-scale structures remains uncertain. Results Here we present results of numerical simulations of a discrete filament-motor protein model confined to a pressurised cylindrical box. Stable spindles, nematic configurations, asters and high-density semi-asters spontaneously emerge, the latter pair having also been observed in cytosol confined within emulsion droplets. State diagrams are presented delineating each stationary state as the pressure, motor speed and motor density are varied. We further highlight a parameter regime where vortices form exhibiting collective rotation of all filaments, but have a finite life-time before contracting to a semi-aster. Quantifying the distribution of life-times suggests this contraction is a Poisson process. Equivalent systems with fixed volume exhibit persistent vortices with stochastic switching in the direction of rotation, with switching times obeying similar statistics to contraction times in pressurised systems. Furthermore, we show that increasing the detachment rate of motors from filament plus-ends can both destroy vortices and turn some asters into vortices. Conclusions We have shown that discrete filament-motor protein models provide new insights into the stationary and dynamical behavior of active gels and subcellular structures, because many phenomena occur on the length-scale of single filaments. Based on our findings, we argue

Male gametogenesis without centrioles.

Science.gov (United States)

Riparbelli, Maria Giovanna; Callaini, Giuliano

2011-01-15

The orientation of the mitotic spindle plays a central role in specifying stem cell-renewal by enabling interaction of the daughter cells with external cues: the daughter cell closest to the hub region is instructed to self-renew, whereas the distal one starts to differentiate. Here, we have analyzed male gametogenesis in DSas-4 Drosophila mutants and we have reported that spindle alignment and asymmetric divisions are properly executed in male germline stem cells that lack centrioles. Spermatogonial divisions also correctly proceed in the absence of centrioles, giving rise to cysts of 16 primary spermatocytes. By contrast, abnormal meiotic spindles assemble in primary spermatocytes. These results point to different requirements for centrioles during male gametogenesis of Drosophila. Spindle formation during germ cell mitosis may be successfully supported by an acentrosomal pathway that is inadequate to warrant the proper execution of meiosis. Copyright © 2010 Elsevier Inc. All rights reserved.

The Thermohydrodynamic Analysis of Sliding Bearing High-Speed Motorized Spindle by Rotor Dynamic

Directory of Open Access Journals (Sweden)

Li Songsheng

2017-01-01

Full Text Available This is paper presents thermohydrodynamic characteristics of high speed motorized spindle sliding bearing rotor system. The dynamic characteristic of the oil film bearing is affected by temperature increment, thereby affecting the high-speed spindle rotor system dynamics. This study applied the hydrodynamic lubrication theory, the influence of temperature on the viscosity of lubricating oil, associated with the bearing stiffness, oil film damping and other performance parameters, is considered in generalized Reynolds equation of oil film bearing. The theoretical model of the sliding bearing rotor system is established by using the transfer matrix method to analyze the dynamic characteristic and verified by experiments. The results show the high temperature environment in the motorized spindle and the friction of the bearing lead to oil temperature rise and viscosity reduction, which influences the bearing capacity, stiffness and damping, hence impact on the critical speeds and modal shapes of the sliding bearing rotor system.

Combined classical spindle cell/pleomorphic lipoma spectrum imaging and clinical data

Energy Technology Data Exchange (ETDEWEB)

Younan, Yara; Gonzalez, Felix; Umpierrez, Monica; Singer, Adam D. [Emory University Hospital, Department of Radiology and Imaging Sciences Section of Musculoskeletal Imaging, Atlanta, GA (United States); Martinez, Anthony; Edgar, Mark [Emory University Hospital, Department of Pathology, Atlanta, GA (United States); Reimer, Nickolas [Emory University Hospital, Department of Orthopedic Surgery, Atlanta, GA (United States); Subhawong, Ty [University of Miami, Department of Radiology, Miami, FL (United States)

2018-01-15

Compile the largest study to date on the imaging and clinical features of the classic spindle cell/pleomorphic lipoma spectrum and suggest this diagnosis be included in the differential for benign and malignant macroscopic fat-containing soft tissue masses regardless of the mass location or patient demographics. An institutional search was performed to identify all available classic-type spindle cell/pleomorphic lipomas with available demographic and imaging data. Images and reports were analyzed by one MSK-trained radiologist and radiographic, anatomic and clinical data were recorded. Additionally, a literature search was performed to identify studies describing the spindle cell lipoma spectrum imaging features and were combined with institutional data. Forty-two institutional cases were identified, 37 of which had MRIs performed among which 21 had images available (T1- and T2-weighted pulse sequences) for review while the remainder had outside reports detailing the mass imaging features. There was a mean age of 57 with 79% of cases occurring in males. Contrary to prior reports, 57% of masses were subcutaneous, and the neck and back region accounted for 26% of cases. When the institutional cases were combined with available data in the literature, there was a new sample size of 91 masses, 74 of which had MRI and/or CT data. Eighty-seven percent of masses were heterogeneous, 51% were composed of less than 75% fat, 65% were in the back, neck or shoulder region, 27% of masses were deep and 91% demonstrated enhancement. Eighty-two percent of patients were males with a mean age of 58 at excision. Imaging features, patient demographics and tumor location alone are not enough to differentiate tumors of the spindle cell lipoma spectrum from other macroscopic fat-containing benign and malignant tumors, and these entities should be included in the same imaging differential diagnosis. (orig.)

Lateralised sleep spindles relate to false memory generation.

Science.gov (United States)

Shaw, John J; Monaghan, Padraic

2017-12-01

Sleep is known to enhance false memories: After presenting participants with lists of semantically related words, sleeping before recalling these words results in a greater acceptance of unseen "lure" words related in theme to previously seen words. Furthermore, the right hemisphere (RH) seems to be more prone to false memories than the left hemisphere (LH). In the current study, we investigated the sleep architecture associated with these false memory and lateralisation effects in a nap study. Participants viewed lists of related words, then stayed awake or slept for approximately 90min, and were then tested for recognition of previously seen-old, unseen-new, or unseen-lure words presented either to the LH or RH. Sleep increased acceptance of unseen-lure words as previously seen compared to the wake group, particularly for RH presentations of word lists. RH lateralised stage 2 sleep spindle density relative to the LH correlated with this increase in false memories, suggesting that RH sleep spindles enhanced false memories in the RH. Copyright © 2017 Elsevier Ltd. All rights reserved.

In-situ hot corrosion testing of candidate materials for exhaust valve spindles

DEFF Research Database (Denmark)

Bihlet, Uffe; Hoeg, Harro A.; Dahl, Kristian Vinter

2011-01-01

The two stroke diesel engine has been continually optimized since its invention more than a century ago. One of the ways to increase fuel efficiency further is to increase the compression ratio, and thereby the temperature in the combustion chamber. Because of this, and the composition of the fuel...... used, exhaust valve spindles in marine diesel engines are subjected to high temperatures and stresses as well as molten salt induced corrosion. To investigate candidate materials for future designs which will involve the HIP process, a spindle with Ni superalloy material samples inserted in a HIPd Ni49...

Establishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant

Directory of Open Access Journals (Sweden)

Nicolas Lecland

2013-01-01

In animal cells the centrosome is commonly viewed as the main cellular structure driving microtubule (MT assembly into the mitotic spindle apparatus. However, additional pathways, such as those mediated by chromatin and augmin, are involved in the establishment of functional spindles. The molecular mechanisms involved in these pathways remain poorly understood, mostly due to limitations inherent to current experimental systems available. To overcome these limitations we have developed six new Drosophila cell lines derived from Drosophila homozygous mutants for DSas-4, a protein essential for centriole biogenesis. These cells lack detectable centrosomal structures, astral MT, with dispersed pericentriolar proteins D-PLP, Centrosomin and γ-tubulin. They show poorly focused spindle poles that reach the plasma membrane. Despite being compromised for functional centrosome, these cells could successfully undergo mitosis. Live-cell imaging analysis of acentriolar spindle assembly revealed that nascent MTs are nucleated from multiple points in the vicinity of chromosomes. These nascent MTs then grow away from kinetochores allowing the expansion of fibers that will be part of the future acentriolar spindle. MT repolymerization assays illustrate that acentriolar spindle assembly occurs “inside-out” from the chromosomes. Colchicine-mediated depolymerization of MTs further revealed the presence of a functional Spindle Assembly Checkpoint (SAC in the acentriolar cells. Finally, pilot RNAi experiments open the potential use of these cell lines for the molecular dissection of anastral pathways in spindle and centrosome assembly.

Abnormal spindle orientation during microsporogenesis in an interspecific Brachiaria (Gramineae hybrid

Directory of Open Access Journals (Sweden)

Andréa Beatriz Mendes-Bonato

2006-01-01

Full Text Available This paper reports a case of abnormal spindle orientation during microsporogenesis in an interspecific hybrid of the tropical grass Brachiaria. In the affected plant, prophase I was normal. In metaphase I, bivalents were regularly co-oriented but distantly positioned and spread over the equatorial plate. In anaphase I, chromosomes failed to converge into focused poles due to parallel spindle fibers. As a consequence, in telophase I, an elongated nucleus or several micronuclei were observed in each pole. In the second division, the behavior was the same, leading to polyads with several micronuclei. A total of 40% of meiotic products were affected. The use of this hybrid in production systems needing good-quality seeds is discussed.

Dynamics modeling and modal experimental study of high speed motorized spindle

International Nuclear Information System (INIS)

Li, Yunsong; Chen, Xiaoan; Zhang, Peng; Zhou, Jinming

2017-01-01

This paper presents a dynamical model of high speed motorized spindles in free state and work state. In the free state, the housing is modeled as a rotor with equivalent masses including bearing pedestals, motor stator and rear end cover. As a consequence, a double rotor dynamics can be modeled for high speed motorized spindles by a bearing element which connects the housing and bearing pedestals. In the work state, the housing is fixed and the system becomes a bearing-rotor dynamical model. An excitation-measurement test in the free state is designed to analyze the cross spectral density and auto spectral density of input and output signals. Then the frequency response function of system and coherence function of input and output signals which are used to analyze the inherent characteristics of the double- rotor model can be obtained. The other vibration test in the work state is designed to research the dynamical supporting characteristics of bearings and the effects from bearings on the inherent characteristics of the system. The good agreement between the experimental data and theoretical results indicates that the dynamical model in two states is capable of accurately predicting the dynamic behavior of high speed motorized spindles

Dynamics modeling and modal experimental study of high speed motorized spindle

Energy Technology Data Exchange (ETDEWEB)

Li, Yunsong; Chen, Xiaoan; Zhang, Peng; Zhou, Jinming [Chongqing Univ., Chongqing (China)

2017-03-15

This paper presents a dynamical model of high speed motorized spindles in free state and work state. In the free state, the housing is modeled as a rotor with equivalent masses including bearing pedestals, motor stator and rear end cover. As a consequence, a double rotor dynamics can be modeled for high speed motorized spindles by a bearing element which connects the housing and bearing pedestals. In the work state, the housing is fixed and the system becomes a bearing-rotor dynamical model. An excitation-measurement test in the free state is designed to analyze the cross spectral density and auto spectral density of input and output signals. Then the frequency response function of system and coherence function of input and output signals which are used to analyze the inherent characteristics of the double- rotor model can be obtained. The other vibration test in the work state is designed to research the dynamical supporting characteristics of bearings and the effects from bearings on the inherent characteristics of the system. The good agreement between the experimental data and theoretical results indicates that the dynamical model in two states is capable of accurately predicting the dynamic behavior of high speed motorized spindles.

Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas.

Science.gov (United States)

Arai, Eri; Gotoh, Masahiro; Tian, Ying; Sakamoto, Hiromi; Ono, Masaya; Matsuda, Akio; Takahashi, Yoriko; Miyata, Sayaka; Totsuka, Hirohiko; Chiku, Suenori; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Matsumoto, Kenji; Yamada, Tesshi; Yoshida, Teruhiko; Kanai, Yae

2015-12-01

CpG-island methylator phenotype (CIMP)-positive clear cell renal cell carcinomas (RCCs) are characterized by accumulation of DNA hypermethylation of CpG islands, clinicopathological aggressiveness and poor patient outcome. The aim of this study was to clarify the molecular pathways participating in CIMP-positive renal carcinogenesis. Genome (whole-exome and copy number), transcriptome and proteome (two-dimensional image converted analysis of liquid chromatography-mass spectrometry) analyses were performed using tissue specimens of 87 CIMP-negative and 14 CIMP-positive clear cell RCCs and corresponding specimens of non-cancerous renal cortex. Genes encoding microtubule-associated proteins, such as DNAH2, DNAH5, DNAH10, RP1 and HAUS8, showed a 10% or higher incidence of genetic aberrations (non-synonymous single-nucleotide mutations and insertions/deletions) in CIMP-positive RCCs, whereas CIMP-negative RCCs lacked distinct genetic characteristics. MetaCore pathway analysis of CIMP-positive RCCs revealed that alterations of mRNA or protein expression were significantly accumulated in six pathways, all participating in the spindle checkpoint, including the "The metaphase checkpoint (p = 1.427 × 10(-6))," "Role of Anaphase Promoting Complex in cell cycle regulation (p = 7.444 × 10(-6))" and "Spindle assembly and chromosome separation (p = 9.260 × 10(-6))" pathways. Quantitative RT-PCR analysis revealed that mRNA expression levels for genes included in such pathways, i.e., AURKA, AURKB, BIRC5, BUB1, CDC20, NEK2 and SPC25, were significantly higher in CIMP-positive than in CIMP-negative RCCs. All CIMP-positive RCCs showed overexpression of Aurora kinases, AURKA and AURKB, and this overexpression was mainly attributable to increased copy number. These data suggest that abnormalities of the spindle checkpoint pathway participate in CIMP-positive renal carcinogenesis, and that AURKA and AURKB may be potential therapeutic targets in more aggressive CIMP-positive RCCs. �

IL-6 and mouse oocyte spindle.

Directory of Open Access Journals (Sweden)

Jashoman Banerjee

Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

Gas flow through the clearances of screw spindle vacuum pumps; Gasspaltstroemungen in Schraubenspindel-Vakuumpumpen

Energy Technology Data Exchange (ETDEWEB)

Kauder, K.; Wenderott, D. [Dortmund Univ. (Germany). FG Fluidenergiemaschinen

1998-12-31

The documentation `Schraubenmaschinen` deals with the subject `screw spindle vacuum pump` for the first time. Therefore, this paper presents the type of maschine `screw spindle vacuum pump`, fixes its limits to the better known screw type compressor and finally classifies it in the crossover of vacuum-technology, characteristic geometry and the numerical simulation. The suggested reflections to choose a proper model of flow are based on the geometry of the screw spindle vacuum pump and fundamentals concerning the vacuum-technology and the state of flow. (orig.) [Deutsch] Die Schriftenreihe `Schraubenmaschinen` behandelt erstmals das Thema `Schraubenspindel-Vakuumpumpe`. Aus diesem Grund stellt der vorliegende Beitrag den Maschinentyp Schraubenspindel-Vakuumpumpe vor, grenzt ihn zur bekannteren Schraubenmaschine ab und ordnet ihn in der Schnittmenge aus Vakuumtechnik, charakteristischer Maschinengeometrie und der Simulation ein. Auf den vakuumtechnischen und stroemungstechnischen Grundlagen sowie geometrischen Betrachtungen basieren die genannten Ueberlegungen zur Auswahl geeigneter Stroemungsmodelle. (orig.)

Research on a power management system for thermoelectric generators to drive wireless sensors on a spindle unit.

Science.gov (United States)

Li, Sheng; Yao, Xinhua; Fu, Jianzhong

2014-07-16

Thermoelectric energy harvesting is emerging as a promising alternative energy source to drive wireless sensors in mechanical systems. Typically, the waste heat from spindle units in machine tools creates potential for thermoelectric generation. However, the problem of low and fluctuant ambient temperature differences in spindle units limits the application of thermoelectric generation to drive a wireless sensor. This study is devoted to presenting a transformer-based power management system and its associated control strategy to make the wireless sensor work stably at different speeds of the spindle. The charging/discharging time of capacitors is optimized through this energy-harvesting strategy. A rotating spindle platform is set up to test the performance of the power management system at different speeds. The experimental results show that a longer sampling cycle time will increase the stability of the wireless sensor. The experiments also prove that utilizing the optimal time can make the power management system work more effectively compared with other systems using the same sample cycle.

Distribution of TTX-sensitive voltage-gated sodium channels in primary sensory endings of mammalian muscle spindles.

Science.gov (United States)

Carrasco, Dario I; Vincent, Jacob A; Cope, Timothy C

2017-04-01

Knowledge of the molecular mechanisms underlying signaling of mechanical stimuli by muscle spindles remains incomplete. In particular, the ionic conductances that sustain tonic firing during static muscle stretch are unknown. We hypothesized that tonic firing by spindle afferents depends on sodium persistent inward current (INaP) and tested for the necessary presence of the appropriate voltage-gated sodium (NaV) channels in primary sensory endings. The NaV 1.6 isoform was selected for both its capacity to produce INaP and for its presence in other mechanosensors that fire tonically. The present study shows that NaV 1.6 immunoreactivity (IR) is concentrated in heminodes, presumably where tonic firing is generated, and we were surprised to find NaV 1.6 IR strongly expressed also in the sensory terminals, where mechanotransduction occurs. This spatial pattern of NaV 1.6 IR distribution was consistent for three mammalian species (rat, cat, and mouse), as was tonic firing by primary spindle afferents. These findings meet some of the conditions needed to establish participation of INaP in tonic firing by primary sensory endings. The study was extended to two additional NaV isoforms, selected for their sensitivity to TTX, excluding TTX-resistant NaV channels, which alone are insufficient to support firing by primary spindle endings. Positive immunoreactivity was found for NaV 1.1 , predominantly in sensory terminals together with NaV 1.6 and for NaV 1.7 , mainly in preterminal axons. Differential distribution in primary sensory endings suggests specialized roles for these three NaV isoforms in the process of mechanosensory signaling by muscle spindles. NEW & NOTEWORTHY The molecular mechanisms underlying mechanosensory signaling responsible for proprioceptive functions are not completely elucidated. This study provides the first evidence that voltage-gated sodium channels (NaVs) are expressed in the spindle primary sensory ending, where NaVs are found at every site

Nicotine-induced Disturbances of Meiotic Maturation in Cultured Mouse Oocytes: Alterations of Spindle Integrity and Chromosome Alignment

Directory of Open Access Journals (Sweden)

Zenzes Maria

2004-09-01

Full Text Available Abstract We investigated whether nicotine exposure in vitro of mouse oocytes affects spindle and chromosome function during meiotic maturation (M-I and M-II. Oocytes in germinal vesicle (GV stage were cultured in nicotine for 8 h or for 16 h, to assess effects in M-I and in metaphase II (M-II. The latter culture setting used the three protocols: 8 h nicotine then 8 h medium (8N + 8M; 16 h nicotine (16N; 8 h medium then 8 h nicotine (8M + 8N. Non-toxic concentrations of nicotine at 1.0, 2.5, 5.0 and 10.0 mmol/L were used. Spindle-chromosome configurations were analyzed with wide-field optical sectioning microscopy. In 8 h cultures, nicotine exposure resulted in dose-related increased proportions of M-I oocytes with defective spindle-chromosome configurations. A dose-related delayed entry into anaphase I was also detected. In 16 h cultures, nicotine exposure for the first 8 h (8N + 8M, or for 16 h (16N, resulted in dose- and time-related increased proportions of oocytes arrested in M-I (10 mmol/L; 8 h: 53.2%, controls 9.6%; 16 h: 87.6%, controls 8.5%. Defects in M-I spindles and chromosomes caused M-I arrest leading to dose-related decreased proportions of oocytes that reached metaphase-II (10 mmol/L 8 h: 46.8%, controls 90.4%;16 h: 12.4%, controls 91.5%. A delayed anaphase-I affected the normal timing of M-II, leading to abnormal oocytes with dispersed chromosomes, or with double spindles and no polar body. Nicotine exposure during the second 8 h (8M + 8N resulted in dose-related, increased proportions of M-II oocytes with defective spindles and chromosomes (10 mmol/L: 42.9%, controls 2.0%. Nicotine has no adverse effects on GV break down, but induces spindle and chromosome defects compromising oocyte meiotic maturation and development.

Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

Science.gov (United States)

Boekhout, Michiel; Wolthuis, Rob

2015-04-15

Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. © 2015. Published by The Company of Biologists Ltd.

New mitotic regulators released from chromatin

Directory of Open Access Journals (Sweden)

Hideki eYokoyama

2013-12-01

Full Text Available Faithful action of the mitotic spindle segregates duplicated chromosomes into daughter cells. Perturbations of this process result in chromosome mis-segregation, leading to chromosomal instability and cancer development. Chromosomes are not simply passengers segregated by spindle microtubules but rather play a major active role in spindle assembly. The GTP bound form of the Ran GTPase (RanGTP, produced around chromosomes, locally activates spindle assembly factors. Recent studies have uncovered that chromosomes organize mitosis beyond spindle formation. They distinctly regulate other mitotic events, such as spindle maintenance in anaphase, which is essential for chromosome segregation. Furthermore, the direct function of chromosomes is not only to produce RanGTP but, in addition, to release key mitotic regulators from chromatin. Chromatin-remodeling factors and nuclear pore complex proteins, which have established functions on chromatin in interphase, dissociate from mitotic chromatin and function in spindle assembly or maintenance. Thus, chromosomes actively organize their own segregation using chromatin-releasing mitotic regulators as well as RanGTP.

The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression.

Science.gov (United States)

Silva, Nicola; Ferrandiz, Nuria; Barroso, Consuelo; Tognetti, Silvia; Lightfoot, James; Telecan, Oana; Encheva, Vesela; Faull, Peter; Hanni, Simon; Furger, Andre; Snijders, Ambrosius P; Speck, Christian; Martinez-Perez, Enrique

2014-11-24

Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, and poorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint. Copyright © 2014 Elsevier Inc. All rights reserved.

Glucose assisted synthesis of hollow spindle LiMnPO_4/C nanocomposites for high performance Li-ion batteries

International Nuclear Information System (INIS)

Fu, Xiaoning; Chang, Zhaorong; Chang, Kun; Li, Bao; Tang, Hongwei; Shangguan, Enbo; Yuan, Xiao-Zi; Wang, Haijiang

2015-01-01

Graphical abstract: Nano-sized hollow spindle LiMnPO_4 with a well-developed olivine-type structure exhibits a high specific capacity and cycling performance. - Highlights: • A pure and well-crystallized LiMnPO_4 are synthesized via a solution-phase method. • The LiMnPO_4/C composite constitutes highly and uniformly distributed hollow spindles. • The LiMnPO_4/C composite exhibits a high specific capacity and cycling performance. • The growth process of the hollow spindle LiMnPO_4 particles is revealed. - Abstract: Nano-sized hollow spindle LiMnPO_4 with a well-developed olivine-type structure was synthesized with the assistance of glucose in dimethyl sulfoxide (DMSO)/H_2O under ambient pressure and 108 °C. The scanning electron microscopy (SEM) and transmission electron microscope (TEM) images show that the LiMnPO_4 particles consist of hollow spindles with a mean width of 200 nm, length of 500-700 nm, and wall thickness of about 30-60 nm. The LiMnPO_4/C nanocomposite was obtained by sintering nano-sized LiMnPO_4 with glucose at 650 °C under an inert atmosphere for 4 h. With a coated carbon thickness of about 10 nm, the obtained composite maintained the morphology and size of the hollow spindle. The electrochemical tests show the specific capacity of LiMnPO_4/C nanocomposite is 161.8 mAh g"−"1 at 0.05C, 137.7 mAh g"−"1 at 0.1C and 110.8 mAh g"−"1 at 0.2 C. The retention of discharge capacity maintains 92% after 100 cycles at 0.2 C. After different rate cycles the high capacity of the LiMnPO_4/C nanocomposite can be recovered. This high performance is attributed to the composite material's hollow spindle structure, which facilitates the electrolyte infiltration, resulting in an increased solid-liquid interface. The carbon layer covering the hollow spindle also contributes to the high performance of the LiMnPO_4/C material as the carbon layer improves its electronic conductivity and the nano-scaled wall thickness decreases the paths of Li

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.

Primary histiocytic sarcoma arising in the head and neck with predominant spindle cell component

Directory of Open Access Journals (Sweden)

Zhao XF

2007-02-01

Full Text Available Abstract This is the first case report of Histiocytic Sarcoma (HS with predominant spindle cell component occurring in the head and neck region of a 41-year-old man. The tumor was composed of sheets of large round to oval cells with pleomorphic vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. Multinucleated forms, numerous mitoses, and tumor necrosis were also noted. Sheets, fascicles, and whorls of spindle cells with spindled to ovoid vesicular nuclei, small to medium-sized distinct nucleoli, and eosinophilic cytoplasm were frequently observed. Immunohistochemical staining in the tumor cells was positive for CD163, CD68, lysozyme, CD45, and NSE. Focal expression of CD4 and S-100 was also noted. Electron microscopy demonstrated an abundance of lysosomes in the cytoplasm of tumor cells. Chromosome study revealed a 57–80 hyperdiploid [7]/46, XY [13] karyotype, including 3 to 4 copies of various chromosomes. The immunohistochemical and ultrastructural findings confirmed the diagnosis of HS.

Mitotic Spindle Asymmetry: A Wnt/PCP-Regulated Mechanism Generating Asymmetrical Division in Cortical Precursors

Directory of Open Access Journals (Sweden)

Delphine Delaunay

2014-01-01

Full Text Available The regulation of asymmetric cell division (ACD during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis. Imaging of spindle behavior and division outcome reveals that neurons preferentially arise from the larger-spindle pole. Mechanistically, SSA magnitude is controlled by Wnt7a and Vangl2, both members of the Wnt/planar cell polarity (PCP-signaling pathway, and relayed to the cell cortex by P-ERM proteins. In vivo, Vangl2 and P-ERM downregulation promotes early cell-cycle exit and prevents the proper generation of late-born neurons. Thus, SSA is a core component of ACD that is conserved in invertebrates and vertebrates and plays a key role in the tight spatiotemporal control of self-renewal and differentiation during mammalian corticogenesis.

Spindle-like thalamocortical synchronization in a rat brain slice preparation.

Science.gov (United States)

Tancredi, V; Biagini, G; D'Antuono, M; Louvel, J; Pumain, R; Avoli, M

2000-08-01

We obtained rat brain slices (550-650 microm) that contained part of the frontoparietal cortex along with a portion of the thalamic ventrobasal complex (VB) and of the reticular nucleus (RTN). Maintained reciprocal thalamocortical connectivity was demonstrated by VB stimulation, which elicited orthodromic and antidromic responses in the cortex, along with re-entry of thalamocortical firing originating in VB neurons excited by cortical output activity. In addition, orthodromic responses were recorded in VB and RTN following stimuli delivered in the cortex. Spontaneous and stimulus-induced coherent rhythmic oscillations (duration = 0.4-3.5 s; frequency = 9-16 Hz) occurred in cortex, VB, and RTN during application of medium containing low concentrations of the K(+) channel blocker 4-aminopyridine (0.5-1 microM). This activity, which resembled electroencephalograph (EEG) spindles recorded in vivo, disappeared in both cortex and thalamus during application of the excitatory amino acid receptor antagonist kynurenic acid in VB (n = 6). By contrast, cortical application of kynurenic acid (n = 4) abolished spindle-like oscillations at this site, but not those recorded in VB, where their frequency was higher than under control conditions. Our findings demonstrate the preservation of reciprocally interconnected cortical and thalamic neuron networks that generate thalamocortical spindle-like oscillations in an in vitro rat brain slice. As shown in intact animals, these oscillations originate in the thalamus where they are presumably caused by interactions between RTN and VB neurons. We propose that this preparation may help to analyze thalamocortical synchronization and to understand the physiopathogenesis of absence attacks.

Rotor assembly and assay method

Science.gov (United States)

Burtis, C.A.; Johnson, W.F.; Walker, W.A.

1993-09-07

A rotor assembly for carrying out an assay includes a rotor body which is rotatable about an axis of rotation, and has a central chamber and first, second, third, fourth, fifth, and sixth chambers which are in communication with and radiate from the central chamber. The rotor assembly further includes a shuttle which is movable through the central chamber and insertable into any of the chambers, the shuttle including a reaction cup carrying an immobilized antigen or an antibody for transport among the chambers. A method for carrying out an assay using the rotor assembly includes moving the reaction cup among the six chambers by passing the cup through the central chamber between centrifugation steps in order to perform the steps of: separating plasma from blood cells, binding plasma antibody or antigen, washing, drying, binding enzyme conjugate, reacting with enzyme substrate and optically comparing the resulting reaction product with unreacted enzyme substrate solution. The movement of the reaction cup can be provided by attaching a magnet to the reaction cup and supplying a moving magnetic field to the rotor. 34 figures.

Sleep spindle and K-complex detection using tunable Q-factor wavelet transform and morphological component analysis

Directory of Open Access Journals (Sweden)

Tarek eLajnef

2015-07-01

Full Text Available A novel framework for joint detection of sleep spindles and K-complex events, two hallmarks of sleep stage S2, is proposed. Sleep electroencephalography (EEG signals are split into oscillatory (spindles and transient (K-complex components. This decomposition is conveniently achieved by applying morphological component analysis (MCA to a sparse representation of EEG segments obtained by the recently introduced discrete tunable Q-factor wavelet transform (TQWT. Tuning the Q-factor provides a convenient and elegant tool to naturally decompose the signal into an oscillatory and a transient component. The actual detection step relies on thresholding (i the transient component to reveal K-complexes and (ii the time-frequency representation of the oscillatory component to identify sleep spindles. Optimal thresholds are derived from ROC-like curves (sensitivity versus FDR on training sets and the performance of the method is assessed on test data sets. We assessed the performance of our method using full-night sleep EEG data we collected from 14 participants. In comparison to visual scoring (Expert 1, the proposed method detected spindles with a sensitivity of 83.18% and false discovery rate (FDR of 39%, while K-complexes were detected with a sensitivity of 81.57% and an FDR of 29.54%. Similar performances were obtained when using a second expert as benchmark. In addition, when the TQWT and MCA steps were excluded from the pipeline the detection sensitivities dropped down to 70% for spindles and to 76.97% for K-complexes, while the FDR rose up to 43.62% and 49.09% respectively. Finally, we also evaluated the performance of the proposed method on a set of publicly available sleep EEG recordings. Overall, the results we obtained suggest that the TQWT-MCA method may be a valuable alternative to existing spindle and K-complex detection methods. Paths for improvements and further validations with large-scale standard open-access benchmarking data sets are

A Balance between Nuclear and Cytoplasmic Volumes Controls Spindle Length

Czech Academy of Sciences Publication Activity Database

Nováková, Lucia; Kovačovicová, Kristina; Dang-Nguyen, T.; Šodek, Martin; Škultéty, M.; Anger, Martin

2016-01-01

Roč. 11, č. 2 (2016), e0149535-e0149535 E-ISSN 1932-6203 R&D Projects: GA ČR GAP502/12/2201 Institutional support: RVO:67985904 Keywords : mitotoc spindle * size * cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

Regulation of mitotic spindle formation by the RhoA guanine nucleotide exchange factor ARHGEF10

Directory of Open Access Journals (Sweden)

Satoh Takaya

2009-07-01

Full Text Available Abstract Background The Dbl family guanine nucleotide exchange factor ARHGEF10 was originally identified as the product of the gene associated with slowed nerve-conduction velocities of peripheral nerves. However, the function of ARHGEF10 in mammalian cells is totally unknown at a molecular level. ARHGEF10 contains no distinctive functional domains except for tandem Dbl homology-pleckstrin homology and putative transmembrane domains. Results Here we show that RhoA is a substrate for ARHGEF10. In both G1/S and M phases, ARHGEF10 was localized in the centrosome in adenocarcinoma HeLa cells. Furthermore, RNA interference-based knockdown of ARHGEF10 resulted in multipolar spindle formation in M phase. Each spindle pole seems to contain a centrosome consisting of two centrioles and the pericentriolar material. Downregulation of RhoA elicited similar phenotypes, and aberrant mitotic spindle formation following ARHGEF10 knockdown was rescued by ectopic expression of constitutively activated RhoA. Multinucleated cells were not increased upon ARHGEF10 knockdown in contrast to treatment with Y-27632, a specific pharmacological inhibitor for the RhoA effector kinase ROCK, which induced not only multipolar spindle formation, but also multinucleation. Therefore, unregulated centrosome duplication rather than aberration in cytokinesis may be responsible for ARHGEF10 knockdown-dependent multipolar spindle formation. We further isolated the kinesin-like motor protein KIF3B as a binding partner of ARHGEF10. Knockdown of KIF3B again caused multipolar spindle phenotypes. The supernumerary centrosome phenotype was also observed in S phase-arrested osteosarcoma U2OS cells when the expression of ARHGEF10, RhoA or KIF3B was abrogated by RNA interference. Conclusion Collectively, our results suggest that a novel RhoA-dependent signaling pathway under the control of ARHGEF10 has a pivotal role in the regulation of the cell division cycle. This pathway is not involved in

Mechanisms for focusing mitotic spindle poles by minus end-directed motor proteins.

Science.gov (United States)

Goshima, Gohta; Nédélec, François; Vale, Ronald D

2005-10-24

During the formation of the metaphase spindle in animal somatic cells, kinetochore microtubule bundles (K fibers) are often disconnected from centrosomes, because they are released from centrosomes or directly generated from chromosomes. To create the tightly focused, diamond-shaped appearance of the bipolar spindle, K fibers need to be interconnected with centrosomal microtubules (C-MTs) by minus end-directed motor proteins. Here, we have characterized the roles of two minus end-directed motors, dynein and Ncd, in such processes in Drosophila S2 cells using RNA interference and high resolution microscopy. Even though these two motors have overlapping functions, we show that Ncd is primarily responsible for focusing K fibers, whereas dynein has a dominant function in transporting K fibers to the centrosomes. We also report a novel localization of Ncd to the growing tips of C-MTs, which we show is mediated by the plus end-tracking protein, EB1. Computer modeling of the K fiber focusing process suggests that the plus end localization of Ncd could facilitate the capture and transport of K fibers along C-MTs. From these results and simulations, we propose a model on how two minus end-directed motors cooperate to ensure spindle pole coalescence during mitosis.

v-Src causes delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone during cytokinesis failure

Energy Technology Data Exchange (ETDEWEB)

Soeda, Shuhei [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan); Nakayama, Yuji, E-mail: nakayama@mb.kyoto-phu.ac.jp [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan); Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414 (Japan); Honda, Takuya; Aoki, Azumi; Tamura, Naoki; Abe, Kohei; Fukumoto, Yasunori [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan); Yamaguchi, Naoto, E-mail: nyama@faculty.chiba-u.jp [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan)

2013-06-10

Src-family tyrosine kinases are aberrantly activated in cancers, and this activation is associated with malignant tumor progression. v-Src, encoded by the v-src transforming gene of the Rous sarcoma virus, is a mutant variant of the cellular proto-oncogene c-Src. Although investigations with temperature sensitive mutants of v-Src have shown that v-Src induces many oncogenic processes, the effects on cell division are unknown. Here, we show that v-Src inhibits cellular proliferation of HCT116, HeLa S3 and NIH3T3 cells. Flow cytometry analysis indicated that inducible expression of v-Src results in an accumulation of 4N cells. Time-lapse analysis revealed that binucleation is induced through the inhibition of cytokinesis, a final step of cell division. The localization of Mklp1, which is essential for cytokinesis, to the spindle midzone is inhibited in v-Src-expressing cells. Intriguingly, Aurora B, which regulates Mklp1 localization at the midzone, is delocalized from the spindle midzone and the midbody but not from the metaphase chromosomes upon v-Src expression. Mklp2, which is responsible for the relocation of Aurora B from the metaphase chromosomes to the spindle midzone, is also lost from the spindle midzone. These results suggest that v-Src inhibits cytokinesis through the delocalization of Mklp1 and Aurora B from the spindle midzone, resulting in binucleation. -- Highlights: • v-Src inhibits cell proliferation of HCT116, HeLa S3 and NIH3T3 cells. • v-Src induces binucleation together with cytokinesis failure. • v-Src causes delocalization of Mklp1, Aurora B and INCENP from the spindle midzone.

Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

Science.gov (United States)

Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

2015-07-02

Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

One-pot synthesis and electrochemical reactivity of carbon coated LiFePO4 spindles

International Nuclear Information System (INIS)

Yu Juanjuan; Hu Juncheng; Li Jinlin

2012-01-01

Highlights: ► Carbon coated LiFePO 4 spindles have been successfully synthesized via a novel supercritical method. ► The concentrations of lithium have an effect on the morphology of carbon coated LiFePO 4 . ► Amorphous carbon layer formed on the surface of LiFePO 4 by adding glucose. ► The carbon coating is responsible for the enhanced electrochemical performance. - Abstract: Spindle-like carbon coated LiFePO 4 (LiFePO 4 /C) composites have been successfully synthesized via a novel one-pot supercritical methanol method. The products were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). The particle size, morphology and electrochemical reactivity changed with the concentration of lithium and carbon source. A possible morphology evolution process was also proposed. The glucose not only facilitates the formation of single crystalline LiFePO 4 , but also gives an amorphous carbon layer on the surface LiFePO 4 spindles.

Pengaturan Kecepatan Motor Spindle pada Retrofit Mesin Bubut CNC Menggunakan Kontroler PID Gain Scheduling

Directory of Open Access Journals (Sweden)

Fikri Yoga Permana

2013-03-01

Full Text Available Pada mesin bubut Computerized Numerical Control (CNC, proses pemahatan benda kerja memerlukan kecepatan potong yang tetap agar hasil kerja memiliki tingkat presisi tinggi. Dalam prakteknya, ketika terjadi pemotongan, diameter benda kerja akan selalu berkurang dan tingkat kedalaman pahat berubah-ubah sesuai dengan proses yang dilakukan sehingga mempengaruhi kecepatan putar motor spindle sehingga mengakibatkan tingkat presisi hasil kerja menjadi berkurang. Pada penelitian ini, digunakan kontroler PI Gain Scheduling untuk mengatur kecapatan motor spindle. Hasil yang didapatkan berupa simulasi kontroler PI Gain Scheduling. Dari hasil simulasi didapatkan kontroler PI Gain Scheduling mampu membuat respon sistem sesuai dengan yang diinginkan.

Bola-amphiphile self-assembly

DEFF Research Database (Denmark)

Svaneborg, Carsten

2012-01-01

Bola-amphiphiles are rod-like molecules where both ends of the molecule likes contact with water, while the central part of the molecule dislikes contact with water. What do such molecules do when they are dissolved in water? They self-assemble into micelles. This is a Dissipartive particle...... dynamics simulation of this self-assembly behaviour....

"Fast" and "slow" skeleto-fusimotor innervation in cat tenuissimus spindles; a study with the glycogen-depletion method.

Science.gov (United States)

Jami, L; Lan-Couton, D; Malmgren, K; Petit, J

1978-07-01

The glycogen-depletion method was used to investigate the motor supply to tenuissimus with respect to the presence of fast beta axons and to assess the total proportion of both fast and slow beta-innervated spindles in this muscle. In a first series of 5 expts., groups of motor axons with conduction velocities higher than 85 m/s were repetitively stimulated so as to produce glycogen depletion in the muscle fibres they innervated. The whole muscle was then quick-frozen, serially cut, stained to demonstrate glycogen and examined for intrafusal glycogen depletion. Zones of glycogen depletion were found in 16 of the 46 examined spindles; they were most frequently located in the longest of the chain intrafusal muscle fibres. Since it is known that there are no purely fusimotor axons to tenuissimus with conduction velocities above 50 m/s, it was concluded that beta axons are present among the fastest axons to this muscle. In a second series of 5 expts. as many motor axons as possible with conduction velocities above 60 m/s were stimulated. Zones of glycogen depletion were found in 19 of the 47 examined spindles. They affected chain fibres in about half of the instances and bag1 fibers in the others. As this latter location is characteristic of slow dynamic beta axons, it was concluded that both slow and fast beta axons occur regularly in the motor supply to tenuissimus. beta-innervation is present in at least 40% of tenuissimus spindles with almost no convergence of fast and slow beta axons onto the same spindle.

Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1I4895T/wt mouse model of core myopathy

International Nuclear Information System (INIS)

Zvaritch, Elena; MacLennan, David H.

2015-01-01

Muscle spindles from the hind limb muscles of adult Ryr1 I4895T/wt (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies. - Highlights: • Muscle spindles exhibit structural abnormalities in a mouse model of core myopathy. • Myofibrillar collapse and mitochondrial clumping is observed in intrafusal fibers. • Myofibrillar degeneration follows a pattern similar to core formation in extrafusal myofibers. • Muscle spindle abnormalities are a part of the pathological phenotype in the mouse model of core myopathy. • Direct involvement of muscle spindles in the pathology of human RYR1-related myopathies is proposed

Spindle Cell Carcinoma of Nasal Cavity- A Case Report

Science.gov (United States)

Mittal, Abhishek; Nagpal, Tapan

2016-01-01

Spindle Cell Carcinoma (SpCC), also known as Sarcomatoid Carcinoma, is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aero-digestive tract, mostly in larynx. SCC accounts for 3% of all squamous cell carcinomas (SCCs) in the head and neck region. It is a rare variant of SCC which shows spindled or pleomorphic tumour cells simulating a true sarcoma. We present a case report of SpCC nasal cavity in a 50-year-old female patient, presented with intermittent epistaxis from left nasal cavity. On physical examination, the patient had an ulcero-exophytic type of mass in the left nasal cavity and a smooth bulge on the left side of anterior hard palate. Patient underwent excision of nasal mass along with partial palatectomy by facial degloving approach and reconstruction of palate with naso-labial flap. The postoperative histopathological report showed SCC. Surgery forms the mainstay of treatment. Radiotherapy and Chemotherapy is warranted in order to improve treatment results. As only few cases have been reported, we report a case of this rare entity to contribute for better understanding and awareness of this rare malignancy. PMID:27190843

Spindle-cell squamous carcinoma of the esophagus: a tumor with biphasic morphology

International Nuclear Information System (INIS)

Agha, F.P.; Keren, D.F.

1985-01-01

Spindle-cell squamous carcinoma of the esophagus is a rare malignant tumor. It is characterized by a large bulky mass in the middle third of the esophagus with a lobulated surface and local expansion of the esophagus. This lesion may be pedunculated and cause relatively little obstruction despite its bulk. The current view, based on ultrastructure and immunohistochemical evidence, has confirmed that the sarcomatous component of the squamous cell carcinoma originates from mesenchymal metaplasia of squamous cells. On the basis of this evidence and clinical behavior, it seems appropriate to consider carcinosarcoma and pseudosarcoma as equivalents and as variants of squamous cell carcinoma. Four patients with spindle-cell squamous carcinoma, an unusual subset of squamous carcinoma, are described, and the salient radiographic and pathologic features of this disorder's distinctive biphasic morphology are discussed

Daam1 regulates fascin for actin assembly in mouse oocyte meiosis.

Science.gov (United States)

Lu, Yujie; Zhang, Yu; Pan, Meng-Hao; Kim, Nam-Hyung; Sun, Shao-Chen; Cui, Xiang-Shun

2017-07-18

As a formin protein, Daam1 (Dishevelled-associated activator of morphogenesis 1) is reported to regulate series of cell processes like endocytosis, cell morphology and migration via its effects on actin assembly in mitosis. However, whether Daam1 plays roles in female meiosis remains uncertain. In this study, we investigated the expression and functions of Daam1 during mouse oocyte meiosis. Our results indicated that Daam1 localized at the cortex of oocytes, which was similar with actin filaments. After Daam1 morpholino (MO) microinjection, the expression of Daam1 significantly decreased, which resulted in the failure of oocyte polar body extrusion. These results might be due to the defects of actin assembly, since the decreased fluorescence intensity of actin filaments in oocyte cortex and cytoplasm were observed. However, Daam1 knockdown seemed not to affect the meiotic spindle movement. In addition, we found that fascin might be the down effector of Daam1, since the protein expression of fascin decreased after Daam1 knockdown. Thus, our data suggested that Daam1 affected actin assembly during oocyte meiotic division via the regulation of fascin expression.

Sleep spindles during a nap correlate with post sleep memory performance for highly rewarded word-pairs.

Science.gov (United States)

Studte, Sara; Bridger, Emma; Mecklinger, Axel

2017-04-01

The consolidation of new associations is thought to depend in part on physiological processes engaged during non-REM (NREM) sleep, such as slow oscillations and sleep spindles. Moreover, NREM sleep is thought to selectively benefit associations that are adaptive for the future. In line with this, the current study investigated whether different reward cues at encoding are associated with changes in sleep physiology and memory retention. Participants' associative memory was tested after learning a list of arbitrarily paired words both before and after taking a 90-min nap. During learning, word-pairs were preceded by a cue indicating either a high or a low reward for correct memory performance at test. The motivation manipulation successfully impacted retention such that memory declined to a greater extent from pre- to post sleep for low rewarded than for high rewarded word-pairs. In line with previous studies, positive correlations between spindle density during NREM sleep and general memory performance pre- and post-sleep were found. In addition to this, however, a selective positive relationship between memory performance for highly rewarded word-pairs at posttest and spindle density during NREM sleep was also observed. These results support the view that motivationally salient memories are preferentially consolidated and that sleep spindles may be an important underlying mechanism for selective consolidation. Copyright © 2016 Elsevier Inc. All rights reserved.

Spindle-F Is the Central Mediator of Ik2 Kinase-Dependent Dendrite Pruning in Drosophila Sensory Neurons.

Directory of Open Access Journals (Sweden)

Tzu Lin

2015-11-01

Full Text Available During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons.

Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint

DEFF Research Database (Denmark)

Hein, Jamin B; Nilsson, Jakob

2014-01-01

stably to the APC/C. Whether MCC formation per se is sufficient for a functional SAC or MCC association with the APC/C is required remains unclear. Here, we analyze the role of two conserved motifs in Cdc20, IR and C-Box, in binding of the MCC to the APC/C. Mutants in both motifs assemble the MCC....../C is critical for a functional SAC....

Modeling and characterization of an electromagnetic system for the estimation of Frequency Response Function of spindle

Science.gov (United States)

Tlalolini, David; Ritou, Mathieu; Rabréau, Clément; Le Loch, Sébastien; Furet, Benoit

2018-05-01

The paper presents an electromagnetic system that has been developed to measure the quasi-static and dynamic behavior of machine-tool spindle, at different spindle speeds. This system consists in four Pulse Width Modulation amplifiers and four electromagnets to produce magnetic forces of ± 190 N for the static mode and ± 80 N for the dynamic mode up to 5 kHz. In order to measure the Frequency Response Function (FRF) of spindle, the applied force is required, which is a key issue. A dynamic force model is proposed in order to obtain the load from the measured current in the amplifiers. The model depends on the exciting frequency and on the magnetic characteristics of the system. The predicted force at high speed is validated with a specific experiment and the performance limits of the experimental device are investigated. The FRF obtained with the electromagnetic system is compared to a classical tap test measurement.

Sleep spindles: a physiological marker of age-related changes in gray matter in brain regions supporting motor skill memory consolidation.

Science.gov (United States)

Fogel, Stuart; Vien, Catherine; Karni, Avi; Benali, Habib; Carrier, Julie; Doyon, Julien

2017-01-01

Sleep is necessary for the optimal consolidation of procedural learning, and in particular, for motor sequential skills. Motor sequence learning remains intact with age, but sleep-dependent consolidation is impaired, suggesting that memory deficits for procedural skills are specifically impacted by age-related changes in sleep. Age-related changes in spindles may be responsible for impaired motor sequence learning consolidation, but the morphological basis for this deficit is unknown. Here, we found that gray matter in the hippocampus and cerebellum was positively correlated with both sleep spindles and offline improvements in performance in young participants but not in older participants. These results suggest that age-related changes in gray matter in the hippocampus relate to spindles and may underlie age-related deficits in sleep-related motor sequence memory consolidation. In this way, spindles can serve as a biological marker for structural brain changes and the related memory deficits in older adults. Copyright © 2016 Elsevier Inc. All rights reserved.

The TileCal Barrel Test Assembly

CERN Multimedia

Leitner, R

On 30th October, the mechanics test assembly of the central barrel of the ATLAS tile hadronic calorimeter was completed in building 185. It started on 23rd June and is the second wheel for the Tilecal completely assembled this year. The ATLAS engineers and technicians are quick: instead of the 27 weeks initially foreseen for assembling the central barrel of the tile hadronic calorimeter (Tilecal) in building 185, they inserted the last of the 64 modules on 30th October after only 19 weeks. In part, this was due to the experience gained in the dry run assembly of the first extended barrel, produced in Spain, in spring this year (see Bulletin 23/2003); however, the central barrel is twice as long - and twice as heavy. With a length of 6.4 metres, an outer diameter of 8.5 metres and an inner diameter of 4.5 metres, the object weight is 1300 tonnes. The whole barrel cylinder is supported by the stainless steel support structure weighing only 27 tons. The barrel also has to have the right shape: over the whole 8...

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.

Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer

Directory of Open Access Journals (Sweden)

Marco R. Cosenza

2017-08-01

Full Text Available Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer.

EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus

International Nuclear Information System (INIS)

Nijs, Laurence de; Lakaye, Bernard; Coumans, Bernard; Leon, Christine; Ikeda, Takashi; Delgado-Escueta, Antonio V.; Grisar, Thierry; Chanas, Grazyna

2006-01-01

A novel gene, EFHC1, mutated in juvenile myoclonic epilepsy (JME) encodes a protein with three DM10 domains of unknown function and one putative EF-hand motif. To study the properties of EFHC1, we expressed EGFP-tagged protein in various cell lines. In interphase cells, the fusion protein was present in the cytoplasm and in the nucleus with specific accumulation at the centrosome. During mitosis EGFP-EFHC1 colocalized with the mitotic spindle, especially at spindle poles and with the midbody during cytokinesis. Using a specific antibody, we demonstrated the same distribution of the endogenous protein. Deletion analyses revealed that the N-terminal region of EFHC1 is crucial for the association with the mitotic spindle and the midbody. Our results suggest that EFHC1 could play an important role during cell division

Parameter Estimation of the Thermal Network Model of a Machine Tool Spindle by Self-made Bluetooth Temperature Sensor Module

Directory of Open Access Journals (Sweden)

Yuan-Chieh Lo

2018-02-01

Full Text Available Thermal characteristic analysis is essential for machine tool spindles because sudden failures may occur due to unexpected thermal issue. This article presents a lumped-parameter Thermal Network Model (TNM and its parameter estimation scheme, including hardware and software, in order to characterize both the steady-state and transient thermal behavior of machine tool spindles. For the hardware, the authors develop a Bluetooth Temperature Sensor Module (BTSM which accompanying with three types of temperature-sensing probes (magnetic, screw, and probe. Its specification, through experimental test, achieves to the precision ±(0.1 + 0.0029|t| °C, resolution 0.00489 °C, power consumption 7 mW, and size Ø40 mm × 27 mm. For the software, the heat transfer characteristics of the machine tool spindle correlative to rotating speed are derived based on the theory of heat transfer and empirical formula. The predictive TNM of spindles was developed by grey-box estimation and experimental results. Even under such complicated operating conditions as various speeds and different initial conditions, the experiments validate that the present modeling methodology provides a robust and reliable tool for the temperature prediction with normalized mean square error of 99.5% agreement, and the present approach is transferable to the other spindles with a similar structure. For realizing the edge computing in smart manufacturing, a reduced-order TNM is constructed by Model Order Reduction (MOR technique and implemented into the real-time embedded system.

Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up

Directory of Open Access Journals (Sweden)

Nisa Azizun

2010-10-01

Full Text Available Spindle epithelial tumor with thymus-like differentiation (SETTLE is a rare malignant thyroid tumor showing thymic or related branchial pouch differentiation. The tumors are composed predominantly of spindle cells along with focal epithelial component and ductular formations. SETTLE occurs in young patients, with indolent growth and a tendency to develop delayed blood-borne metastases. We herein report two cases of SETTLE with a follow-up period of 64 months and 30 months, respectively.

Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol.

Science.gov (United States)

Hayashi, K; Tsuda, N; Sawa, T; Hagihira, S

2007-09-01

The reticular and thalamocortical system is known to play a prominent role in spindle wave activity, and the spindle wave is related to the sedative effects of anaesthetics. Recently, bispectral analysis of the EEG has been developed as a better method to indicate nonlinear regulation including the thalamocortical system linking to the cortical area. In the present study, in order to explore the interference of ketamine with the nonlinear regulation of the sub-cortical system, we examined the effect of ketamine on spindle alpha waves through the bispectral analysis. The study included 21 patients. Anaesthesia was induced and maintained using a propofol-TCI system (target-controlled infusion, with target concentration 3.5 microg ml(-1)). An A-2000 BIS monitor was used and the raw EEG signals were collected via an RS232 interface on a personal computer. Bicoherence, the normalized bispectrum, and power spectrum were analysed before and after i.v. administration of 1 mg kg(-1) racemic ketamine. Propofol caused alpha peaks in both power and bicoherence spectra, with average frequencies of 10.6 (SD 0.9) Hz and 10.7 (1.0) Hz, respectively. The addition of ketamine significantly shifted each peak to frequencies of 14.4 (1.4) Hz and 13.6 (1.5) Hz, respectively [P < 0.05, mean (SD)]. Ketamine shifted the alpha peaks of bicoherence induced by propofol to higher frequencies. This suggests that ketamine changes the alpha spindle rhythms through the modulation of the nonlinear sub-cortical reverberating network.

Expanding the histologic spectrum of mucinous tubular and spindle cell carcinoma of the kidney.

Science.gov (United States)

Fine, Samson W; Argani, Pedram; DeMarzo, Angelo M; Delahunt, Brett; Sebo, Thomas J; Reuter, Victor E; Epstein, Jonathan I

2006-12-01

Mucinous tubular and spindle cell carcinomas (MTSCs) are polymorphic neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied. We identified 17 previously unreported MTSCs from Surgical Pathology and consultative files of the authors and their respective institutions and studied their morphologic features. A total of 10/17 cases were considered "classic," as described above, with 5/10 showing at least focal (20% to 50%) tubular predominance without apparent mucinous matrix. Alcian blue staining revealed abundant (>50%) mucin in all classic cases. Seven of 17 MTSCs were classified as "mucin-poor," with little to no extracellular mucin appreciable by hematoxylin and eosin. Four of these cases showed equal tubular and spindled morphology, 2 cases showed spindle cell predominance (70%; 95%), and 1 case showed tubular predominance (90%). In 5/7 mucin-poor cases, staining for Alcian blue revealed scant (<10%) mucin in cellular areas with the other 2 cases having 30% mucin. Unusual histologic features identified in the 17 cases were: foamy macrophages (n=8), papillations/well formed papillae (n=6/n=1), focal clear cells in tubules (n=3), necrosis (n=3), oncocytic tubules (n=2; 40%, 5%), numerous small vacuoles (n=2), heterotopic bone (n=1), psammomatous calcification (n=1), and nodular growth with lymphocytic cuffing (n=1). An exceptional case contained a well-circumscribed, HMB45-positive angiomyolipoma within the MTSC. MTSCs may be "mucin-poor" and show a marked predominance of either of its principal morphologic components, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, and necrosis, may mimic other forms of renal cell carcinoma. Pathologists must be aware of the spectrum of histologic findings within MTSCs to ensure their accurate diagnosis.

Topological defects in confined populations of spindle-shaped cells

Science.gov (United States)

Duclos, Guillaume; Erlenkämper, Christoph; Joanny, Jean-François; Silberzan, Pascal

2017-01-01

Most spindle-shaped cells (including smooth muscles and sarcomas) organize in vivo into well-aligned `nematic’ domains, creating intrinsic topological defects that may be used to probe the behaviour of these active nematic systems. Active non-cellular nematics have been shown to be dominated by activity, yielding complex chaotic flows. However, the regime in which live spindle-shaped cells operate, and the importance of cell-substrate friction in particular, remains largely unexplored. Using in vitro experiments, we show that these active cellular nematics operate in a regime in which activity is effectively damped by friction, and that the interaction between defects is controlled by the system’s elastic nematic energy. Due to the activity of the cells, these defects behave as self-propelled particles and pairwise annihilate until all displacements freeze as cell crowding increases. When confined in mesoscopic circular domains, the system evolves towards two identical +1/2 disclinations facing each other. The most likely reduced positions of these defects are independent of the size of the disk, the cells’ activity or even the cell type, but are well described by equilibrium liquid crystal theory. These cell-based systems thus operate in a regime more stable than other active nematics, which may be necessary for their biological function.

Vibration of rotating-shaft design spindles with flexible bases

Science.gov (United States)

Tseng, Chaw-Wu

The purpose of this study is to demonstrate an accurate mathematical model predicting forced vibration of rotating-shaft HDD spindle motors with flexible stationary parts. The mathematical model consists of three parts: a rotating part, a stationary part, and bearings. The rotating part includes a flexible hub, a flexible shaft press-fit into the hub, and N elastic disks mounted on the hub. The stationary part can include motor bracket (stator), base casting, and top cover. The bearings under consideration can be ball bearings or hydrodynamic bearings (HDB). The rotating disks are modelled through the classical plate theory. The rotating part (except the disks) and the stationary part are modelled through finite element analyses (FEA). With mode shapes and natural frequencies obtained from FEA, the kinetic and potential energies of the rotating and stationary parts are formulated and discretized to compensate for the gyroscopic effects from rotation. Finally, use of Lagrange equation results in the equations of motion. To verify the mathematical model, frequency response functions are measured experimentally for an HDB spindle carrying two identical disks at motor and drive levels. Experimental measurements agree very well with theoretical predictions not only in resonance frequency but also in resonance amplitude.

Spindle vibration and sound field measurement using optical vibrometry

OpenAIRE

Tatar, Kourosh

2008-01-01

Mechanical systems often produce a considerable amount of vibration and noise. To be able to obtain a complete picture of the dynamic behaviour of these systems, vibration and sound measurements are of significant importance. Optical metrology is well-suited for non-intrusive measurements on complex objects. The development and the use of remote non-contact vibration measurement methods for spindles are described and vibration measurements on thin- walled structures and sound field measuremen...

Muscle spindles in elongation of the extremity: proprioceptive conflict or activity deficit?

Science.gov (United States)

Shevtsov, V I; Saifutdinov, M S; Chikorina, N K

2008-07-01

Comparison of electrophysiological and morphological parameters of shin muscles of experimental animals during shin elongation by Ilizarov's method indicates involvement of muscle spindles into reconstruction of the skeletal muscular tissue in response to its dosed distraction, which results in temporary deficit of specific somatosensory afferentation.

Sleep spindle density in narcolepsy

DEFF Research Database (Denmark)

Christensen, Julie Anja Engelhard; Nikolic, Miki; Hvidtfelt, Mathias

2017-01-01

BACKGROUND: Patients with narcolepsy type 1 (NT1) show alterations in sleep stage transitions, rapid-eye-movement (REM) and non-REM sleep due to the loss of hypocretinergic signaling. However, the sleep microstructure has not yet been evaluated in these patients. We aimed to evaluate whether...... the sleep spindle (SS) density is altered in patients with NT1 compared to controls and patients with narcolepsy type 2 (NT2). METHODS: All-night polysomnographic recordings from 28 NT1 patients, 19 NT2 patients, 20 controls (C) with narcolepsy-like symptoms, but with normal cerebrospinal fluid hypocretin...... levels and multiple sleep latency tests, and 18 healthy controls (HC) were included. Unspecified, slow, and fast SS were automatically detected, and SS densities were defined as number per minute and were computed across sleep stages and sleep cycles. The between-cycle trends of SS densities in N2...

Piezoelectric self-sensing actuator for active vibration control of motorized spindle based on adaptive signal separation

Science.gov (United States)

He, Ye; Chen, Xiaoan; Liu, Zhi; Qin, Yi

2018-06-01

The motorized spindle is the core component of CNC machine tools, and the vibration of it reduces the machining precision and service life of the machine tools. Owing to the fast response, large output force, and displacement of the piezoelectric stack, it is often used as the actuator in the active vibration control of the spindle. A piezoelectric self-sensing actuator (SSA) can reduce the cost of the active vibration control system and simplify the structure by eliminating the use of a sensor, because a SSA can have both actuating and sensing functions at the same time. The signal separation method of a SSA based on a bridge circuit is widely applied because of its simple principle and easy implementation. However, it is difficult to maintain dynamic balance of the circuit. Prior research has used adaptive algorithm to balance of the bridge circuit on the flexible beam dynamically, but those algorithms need no correlation between sensing and control voltage, which limit the applications of SSA in the vibration control of the rotor-bearing system. Here, the electromechanical coupling model of the piezoelectric stack is established, followed by establishment of the dynamic model of the spindle system. Next, a new adaptive signal separation method based on the bridge circuit is proposed, which can separate relative small sensing voltage from related mixed voltage adaptively. The experimental results show that when the self-sensing signal obtained from the proposed method is used as a displacement signal, the vibration of the motorized spindle can be suppressed effectively through a linear quadratic Gaussian (LQG) algorithm.

Slow Freezing or Vitrification of Oocytes: Their Effects on Survival and Meiotic Spindles, and the Time Schedule for Clinical Practice

Directory of Open Access Journals (Sweden)

Shee-Uan Chen

2009-03-01

Full Text Available Both the slow-freezing method with increased sucrose concentration and new vitrification techniques significantly improve the results of cryopreservation of human oocytes. The recent perfection for vitrification includes the concepts of increase of cooling and warming rates using minimum volume methods, and decrease of toxicity by reducing the concentration of cryoprotectants. In the recent literature, the survival of cryopreserved oocytes ranged from 74% to 90% using the slow-freezing method and from 84% to 99% by vitrification. Overall, the survival rate of oocytes from vitrification (95%, 899/948 appeared higher than that of the slow-freezing method (75%, 1,275/1,683. The microtubules of meiotic spindles are vulnerable to the thermal changes and will depolymerize. After incubation, the microtubules repolymerize. Spindle recovery is faster after vitrification than slow freezing. Even so, after 3 hours of incubation, spindle recuperation is similar between vitrification and slow freezing. Considering both aspects of spindle recovery and oocyte aging, the time schedule for oocyte cryopreservation program makes fertilization in the optimal time. Intracytoplasmic sperm injection is performed for oocytes at 3 hours of post-thaw incubation from the slow-freezing method and 2 hours from vitrification, with restoration of meiotic spindles. The pregnancy potential of cryopreserved oocytes is comparable to that of fresh oocytes or frozen embryos. Cryopreservation of oocytes would importantly contribute to oocyte donation and preservation of fertility for cancer patients.

Relations between ultrastructure of mitotic spindle and chromosome translocation

OpenAIRE

Jadwiga A. Tarkowska

2014-01-01

Dividing endosperm cells of Haemanthus katherinae Bak. treated with an 0.25 per cent mixture of water-soluble glycosides from Nerium oleander were insepected in a light microscope (LM) and severe disturbances were found in all phases of mitosis. The same cells were observed in the electron microscope (EM) and relations were noted and analysed between the chromosome arrangement and the submicroscopic structure of the mitotuc spindle. The successive steps in the disintegration of the formed spi...

Plane of vertebral movement eliciting muscle lengthening history in the low back influences the decrease in muscle spindle responsiveness of the cat.

Science.gov (United States)

Ge, Weiqing; Cao, Dong-Yuan; Long, Cynthia R; Pickar, Joel G

2011-12-01

Proprioceptive feedback is thought to play a significant role in controlling both lumbopelvic and intervertebral orientations. In the lumbar spine, a vertebra's positional history along the dorsal-ventral axis has been shown to alter the position, movement, and velocity sensitivity of muscle spindles in the multifidus and longissimus muscles. These effects appear due to muscle history. Because spinal motion segments have up to 6 degrees of freedom for movement, we were interested in whether the axis along which the history is applied differentially affects paraspinal muscle spindles. We tested the null hypothesis that the loading axis, which creates a vertebra's positional history, has no effect on a lumbar muscle spindle's subsequent response to vertebral position or movement. Identical displacements were applied along three orthogonal axes directly at the L(6) spinous process using a feedback motor system under displacement control. Single-unit nerve activity was recorded from 60 muscle spindle afferents in teased filaments from L(6) dorsal rootlets innervating intact longissimus or multifidus muscles of deeply anesthetized cats. Muscle lengthening histories along the caudal-cranial and dorsal-ventral axis, compared with the left-right axis, produced significantly greater reductions in spindle responses to vertebral position and movement. The spinal anatomy suggested that the effect of a lengthening history is greatest when that history had occurred along an axis lying within the anatomical plane of the facet joint. Speculation is made that the interaction between normal spinal mechanics and the inherent thixotropic property of muscle spindles poses a challenge for feedback and feedforward motor control of the lumbar spine.

Plutonium demonstration assemblies in the CNA core

International Nuclear Information System (INIS)

Romain, J.L.

1975-01-01

The SENA (Societe d'Exploitation Nucleaire des Ardennes) has decided to load two plutonium assemblies at the beginning of the 6th cycle of the CNA (Centrale Nucleaire des Ardennes). These assemblies will be loaded in September 1975 and will undergo three irradiation cycles. A general description of these two assemblies and nuclear design calculations that have been performed are presented [fr

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

Directory of Open Access Journals (Sweden)

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.

Finite Element Analysis of Flexural Vibrations in Hard Disk Drive Spindle Systems

Science.gov (United States)

LIM, SEUNGCHUL

2000-06-01

This paper is concerned with the flexural vibration analysis of the hard disk drive (HDD) spindle system by means of the finite element method. In contrast to previous research, every system component is here analytically modelled taking into account its structural flexibility and also the centrifugal effect particularly on the disk. To prove the effectiveness and accuracy of the formulated models, commercial HDD systems with two and three identical disks are selected as examples. Then their major natural modes are computed with only a small number of element meshes as the shaft rotational speed is varied, and subsequently compared with the existing numerical results obtained using other methods and newly acquired experimental ones. Based on such a series of studies, the proposed method can be concluded as a very promising tool for the design of HDDs and various other high-performance computer disk drives such as floppy disk drives, CD ROM drives, and their variations having spindle mechanisms similar to those of HDDs.

p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex

Directory of Open Access Journals (Sweden)

Camille Belzil

2014-05-01

Full Text Available Apical neural progenitors (aNPs drive neurogenesis by means of a program consisting of self-proliferative and neurogenic divisions. The balance between these two manners of division sustains the pool of apical progenitors into late neurogenesis, thereby ensuring their availability to populate the brain with terminal cell types. Using knockout and in utero electroporation mouse models, we report a key role for the microtubule-associated protein 600 (p600 in the regulation of spindle orientation in aNPs, a cellular event that has been associated with cell fate and neurogenesis. We find that p600 interacts directly with the neurogenic protein Ndel1 and that aNPs knockout for p600, depleted of p600 by shRNA or expressing a Ndel1-binding p600 fragment all display randomized spindle orientation. Depletion of p600 by shRNA or expression of the Ndel1-binding p600 fragment also results in a decreased number of Pax6-positive aNPs and an increased number of Tbr2-positive basal progenitors destined to become neurons. These Pax6-positive aNPs display a tilted mitotic spindle. In mice wherein p600 is ablated in progenitors, the production of neurons is significantly impaired and this defect is associated with microcephaly. We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis.

Yeast Interacting Proteins Database: YOL069W, YIL144W [Yeast Interacting Proteins Database

Lifescience Database Archive (English)

Full Text Available complex (Ndc80p-Nuf2p-Spc24p-Spc25p); involved in chromosome segregation, spindle checkpoint activity and kinetochore clustering...vity, kinetochore assembly and clustering Rows with this prey as prey (2) Rows with this prey as bait (0) 12...-Nuf2p-Spc24p-Spc25p); involved in chromosome segregation, spindle checkpoint activity and kinetochore clustering...d coiled-coil protein involved in chromosome segregation, spindle checkpoint activity, kinetochore assembly and clustering

A gene encoding the major beta tubulin of the mitotic spindle in Physarum polycephalum plasmodia

Energy Technology Data Exchange (ETDEWEB)

Burland, T.G.; Paul, E.C.A.; Oetliker, M.; Dove, W.F.

1988-03-01

The multinucleate plasmodium of Physarum polycephalum is unusual among eucaryotic cells in that it uses tubulins only in mitotic-spindle microtubules; cytoskeletal, flagellar, and centriolar microtubules are absent in this cell type. The authors identified a ..beta..-tubulin cDNA clone, ..beta..105, which is shown to correspond to the transcript of the betC ..beta..-tubulin locus and to encode ..beta..2 tubulin, the ..beta.. tubulin expressed specifically in the plasmodium and used exclusively in the mitotic spindle. Physarum amoebae utilize tubulins in the cytoskeleton, centrioles, and flagella, in addition to the mitotic spindle. Sequence analysis shows that ..beta..2 tubulin is only 83% identical to the two ..beta.. tubulins expressed in amoebae. This compares with 70 to 83% identity between Physarum ..beta..2 tubulin and the ..beta.. tubulins of yeasts, fungi, alga, trypanosome, fruit fly, chicken, and mouse. On the other hand, Physarum ..beta..2 tubulin is no more similar to, for example, Aspergillus ..beta.. tubulins than it is to those of Drosophila melanogaster or mammals. Several eucaryotes express at least one widely diverged ..beta.. tubulin as well as one or more ..beta.. tubulins that conform more closely to a consensus ..beta..-tubulin sequence. The authors suggest that ..beta..-tubulins diverge more when their expression pattern is restricted, especially when this restriction results in their use in fewer functions. This divergence among ..beta.. tubulins could have resulted through neutral drift. For example, exclusive use of Physarum ..beta..2 tubulin in the spindle may have allowed more amino acid substitutions than would be functionally tolerable in the ..beta.. tubulins that are utilized in multiple microtubular organelles. Alternatively, restricted use of ..beta.. tubulins may allow positive selection to operate more freely to refine ..beta..-tubulin function.

State-Sponsored Homophobia and the Denial of the Right of Assembly in Central and Eastern Europe : The "Boomerang" and the "Ricochet" between European Organizations and Civil Society to Uphold Human Rights

NARCIS (Netherlands)

Holzhacker, Ronald

2013-01-01

State-sponsored homophobia emerged in certain Central and Eastern European states in the past decade, with the denial of the right of assembly for gay pride marches. However, more recently there has been progress in the recognition of the fundamental democratic right of assembly. What accounts for

FUSIMOTOR EFFECTS OF MIDBRAIN STIMULATION ON JAW MUSCLE-SPINDLES OF THE ANESTHETIZED CAT

NARCIS (Netherlands)

TAYLOR, A; JUCH, PJW

The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine

Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.

Science.gov (United States)

Chen, Kai; Duan, Wenxiu; Han, Qianqian; Sun, Xuan; Li, Wenqian; Hu, Shuangyun; Wan, Jiajia; Wu, Jiang; Ge, Yushu; Liu, Dan

2018-03-08

Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay. Comparative study of stability and flexibility of three systems reveals position shifting of β-sheet region within the catalytic site, which indicates inhibition mechanism was through stabilizing the β-sheet region. Binding free energies calculated with MM-GB/PBSA method shows different binding affinity for inhibitor and ATP. Finally, interactions between protein and inhibitor during molecular dynamic simulations were measured and counted. Residue Gly605 and Leu654 were suggested as important hot spots for stable binding of inhibitor by molecular dynamic simulation. Our results reveal an important position shifting within catalytic site for non-inhibited proteins. Together with hot spots found by molecular dynamic simulation, the results provide important information of inhibition mechanism and will be referenced for designing novel inhibitors.

Investigation the gas film in micro scale induced error on the performance of the aerostatic spindle in ultra-precision machining

Science.gov (United States)

Chen, Dongju; Huo, Chen; Cui, Xianxian; Pan, Ri; Fan, Jinwei; An, Chenhui

2018-05-01

The objective of this work is to study the influence of error induced by gas film in micro-scale on the static and dynamic behavior of a shaft supported by the aerostatic bearings. The static and dynamic balance models of the aerostatic bearing are presented by the calculated stiffness and damping in micro scale. The static simulation shows that the deformation of aerostatic spindle system in micro scale is decreased. For the dynamic behavior, both the stiffness and damping in axial and radial directions are increased in micro scale. The experiments of the stiffness and rotation error of the spindle show that the deflection of the shaft resulting from the calculating parameters in the micro scale is very close to the deviation of the spindle system. The frequency information in transient analysis is similar to the actual test, and they are also higher than the results from the traditional case without considering micro factor. Therefore, it can be concluded that the value considering micro factor is closer to the actual work case of the aerostatic spindle system. These can provide theoretical basis for the design and machining process of machine tools.

A conceptual design of assembly strategy and dedicated tools for assembly of 40o sector

International Nuclear Information System (INIS)

Park, H.K.; Nam, K.O.; Kim, D.J.; Ahn, H.J.; Lee, J.H.; Im, K.; Shaw, R.

2010-01-01

The International Thermanuclear Experimental Reactor (ITER) tokamak device is composed of 9 vacuum vessel (VV)/toroidal field coils (TFCs)/vacuum vessel thermal shields (VVTS) 40 o sectors. Each VV/TFCs/VVTS 40 o sector is made up of one 40 o VV, two 20 o TFCs and associated VVTS segments. The 40 o sectors are sub-assembled at assembly hall respectively and then nine 40 o sectors sub-assembled at assembly hall are finally assembled at tokamak in-pit hall. The assembly strategy and tools for the 40 o sector sub-assembly and final assembly should be developed to satisfy the basic assembly requirements of the ITER tokamak device. Accordingly, the purpose-built assembly tools should be designed and manufactured considering assembly plan, available space, cost, safety, easy operation, efficient maintenance, and so on. The 40 o sector assembly tools are classified into 2 groups. One group is the sub-assembly tools including upending tool, lifting tool, sub-assembly tool, VV supports and bracing tools used at assembly hall and the other group is the in-pit assembly tools including lifting tool, central column, radial beams and their supports. This paper describes the current status of the assembly strategy and major tools for the VV/TFCs/VVTS 40 o sector assembly at in-pit hall and assembly hall. The conceptual design of the major assembly tools and assembly process at assembly hall and tokamak in-pit hall are presented also.

Sleep spindle-related reactivation of category-specific cortical regions after learning face-scene associations

DEFF Research Database (Denmark)

Bergmann, Til O; Mölle, Matthias; Diedrichs, Jens

2012-01-01

Newly acquired declarative memory traces are believed to be reactivated during NonREM sleep to promote their hippocampo-neocortical transfer for long-term storage. Yet it remains a major challenge to unravel the underlying neuronal mechanisms. Using simultaneous electroencephalography (EEG......-coupled reactivation of brain regions representing the specific task stimuli was traced during subsequent NonREM sleep with EEG-informed fMRI. Relative to the control task, learning face-scene associations triggered a stronger combined activation of neocortical and hippocampal regions during subsequent sleep. Notably......) and functional magnetic resonance imaging (fMRI) recordings in humans, we show that sleep spindles play a key role in the reactivation of memory-related neocortical representations. On separate days, participants either learned face-scene associations or performed a visuomotor control task. Spindle...

A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis.

Science.gov (United States)

Fuchs, Margit; Luthold, Carole; Guilbert, Solenn M; Varlet, Alice Anaïs; Lambert, Herman; Jetté, Alexandra; Elowe, Sabine; Landry, Jacques; Lavoie, Josée N

2015-10-01

The co-chaperone BAG3, in complex with the heat shock protein HSPB8, plays a role in protein quality control during mechanical strain. It is part of a multichaperone complex that senses damaged cytoskeletal proteins and orchestrates their seclusion and/or degradation by selective autophagy. Here we describe a novel role for the BAG3-HSPB8 complex in mitosis, a process involving profound changes in cell tension homeostasis. BAG3 is hyperphosphorylated at mitotic entry and localizes to centrosomal regions. BAG3 regulates, in an HSPB8-dependent manner, the timely congression of chromosomes to the metaphase plate by influencing the three-dimensional positioning of the mitotic spindle. Depletion of BAG3 caused defects in cell rounding at metaphase and dramatic blebbing of the cortex associated with abnormal spindle rotations. Similar defects were observed upon silencing of the autophagic receptor p62/SQSTM1 that contributes to BAG3-mediated selective autophagy pathway. Mitotic cells depleted of BAG3, HSPB8 or p62/SQSTM1 exhibited disorganized actin-rich retraction fibres, which are proposed to guide spindle orientation. Proper spindle positioning was rescued in BAG3-depleted cells upon addition of the lectin concanavalin A, which restores cortex rigidity. Together, our findings suggest the existence of a so-far unrecognized quality control mechanism involving BAG3, HSPB8 and p62/SQSTM1 for accurate remodelling of actin-based mitotic structures that guide spindle orientation.

A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis.

Directory of Open Access Journals (Sweden)

Margit Fuchs

2015-10-01

Full Text Available The co-chaperone BAG3, in complex with the heat shock protein HSPB8, plays a role in protein quality control during mechanical strain. It is part of a multichaperone complex that senses damaged cytoskeletal proteins and orchestrates their seclusion and/or degradation by selective autophagy. Here we describe a novel role for the BAG3-HSPB8 complex in mitosis, a process involving profound changes in cell tension homeostasis. BAG3 is hyperphosphorylated at mitotic entry and localizes to centrosomal regions. BAG3 regulates, in an HSPB8-dependent manner, the timely congression of chromosomes to the metaphase plate by influencing the three-dimensional positioning of the mitotic spindle. Depletion of BAG3 caused defects in cell rounding at metaphase and dramatic blebbing of the cortex associated with abnormal spindle rotations. Similar defects were observed upon silencing of the autophagic receptor p62/SQSTM1 that contributes to BAG3-mediated selective autophagy pathway. Mitotic cells depleted of BAG3, HSPB8 or p62/SQSTM1 exhibited disorganized actin-rich retraction fibres, which are proposed to guide spindle orientation. Proper spindle positioning was rescued in BAG3-depleted cells upon addition of the lectin concanavalin A, which restores cortex rigidity. Together, our findings suggest the existence of a so-far unrecognized quality control mechanism involving BAG3, HSPB8 and p62/SQSTM1 for accurate remodelling of actin-based mitotic structures that guide spindle orientation.

CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis.

Science.gov (United States)

Smolikov, Sarit; Schild-Prüfert, Kristina; Colaiácovo, Mónica P

2008-06-06

The synaptonemal complex (SC), a tripartite proteinaceous structure that forms between homologous chromosomes during meiosis, is crucial for faithful chromosome segregation. Here we identify CRA-1, a novel and conserved protein that is required for the assembly of the central region of the SC during C. elegans meiosis. In the absence of CRA-1, central region components fail to extensively localize onto chromosomes at early prophase and instead mostly surround the chromatin at this stage. Later in prophase, central region proteins polymerize along chromosome axes, but for the most part fail to connect the axes of paired homologous chromosomes. This defect results in an inability to stabilize homologous pairing interactions, altered double-strand break (DSB) repair progression, and a lack of chiasmata. Surprisingly, DSB formation and repair are required to promote the polymerization of the central region components along meiotic chromosome axes in cra-1 mutants. In the absence of both CRA-1 and any one of the C. elegans homologs of SPO11, MRE11, RAD51, or MSH5, the polymerization observed along chromosome axes is perturbed, resulting in the formation of aggregates of the SC central region proteins. While radiation-induced DSBs rescue this polymerization in cra-1; spo-11 mutants, they fail to do so in cra-1; mre-11, cra-1; rad-51, and cra-1; msh-5 mutants. Taken together, our studies place CRA-1 as a key component in promoting the assembly of a tripartite SC structure. Moreover, they reveal a scenario in which DSB formation and repair can drive the polymerization of SC components along chromosome axes in C. elegans.

The nature of assembly bias - III. Observational properties

Science.gov (United States)

Lacerna, Ivan; Padilla, Nelson; Stasyszyn, Federico

2014-10-01

We analyse galaxies in groups in the Sloan Digital Sky Survey (SDSS) and find a weak but significant assembly-type bias, where old central galaxies have a higher clustering amplitude (61 ± 9 per cent) at scales >1 h-1 Mpc than young central galaxies of equal host halo mass (Mh ˜ 1011.8 h- 1 M⊙). The observational sample is volume limited out to z = 0.1 with Mr - 5 log (h) ≤ -19.6. We construct a mock catalogue of galaxies that shows a similar signal of assembly bias (46 ± 9 per cent) at the same halo mass. We then adapt the model presented by Lacerna & Padilla (Paper I) to redefine the overdensity peak height, which traces the assembly bias such that galaxies in equal density peaks show the same clustering regardless of their stellar age, but this time using observational features such as a flux limit. The proxy for peak height, which is proposed as a better alternative than the virial mass, consists in the total mass given by the mass of neighbour host haloes in cylinders centred at each central galaxy. The radius of the cylinder is parameterized as a function of stellar age and virial mass. The best-fitting sets of parameters that make the assembly bias signal lower than 5-15 per cent for both SDSS and mock central galaxies are similar. The idea behind the parameterization is not to minimize the bias, but it is to use this method to understand the physical features that produce the assembly bias effect. Even though the tracers of the density field used here differ significantly from those used in Paper I, our analysis of the simulated catalogue indicates that the different tracers produce correlated proxies, and therefore the reason behind assembly bias is the crowding of peaks in both simulations and the SDSS.

Assembling Sustainable Territories

DEFF Research Database (Denmark)

Vandergeest, Peter; Ponte, Stefano; Bush, Simon

2015-01-01

that territorialisation is accomplished not just through (re)defining bounded space, but more broadly through the assembling of four elements: space, subjects, objects, and expertise. Four case studies of sustainability certification in seafood are analyzed to show that ‘green gabbing’ is not necessarily the central...

Mucinous tubular and spindle cell carcinoma of kidney: A rare case report and review of the literature

Directory of Open Access Journals (Sweden)

Geramizadeh Bita

2009-10-01

Full Text Available Low grade mucinous tubular and spindle cell carcinoma of kidney was newly established as a distinct renal cell carcinoma in the World Health Organization (WHO classification of 2004. Until now, less than 60 cases have been reported and the largest series represented approximately 15 patients with this type of tumor. Herein, we report a case of mucinous tubular and spindle cell carcinoma in a 63-year-old male presented with right flank pain which was diagnosed after nephrectomy. Pathologists should consider this diagnosis and its spectrum of histopathologic features in mind to ensure an accurate diagnosis.

Critical Importance of Protein 4.1 in Centrosome and Mitiotic Spindle Aberrations in Breast Cancer Pathogenesis

National Research Council Canada - National Science Library

Krauss, Sharon W

2005-01-01

Important pathological hallmarks of many breast cancers include centrosome amplification, spindle pole defects leading to aberrant chromosome segregation, altered nucleoskeletal proteins and perturbed cytokinesis...

Spindle cell oncocytoma of adenohypophysis: Cytogenetics and β-catenin findings with pathology differential diagnosis and review of the literature

Directory of Open Access Journals (Sweden)

Jianwu Xie

2017-09-01

Full Text Available Spindle cell oncocytoma (SCO is an extremely rare neoplasm arising in the anterior pituitary. We report comprehensive pathological description of a case of SCO in a 60 year-old male who presented with nausea, vomiting and severe hyponatremia, and pan hypopituitarism. Magnetic resonance imaging (MRI showed a 3.1 × 2.3 × 2.0 cm homogeneously enhancing bilobed mass within the sella turcica and suprasellar cistern. Intraoperative frozen section and touch imprint cytology showed cohesive spindle cells with abundant oncocytic cytoplasm. Histologic sections revealed the tumor was composed of interlacing fascicles of compact spindled cells with abundant dense oncocytic cytoplasm. There was no mitosis or necrosis present. Ki-67 index varied in areas, with an average of 3%. By immunohistochemistry (IHC, the tumor cells were negative for Cam5.2, AE1/3, neurofilament (NF, NeuN, glial fibrillary acidic protein (GFAP and synaptophysin, and strongly positive for vimentin, TTF-1 and EMA. S-100 showed focal weakly positivity. By electron microscopy (EM, the cytoplasm of the spindle cells contained numerous abundant, back-to-back, uniform, round, normal-sized mitochondria with long and lamellar cristae. Beta-catenin showed diffuse membranous and partial cytoplasmic positivity. Cytogenetic analysis showed extra copies of chromosome 1 (74%, up to 8 copies, and loss of chromosome 2 (35%. The histogenesis, classification and differential diagnosis are discussed.

Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells.

Directory of Open Access Journals (Sweden)

Daisuke Sakai

Full Text Available The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1(+/- mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1, and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly.

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.

Spindle cell carcinoma of the breast as complex cystic lesion: a case report

International Nuclear Information System (INIS)

Kitada, Masahiro; Hayashi, Satoshi; Matsuda, Yoshinari; Ishibashi, Kei; Oikawa, Keisuke; Miyokawa, Naoyuki

2014-01-01

Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammography showed a category four mass with a diameter of 2.5 cm. Ultrasonography (US) revealed a complex cystic lesion, and fine-needle aspiration (FNA) cytology demonstrated bloody fluid and malignant cells. Partial breast resection and sentinel lymph node biopsy were performed. Immunohistology revealed spindle cells with positive results for cytokeratin (AE1/AE3) and vimentin, partially positive results for s-100, and negative results for desmin and α-actin. The pathological stage was IIA, and biochemical characterization showed that the tumor was triple negative. Six courses of FEC-100 chemotherapy (5-fluorouracil 500 mg/m 2 , epirubicin 100 mg/m 2 , and cyclophosphamide 500 mg/m 2 ) were administered. Radiotherapy was performed. This case is discussed with reference to the literature

Synthesis, structural and optical properties of ZnO spindle/reduced graphene oxide composites with enhanced photocatalytic activity under visible light irradiation

Science.gov (United States)

Prabhu, S.; Pudukudy, M.; Sohila, S.; Harish, S.; Navaneethan, M.; Navaneethan, D.; Ramesh, R.; Hayakawa, Y.

2018-05-01

In the present work, spindle-shaped ZnO and reduced graphene oxide sheets were successfully synthesized by a hydrothermal method and then ZnO/r-GO composite was prepared by a direct solution mixing method. Various characterization results confirmed the interior and surface decoration of spindle-shaped ZnO on the reduced graphene oxide sheets. The phase formation, crystalline structure, morphology, surface states and optical properties were characterized using Powder X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier Transform Infrared Spectroscopy (FTIR) and UV-Vis spectroscopy. The X-ray diffraction analysis showed the formation of the hexagonal wurtzite crystalline structure of ZnO with high crystalline quality. The band gap of the ZnO/r-GO composite was found to be low (3.03eV) compared to the band gap of spindle shaped ZnO (3.13 eV), as calculated from optical studies. The spindle-like morphology of the single crystalline ZnO was clearly shown in the electron microscopic images. The chemical bonding and surface states of the samples were studied using XPS measurement. Moreover, a possible growth mechanism for the ZnO spindle was proposed. The catalytic activity of the as-synthesized samples was evaluated for the photodegradation of methylene blue under visible light irradiation. Among the synthesized samples, the ZnO/r-GO composite showed higher degradation efficiency of 93% and successfully reused for four consecutive run without any activity loss.

The SUMO protease SENP1 is required for cohesion maintenance and mitotic arrest following spindle poison treatment

Energy Technology Data Exchange (ETDEWEB)

Era, Saho [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Abe, Takuya; Arakawa, Hiroshi [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Kobayashi, Shunsuke [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Szakal, Barnabas [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy); Yoshikawa, Yusuke; Motegi, Akira; Takeda, Shunichi [Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501 (Japan); Branzei, Dana, E-mail: dana.branzei@ifom.eu [Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM-IEO campus, Via Adamello 16, 20139 Milan (Italy)

2012-09-28

Highlights: Black-Right-Pointing-Pointer SENP1 knockout chicken DT40 cells are hypersensitive to spindle poisons. Black-Right-Pointing-Pointer Spindle poison treatment of SENP1{sup -/-} cells leads to increased mitotic slippage. Black-Right-Pointing-Pointer Mitotic slippage in SENP1{sup -/-} cells associates with apoptosis and endoreplication. Black-Right-Pointing-Pointer SENP1 counteracts sister chromatid separation during mitotic arrest. Black-Right-Pointing-Pointer Plk1-mediated cohesion down-regulation is involved in colcemid cytotoxicity. -- Abstract: SUMO conjugation is a reversible posttranslational modification that regulates protein function. SENP1 is one of the six SUMO-specific proteases present in vertebrate cells and its altered expression is observed in several carcinomas. To characterize SENP1 role in genome integrity, we generated Senp1 knockout chicken DT40 cells. SENP1{sup -/-} cells show normal proliferation, but are sensitive to spindle poisons. This hypersensitivity correlates with increased sister chromatid separation, mitotic slippage, and apoptosis. To test whether the cohesion defect had a causal relationship with the observed mitotic events, we restored the cohesive status of sister chromatids by introducing the TOP2{alpha}{sup +/-} mutation, which leads to increased catenation, or by inhibiting Plk1 and Aurora B kinases that promote cohesin release from chromosomes during prolonged mitotic arrest. Although TOP2{alpha} is SUMOylated during mitosis, the TOP2{alpha}{sup +/-} mutation had no obvious effect. By contrast, inhibition of Plk1 or Aurora B rescued the hypersensitivity of SENP1{sup -/-} cells to colcemid. In conclusion, we identify SENP1 as a novel factor required for mitotic arrest and cohesion maintenance during prolonged mitotic arrest induced by spindle poisons.

Synthesis of spindle-shaped AgI/TiO{sub 2} nanoparticles with enhanced photocatalytic performance

Energy Technology Data Exchange (ETDEWEB)

Yang, Liu; Gao, Minggang; Dai, Bin; Guo, Xuhong; Liu, Zhiyong; Peng, Banghua, E-mail: banghuapeng@hotmail.com

2016-11-15

Highlights: • Nanoporous spindle-shaped AgI/TiO{sub 2} was synthesized by the solvothermal approach. • The spindle-shaped TiO{sub 2} was an excellent support for loading nanoparticles, such as AgI, transferring electrons quickly from AgI, which is beneficial for stabilizing the AgI. • AgI/TiO{sub 2} nanoparticles showed enhanced absorption intensity in the visible region and exhibited excellent photocatalytic activity. - Abstract: A novel synthetic route has been developed to prepare silver iodide (AgI) loaded spindle-shaped TiO{sub 2} nanoparticles (NPs). The morphology and crystallinity characterization revealed that small AgI NPs, with an average diameter of 15 nm were dispersed on the surface and interior of nanoporous anatase TiO{sub 2} support. High-resolution transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller (BET) surface area, Raman and X-ray photoelectron spectroscopy (XPS) were used to identify the nanoporous structure of TiO{sub 2} and the existence of AgI NPs. Diffuse reflectance spectra (DRS) showed that AgI/TiO{sub 2} composite exhibited a remarkable enhancement of visible light absorption, which is ascribed to the addition of AgI. For illustrating the superior property of this hybrid as photocatalyst, the degradation experiments were carried out for processing rhodamine B (RhB) solution under visible light irradiation and it was found that the photocatalytic activity was dramatically improved for AgI/TiO{sub 2} compared with nanoporous TiO{sub 2} and commercial P25 TiO{sub 2}. The enhanced photocatalytic properties could be attributed to the large surface area of porous TiO{sub 2}, good stability of AgI particles, and the effective charge separation due to the synergetic effect between AgI and TiO{sub 2} that can facilitate the separation of electron-hole pairs. Our novel composite based on nanoporous spindle-shaped TiO{sub 2} represents a promising new pathway for the design of high-performance photocatalysts for environmental

Electrostatics and the assembly of an RNA virus

NARCIS (Netherlands)

Schoot, van der P.P.A.M.; Bruinsma, R.

2005-01-01

Electrostatic interactions play a central role in the assembly of single-stranded RNA viruses. Under physiological conditions of salinity and acidity, virus capsid assembly requires the presence of genomic material that is oppositely charged to the core proteins. In this paper we apply basic polymer

Machinability evaluation of titanium alloys (Part 2)--Analyses of cutting force and spindle motor current.

Science.gov (United States)

Kikuchi, Masafumi; Okuno, Osamu

2004-12-01

To establish a method of determining the machinability of dental materials for CAD/CAM systems, the machinability of titanium, two titanium alloys (Ti-6Al-4V and Ti-6Al-7Nb), and free-cutting brass was evaluated through cutting force and spindle motor current. The metals were slotted using a milling machine and square end mills at four cutting conditions. Both the static and dynamic components of the cutting force represented well the machinability of the metals tested: the machinability of Ti-6Al-4V and Ti-6Al-7Nb was worse than that of titanium, while that of free-cutting brass was better. On the other hand, the results indicated that the spindle motor current was not sensitive enough to detect the material difference among the titanium and its alloys.

Nuclear reactor fuel assembly

International Nuclear Information System (INIS)

Sakurai, Shungo; Ogiya, Shunsuke.

1990-01-01

In a fuel assembly, if the entire fuels comprise mixed oxide fuels, reactivity change in cold temperature-power operation is increased to worsen the reactor shutdown margin. The reactor shutdown margin has been improved by increasing the burnable poison concentration thereby reducing the reactivity of the fuel assembly. However, since unburnt poisons are present at the completion of the reactor operation, the reactivity can not be utilized effectively to bring about economical disadvantage. In view of the above, the reactivity change between lower temperature-power operations is reduced by providing a non-boiling range with more than 9.1% of cross sectional area at the inside of a channel at the central portion of the fuel assembly. As a result, the amount of the unburnt burnable poisons is decreased, the economy of fuel assembly is improved and the reactor shutdown margin can be increase. (N.H.)

Controllable synthesis of spindle-like ZnO nanostructures by a simple low-temperature aqueous solution route

International Nuclear Information System (INIS)

Lu Hongxia; Zhao Yunlong; Yu Xiujun; Chen Deliang; Zhang Liwei; Xu Hongliang; Yang Daoyuan; Wang Hailong; Zhang Rui

2011-01-01

Spindle-like ZnO nanostructures were successfully synthesized through direct precipitation of zinc acetate aqueous solution at 60 deg. C. Phase structure, morphology and microstructure of the products were investigated by X-ray diffraction, TG-DTA, FTIR and field emission scanning electron microscopy (FESEM). Result showed that hexagonal wurtzite structure ZnO nanostructures with about 100 nm in diameter and 100-200 nm in length were obtained. HMTA acted as a soft template in the process and played an important role in the formation of spindle-like ZnO nanostructures. Meanwhile, different morphologies were also obtained by altering synthetic temperature, additional agents and the ratios of Zn 2+ /OH - . Possible mechanism for the variations of morphology with synthesis parameters was also discussed in this paper.

Thermal Error Test and Intelligent Modeling Research on the Spindle of High Speed CNC Machine Tools

Science.gov (United States)

Luo, Zhonghui; Peng, Bin; Xiao, Qijun; Bai, Lu

2018-03-01

Thermal error is the main factor affecting the accuracy of precision machining. Through experiments, this paper studies the thermal error test and intelligent modeling for the spindle of vertical high speed CNC machine tools in respect of current research focuses on thermal error of machine tool. Several testing devices for thermal error are designed, of which 7 temperature sensors are used to measure the temperature of machine tool spindle system and 2 displacement sensors are used to detect the thermal error displacement. A thermal error compensation model, which has a good ability in inversion prediction, is established by applying the principal component analysis technology, optimizing the temperature measuring points, extracting the characteristic values closely associated with the thermal error displacement, and using the artificial neural network technology.

Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue

NARCIS (Netherlands)

Quyn, A.J.; Appleton, P.L.; Carey, F.A.; Steele, R.J.; Barker, N.; Clevers, H.; Ridgway, R.A.; Sansom, O.J.; Nathke, I.S.

2010-01-01

The importance of asymmetric divisions for stem cell function and maintenance is well established in the developing nervous system and the skin; however, its role in gut epithelium and its importance for tumorigenesis is still debated. We demonstrate alignment of mitotic spindles perpendicular to

Critical Importance of Protein 4.1 in Centrosome and Mitotic Spindle Aberrations in Breast Cancer Pathogenesis

National Research Council Canada - National Science Library

Krauss, Sharon W

2006-01-01

We proposed to test the novel hypothesis that protein 4.1 is of critical importance to centrosome and mitotic spindle aberrations that directly impact aspects of breast cancer pathogenesis. We characterized...

Live Imaging of Meiosis I in Late-Stage Drosophila melanogaster Oocytes.

Science.gov (United States)

Hughes, Stacie E; Hawley, R Scott

2017-01-01

Drosophila melanogaster has been studied for a century as a genetic model to understand recombination, chromosome segregation, and the basic rules of inheritance. However, it has only been about 25 years since the events that occur during nuclear envelope breakdown, spindle assembly, and chromosome orientation during D. melanogaster female meiosis I were first visualized by fixed cytological methods (Theurkauf and Hawley, J Cell Biol 116:1167-1180, 1992). Although these fixed cytological studies revealed many important details about the events that occur during meiosis I, they failed to elucidate the timing or order of these events. The development of protocols for live imaging of meiotic events within the oocyte has enabled collection of real-time information on the kinetics and dynamics of spindle assembly, as well as the behavior of chromosomes during prometaphase I. Here, we describe a method to visualize spindle assembly and chromosome movement during meiosis I by injecting fluorescent dyes to label microtubules and DNA into stage 12-14 oocytes. This method enables the events during Drosophila female meiosis I, such as spindle assembly and chromosome movement, to be observed in vivo, regardless of genetic background, with exceptional spatial and temporal resolution.

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.

Triangular relationship between sleep spindle activity, general cognitive ability and the efficiency of declarative learning.

Directory of Open Access Journals (Sweden)

Caroline Lustenberger

Full Text Available EEG sleep spindle activity (SpA during non-rapid eye movement (NREM sleep has been reported to be associated with measures of intelligence and overnight performance improvements. The reticular nucleus of the thalamus is generating sleep spindles in interaction with thalamocortical connections. The same system enables efficient encoding and processing during wakefulness. Thus, we examined if the triangular relationship between SpA, measures of intelligence and declarative learning reflect the efficiency of the thalamocortical system. As expected, SpA was associated with general cognitive ability, e.g. information processing speed. SpA was also associated with learning efficiency, however, not with overnight performance improvement in a declarative memory task. SpA might therefore reflect the efficiency of the thalamocortical network and can be seen as a marker for learning during encoding in wakefulness, i.e. learning efficiency.

A comparative study of using spindle motor power and eddy current for the detection of tool conditions in milling processes

OpenAIRE

Abbass, JK; Al-Habaibeh, A

2015-01-01

This paper investigates the use of the power of the driving motor of a CNC spindle in comparison to two perpendicular eddy current sensors for the detection of tool wear in milling processes. Monitoring the power through the current profile is a low cost system which has been utilised in this study as an attempt to detect the fluctuation in the motor load as a result of the conditions of the cutting tool. Eddy current sensors are dedicated sensors that are installed on the spindle to measure ...

Self-assembling peptide semiconductors

Science.gov (United States)

Tao, Kai; Makam, Pandeeswar; Aizen, Ruth; Gazit, Ehud

2017-01-01

Semiconductors are central to the modern electronics and optics industries. Conventional semiconductive materials bear inherent limitations, especially in emerging fields such as interfacing with biological systems and bottom-up fabrication. A promising candidate for bioinspired and durable nanoscale semiconductors is the family of self-assembled nanostructures comprising short peptides. The highly ordered and directional intermolecular π-π interactions and hydrogen-bonding network allow the formation of quantum confined structures within the peptide self-assemblies, thus decreasing the band gaps of the superstructures into semiconductor regions. As a result of the diverse architectures and ease of modification of peptide self-assemblies, their semiconductivity can be readily tuned, doped, and functionalized. Therefore, this family of electroactive supramolecular materials may bridge the gap between the inorganic semiconductor world and biological systems. PMID:29146781

Separation and estimation of muscle spindle and tension receptor populations by vibration of the biceps muscle in the frog.

Science.gov (United States)

Giszter, S F; Kargo, W J

2002-10-01

Frog spinal cord reflex behaviors have been used to test the idea of spinal primitives. We have suggested a significant role for proprioception in regulation of primitives. However the in vivo behavior of spindle and golgi tendon receptors in frogs in response to vibration are not well described and the proportions of these proprioceptors are not established. In this study, we examine the selectivity of muscle vibration in the spinal frog. The aim of the study was (1) to examine how hindlimb muscle spindles and GTO receptors are activated by muscle vibration and (2) to estimate the relative numbers of GTO receptors and spindle afferents in a selected muscle, for comparison with the mammal. Single muscle afferents from the biceps muscle were identified in the dorsal roots. These were tested in response to biceps vibration, intramuscular stimulation and biceps nerve stimulation. Biceps units were categorized into two types: First, spindle afferents which had a high conduction velocity (approximately 20-30 m/s), responded reliably (were entrained 1:1) to muscle vibration, and exhibited distinct pauses to shortening muscle contractions. Second, golgi tendon organ afferents, which had a lower conduction velocity (approximately 10-20 m/s), responded less reliably to muscle vibration at physiologic muscle lengths, but responded more reliably at extended lengths or with background muscle contraction, and exhibited distinct bursts to shortening muscle contractions. Vibration responses of these units were tested with and without muscle curarization. Ensemble (suction electrode) recordings from the dorsal roots were used to provide rough estimates of the proportions of the two muscle afferent types.

Improved lithium-ion battery anode capacity with a network of easily fabricated spindle-like carbon nanofibers.

Science.gov (United States)

Liu, Mengting; Xie, Wenhe; Gu, Lili; Qin, Tianfeng; Hou, Xiaoyi; He, Deyan

2016-01-01

A novel network of spindle-like carbon nanofibers was fabricated via a simplified synthesis involving electrospinning followed by preoxidation in air and postcarbonization in Ar. Not only was the as-obtained carbon network comprised of beads of spindle-like nanofibers but the cubic MnO phase and N elements were successfully anchored into the amorphous carbon matrix. When directly used as a binder-free anode for lithium-ion batteries, the network showed excellent electrochemical performance with high capacity, good rate capacity and reliable cycling stability. Under a current density of 0.2 A g -1 , it delivered a high reversible capacity of 875.5 mAh g -1 after 200 cycles and 1005.5 mAh g -1 after 250 cycles with a significant coulombic efficiency of 99.5%.

The meiosis-specific nuclear passenger protein is required for proper assembly of forespore membrane in fission yeast.

Science.gov (United States)

Takaine, Masak; Imada, Kazuki; Numata, Osamu; Nakamura, Taro; Nakano, Kentaro

2014-10-15

Sporulation, gametogenesis in yeast, consists of meiotic nuclear division and spore morphogenesis. In the fission yeast Schizosaccharomyces pombe, the four haploid nuclei produced after meiosis II are encapsulated by the forespore membrane (FSM), which is newly synthesized from spindle pole bodies (SPBs) in the cytoplasm of the mother cell as spore precursors. Although the coordination between meiosis and FSM assembly is vital for proper sporulation, the underlying mechanism remains unclear. In the present study, we identified a new meiosis-specific protein Npg1, and found that it was involved in the efficient formation of spores and spore viability. The accumulation and organization of the FSM was compromised in npg1-null cells, leading to the error-prone envelopment of nuclei. Npg1 was first seen as internuclear dots and translocated to the SPBs before the FSM assembled. Genetic analysis revealed that Npg1 worked in conjunction with the FSM proteins Spo3 and Meu14. These results suggest a possible signaling link from the nucleus to the meiotic SPBs in order to associate the onset of FSM assembly with meiosis II, which ensures the successful partitioning of gametic nuclei. © 2014. Published by The Company of Biologists Ltd.

THE SPINDLE: AN IRRADIATED DISK AND BENT PROTOSTELLAR JET IN ORION

Energy Technology Data Exchange (ETDEWEB)

Bally, John; Youngblood, Allison; Ginsburg, Adam, E-mail: John.Bally@colorado.edu, E-mail: Allison.Youngblood@colorado.edu, E-mail: Adam.Ginsburg@colorado.edu [Department of Astrophysical and Planetary Sciences, University of Colorado, UCB 389, Boulder, CO 80309 (United States)

2012-09-10

We present Hubble Space Telescope observations of a bent, pulsed Herbig-Haro jet, HH 1064, emerging from the young star Parenago 2042 embedded in the H II region NGC 1977 located about 30' north of the Orion Nebula. This outflow contains eight bow shocks in the redshifted western lobe and five bow shocks in the blueshifted eastern lobe. Shocks within a few thousand AU of the source star exhibit proper motions of {approx}160 km s{sup -1} but motions decrease with increasing distance. Parenago 2042 is embedded in a proplyd-a photoevaporating protoplanetary disk. A remarkable set of H{alpha} arcs resembling a spindle surround the redshifted (western) jet. The largest arc with a radius of 500 AU may trace the ionized edge of a circumstellar disk inclined by {approx}30 Degree-Sign . The spindle may be the photoionized edge of either a {approx}3 km s{sup -1} FUV-driven wind from the outer disk or a faster MHD-powered flow from an inner disk. The HH 1064 jet appears to be deflected north by photoablation of the south-facing side of a mostly neutral jet beam. V2412 Ori, located 1' west of Parenago 2042 drives a second bent flow, HH 1065. Both HH 1064 and 1065 are surrounded by LL Ori-type bows marking the boundary between the outflow cavity and the surrounding nebula.

Study of Contactless Power Supply for Spindle Ultrasonic Vibrator

Science.gov (United States)

Chen, T. R.; Lee, Y. L.; Liu, H. T.; Chen, S. M.; Chang, H. Z.

2017-11-01

In this study, a contactless power supply for the ultrasonic motor on the spindle is proposed. The proposed power supply is composed of a series-parallel resonant circuit and a cylindrical contactless transformer. Based on the study and rotation experiments, it can be seen that the proposed power supply can both provide a stable ac power with 25 kHz / 70 V to the ultrasonic motor. When the output power is 250 W, the efficiency of the proposed supply is 89.8 % in respectively rotation tests. When the output power is more than 150 W, the efficiency of the proposed supply is higher than 80 % within the rated output power range.

The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression.

Directory of Open Access Journals (Sweden)

Li Bie

Full Text Available Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001, and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67 labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time.

Centrosome-Based Mechanisms, Prognostics and Therapeutics in Prostate Cancer

Science.gov (United States)

2006-12-01

Roberts, J. M. CDK inhibitors: positive and negative regulators of G1- phase progression. Genes Dev. 13, 1501–1512 (1999). 20. La Terra , S. et al. The...centrosome matura - tion because disruption of the tubulin–pericentrin inter- action disrupts spindle pole assembly and possibly centrosome maturation...monitoring. We favor a model in which the check- point senses spindle pole assembly/centrosome matura - tion because disruption of the tubulin

Germline-specific MATH-BTB substrate adaptor MAB1 regulates spindle length and nuclei identity in maize.

Science.gov (United States)

Juranič, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanic, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas

2012-12-01

Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle-dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s).

Nuclear reactor seismic fuel assembly grid

International Nuclear Information System (INIS)

Anthony, A.J.

1977-01-01

The strength of a nuclear reactor fuel assembly is enhanced by increasing the crush strength of the zircaloy spacer grids which locate and support the fuel elements in the fuel assembly. Increased resistance to deformation as a result of laterally directed forces is achieved by increasing the section modulus of the perimeter strip through bending the upper and lower edges thereof inwardly. The perimeter strip is further rigidized by forming, in the central portion thereof, dimples which extend inwardly with respect to the fuel assembly. The integrity of the spacer grid may also be enhanced by providing back-up arches for some or all of the integral fuel element locating springs and the strength of the fuel assembly may be further enhanced by providing, intermediate its ends, a steel seismic grid. 13 claims, 6 figures

Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin.

Science.gov (United States)

Baumann, Claudia; Wang, Xiaotian; Yang, Luhan; Viveiros, Maria M

2017-04-01

Mouse oocytes lack canonical centrosomes and instead contain unique acentriolar microtubule-organizing centers (aMTOCs). To test the function of these distinct aMTOCs in meiotic spindle formation, pericentrin (Pcnt), an essential centrosome/MTOC protein, was knocked down exclusively in oocytes by using a transgenic RNAi approach. Here, we provide evidence that disruption of aMTOC function in oocytes promotes spindle instability and severe meiotic errors that lead to pronounced female subfertility. Pcnt-depleted oocytes from transgenic (Tg) mice were ovulated at the metaphase-II stage, but show significant chromosome misalignment, aneuploidy and premature sister chromatid separation. These defects were associated with loss of key Pcnt-interacting proteins (γ-tubulin, Nedd1 and Cep215) from meiotic spindle poles, altered spindle structure and chromosome-microtubule attachment errors. Live-cell imaging revealed disruptions in the dynamics of spindle assembly and organization, together with chromosome attachment and congression defects. Notably, spindle formation was dependent on Ran GTPase activity in Pcnt-deficient oocytes. Our findings establish that meiotic division is highly error-prone in the absence of Pcnt and disrupted aMTOCs, similar to what reportedly occurs in human oocytes. Moreover, these data underscore crucial differences between MTOC-dependent and -independent meiotic spindle assembly. © 2017. Published by The Company of Biologists Ltd.

Mucinous tubular and spindle cell carcinoma of kidney: A clinicopathologic study of six cases

Directory of Open Access Journals (Sweden)

Mudassar Hussain

2012-01-01

Full Text Available Background: Mucinous tubular and spindle carcinoma (MTSCC of kidney is a rare, low-grade polymorphic tumor. Recent studies have described a wide morphology spectrum of this tumor. Aim: To report the clinico-pathologic features of six cases of MTSCC of kidney. Materials and Methods: Six cases of MTSCC of kidney were studied and literature was reviewed. Immunohistochemistry was done by Envision method. Results: The age of the patients ranged from 44 to 84 years (mean 58.5 years. Four patients were males and two were females. The tumor was located in the left kidney in four cases and in the right kidney in two cases. The tumor size ranged from 4.5 to 15 cm (mean 6.4 cm. All tumors exhibited an admixture of tubules, spindle cells, and mucinous stroma in variable proportions. Tubules were predominant in five cases and spindle cells in one case. Psammomatous calcifications, papillations, and necrosis were seen in two cases. Collections of foamy histiocytes were noted in four cases. Cytoplasmic vacuoles and osseous metaplasia were seen in one case each. All cases were Fuhrman′s nuclear grade II. Five cases were of stage pT1, and one was pT3. All cases stained positive for alcian blue at pH 2.5. Immunohistochemical stain CK7 was positive in all cases and CD10 was positive in 1/1 case. All patients were alive and well at follow-up of 12-59 months (mean 33.5 months. No metastases were detected. Conclusions: We report six cases of MTSCC of kidney, a rare distinct variant of RCC, with a favorable prognosis. A male predominance was seen in our cases. MTSCC shares histologic and immunohistochemical overlap with papillary renal cell carcinoma (PRCC and cytogenetic analysis should be performed in difficult cases to avoid a misdiagnosis.

Neural mechanisms of mental schema: a triplet of delta, low beta/spindle and ripple oscillations.

Science.gov (United States)

Ohki, Takefumi; Takei, Yuichi

2018-02-06

Schemas are higher-level knowledge structures that integrate and organise lower-level representations. As internal templates, schemas are formed according to how events are perceived, interpreted and remembered. Although these higher-level units are assumed to play a fundamental role in our daily life from an early age, the neuronal basis and mechanisms of schema formation and use remain largely unknown. It is important to elucidate how the brain constructs and maintains these higher-level units. In order to examine the possible neural underpinnings of schema, we recapitulate previous work and discuss their findings related to schemas as the brain template. We specifically focused on low beta/spindle oscillations, which are assumed to be the key components of schemas, and propose that the brain template is implemented with a triplet of neural oscillations, that is delta, low beta/spindle and ripple oscillations. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Epistatic determinism of durum wheat resistance to the wheat spindle streak mosaic virus.

Science.gov (United States)

Holtz, Yan; Bonnefoy, Michel; Viader, Véronique; Ardisson, Morgane; Rode, Nicolas O; Poux, Gérard; Roumet, Pierre; Marie-Jeanne, Véronique; Ranwez, Vincent; Santoni, Sylvain; Gouache, David; David, Jacques L

2017-07-01

The resistance of durum wheat to the Wheat spindle streak mosaic virus (WSSMV) is controlled by two main QTLs on chromosomes 7A and 7B, with a huge epistatic effect. Wheat spindle streak mosaic virus (WSSMV) is a major disease of durum wheat in Europe and North America. Breeding WSSMV-resistant cultivars is currently the only way to control the virus since no treatment is available. This paper reports studies of the inheritance of WSSMV resistance using two related durum wheat populations obtained by crossing two elite cultivars with a WSSMV-resistant emmer cultivar. In 2012 and 2015, 354 recombinant inbred lines (RIL) were phenotyped using visual notations, ELISA and qPCR and genotyped using locus targeted capture and sequencing. This allowed us to build a consensus genetic map of 8568 markers and identify three chromosomal regions involved in WSSMV resistance. Two major regions (located on chromosomes 7A and 7B) jointly explain, on the basis of epistatic interactions, up to 43% of the phenotypic variation. Flanking sequences of our genetic markers are provided to facilitate future marker-assisted selection of WSSMV-resistant cultivars.

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...

Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2

Science.gov (United States)

Petry, Sabine; Groen, Aaron C.; Ishihara, Keisuke; Mitchison, Timothy J.; Vale, Ronald D.

2013-01-01

Summary The microtubules that comprise mitotic spindles in animal cells are nucleated at centrosomes and by spindle assembly factors that are activated in the vicinity of chromatin. Indirect evidence also has suggested that microtubules might be nucleated from pre-existing microtubules throughout the spindle, but this process has not been observed directly. Here, we demonstrate microtubule nucleation from the sides of existing microtubules in meiotic Xenopus egg extracts. Daughter microtubules grow at a low branch angle and with the same polarity as mother filaments. Branching microtubule nucleation requires gamma-tubulin and augmin and is stimulated by GTP-bound Ran and its effector TPX2, factors previously implicated in chromatin-stimulated nucleation. Because of the rapid amplification of microtubule numbers and the preservation of microtubule polarity, microtubule-dependent microtubule nucleation is well suited for spindle assembly and maintenance. PMID:23415226

DNA-Directed Assembly of Capture Tools for Constitutional Studies of Large Protein Complexes.

Science.gov (United States)

Meyer, Rebecca; Faesen, Alex; Vogel, Katrin; Jeganathan, Sadasivam; Musacchio, Andrea; Niemeyer, Christof M

2015-06-10

Large supramolecular protein complexes, such as the molecular machinery involved in gene regulation, cell signaling, or cell division, are key in all fundamental processes of life. Detailed elucidation of structure and dynamics of such complexes can be achieved by reverse-engineering parts of the complexes in order to probe their interactions with distinctive binding partners in vitro. The exploitation of DNA nanostructures to mimic partially assembled supramolecular protein complexes in which the presence and state of two or more proteins are decisive for binding of additional building blocks is reported here. To this end, four-way DNA Holliday junction motifs bearing a fluorescein and a biotin tag, for tracking and affinity capture, respectively, are site-specifically functionalized with centromeric protein (CENP) C and CENP-T. The latter serves as baits for binding of the so-called KMN component, thereby mimicking early stages of the assembly of kinetochores, structures that mediate and control the attachment of microtubules to chromosomes in the spindle apparatus. Results from pull-down experiments are consistent with the hypothesis that CENP-C and CENP-T may bind cooperatively to the KMN network. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Paired replacement fuel assemblies for BWR-type reactor

International Nuclear Information System (INIS)

Oguchi, Kazushige.

1997-01-01

There are disposed a large-diameter water rod constituting a non-boiling region at a central portion and paired replacement fuel assemblies for two streams having the same average enrichment degree and different amount of burnable poisons. The paired replacement fuel assemblies comprise a first fuel assembly having a less amount of burnable poisons and a second fuel assembly having a larger amount of burnable poisons. A number of burnable poison-containing fuel rods in adjacent with the large diameter water rod is increased in the second fuel assembly than the first fuel assembly. Then, the poison of the paired replacement fuel assemblies for the BWR type reactor can be annihilated simultaneously at the final stage of the cycle. Accordingly, fuels for a BWR type reactor excellent in economical property and safety and facilitating the design of the replacement reactor core can be obtained. (N.H.)

Fuel assemblies for use in nuclear reactors

International Nuclear Information System (INIS)

Mochida, Takaaki.

1987-01-01

Purpose: To increase the plutonium utilization amount and improve the uranium-saving effect in the fuel assemblies of PWR type reactor using mixed uranium-plutonium oxides. Constitution: MOX fuel rods comprising mixed plutonium-uranium oxides are disposed to the outer circumference of a fuel assembly and uranium fuel rods only composed of uranium oxides are disposed to the central portion thereof. In such a fuel assembly, since the uranium fuel rods are present at the periphery of the control rod, the control rod worth is the same as that of the uranium fuel assembly in the prior art. Further, since about 25 % of the entire fuel rods is composed of the MOX fuel rods, the plutonium utilization amount is increased. Further, since the MOX fuel rods at low enrichment degree are present at the outer circumferential portion, mismatching at the boundary to the adjacent MOX fuel assembly is reduced and the problem of local power peaking increase in the MOX fuel assembly is neither present. (Kamimura, M.)

ATP-dependent human RISC assembly pathways.

Science.gov (United States)

Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide

2010-01-01

The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

Pacemaker activity in a sensory ending with multiple encoding sites : The cat muscle spindle primary ending

NARCIS (Netherlands)

Banks, RW; Hulliger, M; Scheepstra, KA; Otten, E

1997-01-01

1. A combined physiological, histological and computer modelling study was carried out on muscle spindles of the cat tenuissimus muscle to examine whether there was any correlation between the functional interaction of putative encoding sites, operated separately by static and dynamic fusimotor

Chaperoning 5S RNA assembly.

Science.gov (United States)

Madru, Clément; Lebaron, Simon; Blaud, Magali; Delbos, Lila; Pipoli, Juliana; Pasmant, Eric; Réty, Stéphane; Leulliot, Nicolas

2015-07-01

In eukaryotes, three of the four ribosomal RNAs (rRNAs)—the 5.8S, 18S, and 25S/28S rRNAs—are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2-Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2-Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2-Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. © 2015 Madru et al.; Published by Cold Spring Harbor Laboratory Press.

A combined quantitative mass spectrometry and electron microscopy analysis of ribosomal 30S subunit assembly in E. coli.

Science.gov (United States)

Sashital, Dipali G; Greeman, Candacia A; Lyumkis, Dmitry; Potter, Clinton S; Carragher, Bridget; Williamson, James R

2014-10-14

Ribosome assembly is a complex process involving the folding and processing of ribosomal RNAs (rRNAs), concomitant binding of ribosomal proteins (r-proteins), and participation of numerous accessory cofactors. Here, we use a quantitative mass spectrometry/electron microscopy hybrid approach to determine the r-protein composition and conformation of 30S ribosome assembly intermediates in Escherichia coli. The relative timing of assembly of the 3' domain and the formation of the central pseudoknot (PK) structure depends on the presence of the assembly factor RimP. The central PK is unstable in the absence of RimP, resulting in the accumulation of intermediates in which the 3'-domain is unanchored and the 5'-domain is depleted for r-proteins S5 and S12 that contact the central PK. Our results reveal the importance of the cofactor RimP in central PK formation, and introduce a broadly applicable method for characterizing macromolecular assembly in cells.

Central posterior capsule pigmentation in a patient with pigment dispersion and previous ocular trauma: a case report.

Science.gov (United States)

Al-Mezaine, Hani S

2010-01-01

We report a 55-year-old man with unusually dense, unilateral central posterior capsule pigmentation associated with the characteristic clinical features of pigment dispersion syndrome, including a Krukenberg's spindle and dense trabecular pigmentation in both eyes. A history of an old blunt ocular trauma probably caused separation of the anterior hyaloid from the back of the lens, thereby creating an avenue by which pigment could reach the potential space of Berger's from the posterior chamber.

Germline-Specific MATH-BTB Substrate Adaptor MAB1 Regulates Spindle Length and Nuclei Identity in Maize[W

Science.gov (United States)

Juranić, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanić, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas

2012-01-01

Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle–dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s). PMID:23250449

Cooling Acoustic Transcucer with Heat Pipes

Science.gov (United States)

2009-07-19

circuits to a heat sink. [0009] In Kan et al (United States Patent No. 6,528,909), a spindle motor assembly is disclosed which has a shaft with an...integral heat pipe. The shaft with the integral heat pipe improves the thermal conductively of the shaft and the spindle motor assembly. The shaft ...2) Description of the Prior Art [0004] It is known in the art that transducers, designed to project acoustic power, are often limited by the

Cooling Acoustic Transducer with Heat Pipes

Science.gov (United States)

2009-07-29

a heat sink. [0009] In Kan et al (United States Patent No. 6,528,909), a spindle motor assembly is disclosed which has a shaft with an integral...heat pipe. The shaft with the integral heat pipe improves the thermal conductively of the shaft and the spindle motor assembly. The shaft includes...Description of the Prior Art [0004] It is known in the art that transducers, designed to project acoustic power, are often limited by the build

Responding to chromosomal breakage during M-phase: insights from a cell-free system

Directory of Open Access Journals (Sweden)

Costanzo Vincenzo

2009-07-01

Full Text Available Abstract DNA double strand breaks (DSBs activate ATM and ATR dependent checkpoints that prevent the onset of mitosis. However, how cells react to DSBs occurring when they are already in mitosis is poorly understood. The Xenopus egg extract has been utilized to study cell cycle progression and DNA damage checkpoints. Recently this system has been successfully used to uncover an ATM and ATR dependent checkpoint affecting centrosome driven spindle assembly. These studies have led to the identification of XCEP63 as major target of this pathway. XCEP63 is a coiled-coil rich protein localized at centrosome essential for proper spindle assembly. ATM and ATR directly phosphorylate XCEP63 on serine 560 inducing its delocalization from centrosome, which in turn delays spindle assembly. This pathway might contribute to regulate DNA repair or mitotic cell survival in the presence of chromosome breakage.

Rho-GTPase effector ROCK phosphorylates cofilin in actin-meditated cytokinesis during mouse oocyte meiosis.

Science.gov (United States)

Duan, Xing; Liu, Jun; Dai, Xiao-Xin; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Wang, Zhen-Bo; Wang, Qiang; Sun, Shao-Chen

2014-02-01

During oocyte meiosis, a spindle forms in the central cytoplasm and migrates to the cortex. Subsequently, the oocyte extrudes a small body and forms a highly polarized egg; this process is regulated primarily by actin. ROCK is a Rho-GTPase effector that is involved in various cellular functions, such as stress fiber formation, cell migration, tumor cell invasion, and cell motility. In this study, we investigated possible roles for ROCK in mouse oocyte meiosis. ROCK was localized around spindles after germinal vesicle breakdown and was colocalized with cytoplasmic actin and mitochondria. Disrupting ROCK activity by RNAi or an inhibitor resulted in cell cycle progression and polar body extrusion failure. Time-lapse microscopy showed that this may have been due to spindle migration and cytokinesis defects, as chromosomes segregated but failed to extrude a polar body and then realigned. Actin expression at oocyte membranes and in cytoplasm was significantly decreased after these treatments. Actin caps were also disrupted, which was confirmed by a failure to form cortical granule-free domains. The mitochondrial distribution was also disrupted, which indicated that mitochondria were involved in the ROCK-mediated actin assembly. In addition, the phosphorylation levels of Cofilin, a downstream molecule of ROCK, decreased after disrupting ROCK activity. Thus, our results indicated that a ROCK-Cofilin-actin pathway regulated meiotic spindle migration and cytokinesis during mouse oocyte maturation.

The central responsiveness of the acute cerveau isolé rat.

Science.gov (United States)

User, P; Gottesmann, C

1982-01-01

The electrophysiological patterns of the frontal cortex and dorsal hippocampus were studied in the acute cerveau isolé rat. Central and peripheral stimulations were performed in order to modulate these patterns. The results showed that the permanent alternation of high amplitude spindle bursts and low voltage activity in the anterior neocortex of the acute cerveau isolé was influenced neither by olfactory nor by posterior hypothalamic stimulation. In contrast, these two kinds of stimulation easily modulated the continuous low frequency theta rhythm, recorded in the dorsal hippocampus, in terms of amplitude and in overall frequency. This modulation of the theta rhythm in the acute cerveau isolé rat mimics the changes observed when the normal rat comes from the intermediate stage of sleep (as characterized in the the acute intercollicular transected rat by high amplitude spindle bursts at frontal cortex level and low frequency theta activity in the dorsal hippocampus) to rapid sleep. These results further suggest that, during the intermediate stage (as in the cerveau isolé preparation), the hippocampus montonous theta activity appears through a brainstem disinhibitory process releasing the forebrain limbic pacemaker(s). During the following rapid sleep phase, the theta rhythm would be modulated by pontine activity influences acting on the theta generators.

Primary spindle cell sarcoma of the prostate and 18 F-fluorodeoxyglucose-positron-emission tomography/computed tomography findings

Directory of Open Access Journals (Sweden)

Hakan Öztürk

2015-01-01

Conclusion: Spindle sarcomas of the prostate have quite aggressive nature and they have high potential to metastase. Average life expectancy is <1 year and the prognosis is poor. CTx and radiation therapy can′t yield curative effects due to poor differentiation.

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...

Sulfolobus tengchongensis Spindle-Shaped Virus STSV1: Virus-Host Interactions and Genomic Features

DEFF Research Database (Denmark)

Xiang, X.; Chen, L.; Huang, X

2005-01-01

of variable length (68 nm on average) at one end and is the largest of the known spindle-shaped viruses. After infecting its host, the virus multiplied rapidly to high titers (>1010 PFU/ml). Replication of the virus retarded host growth but did not cause lysis of the host cells. STSV1 did not integrate...

Design and Delivery of HMT Half-Shaft Prototype

Science.gov (United States)

2012-11-01

spindle welded to the outer joint output is ease of Design  and Delivery of HMT Half‐ Shaft  Prototype    24    assembly. Flange 1 contains threaded... spindle , and splined shafts . Also, the spindle of the production design is splined to match the splines of the hub internals. 2.2. Analysis The...inner-joint (Figure 33). Design  and Delivery of HMT Half‐ Shaft  Prototype    27      Figure 33: FBD of Flange/ Spindle Applying Newton’s Laws to the

A conceptual design and structural stabilities of in-pit assembly tools for the completion of final sector assembly at tokamak hall

International Nuclear Information System (INIS)

Nam, K.O.; Park, H.K.; Kim, D.J.; Ahn, H.J.; Kim, K.K.; Im, K.; Shaw, R.

2010-01-01

The final assembly of main components of the International Thermonuclear Experimental Reactor (ITER) tokamak, Vacuum Vessel (VV) and Toroidal Field Coils (TFCs), is achieved by the sequential assembly of the nine sub-assembled 40 o sectors in tokamak pit. Each sub-assembled 40 o sector is composed of one VV 40 o sector, two TFCs, and in-between Vacuum Vessel Thermal Shield (VVTS) segments. Sub-assembly is carried out in the assembly building and then the sub-assembled sectors are transferred into tokamak pit, in sequence, to complete sector assembly. The role of in-pit assembly tool is to support and align the sub-assembled sectors in tokamak pit. It also plays the role of reference datum during assembly until the completion of main components assembly. Korea Domestic Agency (KO DA) has developed the conceptual design of most ITER purpose-built assembly tools under the collaboration with the ITER Organization. Among the conceptual designs carried out, this paper describes the function, the structure, the selected material and the design results of the in-pit assembly tools comprising central column, radial beams and their supports, TF inner supports and in-pit working floor. The results of structural analysis using ANSYS for the various loading cases are given as well. The resultant stresses and deflections turned out to fall within the allowable ranges.

Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores

NARCIS (Netherlands)

Vleugel, Mathijs; Omerzu, Manja; Groenewold, Vincent; Hadders, Michael A; Lens, Susanne M A; Kops, Geert J P L

2015-01-01

Regulated recruitment of the kinase-adaptor complex BUB1/BUB3 to kinetochores is crucial for correcting faulty chromosome-spindle attachments and for spindle assembly checkpoint (SAC) signaling. BUB1/BUB3 localizes to kinetochores by binding phosphorylated MELT motifs (MELpT) in the kinetochore

Analysis on machine tool systems using spindle vibration monitoring for automatic tool changer

OpenAIRE

Shang-Liang Chen; Yin-Ting Cheng; Chin-Fa Su

2015-01-01

Recently, the intelligent systems of technology have become one of the major items in the development of machine tools. One crucial technology is the machinery status monitoring function, which is required for abnormal warnings and the improvement of cutting efficiency. During processing, the mobility act of the spindle unit determines the most frequent and important part such as automatic tool changer. The vibration detection system includes the development of hardware and software, such as ...

Apparatus for integrated fuel assembly inspection system

International Nuclear Information System (INIS)

Ahmed, H.J.; Burchill, S.R.

1988-01-01

In a fuel assembly inspection apparatus, the combination is described comprising: (a) an elongated fixture mounted in a stationary upright position; (b) upper means mounted to an upper portion of the fixture and lower means mounted adjacent to a lower portion of the fixture, the upper and lower means being disposed outwardly from a side of the fixture for supporting a nuclear fuel assembly therebetween and extending along the side of the fixture; (c) a bottom carriage having a central opening adapted to receive the fuel assembly therethrough when supported between the upper and lower means such that the bottom carriage being connected only to, and extending in cantilever fashion outwardly from, the side of the fixture for generally vertical movement along the side of the fixture and along the fuel assembly extending along the side of the fixture; (d) drive means for selectively moving the bottom carriage; and (e) means disposed on the bottom carriage for measuring the envelop, of the fuel assembly when the bottom carriage is moved to and stationed at selected axial positions along the fuel assembly

Uncovering the Molecular Machinery of the Human Spindle-An Integration of Wet and Dry Systems Biology

DEFF Research Database (Denmark)

Rojas, Ana M.; Santamaria, Anna; Malik, Rainer

2012-01-01

apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called "hidden spindle hub'', proteins whose network...

Spindle trees (Euonymus japonica Thunb.) growing in a polluted environment are less sensitive to gamma irradiation

Czech Academy of Sciences Publication Activity Database

Kim, J. K.; Cha, M.; Mukherjee, A.; Wilhelmová, Naděžda

2013-01-01

Roč. 11, č. 4 (2013), s. 233-243 ISSN 2322-3243 Institutional research plan: CEZ:AV0Z50380511 Keywords : Spindle tree * oxidative stress * ionizing radiation Subject RIV: EF - Botanics http://www.ijrr.com/browse.php?a_code=A-10-1-478&slc_lang=en&sid=1

Evaluate of the Effects of Drilling with Varying Spindle Speed Using Different Thickness of GFRP on the Damage Factor

Directory of Open Access Journals (Sweden)

Keong Woo Tze

2014-07-01

Full Text Available Composite have been widely used in industries which such as aircraft structural components, electric and electronics components, aerospace, and oil and gas fields due to their superior mechanical properties. Among machining process, drilling can be considered as one of the most important process in final machining of composite. In this research, vacuum assisted resin infusion method is use in fabricating the glass fiber reinforcement polymer samples, where different thickness of GFRP were used in the drilling process with different spindle speed. The results show that the temperature influences the damage factor of the drilling. Higher spindle speed will generate higher temperature that softens the matrix thus generating lower damage factor. The suitable drill bit temperature is between 150-200°C

Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

Science.gov (United States)

Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

2016-02-01

We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

Verification of the enrichment of fresh VVER-440 fuel assemblies at NPP Paks

Energy Technology Data Exchange (ETDEWEB)

Almasia, I.; Hlavathya, Z.; Nguyena, C. T. [Institute of Isotopes, Hungarian Academy of Sciences, Budapest, (Hungary); others, and

2012-06-15

A Non Destructive Analysis (NDA) method was developed for the verification of {sup 235}U enrichment of both homogeneous and profiled VVER-440 reactor fresh fuel assemblies by means of gamma spectrometry. A total of ca. 30 assemblies were tested, five of which were homogeneous, with {sup 235}U enrichment in the range 1,6% to 3,6%, while the others were profiled with pins of 3,3% to 4,4% enrichment. Two types of gamma detectors were used for the test measurements: 2 coaxial HPGe detectors and a miniature CdZnTe (CZT) detector fitting into the central tube of the assemblies. It was therefore possible to obtain information from both the inside and the outside of the assemblies. It was shown that it is possible to distinguish between different types of assemblies within a reasonable measurement time (about 1000 sec). For the HPGe measurements the assemblies had to be lifted out from their storage rack, while for the CZT detector measurements the assemblies could be left at their storage position, as it was shown that the neighbouring assemblies do not affect measurement inside the assemblies' central tube. The measured values were compared to Monte Carlo simulations carried out using the MCNP code, and a recommendation for the optimal approach to verify the {sup 235}U enrichment of fresh VVER-440 reactor fuel assemblies is suggested.

Temporal and SUMO-specific SUMOylation contribute to the dynamics of Polo-like kinase 1 (PLK1) and spindle integrity during mouse oocyte meiosis.

Science.gov (United States)

Feitosa, Weber Beringui; Hwang, KeumSil; Morris, Patricia L

2018-02-15

During mammalian meiosis, Polo-like kinase 1 (PLK1) is essential during cell cycle progression. In oocyte maturation, PLK1 expression is well characterized but timing of posttranslational modifications regulating its activity and subcellular localization are less clear. Small ubiquitin-related modifier (SUMO) posttranslational modifier proteins have been detected in mammalian gametes but their precise function during gametogenesis is largely unknown. In the present paper we report for mouse oocytes that both PLK1 and phosphorylated PLK1 undergo SUMOylation in meiosis II (MII) oocytes using immunocytochemistry, immunoprecipitation and in vitro SUMOylation assays. At MII, PLK1 is phosphorylated at threonine-210 and serine-137. MII oocyte PLK1 and phosphorylated PLK1 undergo SUMOylation by SUMO-1, -2 and -3 as shown by individual in vitro assays. Using these assays, forms of phosphorylated PLK1 normalized to PLK1 increased significantly and correlated with SUMOylated PLK1 levels. During meiotic progression and maturation, SUMO-1-SUMOylation of PLK1 is involved in spindle formation whereas SUMO-2/3-SUMOylation may regulate PLK1 activity at kinetochore-spindle attachment sites. Microtubule integrity is required for PLK1 localization with SUMO-1 but not with SUMO-2/3. Inhibition of SUMOylation disrupts proper meiotic bipolar spindle organization and spindle-kinetochore attachment. The data show that both temporal and SUMO-specific-SUMOylation play important roles in orchestrating functional dynamics of PLK1 during mouse oocyte meiosis, including subcellular compartmentalization. Copyright © 2018 Elsevier Inc. All rights reserved.

Physical principles for DNA tile self-assembly.

Science.gov (United States)

Evans, Constantine G; Winfree, Erik

2017-06-19

DNA tiles provide a promising technique for assembling structures with nanoscale resolution through self-assembly by basic interactions rather than top-down assembly of individual structures. Tile systems can be programmed to grow based on logical rules, allowing for a small number of tile types to assemble large, complex assemblies that can retain nanoscale resolution. Such algorithmic systems can even assemble different structures using the same tiles, based on inputs that seed the growth. While programming and theoretical analysis of tile self-assembly often makes use of abstract logical models of growth, experimentally implemented systems are governed by nanoscale physical processes that can lead to very different behavior, more accurately modeled by taking into account the thermodynamics and kinetics of tile attachment and detachment in solution. This review discusses the relationships between more abstract and more physically realistic tile assembly models. A central concern is how consideration of model differences enables the design of tile systems that robustly exhibit the desired abstract behavior in realistic physical models and in experimental implementations. Conversely, we identify situations where self-assembly in abstract models can not be well-approximated by physically realistic models, putting constraints on physical relevance of the abstract models. To facilitate the discussion, we introduce a unified model of tile self-assembly that clarifies the relationships between several well-studied models in the literature. Throughout, we highlight open questions regarding the physical principles for DNA tile self-assembly.

Nuclear fuel assemblies

International Nuclear Information System (INIS)

Natori, Hisahide; Kurihara, Kunitoshi.

1982-01-01

Purpose: To increase the fuel safety by decreasing the gap conductance between fuels and cladding tubes, as well as improve the reactor core controllability by rendering the void coefficient negative. Constitution: Fuel assemblies in a pressure tube comprise a tie-rod, fuel rods in a central region, and fuel rods with burnable poison in the outer circumference region. Here, B 4 C is used as the burnable poison by 1.17 % by weight ratio. The degrees of enrichment for the fissile plutonium as PuO 2 -UO 2 fuel used in the assemblies are 2.7 %, 2.7 % and 1.5 % respectively in the innermost layer, the intermediate layer and the outermost layer. This increases the burn-up degree to improve the plant utilizability, whereby the void coefficient is rendered negative to improve the reactor core controllability. (Horiuchi, T.)

The relationship between cell killing, chromosome aberrations, spindle defects, and mitotic delay in mouse lymphoma cells of differential sensitivity to X-rays

International Nuclear Information System (INIS)

Scott, D.; Zampetti-Bosseler, F.

1980-01-01

A study has been made of the effects of x radiation on an ultrasensitive subline of L5178Y mouse lymphoma cells. It has been shown that at survival levels above about 20 per cent, chromosome structural aberrations which lead to bridges and fragments at anaphase are about four times more frequent than spindle defects. The results demonstrated the higher frequency of structural aberrations and spindle defects, and the greater mitotic delay in the X-ray-sensitive than in the X-ray-resistant cell line. A model is proposed which causally relates these end-points to cell killing and DNA repair. (author)

Cellular angiofibroma: analysis of 25 cases emphasizing its relationship to spindle cell lipoma and mammary-type myofibroblastoma

NARCIS (Netherlands)

Flucke, U.E.; Krieken, J.H. van; Mentzel, T.

2011-01-01

Cellular angiofibroma represents a rare benign mesenchymal tumor, occurring mainly in the superficial soft tissue of the genital region. The involvement of 13q14 in some cases confirmed the morphological suggested link with spindle cell lipoma and mammary-type myofibroblastoma. We analyzed the

Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

Science.gov (United States)

Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

2014-01-01

Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

Central posterior capsule pigmentation in a patient with pigment dispersion and previous ocular trauma: A case report

Directory of Open Access Journals (Sweden)

Al-Mezaine Hani

2010-01-01

Full Text Available We report a 55-year-old man with unusually dense, unilateral central posterior capsule pigmentation associated with the characteristic clinical features of pigment dispersion syndrome, including a Krukenberg′s spindle and dense trabecular pigmentation in both eyes. A history of an old blunt ocular trauma probably caused separation of the anterior hyaloid from the back of the lens, thereby creating an avenue by which pigment could reach the potential space of Berger′s from the posterior chamber.

A Structural analysis of M protein in coronavirus assembly and morphology

DEFF Research Database (Denmark)

W. Neuman, Benjamin; Kiss, Gabriella; H. Kunding, Andreas

2011-01-01

The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy...... protein functions to promote virus assembly....

Life Cycle Characterization of Sulfolobus Monocaudavirus 1, an Extremophilic Spindle-Shaped Virus with Extracellular Tail Development.

Science.gov (United States)

Uldahl, Kristine B; Jensen, Signe B; Bhoobalan-Chitty, Yuvaraj; Martínez-Álvarez, Laura; Papathanasiou, Pavlos; Peng, Xu

2016-06-15

We provide here, for the first time, insights into the initial infection stages of a large spindle-shaped archaeal virus and explore the following life cycle events. Our observations suggest that Sulfolobus monocaudavirus 1 (SMV1) exhibits a high adsorption rate and that virions adsorb to the host cells via three distinct attachment modes: nosecone association, body association, and body/tail association. In the body/tail association mode, the entire virion, including the tail(s), aligns to the host cell surface and the main body is greatly flattened, suggesting a possible fusion entry mechanism. Upon infection, the intracellular replication cycle lasts about 8 h, at which point the virions are released as spindle-shaped tailless particles. Replication of the virus retarded host growth but did not cause lysis of the host cells. Once released from the host and at temperatures resembling that of its natural habitat, SMV1 starts developing one or two tails. This exceptional property of undergoing a major morphological development outside, and independently of, the host cell has been reported only once before for the related Acidianus two-tailed virus. Here, we show that SMV1 can develop tails of more than 900 nm in length, more than quadrupling the total virion length. Very little is known about the initial life cycle stages of viruses infecting hosts of the third domain of life, Archaea This work describes the first example of an archaeal virus employing three distinct association modes. The virus under study, Sulfolobus monocaudavirus 1, is a representative of the large spindle-shaped viruses that are frequently found in acidic hot springs. The results described here will add valuable knowledge about Archaea, the least studied domain in the virology field. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

International Nuclear Information System (INIS)

Hori, Akiko; Morand, Agathe; Ikebe, Chiho; Frith, David; Snijders, Ambrosius P.; Toda, Takashi

2015-01-01

The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. - Highlights: • Human Wdr8 is a centrosomal protein enriched in the proximal end of the centriole. • Wdr8 and hMsd1/SSX2IP form a complex conserved in fungi. • Depletion of Wdr8 results in shorter, tilted spindle microtubules. • Depletion phenotypes of Wdr8 are very similar to those of hMsd1/SSX2IP knockdown.

The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

Energy Technology Data Exchange (ETDEWEB)

Hori, Akiko; Morand, Agathe; Ikebe, Chiho; Frith, David; Snijders, Ambrosius P.; Toda, Takashi, E-mail: takashi-toda@hiroshima-u.ac.jp

2015-12-04

The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. - Highlights: • Human Wdr8 is a centrosomal protein enriched in the proximal end of the centriole. • Wdr8 and hMsd1/SSX2IP form a complex conserved in fungi. • Depletion of Wdr8 results in shorter, tilted spindle microtubules. • Depletion phenotypes of Wdr8 are very similar to those of hMsd1/SSX2IP knockdown.

Analysis of the failure of a vacuum spin-pit drive turbine spindle shaft

OpenAIRE

Pettitt, Jason M.

2005-01-01

The Naval Postgraduate School's Rotor Spin Research Facility experienced a failure in the Spring of 2005 in which the rotor dropped from the drive turbine and caused extensive damage. A failure analysis of the drive turbine spindle shaft was conducted in order to determine the cause of failure: whether due to a material or design flaw. Also, a dynamic analysis was conducted in order to determine the natural modes present in the system and the associated frequencies that could have contributed...

An unusual and spectacular case of spindle cell lipoma of the posterior neck invading the spinal cervical canal and posterior cranial fossa.

Science.gov (United States)

Petit, Damien; Menei, Philippe; Fournier, Henri-Dominique

2011-11-01

The authors describe the first case of spindle cell lipoma of the posterior neck invading the upper cervical spinal canal and the posterior cranial fossa. Spindle cell lipoma is an extremely rare variant of benign lipoma. It usually occurs as a solitary subcutaneous well-circumscribed lesion in the posterior neck or shoulders of adult men. Local aggressiveness is unusual. This 61-year-old man presented with an increased left cerebellar syndrome and headaches. He also had a posterior neck tumefaction, which had been known about for a long time. Computed tomography and MR imaging studies revealed a voluminous mass extending to the upper cervical canal and posterior cranial fossa and eroding the neighboring bones. The lesion was well delimited, and contrast enhancement was intense and heterogeneous. The tumor, which had initially developed under the muscles of the posterior neck, was totally resected. Histological assessment revealed numerous fat cells with spindle cells secreting collagen. The large size of the tumor and the submuscular location, bone erosion, and compression of the CNS were unusual in this rare subtype of benign adipose tumor. Its presentation could simulate a sarcoma.

Self-assembled three-dimensional chiral colloidal architecture

Science.gov (United States)

Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna C.; Sha, Ruojie; Seeman, Nadrian C.; Chaikin, Paul M.

2017-11-01

Although stereochemistry has been a central focus of the molecular sciences since Pasteur, its province has previously been restricted to the nanometric scale. We have programmed the self-assembly of micron-sized colloidal clusters with structural information stemming from a nanometric arrangement. This was done by combining DNA nanotechnology with colloidal science. Using the functional flexibility of DNA origami in conjunction with the structural rigidity of colloidal particles, we demonstrate the parallel self-assembly of three-dimensional microconstructs, evincing highly specific geometry that includes control over position, dihedral angles, and cluster chirality.

Inspection experience with RA-3 spent nuclear fuel assemblies at CNEA's central storage facility

International Nuclear Information System (INIS)

Novara, Oscar; LaFuente, Jose; Large, Steve; Andes, Trent; Messick, Charles

2000-01-01

Aluminum-based spent nuclear fuel from Argentina's RA-3 research reactor is to be shipped to the Savannah River Site near Aiken, South Carolina, USA. The spent nuclear fuel contains highly enriched uranium of U.S. origin and is being returned under the US Department of Energy's Foreign Research Reactor/Domestic Research Reactor (FRR/DRR) Receipt Program. An intensive inspection of 207 stored fuel assemblies was conducted to assess shipping cask containment limitations and assembly handling considerations. The inspection was performed with video equipment designed for remote operation, high portability, easy setup and usage. Fuel assemblies were raised from their vertical storage tubes, inspected by remote video, and then returned to their original storage tube or transferred to an alternate location. The inspections were made with three simultaneous video systems, each with dedicated viewing, digital recording, and tele-operated control from a shielded location. All 207 fuel assemblies were safely and successfully inspected in fifteen working days. Total dose to personnel was about one-half of anticipated dose. (author)

Spatial factors and muscle spindle input influence the generation of neuromuscular responses to stimulation of the human foot

Science.gov (United States)

Layne, Charles S.; Forth, Katharine E.; Abercromby, Andrew F. J.

2005-05-01

Removal of the mechanical pressure gradient on the soles leads to physiological adaptations that ultimately result in neuromotor degradation during spaceflight. We propose that mechanical stimulation of the soles serves to partially restore the afference associated with bipedal loading and assists in attenuating the negative neuromotor consequences of spaceflight. A dynamic foot stimulus device was used to stimulate the soles in a variety of conditions with different stimulation locations, stimulation patterns and muscle spindle input. Surface electromyography revealed the lateral side of the sole elicited the greatest neuromuscular response in ankle musculature, followed by the medial side, then the heel. These responses were modified by preceding stimulation. Neuromuscular responses were also influenced by the level of muscle spindle input. These results provide important information that can be used to guide the development of a "passive" countermeasure that relies on sole stimulation and can supplement existing exercise protocols during spaceflight.

Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

Science.gov (United States)

Okada, Naoyuki; Sato, Masamitsu

2015-01-01

Spindle microtubules capture and segregate chromosomes and, therefore, their assembly is an essential event in mitosis. To carry out their mission, many key players for microtubule formation need to be strictly orchestrated. Particularly, proteins that assemble the spindle need to be translocated at appropriate sites during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran, controls this translocation. Ran plays many roles in many cellular events: nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic spindle, and reorganization of the nuclear envelope at the mitotic exit. Although these events are seemingly distinct, recent studies demonstrate that the mechanisms underlying these phenomena are substantially the same as explained by molecular interplay of the master regulator Ran, the transport factor importin, and its cargo proteins. Our review focuses on how the transport machinery regulates mitotic progression of cells. We summarize translocation mechanisms governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP targets in fission yeast that promote spindle formation. We also discuss the coordination of the spatial and temporal regulation of proteins from the viewpoint of transport machinery. We propose that the transport machinery is an essential key that couples the spatial and temporal events in cells. PMID:26308057

Fuel assembly

International Nuclear Information System (INIS)

Kurihara, Kunitoshi; Azekura, Kazuo.

1992-01-01

In a reactor core of a heavy water moderated light water cooled pressure tube type reactor, no sufficient effects have been obtained for the transfer width to a negative side of void reactivity change in a region of a great void coefficient. Then, a moderation region divided into upper and lower two regions is disposed at the central portion of a fuel assembly. Coolants flown into the lower region can be discharged to the cooling region from an opening disposed at the upper end portion of the lower region. Light water flows from the lower region of the moderator region to the cooling region of the reactor core upper portion, to lower the void coefficient. As a result, the reactivity performance at low void coefficient, i.e., a void reaction rate is transferred to the negative side. Thus, this flattens the power distribution in the fuel assembly, increases the thermal margin and enables rapid operaiton and control of the reactor core, as well as contributes to the increase of fuel burnup ratio and reduction of the fuel cycle cost. (N.H.)

Automated ensemble assembly and validation of microbial genomes

Science.gov (United States)

2014-01-01

Background The continued democratization of DNA sequencing has sparked a new wave of development of genome assembly and assembly validation methods. As individual research labs, rather than centralized centers, begin to sequence the majority of new genomes, it is important to establish best practices for genome assembly. However, recent evaluations such as GAGE and the Assemblathon have concluded that there is no single best approach to genome assembly. Instead, it is preferable to generate multiple assemblies and validate them to determine which is most useful for the desired analysis; this is a labor-intensive process that is often impossible or unfeasible. Results To encourage best practices supported by the community, we present iMetAMOS, an automated ensemble assembly pipeline; iMetAMOS encapsulates the process of running, validating, and selecting a single assembly from multiple assemblies. iMetAMOS packages several leading open-source tools into a single binary that automates parameter selection and execution of multiple assemblers, scores the resulting assemblies based on multiple validation metrics, and annotates the assemblies for genes and contaminants. We demonstrate the utility of the ensemble process on 225 previously unassembled Mycobacterium tuberculosis genomes as well as a Rhodobacter sphaeroides benchmark dataset. On these real data, iMetAMOS reliably produces validated assemblies and identifies potential contamination without user intervention. In addition, intelligent parameter selection produces assemblies of R. sphaeroides comparable to or exceeding the quality of those from the GAGE-B evaluation, affecting the relative ranking of some assemblers. Conclusions Ensemble assembly with iMetAMOS provides users with multiple, validated assemblies for each genome. Although computationally limited to small or mid-sized genomes, this approach is the most effective and reproducible means for generating high-quality assemblies and enables users to

A spindle cell anaplastic pancreatic carcinoma with rhabdoid features following curative resection.

Science.gov (United States)

Abe, Tomoyuki; Amano, Hironobu; Hanada, Keiji; Okazaki, Akihisa; Yonehara, Shuji; Kuranishi, Fumito; Nakahara, Masahiro; Kuroda, Yoshinori; Noriyuki, Toshio

2016-08-01

Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5×8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0×10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18 F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed.

Central Reactivity Measurements on Assemblies 1 and 3 of the Fast Reactor FR0

International Nuclear Information System (INIS)

Londen, S.O.

1966-01-01

The reactivity effects of small samples of various materials have been measured, by the period method at the core centre of Assemblies 1 and 3 of the fast zero power reactor FR0. For some materials the reactivity change as a function of sample size has also been determined experimentally. The core of Assembly 1 consisted only of uranium enriched to 20 % whereas the core of Assembly 3 was diluted with 30 % graphite. The results have been compared with calculated values obtained with a second-order transport-theoretical perturbation model and using differently shielded cross sections depending upon sample size. Qualitative agreement has generally been found, although discrepancies still exist. The spectrum perturbation caused by the experimental arrangement has been analyzed and found to be rather important

Central Reactivity Measurements on Assemblies 1 and 3 of the Fast Reactor FR0

Energy Technology Data Exchange (ETDEWEB)

Londen, S O

1966-01-15

The reactivity effects of small samples of various materials have been measured, by the period method at the core centre of Assemblies 1 and 3 of the fast zero power reactor FR0. For some materials the reactivity change as a function of sample size has also been determined experimentally. The core of Assembly 1 consisted only of uranium enriched to 20 % whereas the core of Assembly 3 was diluted with 30 % graphite. The results have been compared with calculated values obtained with a second-order transport-theoretical perturbation model and using differently shielded cross sections depending upon sample size. Qualitative agreement has generally been found, although discrepancies still exist. The spectrum perturbation caused by the experimental arrangement has been analyzed and found to be rather important.

An overview of CMS central hadron calorimeter

CERN Document Server

Katta, S

2002-01-01

The central hadron calorimeter for CMS detector is a sampling calorimeter with active medium as scintillator plates interleaved with brass absorber plates. It covers the central pseudorapidity region (¿ eta ¿<3.0). The design and construction aspects are reported. The status of construction and assembly of various subdetectors of HCAL are presented. (5 refs).

Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization

Energy Technology Data Exchange (ETDEWEB)

Gualtieri, Maurizio [Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Ovrevik, Johan [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Mollerup, Steen [Section for Toxicology, National Institute of Occupational Health, N-0033 Oslo (Norway); Asare, Nana [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Longhin, Eleonora [Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Dahlman, Hans-Jorgen [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Camatini, Marina [Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Centre Research POLARIS, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Holme, Jorn A., E-mail: jorn.holme@fhi.no [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway)

2011-08-01

Highlights: {yields} PM2.5 induces mitotic arrest in BEAS-2B cells. {yields} PM2.5 induces DNA damage and activates DNA damage response. {yields} AhR regulated genes (Cyp1A1, Cyp1B1 and AhRR) are upregulated after PM exposure. {yields} Mitotic spindle assembly is perturbed in PM exposed cells. - Abstract: Airborne particulate matter (PM) is considered to be an important contributor to lung diseases. In the present study we report that Milan winter-PM2.5 inhibited proliferation in human bronchial epithelial cells (BEAS-2B) by inducing mitotic arrest. The cell cycle arrest was followed by an increase in mitotic-apoptotic cells, mitotic slippage and finally an increase in 'classical' apoptotic cells. Exposure to winter-PM10 induced only a slight effect which may be due to the presence of PM2.5 in this fraction while pure combustion particles failed to disturb mitosis. Fewer cells expressing the mitosis marker phospho-histone H3 compared to cells with condensed chromosomes, suggest that PM2.5 induced premature mitosis. PM2.5 was internalized into the cells and often localized in laminar organelles, although particles without apparent plasma membrane covering were also seen. In PM-containing cells mitochondria and lysosomes were often damaged, and in mitotic cells fragmented chromosomes often appeared. PM2.5 induced DNA strands breaks and triggered a DNA-damage response characterized by increased phosphorylation of ATM, Chk2 and H2AX; as well as induced a marked increase in expression of the aryl hydrocarbon receptor (AhR)-regulated genes, CYP1A1, CYP1B1 and AhRR. Furthermore, some disturbance of the organization of microtubules was indicated. It is hypothesized that the induced mitotic arrest and following cell death was due to a premature chromosome condensation caused by a combination of DNA, mitochondrial and spindle damage.

Function of donor cell centrosome in intraspecies and interspecies nuclear transfer embryos

International Nuclear Information System (INIS)

Zhong Zhisheng; Zhang Gang; Meng Xiaoqian; Zhang Yanling; Chen Dayuan; Schatten, Heide; Sun Qingyuan

2005-01-01

Centrosomes, the main microtubule-organizing centers (MTOCs) in most animal cells, are important for many cellular activities such as assembly of the mitotic spindle, establishment of cell polarity, and cell movement. In nuclear transfer (NT), MTOCs that are located at the poles of the meiotic spindle are removed from the recipient oocyte, while the centrosome of the donor cell is introduced. We used mouse MII oocytes as recipients, mouse fibroblasts, rat fibroblasts, or pig granulosa cells as donor cells to construct intraspecies and interspecies nuclear transfer embryos in order to observe centrosome dynamics and functions. Three antibodies against centrin, γ-tubulin, and NuMA, respectively, were used to stain the centrosome. Centrin was not detected either at the poles of transient spindles or at the poles of first mitotic spindles. γ-tubulin translocated into the two poles of the transient spindles, while no accumulated γ-tubulin aggregates were detected in the area adjacent to the two pseudo-pronuclei. At first mitotic metaphase, γ-tubulin was translocated to the spindle poles. The distribution of γ-tubulin was similar in mouse intraspecies and rat-mouse interspecies embryos. The NuMA antibody that we used can recognize porcine but not murine NuMA protein, so it was used to trace the NuMA protein of donor cell in reconstructed embryos. In the pig-mouse interspecies reconstructed embryos, NuMA concentrated between the disarrayed chromosomes soon after activation and translocated to the transient spindle poles. NuMA then immigrated into pseudo-pronuclei. After pseudo-pronuclear envelope breakdown, NuMA was located between the chromosomes and then translocated to the spindle poles of first mitotic metaphase. γ-tubulin antibody microinjection resulted in spindle disorganization and retardation of the first cell division. NuMA antibody microinjection also resulted in spindle disorganization. Our findings indicate that (1) the donor cell centrosome, defined as

Analysis of EEG activity during sleep - brain hemisphere symmetry of two classes of sleep spindles

Science.gov (United States)

Smolen, Magdalena M.

2009-01-01

This paper presents automatic analysis of some selected human electroencephalographic patterns during deep sleep using the Matching Pursuit (MP) algorithm. The periodicity of deep sleep EEG patterns was observed by calculating autocorrelation functions of their percentage contributions. The study confirmed the increasing trend of amplitude-weighted average frequency of sleep spindles from frontal to posterior derivations. The dominant frequencies from the left and the right brain hemisphere were strongly correlated.

Short-Spindled Cell Haemangioblastoma with CD34 Expression: New Histopathological Variant or Just a Stochastic Cytological Singularity?

Directory of Open Access Journals (Sweden)

Miguel Fdo. Salazar

2016-01-01

Full Text Available Haemangioblastomas are neoplasms of uncertain histogenesis with cellular and reticular variants advocated in current lore. Herein we describe an intriguing cerebellar specimen with unusual traits including spindle cell morphology and CD34 positivity. A thirty-nine-year old man had an infratentorial tumour discovered incidentally and resected three times. In all the instances, histopathological diagnosis was haemangioblastoma; nonetheless, he had neither physical stigmata nor family history of von Hippel-Lindau disease. By histology, the lesion was composed of areas of conventional stromal cells admixed with territories populated by short-spindled cells packed in lobules, sometimes giving the appearance of gomitoli. Immunoperoxidase-coupled reactions confirmed the expression of inhibin A, neuron-specific enolase (NSE, PS100, and CD57 but also revealed focal immunolabeling for CD34, CD99, and FXIIIa. This case highlights the potential phenotypical diversity that can be found within these neoplasms. Rather than uncertain histogenesis, it may in fact reflect multiple lines of differentiation—histomimesis—prone to adopt unusual morpho- and immunophenotypes in a subset of haemangioblastomas.

Fuel assembly manufacturing device

International Nuclear Information System (INIS)

Picard, P.; Villaeys, R.

1995-01-01

The device comprises a central support on which the frame is mounted, a magazine which supports the fuel rods in passages aligned with those in the frame and a traction assembly on the opposite side of the magazine and including an array of pull rods designed to be advanced through the passages in the frame, to grip respective fuel rods in magazine and to pull those rods into the passages on the return stroke. 13 figs

Observational Study on the Occurrence of Muscle Spindles in Human Digastric and Mylohyoideus Muscles

Directory of Open Access Journals (Sweden)

Daniele Saverino

2014-01-01

Full Text Available Although the occurrence of muscle spindles (MS is quite high in most skeletal muscles of humans, few MS, or even absence, have been reported in digastric and mylohyoideus muscles. Even if this condition is generally accepted and quoted in many papers and books, observational studies are scarce and based on histological sections of a low number of specimens. The aim of the present study is to confirm previous data, assessing MS number in a sample of digastric and mylohyoideus muscles. We investigated 11 digastric and 6 mylohyoideus muscles from 13 donors. Muscle samples were embedded in paraffin wax, cross-sectioned in a rostrocaudal direction, and stained using haematoxylin-eosin. A mean of 5.1 ± 1.1 (range 3–7 MS was found in digastric muscles and mean of 0.5 ± 0.8 (range 0–2 in mylohyoideus muscles. A significant difference (P<0.001 was found with the control sample, confirming the correctness of the histological procedure. Our results support general belief that the absolute number of spindles is sparse in digastric and mylohyoideus muscles. External forces, such as food resistance during chewing or gravity, do not counteract jaw-opening muscles. It is conceivable that this condition gives them a limited proprioceptive importance and a reduced need for having specific receptors as MS.

Sub-cell turning to accomplish micron-level alignment of precision assemblies

Science.gov (United States)

Kumler, James J.; Buss, Christian

2017-08-01

Higher performance expectations for complex optical systems demand tighter alignment requirements for lens assembly alignment. In order to meet diffraction limited imaging performance over wide spectral bands across the UV and visible wavebands, new manufacturing approaches and tools must be developed if the optical systems will be produced consistently in volume production. This is especially applicable in the field of precision microscope objectives for life science, semiconductor inspection and laser material processing systems. We observe a rising need for the improvement in the optical imaging performance of objective lenses. The key challenge lies in the micron-level decentration and tilt of each lens element. One solution for the production of high quality lens systems is sub-cell assembly with alignment turning. This process relies on an automatic alignment chuck to align the optical axis of a mounted lens to the spindle axis of the machine. Subsequently, the mount is cut with diamond tools on a lathe with respect to the optical axis of the mount. Software controlled integrated measurement technology ensures highest precision. In addition to traditional production processes, further dimensions can be controlled in a very precise manner, e.g. the air gaps between the lenses. Using alignment turning simplifies further alignment steps and reduces the risk of errors. This paper describes new challenges in microscope objective design and manufacturing, and addresses difficulties with standard production processes. A new measurement and alignment technique is described, and strengths and limitations are outlined.

HOW ECOLOGICAL COMMUNITIES ARE STRUCTURED: A REVIEW ON ECOLOGICAL ASSEMBLY RULES

Directory of Open Access Journals (Sweden)

Gabriel Jaime Colorado Zuluaga

Full Text Available Whether biological communities are deterministic or stochastic assemblages of species has long been a central topic of ecology. The widely demonstrated presence of structural patterns in nature may imply the existence of rules that regulate the organization of ecological communities. In this review, I present a compilation of major assembly rules that fundament, in a great proportion, the community assembly theory. Initially, I present a general overview of key concepts associated to the assembly of communities, in particular the origin of assembly rules, definition, the problem of scale and underlying mechanisms in the structure of ecological communities. Subsequently, two major approaches or paradigms (i.e. species-based and trait-based for the assembly of communities are discussed. Finally, major tested assembly rules are explored and discussed under the light of available published literature.

Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.

Science.gov (United States)

Krause, Lutz; Nones, Katia; Loffler, Kelly A; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J; Watson, David I; Lord, Reginald V; Phillips, Wayne A; Gotley, David; Smithers, B Mark; Whiteman, David C; Hayward, Nicholas K; Grimmond, Sean M; Waddell, Nicola; Barbour, Andrew P

2016-04-01

The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. © The Author 2016. Published by Oxford University Press.

How oocytes try to get it right: spindle checkpoint control in meiosis.

Science.gov (United States)

Touati, Sandra A; Wassmann, Katja

2016-06-01

The generation of a viable, diploid organism depends on the formation of haploid gametes, oocytes, and spermatocytes, with the correct number of chromosomes. Halving the genome requires the execution of two consecutive specialized cell divisions named meiosis I and II. Unfortunately, and in contrast to male meiosis, chromosome segregation in oocytes is error prone, with human oocytes being extraordinarily "meiotically challenged". Aneuploid oocytes, that are with the wrong number of chromosomes, give rise to aneuploid embryos when fertilized. In humans, most aneuploidies are lethal and result in spontaneous abortions. However, some trisomies survive to birth or even adulthood, such as the well-known trisomy 21, which gives rise to Down syndrome (Nagaoka et al. in Nat Rev Genet 13:493-504, 2012). A staggering 20-25 % of oocytes ready to be fertilized are aneuploid in humans. If this were not bad enough, there is an additional increase in meiotic missegregations as women get closer to menopause. A woman above 40 has a risk of more than 30 % of getting pregnant with a trisomic child. Worse still, in industrialized western societies, child birth is delayed, with women getting their first child later in life than ever. This trend has led to an increase of trisomic pregnancies by 70 % in the last 30 years (Nagaoka et al. in Nat Rev Genet 13:493-504, 2012; Schmidt et al. in Hum Reprod Update 18:29-43, 2012). To understand why errors occur so frequently during the meiotic divisions in oocytes, we review here the molecular mechanisms at works to control chromosome segregation during meiosis. An important mitotic control mechanism, namely the spindle assembly checkpoint or SAC, has been adapted to the special requirements of the meiotic divisions, and this review will focus on our current knowledge of SAC control in mammalian oocytes. Knowledge on how chromosome segregation is controlled in mammalian oocytes may help to identify risk factors important for questions

Investigation of Flow Behavior around Corotating Blades in a Double-Spindle Lawn Mower Deck

OpenAIRE

Chon W.; Amano R. S.

2005-01-01

When the airflow patterns inside a lawn mower deck are understood, the deck can be redesigned to be efficient and have an increased cutting ability. To learn more, a combination of computational and experimental studies was performed to investigate the effects of blade and housing designs on a flow pattern inside a 1.1m wide corotating double-spindle lawn mower deck with side discharge. For the experimental portion of the study, air velocities inside the deck were measured using a laser Do...

Yeast Interacting Proteins Database: YDR176W, YDL239C [Yeast Interacting Proteins Database

Lifescience Database Archive (English)

Full Text Available a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle pole...ining structure at the leading edge of the prospore membrane via interaction with spindle pole body componen...DY3 Prey description Protein required for spore wall formation, thought to mediate assembly of a Don1p-conta

Comparisons of thermal SCWR assembly designs by in- or inter-assembly moderation

International Nuclear Information System (INIS)

Zhang, P.; Wang, K.

2010-01-01

As one of the six GEN-IV reactor systems and the only one with water as coolant, SCWR is thought to be the most hopeful future nuclear energy system. Many designs have already been proposed worldwide. For thermal SCWR designs, a key consideration factor is how to provide the dedicated moderation, which leads to various designs with water as moderator. It is much like BWR, where under-moderation is an important issue and central water rods are adopted to account for it. Naturally, water rods can be adopted in SCWR assemblies too, but with counter-flow scheme to increase the outlet temperature and thermal efficiency which is unlike the co-flow scheme in BWR. This type can be seen in the American, Japanese and European HPLWR designs. As the other option, moderation could be provided with inter-assembly gap like CANDU-SCWR design. It is worthy of review of these designs for better understanding the water moderating effects and putting forward any new designs. (author)

Focusing on RISC assembly in mammalian cells.

Science.gov (United States)

Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

2008-04-11

RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

Focusing on RISC assembly in mammalian cells

International Nuclear Information System (INIS)

Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

2008-01-01

RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

Proposed method of assembly for the BCD silicon strip vertex detector modules

International Nuclear Information System (INIS)

Lindenmeyer, C.

1989-01-01

The BCD Silicon strip Vertex Detector is constructed of 10 identical central region modules and 18 similar forward region modules. This memo describes a method of assembling these modules from individual silicon wafers. Each wafer is fitted with associated front end electronics and cables and has been tested to insure that only good wafers reach the final assembly stage. 5 figs

IMPROVEMENT FOR AN ASSEMBLY FLOW FOR A GIVEN COMPONENT (1

Directory of Open Access Journals (Sweden)

Ancuţa BĂLTEANU,

2017-05-01

Full Text Available This study is carried out in a line of assembly of a finite wiring product. The assembly of this finished product is done in two specific sections. For the analysis of the activities in the assembly section, the timing method of the work stations was used. On the basis of the work times obtained and their centralization, the Keizen method was subsequently applied to obtain an improvement in the installation flow. Finally, a reduction in working times was achieved, as well as a more ergonomic arrangement of jobs. This paper is the first in a series of 3 papers to deal with this subject.

Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint

DEFF Research Database (Denmark)

Sironi, L; Melixetian, M; Faretta, M

2001-01-01

Mad2 is a key component of the spindle checkpoint, a device that controls the fidelity of chromosome segregation in mitosis. The ability of Mad2 to form oligomers in vitro has been correlated with its ability to block the cell cycle upon injection into Xenopus embryos. Here we show that Mad2 forms...

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly.

Science.gov (United States)

Schneider, Valerie A; Graves-Lindsay, Tina; Howe, Kerstin; Bouk, Nathan; Chen, Hsiu-Chuan; Kitts, Paul A; Murphy, Terence D; Pruitt, Kim D; Thibaud-Nissen, Françoise; Albracht, Derek; Fulton, Robert S; Kremitzki, Milinn; Magrini, Vincent; Markovic, Chris; McGrath, Sean; Steinberg, Karyn Meltz; Auger, Kate; Chow, William; Collins, Joanna; Harden, Glenn; Hubbard, Timothy; Pelan, Sarah; Simpson, Jared T; Threadgold, Glen; Torrance, James; Wood, Jonathan M; Clarke, Laura; Koren, Sergey; Boitano, Matthew; Peluso, Paul; Li, Heng; Chin, Chen-Shan; Phillippy, Adam M; Durbin, Richard; Wilson, Richard K; Flicek, Paul; Eichler, Evan E; Church, Deanna M

2017-05-01

The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health. © 2017 Schneider et al.; Published by Cold Spring Harbor Laboratory Press.

Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation

OpenAIRE

Hori, Akiko; Ikebe, Chiho; Tada, Masazumi; Toda, Takashi

2014-01-01

Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator ?-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity....

A theory for viral capsid assembly around electrostatic cores

Science.gov (United States)

Hagan, Michael F.

2009-03-01

We develop equilibrium and kinetic theories that describe the assembly of viral capsid proteins on a charged central core, as seen in recent experiments in which brome mosaic virus capsids assemble around nanoparticles functionalized with polyelectrolyte. We model interactions between capsid proteins and nanoparticle surfaces as the interaction of polyelectrolyte brushes with opposite charge using the nonlinear Poisson Boltzmann equation. The models predict that there is a threshold density of functionalized charge, above which capsids efficiently assemble around nanoparticles, and that light scatter intensity increases rapidly at early times without the lag phase characteristic of empty capsid assembly. These predictions are consistent with and enable interpretation of preliminary experimental data. However, the models predict a stronger dependence of nanoparticle incorporation efficiency on functionalized charge density than measured in experiments and do not completely capture a logarithmic growth phase seen in experimental light scatter. These discrepancies may suggest the presence of metastable disordered states in the experimental system. In addition to discussing future experiments for nanoparticle-capsid systems, we discuss broader implications for understanding assembly around charged cores such as nucleic acids.

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

OpenAIRE

Hernández-García, Susana; San-Segundo, Laura; González-Méndez, Lorena; Corchete, Luis A; Misiewicz-Krzeminska, Irena; Martín-Sánchez, Montserrat; López-Iglesias, Ana-Alicia; Algarín, Esperanza Macarena; Mogollón, Pedro; Díaz-Tejedor, Andrea; Paíno, Teresa; Tunquist, Brian; Mateos, María-Victoria; Gutiérrez, Norma C; Díaz-Rodriguez, Elena

2017-01-01

[EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomali...

Assembly and patterning of the vascular network of the vertebrate hindbrain

OpenAIRE

Fujita, Misato; Cha, Young R.; Pham, Van N.; Sakurai, Atsuko; Roman, Beth L.; Gutkind, J. Silvio; Weinstein, Brant M.

2011-01-01

The cranial vasculature is essential for the survival and development of the central nervous system and is important in stroke and other brain pathologies. Cranial vessels form in a reproducible and evolutionarily conserved manner, but the process by which these vessels assemble and acquire their stereotypic patterning remains unclear. Here, we examine the stepwise assembly and patterning of the vascular network of the zebrafish hindbrain. The major artery supplying the hindbrain, the basilar...

Complex Colloidal Structures by Self-assembly in Electric Fields

NARCIS (Netherlands)

Vutukuri, H.R.

2012-01-01

The central theme of this thesis is exploiting the directed self-assembly of both isotropic and anisotropic colloidal particles to achieve the fabrication of one-, two-, and three-dimensional complex colloidal structures using external electric fields and/or a simple in situ thermal annealing

SNEAK assembly 12B - Construction and experimental program

International Nuclear Information System (INIS)

Helm, F.

1982-10-01

The assembly SNEAK 12A is the second SNEAK assembly in which the neutron physics of disturbed material configurations, as they might occur in a postulated fast reactor accident, is investigated. The core is characterized by a central zone with fuel rods containing PuO 2 UO 2 mixed oxide pellets. This zone is cylindrically surrounded by a buffer zone for spectral adaptation, a driver zone sufficiently reactive to maintain criticality and a radial depleted uranium blanket. The purpose of the experiments is to test calculational methods of neutron physics which are used in the accident analysis of fast breeder reactors. The report describes the construction of the core and its assemblies and their content and outlines the foreseen experimental program. It includes measurements in the clean critical core and investigations of vertical and horizontal fuel relocations and steel blockages

Coordination in the Decentralized Assembly System with Dual Supply Modes

Directory of Open Access Journals (Sweden)

Xu Guan

2013-01-01

Full Text Available This paper investigates a decentralized assembly system that consists of one assembler and two independent suppliers; wherein one supplier is perfectly reliable for the production, while the other generates yield uncertainty. Facing the random market demand, the assembler has to order the components from one supplier in advance and meanwhile requires the other supplier to deliver the components under VMI mode. We construct a Nash game between the supplier and the assembler so as to derive their equilibrium procurement/production strategies. The results show that the channel’s performance is highly undermined by the decentralization between players and also the combination of two supply modes. Compared to the centralized system, we propose an advance payment contract to perfectly coordinate the supply chain performance. The numerical examples indicate some management implications on the supply mode comparison and sensitivity analysis.

Role of immunohistochemistry and fluorescence in-situ hybridization (FISH in the diagnosis of spindle and round cell tumors of the kidney

Directory of Open Access Journals (Sweden)

M. Abbas

2015-09-01

Conclusion: In summary we advise an immunohistochemical panel for round/spindle cell tumors of the kidney and for unclear cases we advise to add (FISH to get the correct diagnosis, as they are completely different regarding surgical approach and post-operative adjuvant therapy.

Molecular Mechanism of Arenavirus Assembly and Budding

Directory of Open Access Journals (Sweden)

Shuzo Urata

2012-10-01

Full Text Available Arenaviruses have a bisegmented negative-strand RNA genome, which encodes four viral proteins: GP and NP by the S segment and L and Z by the L segment. These four viral proteins possess multiple functions in infection, replication and release of progeny viruses from infected cells. The small RING finger protein, Z protein is a matrix protein that plays a central role in viral assembly and budding. Although all arenaviruses encode Z protein, amino acid sequence alignment showed a huge variety among the species, especially at the C-terminus where the L-domain is located. Recent publications have demonstrated the interactions between viral protein and viral protein, and viral protein and host cellular protein, which facilitate transportation and assembly of viral components to sites of virus egress. This review presents a summary of current knowledge regarding arenavirus assembly and budding, in comparison with other enveloped viruses. We also refer to the restriction of arenavirus production by the antiviral cellular factor, Tetherin/BST-2.

Improving Legacy Aircraft Systems Through Condition-Based Maintenance: An H-60 Case Study

Science.gov (United States)

2014-09-01

level functions. These decompositions are equivalent to a detailed design effort in systems engineering. NAMPSOPs have a common architectural structure...Assembly Power Available Spindle Cables No.1 Engine Load Demand Spindle Control Cables Engine Pneumatic Starters Auxiliary Power Unit IRCM FLIR Mission...Analysis Fuel System Main Rotor Head Main Module Main Gear Box Radiator Engine Output Shaft Auxiliary Power Unit Flight Control Cables Tail Landing

Establishment of Harrop, High-Temperature Viscometer

Energy Technology Data Exchange (ETDEWEB)

Schumacher, R.F.

1999-11-05

This report explains how the Harrop, High-Temperature Viscometer was installed, calibrated, and operated. This report includes assembly and alignment of the furnace, viscometer, and spindle, and explains the operation of the Brookfield Viscometer, the Harrop furnace, and the UDC furnace controller. Calibration data and the development of the spindle constant from NIST standard reference glasses is presented. A simple operational procedure is included.

Status of Conceptual Design Progress for ITER Sector Sub-assembly Tools

Energy Technology Data Exchange (ETDEWEB)

Nam, Kyoung O; Park, Hyun Ki; Kim, Dong Jin [National Fusion Research Institute, Daejeon (Korea, Republic of); Lee, Jae Hyuk; Kim, Kyung Kyu [SFA Engineering Corp., Changwon (Korea, Republic of); Im, Ki Hak; Robert, Shaw [ITER Organization, Paul lez Durance (France)

2010-05-15

-pit assembly tools that include lifting tools, radial beams, central column and supports

Yeast Interacting Proteins Database: YDL239C, YDR273W [Yeast Interacting Proteins Database

Lifescience Database Archive (English)

Full Text Available of a Don1p-containing structure at the leading edge of the prospore membrane via interaction with spindle p...it as prey (1) YDR273W DON1 Meiosis-specific component of the spindle pole body, part of the leading... edge protein (LEP) coat, forms a ring-like structure at the leading edge of the prospore...ption Protein required for spore wall formation, thought to mediate assembly of a Don1p-containing structure at the leading...description Meiosis-specific component of the spindle pole body, part of the leading edge protein (LEP) coat

E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells.

Directory of Open Access Journals (Sweden)

Mayu Inaba

2010-08-01

Full Text Available Many adult stem cells reside in a special microenvironment known as the niche, where they receive essential signals that specify stem cell identity. Cell-cell adhesion mediated by cadherin and integrin plays a crucial role in maintaining stem cells within the niche. In Drosophila melanogaster, male germline stem cells (GSCs are attached to niche component cells (i.e., the hub via adherens junctions. The GSC centrosomes and spindle are oriented toward the hub-GSC junction, where E-cadherin-based adherens junctions are highly concentrated. For this reason, adherens junctions are thought to provide a polarity cue for GSCs to enable proper orientation of centrosomes and spindles, a critical step toward asymmetric stem cell division. However, understanding the role of E-cadherin in GSC polarity has been challenging, since GSCs carrying E-cadherin mutations are not maintained in the niche. Here, we tested whether E-cadherin is required for GSC polarity by expressing a dominant-negative form of E-cadherin. We found that E-cadherin is indeed required for polarizing GSCs toward the hub cells, an effect that may be mediated by Apc2. We also demonstrated that E-cadherin is required for the GSC centrosome orientation checkpoint, which prevents mitosis when centrosomes are not correctly oriented. We propose that E-cadherin orchestrates multiple aspects of stem cell behavior, including polarization of stem cells toward the stem cell-niche interface and adhesion of stem cells to the niche supporting cells.

Evolution of Parallel Spindles Like genes in plants and highlight of unique domain architecture#

Directory of Open Access Journals (Sweden)

Consiglio Federica M

2011-03-01

Full Text Available Abstract Background Polyploidy has long been recognized as playing an important role in plant evolution. In flowering plants, the major route of polyploidization is suggested to be sexual through gametes with somatic chromosome number (2n. Parallel Spindle1 gene in Arabidopsis thaliana (AtPS1 was recently demonstrated to control spindle orientation in the 2nd division of meiosis and, when mutated, to induce 2n pollen. Interestingly, AtPS1 encodes a protein with a FHA domain and PINc domain putatively involved in RNA decay (i.e. Nonsense Mediated mRNA Decay. In potato, 2n pollen depending on parallel spindles was described long time ago but the responsible gene has never been isolated. The knowledge derived from AtPS1 as well as the availability of genome sequences makes it possible to isolate potato PSLike (PSL and to highlight the evolution of PSL family in plants. Results Our work leading to the first characterization of PSLs in potato showed a greater PSL complexity in this species respect to Arabidopsis thaliana. Indeed, a genomic PSL locus and seven cDNAs affected by alternative splicing have been cloned. In addition, the occurrence of at least two other PSL loci in potato was suggested by the sequence comparison of alternatively spliced transcripts. Phylogenetic analysis on 20 Viridaeplantae showed the wide distribution of PSLs throughout the species and the occurrence of multiple copies only in potato and soybean. The analysis of PSLFHA and PSLPINc domains evidenced that, in terms of secondary structure, a major degree of variability occurred in PINc domain respect to FHA. In terms of specific active sites, both domains showed diversification among plant species that could be related to a functional diversification among PSL genes. In addition, some specific active sites were strongly conserved among plants as supported by sequence alignment and by evidence of negative selection evaluated as difference between non-synonymous and

The role of sleep spindles and slow-wave activity in integrating new information in semantic memory.

Science.gov (United States)

Tamminen, Jakke; Lambon Ralph, Matthew A; Lewis, Penelope A

2013-09-25

Assimilating new information into existing knowledge is a fundamental part of consolidating new memories and allowing them to guide behavior optimally and is vital for conceptual knowledge (semantic memory), which is accrued over many years. Sleep is important for memory consolidation, but its impact upon assimilation of new information into existing semantic knowledge has received minimal examination. Here, we examined the integration process by training human participants on novel words with meanings that fell into densely or sparsely populated areas of semantic memory in two separate sessions. Overnight sleep was polysomnographically monitored after each training session and recall was tested immediately after training, after a night of sleep, and 1 week later. Results showed that participants learned equal numbers of both word types, thus equating amount and difficulty of learning across the conditions. Measures of word recognition speed showed a disadvantage for novel words in dense semantic neighborhoods, presumably due to interference from many semantically related concepts, suggesting that the novel words had been successfully integrated into semantic memory. Most critically, semantic neighborhood density influenced sleep architecture, with participants exhibiting more sleep spindles and slow-wave activity after learning the sparse compared with the dense neighborhood words. These findings provide the first evidence that spindles and slow-wave activity mediate integration of new information into existing semantic networks.

Expression of nestin, desmin and vimentin in intact and regenerating muscle spindles of rat hind limb skeletal muscles

Czech Academy of Sciences Publication Activity Database

Čížková, D.; Soukup, Tomáš; Mokrý, J.

2009-01-01

Roč. 131, č. 2 (2009), s. 197-206 ISSN 0948-6143 R&D Projects: GA ČR(CZ) GA304/08/0256 Grant - others:GA ČR(CZ) GA304/08/0329; EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : intermediate filaments * muscle spindles * muscle reganeration Subject RIV: ED - Physiology Impact factor: 3.021, year: 2009

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.

Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

OpenAIRE

Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

2016-01-01

Background Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Methods Patients receiving G 900?mg/m2 d 1, 8; D 75?mg/m2 d 8, every 21?days were eligible. Primary end-point: progression-free survival (PFS) at 4?months; secondary end-point: overall survival (OS) and response rate. Results Fifty-one patients w...

Structural and thermodynamic analysis of modified nucleosides in self-assembled DNA cross-tiles.

Science.gov (United States)

Hakker, Lauren; Marchi, Alexandria N; Harris, Kimberly A; LaBean, Thomas H; Agris, Paul F

2014-01-01

DNA Holliday junctions are important natural strand-exchange structures that form during homologous recombination. Immobile four-arm junctions, analogs to Holliday junctions, have been designed to self-assemble into cross-tile structures by maximizing Watson-Crick base pairing and fixed crossover points. The cross-tiles, self-assembled from base pair recognition between designed single-stranded DNAs, form higher order lattice structures through cohesion of self-associating sticky ends. These cross-tiles have 16 unpaired nucleosides in the central loop at the junction of the four duplex stems. The importance of the centralized unpaired nucleosides to the structure's thermodynamic stability and self-assembly is unknown. Cross-tile DNA nanostructures were designed and constructed from nine single-stranded DNAs with four shell strands, four arms, and a central loop containing 16 unpaired bases. The 16 unpaired bases were either 2'-deoxyribothymidines, 2'-O-methylribouridines, or abasic 1',2'-dideoxyribonucleosides. Thermodynamic profiles and structural base-stacking contributions were assessed using UV absorption spectroscopy during thermal denaturation and circular dichroism spectroscopy, respectively, and the resulting structures were observed by atomic force microscopy. There were surprisingly significant changes in the thermodynamic and structural properties of lattice formation as a result of altering only the 16 unpaired, centralized nucleosides. The 16 unpaired 2'-O-methyluridines were stabilizing and produced uniform tubular structures. In contrast, the abasic nucleosides were destabilizing producing a mixture of structures. These results strongly indicate the importance of a small number of centrally located unpaired nucleosides within the structures. Since minor modifications lead to palpable changes in lattice formation, DNA cross-tiles present an easily manipulated structure convenient for applications in biomedical and biosensing devices.

Cryotops versus open-pulled straws (OPS) as carriers for the cryopreservation of bovine oocytes: effects on spindle and chromosome configuration and embryo development.

Science.gov (United States)

Morató, Roser; Izquierdo, Dolors; Paramio, Maria Teresa; Mogas, Teresa

2008-10-01

Two experiments were designed to assess the effectiveness of cryopreserving bovine MII oocytes using cryotops as the carrier system for vitrification. In the first experiment, we examined the developmental competence of oocytes after: (i) vitrification in open-pulled straws (OPS method); or (ii) vitrification in plastic handle (Cryotop method). In the second experiment, warmed oocytes that had been vitrified in OPS or cryotops were fixed to analyze spindle and chromosome configuration. In all experiments both cow and calf oocytes were used. Significantly different fertilization rates were observed between the vitrification groups: 31.5% and 20.2% for the cow and calf oocytes vitrified in OPS, respectively, versus 46.1% and 46.4% for the oocytes vitrified using cryotops. After in vitro fertilization, 3.8% of the calf oocytes and 5.3% of the cow oocytes developed to the blastocyst stage. All blastocysts from vitrified oocytes resulted from the Cryotop method. A significantly lower percentage of the OPS-vitrified calf oocytes showed a normal spindle configuration (37.8%) compared to control fresh oocytes (69.9%), while normal spindle and chromosome configurations were observed in a significantly higher proportion of the cryotop-vitrified calf oocytes (60.2%). For the cow oocytes, 60.6% in the OPS group and 60.3% in the Cryotop group exhibited a normal morphology after warming. These findings suggest the cryotop system is a more efficient carrier for vitrification than OPS for the cryopreservation of bovine oocytes.

Validating Future Force Performance Measures (Army Class): Reclassification Test and Criterion Development

Science.gov (United States)

2009-09-01

Replace CV boot assembly. 11 Replace propeller shafts , universal joints, and center bearings. 11 Replace front axle spindle . 5 Replace...propeller shafts , universal joints, and center bearings. (SL1/2) 12 Troubleshoot axles. (SL1/2) 11 Replace front axle spindle . (SL1/2) 6...Social Sciences. NOTE: The findings in this report are not to be construed as an official Department of the Army position, unless so designated by

Measurements in Los Alamos benchmark criticals and the central reactivity discrepancy

International Nuclear Information System (INIS)

Davey, W.G.; Hansen, G.E.; Koelling, J.J.; McLaughlin, T.P.

1978-01-01

Measurements in seven Los Alamos fast critical facilities are described; all are related to elucidating the causes of the central reactivity discrepancy in fast reactors. Specific capabilities of these specialized assemblies permit measurements well-above delayed critical and these confirm the validity of the delayed neutron data used for calibration; there is therefore no reactivity-scale error. Reactivity measurements in these homogeneous assemblies exhibit no discrepancy. It is concluded that nuclear data should not be adjusted to eliminate the discrepancy found in other, heterogeneous assemblies

Nondestructive Assay Data Integration with the SKB-50 Assemblies - FY16 Update

International Nuclear Information System (INIS)

Tobin, Stephen Joseph; Fugate, Michael Lynn; Trellue, Holly Renee; DeBaere, Paul; Sjoland, Anders; Liljenfeldt, Henrik; Hu, Jianwei; Backstrom, Ulrika; Bengtsson, Martin; Burr, Tomas; Eliasson, Annika; Favalli, Andrea; Gauld, Ian; Grogan, Brandon; Jansson, Peter; Junell, Henrik; Schwalbach, Peter; Vaccaro, Stefano; Vo, Duc Ta; Wildestrand, Henrik

2016-01-01

A project to research the application of non-destructive assay (NDA) techniques for spent fuel assemblies is underway at the Central Interim Storage Facility for Spent Nuclear Fuel (for which the Swedish acronym is Clab) in Oskarshamn, Sweden. The research goals of this project contain both safeguards and non-safeguards interests. These nondestructive assay (NDA) technologies are designed to strengthen the technical toolkit of safeguard inspectors and others to determine the following technical goals more accurately; Verify initial enrichment, burnup, and cooling time of facility declaration for spent fuel assemblies; Detect replaced or missing pins from a given spent fuel assembly to confirm its integrity; and Estimate plutonium mass and related plutonium and uranium fissile mass parameters in spent fuel assemblies. Estimate heat content, and measure reactivity (multiplication).

Nondestructive Assay Data Integration with the SKB-50 Assemblies - FY16 Update

Energy Technology Data Exchange (ETDEWEB)

Tobin, Stephen Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fugate, Michael Lynn [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Trellue, Holly Renee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); DeBaere, Paul [DG Energy, Luxembourg (Germany); Sjoland, Anders [Swedish Nuclear Fuel and Waste Management Company, Stockholm (Sweden); Liljenfeldt, Henrik [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hu, Jianwei [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Backstrom, Ulrika [Swedish Nuclear Fuel and Waste Management Company, Stockholm (Sweden); Vattenfall AB, Stockholm (Sweden); Bengtsson, Martin [Swedish Nuclear Fuel and Waste Management Company, Stockholm (Sweden); Vattenfall AB, Stockholm (Sweden); Burr, Tomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); International Atomic Energy Agency, Vienna (Austria); Eliasson, Annika [Swedish Nuclear Fuel and Waste Management Company, Stockholm (Sweden); Favalli, Andrea [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gauld, Ian [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Grogan, Brandon [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jansson, Peter [Uppsala Univ. (Sweden); Junell, Henrik [Swedish Nuclear Fuel and Waste Management Company, Stockholm (Sweden); Schwalbach, Peter [DG Energy, Luxembourg (Germany); Vaccaro, Stefano [DG Energy, Luxembourg (Germany); Vo, Duc Ta [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wildestrand, Henrik [Swedish Nuclear Fuel and Waste Management Company, Stockholm (Sweden); Vattenfall AB, Stockholm (Sweden)

2016-10-28

A project to research the application of non-destructive assay (NDA) techniques for spent fuel assemblies is underway at the Central Interim Storage Facility for Spent Nuclear Fuel (for which the Swedish acronym is Clab) in Oskarshamn, Sweden. The research goals of this project contain both safeguards and non-safeguards interests. These nondestructive assay (NDA) technologies are designed to strengthen the technical toolkit of safeguard inspectors and others to determine the following technical goals more accurately; Verify initial enrichment, burnup, and cooling time of facility declaration for spent fuel assemblies; Detect replaced or missing pins from a given spent fuel assembly to confirm its integrity; and Estimate plutonium mass and related plutonium and uranium fissile mass parameters in spent fuel assemblies. Estimate heat content, and measure reactivity (multiplication).

Experience in programming Assembly language of CDC CYBER 170/750 computer

International Nuclear Information System (INIS)

Caldeira, A.D.

1987-10-01

Aiming to optimize processing time of BCG computer code in the CDC CYBER 170/750 computer, the FORTRAN-V language of INTERP subroutine was converted to Assembly language. The BCG code was developed for solving neutron transport equation by iterative method, and the INTERP subroutine is innermost loop of the code carrying out 5 interpolation types. The central processor unit Assembly language of the CDC CYBER 170/750 computer and its application in implementing the interpolation subroutine of BCG code are described. (M.C.K.)

Biolistic transmission of potato spindle tuber viroid (PSTVd) populations to weeds frequently grown on potato fields and PSTVd pathogenesis on cultured Chamomilla recutita

Czech Academy of Sciences Publication Activity Database

Matoušek, Jaroslav; Orctová, Lidmila; Ptáček, J.; Dědič, P.

2009-01-01

Roč. 16, č. 1 (2009), s. 43-55 ISSN 1802-940X Institutional research plan: CEZ:AV0Z50510513 Keywords : potato fields * weed plants * potato spindle tuber viroid (PSTVd) Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection

Mycobacterium genavense-induced spindle cell pseudotumor in a pediatric hematopoietic stem cell transplant recipient: Case report and review of the literature.

Science.gov (United States)

Coelho, Ritika; Hanna, Rabi; Flagg, Aron; Stempak, Lisa M; Ondrejka, Sarah; Procop, Gary W; Harrington, Susan; Zembillas, Anthony; Kusick, Karissa; Gonzalez, Blanca E

2017-04-01

We describe the first reported pediatric patient to our knowledge with a spindle cell pseudotumor caused by Mycobacterium genavense in a hematopoietic stem cell transplant recipient, and review the literature of such an entity in the transplant population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Design and analysis of drum lathe for manufacturing large-scale optical microstructured surface and load characteristics of aerostatic spindle

Science.gov (United States)

Wu, Dongxu; Qiao, Zheng; Wang, Bo; Wang, Huiming; Li, Guo

2014-08-01

In this paper, a four-axis ultra-precision lathe for machining large-scale drum mould with microstructured surface is presented. Firstly, because of the large dimension and weight of drum workpiece, as well as high requirement of machining accuracy, the design guidelines and component parts of this drum lathe is introduced in detail, including control system, moving and driving components, position feedback system and so on. Additionally, the weight of drum workpiece would result in the structural deformation of this lathe, therefore, this paper analyses the effect of structural deformation on machining accuracy by means of ANSYS. The position change is approximately 16.9nm in the X-direction(sensitive direction) which could be negligible. Finally, in order to study the impact of bearing parameters on the load characteristics of aerostatic journal bearing, one of the famous computational fluid dynamics(CFD) software, FLUENT, is adopted, and a series of simulations are carried out. The result shows that the aerostatic spindle has superior performance of carrying capacity and stiffness, it is possible for this lathe to bear the weight of drum workpiece up to 1000kg since there are two aerostatic spindles in the headstock and tailstock.

Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Purcell, James W; Davis, Jefferson; Reddy, Mamatha; Martin, Shamra; Samayoa, Kimberly; Vo, Hung; Thomsen, Karen; Bean, Peter; Kuo, Wen Lin; Ziyad, Safiyyah; Billig, Jessica; Feiler, Heidi S; Gray, Joe W; Wood, Kenneth W; Cases, Sylvaine

2009-06-10

Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein (KSP), a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have demonstrated a 9% response rate in patients with locally advanced or metastatic breast cancer, and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer we explored the activity of ispinesib alone and in combination several therapies approved for the treatment of breast cancer. We measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo, and tested the ability of ispinesib to enhance the anti-tumor activity of approved therapies. In vitro, ispinesib displayed broad anti-proliferative activity against a panel of 53 breast cell-lines. In vivo, ispinesib produced regressions in each of five breast cancer models, and tumor free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the anti-tumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine, and exhibited activity comparable to paclitaxel and ixabepilone. These findings support further clinical exploration of KSP inhibitors for the treatment of breast cancer.

Morphology and orientational behavior of silica-coated spindle-type hematite particles in a magnetic field probed by small-angle X-ray scattering.

Science.gov (United States)

Reufer, Mathias; Dietsch, Hervé; Gasser, Urs; Hirt, Ann; Menzel, Andreas; Schurtenberger, Peter

2010-04-15

Form factor and magnetic properties of silica-coated spindle-type hematite nanoparticles are determined from SAXS measurements with applied magnetic field and magnetometry measurements. The particle size, polydispersity and porosity are determined using a core-shell model for the form factor. The particles are found to align with their long axis perpendicular to the applied field. The orientational order is determined from the SAXS data and compared to the orientational order obtained from magnetometry. The direct access to both, the orientational order of the particles, and the magnetic moments allow one to determine the magnetic properties of the individual spindle-type hematite particles. We study the influence of the silica coating on the magnetic properties and find a fundamentally different behavior of silica-coated particles. The silica coating reduces the effective magnetic moment of the particles. This effect is enhanced with field strength and can be explained by superparamagnetic relaxation in the highly porous particles.

Mutations in AtPS1 (Arabidopsis thaliana parallel spindle 1 lead to the production of diploid pollen grains.

Directory of Open Access Journals (Sweden)

Isabelle d'Erfurth

2008-11-01

Full Text Available Polyploidy has had a considerable impact on the evolution of many eukaryotes, especially angiosperms. Indeed, most--if not all-angiosperms have experienced at least one round of polyploidy during the course of their evolution, and many important crop plants are current polyploids. The occurrence of 2n gametes (diplogametes in diploid populations is widely recognised as the major source of polyploid formation. However, limited information is available on the genetic control of diplogamete production. Here, we describe the isolation and characterisation of the first gene, AtPS1 (Arabidopsis thaliana Parallel Spindle 1, implicated in the formation of a high frequency of diplogametes in plants. Atps1 mutants produce diploid male spores, diploid pollen grains, and spontaneous triploid plants in the next generation. Female meiosis is not affected in the mutant. We demonstrated that abnormal spindle orientation at male meiosis II leads to diplogamete formation. Most of the parent's heterozygosity is therefore conserved in the Atps1 diploid gametes, which is a key issue for plant breeding. The AtPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. The isolation of a gene involved in diplogamete production opens the way for new strategies in plant breeding programmes and progress in evolutionary studies.

Assembly constraints drive co-evolution among ribosomal constituents.

Science.gov (United States)

Mallik, Saurav; Akashi, Hiroshi; Kundu, Sudip

2015-06-23

Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein-RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein-rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a 'proof of concept' that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effects of low heterogeneity in fast critical assemblies

International Nuclear Information System (INIS)

Belov, S.P.; Dulin, V.A.; Zhukov, A.V.; Kuzin, E.N.; Mozhaev, V.K.; Sitnikov, V.I.; Tsibulya, A.M.; Shapar', A.V.; Zayfert, E.; Kuntsman, B.; Khayntsel'man, B.

1989-01-01

The problem of the low heterogeneity of fast critical assemblies, which are used to simulate fast reactors that are under design, has begun to assume increasing importance as the errors in nuclear data and group constants decrease and the capabilities of design codes improve. The design of the fuel channels of the fast critical assemblies of a BFS differs from that of the fuel subassemblies of a power reactor. The principal difference is that critical assemblies have a more heterogeneous structure than a reactor core does. As a result, the effects of this heterogeneity turn out to be appreciable for a number of functionals. Of particular interest was the measurement of the main neutronic characteristics of a fast reactor in its actual design and in the mockup produced by using BFS facilities. The authors measured and calculated the most important functionals (the ratios of the average cross sections of the main absorbing and fissioning elements, etc.) for both a homogeneous medium (fuel assemblies) and a heterogeneous medium (slugs, tubes) of practically identical composition. The objective of this work was to compare the discrepancy between experiment and calculations for the central functionals in the homogeneous and heterogeneous cases after corrections. This is a check of the accuracy of the simulation of homogeneous cores in fast power reactors by using the tools of the BFS fast critical assembly

Rail-Guided Multi-Robot System for 3D Cellular Hydrogel Assembly with Coordinated Nanomanipulation

Directory of Open Access Journals (Sweden)

Huaping Wang

2014-08-01

Full Text Available The 3D assembly of micro-/nano-building blocks with multi-nanomanipulator coordinated manipulation is one of the central elements of nanomanipulation. A novel rail-guided nanomanipulation system was proposed for the assembly of a cellular vascular-like hydrogel microchannel. The system was equipped with three nanomanipulators and was restricted on the rail in order to realize the arbitrary change of the end-effectors during the assembly. It was set up with hybrid motors to achieve both a large operating space and a 30 nm positional resolution. The 2D components such as the assembly units were fabricated through the encapsulation of cells in the hydrogel. The coordinated manipulation strategies among the multi-nanomanipulators were designed with vision feedback and were demonstrated through the bottom-up assembly of the vascular-like microtube. As a result, the multi-layered microchannel was assembled through the cooperation of the nanomanipulation system.

Actinide Sequestration Using Self-Assembled Monolayers on Mesoporous Supports

International Nuclear Information System (INIS)

Fryxell, Glen E.; Lin, Yuehe; Fiskum, Sandra K.; Birnbaum, Jerome C.; Wu, Hong; Kemner, K. M.; Kelly, Shelley

2005-01-01

Surfactant templated synthesis of mesoporous ceramics provides a versatile foundation upon which to create high efficiency environmental sorbents. These nanoporous ceramic oxides condense a huge amount of surface area into a very small volume. The ceramic oxide interface is receptive to surface functionalization through molecular self-assembly. The marriage of mesoporous ceramics with self-assembled monolayer chemistry creates a powerful new class of environmental sorbent materials called self-assembled monolayers on mesoporous supports (SAMMS). These SAMMS materials are highly efficient sorbents, whose interfacial chemistry can be fine-tuned to selectively sequester a specific target species, such as heavy metals, tetrahedral oxometallate anions and radionuclides. Details addressing the design, synthesis and characterization of SAMMS materials specifically designed to sequester actinides, of central importance to the environmental clean-up necessary after 40 years of weapons grade plutonium production, as well as evaluation of their binding affinities and kinetics are presented

The SUN protein Mps3 is required for spindle pole body insertion into the nuclear membrane and nuclear envelope homeostasis.

Directory of Open Access Journals (Sweden)

Jennifer M Friederichs

2011-11-01

Full Text Available The budding yeast spindle pole body (SPB is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition.

Encapsulation of gold nanoparticles into self-assembling protein nanoparticles

Directory of Open Access Journals (Sweden)

Yang Yongkun

2012-10-01

Full Text Available Abstract Background Gold nanoparticles are useful tools for biological applications due to their attractive physical and chemical properties. Their applications can be further expanded when they are functionalized with biological molecules. The biological molecules not only provide the interfaces for interactions between nanoparticles and biological environment, but also contribute their biological functions to the nanoparticles. Therefore, we used self-assembling protein nanoparticles (SAPNs to encapsulate gold nanoparticles. The protein nanoparticles are formed upon self-assembly of a protein chain that is composed of a pentameric coiled-coil domain at the N-terminus and trimeric coiled-coil domain at the C-terminus. The self-assembling protein nanoparticles form a central cavity of about 10 nm in size, which is ideal for the encapsulation of gold nanoparticles with similar sizes. Results We have used SAPNs to encapsulate several commercially available gold nanoparticles. The hydrodynamic size and the surface coating of gold nanoparticles are two important factors influencing successful encapsulation by the SAPNs. Gold nanoparticles with a hydrodynamic size of less than 15 nm can successfully be encapsulated. Gold nanoparticles with citrate coating appear to have stronger interactions with the proteins, which can interfere with the formation of regular protein nanoparticles. Upon encapsulation gold nanoparticles with polymer coating interfere less strongly with the ability of the SAPNs to assemble into nanoparticles. Although the central cavity of the SAPNs carries an overall charge, the electrostatic interaction appears to be less critical for the efficient encapsulation of gold nanoparticles into the protein nanoparticles. Conclusions The SAPNs can be used to encapsulate gold nanoparticles. The SAPNs can be further functionalized by engineering functional peptides or proteins to either their N- or C-termini. Therefore encapsulation of gold

The Roles of Fission Yeast Ase1 in Mitotic Cell Division, Meiotic Nuclear Oscillation, and Cytokinesis Checkpoint SignalingD⃞V⃞

OpenAIRE

Yamashita, Akira; Sato, Masamitsu; Fujita, Akiko; Yamamoto, Masayuki; Toda, Takashi

2005-01-01

The Ase1/Prc1 proteins constitute a conserved microtubule-associated protein family that is implicated in central spindle formation and cytokinesis. Here we characterize a role for fission yeast Ase1. Ase1 localizes to microtubule overlapping zones and displays dynamic alterations of localization during the cell cycle. In particular, its spindle localization during metaphase is reduced substantially, followed by robust appearance at the spindle midzone in anaphase. ase1 deletions are viable b...

Trafficking of the potato spindle tuber viroid between tomato and Orobanche ramosa.

Science.gov (United States)

Vachev, T; Ivanova, D; Minkov, I; Tsagris, M; Gozmanova, M

2010-04-10

Viroids, small RNA pathogens capable of infecting flowering plants, coexist in the field with parasitic plants that infest many crops. The ability of viroids to be exchanged between host and parasitic plants and spread in the latter has not yet been investigated. We studied the interaction between the Potato spindle tuber viroid (PSTVd) and Branched bromrape (Orobanche ramosa) using the tomato, Solanum lycopersicon, as a common host. We report the long distance trafficking of PSTVd RNA via the phloem from tomato to O. ramosa, but not vice versa. Furthermore, we identify O. ramosa as a novel host with the ability to facilitate the replication and processing of PSTVd. Finally, molecular variants of PSTVd with single nucleotide substitutions that replicate with different efficiencies in tomato were isolated from O. ramosa. Copyright 2010 Elsevier Inc. All rights reserved.

Multiscale modeling and simulation of microtubule–motor-protein assemblies

Science.gov (United States)

Gao, Tong; Blackwell, Robert; Glaser, Matthew A.; Betterton, M. D.; Shelley, Michael J.

2016-01-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate–consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation. PMID:26764729

Multiscale modeling and simulation of microtubule-motor-protein assemblies.

Science.gov (United States)

Gao, Tong; Blackwell, Robert; Glaser, Matthew A; Betterton, M D; Shelley, Michael J

2015-01-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

Multiscale modeling and simulation of microtubule-motor-protein assemblies

Science.gov (United States)

Gao, Tong; Blackwell, Robert; Glaser, Matthew A.; Betterton, M. D.; Shelley, Michael J.

2015-12-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

A preliminary design and structural analysis on the central column for supporting the full 40 .deg. Sectors at tokamak in pit

International Nuclear Information System (INIS)

Nam, Kyoungo; Park, Hyun Ki; Kim, Dong Jin; Moon, Jaeh Wan; Kim, Byung Seok; Watson, Emma; Shaw, Robert

2012-01-01

The ITER Tokamak machine is composed of nine 40 .deg. sectors shaped of torus. Each 40.deg. sector is made up of one 40 .deg. vacuum vessel (VV), two 20 .deg. toroidal filed coils and associated vacuum vessel thermal shield (VVTS) segments which consist of one inboard and two outboard VVTS. The VV/TFC/VVTS 40 .deg. sectors are sub assembled at assembly building respectively at sector sub assembly tool and then nine sub assembled 40 .deg. sectors are finally assembled at in-pit of Tokamak building. ITER sector assembly tools are the purpose built assembly tools to assemble nine 40 .deg. sectors into the complete ITER Tokamak machine at Tokamak in pit. Based on the design description document, final report prepared by the ITER organization (IO) and tooling requirements, Korea has carried out the conceptual and preliminary design of these assembly tools. Especially, the central column is the main tool, which is composed of some hollow cylinders, to support full nine 40 .deg. sectors at Tokamak in pit. Configuration and structural analysis of the central column are presented

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.

Science.gov (United States)

Ye, Qiaozhen; Rosenberg, Scott C; Moeller, Arne; Speir, Jeffrey A; Su, Tiffany Y; Corbett, Kevin D

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

Energy Technology Data Exchange (ETDEWEB)

Ye, Qiaozhen [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Rosenberg, Scott C. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Moeller, Arne [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Speir, Jeffrey A. [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Su, Tiffany Y. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Corbett, Kevin D. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

Diverted assembly for radioactive material