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Spindle
Kinds of Spindle Terms modified by Spindle Selected AbstractsSTUDY ON THE MOTION ERROR OF MAIN SPINDLE OF LATHE BASED ON THE HARMONIC WAVELET NEURAL NETWORKEXPERIMENTAL TECHNIQUES, Issue 3 2009X.-J. Fu First page of article [source] Curcumin disrupts meiotic and mitotic divisions via spindle impairment and inhibition of CDK1 activityCELL PROLIFERATION, Issue 4 2010A. Bielak-Zmijewska Objectives:, Curcumin, a natural compound, is a potent anti-cancer agent, which inhibits cell division and/or induces cell death. It is believed that normal cells are less sensitive to curcumin than malignant cells; however, the mechanism(s) responsible for curcumin's effect on normal cells are poorly understood. The aim of this study was to verify the hypothesis that curcumin affects normal cell division by influencing microtubule stability, using mouse oocyte and early embryo model systems. Materials and methods:, Maturating mouse oocytes and two-cell embryos were treated with different concentrations of curcumin (10,50 ,m), and meiotic resumption and mitotic cleavage were analysed. Spindle and chromatin structure were visualized using confocal microscopy. In addition, acetylation and in vitro polymerization of tubulin, in the presence of curcumin, were investigated and the damage to double-stranded DNA was studied using ,H2A.X. CDK1 activity was measured. Results and conclusions:, We have shown for the first time, that curcumin, in a dose-dependent manner, delays and partially inhibits meiotic resumption of oocytes and inhibits meiotic and mitotic divisions by causing disruption of spindle structure and does not induce DNA damage. Our analysis indicated that curcumin affects CDK1 kinase activity but does not directly affect microtubule polymerization and tubulin acetylation. As our study showed that curcumin impairs generative and somatic cell division, its future clinical use or of its derivatives with improved bioavailability after oral administration, should take into consideration the possibility of extensive side-effects on normal cells. [source] A population-based model of the nonlinear dynamics of the thalamocortical feedback network displays intrinsic oscillations in the spindling (7,14 Hz) rangeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005Nada A. B. Yousif Abstract The thalamocortical network is modelled using the Wilson,Cowan equations for neuronal population activity. We show that this population model with biologically derived parameters possesses intrinsic nonlinear oscillatory dynamics, and that the frequency of oscillation lies within the spindle range. Spindle oscillations are an early sleep oscillation characterized by high-frequency bursts of action potentials followed by a period of quiescence, at a frequency of 7,14 Hz. Spindles are generally regarded as being generated by intrathalamic circuitry, as decorticated thalamic slices and the isolated thalamic reticular nucleus exhibit spindles. However, the role of cortical feedback has been shown to regulate and synchronize the oscillation. Previous modelling studies have mainly used conductance-based models and hence the mechanism relied upon the inclusion of ionic currents, particularly the T-type calcium current. Here we demonstrate that spindle-frequency oscillatory activity can also arise from the nonlinear dynamics of the thalamocortical circuit, and we use bifurcation analysis to examine the robustness of this oscillation in terms of the functional range of the parameters used in the model. The results suggest that the thalamocortical circuit has intrinsic nonlinear population dynamics which are capable of providing robust support for oscillatory activity within the frequency range of spindle oscillations. [source] Spindles losing their bearings: Does disruption of orientation in stem cells predict the onset of cancer?BIOESSAYS, Issue 6 2010Trevor A. Graham Abstract Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti-tumourigenic mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers. [source] Kinesin-5 is not essential for mitotic spindle elongation in DictyosteliumCYTOSKELETON, Issue 11 2008Irina Tikhonenko Abstract The proper assembly and operation of the mitotic spindle is essential to ensure the accurate segregation of chromosomes and to position the cytokinetic furrow during cell division in eukaryotes. Not only are dynamic microtubules required but also the concerted actions of multiple motor proteins are necessary to effect spindle pole separation, chromosome alignment, chromatid segregation, and spindle elongation. Although a number of motor proteins are known to play a role in mitosis, there remains a limited understanding of their full range of functions and the details by which they interact with other spindle components. The kinesin-5 (BimC/Eg5) family of motors is largely considered essential to drive spindle pole separation during the initial and latter stages of mitosis. We have deleted the gene encoding the kinesin-5 member in Dictyostelium, (kif13), and find that, in sharp contrast with results found in vertebrate, fly, and yeast organisms, kif13, cells continue to grow at rates indistinguishable from wild type. Phenotype analysis reveals a slight increase in spindle elongation rates in the absence of Kif13. More importantly, there is a dramatic, premature separation of spindle halves in kif13, cells, suggesting a novel role of this motor in maintaining spindle integrity at the terminal stages of division. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source] Native nonmuscle myosin II stability and light chain binding in Drosophila melanogasterCYTOSKELETON, Issue 10 2006Josef D. Franke Abstract Native nonmuscle myosin IIs play essential roles in cellular and developmental processes throughout phylogeny. Individual motor molecules consist of a heterohexameric complex of three polypeptides which, when properly assembled, are capable of force generation. Here, we more completely characterize the properties, relationships and associations that each subunit has with one another in Drosophila melanogaster. All three native nonmuscle myosin II polypeptide subunits are expressed in close to constant stoichiometry to each other throughout development. We find that the stability of two subunits, the heavy chain and the regulatory light chain, depend on one another whereas the stability of the third subunit, the essential light chain, does not depend on either the heavy chain or regulatory light chain. We demonstrate that heavy chain aggregates, which form when regulatory light chain is lacking, associate with the essential light chain in vivo,thus showing that regulatory light chain association is required for heavy chain solubility. By immunodepletion we find that the majority of both light chains are associated with the nonmuscle myosin II heavy chain but pools of free light chain and/or light chain bound to other proteins are present. We identify four myosins (myosin II, myosin V, myosin VI and myosin VIIA) and a microtubule-associated protein (asp/Abnormal spindle) as binding partners for the essential light chain (but not the regulatory light chain) through mass spectrometry and co-precipitation. Using an in silico approach we identify six previously uncharacterized genes that contain IQ-motifs and may be essential light chain binding partners. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source] Shaggy/GSK-3, kinase localizes to the centrosome and to specialized cytoskeletal structures in DrosophilaCYTOSKELETON, Issue 6 2006Yves Bobinnec Abstract The assembly of a functional bipolar mitotic spindle requires an exquisite regulation of microtubule behavior in time and space. To characterize new elements of this machinery we carried out a GFP based "protein trap" screen and selected fusion proteins which localized to the spindle apparatus. By this method we identified Shaggy, the Drosophila homologue of glycogen synthase kinase-3, (GSK-3,), as a component of centrosomes. GSK-3, acting in the Wingless signaling pathway is involved in a vast range of developmental processes, from pattern formation to cell-fate specification, and is a key factor for cell proliferation in most animals. We exploited our Shaggy::GFP Drosophila line to analyze the subcellular localizations of GSK-3,/Shaggy and shed light on its multiple roles during embryogenesis. We found that Shaggy becomes enriched transiently in a variety of specialized cytoskeletal structures of the embryo, including centrosomes throughout mitosis, suggesting that this kinase is involved in the regulation of many aspects of the cytoskeleton function. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source] Glutamylated tubulin: Diversity of expression and distribution of isoformsCYTOSKELETON, Issue 1 2003Marie-Louise Kann Abstract Glutamylation of , and , tubulin isotypes is a major posttranslational modification giving rise to diversified isoforms occurring mainly in neurotubules, centrioles, and axonemes. Monoglutamylated tubulin isoforms can be differentially recognized by two mAbs, B3 and GT335, which both recognize either polyglutamylated isoforms. In the present study, immunoelectron microscopy and immunofluorescence analyses were performed with these two mAbs to determine the expression and distribution of glutamylated tubulin isoforms in selected biological models whose tubulin isotypes are characterized. In mouse spermatozoa, microtubules of the flagellum contain polyglutamylated isoforms except in the tip where only monoglutamylated isoforms are detected. In spermatids, only a subset of manchette microtubules contain monoglutamylated tubulin isoforms. Cytoplasmic microtubules of Sertoli cells are monoglutamylated. Mitotic and meiotic spindles of germ cells are monoglutamylated whereas the HeLa cell mitotic spindle is polyglutamylated. Three models of axonemes are demonstrated as a function of the degree and extent of tubulin glutamylation. In lung ciliated cells, axonemes are uniformly polyglutamylated. In sea urchin sperm and Chlamydomonas, flagellar microtubules are polyglutamylated in their proximal part and monoglutamylated in their distal part. In Paramecium, cilia are bi- or monoglutamylated only at their base. In all cells, centrioles or basal bodies are polyglutamylated. These new data emphasize the importance of glutamylation in all types of microtubules and strengthen the hypothesis of its role in the regulation of the intracellular traffic and flagellar motility. Cell Motil. Cytoskeleton 55:14,25, 2003. © 2003 Wiley-Liss, Inc. [source] Arabidopsis thaliana protein, ATK1, is a minus-end directed kinesin that exhibits non-processive movementCYTOSKELETON, Issue 3 2002Adam I. Marcus Abstract The microtubule cytoskeleton forms the scaffolding of the meiotic spindle. Kinesins, which bind to microtubules and generate force via ATP hydrolysis, are also thought to play a critical role in spindle assembly, maintenance, and function. The A. thaliana protein, ATK1 (formerly known as KATA), is a member of the kinesin family based on sequence similarity and is implicated in spindle assembly and/or maintenance. Thus, we want to determine if ATK1 behaves as a kinesin in vitro, and if so, determine the directionality of the motor activity and processivity character (the relationship between molecular "steps" and microtubule association). The results show that ATK1 supports microtubule movement in an ATP-dependent manner and has a minus-end directed polarity. Furthermore, ATK1 exhibits non-processive movement along the microtubule and likely requires at least four ATK1 motors bound to the microtubule to support movement. Based on these results and previous data, we conclude that ATK1 is a non-processive, minus-end directed kinesin that likely plays a role in generating forces in the spindle during meiosis. Cell Motil. Cytoskeleton 52:144,150, 2002. © 2002 Wiley-Liss, Inc. [source] Asator, a tau-tubulin kinase homolog in Drosophila localizes to the mitotic spindleDEVELOPMENTAL DYNAMICS, Issue 12 2009Hongying Qi Abstract We have used a yeast two-hybrid interaction assay to identify Asator, a tau-tubulin kinase homolog in Drosophila that interacts directly with the spindle matrix protein Megator. Using immunocytochemical labeling by an Asator-specific mAb as well as by transgenic expression of a GFP-labeled Asator construct, we show that Asator is localized to the cytoplasm during interphase but redistributes to the spindle region during mitosis. Determination of transcript levels using qRT-PCR suggested that Asator is expressed throughout development but at relatively low levels. By P-element excision, we generated a null or strong hypomorphic Asatorexc allele that resulted in complete adult lethality when homozygous, indicating that Asator is an essential gene. That the observed lethality was caused by impaired Asator function was further supported by the partial restoration of viability by transgenic expression of Asator-GFP in the Asatorexc homozygous mutant background. The finding that Asator localizes to the spindle region during mitosis and directly can interact with Megator suggests that its kinase activity may be involved in regulating microtubule dynamics and microtubule spindle function. Developmental Dynamics 238:3248,3256, 2009. © 2009 Wiley-Liss, Inc. [source] Bipolar, anastral spindle development in artificially activated sea urchin eggsDEVELOPMENTAL DYNAMICS, Issue 5 2008John H. Henson Abstract The mitotic apparatus of the early sea urchin embryo is the archetype example of a centrosome-dominated, large aster spindle organized by means of the centriole of the fertilizing sperm. In this study, we tested the hypothesis that artificially activated sea urchin eggs possess the capacity to assemble the anastral, bipolar spindles present in many acentrosomal systems. Control fertilized Lytechinus pictus embryos and ammonia-activated eggs were immunolabeled for tubulin, centrosomal material, the spindle pole structuring protein NuMA and the mitotic kinesins MKLP1/Kinesin-6, Eg5/Kinesin-5, and KinI/Kinesin-13. Confocal imaging showed that a subset of ammonia-activated eggs contained bipolar "mini-spindles" that were anastral; displayed metaphase and anaphase-like stages; labeled for centrosomal material, NuMA, and the three mitotic kinesins; and were observed in living eggs using polarization optics. These results suggest that spindle structural and motor proteins have the ability to organize bipolar, anastral spindles in sea urchin eggs activated in the absence of the paternal centriole. Developmental Dynamics 237:1348-1358, 2008. © 2008 Wiley-Liss, Inc. [source] Infarcted intraductal papilloma of the breast: Cytologic features with stage of infarctionDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2006Akinori Ishihara M.D., F.I.A.C., Ph.D. Abstract Fine-needle aspiration cytology (FNAC) is being employed with increasing frequency for the pre-operative diagnostic workup of breast lesions. Although most cases show morphologic features very characteristic of specific entities, rare lesions with infarcted breast can cause problems in interpretation. We present cytologic findings in seven cases of an infarcted intraductal papilloma of the breast (IDPB) that was diagnosed by FNAC, and we also report the correlation of cytological features and stages of infarcted IDPB. In the early stage of infarction, numerous degenerative cells and necrotic debris were demonstrated. Isolated degenerative cells showed columnar, spindle, polygonal and fiber-like cells, with coagulated and smudged nuclei. Ghost cells were also seen. Extensive necrosis was demonstrated with a few sheets of ductal cells in the mid-stage of infarction. In the late stage of infarction, clusters of fibroblasts, ductal cells and necrotic debris were found. Knowledge of the characteristic cytologic pattern in different stages of infarcted IDPB may be helpful to suggest the probable pre-operative diagnosis of those lesions. Familiarity with this entity is important in preventing misdiagnosis of malignancy. Diagn. Cytopathol. 2006;34:373,376. © 2006 Wiley-Liss, Inc. [source] Fine-needle aspiration cytology of pleomorphic hyalinized angiectatic tumor: A case reportDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2005Oscar Lin M.D., Ph.D. Abstract Pleomorphic hyalinized angiectatic tumor (PHAT) of soft parts is a neoplasm characterized by spindle and pleomorphic cells associated with an angiectatic vasculature. We describe the cytological findings of a fine-needle aspiration biopsy (FNAB) from the right medial knee of a 45-yr-old woman. The aspirate material was entirely submitted in Cytolit solution. The specimen was moderately cellular and was comprised of spindle cells in a background of fibrinous material. The cells varied from small, bland spindle cells with a fine chromatin pattern and inconspicuous nucleoli to larger pleomorphic cells with coarser chromatin and occasional intranuclear inclusions. Most of the cells were arranged singly with sporadic small cluster formation with indistinct cell borders. Rare mononuclear inflammatory cells morphologically compatible with mast cells were identified. The differential diagnosis include solitary fibrous tumor (SFT) and ancient schwannoma, which also shows fibrous-like material and spindle cells that may have intranuclear inclusions. Diagn. Cytopathol. 2005;32:238,242. © 2005 Wiley-Liss, Inc. [source] Aspiration cytology of sarcomatoid carcinoma of the breast: Report of a case with cystic changeDIAGNOSTIC CYTOPATHOLOGY, Issue 1 2004Smita Mary Matthai MBBS Abstract Sarcomatoid/metaplastic carcinomas of the breast are rare breast malignancies that show a myriad of cytohistologic patterns in aspirates. These poorly differentiated invasive carcinomas contain both ductal and mesenchymal elements with transitional forms displaying either spindle, squamous, chondroid, or osseous differentiation. We describe such a neoplasm in a 68-yr-old woman, the diagnosis of which was missed at the initial fine-needle aspiration (FNA) due to cystic change. Extensive cystic change in a sarcomatoid carcinoma is unusual and is reported for the first time in the English literature. Diagn. Cytopathol. 2004;31:10,13. © 2004 Wiley-Liss, Inc. [source] Mammalian CLASPs are required for mitotic spindle organization and kinetochore alignmentGENES TO CELLS, Issue 8 2006Yuko Mimori-Kiyosue CLASP1 and CLASP2 are homologous mammalian proteins, which associate with the ends of growing microtubules, as well as the cell cortex and the kinetochores of mitotic chromosomes. Previous studies have shown that in interphase cells CLASPs can attach microtubule plus ends to the cortex and stabilize them by repeatedly rescuing them from depolymerization. Here we show that CLASP1 and 2 play similar and redundant roles in organizing the mitotic apparatus in HeLa cells. Simultaneous depletion of both CLASPs causes mitotic spindle defects and a significant metaphase delay, which often results in abnormal exit from mitosis. Metaphase delay is associated with decreased kinetochore tension, increased kinetochore oscillations and more rapid microtubule growth. We show that the association of CLASP2 with the kinetochores relies on its C-terminal domain, but is independent of microtubules or association with CLIP-170. We propose that CLASPs exhibit at the kinetochores an activity similar to that at the cortex, providing apparent stabilization of microtubules by locally reducing the amplitude of growth/shortening episodes at the microtubule ends. This local stabilization of microtubules is essential for the formation of normal metaphase spindle, completion of anaphase and cytokinesis. [source] Schizosaccharomyces pombe homolog of Survivin, Bir1p, exhibits a novel dynamic behavior at the spindle mid-zoneGENES TO CELLS, Issue 7 2006Srividya Rajagopalan Members of the BIR-domain containing Survivin family of proteins have been identified in a variety of eukaryotes and are known to play important roles in the regulation of mitosis. The Schizosaccharomyces pombe homolog of Survivin, Bir1p, is essential for chromosome condensation and spindle elongation and integrity. Bir1p, a nuclear protein, resides at the kinetochores in metaphase and anaphase A and spreads to the spindle mid-zone in anaphase B. Here we show that this relocation requires Cdk (Cyclin dependent kinase) inactivation and intact microtubules. With the aid of a kinesin mutant, klp5,, we also show that completion of anaphase A is vital for effecting Bir1p re-location to the spindle mid-zone. Although minimal exchange of Bir1p sub-units occurs between the spindle and the nucleoplasm, the protein redistributes laterally within the mid-zone region. Bir1p dynamics therefore significantly differs from that of tubulin on an anaphase B spindle, which is loaded at the plus ends of growing microtubules and shows no lateral redistribution within the spindle. Thus, Bir1p, and possibly its associated proteins, might organize a dynamic mid-zone region that helps spindle elongation and maintenance. [source] Cut1/separase C-terminus affects spindle pole body positioning in interphase of fission yeast: pointed nuclear formationGENES TO CELLS, Issue 11 2002Takahiro Nakamura Background: The separase-securin complex is required for anaphase. Separase activated by securin destruction cleaves the cohesin subunit Scc1/Rad21 enriched in kinetochores. Fission yeast Cut1/separase resides in interphase cytoplasm and mobilizes to the spindle and the spindle pole bodies (SPBs) in mitosis, while Cut2/securin remains in the nucleus from interphase to metaphase, and temporarily locates at the short spindle. Results: We here report a novel SPB-led dynamic nuclear movement in fission yeast, when the Cut1 C-terminal fragment is over-expressed. The tip of the pointed nucleus contained both SPB and centromeric DNA, and rapidly moved along the bundled cytoplasmic microtubules. The same pointed nucleus was produced when the human separase C-fragment was over-expressed. The pointed nuclear formation did not require the protease site of separase, but required the conserved C-terminus and a microtubule- and kinetochore-binding protein Mtc1/Alp14, a homologue of frog XMAP215 and budding yeast Stu2. The movement-inducing C-fragment should be cytoplasmic, as the pointed nucleus was abolished when the fragment contained the NLS (nuclear localization signal). Conclusions: Overproduced separase C-fragment abolishes correct SPB-positioning in interphase. Resulting pointed nuclear formation (alternatively called ,pigtail movement') requires cytoplasmic microtubules and Mtc1/Alp14. [source] The ,-tubulin complex protein Alp4 provides a link between the metaphase checkpoint and cytokinesis in fission yeastGENES TO CELLS, Issue 4 2002Leah Vardy Background:, The progression of cytokinesis requires cyclin B destruction by the anaphase promoting complex (APC/C) and, in fission yeast, activation of the septation initiation network (SIN) is also essential. The ,-tubulin complex (,-TuC) localizes to the centrosome throughout the cell cycle and is directly involved in the organization of the mitotic spindle. Results:, We have previously shown that the mutant defective in alp4+ (Spc97/GCP2) displays bipolar spindle defects due to a failure in the recruitment of the ,-TuC on to the spindle pole body (SPB, the centrosome equivalent). Here we show that in these mutants the Mad2 checkpoint is activated, yet septation proceeds due to the untimely activation of the SIN. The Sid1 kinase, the downstream effector of the SIN, is recruited prematurely to both, instead of only one, of the SPBs, which triggers septation despite the presence of monopolar spindles. Remarkably, cyclin B levels, which would normally have declined, remain high at the SPB in septated mutant cells. Conclusions:, We propose a novel role of the ,-TuC in inhibiting activation of the SIN until cyclin B is destroyed. Given the ubiquitous existence of the ,-TuC, this mechanism may be conserved throughout evolution and function to couple cytokinesis to mitotic exit. [source] Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repairGENES TO CELLS, Issue 9 2001Jun Morishita Background In mammals, proteins containing BIR domains (IAPs and survivin) are implicated in inhibiting apoptosis and sister chromatid separation. In the nematode, Bir1 is required for a proper localization of aurora kinase, which moves from the mitotic chromosome in metaphase to the spindle midzone in anaphase as a passenger. Fission yeast Bir1/Pbh1 is essential for normal mitosis. Results A temperature sensitive mutant cut17-275 exhibits the defect in condensation and spindle elongation at 36 °C, while securin is degraded. Gene cloning shows that the cut17+ gene is identical to bir1+/pbh1+. At 26 °C, cut17-275 is UV sensitive as the repair of DNA damage is severely compromised. Bir1/Cut17 is a nuclear protein in interphase, which is then required for recruiting condensin to the mitotic nucleus, and concentrates to form a discrete number of dots from prometaphase to metaphase. Once the chromatids are separated, Bir1/Cut17 no longer binds to kinetochores and instead moves to the middle of spindle. Chromatin immunoprecipitation suggested that Bir1/Cut17 associates with the outer repetitious centromere region in metaphase. Following the initiation of anaphase the protein switches from being a chromosomal protein to a spindle protein. This transit is stringently regulated by the state of sister chromatid cohesion proteins Mis4 and Rad21. Ark1, is an aurora kinase homologue whose mitotic distribution is identical to, and under the control of Bir1/Cut17. Conclusions Bir1/Cut17 and Ark1 act as ,passengers' but they may play a main role as a recruitment factor, essential for condensation, spindle elongation and DNA repair. Bir1/Cut17 should have roles both in mitotic and in interphase chromosome. The proper location of Ark1 requires Bir1/Cut17, and the mitotic localization of Bir1/Cut17 requires sister cohesion. [source] Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cellsGENES, CHROMOSOMES AND CANCER, Issue 10 2010Chikako Fukukawa To investigate the molecular mechanism of mammary carcinogenesis and identify novel molecular targets for breast cancer therapy, we analyzed genome-wide gene expression profiles of 81 clinical breast cancer samples. Here, we report the critical role of LGN/GPSM2 (Leu-Gly-Asn repeat-enriched protein/G-protein signaling modulator 2) in the growth of breast cancer cells. Semiquantitative RT-PCR and Northern blot analyses confirmed upregulation of LGN/GPSM2 in a large proportion of breast cancers. Immunocytochemical staining identified LGN/GPSM2 at the spindle in cells at metaphase, and at midzone and midbody in cytokinetic cells. Western blot analysis indicated the highest expression and the phosphorylated form of LGN/GPSM2 protein in G2/M phase. Treatment with small-interfering RNAs (siRNAs) targeting LGN/GPSM2 caused incompletion of cell division and resulted in significant growth suppression of breast cancer cells. We found that the 450th threonine (Thr450) of LGN/GPSM2 was phosphorylated by the serine/threonine kinase PBK/TOPK during mitosis. Overexpression of LGN/GPSM2-T450A in which Thr450 was substituted with alanine induced growth suppression and aberrant chromosomal segregation. These findings imply an important role of LGN/GPSM2 in cell division of breast cancer cells and suggest that the PBK/TOPK-LGN/GPSM2 pathway might be a promising molecular target for treatment of breast cancer. © 2010 Wiley-Liss, Inc. [source] Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zoneGLIA, Issue 2 2009Alexandre I. Danilov Abstract Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate olfactory bulb interneurons in the adult rodent brain. Based on their ultrastructural and antigenic properties, NSCs, transient amplifying precursor cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ ultrastructurally and at the light microscopy level, and to determine the antigenic properties of each cell type using gold and fluorescence immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal cells, displaced ependymal cells, and mature astrocytes. In contrast, transient amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts had epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFR,) expressed on the ciliary apparatus and were the only cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR and PDGFR, were associated with the microtubule of the mitotic spindle. Ependymal and displaced ependymal cells also expressed EGFR and PDGFR, on their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs disassemble the primary cilium and symmetrically distribute EGFR and PDGFR, among their progeny. © 2008 Wiley-Liss, Inc. [source] Cover Picture: J. Basic Microbiol.JOURNAL OF BASIC MICROBIOLOGY, Issue 1 20101/2010 This issue gives excellent examples for basic mycology, both from mushroom forming basidioymcetes and ascomycetes, including yeasts. The composite title photo shows two fungi, one basidiomycete and a yeast. A mitotic spindle of the mushroom forming basidiomycete Schizophyllum commune, stained for tubulin by immunofl uorescence and for DNA using DAPI (photo: Elke-Martina Jung, Jena) is shown, as well as a fruitbody forming in culture (insert on the left, photo: Nicole Knabe, Jena). Endocytosis of fl uorescein labelled, linear DNA is shown in a second insert (green stain) which is accompanied by a phase-contrast picture of the Saccharomyces cerevisiae cells used (see article by Lang et al. in this issue). (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Centrosome function in normal and tumor cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2006Satish Sankaran Abstract Centrosomes nucleate microtubules that form the mitotic spindle and regulate the equal division of chromosomes during cell division. In cancer, centrosomes are often found amplified to greater than two per cell, and these tumor cells frequently have aneuploid genomes. In this review, we will discuss the cellular factors that regulate the proper duplication of the centrosome and how these regulatory steps can lead to abnormal centrosome numbers and abnormal mitoses. In particular, we highlight the newly emerging role of the Breast Cancer 1 (BRCA1) ubiquitin ligase in this process. J. Cell. Biochem. 99: 1240,1250, 2006. © 2006 Wiley-Liss, Inc. [source] Fibroblastic rheumatism: fibromatosis rather than non-Langerhans cell histiocytosisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2010Nicolas Kluger Background: Fibroblastic rheumatism is a unique fibro-proliferative disease affecting the skin and joints. It is characterized by distinctive clinical and histological features related to benign spindle-shaped cells proliferation. Pediatric reports are scarce in the literature. Objective: We describe here a new case in a 10-year-old boy and discuss the potential origin of the cell proliferation. Methods: Clinical findings, radiology, microscopic examination and outcome are reviewed. Histopathology and immunochemistry studies were performed on skin biospies using CD68, CD163, desmin, factor XIIIa, CD34, smooth muscle actin, PS100, epithelial membrane antigen, and calponin. Results: Histological sections disclosed a rather circumscribed nonencapsulated nodular infiltrate, invading the dermis and the upper subcutaneous tissue, consisted of a proliferation of spindle or stellate-shaped cells and thickened collagen fibers. Orcein staining showed disappearance of the elastic network. Aponeurosis and muscle were normal. A mild perivascular lymphohistiocytic infiltrate was noted. Calponin-staining was less strongly expressed as SMA, and some of them but not all were CD68 positive, as well. On the other hand, all were CD34, CD163, FXIIIa, PS100, EMA and desmin-negative. Conclusion: The true origin of these cells remains unclear. Some authors have speculated a histiocytic origin. However, immuno-chemical staining in our case failed to confirm this hypothesis and instead supported a fibroblastic/myofibroblastic origin. Given the clinical course and the histological and immunohistochemical results, we suggest that FR should be added to the group of fibromatoses. Kluger N, Dumas-Tesici A, Hamel D, Brousse N, Fraitag S. Fibroblastic rheumatism: fibromatosis rather than non-Langerhans cell histiocytosis. [source] Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls: a reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2010tjan Luzar The present manuscript gives emphasis on recognizing different morphological variants of atypical fibroxanthoma (AFX), on validation of immunohistochemical markers and on discussing potential diagnostic pitfalls. Material and methods: Histological features analyzed in 66 AFXs were: ulceration, morphological variants, growth pattern, location in the skin and vascular/perineural invasion. The antibodies used were CK-MNF116, CK-AE1/AE3, S100, smooth muscle actin, desmin, CD31 and EMA. Results: The study included 59 males, 7 females, aged 55,95 years, mean 77 years. All developed on sun damaged skin. Ulceration was present in 50%. Morphological patterns were pleomorphic spindle and epithelioid cells (60.6%), predominantly spindle cells (19.7%), purely spindle-cells (13.6%), and predominantly epithelioid cells (6.1%). Most were localized in the dermis (57.6%). An expansile (36.4%) rather than infiltrative (6.1%) growth into superficial subcutis was also noted. No vascular/perineural invasion was seen. Additional changes were hemorrhagic and pseudoangiomatous areas (24.2%), granular cell change (22.7%), keloid-like areas (9.1%), myxoid change (7.6%), osteoclast-like giant cells (6.1%) and clear cell change (4.6%). AFXs were consistently negative for S100, CK-MNF116, CK-AE1/AE3 and desmin. Focal positivity for SMA (45.2%), EMA (24.4%) and CD 31 (9.5%) was seen. Conclusions: A diagnosis of AFX is still made by exclusion of other malignant neoplasms with similar morphology. Immunohistochemistry plays a crucial role in this distinction, but can also be misleading. This study expands the spectrum of non-vascular CD31 positive tumors. Luzar B, Calonje E. Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls. [source] A case of cutaneous symplastic leiomyoma , a rare variant of cutaneous pilar leiomyomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2008Naila Usmani We describe the case of a cutaneous symplastic leiomyoma in a 37-year-old woman who presented with a 4-year history of a painful slow growing lesion on the left upper arm. The lesion was excised and subjected to histological examination. A poorly circumscribed lesion was seen in the dermis composed of spindle shaped cells with marked nuclear pleomorphism. No mitotic figures or necrosis were seen. The cells stained strongly positive with desmin and smooth muscle actin, and negative with S100, melan A, MNF116 a mouse monoclonal antibody to cytokeratin and CK5/6. The diagnosis was felt to be in keeping with a cutaneous symplastic leiomyoma, a rarely reported variant of the pilar leiomyoma. Histologically, it shows features similar to the symplastic variant of uterine leiomyoma with cytological atypia, nuclear pleomorphism and minimal mitotic activity. Although the long-term outlook is probably benign, the presence of cytological atypia and mitoses in any spindle cell tumor is generally a concerning feature and warrants long-term follow up. [source] Transitions in the evolution of meiosisJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2000Hurst Meiosis may have evolved gradually within the eukaryotes with the earliest forms having a one-step meiosis. It has been speculated that the putative transition from a one-step meiosis without recombination to one with recombination may have been stimulated by the invasion of Killer alleles. These imaginary selfish elements are considered to act prior to recombination. They prime for destruction (which occurs after cell division) the half of the cell on the opposite side of the meiotic spindle. Likewise the transition from one-step to two-step meiosis might have been stimulated by a subtly different sort of imaginary distorter allele, a SisterKiller. These are proposed to act after recombination. It has yet to be established that the presence of such distorter alleles could induce the transitions in question. To investigate these issues we have analysed the dynamics of a modifier (1) of recombination and (2) of the number of steps of meiosis, as they enter a population with one-step meiosis. For the modifier of recombination, we find that invasion conditions are very broad and that persistence of Killer and modifier is likely through most parameter space, even when the recombination rate is low. However, if we allow a Killer element to mutate into one that is self-tolerant, the modifier and the nonself-tolerant alleles are typically both lost from the population. The modifier of the number of steps can invade if the SisterKiller acts at meiosis II. However, a SisterKiller acting at meiosis I, far from promoting the modifier's spread, actually impedes it. In the former case the invasion is easiest if there is no recombination. The SisterKiller hypothesis therefore fails to provide a reasonable account of the evolution of two-step meiosis with recombination. As before, the evolution of self-tolerance on the part of the selfish element destroys the process. We conclude that the conditions under which SisterKillers promote the evolution of two-step meiosis are very much more limited than originally considered. We also conclude that there is no universal agreement between ESS and modifier analyses of the same transitions. [source] Malignant peripheral nerve sheath tumor of the uterine cervix expressing both S-100 protein and HMB-45JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2009Na Rae Kim Abstract A 50-year-old woman presented with a large cervical polypoid mass. Grossly, the mass occupied a substantial proportion of the cervical canal, measuring 6 cm. Histologically, the mass showed a spindle cell malignancy arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The spindle cells were immunoreactive for both S-100 protein and HMB-45 antigen, but were negative for Melan-A. Electron microscopy showed that cytoplasmic processes of the spindle to oval tumor cells contained microtubules and were lined by basal lamina and abundant intercellular collagen spacing with no melanosomes in any stage. As far as we are aware, this is the ninth reported case of cervical malignant peripheral nerve sheath tumor (MPNST), and the second reported case of MPNST expressing HMB-45 antigen. [source] Cortical locations of maximal spindle activity: magnetoencephalography (MEG) studyJOURNAL OF SLEEP RESEARCH, Issue 2 2009VALENTINA GUMENYUK Summary The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 ± 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence. [source] Intensity-based signal separation algorithm for accurate quantification of clustered centrosomes in tissue sectionsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 12 2006Markus C. Fleisch Abstract Centrosomes are small organelles that organize the mitotic spindle during cell division and are also involved in cell shape and polarity. Within epithelial tumors, such as breast cancer, and some hematological tumors, centrosome abnormalities (CAs) are common, occur early in disease etiology, and correlate with chromosomal instability and disease stage. In situ quantification of CA by optical microscopy is hampered by overlap and clustering of these organelles, which appear as focal structures. CA has been frequently associated with Tp53 status in premalignant lesions and tumors. Here the authors described an approach to accurately quantify centrosome frequencies in tissue sections and tumors, independently of background or noise levels. Applying simple optical rules in nondeconvolved conventional 3D images of stained tissue sections, the authors showed that they could evaluate more accurately and rapidly centrosome frequencies than with traditional investigator-based visual analysis or threshold-based techniques. The resulting population-based frequency of centrosomes per nucleus could then be used to approximate the proportion of cells with CA in that same population. This was done by taking into account baseline centrosome amplification and proliferation rates measured in the tissue. Using this technique, the authors showed that 20,30% of cells have amplified centrosomes in Tp53 null mammary tumors. Microsc. Res. Tech., 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||