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1
Santos, Herbert J., Yuki Hanadate, Kenichiro Imai, and Tomoyoshi Nozaki. "An Entamoeba-Specific Mitosomal Membrane Protein with Potential Association to the Golgi Apparatus." Genes 10, no. 5 (May 13, 2019): 367. http://dx.doi.org/10.3390/genes10050367.
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The aerobic mitochondrion had undergone evolutionary diversification, most notable among lineages of anaerobic protists. Entamoeba is one of the genera of parasitic protozoans that lack canonical mitochondria, and instead possess mitochondrion-related organelles (MROs), specifically mitosomes. Entamoeba mitosomes exhibit functional reduction and divergence, most exemplified by the organelle’s inability to produce ATP and synthesize iron-sulfur cluster. Instead, this organelle is capable of sulfate activation, which has been linked to amoebic stage conversion. In order to understand other unique features and components of this MRO, we utilized an in silico prediction tool to screen transmembrane domain containing proteins in the mitosome proteome. Here, we characterize a novel lineage-specific mitosomal membrane protein, named Entamoeba transmembrane mitosomal protein of 30 kDa (ETMP30; EHI_172170), predicted to contain five transmembrane domains. Immunofluorescence analysis demonstrated colocalization of hemagglutinin (HA)-tagged ETMP30 with the mitosomal marker, adenosine-5’-phosphosulfate kinase. Mitosomal membrane localization was indicated by immunoelectron microscopy analysis, which was supported by carbonate fractionation assay. Transcriptional gene silencing successfully repressed RNA expression by 60%, and led to a defect in growth and partial elongation of mitosomes. Immunoprecipitation of ETMP30 from ETMP30-HA-expressing transformant using anti-HA antibody pulled down one interacting protein of 126 kDa. Protein sequencing by mass spectrometry revealed this protein as a cation-transporting P-type ATPase, previously reported to localize to vacuolar compartments/Golgi-like structures, hinting at a possible mitosome-vacuole/Golgi contact site.
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Martincová, Eva, Luboš Voleman, Jan Pyrih, Vojtěch Žárský, Pavlína Vondráčková, Martin Kolísko, Jan Tachezy, and Pavel Doležal. "Probing the Biology of Giardia intestinalis Mitosomes UsingIn VivoEnzymatic Tagging." Molecular and Cellular Biology 35, no. 16 (June 8, 2015): 2864–74. http://dx.doi.org/10.1128/mcb.00448-15.
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Giardia intestinalisparasites contain mitosomes, one of the simplest mitochondrion-related organelles. Strategies to identify the functions of mitosomes have been limited mainly to homology detection, which is not suitable for identifying species-specific proteins and their functions. Anin vivoenzymatic tagging technique based on theEscherichia colibiotin ligase (BirA) has been introduced toG. intestinalis; this method allows for the compartment-specific biotinylation of a protein of interest. Known proteins involved in the mitosomal protein import werein vivotagged, cross-linked, and used to copurify complexes from the outer and inner mitosomal membranes in a single step. New proteins were then identified by mass spectrometry. This approach enabled the identification of highly diverged mitosomal Tim44 (GiTim44), the first known component of the mitosomal inner membrane translocase (TIM). In addition, our subsequent bioinformatics searches returned novel diverged Tim44 paralogs, which mediate the translation and mitosomal insertion of mitochondrially encoded proteins in other eukaryotes. However, most of the identified proteins are specific toG. intestinalisand even absent from the related diplomonad parasiteSpironucleus salmonicida, thus reflecting the unique character of the mitosomal metabolism. Thein vivoenzymatic tagging also showed that proteins enter the mitosome posttranslationally in an unfolded state and without vesicular transport.
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Rada, Petr, Ondřej Šmíd, Robert Sutak, Pavel Doležal, Jan Pyrih, Vojtěch Žárský, Jean-Jacques Montagne, Ivan Hrdý, Jean-Michel Camadro, and Jan Tachezy. "The Monothiol Single-Domain Glutaredoxin Is Conserved in the Highly Reduced Mitochondria of Giardia intestinalis." Eukaryotic Cell 8, no. 10 (August 28, 2009): 1584–91. http://dx.doi.org/10.1128/ec.00181-09.
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ABSTRACT The highly reduced mitochondria (mitosomes) of Giardia intestinalis are recently discovered organelles for which, it was suggested, iron-sulfur cluster assembly was their only conserved function. However, only an incomplete set of the components required for FeS cluster biogenesis was localized to the mitosomes. Via proteomic analysis of a mitosome-rich cellular fraction together with immunofluorescence microscopy, we identified a novel mitosomal protein homologous to monothiol glutaredoxins containing a CGFS motif at the active site. Sequence analysis revealed the presence of long nonconserved N-terminal extension of 77 amino acids, which was absent in the mature protein. Expression of the complete and N-terminally truncated forms of the glutaredoxin indicated that the extension is involved in glutaredoxin import into mitosomes. However, the mechanism of preprotein processing is unclear, as the mitosomal processing peptidase is unable to cleave this type of extension. The recombinant mature protein was shown to form a homodimeric structure, which binds a labile FeS cluster. The cluster is stabilized by glutathione and dithiothreitol. Phylogenetic analysis showed that giardial glutaredoxin is related to the mitochondrial monothiol glutaredoxins involved in FeS cluster assembly. The identification of a mitochondrial-type monothiol glutaredoxin in the mitosomes of G. intestinalis thus completes the mitosomal FeS cluster biosynthetic pathway and provides further evidence for the mitochondrial origin of these organelles.
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Santos, Herbert J., Yoko Chiba, Takashi Makiuchi, Saki Arakawa, Yoshitaka Murakami, Kentaro Tomii, Kenichiro Imai, and Tomoyoshi Nozaki. "Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences." Microorganisms 8, no. 8 (August 12, 2020): 1229. http://dx.doi.org/10.3390/microorganisms8081229.
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Mitochondrial matrix proteins synthesized in the cytosol often contain amino (N)-terminal targeting sequences (NTSs), or alternately internal targeting sequences (ITSs), which enable them to be properly translocated to the organelle. Such sequences are also required for proteins targeted to mitochondrion-related organelles (MROs) that are present in a few species of anaerobic eukaryotes. Similar to other MROs, the mitosomes of the human intestinal parasite Entamoeba histolytica are highly degenerate, because a majority of the components involved in various processes occurring in the canonical mitochondria are either missing or modified. As of yet, sulfate activation continues to be the only identified role of the relic mitochondria of Entamoeba. Mitosomes influence the parasitic nature of E. histolytica, as the downstream cytosolic products of sulfate activation have been reported to be essential in proliferation and encystation. Here, we investigated the position of the targeting sequence of one of the mitosomal matrix enzymes involved in the sulfate activation pathway, ATP sulfurylase (AS). We confirmed by immunofluorescence assay and subcellular fractionation that hemagluttinin (HA)-tagged EhAS was targeted to mitosomes. However, its ortholog in the δ-proteobacterium Desulfovibrio vulgaris, expressed as DvAS-HA in amoebic trophozoites, indicated cytosolic localization, suggesting a lack of recognizable mitosome targeting sequence in this protein. By expressing chimeric proteins containing swapped sequences between EhAS and DvAS in amoebic cells, we identified the ITSs responsible for mitosome targeting of EhAS. This observation is similar to other parasitic protozoans that harbor MROs, suggesting a convergent feature among various MROs in favoring ITS for the recognition and translocation of targeted proteins.
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Emelyanov, Victor V., and Alina V. Goldberg. "Fermentation enzymes of Giardia intestinalis, pyruvate:ferredoxin oxidoreductase and hydrogenase, do not localize to its mitosomes." Microbiology 157, no. 6 (June 1, 2011): 1602–11. http://dx.doi.org/10.1099/mic.0.044784-0.
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It is becoming increasingly clear that the so-called remnant organelles of microaerophilic unicellular eukaryotes, hydrogenosomes and mitosomes, are significantly reduced versions of mitochondria. They normally lack most of the classic mitochondrial attributes, such as an electron transport chain and a genome. While hydrogenosomes generate energy by substrate-level phosphorylation along a hydrogen-producing fermentation pathway, involving iron–sulfur-cluster-containing enzymes pyruvate : ferredoxin oxidoreductase (PFO) and hydrogenase, whether mitosomes participate in ATP synthesis is currently unknown. Both enzymes were recently described in the mitosome-bearing diplomonad Giardia intestinalis, also shown to produce molecular hydrogen. As published data show that giardial PFO is a membrane-associated enzyme, it could be suspected that PFO and hydrogenase operate in the mitosome, in which case the latter would by definition be a hydrogenosome. Using antibodies against recombinant enzymes of G. intestinalis, it was shown by Western blot analysis of subcellular fractions and by confocal immunofluorescence microscopy of whole cells that neither PFO nor hydrogenase localize to the mitosome, but are mostly found in the cytosol. The giardial mitosome is known to play a role in iron–sulfur cluster assembly and to contain chaperones Cpn60 and mtHsp70, which assist, in particular, in protein import. In mitochondria, transmembrane potential is essential for this complex process. Using MitoTracker Red and organelle-specific antibodies, transmembrane potential could be detected in the Trichomonas vaginalis hydrogenosome, but not in the G. intestinalis mitosome. These results provide further evidence that the Giardia mitosome is one of the most highly reduced mitochondrial homologues.
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Steinbeck, RG. "Pathologic mitoses and pathology of mitosis in tumorigenesis." European Journal of Histochemistry 45, no. 4 (December 30, 2009): 311. http://dx.doi.org/10.4081/1640.
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Mi-ichi, Fumika, Akira Nozawa, Hiroki Yoshida, Yuzuru Tozawa, and Tomoyoshi Nozaki. "Evidence that the Entamoeba histolytica Mitochondrial Carrier Family Links Mitosomal and Cytosolic Pathways through Exchange of 3′-Phosphoadenosine 5′-Phosphosulfate and ATP." Eukaryotic Cell 14, no. 11 (September 18, 2015): 1144–50. http://dx.doi.org/10.1128/ec.00130-15.
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ABSTRACT Entamoeba histolytica , a microaerophilic protozoan parasite, possesses mitosomes. Mitosomes are mitochondrion-related organelles that have largely lost typical mitochondrial functions, such as those involved in the tricarboxylic acid cycle and oxidative phosphorylation. The biological roles of Entamoeba mitosomes have been a long-standing enigma. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. Sulfate activation cooperates with cytosolic enzymes, i.e., sulfotransferases (SULTs), for the synthesis of sulfolipids, one of which is cholesteryl sulfate. Notably, cholesteryl sulfate plays an important role in encystation, an essential process in the Entamoeba life cycle. These findings identified a biological role for Entamoeba mitosomes; however, they simultaneously raised a new issue concerning how the reactions of the pathway, separated by the mitosomal membranes, cooperate. Here, we demonstrated that the E. histolytica mitochondrial carrier family (EhMCF) has the capacity to exchange 3′-phosphoadenosine 5′-phosphosulfate (PAPS) with ATP. We also confirmed the cytosolic localization of all the E. histolytica SULTs, suggesting that in Entamoeba , PAPS, which is produced through mitosomal sulfate activation, is translocated to the cytosol and becomes a substrate for SULTs. In contrast, ATP, which is produced through cytosolic pathways, is translocated into the mitosomes and is a necessary substrate for sulfate activation. Taking our findings collectively, we suggest that EhMCF functions as a PAPS/ATP antiporter and plays a crucial role in linking the mitosomal sulfate activation pathway to cytosolic SULTs for the production of sulfolipids.
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Kantsavaya, I., and O. Alekseenko. "Effect of Beta-lactam Antibiotics on Microscopic Parameters in the Allium-test." Bulletin of Science and Practice 5, no. 10 (October 15, 2019): 25–31. http://dx.doi.org/10.33619/2414-2948/47/03.
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The work examines the effect of beta-lactam antibiotics (cefotaxime, ampicillin, augmentin) on the pathology of mitosis in the Allium–test. Research methods: Allium–test, cytogenetic analysis, statistical analysis. It was established that the use of individual tested beta-lactam antibiotics increases the percentage of pathological mitoses in the cell by 1.8–3.3 times compared with the value in the control. With the combined use of cefotaxime and Augmentin, synergism appeared, as a result, the value of mitosis pathology turned out to be at the level of the number in the control; minimally represented pathologies indicating damage to the mitotic apparatus. It was revealed that all three beta-lactam antibiotics tested had a pronounced statmokinetic effect. At the same time, with the joint use of cefotaxime and Augmentin, k-mitosis was not registered in dividing cells. Comparison of the spectrum of pathological mitoses in the variants of the experiment showed that the pathology ‘chromosome runaway/backlog’ in anaphase of mitosis dominates in all variants. An increase in the concentration of Augmentin and ampicillin caused the suppression of pathological processes in onion meristematic cells, a decrease in PM values was observed. An increase in Augmentin concentration does not affect the composition and spectrum of pathological mitoses; ampicillin has a decrease in the level of most of the recorded pathologies of mitosis.
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Ma, Li, Xiangshan Zhao, and Xueliang Zhu. "Mitosin/CENP-F in mitosis, transcriptional control, and differentiation." Journal of Biomedical Science 13, no. 2 (February 3, 2006): 205–13. http://dx.doi.org/10.1007/s11373-005-9057-3.
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Helfer, Hanspeter, and Amy S. Gladfelter. "AgSwe1p Regulates Mitosis in Response to Morphogenesis and Nutrients in Multinucleated Ashbya gossypii Cells." Molecular Biology of the Cell 17, no. 10 (October 2006): 4494–512. http://dx.doi.org/10.1091/mbc.e06-03-0215.
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Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. We have investigated what internal and external signals spatially direct mitosis within these hyphal cells. Mitoses are most common near cortical septin rings found at growing tips and branchpoints. In septin mutants, mitoses are no longer concentrated at branchpoints, suggesting that the septin rings function to locally promote mitosis near new branches. Similarly, cells lacking AgSwe1p kinase (a Wee1 homologue), AgHsl1p (a Nim1-related kinase), and AgMih1p phosphatase (the Cdc25 homologue that likely counteracts AgSwe1p activity) also have mitoses distributed randomly in the hyphae as opposed to at branchpoints. Surprisingly, however, no phosphorylation of the CDK tyrosine 18 residue, the conserved substrate of Swe1p kinases, was detected in normally growing cells. In contrast, abundant CDK tyrosine phosphorylation was apparent in starving cells, resulting in diminished nuclear density. This starvation-induced CDK phosphorylation is AgSwe1p dependent, and overexpressed AgSwe1p is sufficient to delay nuclei even in rich nutrient conditions. In starving cells lacking septins or AgSwe1p negative regulators, the nuclear density is further diminished compared with wild type. We have generated a model in which AgSwe1p may regulate mitosis in response to cell intrinsic morphogenesis cues and external nutrient availability in multinucleated cells.
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Nasuda, Shuhei, Bernd Friebe, and Bikram S. Gill. "Gametocidal Genes Induce Chromosome Breakage in the Interphase Prior to the First Mitotic Cell Division of the Male Gametophyte in Wheat." Genetics 149, no. 2 (June 1, 1998): 1115–24. http://dx.doi.org/10.1093/genetics/149.2.1115.
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Abstract Male gametogenesis was cytologically analyzed in wheat lines homozygous or hemizygous for gametocidal (Gc) factors with different modes of action. The first and second meiotic divisions in all lines were cytologically normal. The postmeiotic mitoses were normal in the homozygous lines; however, chromosome fragments and bridges were observed in the mitoses of the hemizygous lines. The morphology of the chromosome fragments suggests that the Gc genes induce chromosome breaks in the G1 phase prior to DNA synthesis of the first postmeiotic mitosis. The age of an anther was correlated with the frequency of aberrant second mitosis. Younger anthers contained a higher number of pollen undergoing normal second mitosis. This observation suggests that the arresting of the cell cycle occurs as the result of chromosome breaks during the first mitosis. Because chromosome bridges were more frequent than fragments in the second mitosis, breakage-fusion-bridge cycles possibly occurred during gametogenesis, which led to further chromosomal rearrangements. The Gc factors located on chromosomes 2S of Aegilops speltoides and 4Ssh of Ae. sharonensis induce severe chromosome breakage in pollen lacking them. However, the Gc factor on telosome 2CcL of Ae. cylindrica only induced chromosome breaks at a low frequency. The observed partial fertility of Gc lines is presumably due to cell cycle arrest and the competition among gametes with and without chromosome breakage.
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Solnica-Krezel, L., T. G. Burland, and W. F. Dove. "Variable pathways for developmental changes of mitosis and cytokinesis in Physarum polycephalum." Journal of Cell Biology 113, no. 3 (May 1, 1991): 591–604. http://dx.doi.org/10.1083/jcb.113.3.591.
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The development of a uninucleate ameba into a multinucleate, syncytial plasmodium in myxomycetes involves a change from the open, astral mitosis of the ameba to the intranuclear, anastral mitosis of the plasmodium, and the omission of cytokinesis from the cell cycle. We describe immunofluorescence microscopic studies of the amebal-plasmodial transition (APT) in Physarum polycephalum. We demonstrate that the reorganization of mitotic spindles commences in uninucleate cells after commitment to plasmodium formation, is completed by the binucleate stage, and occurs via different routes in individual developing cells. Most uninucleate developing cells formed mitotic spindles characteristic either of amebae or of plasmodia. However, chimeric mitotic figures exhibiting features of both amebal and plasmodial mitoses, and a novel star microtubular array were also observed. The loss of the ameba-specific alpha 3-tubulin and the accumulation of the plasmodium-specific beta 2-tubulin isotypes during development were not sufficient to explain the changes in the organization of mitotic spindles. The majority of uninucleate developing cells undergoing astral mitoses (amebal and chimeric) exhibited cytokinetic furrows, whereas cells with the anastral plasmodial mitosis exhibited no furrows. Thus, the transition from astral to anastral mitosis during the APT could be sufficient for the omission of cytokinesis from the cell cycle. However, astral mitosis may not ensure cytokinesis: some cells undergoing amebal or chimeric mitosis contained unilateral cytokinetic furrows or no furrow at all. These cells would, most probably, fail to divide. We suggest that a uninucleate committed cell undergoing amebal or chimeric mitosis can either divide or else form a binucleate cell. In contrast, a uninucleate cell with a mitotic spindle of the plasmodial type gives rise only to a binucleate cells. Further, the decision to enter mitosis after commitment to the APT is independent of the developmental changes in the organization of the mitotic spindle and cytokinesis.
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Staiber, Wolfgang. "Chromosome elimination in germ line – soma differentiation of Acricotopus lucidus (Diptera, Chironomidae)." Genome 49, no. 3 (March 1, 2006): 269–74. http://dx.doi.org/10.1139/g05-103.
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During germ line – soma differentiation in early syncytial embryonic development of the chironomid Acricotopus lucidus, a complement of supernumerary chromosomes, the so-called germ line limited chromosomes (Ks), is excluded from the future somatic nuclei in the course of elimination mitoses. The Ks lag behind in the equatorial plane, while the somatic chromosomes (Ss) segregate equally. After elimination mitoses, the Ks are only present in the pole cells, the primary germ cells. In the divisions before their elimination, the Ks frequently showed delayed separation of sister chromatids with high-frequency formation of anaphasic bridges and lagging in pole movement as detected in 4′,6-diamidino-2-phenylindole (DAPI)-stained squash preparations of early embryos. To determine if all of the Ks are eliminated in one step during a single mitosis, a fluorescence in situ hybridization (FISH) analysis of early embryonic divisions was performed using probes of germ line specific repetitive DNA sequences, which specifically label the Ks in their centromeric regions. In most cases, all of the Ks are lost in one mitosis; however, occasionally one or several of the Ks can escape their elimination by segregating and moving poleward together with the Ss. The escaping Ks will then be eliminated in one of the following mitoses. This clearly indicates that the specific conditions to eliminate Ks are not restricted to only one division. Possible mechanisms of elimination of Ks are discussed.Key words: germ line limited chromosomes, elimination mitosis, germ line – soma differentiation, FISH.
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Kuraś, M., and A. Malinowska. "Influence of 1-p-D-arabinofuranosylcytosine on mitotic activity of apical meristem of onion (Allium cepa L.) roots." Acta Societatis Botanicorum Poloniae 47, no. 1–2 (2015): 173–87. http://dx.doi.org/10.5586/asbp.1978.015.
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The influence of increasing cytosine arabinoside (ara-C) concentration (50, 100, 300 and 500 μg/ml) on the mitotic activity of the apical meristem of onion adventitious roots was investigated during 24-h incubation in ara-C and postincubation in water. Incubation in ara-C inhibits reversibly mitosis, the degree of inhibition being dependent on the concentration used. 50 μg/ml ara-C causes only a slight and transitional mitotic depression, while 100—500 μg/ml reduces the per cent of mitoses in various degrees after 12-h incubation whereas after 24 h all concentrations (100—500) reduce mitosis to the same level of about 2 per cent (80% inhibition). During postincubation in water there occurs after treatment with 100—500 μg/ml ara-C, a wave of highly synchronized mitoses with a peak after 12 h. The highest frequency of synchronized mitoses (60°/o) appeared in roots treated with 300 μg/ml ara-C. The main wave is preceded by a small one with a peak after 2-4 h of postincubation. This seems to be the consequence of phases S and G<sub>2</sub> inhibition by ara-C. It was found that under the influence of ara-C the per cent of mitoses with chromosome aberration and of cells with micronuclei increased only slightly.
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Chow, Zi Long, Aye Aye Thike, Hui Hua Li, Nur Diyana Md Nasir, Joe Poh Sheng Yeong, and Puay Hoon Tan. "Counting Mitoses With Digital Pathology in Breast Phyllodes Tumors." Archives of Pathology & Laboratory Medicine 144, no. 11 (March 9, 2020): 1397–400. http://dx.doi.org/10.5858/arpa.2019-0435-oa.
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Context.— Mitotic count is an important histologic criterion for grading and prognostication in phyllodes tumors (PTs). Counting mitoses is a routine practice for pathologists evaluating neoplasms, but different microscopes, variable field selection, and areas have led to possible misclassification. Objective.— To determine whether 10 high-power fields (HPFs) or whole slide mitotic counts correlated better with PT clinicopathologic parameters using digital pathology (DP). We also aimed to find out whether this study might serve as a basis for an artificial intelligence (AI) protocol to count mitosis. Design.— Representative slides were chosen from 93 cases of PTs diagnosed between 2014 and 2015. The slides were scanned and viewed with DP. Mitotic counting was conducted on the whole slide image, before choosing 10 HPFs and demarcating the tumor area in DP. Values of mitoses per millimeter squared were used to compare results between 10 HPFs and the whole slide. Correlations with clinicopathologic parameters were conducted. Results.— Both whole slide counting of mitoses and 10 HPFs had similar statistically significant correlation coefficients with grade, stromal atypia, and stromal hypercellularity. Neither whole slide mitotic counts nor mitoses per 10 HPFs showed statistically significant correlations with patient age and tumor size. Conclusions.— Accurate mitosis counting in breast PTs is important for grading. Exploring machine learning on digital whole slides may influence approaches to training, testing, and validation of a future AI algorithm.
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Bernard, Pascal, Kevin Hardwick, and Jean-Paul Javerzat. "Fission Yeast Bub1 Is a Mitotic Centromere Protein Essential for the Spindle Checkpoint and the Preservation of Correct Ploidy through Mitosis." Journal of Cell Biology 143, no. 7 (December 28, 1998): 1775–87. http://dx.doi.org/10.1083/jcb.143.7.1775.
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The spindle checkpoint ensures proper chromosome segregation by delaying anaphase until all chromosomes are correctly attached to the mitotic spindle. We investigated the role of the fission yeast bub1 gene in spindle checkpoint function and in unperturbed mitoses. We find that bub1+ is essential for the fission yeast spindle checkpoint response to spindle damage and to defects in centromere function. Activation of the checkpoint results in the recruitment of Bub1 to centromeres and a delay in the completion of mitosis. We show that Bub1 also has a crucial role in normal, unperturbed mitoses. Loss of bub1 function causes chromosomes to lag on the anaphase spindle and an increased frequency of chromosome loss. Such genomic instability is even more dramatic in Δbub1 diploids, leading to massive chromosome missegregation events and loss of the diploid state, demonstrating that bub1+ function is essential to maintain correct ploidy through mitosis. As in larger eukaryotes, Bub1 is recruited to kinetochores during the early stages of mitosis. However, unlike its vertebrate counterpart, a pool of Bub1 remains centromere-associated at metaphase and even until telophase. We discuss the possibility of a role for the Bub1 kinase after the metaphase–anaphase transition.
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Hand, A. R., and B. Ho. "Mitosis and Hypertrophy of Intercalated Duct Cells and Endothelial Cells in the Isoproterenol-treated Rat Parotid Gland." Journal of Dental Research 64, no. 8 (August 1985): 1031–38. http://dx.doi.org/10.1177/00220345850640080201.
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Chronic treatment of rats with isoproterenol (IPR) induces mitosis and differentiation of intercalated duct cells, and mitosis and hypertrophy of endothelial cells of the microvasculature in the parotid gland. Mitoses occurred in duct cells situated at or near the acinar-intercalated duct junction, and were most numerous after six IPR injections. These cells increased in size, contained numerous electronlucent granules, and were incorporated into the hypertrophic acini. The granules contained branching filamentous or finely reticulated material, and did not react with histochemical stains for carbohydrate. Capillary and venule endothelial cell mitoses were frequently seen after four to six IPR injections. The endothelial cells increased in thickness, contained abundant cytoplasmic organelles, lacked fenestrations, and had few pinocytotic vesicles. These results demonstrate the extensive nature of the response to chronic IPR treatment, and are consistent with the concept that the intercalated ducts have an important role in salivary gland physiology.
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Quintanar-Stephano, A., and C. Valverde-R. "Mitogenic effects of thyroxine and TRH on thyrotrophs and somatotrophs of the anterior pituitary gland in thyroidectomized rats." Journal of Endocrinology 154, no. 1 (July 1997): 149–53. http://dx.doi.org/10.1677/joe.0.1540149.
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Abstract The question of whether thyroxine (T4) and TRH have a mitogenic effect on pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated. Mitoses were counted in hematoxylin–eosin-stained or periodic acid–Schiff–hematoxylin-stained pituitary slides or immunostained for TSH or GH using male rats thyroidectomized for 5 months. Ten days before they were killed groups of rats were injected with different doses of T4 (0·5, 3 or 10 μg i.m. every second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days), or T4 plus TRH (same doses as above). Mitoses (stopped with colchicine) were counted in 1 mm2 areas at a magnification of × 1000. In thyroidectomized rats, mitoses were not significantly increased and treatment with TRH or 0·5 μg T4 alone in thyroidectomized rats did not affect mitotic counts. In thyroidectomized rats treated with higher doses of T4, mitoses were increased in a dose-dependent fashion. Simultaneous administration of TRH and T4 had a significant synergistic effect on pituitary mitoses in a T4 dose-dependent manner. The treatments also had differential effects on the relative percentages of cellular types in mitosis. Thus, 60% somatotrophs and 12·5% thyrotrophs were found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28·5% and 33·3% respectively. In thyroidectomized rats treated with low doses of T4, somatotrophs and thyrotrophs in mitosis increased to 38·4% and 80% respectively and, with simultaneous administration of a low dose of T4 plus TRH, although less effective than T4 alone, mitosis increased in somatotrophs and thyrotrophs to 11·1% and 54·5% respectively. A high dose of T4 alone did not increase the mitotic figures in somatotrophs (38·8%), while it diminished the percentage of thyrotrophs to 25%. The administration of high doses of T4 plus TRH had an opposite effect on the mitotic figures of somatotrophs and thyrotrophs and thus the percentage of somatotrophs increased to 50% while thyrotrophs decreased to 5·5%. Ten days of treatment with T4 were insufficient to reverse the histology to euthyroidism. It can be concluded that in long-standing hypothyroidism: (1) thyroid hormone replacement elicits a dose-dependent and differential proliferative response on pituitary thyrotrophs and somatotrophs, (2) TRH is devoid of mitogenic effects when administered alone and (3) the proliferative response of somatotrophs to T4 is enhanced by its co-administration with TRH, suggesting a permissive and/or synergistic effect of the thyroid hormone and TRH. Journal of Endocrinology (1997) 154, 149–153
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Douglas, Pauline, Ruiqiong Ye, Nicholas Morrice, Sébastien Britton, Laura Trinkle-Mulcahy, and Susan P. Lees-Miller. "Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis." Molecular and Cellular Biology 35, no. 15 (May 18, 2015): 2699–713. http://dx.doi.org/10.1128/mcb.01312-14.
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Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis.
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Wang, Richard R. C., Xiaomei Li, and N. Jerry Chatterton. "Cytological evidence for assortment mitosis leading to loss of heterozygosity in rice." Genome 49, no. 5 (May 1, 2006): 556–57. http://dx.doi.org/10.1139/g06-015.
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In the root meristem cells of the rice line AMR, which causes loss of heterozygosity in its hybrids, both normal and assortment mitoses were observed. During normal mitosis, chromosomes did not form homologous pairs at metaphase; all chromosomes lined up at the equatorial plate and 2 chromatids of each chromosome disjoined at the centromere and moved toward opposite poles. During assortment mitosis, varying numbers of paired homologues were observed at mitotic metaphase. Two groups of 12 chromosomes separated and moved towards the opposite poles of daughter cells with few chromosomes having their chromatids separated at anaphase. These observations support the proposed mechanism that is responsible for early genotype fixation in rice hybrids involving AMR.Key words: mitosis, homologous chromosome, genotype fixation, loss of heterozygosity, rice.
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Trinkaus, J. P. "The midblastula transition, the YSL transition and the onset of gastrulation in Fundulus." Development 116, Supplement (April 1, 1992): 75–80. http://dx.doi.org/10.1242/dev.116.supplement.75.
Full textAbstract:
The first signs of cell motility appear in Fundulus toward the end of cleavage, after cleavages 11 and 12. When blastomeres cease cleaving, their surfaces undulate and form blebs. At first, these blebbing cells remain in place. Gradually thereafter they begin movement, with blebs and fllolamellipodia serving as organs of locomotion. Non-motile cleaving blastomeres have thus differentiated into motile blastula cells. This transformation corresponds to the midblastula transition of amphibian embryos. Gastrulation in Fundulus begins with vegetalward contraction of the external yolk syncytial layer. This causes narrowing of the E- YSL and initiates the epibolic expansion of the blastoderm. Convergent movements of deep cells within the blastoderm begin toward the end of this contraction. The YSL forms as a result of invasion of the yolk cell cytoplasm by nuclei from open marginal blastomeres during cleavage. These YSL nuclei then undergo five metachronous divisions. After this, they divide no more. YSL contraction begins approximately 1.5 hours after cessation of these divisions (21–22°C). This cessation of nuclear divisions is preceded by a gradual decrease in rate. (1) The duration of each succeeding mitosis increases steadily and often some nuclei do not divide at mitosis V. (2) The duration of interphases between succeeding mitoses also increases, but to a much greater degree, and the longest interphase by far is the last one, I-FV, between mitoses FV and V. (3) The mitotic waves responsible for mitosis V move much more slowly than those for the first four mitoses and invariably decelerate. This gradual cessation of YSL nuclear divisions clearly sets the stage for the contraction of YSL cytoplasm and thus the beginning of gastrulation. We call this the YSL transition. It is not to be confused with the midblastula transition, which occurs 3–4 hours earlier. The MBT commences cytodifferentiation; the YSL transition commences morphogenesis.
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Ciemerych, Maria A., Bernard Maro, and Jacek Z. Kubiak. "Control of duration of the first two mitoses in a mouse embryo." Zygote 7, no. 4 (November 1999): 293–300. http://dx.doi.org/10.1017/s0967199499000696.
Full textAbstract:
The duration of M-phase is largely determined by the time necessary for the formation of a functional metaphase spindle and the correct alignment of all chromosomes on the metaphase plate. The spindle assembly checkpoint prevents the exit from M-phase before the proper alignment of all chromosomes on a metaphase plate in many cell types. In the present paper we show that the first mitotic M-phase of the mouse embryo lasts about 119 min, while the second embryonic M-phase lasts only about 70 min. Histone H1 kinase is activated rapidly during nuclear envelope breakdown in both mitoses. Its maximum, however, is followed by a plateau only during the first mitosis. In the second mitosis, the inactivation of histone H1 kinase activity follows its maximum directly. Histone H1 kinase is more stable in the cytoplasts obtained from mouse embryos during the first embryonic M-phase than during the second one. The stability of histone H1 kinase is greatly increased by the presence of the mitotic apparatus in both M-phases. The mitotic spindle assembly during the first and the second mitoses differs and the first metaphase spindle is stabilised during the period of maximum histone H1 kinase activity. These data show that an unknown developmentally regulated mechanism controls the duration of the two first mitoses in the mouse embryo.
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Sillem, Martin, Sylvia Timme, Peter Bronsert, Lioudmila Bogatyreva, Dieter Hauschke, Axel zur Hausen, Martin Werner, and Elmar Stickeler. "Anti-Phosphohistone H3-Positive Mitoses Are Linked to Pathological Response in Neoadjuvantly Treated Breast Cancer." Breast Care 12, no. 4 (2017): 244–50. http://dx.doi.org/10.1159/000463377.
Full textAbstract:
Background: We evaluated breast cancer (BC) core biopsies taken before neoadjuvant chemotherapy (NACT) by immunohistochemistry using anti-phosphohistone H3 (PHH3) antibody to determine mitosis, and correlated the results to clinicopathological data and histopathological regression of resected tumor specimens after NACT. Methods: 72 patients with either triple-negative (TN) or luminal type BC received NACT with epirubicin/cyclophosphamide (EC) and Taxotere®. Tumor regression was analyzed in resected specimens; pathological complete response (pCR) was achieved in 22.2%. Immunohistochemistry with PHH3 was performed on biopsy samples taken before treatment, and mitotic figures were evaluated in 10 high-power fields (HPF). Results: PHH3-detected mitoses correlated significantly with tumor grading (p = 0.001). TNBC showed > 10 PHH3-positive mitoses/10 HPF significantly more frequently than luminal type BC (p = 0.003). Tumors with > 10 PHH3-positive mitoses/10 HPF achieved pCR significantly more often than those with ≤ 10 PHH3-positive mitoses/10 HPF (p = 0.031). Even luminal type BC with > 10 PHH3-positive mitoses/10 HPF was associated significantly with pCR compared to luminal type BC with ≤ 10 PHH3-positive mitoses/10 HPF (p = 0.016). Conclusion: NACT with EC and Taxotere is suitable for strong proliferating TNBC and luminal BC (> 10 PHH3-positive mitoses/10 HPF). Immunohistochemical determination of mitoses using anti-PHH3 antibody is a simple and robust method for predicting therapy response to NACT in BC tissue.
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Schatten, Heide, Christopher N. Hueser, and Amitabha Chakrabarti. "Centrosome Structure And Function Is Altered By Experimental Manipulations With Formamide: Implications For Abnormal Cell Divisions During Cancer." Microscopy and Microanalysis 5, S2 (August 1999): 1286–87. http://dx.doi.org/10.1017/s1431927600019759.
Full textAbstract:
The formation of abnormal mitosis associated with cancer has been intriguing for many decades. While microtubules had been the focus of previous studies, recent research has focused on centrosomes, microtubule organizing centers which organize the mitotic apparatus during cell division. During normal mitosis centrosomes form two poles but in cancer, centrosomes can form three, four, or more poles, and organize tripolar, quadripolar, and multipolar mitoses, respectively. This has severe consequences for genomic stability because chromosomes are separated unequally to three, four, or more poles. This can result in aneuploidy and gene amplifications with multiple defects in cellular regulation. It can result in malignancy that is accompanied by cell cycle imbalances and abnormal cell proliferation. While radiation and chemical agents are known to damage DNA and can lead to cell cycle abnormalities, the damage of centrosome structure leading to abnormal mitosis deserves also consideration.
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Brodzki, P. "DNA synthesis in the nuclei of Pinus silvestris embryos during." Acta Societatis Botanicorum Poloniae 43, no. 4 (2015): 459–64. http://dx.doi.org/10.5586/asbp.1974.042.
Full textAbstract:
DNA synthesis starts earliest in the apical meristem of the shoot, and latest in the cotyledons. Mitoses appear simultaneously in the apical meristem and in the hypocotyl cortex. Synthesis continues in the mother cells of vascular elements and cotyledon parenchyma when mitosis ceases. In the cotyledons DNA synthesis is rather synchronous and leads to the elimination of 2 C nuclei.
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Cavallini, A., R. Cremonini, G. Cionini, and P. G. Cionini. "Polysomaty and somatic reduction in Phaseolus coccineus L." Genome 30, no. 5 (October 1, 1988): 671–76. http://dx.doi.org/10.1139/g88-113.
Full textAbstract:
By means of karyological, cytophotometric, and autoradiographic analyses it has been shown that, owing to alterations in the DNA synthesis – mitosis sequence, cells with different nuclear conditions are continuously formed de novo and proliferate in Phaseolus coccineus meristems. Besides diploid cells, the following also occur: (i) polyploid cells as the result of chromosome endoreduplication followed by mitosis; (ii) haploid cells as the result of the separation of the two groups of homologous chromosomes in cells that have omitted DNA reduplication; and (iii) since haploid cells undergo chromosome endoreduplication and divide, isogenic cells can be produced. Diploid mitoses alone are present in the meristems of early embryos; haploid mitoses first appear in both root and shoot meristems with increasing embryo development, followed later by cells undergoing chromosome endoreduplication. The study of the root apex has shown that neither polyploid nor reduced cells occur with the same frequency in its various portions. These results are discussed in relation to pertinent data in the literature and the mechanisms responsible for the occurrence of polysomaty and somatic reduction are suggested.Key words: isogenic cells, Phaseolus coccineus, polysomaty, somatic reduction.
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Su, Tin Tin, and Patrick H. O'Farrell. "Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Mitotic Cycles." Journal of Cell Biology 139, no. 1 (October 6, 1997): 13–21. http://dx.doi.org/10.1083/jcb.139.1.13.
Full textAbstract:
Minichromosome maintenance (MCM) proteins are essential DNA replication factors conserved among eukaryotes. MCMs cycle between chromatin bound and dissociated states during each cell cycle. Their absence on chromatin is thought to contribute to the inability of a G2 nucleus to replicate DNA. Passage through mitosis restores the ability of MCMs to bind chromatin and the ability to replicate DNA. In Drosophila early embryonic cell cycles, which lack a G1 phase, MCMs reassociate with condensed chromosomes toward the end of mitosis. To explore the coupling between mitosis and MCM–chromatin interaction, we tested whether this reassociation requires mitotic degradation of cyclins. Arrest of mitosis by induced expression of nondegradable forms of cyclins A and/or B showed that reassociation of MCMs to chromatin requires cyclin A destruction but not cyclin B destruction. In contrast to the earlier mitoses, mitosis 16 (M16) is followed by G1, and MCMs do not reassociate with chromatin at the end of M16. dacapo mutant embryos lack an inhibitor of cyclin E, do not enter G1 quiescence after M16, and show mitotic reassociation of MCM proteins. We propose that cyclin E, inhibited by Dacapo in M16, promotes chromosome binding of MCMs. We suggest that cyclins have both positive and negative roles in controlling MCM–chromatin association.
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Su, Tin Tin, and Patrick H. O'Farrell. "Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Endoreplication Cycles." Journal of Cell Biology 140, no. 3 (February 9, 1998): 451–60. http://dx.doi.org/10.1083/jcb.140.3.451.
Full textAbstract:
Minichromosome maintenance (MCM) proteins are essential eukaryotic DNA replication factors. The binding of MCMs to chromatin oscillates in conjunction with progress through the mitotic cell cycle. This oscillation is thought to play an important role in coupling DNA replication to mitosis and limiting chromosome duplication to once per cell cycle. The coupling of DNA replication to mitosis is absent in Drosophila endoreplication cycles (endocycles), during which discrete rounds of chromosome duplication occur without intervening mitoses. We examined the behavior of MCM proteins in endoreplicating larval salivary glands, to determine whether oscillation of MCM–chromosome localization occurs in conjunction with passage through an endocycle S phase. We found that MCMs in polytene nuclei exist in two states: associated with or dissociated from chromosomes. We demonstrate that cyclin E can drive chromosome association of DmMCM2 and that DNA synthesis erases this association. We conclude that mitosis is not required for oscillations in chromosome binding of MCMs and propose that cycles of MCM–chromosome association normally occur in endocycles. These results are discussed in a model in which the cycle of MCM–chromosome associations is uncoupled from mitosis because of the distinctive program of cyclin expression in endocycles.
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Gupta, Mita, Deborah Trott, and Andrew C. G. Porter. "Rescue of a Human Cell Line from Endogenous Cdk1 Depletion by Cdk1 Lacking Inhibitory Phosphorylation Sites." Journal of Biological Chemistry 282, no. 7 (December 12, 2006): 4301–9. http://dx.doi.org/10.1074/jbc.m607910200.
Full textAbstract:
Cells that transiently overexpress cyclin-dependent kinase 1 lacking inhibitory phosphorylation sites (Cdk1-AF) undergo premature and catastrophic mitosis, reflecting the key role for Cdk1 in promoting a timely transit from G2 into mitosis. Conversely, cells depleted of Cdk1 undergo repeated S phases without intervening mitoses (endoreduplication), reflecting a role for Cdk1 in preventing premature S phases. It is not known how Cdk1 prevents entry into S phase at times in G2 when it does not promote mitosis. Also uncertain is the extent of redundancy between inhibitory phosphorylation and other mechanisms for controlling Cdk1 activity. We describe here human cells that not only tolerate stable Cdk1-AF expression but also rely on it for survival when endogenous Cdk1 is depleted. When residual endogenous Cdk1 expression is further depleted, however, proliferation of Cdk1-AF-rescued cells is inhibited. Interestingly, this inhibition is not accompanied by endoreduplication. These results are consistent with a two-threshold model for Cdk1 kinase activity, one for suppressing endoreduplication and one for promoting mitosis. They also indicate that inhibitory phosphorylation is indispensable for only a fraction of the total cellular complement of Cdk1.
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Su, Tin Tin, Devin H. Parry, Bryon Donahoe, Cheng-Ting Chien, Patrick H. O’Farrell, and Amanda Purdy. "Cell cycle roles for two 14-3-3 proteins during Drosophila development." Journal of Cell Science 114, no. 19 (October 1, 2001): 3445–54. http://dx.doi.org/10.1242/jcs.114.19.3445.
Full textAbstract:
Drosophila 14-3-3ε and 14-3-3ζ proteins have been shown to function in RAS/MAP kinase pathways that influence the differentiation of the adult eye and the embryo. Because 14-3-3 proteins have a conserved involvement in cell cycle checkpoints in other systems, we asked (1) whether Drosophila 14-3-3 proteins also function in cell cycle regulation, and (2) whether cell proliferation during Drosophila development has different requirements for the two 14-3-3 proteins. We find that antibody staining for 14-3-3 family members is cytoplasmic in interphase and perichromosomal in mitosis. Using mutants of cyclins, Cdk1 and Cdc25string to manipulate Cdk1 activity, we found that the localization of 14-3-3 proteins is coupled to Cdk1 activity and cell cycle stage. Relocalization of 14-3-3 proteins with cell cycle progression suggested cell-cycle-specific roles. This notion is confirmed by the phenotypes of 14-3-3ε and 14-3-3ζ mutants: 14-3-3ε is required to time mitosis in undisturbed post-blastoderm cell cycles and to delay mitosis following irradiation; 14-3-3ζ is required for normal chromosome separation during syncytial mitoses. We suggest a model in which 14-3-3 proteins act in the undisturbed cell cycle to set a threshold for entry into mitosis by suppressing Cdk1 activity, to block mitosis following radiation damage and to facilitate proper exit from mitosis.
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Gillett, Emily S., Christopher W. Espelin, and Peter K. Sorger. "Spindle checkpoint proteins and chromosome–microtubule attachment in budding yeast." Journal of Cell Biology 164, no. 4 (February 9, 2004): 535–46. http://dx.doi.org/10.1083/jcb.200308100.
Full textAbstract:
Accurate chromosome segregation depends on precise regulation of mitosis by the spindle checkpoint. This checkpoint monitors the status of kinetochore–microtubule attachment and delays the metaphase to anaphase transition until all kinetochores have formed stable bipolar connections to the mitotic spindle. Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1–3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3. In animal cells, all known spindle checkpoint proteins are recruited to kinetochores during normal mitoses. In contrast, we show that whereas Saccharomyces cerevisiae Bub1p and Bub3p are bound to kinetochores early in mitosis as part of the normal cell cycle, Mad1p and Mad2p are kinetochore bound only in the presence of spindle damage or kinetochore lesions that interfere with chromosome–microtubule attachment. Moreover, although Mad1p and Mad2p perform essential mitotic functions during every division cycle in mammalian cells, they are required in budding yeast only when mitosis goes awry. We propose that differences in the behavior of spindle checkpoint proteins in animal cells and budding yeast result primarily from evolutionary divergence in spindle assembly pathways.
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Kato, Y., and L. M. Riddiford. "The role of 20-hydroxyecdysone in stimulating epidermal mitoses during the laval-pupal transformation of the tobacco hornworm, Manduca sexta." Development 100, no. 2 (June 1, 1987): 227–36. http://dx.doi.org/10.1242/dev.100.2.227.
Full textAbstract:
Temporal and regional changes in mitotic frequency were examined in the dorsal epidermis of the fourth and fifth abdominal segments of Manduca sexta during metamorphosis. Mitoses occurred only in the middle intrasegmental region, but not in the segmental margins. The mitoses began early on day 5 and rose to maximum of 2á6–4á6% about 10h later. When the integument from day 4 (wandering) larvae was cultured in Grace's medium containing 0.3 to 1μgml-1 20-hydroxyecdysone (20HE), the mitotic index increased with a peak at 18–24h exposure approximately equal to that found in situ. The level of 20HE required to initiate mitoses was similar to that found in vivo during the beginning of the prepupal rise in ecdysteroid and therefore is likely to be the signal for these cells to decrease their ploidy level of 4–32C to 2–8C at this time. The polyploid cells had larger mitotic figures and required a longer exposure to 20-hydroxyecdysone to initiate mitosis. Some multipolar mitotic figures were observed.
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Skok, Anna V., Igor’ N. Glazun, and Vladimir N. Sorokopudov. "Influence of Chronic Ionizing Radiation on the Variability of Mitotic Activity of Pinus sylvestris L. Tissues." Lesnoy Zhurnal (Forestry Journal), no. 1 (February 9, 2021): 112–19. http://dx.doi.org/10.37482/0536-1036-2021-1-112-119.
Full textAbstract:
The development of nuclear power engineering will increase in the future, due to the continued likelihood of radionuclides entering the environment. The relevance of studying the genetic material of conifers as a reliable bioindicator was revealed. It is known that under the influence of ionizing radiation there is an accumulation of genetic abnormalities in pine (Pinus sylvestris L.) progeny. The stages of gametogenesis, zygotes and young seedlings of plant organisms are most sensitive to ionizing radiation. It is important to determine the variability of the mitotic index (MI) of tissues of Scots pine (Pinus sylvestris L.) progeny in areas with different levels of ionizing radiation, including in the exclusion zone. The exposure dose rate was measured at the soil level and 1 m from the ground surface. Germination of seeds was carried out in a thermostat on wet filter paper. Roots of seedlings 0.5–1 cm long were fixed in a mixture of 96 % ethanol and glacial acetic acid. Root staining was carried out in a solution of acetocarmine. Tissue softening was carried out with a strong chloral hydrate solution. The total number of dividing cells, as well as pathological mitoses (PM) were counted on squash preparations using a microscope. The mitotic index and the duration of the phases of mitosis were determined. An increase in the level of radioactive contamination increases the cell division rate in prophase, anaphase, and telophase, but decreases the duration of metaphase, and also changes the relative duration of mitosis phases. With an increase in the exposure dose rate, the number of pathological mitoses naturally increases. The spectrum of mitosis disorders is represented by various abnormalities of the chromosome apparatus in anaphase: exit and lagging of chromosomes, bridges. Herewith, the number of anaphases with bridges increases significantly with simultaneous exit and lagging of chromosomes.
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HOŞGÖR, Kubilay. "Dil ve Mitosun Dünyası: Kültürün Arkeolojisine İlişkin Bir İnceleme." Ankara Üniversitesi Dil ve Tarih-Coğrafya Fakültesi Dergisi 58, no. 1 (October 5, 2018): 327. http://dx.doi.org/10.33171/dtcfjournal.2018.58.1.17.
Full textAbstract:
Bu çalışmada Ernst Cassirer’in sembolik formlar sistemine odaklanarak onun mitos analizini inceliyorum. Onun mitos kavrayışını dilin ortaya çıkışında mitsel bilinç formlarının etkisini belirlemeyi denerken de benimsiyorum. Bu çerçeve içinde Cassirer ile Chomsky’nin dile bakışlarını karşılaştırıyorum. Dilin mitos ile ilgisi bakımından ele alınınca, Chomsky’nin teorisinin kültürel farklılaşmaları açıklamada zorlanacağını ileri sürüyorum. Çünkü o, dil fenomenlerinin bütünüyle intrinsik olduklarını iddia eder. Bu iddia bana göre arkasında nedensellik beklentisini gizlemektedir. Bu beklenti geleceğin geçmişe uygun gerçekleşeceği sayıltısını içerir. Ne var ki, bana göre dilin köklerine inmek üzere mitsel bilincin dünyasına yöneldiğimizde, bu beklenti bizi yanılgılar içinde bırakır. Dünyaya ait olanı türümüzün bir karakteristiği sanma yanılgısına yol açabilir. Bu noktadan hareketle, dilin analizini zihin-beden problemi ile ilgisi açısından ele alıyorum. Bu problemin ontolojik karakterde olduğunu ve ontolojik kategorilerle mitosun dünyasını kavramaya çalışmanın yanılgıya yol açacağını ileri sürüyorum. Çünkü görünüşlerin dünyası olarak mitosun dünyası fenomenolojik karakterdedir. Bu sorunu burada şu temel iddiayı ortaya koyabilmek için ele alıyorum: Mitsel ifade fonksiyonu teorik bilincimize zaman zaman etki etmeyi sürdürür. Bunu en belirgin biçimde bir duygunun fizyonomik ifadesinde yaşarız. Bu nasıl mümkün oluyor? Bu soruya yanıt bulma girişimi bizi her zaman homunculus yanılgısına sürükler. Bu yanılgının nedensellik beklentisine dayandığını ima ediyorum. Bu türden bir beklenti içinde evrimsel perspektifin mitik bilinci doğru kavrayamayacağı fikrine dönüyorum yeniden. Bu çalışmanın finalinde ise teleolojik bir perspektifi önererek açıklıyorum.
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Lorson, Monique A., H. Robert Horvitz, and Sander van den Heuvel. "LIN-5 Is a Novel Component of the Spindle Apparatus Required for Chromosome Segregation and Cleavage Plane Specification in Caenorhabditis elegans." Journal of Cell Biology 148, no. 1 (January 10, 2000): 73–86. http://dx.doi.org/10.1083/jcb.148.1.73.
Full textAbstract:
Successful divisions of eukaryotic cells require accurate and coordinated cycles of DNA replication, spindle formation, chromosome segregation, and cytoplasmic cleavage. The Caenorhabditis elegans gene lin-5 is essential for multiple aspects of cell division. Cells in lin-5 null mutants enter mitosis at the normal time and form bipolar spindles, but fail chromosome alignment at the metaphase plate, sister chromatid separation, and cytokinesis. Despite these defects, cells exit from mitosis without delay and progress through subsequent rounds of DNA replication, centrosome duplication, and abortive mitoses. In addition, early embryos that lack lin-5 function show defects in spindle positioning and cleavage plane specification. The lin-5 gene encodes a novel protein with a central coiled-coil domain. This protein localizes to the spindle apparatus in a cell cycle- and microtubule-dependent manner. The LIN-5 protein is located at the centrosomes throughout mitosis, at the kinetochore microtubules in metaphase cells, and at the spindle during meiosis. Our results show that LIN-5 is a novel component of the spindle apparatus required for chromosome and spindle movements, cytoplasmic cleavage, and correct alternation of the S and M phases of the cell cycle.
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Januschke, Jens, and Cayetano Gonzalez. "The interphase microtubule aster is a determinant of asymmetric division orientation in Drosophila neuroblasts." Journal of Cell Biology 188, no. 5 (March 1, 2010): 693–706. http://dx.doi.org/10.1083/jcb.200905024.
Full textAbstract:
The mechanisms that maintain the orientation of cortical polarity and asymmetric division unchanged in consecutive mitoses in Drosophila melanogaster neuroblasts (NBs) are unknown. By studying the effect of transient microtubule depolymerization and centrosome mutant conditions, we have found that such orientation memory requires both the centrosome-organized interphase aster and centrosome-independent functions. We have also found that the span of such memory is limited to the last mitosis. Furthermore, the orientation of the NB axis of polarity can be reset to any angle with respect to the surrounding tissue and is, therefore, cell autonomous.
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Di Bari, Maria, Vanessa Tombolillo, Francesco Alessandrini, Claudia Guerriero, Mario Fiore, Italia Anna Asteriti, Emilia Castigli, et al. "M2 Muscarinic Receptor Activation Impairs Mitotic Progression and Bipolar Mitotic Spindle Formation in Human Glioblastoma Cell Lines." Cells 10, no. 7 (July 8, 2021): 1727. http://dx.doi.org/10.3390/cells10071727.
Full textAbstract:
Background: Glioblastoma multiforme (GBM) is characterized by several genetic abnormalities, leading to cell cycle deregulation and abnormal mitosis caused by a defective checkpoint. We previously demonstrated that arecaidine propargyl ester (APE), an orthosteric agonist of M2 muscarinic acetylcholine receptors (mAChRs), arrests the cell cycle of glioblastoma (GB) cells, reducing their survival. The aim of this work was to better characterize the molecular mechanisms responsible for this cell cycle arrest. Methods: The arrest of cell proliferation was evaluated by flow cytometry analysis. Using immunocytochemistry and time-lapse analysis, the percentage of abnormal mitosis and aberrant mitotic spindles were assessed in both cell lines. Western blot analysis was used to evaluate the modulation of Sirtuin2 and acetylated tubulin—factors involved in the control of cell cycle progression. Results: APE treatment caused arrest in the M phase, as indicated by the increase in p-HH3 (ser10)-positive cells. By immunocytochemistry, we found a significant increase in abnormal mitoses and multipolar mitotic spindle formation after APE treatment. Time-lapse analysis confirmed that the APE-treated GB cells were unable to correctly complete the mitosis. The modulated expression of SIRT2 and acetylated tubulin in APE-treated cells provides new insights into the mechanisms of altered mitotic progression in both GB cell lines. Conclusions: Our data show that the M2 agonist increases aberrant mitosis in GB cell lines. These results strengthen the idea of considering M2 acetylcholine receptors a novel promising therapeutic target for the glioblastoma treatment.
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Dawidowicz-Grzegorzewska, A. "Effects of water soluble oncostatic fraction from Rheum officinale Baill. rhizomes on Allium cepa root meristem. I. The mitotic activity." Acta Societatis Botanicorum Poloniae 45, no. 4 (2015): 429–43. http://dx.doi.org/10.5586/asbp.1976.038.
Full textAbstract:
The effects of the oncostatic extracts from <i>Rheum officinale</i> rhizomes on the activity of meristematic cells from <i>Allium cepa</i> roots were investigated. A statistically significant decrease of the IM value was noted as well as of the total number of mitoses during incubation. The disturbances in the course of mitosis and cytokinesis are described and discussed. The kind of disturbances during postincubation points to damage of the S and G2 phases of the interphase nuclei. Cytochemical and autoradiographic studies demonstrated a diminished intensity of staining of DNA and RNA and inhibition of DNA synthesis during incubation, this leading in tum to a lower intensity of protein staining in postincubation. Disturbances in mitosis and cytokinesis after treatment wth 2,6-dihydroxyantraquinone, supposed to be the antimitotically active compound of the extract, are the same as those produced by the total water soluble fraction.
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Leung, Hei, and P. H. Williams. "Nuclear division and chromosome behavior during meiosis and ascosporogenesis in Pyricularia oryzae." Canadian Journal of Botany 65, no. 1 (January 1, 1987): 112–23. http://dx.doi.org/10.1139/b87-016.
Full textAbstract:
Meiosis and mitoses during ascosporogenesis in fertile mating strains of Pyricularia oryzae Cavara (teleomorph: Magnaporthe grisea) were studied using a propionic–iron–hematoxylin procedure which stained chromosomes, nucleolus, and spindle pole bodies. Meioses and mitoses in P. oryzae resembled those in other ascomycetes. Zygotene chromosomes were highly contracted followed by elongation at pachytene when close pairings of homologous chromosomes were observed. Nucleoli attained a maximum diameter of 3.8 μm during pachytene. Nucleolar growth was accompanied by a rapid growth of the ascus. Chromosome lengths varied among pachytene cells, with the longest chromosome averaging 8.5 and the smallest 2.9 μm. Telomeric knobs and chromomeres were discernible on fully extended pachytene chromosomes. Six chromosomes were observed at pachytene and diakinesis, and during metaphase of ascospore mitosis. Chromosome movement at meiotic and mitotic anaphase was asynchronous, resulting in lagging chromosomes. Electron microscopic observations revealed spindle pole bodies associated with profusion and early meiotic prophase nuclei. In pachytene nuclei, 50 nm wide structures resembling synaptonemal complexes were observed.
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Lin, Bor-Yaw, and E. H. Coe Jr. "Monosomy and trisomy induced by the r-x1 deletion in maize, and associated effects on endosperm development." Canadian Journal of Genetics and Cytology 28, no. 5 (October 1, 1986): 831–34. http://dx.doi.org/10.1139/g86-115.
Full textAbstract:
The r-x1 deficiency on chromosome 10 of maize conditions nondisjunction during embryo sac development. Variations in kernel size associated with r-x1 are found to be correlated with aneuploidy, both monosomy and trisomy, in the embryo. Among a sample of 70 normal-sized kernels only 10% had aneuploid embryos (4 monosomies, 3 trisomies), while 41 selected small kernels had 44% aneuploids (10 monosomies, 1 double monosomic, 7 trisomics) and 32 medium kernels also had 44% aneuploids (1 monosomic, 12 trisomics, 1 triple trisomic). On the assumption that reduced kernel size is due to aneuploidy in the endosperm following nondisjunction at one of the embryo sac mitoses, the observed proportion of hypoploid:hyperploid:euploid embryos among small kernels is inconsistent with nondisjunction at the first or third mitoses but fits well the expectation for nondisjunction occurring at the second mitosis. Nondisjunction at this division leads to both corresponding and noncorresponding constitutions between the embryo, and endosperm.Key words: Zea, aneuploidy, embryo sac, nondisjunction.
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Mehsen, Haytham, Vincent Boudreau, Damien Garrido, Mohammed Bourouh, Myreille Larouche, Paul S. Maddox, Andrew Swan, and Vincent Archambault. "PP2A-B55 promotes nuclear envelope reformation after mitosis in Drosophila." Journal of Cell Biology 217, no. 12 (October 11, 2018): 4106–23. http://dx.doi.org/10.1083/jcb.201804018.
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As a dividing cell exits mitosis and daughter cells enter interphase, many proteins must be dephosphorylated. The protein phosphatase 2A (PP2A) with its B55 regulatory subunit plays a crucial role in this transition, but the identity of its substrates and how their dephosphorylation promotes mitotic exit are largely unknown. We conducted a maternal-effect screen in Drosophila melanogaster to identify genes that function with PP2A-B55/Tws in the cell cycle. We found that eggs that receive reduced levels of Tws and of components of the nuclear envelope (NE) often fail development, concomitant with NE defects following meiosis and in syncytial mitoses. Our mechanistic studies using Drosophila cells indicate that PP2A-Tws promotes nuclear envelope reformation (NER) during mitotic exit by dephosphorylating BAF and suggests that PP2A-Tws targets additional NE components, including Lamin and Nup107. This work establishes Drosophila as a powerful model to further dissect the molecular mechanisms of NER and suggests additional roles of PP2A-Tws in the completion of meiosis and mitosis.
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Hawkins, N. C., J. Thorpe, and T. Schupbach. "Encore, a gene required for the regulation of germ line mitosis and oocyte differentiation during Drosophila oogenesis." Development 122, no. 1 (January 1, 1996): 281–90. http://dx.doi.org/10.1242/dev.122.1.281.
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During Drosophila oogenesis, a stem cell daughter undergoes precisely four rounds of mitosis to generate a cyst of 16 cells interconnected by cytoplasmic bridges. One of the cells becomes the oocyte while the remaining 15 cells differentiate as nurse cells. We hve identified a gene, encore, that is involved both in regulating the number of germline mitoses and in the process of oocyte differentation. Mutations in encore result in exactly one extra round of mitosis in the germline. Genetic and molecular studies indicate that this mitotic defect may be mediated through the gene bag-of-marbles. The isolation and characterization of multiple alleles of encore revealed that they were all temperature sensitive for this phenotype. Mutations in encore also affect the process of oocyte differentiation. Egg chambers are produced in which the oocyte nucleus has undergone endoreplication often resulting in the formation of 16 nurse cells. We argue that these two phenotypes produced by mutations in encore represent two independent requirements for encore during oogenesis.
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Giordano, Manuela, Lucia Infantino, Marco Biggiogera, Alessandra Montecucco, and Giuseppe Biamonti. "Heat Shock Affects Mitotic Segregation of Human Chromosomes Bound to Stress-Induced Satellite III RNAs." International Journal of Molecular Sciences 21, no. 8 (April 17, 2020): 2812. http://dx.doi.org/10.3390/ijms21082812.
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Heat shock activates the transcription of arrays of Satellite III (SatIII) DNA repeats in the pericentromeric heterochromatic domains of specific human chromosomes, the longest of which is on chromosome 9. Long non-coding SatIII RNAs remain associated with transcription sites where they form nuclear stress bodies or nSBs. The biology of SatIII RNAs is still poorly understood. Here, we show that SatIII RNAs and nSBs are detectable up to four days after thermal stress and are linked to defects in chromosome behavior during mitosis. Heat shock perturbs the execution of mitosis. Cells reaching mitosis during the first 3 h of recovery accumulate in pro-metaphase. During the ensuing 48 h, this block is no longer detectable; however, a significant fraction of mitoses shows chromosome segregation defects. Notably, most of lagging chromosomes and chromosomal bridges are bound to nSBs and contain arrays of SatIII DNA. Disappearance of mitotic defects at the end of day 2 coincides with the processing of long non-coding SatIII RNAs into a ladder of small RNAs associated with chromatin and ranging in size from 25 to 75 nt. The production of these molecules does not rely on DICER and Argonaute 2 components of the RNA interference apparatus. Thus, massive transcription of SatIII DNA may contribute to chromosomal instability.
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Paddy, M. R., H. Saumweber, D. A. Agard, and J. W. Sedat. "Time-resolved, in vivo studies of mitotic spindle formation and nuclear lamina breakdown in Drosophila early embryos." Journal of Cell Science 109, no. 3 (March 1, 1996): 591–607. http://dx.doi.org/10.1242/jcs.109.3.591.
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Time-resolved, two-component, three-dimensional fluorescence light microscopy imaging in living Drosophila early embryos is used to demonstrate that a large fraction of the nuclear envelope lamins remain localized to a rim in the nuclear periphery until well into metaphase. The process of lamin delocalization and dispersal, typical of ‘open’ forms of mitosis, does not begin until about the time the final, metaphase geometry of the mitotic spindle is attained. Lamin dispersal is completed about the time that the chromosomal movements of anaphase begin. This pattern of nuclear lamina breakdown appears to be intermediate between traditional designations of ‘open’ and ‘closed’ mitoses. These results thus clarify earlier observations of lamins in mitosis in fixed Drosophila early embryos, clearly showing that the observed lamin localization does not result from a structurally defined ‘spindle envelope’ that persists throughout mitosis. During this extended time interval of lamin localization in the nuclear periphery, the lamina undergoes an extensive series of structural rearrangements that are closely coupled to, and likely driven by, the movements of the centrosomes and microtubules that produce the mitotic spindle. Furthermore, throughout this time the nuclear envelope structure is permeable to large macromolecules, which are excluded in interphase. While the functional significance of these structural dynamics is not yet clear, it is consistent with a functional role for the lamina in mitotic spindle formation.
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van der Giezen, Mark, Gloria León-Avila, and Jorge Tovar. "Characterization of chaperonin 10 (Cpn10) from the intestinal human pathogen Entamoeba histolytica." Microbiology 151, no. 9 (September 1, 2005): 3107–15. http://dx.doi.org/10.1099/mic.0.28068-0.
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Entamoeba histolytica is the causative agent of amoebiasis, a poverty-related disease that kills an estimated 100 000 people each year. E. histolytica does not contain ‘standard mitochondria’, but harbours mitochondrial remnant organelles called mitosomes. These organelles are characterized by the presence of mitochondrial chaperonin Cpn60, but little else is known about the functions and molecular composition of mitosomes. In this study, a gene encoding molecular chaperonin Cpn10 – the functional partner of Cpn60 – was cloned, and its structure and expression were characterized, as well as the cellular localization of its encoded protein. The 5′ untranslated region of the gene contains all of the structural promoter elements required for transcription in this organism. The amoebic Cpn10, like Cpn60, is not significantly upregulated upon heat-shock treatment. Computer-assisted protein modelling, and specific antibodies against Cpn10 and Cpn60, suggest that both proteins interact with each other, and that they function in the same intracellular compartment. Thus, E. histolytica appears to have retained at least two of the key molecular components required for the refolding of imported mitosomal proteins.
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Dovey, Michael, E. Elizabeth Patton, Teresa Bowman, Trista North, Wolfram Goessling, Yi Zhou, and Leonard I. Zon. "Topoisomerase IIα Is Required for Embryonic Development and Liver Regeneration in Zebrafish." Molecular and Cellular Biology 29, no. 13 (April 20, 2009): 3746–53. http://dx.doi.org/10.1128/mcb.01684-08.
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ABSTRACT Topoisomerases solve the topological problems encountered by DNA throughout the lifetime of a cell. Topoisomerase IIα, which is highly conserved among eukaryotes, untangles replicated chromosomes during mitosis and is absolutely required for cell viability. A homozygous lethal mutant, can4, was identified in a screen to identify genes important for cell proliferation in zebrafish by utilizing an antibody against a mitosis-specific marker, phospho-histone H3. Mutant embryos have a decrease in the number of proliferating cells and display increases in DNA content and apoptosis, as well as mitotic spindle defects. Positional cloning revealed that the genetic defect underlying these phenotypes was the result of a mutation in the zebrafish topoisomerase IIα (top2a) gene. top2a was found to be required for decatenation but not for condensation in embryonic mitoses. In addition to being required for development, top2a was found to be a haploinsufficient regulator of adult liver regrowth in zebrafish. Regeneration analysis of other adult tissues, including fins, revealed no heterozygous phenotype. Our results confirm a conserved role for TOP2A in vertebrates as well as a dose-sensitive requirement for top2a in adults.
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Jia, Xianqing, Qijun Zhang, Mengmeng Jiang, Ju Huang, Luyao Yu, Milton Brian Traw, Dacheng Tian, Laurence D. Hurst, and Sihai Yang. "Mitotic gene conversion can be as important as meiotic conversion in driving genetic variability in plants and other species without early germline segregation." PLOS Biology 19, no. 3 (March 22, 2021): e3001164. http://dx.doi.org/10.1371/journal.pbio.3001164.
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In contrast to common meiotic gene conversion, mitotic gene conversion, because it is so rare, is often ignored as a process influencing allelic diversity. We show that if there is a large enough number of premeiotic cell divisions, as seen in many organisms without early germline sequestration, such as plants, this is an unsafe position. From examination of 1.1 million rice plants, we determined that the rate of mitotic gene conversion events, per mitosis, is 2 orders of magnitude lower than the meiotic rate. However, owing to the large number of mitoses between zygote and gamete and because of long mitotic tract lengths, meiotic and mitotic gene conversion can be of approximately equivalent importance in terms of numbers of markers converted from zygote to gamete. This holds even if we assume a low number of premeiotic cell divisions (approximately 40) as witnessed inArabidopsis. A low mitotic rate associated with long tracts is also seen in yeast, suggesting generality of results. For species with many mitoses between each meiotic event, mitotic gene conversion should not be overlooked.
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Murray, Andrew W. "Never-in-mitosis in mitosis." Nature 353, no. 6346 (October 1991): 701–2. http://dx.doi.org/10.1038/353701a0.
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KALAEV, Vladislav N., Svetlana S. KARPOVA, Firas R. H. AL-HACHAMI, Irina V. IGNATOVA, and Vasiliy A. SLAVSKIY. "Cytogenetic polymorphism of seed progeny of walnut (Juglans regia L.) during introduction in the Central Chernozem Region." Notulae Botanicae Horti Agrobotanici Cluj-Napoca 48, no. 3 (August 29, 2020): 1519–33. http://dx.doi.org/10.15835/nbha48311941.
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We studied the cytogenetic characteristics of the seed progeny of the walnut (Juglans regia L.) trees introduced to and grown within the territory of the Central Russian Upland. Three seedling groups with polymorphic cytogenetic characteristics were revealed: mutable (with a high level of pathological mitoses), low mutable (with a low level of cytogenetic disturbances), and intermediate groups. Cytogenetic characteristics (mitotic activity, parts of cells at various stages of mitosis, the level and spectrum of pathological mitoses, sizes of nucleoli and the spectrum of their types, the occurrence of cells with a persistent nucleolus in the stages of meta-, ana-, and telophase) in each of the selected groups were described; homeostatic mechanisms at the cellular level were discussed. The sizes of polymorphic groups were established. The small number of seedlings with a high level of cytogenetic disturbances (7.5%) and the predominance of seedlings with medium (70%) and low (22.5%) values of pathological mitoses indicated a high degree of adaptation of the introduced walnut mother trees to the environmental conditions of the Central Russian Upland. Predictors for assigning any seedling to one of the selected model groups (mutable or low mutable) were established using ROC analysis methods. The obtained data on the qualitative and quantitative polymorphism of cytogenetic characteristics can be used for the development of recommendations for improving the system of seed production and the selection of new forms of walnut in the Central Chernozem Region.
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Roux, Alexandre, Arnault Tauziede-Espariat, Marc Zanello, Sophie Peeters, Gilles Zah-Bi, Eduardo Parraga, Myriam Edjlali, et al. "Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults." Neuro-Oncology 22, no. 7 (February 6, 2020): 993–1005. http://dx.doi.org/10.1093/neuonc/noaa022.
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Abstract Background We quantified the spontaneous imaging growth rate of oligodendrogliomas. We assessed whether (i) it discriminates between World Health Organization (WHO) grade II and grade III oligodendrogliomas, and (ii) grade III oligodendrogliomas with neo-angiogenesis are associated with more fast growth rates (≥8 mm/y). Methods This work employed a retrospective bicentric cohort study (2010–2016) of adult patients harboring a newly diagnosed supratentorial oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (WHO 2016 classification), with a minimum of 2 available MRIs before any treatment (minimum 6-week interval) to measure the spontaneous tumor growth rate. Results We included 108 patients (age 44.7 ± 14.1 y, 60 males). The tumor growth rate was higher in grade III oligodendrogliomas with neo-angiogenesis (n = 37, median 10.4 mm/y, mean 10.0 ± 6.9) than in grade III oligodendrogliomas with increased mitosis count only (cutoff ≥6 mitoses, n = 18, median 3.9 mm/y, mean 4.5 ± 3.2; P = 0.004), and higher than in grade II oligodendrogliomas (n = 53, median 2.3 mm/y, mean 2.8 ± 2.2; P < 0.001). There was increased prevalence of fast tumor growth rates in grade III oligodendrogliomas with neo-angiogenesis (54.1%) compared with grade III oligodendrogliomas with increased mitosis count only (11.1%; P < 0.001), and in grade II oligodendrogliomas (0.0%; P < 0.001). The tumor growth rate trends did not differ between centers (P = 0.121). Neo-angiogenesis (P < 0.001) and mitosis count at ≥9 (P = 0.013) were independently associated with tumor growth rates ≥8 mm/year. A tumor growth rate ≥8 mm/year was the only predictor independently associated with shorter progression-free survival (P = 0.041). Conclusions The spontaneous tumor growth rate recapitulates oligodendroglioma aggressiveness, permits identification of grade III oligodendrogliomas preoperatively when ≥8 mm/year, and questions the grading by mitosis count.