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Acta Neuropathologica Communications Jan 2024Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges...
Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology and propose a computational strategy to enhance pathologists' mitosis assessment. The strategy has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum mitotic count in 10 consecutive high-power fields, which can enhance the preciseness, especially in cases with borderline mitotic count. (2) Implementing a collaborative sphere to group a set of pathologists to detect mitoses under each high-power field, which can mitigate subjective random errors in mitosis detection originating from individual detection errors. By depth-first search algorithm (1) , we analyzed 19 meningioma slides and discovered that the proposed algorithm upgraded two borderline cases verified at consensus conferences. This improvement is attributed to the algorithm's ability to quantify the mitotic count more comprehensively compared to other conventional methods of counting mitoses. In implementing a collaborative sphere (2) , we evaluated the correctness of mitosis detection from grouped pathologists and/or pathology residents, where each member of the group annotated a set of 48 high-power field images for mitotic figures independently. We report that groups with sizes of three can achieve an average precision of 0.897 and sensitivity of 0.699 in mitosis detection, which is higher than an average pathologist in this study (precision: 0.750, sensitivity: 0.667). The proposed computational strategy can be integrated with artificial intelligence workflow, which envisions the future of achieving a rapid and robust mitosis assessment by interactive assisting algorithms that can ultimately benefit patient management.
Topics: Humans; Meningioma; Mitotic Index; Artificial Intelligence; Mitosis; Meningeal Neoplasms
PubMed: 38212848
DOI: 10.1186/s40478-023-01707-6 -
ELife May 2022Cell mass and composition change with cell cycle progression. Our previous work characterized buoyant mass dynamics in mitosis (Miettinen et al., 2019), but how dry mass...
Cell mass and composition change with cell cycle progression. Our previous work characterized buoyant mass dynamics in mitosis (Miettinen et al., 2019), but how dry mass and cell composition change in mitosis has remained unclear. To better understand mitotic cell growth and compositional changes, we develop a single-cell approach for monitoring dry mass and the density of that dry mass every ~75 s with 1.3% and 0.3% measurement precision, respectively. We find that suspension grown mammalian cells lose dry mass and increase dry mass density following mitotic entry. These changes display large, non-genetic cell-to-cell variability, and the changes are reversed at metaphase-anaphase transition, after which dry mass continues accumulating. The change in dry mass density causes buoyant and dry mass to differ specifically in early mitosis, thus reconciling existing literature on mitotic cell growth. Mechanistically, cells in early mitosis increase lysosomal exocytosis, and inhibition of lysosomal exocytosis decreases the dry mass loss and dry mass density increase in mitosis. Overall, our work provides a new approach for monitoring single-cell dry mass and dry mass density, and reveals that mitosis is coupled to extensive exocytosis-mediated secretion of cellular contents.
Topics: Anaphase; Animals; Cell Cycle; Exocytosis; Mammals; Metaphase; Mitosis
PubMed: 35535854
DOI: 10.7554/eLife.76664 -
Biological Reviews of the Cambridge... Feb 2015Mitosis is a fundamental and essential life process. It underlies the duplication and survival of all cells and, as a result, all eukaryotic organisms. Since... (Review)
Review
Mitosis is a fundamental and essential life process. It underlies the duplication and survival of all cells and, as a result, all eukaryotic organisms. Since uncontrolled mitosis is a dreaded component of many cancers, a full understanding of the process is critical. Evolution has led to the existence of three types of mitosis: closed, open, and semi-open. The significance of these different mitotic species, how they can lead to a full understanding of the critical events that underlie the asexual duplication of all cells, and how they may generate new insights into controlling unregulated cell division remains to be determined. The eukaryotic microbe Dictyostelium discoideum has proved to be a valuable biomedical model organism. While it appears to utilize closed mitosis, a review of the literature suggests that it possesses a form of mitosis that lies in the middle between truly open and fully closed mitosis-it utilizes a form of semi-open mitosis. Here, the nucleocytoplasmic translocation patterns of the proteins that have been studied during mitosis in the social amoebozoan D. discoideum are detailed followed by a discussion of how some of them provide support for the hypothesis of semi-open mitosis.
Topics: Active Transport, Cell Nucleus; Dictyostelium; Mitosis
PubMed: 24618050
DOI: 10.1111/brv.12100 -
Current Biology : CB Jun 2018Cohesin is a ring-shaped protein complex that organises the genome, enabling its condensation, expression, repair and transmission. Cohesin is best known for its role in...
Cohesin is a ring-shaped protein complex that organises the genome, enabling its condensation, expression, repair and transmission. Cohesin is best known for its role in chromosome segregation, where it provides the cohesion that is established between the two newly duplicated sister chromatids during S phase. This cohesion enables the proper attachment of sister chromatids to microtubules of the spindle by resisting their opposing pulling forces. Once all chromosomes are correctly attached, cohesin is abruptly destroyed, triggering the equal segregation of sister chromatids to opposite poles in anaphase. Here we summarise the molecular functions and regulation of cohesin that underlie its central role in chromosome segregation during mitosis.
Topics: Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; Chromosome Segregation; Mitosis; Saccharomyces cerevisiae; Cohesins
PubMed: 29920258
DOI: 10.1016/j.cub.2018.05.019 -
Molecular Cell Sep 2022By sequencing sites of mitotic DNA synthesis in cells lacking homologous recombination, Groelly, Bhowmick, and colleagues show how conflicts between transcription and...
By sequencing sites of mitotic DNA synthesis in cells lacking homologous recombination, Groelly, Bhowmick, and colleagues show how conflicts between transcription and replication in early S phase can cause under-replicated DNA to persist into mitosis.
Topics: DNA; DNA Replication; Mitosis; Transcription, Genetic
PubMed: 36113410
DOI: 10.1016/j.molcel.2022.08.026 -
Communications Biology Dec 2021Mitotic divisions achieve equal re-partition of chromosomes into daughter cells. In their recent work in , Sen, Harrison et al. propose that the risk of mis-segregation...
Mitotic divisions achieve equal re-partition of chromosomes into daughter cells. In their recent work in , Sen, Harrison et al. propose that the risk of mis-segregation in human mitotic cells is higher than previously thought and identify the existence of an early-anaphase correction mechanism. The study documents kinetochore dynamics in unprecedented detail, providing a detailed look at the events preceding loss of correct chromosomal numericity and genomic stability.
Topics: Anaphase; Chromosome Segregation; Humans; Kinetochores; Mitosis
PubMed: 34903809
DOI: 10.1038/s42003-021-02933-1 -
Journal of Cell Science Jul 2011Dynamic control of protein phosphorylation is necessary for the regulation of many cellular processes, including mitosis and cytokinesis. Indeed, although the central...
Dynamic control of protein phosphorylation is necessary for the regulation of many cellular processes, including mitosis and cytokinesis. Indeed, although the central role of protein kinases is widely appreciated and intensely studied, the importance of protein phosphatases is often overlooked. Recent studies, however, have highlighted the considerable role of protein phosphatases in both the spatial and temporal control of protein kinase activity, and the modulation of substrate phosphorylation. Here, we will focus on recent advances in our understanding of phosphatase structure, and the importance of phosphatase function in the control of mitotic spindle formation, chromosome architecture and cohesion, and cell division.
Topics: Animals; Humans; Mice; Mitosis; Phosphoprotein Phosphatases; Protein Processing, Post-Translational; Spindle Apparatus
PubMed: 21709074
DOI: 10.1242/jcs.087106 -
Cell Cycle (Georgetown, Tex.) Feb 2021DNA Topoisomerase II (TopoII) uses ATP hydrolysis to decatenate chromosomes so that sister chromatids can faithfully segregate in mitosis. When the TopoII enzyme cycle... (Review)
Review
DNA Topoisomerase II (TopoII) uses ATP hydrolysis to decatenate chromosomes so that sister chromatids can faithfully segregate in mitosis. When the TopoII enzyme cycle stalls due to failed ATP hydrolysis, the onset of anaphase is delayed, presumably to allow extra time for decatenation to be completed. Recent evidence revealed that, unlike the spindle assembly checkpoint, this TopoII checkpoint response requires Aurora B and Haspin kinases and is triggered by SUMOylation of the C-terminal domain of TopoII.
Topics: Animals; Aurora Kinase B; Cell Cycle Proteins; DNA Topoisomerases, Type II; Genes, cdc; Humans; Intracellular Signaling Peptides and Proteins; M Phase Cell Cycle Checkpoints; Metaphase; Mitosis; Protein Serine-Threonine Kinases
PubMed: 33459116
DOI: 10.1080/15384101.2021.1875671 -
ELife Dec 2020Mitosis is a dramatic process that affects all parts of the cell. It is driven by an oscillator whose various components are localized in the nucleus, centrosome, and...
Mitosis is a dramatic process that affects all parts of the cell. It is driven by an oscillator whose various components are localized in the nucleus, centrosome, and cytoplasm. In principle, the cellular location with the fastest intrinsic rhythm should act as a pacemaker for the process. Here we traced the waves of tubulin polymerization and depolymerization that occur at mitotic entry and exit in egg extracts back to their origins. We found that mitosis was commonly initiated at sperm-derived nuclei and their accompanying centrosomes. The cell cycle was ~20% faster at these initiation points than in the slowest regions of the extract. Nuclei produced from phage DNA, which did not possess centrosomes, also acted as trigger wave sources, but purified centrosomes in the absence of nuclei did not. We conclude that the nucleus accelerates mitotic entry and propose that it acts as a pacemaker for cell cycle.
Topics: Animals; Biological Clocks; Cell Cycle; Cell Nucleus; Mitosis; Oocytes; Xenopus laevis
PubMed: 33284106
DOI: 10.7554/eLife.59989 -
The FEBS Journal May 2020The DNA damage response recognizes DNA lesions and coordinates a cell cycle arrest with the repair of the damaged DNA, or removal of the affected cells to prevent the... (Review)
Review
The DNA damage response recognizes DNA lesions and coordinates a cell cycle arrest with the repair of the damaged DNA, or removal of the affected cells to prevent the passage of genetic alterations to the next generation. The mitotic cell division, on the other hand, is a series of processes that aims to accurately segregate the genomic material from the maternal to the two daughter cells. Despite their great importance in safeguarding genomic integrity, the DNA damage response and the mitotic cell division were long viewed as unrelated processes, mainly because animal cells that are irradiated during mitosis continue cell division without repairing the broken chromosomes. However, recent studies have demonstrated that DNA damage proteins play an important role in mitotic cell division. This is performed through regulation of the onset of mitosis, mitotic spindle formation, correction of misattached kinetochore-microtubules, spindle checkpoint signaling, or completion of cytokinesis (abscission), in the absence of DNA damage. In this review, we summarize the roles of DNA damage proteins in unperturbed mitosis, analyze the molecular mechanisms involved, and discuss the potential implications of these findings in cancer therapy.
Topics: Animals; Cell Cycle Proteins; Cell Division; DNA Damage; Genomic Instability; Humans; Mitosis
PubMed: 32027459
DOI: 10.1111/febs.15240