Journal articles: 'Synteleia'

1

Jiang, Rixin, and Shuo Wang. "Syntelia sunwukong sp. nov., the oldest Synteliid beetle (Coleoptera: Histeroidea) from mid-Cretaceous Burmese amber." Cretaceous Research 119 (March 2021): 104709. http://dx.doi.org/10.1016/j.cretres.2020.104709.

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Porter, Iain M., Sarah E. McClelland, Guennadi A. Khoudoli, Christopher J. Hunter, Jens S. Andersen, Andrew D. McAinsh, J. Julian Blow, and Jason R. Swedlow. "Bod1, a novel kinetochore protein required for chromosome biorientation." Journal of Cell Biology 179, no. 2 (October 15, 2007): 187–97. http://dx.doi.org/10.1083/jcb.200704098.

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We have combined the proteomic analysis of Xenopus laevis in vitro–assembled chromosomes with RNA interference and live cell imaging in HeLa cells to identify novel factors required for proper chromosome segregation. The first of these is Bod1, a protein conserved throughout metazoans that associates with a large macromolecular complex and localizes with kinetochores and spindle poles during mitosis. Small interfering RNA depletion of Bod1 in HeLa cells produces elongated mitotic spindles with severe biorientation defects. Bod1-depleted cells form syntelic attachments that can oscillate and generate enough force to separate sister kinetochores, suggesting that microtubule–kinetochore interactions were intact. Releasing Bod1-depleted cells from a monastrol block increases the frequency of syntelic attachments and the number of cells displaying biorientation defects. Bod1 depletion does not affect the activity or localization of Aurora B but does cause mislocalization of the microtubule depolymerase mitotic centromere- associated kinesin and prevents its efficient phosphorylation by Aurora B. Therefore, Bod1 is a novel kinetochore protein that is required for the detection or resolution of syntelic attachments in mitotic spindles.

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Gaede, Kirsten. "Videobrille und Magnesium-Implantate: cdgw-Zukunftspreis für HappyMed und Syntellix." kma - Klinik Management aktuell 21, no. 12 (December 2016): 14–15. http://dx.doi.org/10.1055/s-0036-1594341.

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Eine Videobrille, mit der Patienten während einer OP (lokalnarkotisiert) oder einer Chemotherapie Filme sehen können, und Schrauben und Pins, die im Körper vollständig abgebaut werden – diese beiden Innovationen sind in Berlin mit dem Zukunftspreis des Clubs der Gesundheitswirtschaft (cdgw) ausgezeichnet worden.

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Storchová, Zuzana, Justin S. Becker, Nicolas Talarek, Sandra Kögelsberger, and David Pellman. "Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast." Molecular Biology of the Cell 22, no. 9 (May 2011): 1473–85. http://dx.doi.org/10.1091/mbc.e10-08-0673.

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The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding yeast, but they become essential in cells with higher ploidy. We find that overexpression of SGO1 partially corrects the chromosome segregation defect of bub1Δ haploid cells and restores viability to bub1Δ tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosomal passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP, inner centromere protein), as suppressors of the growth defect of both bub1Δ and sgo1Δ tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Overexpression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1Δ and sgo1Δ cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1Δ cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 overexpression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization or affects Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B–independent function in establishment of biorientation. We found that Sgo1 overexpression rescues defects caused by metaphase inactivation of Mps1 and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of the Aurora B–mediated pathway at the budding yeast kinetochore and that both pathways are required for the efficient turnover of syntelic attachments.

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Yang, Zhenye, Alison E. Kenny, Daniela A. Brito, and Conly L. Rieder. "Cells satisfy the mitotic checkpoint in Taxol, and do so faster in concentrations that stabilize syntelic attachments." Journal of Cell Biology 186, no. 5 (August 31, 2009): 675–84. http://dx.doi.org/10.1083/jcb.200906150.

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To determine why the duration of mitosis (DM) is less in Taxol than in nocodazole or Eg5 inhibitors we studied the relationship between Taxol concentration, the DM, and the mitotic checkpoint. We found that unlike for other spindle poisons, in Taxol the DM becomes progressively shorter as the concentration surpasses ∼0.5 µM. Studies on RPE1 and PtK2 expressing GFP/cyclin B or YFP/Mad2 revealed that cells ultimately satisfy the checkpoint in Taxol and do so faster at concentrations >0.5 µM. Inhibiting the aurora-B kinase in Taxol-treated RPE1 cells accelerates checkpoint satisfaction by stabilizing syntelic kinetochore attachments and reduces the DM to ∼1.5 h regardless of drug concentration. A similar stabilization of syntelic attachments by Taxol itself appears responsible for accelerated checkpoint satisfaction at concentrations >0.5 µM. Our results provide a novel conceptual framework for how Taxol prolongs mitosis and caution against using it in checkpoint studies. They also offer an explanation for why some cells are more sensitive to lower versus higher Taxol concentrations.

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Kline-Smith, Susan L., Alexey Khodjakov, Polla Hergert, and Claire E. Walczak. "Depletion of Centromeric MCAK Leads to Chromosome Congression and Segregation Defects Due to Improper Kinetochore Attachments." Molecular Biology of the Cell 15, no. 3 (March 2004): 1146–59. http://dx.doi.org/10.1091/mbc.e03-08-0581.

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The complex behavior of chromosomes during mitosis is accomplished by precise binding and highly regulated polymerization dynamics of kinetochore microtubules. Previous studies have implicated Kin Is, unique kinesins that depolymerize microtubules, in regulating chromosome positioning. We have characterized the immunofluorescence localization of centromere-bound MCAK and found that MCAK localized to inner kinetochores during prophase but was predominantly centromeric by metaphase. Interestingly, MCAK accumulated at leading kinetochores during congression but not during segregation. We tested the consequences of MCAK disruption by injecting a centromere dominant-negative protein into prophase cells. Depletion of centromeric MCAK led to reduced centromere stretch, delayed chromosome congression, alignment defects, and severe missegregation of chromosomes. Rates of chromosome movement were unchanged, suggesting that the primary role of MCAK is not to move chromosomes. Furthermore, we found that disruption of MCAK leads to multiple kinetochore–microtubule attachment defects, including merotelic, syntelic, and combined merotelic-syntelic attachments. These findings reveal an essential role for Kin Is in prevention and/or correction of improper kinetochore–microtubule attachments.

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Hagelstein, Salome, Michael Seidenstuecker, Adalbert Kovacs, Roland Barkhoff, and Sergej Zankovic. "Fixation Performance of Bioabsorbable Zn-6Ag Pins for Osteosynthesis." Materials 15, no. 9 (May 3, 2022): 3280. http://dx.doi.org/10.3390/ma15093280.

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Bioabsorbable implants have become the focus of the latest research for new bone implant materials. With favorable characteristics such as compatible mechanical characteristics, no long-term side effects, and even osteogenesis enhancing properties they seem to be the future of osteosynthesis. Besides these characteristics, they must perform on the same level as traditional implant materials regarding their mechanical support for bone healing. A particular focus in the research for bioabsorbable implants has been on metal alloys, as these have particularly good mechanical properties such as excellent maximum force and high stability. This study focused on the shear strength of new bioabsorbable zinc and magnesium pins in comparison to traditional implants such as K-wires and cancellous bone screws in bone-implant connections. During quasi-static and fatigue loading experiments, magnesium pins (MAGNEZIX, Syntellix AG, Hannover, Germany) and new zinc silver pins (Zn-6Ag) by Limedion (Limedion GmbH., Mannheim, Germany) were compared with conventional osteosynthetic materials. The pins made of the new bioabsorbable alloys withstood the cyclic loads to the same extent as the conventional osteosynthesis materials. In the quasi-static loading, it was shown that the novel Zn-6Ag from Limedion has the same shear strength as the magnesium pin from Syntellix, which is already in clinical use. In addition, the zinc pin showed significantly better shear strength compared to osteosynthesis with K-wires (p < 0.05).

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8

Ding, Xia, Feng Yan, Phil Yao, Zhihong Yang, Weihong Wan, Xiwei Wang, Jing Liu, et al. "Probing CENP-E function in chromosome dynamics using small molecule inhibitor syntelin." Cell Research 20, no. 12 (November 30, 2010): 1386–89. http://dx.doi.org/10.1038/cr.2010.167.

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9

Liu, Xu, Leilei Xu, Junying Li, Phil Y. Yao, Wanjuan Wang, Hazrat Ismail, Haowei Wang, et al. "Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly." Journal of Molecular Cell Biology 12, no. 8 (September 10, 2019): 654–65. http://dx.doi.org/10.1093/jmcb/mjz051.

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Abstract Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase–anaphase transition. However, the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive. Given the prevalence of chromosome instability phenotype in gastric tumorigenesis, we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids. Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase–anaphase transition and exhibiting chromosome segregation errors during mitosis. High-resolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype. Using biotinylated syntelin as an affinity matrix, we found that CENP-E forms a complex with PRC1 in mitotic cells. Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone. Thus, CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays. These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly. Since CENP-E is absent from yeast, we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis.

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10

Biber, Roland, Johannes Pauser, Markus Geßlein, and Hermann Josef Bail. "Magnesium-Based Absorbable Metal Screws for Intra-Articular Fracture Fixation." Case Reports in Orthopedics 2016 (2016): 1–4. http://dx.doi.org/10.1155/2016/9673174.

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MAGNEZIX® (Syntellix AG, Hanover, Germany) is a biodegradable magnesium-based alloy (MgYREZr) which is currently used to manufacture bioabsorbable compression screws. To date, there are very few studies reporting on a limited number of elective foot surgeries using this innovative implant. This case report describes the application of this screw for osteochondral fracture fixation at the humeral capitulum next to a loose radial head prosthesis, which was revised at the same time. The clinical course was uneventful. Degradation of the magnesium alloy did not interfere with fracture healing. Showing an excellent clinical result and free range-of-motion, the contour of the implant was still visible in a one-year follow-up.

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11

Hauf, Silke, Richard W. Cole, Sabrina LaTerra, Christine Zimmer, Gisela Schnapp, Rainer Walter, Armin Heckel, Jacques van Meel, Conly L. Rieder, and Jan-Michael Peters. "The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint." Journal of Cell Biology 161, no. 2 (April 21, 2003): 281–94. http://dx.doi.org/10.1083/jcb.200208092.

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The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B. Mammalian cells treated with Hesperadin enter anaphase in the presence of numerous monooriented chromosomes, many of which may have both sister kinetochores attached to one spindle pole (syntelic attachment). Hesperadin also causes cells arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3–5 h. Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.

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12

Mailhes, John B., Colette Mastromatteo, and John W. Fuseler. "Transient exposure to the Eg5 kinesin inhibitor monastrol leads to syntelic orientation of chromosomes and aneuploidy in mouse oocytes." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 559, no. 1-2 (April 2004): 153–67. http://dx.doi.org/10.1016/j.mrgentox.2004.01.001.

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13

Steffen, Walter. "Relationship between the arrangement of microtubules and chromosome behaviour of syntelic autosomal univalents during prometaphase in crane fly spermatocytes." Chromosoma 94, no. 5 (December 1986): 412–18. http://dx.doi.org/10.1007/bf00328642.

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14

Cane, Stuart, Anna A. Ye, Sasha J. Luks-Morgan, and Thomas J. Maresca. "Elevated polar ejection forces stabilize kinetochore–microtubule attachments." Journal of Cell Biology 200, no. 2 (January 21, 2013): 203–18. http://dx.doi.org/10.1083/jcb.201211119.

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Chromosome biorientation promotes congression and generates tension that stabilizes kinetochore–microtubule (kt-MT) interactions. Forces produced by molecular motors also contribute to chromosome alignment, but their impact on kt-MT attachment stability is unclear. A critical force that acts on chromosomes is the kinesin-10–dependent polar ejection force (PEF). PEFs are proposed to facilitate congression by pushing chromosomes away from spindle poles, although knowledge of the molecular mechanisms underpinning PEF generation is incomplete. Here, we describe a live-cell PEF assay in which tension was applied to chromosomes by manipulating levels of the chromokinesin NOD (no distributive disjunction; Drosophila melanogaster kinesin-10). NOD stabilized syntelic kt-MT attachments in a dose- and motor-dependent manner by overwhelming the ability of Aurora B to mediate error correction. NOD-coated chromatin stretched away from the pole via lateral and end-on interactions with microtubules, and NOD chimeras with either plus end–directed motility or tip-tracking activity produced PEFs. Thus, kt-MT attachment stability is modulated by PEFs, which can be generated by distinct force-producing interactions between chromosomes and dynamic spindle microtubules.

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Silkworth, William T., Isaac K. Nardi, Raja Paul, Alex Mogilner, and Daniela Cimini. "Timing of centrosome separation is important for accurate chromosome segregation." Molecular Biology of the Cell 23, no. 3 (February 2012): 401–11. http://dx.doi.org/10.1091/mbc.e11-02-0095.

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Spindle assembly, establishment of kinetochore attachment, and sister chromatid separation must occur during mitosis in a highly coordinated fashion to ensure accurate chromosome segregation. In most vertebrate cells, the nuclear envelope must break down to allow interaction between microtubules of the mitotic spindle and the kinetochores. It was previously shown that nuclear envelope breakdown (NEB) is not coordinated with centrosome separation and that centrosome separation can be either complete at the time of NEB or can be completed after NEB. In this study, we investigated whether the timing of centrosome separation affects subsequent mitotic events such as establishment of kinetochore attachment or chromosome segregation. We used a combination of experimental and computational approaches to investigate kinetochore attachment and chromosome segregation in cells with complete versus incomplete spindle pole separation at NEB. We found that cells with incomplete spindle pole separation exhibit higher rates of kinetochore misattachments and chromosome missegregation than cells that complete centrosome separation before NEB. Moreover, our mathematical model showed that two spindle poles in close proximity do not “search” the entire cellular space, leading to formation of large numbers of syntelic attachments, which can be an intermediate stage in the formation of merotelic kinetochores.

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Jin, Fengzhi, Hong Liu, Ping Li, Hong-Guo Yu, and Yanchang Wang. "Loss of Function of the Cik1/Kar3 Motor Complex Results in Chromosomes with Syntelic Attachment That Are Sensed by the Tension Checkpoint." PLoS Genetics 8, no. 2 (February 2, 2012): e1002492. http://dx.doi.org/10.1371/journal.pgen.1002492.

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Kapoor, Tarun M., Thomas U. Mayer, Margaret L. Coughlin, and Timothy J. Mitchison. "Probing Spindle Assembly Mechanisms with Monastrol, a Small Molecule Inhibitor of the Mitotic Kinesin, Eg5." Journal of Cell Biology 150, no. 5 (September 4, 2000): 975–88. http://dx.doi.org/10.1083/jcb.150.5.975.

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Monastrol, a cell-permeable small molecule inhibitor of the mitotic kinesin, Eg5, arrests cells in mitosis with monoastral spindles. Here, we use monastrol to probe mitotic mechanisms. We find that monastrol does not inhibit progression through S and G2 phases of the cell cycle or centrosome duplication. The mitotic arrest due to monastrol is also rapidly reversible. Chromosomes in monastrol-treated cells frequently have both sister kinetochores attached to microtubules extending to the center of the monoaster (syntelic orientation). Mitotic arrest–deficient protein 2 (Mad2) localizes to a subset of kinetochores, suggesting the activation of the spindle assembly checkpoint in these cells. Mad2 localizes to some kinetochores that have attached microtubules in monastrol-treated cells, indicating that kinetochore microtubule attachment alone may not satisfy the spindle assembly checkpoint. Monastrol also inhibits bipolar spindle formation in Xenopus egg extracts. However, it does not prevent the targeting of Eg5 to the monoastral spindles that form. Imaging bipolar spindles disassembling in the presence of monastrol allowed direct observations of outward directed forces in the spindle, orthogonal to the pole-to-pole axis. Monastrol is thus a useful tool to study mitotic processes, detection and correction of chromosome malorientation, and contributions of Eg5 to spindle assembly and maintenance.

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Vader, Gerben, Carin W. A. Cruijsen, Tanja van Harn, Martijn J. M. Vromans, René H. Medema, and Susanne M. A. Lens. "The Chromosomal Passenger Complex Controls Spindle Checkpoint Function Independent from Its Role in Correcting Microtubule–Kinetochore Interactions." Molecular Biology of the Cell 18, no. 11 (November 2007): 4553–64. http://dx.doi.org/10.1091/mbc.e07-04-0328.

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The chromosomal passenger complex (CPC) is a critical regulator of chromosome segregation during mitosis by correcting nonbipolar microtubule-kinetochore interactions. By severing these interactions, the CPC is thought to create unattached kinetochores that are subsequently sensed by the spindle assembly checkpoint (SAC) to prevent premature mitotic exit. We now show that spindle checkpoint function of the CPC and its role in eliminating nonbipolar attachments can be uncoupled. Replacing the chromosomal passenger protein INCENP with a mutant allele that lacks its coiled-coil domain results in an overt defect in a SAC-mediated mitotic arrest in response to taxol treatment, indicating that this domain is critical for CPC function in spindle checkpoint control. Surprisingly, this mutant could restore alignment and cytokinesis during unperturbed cell divisions and was capable of resolving syntelic attachments. Also, Aurora-B kinase was localized and activated normally on centromeres in these cells, ruling out a role for the coiled-coil domain in general Aurora-B activation. Thus, mere microtubule destabilization of nonbipolar attachments by the CPC is insufficient to install a checkpoint-dependent mitotic arrest, and additional, microtubule destabilization–independent CPC signaling toward the spindle assembly checkpoint is required for this arrest, potentially through amplification of the unattached kinetochore-derived checkpoint signal.

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Sherwin, Delaney, Abigail Huetteman, and Yanchang Wang. "Yeast Kinesin-5 Motor Protein CIN8 Promotes Accurate Chromosome Segregation." Cells 11, no. 14 (July 7, 2022): 2144. http://dx.doi.org/10.3390/cells11142144.

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Accurate chromosome segregation depends on bipolar chromosome–microtubule attachment and tension generation on chromosomes. Incorrect chromosome attachment results in chromosome missegregation, which contributes to genome instability. The kinetochore is a protein complex that localizes at the centromere region of a chromosome and mediates chromosome–microtubule interaction. Incorrect chromosome attachment leads to checkpoint activation to prevent anaphase onset. Kinetochore detachment activates the spindle assembly checkpoint (SAC), while tensionless kinetochore attachment relies on both the SAC and tension checkpoint. In budding yeast Saccharomyces cerevisiae, kinesin-5 motor proteins Cin8 and Kip1 are needed to separate spindle pole bodies for spindle assembly, and deletion of CIN8 causes lethality in the absence of SAC. To study the function of Cin8 and Kip1 in chromosome segregation, we constructed an auxin-inducible degron (AID) mutant, cin8-AID. With this conditional mutant, we first confirmed that cin8-AID kip1∆ double mutants were lethal when Cin8 is depleted in the presence of auxin. These cells arrested in metaphase with unseparated spindle pole bodies and kinetochores. We further showed that the absence of either the SAC or tension checkpoint was sufficient to abolish the cell-cycle delay in cin8-AID mutants, causing chromosome missegregation and viability loss. The tension checkpoint-dependent phenotype in cells with depleted Cin8 suggests the presence of tensionless chromosome attachment. We speculate that the failed spindle pole body separation in cin8 mutants could increase the chance of tensionless syntelic chromosome attachments, which depends on functional tension checkpoint for survival.

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Suja, J. A., J. de la Torre, J. F. Giménez-Abián, C. García de la Vega, and J. S. Rufas. "Meiotic chromosome structure. Kinetochores and chromatid cores in standard and B chromosomes of Arcyptera fusca (Orthoptera) revealed by silver staining." Genome 34, no. 1 (February 1, 1991): 19–27. http://dx.doi.org/10.1139/g91-004.

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The behaviour of two chromosome structures in silver-stained chromosomes was analyzed through the first meiotic division in spermatocytes of the acridoid species Arcyptera fusca. Results showed that at diakinesis kinetochores and chromatid cores are individualized while they associate in bivalents of metaphase I; only kinetochores and distal core spots associate in the sex chromosome. Metaphase I is characterized by morphological and localization changes of both kinetochores and cores which define the onset of anaphase I. These changes analyzed in both autosomes and in the sex chromosome allow us to distinguish among three different substages in metaphase I spermatocytes. B chromosomes may be present as univalents, bivalents, or trivalents. Metaphase I B univalents are characterized by separated cores except at their distal ends and individualized and flat sister kinetochores. At anaphase I sister kinetochores of lagging B chromatids remain connected through a silver-stained strand. The behaviour of cores and kinetochores of B bivalents is identical with that found in the autosomal bivalents. The differences in the morphology of kinetochores of every chromosome shown by B trivalents at metaphase I may be related to the balanced forces acting on the multivalent. The results show dramatic changes in chromosome organization of bivalents during metaphase I. These changes suggest that chromatid cores are not involved in the maintenance of bivalents. Moreover, the changes in morphology of kinetochores are independent of the stage of meiosis but correlate with the kind of division (amphitelic–syntelic) that chromosomes undergo.Key words: kinetochore, chromatid core, B chromosomes, meiosis, chromosome structure, silver staining.

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"L'esercito di Ducezio. Guerra e influenze culturali durante il periodo della synteleia." Studi Classici e Orientali, 2015, 53–72. http://dx.doi.org/10.12871/97888674149945.

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Mullen, McKay, Fengrui Yang, Jun Cao, Yang Cao, Xu Liu, Gee Young Lee, Tao Li, et al. "Syntelin inhibits triple-negative breast cancer cell proliferation and metastasis." Journal of Molecular Cell Biology, August 27, 2021. http://dx.doi.org/10.1093/jmcb/mjab054.

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23

Yao, Maomao, Xing Liu, and Xuebiao Yao. "Molecular delineation of CENP‐E in mitotic spindle plasticity using chemical probe syntelin." FASEB Journal 27, S1 (April 2013). http://dx.doi.org/10.1096/fasebj.27.1_supplement.764.3.

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Schrock, Morgan S., Luke Scarberry, Benjamin R. Stromberg, Claire Sears, Adrian E. Torres, David Tallman, Lucas Krupinski, Arnab Chakravarti, and Matthew K. Summers. "MKLP2 functions in early mitosis to ensure proper chromosome congression." Journal of Cell Science, May 31, 2022. http://dx.doi.org/10.1242/jcs.259560.

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Mitotic kinesin-like protein 2 (MKLP2) is a motor protein with a well-established function in promoting cytokinesis. However, our results with siRNAs targeting MKLP2 and small molecule inhibitors of MKLP2 (MKLP2i) suggested a function earlier in mitosis, prior to anaphase. In this study we provide direct evidence that MKLP2 facilitates chromosome congression in prometaphase. We employed live imaging to observe HeLa cells with fluorescently tagged histones treated with MKLP2i and discovered a pronounced chromosome congression defect. We show that MKLP2 facilitates error correction as inhibited cells had a significant increase in unstable, syntelic kinetochore-microtubule attachments. We find that the aberrant attachments are accompanied by elevated Aurora Kinase (A/B) activity and phosphorylation of the downstream target, pHEC1 (Ser 55). Lastly, we show that MKLP2 inhibition results in aneuploidy, confirming that MKLP2 safeguards cells against chromosomal instability.

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Kliuchnikov, Evgenii, Kenneth A. Marx, Alex Mogilner, and Valeri Barsegov. "Interrelated effects of chromosome size, mechanics, number, location-orientation and polar ejection force on the spindle accuracy: a 3D computational study." Molecular Biology of the Cell, February 15, 2023. http://dx.doi.org/10.1091/mbc.e22-11-0507.

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The search-and-capture model of spindle assembly has been a guiding principle for understanding prometaphase for decades. The computational model presented allows one to address two questions: how rapidly the microtubule-kinetochore connections are made, and how accurate these connections are. In most previous numerical simulations, the model geometry was drastically simplified. Using the CellDynaMo computational platform, we previously introduced a geometrically and mechanically realistic 3D model of the prometaphase mitotic spindle, and used it to evaluate thermal noise and microtubule kinetics effects on the capture of a single chromosome. Here, we systematically investigate how geometry and mechanics affect spindle assembly's speed and accuracy, including nuanced distinctions between merotelic, mero-amphitelic and mero-syntelic chromosomes. We find that softening of the centromere spring improves accuracy for short chromosome arms, but accuracy disappears for long chromosome arms. Initial proximity of chromosomes to one spindle pole makes assembly accuracy worse, while initial chromosome orientation matters less. Chromokinesins, added onto flexible chromosome arms, allow modeling of the polar ejection force, improving spindle assembly's accuracy for a single chromosome. However, spindle space crowding by multiple chromosomes worsens assembly accuracy. Our simulations suggest that the complex microtubule network of the early spindle is key to rapid and accurate assembly. [Media: see text] [Media: see text] [Media: see text]

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Petrenko, Victor, Dmytro Dzvin, Mark Liutyi, and Iryna Ozminska. "3S-LEADERSHIP MODEL AS A TOOL OF USING DESIGN THINKING IN THE SYSTEM OF PUBLIC GOVERNANCE." International Journal of Innovative Technologies in Social Science, no. 3(35) (September 30, 2022). http://dx.doi.org/10.31435/rsglobal_ijitss/30092022/7852.

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The problem of integrated implementation of technology and techniques of design thinking, design management and design leadership into public administration should be considered a priority, as this area is the institutional component that determines the level of either innovative development of a society or its stagnation and decline. The dynamic changes in the intellect, mentality, experience, life values and orientations of modern people set new requirements for leaders in the age of intellectual economy, therefore traditional theories and models of leadership no longer meet the needs of group design-thinking. The purpose of this study is to determine a leadership model most adequate to the principles and criteria of design thinking so as to adapt it to the priority use in the processes and procedures of public administration. The tasks of the study are to analyze the expediency of changes in traditional leadership models and tools oriented to new requirements for design leaders; to outline the conditions for the effective management in the “leader-follower” pair in order to substantiate the role of a leader in design-thinking process and identify the leader’s influence on the group’s performance depending on the level of his/her mastery of using design thinking methodology; to assess the level of adequacy of the 3S leadership model to the criteria and methods of design thinking. To reach the objectives of the article the method of comparative analysis was used. The results of the analysis of the known models of design thinking processes revealed that this process is a fundamental condition and basis for leaders to create an atmosphere of effective use of their own intellect and the intellect of their followers in “leader-follower” pair for joint creativity and innovation. The conclusions of the study draw attention to the feasibility of and conditions for integrating the intellect of “leader-follower” pair and using for this purpose a model of 3S-leadership, based on common behavioral phenomena of synarchy, syntelect and synergy of its members. The main condition for the group to use design thinking technology efficiently has been defined as the mastery of design thinking methodology by its leader with the simultaneous use of the 3S-leadership model to influence followers, which will allow all group members to re-orient to the criteria of the 3S-model, their intellectual activity to be organized according to the recommendations of design thinking, and the leader to transform into a real design-leader who ensures a collective synergistic effect, i.e. a joint innovative product. Authors believe that the results of this study will contribute to the development of programs for training design-thinking leaders for the national system of public administration.

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Journal articles on the topic 'Synteleia'

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