14 results on '"Zealley B"'
Search Results
2. Regulation of minimal spindle midzone organization by mitotic kinases.
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Lim, Wei Ming, Chew, Wei-Xiang, Esposito Verza, Arianna, Pesenti, Marion, Musacchio, Andrea, and Surrey, Thomas
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TUBULINS ,SPINDLE apparatus ,CELL division ,ANAPHASE ,CYTOSKELETON ,MICROTUBULES - Abstract
During cell division, the microtubule cytoskeleton undergoes dramatic cell cycle-driven reorganizations of its architecture. Coordinated by changes in the phosphorylation patterns of a multitude of microtubule associated proteins, the mitotic spindle first self-assembles to capture the chromosomes and then reorganizes in anaphase as the chromosomes are segregated. A key protein for this reorganization is PRC1 which is differentially phosphorylated by the mitotic kinases CDK1 and PLK1. How the phosphorylation state of PRC1 orchestrates spindle reorganization is not understood mechanistically. Here, we reconstitute in vitro the transition between metaphase and anaphase-like microtubule architectures triggered by the changes in PRC1 phosphorylation. We find that whereas PLK1 regulates its own recruitment by PRC1, CDK1 controls the affinity of PRC1 for antiparallel microtubule binding. Dephosphorylation of CDK1-phosphorylated PRC1 is required and sufficient to trigger the reorganization of a minimal anaphase midzone in the presence of the midzone length controlling kinesin KIF4A. These results demonstrate how phosphorylation-controlled affinity changes regulate the architecture of active microtubule networks, providing new insight into the mechanistic underpinnings of the cell cycle-driven reorganization of the central spindle during mitosis. Lim et al. reconstitute in vitro the transition between metaphase and anaphase-like spindle midzone architectures and dissect the role of PRC1 phosphorylation by PLK and CDK1 in reorganizing the central spindle during mitosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody.
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Xu, Xiaoyang, Huang, Yuliang, Yang, Feng, Sun, Xiaoxia, Lin, Rijin, Feng, Jiaxing, Yang, Mingyang, Shao, Jiaqi, Liu, Xiaoqi, Zhou, Tianhua, Xie, Shanshan, and Yang, Yuehong
- Abstract
Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation, and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Toward Systemic Lipofuscin Removal.
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Renteln, Michael
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- 2024
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5. Enucleation of the C. elegans embryo revealed dynein-.
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Ken Fujii, Tomo Kondo, and Akatsuki Kimura
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- 2024
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6. Redundant microtubule crosslinkers prevent meiotic spindle bending to ensure diploid offspring in C. elegans.
- Author
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Li, Wenzhe, Crellin, Helena A., Cheerambathur, Dhanya, and McNally, Francis J.
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SPINDLE apparatus ,MICROTUBULES ,CAENORHABDITIS elegans ,TUBULINS ,CHROMOSOME segregation ,PROTEIN crosslinking ,SLEEP spindles - Abstract
Oocyte meiotic spindles mediate the expulsion of ¾ of the genome into polar bodies to generate diploid zygotes in nearly all animal species. Failures in this process result in aneuploid or polyploid offspring that are typically inviable. Accurate meiotic chromosome segregation and polar body extrusion require the spindle to elongate while maintaining its structural integrity. Previous studies have implicated three hypothetical activities during this process, including microtubule crosslinking, microtubule sliding and microtubule polymerization. However, how these activities regulate spindle rigidity and elongation as well as the exact proteins involved in the activities remain unclear. We discovered that C. elegans meiotic anaphase spindle integrity is maintained through redundant microtubule crosslinking activities of the Kinesin-5 family motor BMK-1, the microtubule bundling protein SPD-1/PRC1, and the Kinesin-4 family motor, KLP-19. Using time-lapse imaging, we found that single depletion of KLP-19
KIF4A , SPD-1PRC1 or BMK-1Eg5 had minimal effects on anaphase B spindle elongation velocity. In contrast, double depletion of SPD-1PRC1 and BMK-1Eg5 or double depletion of KLP-19KIF4A and BMK-1Eg5 resulted in spindles that elongated faster, bent in a myosin-dependent manner, and had a high rate of polar body extrusion errors. Bending spindles frequently extruded both sets of segregating chromosomes into two separate polar bodies. Normal anaphase B velocity was observed after double depletion of KLP-19KIF4A and SPD-1PRC1 . These results suggest that KLP-19KIF4A and SPD-1PRC1 act in different pathways, each redundant with a separate BMK-1Eg5 pathway in regulating meiotic spindle elongation. Depletion of ZYG-8, a doublecortin-related microtubule binding protein, led to slower anaphase B spindle elongation. We found that ZYG-8DCLK1 acts by excluding SPD-1PRC1 from the spindle. Thus, three mechanistically distinct microtubule regulation modules, two based on crosslinking, and one based on exclusion of crosslinkers, power the mechanism that drives spindle elongation and structural integrity during anaphase B of C.elegans female meiosis. Author summary: Meiosis reduces the number of chromosomes from four to one during the formation of egg and sperm, so that a fertilized egg has exactly two copies of each chromosome. Meiotic errors result in offspring with an incorrect number of chromosomes, which lead to prenatal death or birth defects. During mitosis, chromosome segregation is mediated by a bipolar mitotic spindle. Microtubules emanating from each spindle pole to the opposite ends of the cell generate pulling forces that must be resisted by the midzone microtubules of the spindle. In contrast, oocyte meiotic spindles are so small relative to the size of the oocyte that both spindle poles are subject to pulling forces from the same side of the oocyte. Normally, only one pole is pulled to the cortex to allow expulsion of half the chromosomes into a tiny cell called a polar body. Here we show that in the roundworm C. elegans, a specific subset of microtubule crosslinking proteins in the midzone are required to prevent the meiotic spindle from bending and expelling all chromosomes into polar bodies. This study reveals a new mechanism that ensures progeny's correct chromosome number. [ABSTRACT FROM AUTHOR]- Published
- 2023
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7. Macular thickness and its associated factors in a Chinese rural adult population: the Handan Eye Study.
- Author
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Jian Wu, Caixia Lin, Yifan Du, Su Jie Fan, Lijie Pan, Qing Pan, Kai Cao, and Ningli Wang
- Abstract
Purpose To describe the normal macular thickness and assess its associations. Methods The Handan Eye Follow-up Study was conducted between 2012 and 2013. Macular thickness was scanned by spectral-domain optical coherence tomography (OCT). The built-in software generated a retinal thickness (RT) map, which was divided into three regions (central, internal and external regions) and nine quadrants (one in central and four in internal and external regions each). Results For 5394 subjects in the Handan Eye Follow-up Study, 4793 received OCT examination, 2946 of whom (accounting for 61.46% of the total subjects, mean age 58.91±10.95, 55.6% were women) were included for analysis. The mean RT in central macula, inner and outer rings were (237.38 µm±23.05 µm), (309.77 µm±18.36 µm) and (278.29 µm±14.38 µm), respectively (overall difference, p<0.001). In inner ring, the RT in temporal was thinnest, followed by nasal, superior and inferior. In outer ring, the RT in superior was thinnest, with the next subfields being temporal, inferior and nasal, respectively. The RT in central macula, inner and outer rings were significantly thicker in men than in women. Multivariate linear regression analysis showed that in central macula, RT increased in subjects younger than 60 years and thinned above the age of 60. In inner and outer rings, RT thinned along with age (p<0.001). Conclusions This study finds that RT in central macula is the thinnest, followed by the outer ring, the RT in the inner ring is the thickest. Age and gender are related to RT. These associated factors need to be considered when explaining RT. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Phosphorylation controls spatial and temporal activities of motor‐PRC1 complexes to complete mitosis.
- Author
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Gluszek‐Kustusz, Agata, Craske, Benjamin, Legal, Thibault, McHugh, Toni, and Welburn, Julie PI
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MICROTUBULES ,CHROMOSOME segregation ,CELL cycle ,TUBULINS ,MITOSIS ,CYTOLOGY ,CYTOKINESIS ,CELL cycle regulation - Abstract
During mitosis, spindle architecture alters as chromosomes segregate into daughter cells. The microtubule crosslinker protein regulator of cytokinesis 1 (PRC1) is essential for spindle stability, chromosome segregation and completion of cytokinesis, but how it recruits motors to the central spindle to coordinate the segregation of chromosomes is unknown. Here, we combine structural and cell biology approaches to show that the human CENP‐E motor, which is essential for chromosome capture and alignment by microtubules, binds to PRC1 through a conserved hydrophobic motif. This binding mechanism is also used by Kinesin‐4 Kif4A:PRC1. Using in vitro reconstitution, we demonstrate that CENP‐E slides antiparallel PRC1‐crosslinked microtubules. We find that the regulation of CENP‐E ‐PRC1 interaction is spatially and temporally coupled with relocalization to overlapping microtubules in anaphase. Finally, we demonstrate that the PRC1–microtubule motor interaction is essential in anaphase to control chromosome partitioning, retain central spindle integrity and ensure cytokinesis. Taken together our findings reveal the molecular basis for the cell cycle regulation of motor‐PRC1 complexes to couple chromosome segregation and cytokinesis. Synopsis: PRC1 associates with microtubule motors to stabilize the anaphase central spindle, however how they interact remains elusive. This study reveals the molecular basis for the cell cycle regulation of mitotic motor‐PRC1 complexes to organize antiparallel microtubule bundle, and to ensure central spindle integrity, midbody assembly and cytokinesis. Kinesin motors Kif4A and CENP‐E bind PRC1 using a bipartite hydrophobic motif.Phosphorylation of CENP‐E controls its affinity for PRC1 to provide temporal and spatial control for the interaction.CENP‐E slides antiparallel microtubules in the presence of PRC1.Disruption of the PRC1:motor interaction disrupts central spindle integrity and midbody assembly. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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9. The Ethical Implications of Tissue Engineering for Regenerative Purposes: A Systematic Review.
- Author
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de Kanter, Anne-Floor J., Jongsma, Karin R., Verhaar, Marianne C., and Bredenoord, Annelien L.
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- 2023
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10. Effects of lifespan-extending interventions on cognitive healthspan.
- Author
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Culig, Luka, Sahbaz, Burcin Duan, and Bohr, Vilhelm A.
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HUNTINGTON disease ,OLDER people ,COGNITIVE aging ,ALZHEIMER'S disease ,ENVIRONMENTAL enrichment - Abstract
Ageing is known to be the primary risk factor for most neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. They are currently incurable and worsen over time, which has broad implications in the context of lifespan and healthspan extension. Adding years to life and even to physical health is suboptimal or even insufficient, if cognitive ageing is not adequately improved. In this review, we will examine how interventions that have the potential to extend lifespan in animals affect the brain, and if they would be able to thwart or delay the development of cognitive dysfunction and/or neurodegeneration. These interventions range from lifestyle (caloric restriction, physical exercise and environmental enrichment) through pharmacological (nicotinamide adenine dinucleotide precursors, resveratrol, rapamycin, metformin, spermidine and senolytics) to epigenetic reprogramming. We argue that while many of these interventions have clear potential to improve cognitive health and resilience, large-scale and long-term randomised controlled trials are needed, along with studies utilising washout periods to determine the effects of supplementation cessation, particularly in aged individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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11. NF-κB, a culprit of both inflamm-ageing and declining immunity?
- Author
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Songkiatisak, Preeyaporn, Rahman, Shah Md Toufiqur, Aqdas, Mohammad, and Sung, Myong-Hee
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CELLULAR aging ,DNA damage ,TELECOMMUNICATION systems ,IMMUNITY ,HOMODIMERS ,AGING ,IMMUNOSENESCENCE - Abstract
NF-κB is generally recognized as an important regulator of ageing, through its roles in cellular senescence and inflammatory pathways. Activated in virtually all cell-cell communication networks of the immune system, NF-κB is thought to affect age-related defects of both innate and adaptive immune cells, relevant to inflamm-ageing and declining adaptive immunity, respectively. Moreover, the family of NF-κB proteins that exist as heterodimers and homodimers exert their function beyond the immune system. Given their involvement in diverse areas such as DNA damage to metabolism, NF-κB has the potential to serve as linkages between known hallmarks of ageing. However, the complexity of NF-κB dimer composition, dynamic signaling, and tissue-specific actions has received relatively little attention in ageing research. Here, we discuss some areas where further research may bear fruit in our understanding the impact of NF-κB in healthy ageing and longevity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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12. Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions.
- Author
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Brauning, Ashley, Rae, Michael, Zhu, Gina, Fulton, Elena, Admasu, Tesfahun Dessale, Stolzing, Alexandra, and Sharma, Amit
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IMMUNOSENESCENCE ,IMMUNE system ,CELL physiology ,CELLULAR aging ,KILLER cells ,AGING ,ALZHEIMER'S disease - Abstract
Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer's and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging ("inflammaging"). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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13. Gradual compaction of the central spindle decreases its dynamicity in PRC1 and EB1 gene-edited cells.
- Author
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Asthana, Jayant, Cade, Nicholas I., Normanno, Davide, Wei Ming Lim, and Surrey, Thomas
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- 2021
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14. Pathy's Principles and Practice of Geriatric Medicine
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Alan J. Sinclair, John E. Morley, Bruno Vellas, Matteo Cesari, Medha Munshi, Alan J. Sinclair, John E. Morley, Bruno Vellas, Matteo Cesari, and Medha Munshi
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- Geriatrics
- Abstract
Pathy's PRINCIPLES AND PRACTICE OF GERIATRIC MEDICINE The latest edition of the gold standard in geriatric medicine references Pathy's Principles and Practice of Geriatric Medicine, Sixth Edition delivers a comprehensive overview of the subject, offering up-to-date, evidence-based, information about the many, and varied, problems suffered by ageing patients. In this latest edition, the authors take a refreshed approach to the material by rigorously applying the latest scientific research to clinical practice and increasing the use of visual examples, algorithms, and clinical practice points. Thoroughly updated throughout, the chapters give readers a truly global perspective on geriatric medicine that reflect the most recent changes in treatment options and medical conditions. In addition to new chapters on a range of recent and emerging topics, clinical practice points, and visual evidence—including MRI scans—the book also offers a: Thorough introduction to relevant biological, social, and community perspectives on caring for mature and ageing patients, as well as medicine prescribing for older patients Comprehensive exploration of eating disorders that commonly occur in the aged and how to maximize the nutritional health of ageing patients Practical discussions of haematological and cardiovascular disorders and diseases in ageing patients In-depth examination of special issues in elder care, including elder abuse, alcoholism and substance abuse, transportation issues, and end-of-life care Perfect for all clinicians working with mature patients, Pathy's Principles and Practice of Geriatric Medicine will also continue to earn a place in the libraries of allied healthcare workers with ageing patients and clients.
- Published
- 2022
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