Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters











Database
Language
Publication year range
1.
Mol Biol Cell ; 31(12): 1206-1217, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32267211

ABSTRACT

Errors during meiotic resumption in oocytes can result in chromosome missegregation and infertility. Several cell cycle kinases have been linked with roles in coordinating events during meiotic resumption, including polo-like kinases (PLKs). Mammals express four kinase-proficient PLKs (PLK1-4). Previous studies assessing the role of PLK1 have relied on RNA knockdown and kinase inhibition approaches, as Plk1 null mutations are embryonically lethal. To further assess the roles of PLK1 during meiotic resumption, we developed a Plk1 conditional knockout (cKO) mouse to specifically mutate Plk1 in oocytes. Despite normal oocyte numbers and follicle maturation, Plk1 cKO mice were infertile. From analysis of meiotic resumption, Plk1 cKO oocytes underwent nuclear envelope breakdown with the same timing as control oocytes. However, Plk1 cKO oocytes failed to form compact bivalent chromosomes, and localization of cohesin and condensin were defective. Furthermore, Plk1 cKO oocytes either failed to organize α-tubulin or developed an abnormally small bipolar spindle. These abnormalities were attributed to aberrant release of the microtubule organizing center (MTOC) linker protein, C-NAP1, and the failure to recruit MTOC components and liquid-like spindle domain (LISD) factors. Ultimately, these defects result in meiosis I arrest before homologous chromosome segregation.


Subject(s)
Cell Cycle Proteins/metabolism , Chromosome Segregation/physiology , Oocytes/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Animals , Cell Cycle Proteins/physiology , Chromosomes/metabolism , Chromosomes/physiology , Female , Meiosis/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Microtubule-Organizing Center/metabolism , Microtubule-Organizing Center/physiology , Microtubules/metabolism , Microtubules/physiology , Protein Serine-Threonine Kinases/physiology , Proto-Oncogene Proteins/physiology , Spindle Apparatus/metabolism , Tubulin/metabolism , Polo-Like Kinase 1
2.
J Biomech ; 41(13): 2868-73, 2008 Sep 18.
Article in English | MEDLINE | ID: mdl-18703196

ABSTRACT

It has been proposed that bone damageability (i.e. bone's susceptibility to formation of damage) increases with the elevation or suppression of bone turnover. Suppression of turnover via bisphosphonates increases local bone mineralization, which theoretically should increase the susceptibility of bone to microcrack formation. Elevation of bone turnover has also been proposed to increase bone microdamage through an increase in bone intracortical porosity and local stresses and strains. The goal of this paper was to investigate the above proposals, i.e., whether or not increases to mineral content and porosity increase bone in-service damageability. To do this, we measured in vivo diffuse damage area (Df.Dm.Ar, %) and microcrack density (Cr.Dn) (cracks/mm(2)) in the same specimen from human cortical bone of the midshaft of the proximal femur obtained from cadavers with an age range of eight decades and examined their relationships with porosity, mineralization and age. Results of this study showed that Cr.Dn and Df.Dm.Ar increased with a decrease in bulk mineralization. This finding does not appear to support the proposal that damage accumulation increases with low bone turnover that results in increases mineralization. It was proposed however that the negative correlation between damage accumulation and mineralization may be attributed to highly mineralized regions of bone existing with under-mineralized regions resulting in an overall decrease in average bone mineralization. It was also found that microdamage accumulates with increasing porosity which does appear to support the proposal that elevated bone turnover that results in increased porosity can accelerate microdamage accumulation. Finally, it was shown that linear microcracks and Df.Dm.Ar accumulate with age differently, but because they correlate with each other, one may be the precursor for the other.


Subject(s)
Bone Density/physiology , Calcification, Physiologic/physiology , Femur/physiology , Adult , Aged , Aged, 80 and over , Bone Development/physiology , Cadaver , Female , Femur/growth & development , Humans , Male , Middle Aged , Multivariate Analysis , Porosity , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL