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A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cd
Cyclin A2 is an essential gene for development and in haematopoietic stem cells and therefore its functions in definitive erythropoiesis have not been investigated. We have ablated cyclin A2 in committed erythroid progenitors in vivo using erythropoietin receptor promoter-driven Cre, which revealed its critical role in regulating erythrocyte morphology and numbers. Erythroid-specific cyclin A2 kno
The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL) MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of
The aim of this study was to evaluate the degree of joint fusion and bone formation in dogs undergoing atlantoaxial arthrodesis after removal of articular cartilage associated or not to implant homogenous or autogenous cancellous bone. Twelve dogs, weighing between 8 and 12kg were randomly divided into three groups. Group I (GI) performed only the removal of joint cartilage and joint immobilizatio
Skeletal development is tightly regulated through the processes of chondrocyte proliferation and differentiation. Although the involvement of transcription and growth factors on the regulation of skeletal development has been extensively studied, the role of cell cycle regulatory proteins in this process remains elusive. To date, through cell-specific loss-of-function experiments in vivo, no cell
The objective of this study is to point out an effective alternative in the treatment of the cranial and caudal cruciate ligaments rupture in dogs, with no association of external immobilization. Six dogs with rupture of both cruciate ligaments were included in the present study. Stifle joint was surgically stabilized by an intracapsular technique, using two polypropylene synthetic implants. The a
The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the exi
Hepatocellular carcinoma (HCC) is associated with high mortality and the current therapy for advanced HCC, Sorafenib, offers limited survival benefits. Here we assessed whether combining the TLR3 agonist: lysine-stabilized polyinosinicpolycytidylic- acid (poly-ICLC) with Sorafenib could enhance tumor control in HCC. Combinatorial therapy with poly-ICLC and Sorafenib increased apoptosis and reduced
The skin presents various important functions to the organism. The maintenance of its integrity is fundamental, among others, to prevent penetration of microorganisms and exit of liquids essential to life maintenance. Due to its constant environment exposure, the skin is highly susceptible to trauma which can result solutions of continuity. The healing of wounded skin should be fast and many alter
Background: The mandibular symphysis is a true joint with a fibrocartilage disc stabilizing both ramus of mandible. The mandibular fracture occurs in 15% of all cases of fracture in cats, and of these, 73% correspond to fracture of the mandibular symphysis. There is a technique for stabilization of symphysis fracture using a nylon cable tie band, however it is necessary to perform two lateral inci
Recent studies suggest that physiological and tumorigenic proliferation of mammalian cells is controlled by multiple cyclin-dependent kinases (CDKs) largely in tissue-specific manners. We and others previously demonstrated that adult mice deficient for the Cyclin D partner CDK4 (Cdk4-/- mice) exhibit hypoplasia in the pituitary and pancreatic islet due to primary postnatal defects in proliferation
Mouse knockouts of Cdk2 and Cdk4 are individually viable whereas the double knockouts are embryonic lethal due to heart defects, and this precludes the investigation of their overlapping roles in definitive hematopoiesis. Here we use a conditional knockout mouse model to investigate the effect of combined loss of Cdk2 and Cdk4 in hematopoietic cells. Cdk2fl/flCdk4-/-vavCre mice are viable but disp
In mitosis, the Greatwall kinase (called microtubuleassociated serine/threonine kinase like [Mastl] in mammals)is essential for prometaphase entry or progression by suppressing protein phosphatase 2A (PP2A) activity. PP2A suppression in turn leads to high levels of Cdk1 substrate phosphorylation. We have used a mouse model with an oocyte-specific deletion of Mastl to show that Mastl-null oocytes r
Cell-cycle inhibition has yet to offer a generally effective approach to cancer treatment, but a full evaluation of different combinations of cell-cycle inhibitors has not been evaluated. Cyclin A2, a core component of the cell cycle, is often aberrantly expressed in cancer where it may impact cell proliferation. In this study, we investigated the role of cyclin A2 in tumorigenesis using a conditi
In this issue of Blood, Matsumoto et al report that T cell-specific deletion of the cyclin-dependent kinase inhibitor p57Kip2(p57) in mice leads to a block in T-cell development as a result of hyperactivation of the E2F-p53 pathway and demonstrate that the loss of p57 accelerates lymphomagenesis in the absence of p53.
The initiation of DNA replication requires two protein kinases: cyclin-dependent kinase (Cdk) and Cdc7. Although S phase Cdk activity has been intensively studied, relatively little is known about how Cdc7 regulates progression through S phase. We have useda Cdc7 inhibitor, PHA-767491, todissect the role of Cdc7 in Xenopus egg extracts. We show that hyperphosphorylation of mini-chromosome maintena
