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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

The indispensable role of cyclin-dependent kinase 1 in skeletal development

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

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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

A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

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

TLR3 agonist and Sorafenib combinatorial therapy promotes immune activation and controls hepatocellular carcinoma progression

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

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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

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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

MEN1 tumorigenesis in the pituitary and pancreatic islet requires CDK4 but not Cdk2

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

Hematopoiesis specific loss of Cdk2 and Cdk4 results in increased erythrocyte size and delayed platelet recovery following stress

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

Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II

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

Loss of Cdk2 and cyclin A2 impairs cell proliferation and tumorigenesis

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

P57Kip2regulates T-cell development and lymphoma

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.

Xenopus Cdc7 executes its essential function early in S phase and is counteracted by checkpoint-regulated protein phosphatase 1

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

The complex relationship between liver cancer and the cell cycle : A story of multiple regulations

The liver acts as a hub for metabolic reactions to keep a homeostatic balance during development and growth. The process of liver cancer development, although poorly understood, is related to different etiologic factors like toxins, alcohol, or viral infection. At the molecular level, liver cancer is characterized by a disruption of cell cycle regulation through many molecular mechanisms. In this

p27 is regulated independently of Skp2 in the absence of Cdk2

Cyclin-dependent kinase 2 (Cdk2) is dispensable for mitotic cell cycle progression and Cdk2 knockout mice are viable due to the compensatory functions of other Cdks. In order to assess the role of Cdk2 under limiting conditions, we used Skp2 knockout mice that exhibit increased levels of Cdk inhibitor, p27Kip1, which is able to inhibit Cdk2 and Cdk1. Knockdown of Cdk2 abrogated proliferation of Sk