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.

Germ-line mutations in BRCA2 have been linked to early-onset familial breast cancer. BRCA2 is known to play a key role in repairing double-strand breaks. Here,we describe the involvement of BRCA2 in O6-alkylguanine DNA alkyltransferase (AGT)-mediated repair of O6-methylguanine adducts. We show that BRCA2 physically associates and undergoes repair-mediated degradation with AGT. In contrast, BRCA2 w

Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2-/- mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial

Centrosomes organize the microtubule cytoskeleton for both interphase and mitotic functions. They are implicated in cell-cycle progression but the mechanism is unknown. Here, we show that depletion of 14 out of 15 centrosome proteins arrests human diploid cells in G1 with reduced Cdk2-cyclin A activity and that expression of a centrosome-disrupting dominant-negative construct gives similar results

Cisplatin is one of the most effective chemotherapeutics, but its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of these studies was to determine the mechanism of cisplatin cytotoxicity. It was shown in vivo that cisplatin administration induces upregulation of the gene for the p21 cyclin-dependent kinase (cdk) inhibitor in kidn

The cyclin-dependent kinase inhibitor p27Kip1 is known as a negative regulator of cell-cycle progression and as a tumour suppressor. Cdk2 is the main target of p27 (refs 2, 3) and therefore we hypothesized that loss of Cdk2 activity should modify the p27-/- mouse phenotype. Here, we show that although p27-/- Cdk2-/- mice developed ovary tumours and tumours in the anterior lobe of the pituitary, we

It has long been believed that Cdk2 and its activator cyclin E play essential roles in the progression of the mitotic cell cycle. However, recent studies using knockout mouse models revealed that neither Cdk2 nor cyclin E are essential in vivo. The purpose of this Perspective is to compare both Cdk2 and cyclin E knockout mice models and to discuss potential mechanisms driving the cell cycle in the

Cyclin-dependent kinases (CDKs) that control cell cycle progression are regulated in many ways, including activating phosphorylation of a conserved threonine residue. This essential phosphorylation is carried out by the CDK-activating kinase (CAK). Here we examine the effects of replacing this threonine residue in human CDK2 by serine. We found that cyclin A bound equally well to wild-type CDK2 (C

Ge nanoparticles embedded in thin films have attracted a lot of attention due to their promising optical and electronic properties that can be tuned by varying the particle size and choice of matrix material. In this study, Ge nanoparticle formation was investigated for Al-Ge-N based thin films by simultaneous measurements of HAXPES and grazing incidence XRD during in situ annealing in vacuum cond

The valence bands of [EMIM][TFSI], [DEME][TFSI] and [PYR1,4][TFSI] gas-phase ion pairs have been investigated using ultraviolet photoelectron spectroscopy (UPS). The photoelectron spectra are interpreted by using several density functional and ab initio calculation methods. Although the experimental vapor phase spectra are similar, the different calculation methods make different predictions about

The world faces major climate challenges and extensive efforts need to be taken to combat this issue. Replacing fossil-derived fuels and chemicals with renewables are one important step on the way. Hydrogen has a great potential as a renewable energy carrier for the transport sector and as a green chemical for the industry. Today, the production of hydrogen stems primarily from fossil resources. A

Background: Carpal tunnel syndrome (CTS) is a common cause of pain, weakness, sensory loss, and activity limitations. Currently, the most common initial treatment is use of a rigid splint immobilizing the wrist, usually during night-Time, for several weeks. Evidence regarding the efficacy and effect durability of wrist splinting is weak. The treatment is associated with costs and may cause discomf

Background: The current study aimed at exploring adolescents' experiences of online sexual contacts leading to online sexual abuse by a perpetrator whom the victim had first met online. Associations with socio demographic background, experience of abuse, relation to parents, health and risk behaviors were studied. Methods: The participants were a representative national sample of 5175 students in

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

Cyclin-dependent kinases (Cdks) are serine/threonine kinases and their catalytic activities are modulated by interactions with cyclins and Cdk inhibitors (CKIs). Close cooperation between this trio is necessary for ensuring orderly progression through the cell cycle. In addition to their well-established function in cell cycle control, it is becoming increasingly apparent that mammalian Cdks, cycl

Geotechnical engineering is the science dealing with mechanics of soils and rocks and its engineering applications. Geotechnical engineering projects vary in a wide range, from evaluation of the stability of natural slopes and man-made soil deposits, to the design of earthworks and foundations. Traditional methods, using manual calculations or simplified computational methods, do not, as a rule, t

Ischemia/reperfusion (I/R) injury to the heart is accompanied by the upregulation and posttranslational modification of a number of proteins normally involved in regulating cell cycle progression. Two such proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play a critical role in the control of apoptosis. Myocardial ischemia activates C

Inactivation of cyclin-dependent kinases (Cdks) and/or cyclins in mice has changed our view of cell cycle regulation. In general, cells are far more resistant to the loss of Cdks than originally anticipated, suggesting widespread compensation among the Cdks. Early embryonic cells are, so far, not sensitive to the lack of multiple Cdks or cyclins. In contrast, differentiated cells are more dependen