Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

Genomic instability can be found in most cancer cells. Cell proliferation is under tight control to ensure accurate DNA replication and chromosome segregation. Cyclin-dependent kinases (Cdks) and their activating subunits, the cyclins, are the driving forces of the cell division cycle. Regulation of cyclin oscillation by ubiquitin-dependent proteolysis thereby has a central role in cell cycle regulation. The anaphase-promoting complex (APC) is a specific ubiquitin ligase and is essential for chromosome segregation, exit from mitosis and a stable subsequent G1 phase allowing cell differentiation or accurate DNA replication in the following S phase. The APC is activated by the regulatory subunits Cdc20 (APC(Cdc20)) and Cdh1 (APC(Cdh1)) to target securin, mitotic cyclins and other cell cycle regulatory proteins for proteasomal degradation. This review is focused on the role of APC-dependent proteolysis in cell cycle regulation and how its deregulation may lead to genomic instability of cancer cells.     

Stiffness of the arterial wall, joints and skin in women with a history of pre-eclampsia

OBJECTIVE: The epidemiology of pre-eclampsia suggests a constitutional component for the disorder. We have recently shown an association for blood pressure (BP) with stiffness of joints and skin in adolescents, suggesting that constitutionally determined stiffness of body tissues is associated with blood pressure. Therefore, we compared stiffness of the arterial wall, joints and skin between women with a history of pre-eclampsia and women with an uncomplicated pregnancy. DESIGN: Cases were 44 women with a history of early onset pre-eclampsia and controls were 46 women with a history of uncomplicated pregnancy. Arterial stiffness was determined non-invasively with pulse wave velocity measurement. As a measure of capsule and ligament stiffness, the active range of motion of various joints was measured. Skin stiffness was measured using a tissue compliance meter. Analysis of variance (ANOVA) multiple comparison tests were used for comparison of the study groups. Linear regression models were used to determine the associations between stiffness parameters and possible confounders. RESULTS: For the cases, body mass index (BMI) was significantly higher and age and parity were significantly lower. BP was significantly higher for the cases. Stiffness of the arterial wall, joints and skin were significantly higher. After adjustment for mean arterial pressure, stiffness of the joints and skin were significantly higher, but no difference remained for arterial stiffness. CONCLUSIONS: Women with a history of pre-eclampsia had a significantly higher stiffness of the arterial wall, joints and skin compared with controls. This suggests a constitutionally determined stiffness of connective tissues in former pre-eclamptic cases.     

Anxiogenic-like effects of Tagetes minuta L essential oil on T-maze and tonic immobility behaviour in domestic chicks

Summary— In a first experiment, four doses (ranging between 0.04 and 0.45 mg/kg of body weight) of the essential oil from Tagetes minuta L. were subcutaneously injected in two-day-old chicks and a dose-response curve assessed for escape performance in a T-maze test. The 0.1, 0.25 and 0.45 mg/kg doses impaired the first escape performance suggesting an anxiogenic-like effect of the essential oil. After 3 h the same chicks were tested for a second escape performance, without being injected again, and no differences were observed compared to controls, suggesting that the essential oil did not affect retention. Furthermore, the effects of the essential oil were observed in the three sections of the T-maze apparatus. So, the performance was impaired in the isolation chamber section, suggesting the induction of increased anxiogenic behaviour, and also in the mirror section, suggesting that the social reinstatement behaviour was modified by an increased anxiety level. Changes in the principal corridor section were not observed, suggesting that the locomotor activity was not affected by these oil doses. The second escape performance was not affected in any of the T-maze sections, confirming that these doses did not affect learning ability. In a second experiment, a middle dose of the essential oil (0.25 mg/kg) increased the tonic immobility reaction in 15 days old chicks similarly to an anxiogenic dose of FG 7142 (1 mg/kg), while an anxiolytic dose of diazepam (0.08 mg/kg) did not affect this behaviour. Taken together, the present results suggest that the essential oil from Tagetes minuta L. may exert a negative modulation on the GABAergic function without affecting the learning ability.     

Low-dose flying spot digital radiography of the chest: sensitivity studies

Standard film examinations of the chest were compared with low-dose flying spot digital radiographic examinations obtained with a prototype unit in 174 patients. Analysis of pooled data from a double-blind study of 120 patients showed that film was more sensitive than digital images in the detection of pulmonary parenchymal abnormalities, that is, abnormal opacities, atelectasis, scar, and interstitial lung disease (P less than .05). Analysis of pooled data from a side-by-side study of 54 patients showed that the digital images were more sensitive than film in the detection of normal mediastinal and pleural soft-tissue contours, including the azygoesophageal recess, paraspinal line, and vertebral disk spaces (P less than .05). However, film was more sensitive than digital images in the detection of abnormalities of the lung, including scar, interstitial lung disease, septal lines, and the presence of vascular catheters (P less than .05). These findings suggest that low-dose flying spot digital radiography of the chest, as performed with this specific prototype unit, is not adequate to replace film in the detection of abnormalities of the lung parenchyma.