beta Recombinase catalyzes inversion and resolution between two inversely oriented six sites on a supercoiled DNA substrate and only inversion on relaxed or linear substrates

The beta recombinase, in the presence of a chromatin-associated protein such as Hbsu, catalyzes DNA resolution or DNA inversion on supercoiled substrates containing two directly or inversely oriented six sites. Hbsu stabilizes the formation of the recombination complex (Alonso, J. C., Weise, F., and Rojo, F. (1995) J. Biol. Chem. 270, 2938-2945). In this study we show that resolution by beta recombinase strictly requires supercoiled DNA, but inversion does not. On a substrate with two inversely oriented six sites, beta recombinase catalyzed both resolution and inversion if the DNA was supercoiled but only inversion if the substrate was relaxed or linear. Hbsu was critical for the formation of synaptic complexes; its concentration relative to that of the supercoiled DNA substrate determined whether resolution or inversion products were preferentially formed. The results suggest that the beta recombinase forms unproductive short-lived synaptic complexes between two juxtaposed inversely oriented six sites; the presence of 3 to 13 Hbsu dimers per supercoiled DNA molecule would stabilize a synaptic complex with a relative geometry of the six sites allowing beta recombinase preferentially to achieve resolution. Supercoiling probably helps to overcome an energetic barrier, since resolution does not occur in relaxed DNA. The presence of >30 Hbsu dimers per DNA molecule probably favors the formation of a recombination complex with a different geometry since the reaction is directed preferentially toward DNA inversion.     

Categorical scaling of time: Implications for clock-counter models.

Pigeons partitioned time into three intervals. Responses to one key could be reinforced after a short time, to a second key after an intermediate time, and to a third key after a long time. The values of the short, intermediate, and long times and the proportion of trials ending with reinforcement were varied. Absolute and relative response rates on each key were an orderly function of time and showed approximately proportional changes with changes in the interval values, consistent with Weber's law, Gibbon's (1977) scalar expectancy theory, and Killeen and Fetterman's (1988) behavioral theory of timing (BeT). Standard deviations of the times at which subjects switched between successive keys increased more slowly within a condition than across conditions, as predicted by BeT. Increases and decreases in reinforcement probability produced both transient and longer lasting changes in timing behavior, once again, in accord with predictions of BeT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integrating neural network technology and noise analysis

The integrated use of neural network and noise analysis technologies offers advantages not available by the use of either technology alone. The application of neural network technology to noise analysis offers an opportunity to expand the scope of problems where noise analysis is useful and unique ways in which the integration of these technologies can be used productively. The two-sensor technique, in which the responses of two sensors to an unknown driving source are related, is used to demonstration such integration. The relationship between power spectral densities (PSDs) of accelerometer signals is derived theoretically using noise analysis to demonstrate its uniqueness. This relationship is modeled from experimental data using a neural network when the system is working properly, and the actual PSD of one sensor is compared with the PSD of that sensor predicted by the neural network using the PSD of the other sensor as an input. A significant deviation between the actual and predicted PSDs indicate that system is changing (i.e., failing). Experiments carried out on check valves and bearings illustrate the usefulness of the methodology developed.     

Maternal complications from tocolytic treatment with beta-mimetics. Three cases of pulmonary edema

We report three cases of pulmonary edema associated with prolonged intravenous tocolytic therapy with beta 2-adrenergic agonists among patients with multiple pregnancies. Although beta 2-adrenergic agonists may have direct myocardial side-effects, the underlying pathophysiologic mechanisms are mainly noncardiogenic. The most important one appears to be the fluid overload, related to amounts of fluids given intravenously and to direct result of beta-sympathomimetic therapy on renal excretion of sodium and water. Neonatal benefit of prolonged tocolytic therapy remains hypothetical. If this strategy is used, the prevention of cardiovascular adverse effects requires an intensive maternal supervision, especially in case of multiple pregnancy, the use of beta 2-adrenergic agonists in concentrated solution in order to reduce the amounts of fluids given intravenously, and the association with progesterone therapy which can reduce the infusion rate and the duration of tocolytic therapy.     

Traumatic myocardial infarction caused by lead shot

The authors report the case of a 32 year old woman who was shot with a shotgun. Acute inferior wall infarction was detected fortuitously on electrocardiography and coronary angiography showed occlusion of the right coronary artery with lead shot. The single coronary lesion, absence, of other cardiac complications (haemopericardium, cardiac perforation, ...) and the favourable outcome with conservative medical treatment has not been previously reported to the authors' knowledge.     

A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors

BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PATIENTS AND METHODS: PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. RESULTS: No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). CONCLUSION: This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.