3-Alkanoyl-5-hydroxymethyl tetronic acid homologues and resistomycin: new inhibitors of HIV-1 protease. I. Fermentation, isolation and biological activity

In the course of a screening program for HIV-1 protease inhibiting activity, six new homologues of 3-alkanoyl-5-hydroxymethyl tetronic acids (1 approximately 6) and the known natural product resistomycin (7) were isolated from cultures of the Actinomycete strain DSM 7357. The substituted tetronic acids belong to a recently described structural class of secondary metabolites. The HIV-1 activity of resistomycin (7) has not been reported before.     

Patterns of symptomatic recovery in psychotherapy.

Using the psychotherapy dosage model in which effect was probability of recovery, this study compared treatment response rates for psychological symptoms. Symptom checklists were administered to 854 psychotherapy outpatients at intake and during treatment. 62 symptoms were grouped into 3 classes on the basis of probit analysis results. Chronic distress symptoms demonstrated the fastest average response rate, whereas characterological symptoms demonstrated the slowest. Acute distress symptoms showed the highest average percentage of patients recovered across doses. A typical outpatient needed about a year of psychotherapy to have a 75% chance of symptomatic recovery. The model holds promise for establishing guidelines for the financing of psychotherapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling of dynamic crack propagation: II. Validation of two-dimensional analysis

The problem of fast fracture and crack arrest in rectangular fracture specimens under plane strain conditions is investigated within the confines of linear elastic fracture mechanics. A development consistent with the energy-balance criterion for fracture is obtained by first expressing the strain and kinetic energies in their finite-difference forms. These forms are used in Lagrange's equations and in the definition of the energy release rate to obtain the governing field equations. This development is subsequently used to make predictions that are compared with their measured counterparts. Agreement of predicted and observed compliances of SEN, CT, and DCB specimens is found to be very good. A direct comparison of predicted and measured results is made for a rapid fracture and crack arrest in an Araldite B DCB specimen. The predicted crack growth, crack-time history, and variations of the dynamic stress intensity factor and crack speed with crack length during propagation agree remarkably well with the experimental data.

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Résumé On étudie à l'aide de la mécanique de la rupture linéaire et élastique le problème de la fissure rapide et de l'arrêt de fissuration dans des éprouvettes de rupture rectangulaires soumises à des conditions d'état plan de déformation. Un développement compatible avec le critère d'équilibre de l'énergie pour la rupture est obtenu en exprimant d'abord les déformations et les énergies cynétiques sous des formes de différences finies. Ces formes sont utilisées dans les équations de Lagrange et dans la définition de la vitesse de relaxation d'énergie, afin d'obtenir des équations de champ. Ce développement est ensuite utilisé pour faire des prédictions qui sont comparées avec les mesures expérimentales. Un accord entre les compliances prédites et observées dans le cas d'éprouvettes SEN, CT et DCB, apparait comme particulièrement satisfaisant. Une comparaison directe des résultats prédits et mesurés est effectuée dans le cas d'une rupture rapide et dans le cas d'un arrêt de fissure dans une éprouvette DCB en Araldite B. La vitesse prédite pour la croissance de la fissure, le déroulement de la fissuration, et les variations dans le facteur d'intensité de contraintes dynamiques et dans la vitesse de fissuration en fonction de la longueur de la fissure au cours de la propagation sont en remarquable accord avec les données expérimentales.

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Part I will be published in the next issue.     

Increased intrusions during verbal recall in traumatic and nontraumatic lesions of the temporal lobe.

The mesial temporal and lateral frontal lobes were the most common sites of parenchymal abnormality on magnetic resonance imaging (MRI) scans for 12 patients with chronic traumatic brain injury (TBI). Ventricular widening was also common, and 3 patients showed increased size of the upper third ventricle. Of 10 right-handed TBI patients with no evidence of learning disability, 6 showed dominant temporal lesions and 3 showed an increase in the size of the upper third ventricle. Only patients with dominant temporal lesions (4 of 6) exceeded the normal confidence interval (based on 20 non-TBI controls) for intrusion errors on delay trials of the California Verbal Learning Test (CVLT), though other patients also demonstrated impaired recall. The pattern of increased intrusions during CVLT delay trials was confirmed in non-TBI patients who had undergone dominant temporal surgery or had dominant or bilateral temporal lesions, even when frontal changes could be ruled out. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinct roles for the mammalian A-type cyclins during oogenesis

There are two A-type cyclins in higher vertebrates, cyclin A1 and A2. Targeted mutagenesis has shown that cyclin A2 is essential for early embryonic development while cyclin A1 is required only for male meiosis. The embryonic lethality of cyclin A2 knockout mice has obviated understanding its role in other aspects of mammalian development, including the germ line. We reported previously that cyclin A2 expression in the male germ line is consistent with a role in both mitotic and meiotic cell cycles. Using in situ hybridization and immunohistochemistry, we now observe high levels of cyclin A2 in granulosa cells and less-abundant but readily detectable expression in ovarian and ovulated oocytes. A decrease in cyclin A2 protein was observed in oocytes from embryonic stages to post-natal and adult ovaries. Interestingly, cyclin A2 protein was nuclear in oocytes from embryonic day 13.5 to 15.5, changing to largely cytoplasmic in oocytes from embryonic day 16.5 to post-natal and adults. Readily detectable expression of the cyclin-dependent kinases Cdk1 and Cdk2, two common partners for the A-type cyclins, was observed in granulosa cells and oocytes at all stages of folliculogenesis. Cdk1 was predominantly cytoplasmic, whereas Cdk2 was both cytoplasmic and nuclear in oocytes. No cyclin A1 expression, at either the mRNA level or the protein level was detected in either embryonic or adult ovaries, consistent with the full fertility observed in female cyclin A1-deficient mice. These results suggest that in the female germ line, cyclin A2 but not cyclin A1 has distinct roles in both mitosis and meiosis.     

Effect of weightlifting upon left ventricular function and markers of cardiomyocyte damage

The purpose of this study was to assess left ventricular (LV) function and biochemical markers of myocyte after prolonged weightlifting activity. Seventeen male subjects (age range 20-34 years) performed a 90-min bout of weightlifting exercise consisting of three sets of 8-10 repetitions at 70% one-repetition maximum. Body mass, heart rate, systolic blood pressure (SBP) and echocardiographically determined indices of LV loading (LV internal diameter during diastole, LV meridonial wall stress), systolic function (stroke volume (SV), ejection fraction (EF), end-systolic pressure volume relationship; SBP/ESV) and diastolic filling (ratio of early to late; E:A) were obtained pre-exercise, immediately after and 24 h post-exercise. A 5-ml venous blood sample was obtained for the assessment of cardiac troponin T (cTnT) via third generation electrochemiluminescence assay. Data were assessed via one-way ANOVA and Pearson's correlation. Although SV declined (80.9 +/- 18.3 vs. 66.9 +/- 17.2, p < 0.05) there was no alteration in LV contractility (EF 62 +/- 6 vs. 59 +/- 7; SBP/ESV 3.51 +/- 1.4 vs. 3.51 +/- 1.4, p > 0.05). The E:A ratio was significantly decreased following exercise (1.78 +/- 0.41 vs. 1.33 +/- 0.37, p < 0.05). This decrease was not fully explained by loading conditions (r2 = 0.05 to 0.24). All values returned to baseline 24 h post-exercise. No cTnT was reported in any of the blood samples. In conclusion, there was no significant evidence of any LV contractile depression and no cTnT was observed post exercise. The small reduction in diastolic filling could not be explained by changes in haemodynamic loading or the post-exercise elevation in heart rate.     

Ward climate and community stay of psychiatric patients.

Administered a Ward Climate Inventory to 173 staff and 254 patients on 7 male wards of a neuropsychiatric hospital. 3 factors emerged from analyses: Factor I-personnel concern for patients; Factor II-patient concern for patients; and Factor III-ward morale. Elopement rate was significantly correlated with staff scores on Factors I and III and with magnitude of patient-staff differences on Factors I and III. Higher elopement rates were associated with lower personnel concern for patients, lower ward morale, and smaller patient-staff discrepancies in perceived personnel concern and ward morale. Release rates and community stay of unmarried schizophrenics were positively correlated with the patient-staff discrepancy score for Factor I. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nutrient digestion and lactation performance of dairy cows fed combinations of prilled fat and canola oil.

Four combinations of prilled fat and canola oil were fed to 10 lactating Holstein cows in a replicated 5 x 5 Latin square to determine whether mixing plant oil with a rumen inert fat had additive effects on digestive and lactation responses. Five diets of concentrate and corn silage (1:1, DM basis) contained either no added fat (control) or 5% fat comprising 100, 67, 33, or 0% prilled fat and the remainder canola oil. The fat supplement containing 100% prilled fat appeared to be rumen-inert because it caused no changes in ruminal VFA concentration, acetate to propionate ratio, or total tract fiber digestion. Prilled fat increased milk production, FCM, and milk fat percentage but decreased milk protein percentage, including casein content. Increasing canola oil in the fat supplement caused linear declines in ruminal VFA, acetate to propionate ratio, and milk production. Milk production efficiency (weight FCM/weight DMI) exceeded the control diet when fat supplements contained 100 or 67% prilled fat but dropped below control for 33 and 0% prilled fat. This study demonstrates additive effects of combining canola oil with hydrogenated, prilled fat on ruminal fermentation but nonadditive effects on milk production efficiency and milk composition. At low levels of supplementation, plant oils, such as the canola oil used in this study, can inhibit ruminal fermentation but still maintain milk production efficiency.