Activitéin vivo de dérivés de la thiourée contre le virus de l'influenza

Summary A large number of sulphur-containing compounds bearing the thiourea group -NH-CS-NH-, including substituted thiocarbanilides, 1-acyl-4-arylthiosemicar-bazides, 1-(arylaminothioformyl)-thiosemicarbazides, 4-aryl-1-(arylaminothioformyl)- thiosemicarbazides, and other related substances have been tested for potential antiviral activity. Several of these compounds have been found chemotherapeutically active against influenza virus.

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Communication présentée au Congrès international de Chimie pure et appliquée de Zürich (Juillet 1955).     

Mutations in SEC63 cause autosomal dominant polycystic liver disease

Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.     

The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5^KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro-irradiated Cdk5^KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5^KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5-dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5^KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5^KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels.     

Superoxide dismutase activity during the plasmodial life cycle ofPhysarum polycephalum

Summary Superoxide dismutase activity was slow throughout the cell cycle of surface cultures ofPhysarum polycephalum. This activity increased markedly when the organism was induced to spherulate. Glutathione (GSH) and hydrogen peroxide (H₂O₂) concentrations changed very little during the cell cycle. During spherulation GSH decreased; H₂O₂ and the cyanide-resistant respiration of plasmodial homogenates increased.     

Activation with (±)N-n-propyl-nor-apomorphine (NPA) of the male rat copulatory behavior

Summary I.p. (±)N-n-propyl-nor-apomorphine HCl (NPA) influences copulatory behavior of vigorous adult male rats in the same ways as apomorphine, i.e., it reduces the latency to ejaculation as well as mount and intromission frequency. Furthermore, NPA administered to impotent male rats restores normal mating behavior in some of them.     

Estimation procedures for understory biomass and fuel loads in sagebrush steppe invaded by woodlands

Regression equations were developed to predict biomass for 9 shrubs, 9 grasses, and 10 forbs that generally dominate sagebrush ecosystems in central Nevada. Independent variables included percent cover, average height, and plant volume. We explored 2 ellipsoid volumes: one with maximum plant height and 2 crown diameters and another with live crown height and 2 crown diameters. Dependent variables were total, live, leaf, and dead biomass. Simple, multiple, linear, and power equations were investigated. Models were chosen based on scatter plots, residual plots, and R 2 and SEE values. In general, simple power equations provided the best-fit regressions. For shrubs, the ellipsoid volume computed with maximum plant height best predicted total plant weight, and the ellipsoid volume computed with the live crown height best predicted shrub foliage weight. In addition to regression equations for biomass, ratios for division of that biomass into 1-, 10-, 100-, and 1000-hour fuels were derived for common large shrubs. Regression equations were also derived to relate litter mat sizes of major shrub species to litter weights. The equations in this paper could be used to predict biomass in other areas of the Great Basin if training data were taken to validate or adjust these models.     

Analytisch-chemische Bestimmung nichtradioaktiver Stoffe mit einem Flüssig-Szintillationsspektrometer durch Radiolumineszenz und Absorptionsphotometrie im Čerenkov-Licht

Summary Three techniques are described which allow a quantitative chemical determination of non-radioactive substances by the means of a liquid scintillation counter. The first method is based on the chemical quenching of a radioluminescent solution through the substance that is to be determined. The second method may be described as absorption photometry in erenkov-light and the third one as absorption photometry in radiofluorescence light.     

Role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion

The role of protein kinase C and Ca²⁺ in glucose-induced sensitization/desensitization of insulin secretion was studied. A 22–24h exposure of mouse pancreatic islets to glucose (16.7 mmol/l) in TCM 199 culture medium, with 0.26 mmol/l or 1.26 mmol/l Ca²⁺, reduced total islet protein kinase C activity to approx. 85% and 60% of control values, respectively. At 0.26 mmol/l Ca²⁺ in TCM 199 medium, exposure to glucose (16.7 mmol/l) led to a potentiation of both phase 1 and phase 2 of glucose-induced insulin secretion, and caused a shift in the dose-response curve with 10 mmol/l and 16.7 mmol/l glucose exhibiting equipotent effects in stimulation of insulin secretion. In glucose-sensitized islets, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (0.16 μmol/l) did not further potentiate induction of secretion by 10 mmol/l or 16.7 mmol/l glucose. At 3.3 mmol/l glucose, however, phorbol ester-induced secretion was augmented, and was characterized by a faster onset of secretion in glucose-sensitized islets relative to control islets. In contrast, a partial reduction in arachidonic acid (100 μmol/l)-induced insulin release was observed in glucose-sensitized islets in the absence of extracellular Ca²⁺. Increasing the Ca²⁺ concentration to 1.26 mmol/l in TCM 199 during the 22–24h exposure to glucose (16.8 mmol/l) led to inhibition of phase 1 and abolition of phase 2 of glucose (10 mmol/l, 16.7 mmol/l)-induced insulin secretion. In addition, this treatment abolished phorbol ester-induced and arachidonic acid-induced insulin secretion at 3.3 mmol/l glucose. Altogether, these data suggest that sensitization of insulin secretion is caused by a preferential down-regulation of the inhibitory effects of protein kinase C, leading to an increased first phase, and an increased coupling of glucose to the stimulatory effects of protein kinase C during the second phase of glucose-induced insulin secretion. Desensitization of insulin secretion appears to be a consequence of sustained Ca²⁺ influx, inducing extensive down-regulation of protein kinase C and also causing deleterious effects on islet cell function in protein kinase C-deprived islets.