Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program.

Based on the high-resolution X-ray crystallographic structure of phospholipase C from Bacillus cereus, the orientation of the phosphatidylcholine substrate in the active site of the enzyme is proposed. The proposal is based on extensive calculations using the GRID program and molecular mechanics geometry relaxations. The substrate model has been constructed by successively placing phosphate, choline and diacylglycerol moieties in the positions indicated from GRID calculations. On the basis of the resulting orientation of a complete phosphatidylcholine molecule, we propose a mechanism for the hydrolysis of the substrate.     

Characterizing the functional significance of the neonatal rat vibrissae prior to the onset of whisking

The present series of experiments assessed how information from the whiskers controls and modulates infant rat behavior during early learning and attachment. Passive vibrissal stimulation can elicit behavioral activity in pups throughout the first two postnatal weeks, although orienting to the source of stimulation is evident only after ontogenetic emergence of whisking. In addition, while pups were capable of demonstrating learning in a classical conditioning paradigm pairing vibrissa stimulation with electric shock, no corresponding changes were detected in the anatomy of the barrel cortex as determined by cytochrome oxidase (CO) staining. Finally, the role of whiskers in a more naturalistic setting was determined in postnatal day (PN)3-5 and PN11-12 pups. Our results showed that both nipple attachment and huddling were disrupted in whisker-clipped PN3-5 pups but only marginally altered in PN11-12 pups. Together, these results suggest that the neonatal whisker system is behaviorally functional and relevant for normal mother-infant interactions, though it lacks the sophistication of a mature whisker system that evokes very specific and directed responses.     

Burden of disease due to cancer in a Southern Brazilian state

Background: Despite the considerable epidemiological relevance of cancer in developing countries, there are very few studies of the burden related to cancer. The aim of this study was to present and discuss data from a burden-of-cancer study performed in a Southern Brazilian state. Methods: An epidemiological study of ecological design was performed to calculate the disability-adjusted life year (DALY) index. The study was based on records of individuals admitted and treated for cancer in the Brazilian National Health System Hospitals, or individuals who had died of cancer while residing in the state of Santa Catarina in 2008. Results: A total of 73,872.9 DALYs were estimated, which generated a rate of 1220.5 DALYs/100,000 inhabitants. The highest DALYs were those for cancer of the trachea, bronchus and lung with 179.0/100,000 inhabitants, gastric cancer with 101.7/100,000 inhabitants, and breast cancer with 99.7/100,000 inhabitants. The percentage contribution of the DALY component varied according to cancer type; however, mortality was the major component in all types. The highest rates were observed in 60–69-year-olds with 6071.3/100,000 inhabitants, in 70–79-year-olds with 5095.4/100,000 inhabitants, and in 45–59-year-olds with 3189.0 DALY/100,000 inhabitants; 53.7% of DALYs occurred in males. Conclusions: The greatest burden of disease due to cancer in Santa Catarina was attributed to cancer of the trachea, bronchus and lung, followed by gastric and breast cancers. The mortality component was responsible for the greatest burden.     

Structure of the Maturing 90S Pre-ribosome in Association with the RNA Exosome

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