Inclusion of salt in the refolding conditions prevents the reversibility of mutant having charge substitution, while the reversibility of mutant with the introduction of proline was unaffected, indicating the role click here of charge mediated interaction in M134E in preventing aggregation. Partial prevention of thermal aggregation in wild-type lipase with single substitution, M137P, incorporated by site-directed mutagenesis, suggests that the affect of M137P is independent of the intrinsic thermostability of lipase. Various effects of the mutations suggest their

role is in prevention of the formation of aggregation prone intermediate(s). These mutations, describe yet another strategy to enhance the thermotolerance of proteins, where their influence is observed only on the denatured ensemble.”
“The behavioral effects of exposure to environmentally relevant low levels of the known neurotoxicants lead (Pb) and manganese (Mn) are of current interest, especially when exposure occurs in the period of early development. The incidence of real life neurodevelopmental toxicity is dependent on co-exposure to multiple neurotoxicants present in the environment, and it is therefore important to study these in combination.

Pregnant rats were given ad libitum access to drinking water solutions containing Pb (10 mu g/mL), Mn (2 mg/mL) or a mixture, from beginning of gestation, through lactation and until

weaning. Metal-exposed pups were born with significantly higher body weights compared to controls. selleck While female pups exposed to metal mixtures displayed the highest body weights through two months of age, differences were not significant among male pups after the first week. Mixture-exposed pups exhibited the fastest righting times when tested between postnatal days (PNDs) 1 and 10. Learning and memory were assessed in five-day Morris water maze (MWM) tests, ending in probe trials out on PNDs 25 and 60. On PND 24, mixture-exposed males performed significantly better than individual metal-exposed males, but this effect was no longer evident between PNDs 56 and 60. Females exposed to Pb or Mn displayed deficits at both behavioral time points. In the open-field test, Mn-exposed males were hypoactive and displayed greater anxiety than controls on PND 24, and showed similar trends when the test was repeated on PND 59. No such differences were observed in female pups or in pups exposed to metal mixture. Metal levels analyzed in blood, brain and milk samples suggested a pharmacokinetic interaction between Pb and Mn. Therefore, developmental exposures to low levels of Pb and Mn can produce gender-specific neurobehavioral deficits, and this study underlines the importance of studying toxicants in combination. (C) 2012 Elsevier Inc. All rights reserved.