Use of a minimum perturbation approach to predict TIM mutant structures

A minimum perturbation conformational search approach is usedto model the structures of the yeast triosephosphate isomerase(TIM) single mutant in which the catalytic base Glul65 is changedto Asp, and the double mutant in which Glul65 is changed toAsp and Ser96 to Pro. In chicken TIM this double mutant is referredto as a pseudo–revertant because some of the catalyticactivity lost due to the first mutation is regained when thesecond mutation occurs. Three minimum energy structures werecalculated for the Asp 165 conformation in the yeast TEM singlemutant and another three for the double mutant One of the calculatedminimum energy conformations for Aspl65 in the E165D structureagrees well with the X–ray structure. However, this conformationis not that of the lowest energy and is not one of the threemost common conformers for Asp found by Ponder and Richards.This suggests that when an amino acid is introduced it may notbe able to conform to the more general rules that apply to proteinstructures of evolutionary origin. While the van der Waals energylargely determines the allowed minima, the relative rankingof the final minima is determined by electrostatic effects andcan therefore be affected by the inclusion of crystal watersin the calculation. When the E165D calculation is repeated withan active–site water molecule fixed in its E165D X–raystructure position, the relative ranking of the minima shiftsand the X–ray conformation for Asp 165 is the lowest interactionenergy conformer. Two of the E165D calculated minimum energystructures are essentially identical to two of the S96P/E165Dminima. All of the calculated minima for both the E165D andS96P/E165D mutants position the Asp side chain such that theanti–orbital, and not the more basic syn–orbital,of the carboxylate would be utilized for proton abstraction.This observation may explain why the chicken TIM S96P/E165Dmutant, for which the X-ray structure indicates that the syn–orbitalis used, is a pseudo–revertant while the yeast TIM doublemutant is not; no X–ray structure is available for thelatter. The multiplicity of minima found in the present analysismakes clear that predicting the exact orientation of a singleside chain is not as simple as might be expected.     

Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking.

Sensorimotor electroencephalogram (EEG) frequencies in cats were evaluated with power spectral analysis before and after 3 doses of atropine sulfate. All doses of atropine tested caused enhanced EEG slow waves (0–7 Hz) and spindles (8–25 Hz) during waking immobility, and postdrug frequency profiles during slow-wave sleep and waking immobility were identical. With 0.75 mg/kg atropine, movement (head movement, locomotion) resulted in EEG desynchronization and reduced power in all frequencies less than 24 Hz. After 1.5 or 3.0 mg/kg atropine, power in low frequencies remained elevated during movement, but power in spindle frequencies was significantly reduced compared with other states. During active REM sleep after 1.5 mg/kg atropine, power in spindle frequencies was significantly lower than that during quiet REM sleep. These results indicate that the sensorimotor cortical EEG in cats is under the control of multiple systems. At least 1 of these systems is active during movement, and its actions are resistant to muscarinic receptor blockade. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

正确选择合适的熔丝

一般而言,电路保护器件通常在电路设计中扮演着最不起眼的角色:人们通常都是在完成设计之后才想起它们,而且对其琐碎的电气特征不胜其烦.     

Failure of stationary but not of flying honeybees (Apis mellifera) to respond to magnetic field stimuli.

Trained individual honeybees (Apis mellifera) to feed to repletion from a well of sucrose solution so constructed that shock could be delivered when the proboscis was in contact with the solution. If shock was signaled by vibration of the substrate or by an airstream, the animals learned readily to avoid it by breaking contact briefly, but there was no response to change (either constant or time-varying) in the ambient magnetic field. When, however, a magnetic field anomaly in the region of the food well signaled to flying animals that contact would be punished with shock, hesitation to settle was greater in presence than absence of the anomaly. Parallel results were obtained with light, to which flying Ss clearly responded but to which stationary Ss hardly responded at all. We conclude that stationary bees detect magnetic field stimuli but do not process them successfully in the training situation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activities and well-being in older age: Effects of self-concept and educational attainment.

The positive effect of activities on well-being is proposed to be mediated by self-conceptualizations and facilitated by socioeconomic status. The hypothesized processes were estimated with LISREL VIII using data from a large cross-sectional survey with a sample of 679 adults aged 65 and older who were representative of older adults living in the Detroit area. Findings indicate that the frequency of performing both leisure and productive activities yields an effect on physical health and depression and that these effects are mediated in part by a sense of self as agentic, but less clearly by a sense of self as social. Furthermore, socioeconomic status, operationalized as formal educational attainment, facilitates the effect of leisure to a greater extent than that of productive activities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parents' ethnic-racial socialization practices: A review of research and directions for future study.

Recently, there has been an emergence of literature on the mechanisms through which parents transmit information, values, and perspectives about ethnicity and race to their children, commonly referred to as racial or ethnic socialization. This literature has sought to document the nature of such socialization, its antecedents in parents' and children's characteristics and experiences, and its consequences for children's well-being and development. In this article, the authors integrate and synthesize what is known about racial and ethnic socialization on the basis of current empirical research, examining studies concerning its nature and frequency; its child, parent, and ecological predictors; and its consequences for children's development, including ethnic identity, self-esteem, coping with discrimination, academic achievement, and psychosocial well-being. The authors also discuss conceptual and methodological limitations of the literature and suggest directions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Methods to Characterize Ricin for the Development of Reference Materials

Ricin is an abundant protein from the castor bean plant Ricinus communis. Because of its high toxicity and the simplicity of producing mass quantities, ricin is considered a biological terrorism agent. We have characterized ricin extensively with a view to develop Reference Materials that could be used to test and calibrate detection devices. The characterization of ricin includes: 1) purity test of a commercial batch of ricin using electrophoresis in polyacrylamide gels, 2) biological activity assay by measuring its ability to inhibit protein synthesis, 3) quantitation of protein concentration by amino acid analysis, 4) detection of ricin by an immunoassay using a flow cytometer, and 5) detection of ricin genomic DNA by polymerase chain reaction using nine different primer sets. By implementing these five methods of characterization, we are in a position to develop a reference material for ricin.     

Mucosal Delivery of Progestational Steroids from a Controlled Release Device: In-Vitro/In-Vivo Relationships

The mucosal delivery of progestational steroids from a model controlled release device was studied using female New Zealand White rabbits as the animal model. A controlled release device was developed which was suitable for nasal, rectal and vaginal application. The in-vitro permeation and in-vivo absorption of progesterone from the model controlled release device was investigated through the nasal, rectal and vaginal mucosa. The influence of penetrant hydrophilicity on the in-vitro permeation and in-vivo absorption from the controlled release device was also investigated using the mono-hydroxy, di-hydroxy and tri-hydroxy derivatives of progesterone. The results indicate that the nasal route demonstrates a significantly higher rate of in-vitro permeation and extent of in-vivo absorption than the rectal and vaginal mucosa. The in-vitro permeation rates and steady-state plasma concentrations achieved from the device tend to decrease with increasing penetrant hydrophilicity. A linear in-vitro/in-vivo correlation was obtained for all the mucosa studied. The slope of the relationship between the in-vitro and in-vivo data was similar for the rectal and vaginal mucosa. The results of this investigation agree with the results of a previous investigation with a solution formulation, and suggest that the hydrodynamic and/or membrane barrier properties of the nasal mucosa may from that of the rectal and vaginal mucosa.