腺嘌呤与氢化可的松大鼠肾阳虚模型造模方法比较

目的比较腺嘌呤诱导与氢化可的松诱导的SD大鼠肾阳虚模型的优劣,从而得到临床症状、生化指标更符合中医“肾阳虚”型的动物模型,以供科研、教学使用。方法雄性SD大鼠100只,随机分成正常组、腺嘌呤造模组及氢化可的松低剂量组、中剂量组、高剂量组各20只,造模成功后检测血肌酐（Scr）、尿素氮（BUN）、尿液中17-羟皮质类固醇（17-OH）和血浆中甲状腺激素（13、T4）、睾丸酮（T）、雌二醇（E2）及模型大鼠骨密度。结果无论从症状主证方面,还是客观指标方面（除骨密度外）,腺嘌呤诱导的SD大鼠肾阳虚型动物模型在生化指标研究方面均优于氢化可的松诱导组。结论腺嘌呤诱导的肾阳虚证SD大鼠模型在症状主证方面及其相关的生化研究方面优于氢化可的松组。     

The effects of ten weeks of lower-body unstable surface training on markers of athletic performance

Initially reserved for rehabilitation programs, unstable surface training (UST) has recently grown in popularity in strength and conditioning and general exercise scenarios. Nonetheless, no studies to date have examined the effects of UST on performance in healthy, trained individuals. The purpose of this study was to determine the effects of 10 weeks of lower-body UST on performance in elite athletes. Nineteen healthy, trained members (ages 18-23 years) of a National Collegiate Athletic Association Division I collegiate men's soccer team participated. The experimental (US) group (n = 10) supplemented their normal conditioning program with lower-body exercises on inflatable rubber discs; the control (ST) group (n = 9) performed the same exercises on stable surfaces. Bounce drop jump (BDJ) and countermovement jump (CMJ) heights, 40- and 10-yard sprint times, and T-test (agility) times were assessed before and after the intervention. The ST group improved significantly on predicted power output on both the BDJ (3.2%) and CMJ (2.4%); no significant changes were noted in the US group. Both groups improved significantly on the 40- (US = -1.8%, ST = -3.9%) and 10-yard sprint times (US = -4.0%, ST = -7.6%). The ST group improved significantly more than the US group in 40-yard sprint time; a trend toward greater improvement in the ST group was apparent on the 10-yard sprint time. Both groups improved significantly (US = 2.9%, ST = -4.4%) on T-test performance; no statistically significant changes were apparent between the groups. These results indicate that UST using inflatable rubber discs attenuates performance improvements in healthy, trained athletes. Such implements have proved valuable in rehabilitation, but caution should be exercised when applying UST to athletic performance and general exercise scenarios.     

Rational design of inhibitors of VirA-VirG two-component signal transduction

VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium.     

Growth of a Molecular Base for Feeding: The Mind Body Dualism

It is often difficult to identify the ‘who, when, and where’ of advances in medicine and surgery because it's a rare advance indeed (such as the use of digitalis by William Withering) that can be clearly related to the astuteness of one person at one time and place.     

A Hidden Markov Model approach to variation among sites in rate of evolution

The method of Hidden Markov Models is used to allow for unequal and unknown evolutionary rates at different sites in molecular sequences. Rates of evolution at different sites are assumed to be drawn from a set of possible rates, with a finite number of possibilities. The overall likelihood of phylogeny is calculated as a sum of terms, each term being the probability of the data given a particular assignment of rates to sites, times the prior probability of that particular combination of rates. The probabilities of different rate combinations are specified by a stationary Markov chain that assigns rate categories to sites. While there will be a very large number of possible ways of assigning rates to sites, a simple recursive algorithm allows the contributions to the likelihood from all possible combinations of rates to be summed, in a time proportional to the number of different rates at a single site. Thus with three rates, the effort involved is no greater than three times that for a single rate. This "Hidden Markov Model" method allows for rates to differ between sites and for correlations between the rates of neighboring sites. By summing over all possibilities it does not require us to know the rates at individual sites. However, it does not allow for correlation of rates at nonadjacent sites, nor does it allow for a continuous distribution of rates over sites. It is shown how to use the Newton-Raphson method to estimate branch lengths of a phylogeny and to infer from a phylogeny what assignment of rates to sites has the largest posterior probability. An example is given using beta-hemoglobin DNA sequences in eight mammal species; the regions of high and low evolutionary rates are inferred and also the average length of patches of similar rates.      

Chronobiological effects on exercise performance and selected physiological responses

Previous studies investigating the impact of circadian rhythms on physiological variables during exercise have yielded conflicting results. The purpose of the present investigation was to examine maximal aerobic exercise performance, as well as the physiological and psychophysiological responses to exercise, at four different intervals (0800 hours, 1200 hours, 1600 hours, and 2000 hours) within the segment of the 24-h day in which strenuous physical activity is typically performed. Ten physically fit, but untrained, male university students served as subjects. The results revealed that exercise performance was unaffected by chronobiological effects. Similarly, oxygen uptake, minute ventilation and heart rate showed no time of day influences under pre-, submaximal, and maximal exercise conditions. Ratings of perceived exertion were unaffected by time of day effects during submaximal and maximal exercise. In contrast, rectal temperature exhibited a significant chronobiological rhythm under all three conditions. Under pre- and submaximal exercise conditions, significant time of day effects were noted for respiratory exchange ratio, while a significant rhythmicity of blood pressure was evident during maximal exercise. However, none of these physiological variables exhibited significant differential responses (percent change from pre-exercise values) to the exercise stimulus at any of the four time points selected for study. Conversely, resting plasma lactate levels and lactate responses to maximal exercise were found to be significantly sensitive to chronobiological influences. Absolute post-exercise plasma norepinephrine values, and norepinephrine responses to exercise (percent change from pre-exercise values), also fluctuated significantly among the time points studied. In summary, these data suggest that aerobic exercise performance does not vary during the time frame within which exercise is normally conducted, despite the fact that some important physiological responses to exercise do fluctuate within that time period. Accepted: 18 August 1997     

ERRATUM: Effects of Loading on the Biomechanical Behavior of Molars of Homo,Pan, and Pongo. Am J Phys Anthropol 109:211–227.

ERRATUM: Macho GA and Spears IR. 1999. Effects of Loading on the Biomechanical Behavior of Molars of Homo, Pan, and Pongo. Am J Phys Anthropol 109:211–227. The correct title of the article is given above. The word “biochemical” should be read as “biomechanical.”     

Crystal Structure and Computational Modeling of the Fab Fragment from a Protective Anti-Ricin Monoclonal Antibody

Background

Many antibody crystal structures have been solved. Structural modeling programs have been developed that utilize this information to predict 3-D structures of an antibody based upon its sequence. Because of the problem of self-reference, the accuracy and utility of these predictions can only be tested when a new structure has not yet been deposited in the Protein Data Bank.

Methods

We have solved the crystal structure of the Fab fragment of RAC18, a protective anti-ricin mAb, to 1.9 Å resolution. We have also modeled the Fv structure of RAC18 using publicly available Ab modeling tools Prediction of Immunoglobulin Structures (PIGS), RosettaAntibody, and Web Antibody Modeling (WAM). The model structures underwent energy minimization. We compared results to the crystal structure on the basis of root-mean-square deviation (RMSD), template modeling score (TM-score), Z-score, and MolProbity analysis.

Findings

The crystal structure showed a pocket formed mainly by AA residues in each of the heavy chain complementarity determining regions (CDRs). There were differences between the crystal structure and structures predicted by the modeling tools, particularly in the CDRs. There were also differences among the predicted models, although the differences were small and within experimental error. No one modeling program was clearly superior to the others. In some cases, choosing structures based only on sequence homology to the crystallized Ab yielded RMSDs comparable to the models.

Conclusions

Molecular modeling programs accurately predict the structure of most regions of antibody variable domains of RAC18. The hypervariable CDRs proved most difficult to model, particularly H chain CDR3. Because CDR3 is most often involved in contact with antigen, this defect must be considered when using models to identify potential contacts between antibody and antigen. Because this study represents only a single case, the results cannot be generalized. Rather they highlight the utility and limitations of modeling programs.