Correction of distortion of histologic sections of arteries

Histologic sections of arteries can be used to generate three-dimensional (3D) geometric models and identify structural constituents. However, geometric distortions are introduced by fixation, embedding and sectioning; distortions which can, for example, lead to errors in stresses predicted by finite element models. We developed a method to measure and correct for distortions caused by acrylic processing and applied it to intact, healthy porcine coronary arteries. Micro-computed tomography was used to image arteries in the fresh and embedded states. Tissue blocks were sectioned, stained and imaged using a light microscope. Each section contained four registration marks used to determine strains introduced by sectioning and staining. Using these three image sets, 3D geometric models were generated and distortions were measured. Fixation, processing, and embedding resulted in shrinkage of 6.4+/-2.3% axially and 35.4+/-5.0% in mean cross-sectional area (n=5). Shrinkage in a cross section was well characterized by a uniform, equibiaxial strain. Sectioning and staining resulted in additional compressive strains in the sectioning direction of 0.067+/-0.011 and, in the direction perpendicular to sectioning, of 0.023+/-0.005 (n=5). These strains are assumed uniform and form the basis for correcting section geometry. Reconstructions using corrections for sectioning and shrinkage-related distortions had errors of 1.6+/-0.5% (n=5) and 4.0+/-1.7% (n=5), respectively.     

Principles of classification of life forms of plants

For classifying life forms of plants a proposal was made to use the principle of parallel divergence based on the hypothesis that life forms diverging to any degree preserve further the potential of evolving in a similar way, that is, in parallel series. Life forms of plants are divided into thirteen types corresponding to the nature of their basic metameres. Further, every type is divided into subtypes and sections according to the character of these metameres and then into smaller grades (classification units of the system of living forms corresponding to one trait and its evolutionary level) according to categories of traits: ramification, vegetative flexibility, rate of changes of metameres, types of habitat and environment. On the basis of the principle of parallel divergence scales of traits were constructed for each category. Corresponding to 26 paires of alternative traits 26 degrees of hierarchic classification were devised and within the limits of every type of life form there were 2(26) grades at the lowest rank. Separate systems were developed for single-celled and colonial forms.     

Shapes of curves of pH-dependence of reactions

A simple case is considered in which the rate of a two-step reaction depends on pH because the intermediate formed in the first step has to gain (or lose) a proton before it can react in the second step, and in which the rate-determining step therefore changes with pH. The curves of reaction rate against pH are shown to be symmetrical, and the sharpest peak possible has a width at half its height of 1.53pH units, i.e. of 2log(3+2 radical2). Any particular curve for this situation proves to be identical with a curve that could be generated for the pH-dependence of a single-step reaction in which the rate is proportional to the concentration of a particular ionic form of a reactant. Curves for the latter situation, however, can have forms impossible for the former case in which the rate-determining step changes, but only if the protonations that activate and deactivate the reactant are co-operative. The peak can then become even sharper, and its width at half its height can fall to 1.14pH units, i.e. to 2log(2+ radical3).     

基于医疗服务绩效信息透明的质量促进效果研究综述

利用描述性综述的方法,总结近10年来医疗服务绩效信息透明对医疗质量促进效果,根据纳入排除标准检索Web of Knowledge、Pubmed等数据库,最终纳入31篇密切相关文献。结果表明,国外一般通过医疗报告卡或网站向公众公开医疗服务绩效信息,改善了医疗服务行为,但对病人选择服务提供者和临床结果的改善作用有限。我国应制定相关政策,推动医疗服务绩效信息向更广泛的使用者公开,引导病人利用医疗服务绩效信息选择医疗服务提供者。     

Effect of composition of cellular lipids of formation of nonspecific antibiotic resistance of alkanotrophic rhodocoocci

The antibiotic resistance and lipid composition of rhodococci grown in rich organic media with gaseous or liquid n-alkanes were studied. Hydrocarbon-grown rhodococci exhibited an increased resistance to a wide range of antibiotics (aminoglycosides, linkosamides, macrolides, beta-lactams, and aromatic compounds). The enhanced antibiotic resistance of rhodococci grown on n-alkanes correlated with an increased content of total cell lipids (up to 14-28%) and saturated straight-chain fatty acids (C16:0, C18:0, C21:0) and was accompanied by the appearance of cardiolipin and phosphatidylglycerol in cells. These lipid compounds were supposed to promote the formation of nonspecific antibiotic resistance in rhodococci by decreasing the permeability of their cell envelope to antibiotics.     

Use of complex assessment of dermatoglyphic signs for prediction of the risk of development of occupational diseases

Dermatoglyphic investigations conducted by the authors made it possible to demonstrate a genetic predisposition to occupational diseases, in particular, to silicosis and silicotuberculosis. Methods based on the mathematical theory of pattern recognition were used for multifactor analysis of the data. It was shown that complex evaluation of 10 dermatoglyphic indices gave a reliable prognosis of the risk of the above two kinds of disease due to silica dust. The dermatoglyphic patterns which predict predisposition to simple silicosis or to silicotuberculosis were found to differ significantly.     

Modulation of phenotypic expression of fibroblasts by alteration of the cytoskeleton

Several studies indicate that the cytoskeleton may be involved in modulating the cellular response to environmental signals. We have studied the role of the cytoskeleton in regulating glycosaminoglycan (GAG) synthesis and secretion, hyaluronate (HA) endocytosis, the activities of hexoglycosidases, protein synthesis and secretion. Fibroblasts were treated with colchicine (1–8 μM ) and nocodazole (1 or 4 μM ) to alter microtubules or cytochalasin B (0·5–4 μM ) to alter microfilaments. Colchicine inhibited GAG synthesis and secretion in a concentration-dependent manner. It reduced protein and sulphated GAG secretion, while HA secretion was not affected. Concentration-dependent disruption of microtubules from the periphery toward the cellular centre with nocodazole inhibited only the secretion of GAG. Centrosomal microtubles appeared to be required to promote GAG synthesis; intact microtubules promoted the transport of secretory products, intercompatmental transport of lysosomal enzymes and lysosome maturation, but not protein synthesis and HA secretion. Cytochalasin B treatment inhibited, in a concentration-dependent manner, the synthesis and secretion of GAGs and proteins, and the endocytosis of HA. Intact microfilament mesh-works appeared to be required to promote synthesis and secretion of proteins and proteoglycans and to contribute to the transmembrane control of receptor-mediated endocytosis. Drug treatment of concanvalin A (Con A)-stimulated fibroblasts inhibited the stimulation of GAG synthesis. It is probable that this effect may result, in part, from drug-induced effects on Con A-mediated endocytosis.     

Relative frequencies of different kinds of spontaneous and induced mutants of pneumococci and streptococci capable of growth in the presence of streptomycin

Ravin, Arnold W. (University of Rochester, Rochester, N.Y.), and Ajit K. Mishra. Relative frequencies of different kinds of spontaneous and induced mutants of pneumococci and streptococci capable of growth in the presence of streptomycin. J. Bacteriol. 90:1161-1173. 1965.-Mutations conferring ability to grow in the presence of streptomycin arise spontaneously and can be induced in pneumococci and streptococci. They prove to be of several phenotypic and genetic types, which may be classified as follows: VLR, LR, and HR, which confer resistance, respectively, to less than 50, between 50 and 500, and 500 or more mug/ml of streptomycin. VLR and LR mutations recombine with each other, whereas HR mutations generally replace (do not recombine with) several of the VLR and LR mutations. Spontaneously, the VLR type is several times more frequent than the LR and HR types, which are equally frequent relative to each other. Nitrous acid treatment of deoxyribonucleic acid (DNA) in vitro or ultraviolet irradiation of cells tends to produce the VLR and LR type of mutation. Streptomycin-dependent mutations are rare in the pneumococci and streptococci. One such mutation, requiring 500 to 1,000 mug/ml of streptomycin for optimal growth, arose spontaneously in a group A streptococcal strain, and was transferred via a DNA-mediated transformation to a pneumococcal strain. In the latter, the mutation proved to be very closely linked to the genetic locus at which the streptomycin-resistance mutations arise.     

Prediction of the power of detection of marker-quantitative trait locus linkages using analysis of variance

Analysis of variance can be used to detect the linkage of segregating quantitative trait loci (QTLs) to molecular markers in outbred populations. Using independent full-sib families and assuming linkage equilibrium, equations to predict the power of detection of a QTL are described. These equations are based on an hierarchical analysis of variance assuming either a completely random model or a mixed model, in which the QTL effect is fixed. A simple prediction of power from the mean squares is used that assumes a random model so that in the mixed-model situation this is an approximation. Simulation is used to illustrate the failure of the random model to predict mean squares and, hence, the power. The mixed model is shown to provide accurate prediction of the mean squares and, using the approximation, of power.     

3种木质素的主要理化性质分析

介绍了木质素、碱木质素和铵化木质素的制备方法,且对这3种木质素的比重、钠元素含量、X射线衍射、热重、溶解度等理化性质进行表征。研究结果表明,铵化木质素不含有碱金属钠,同时具有很好的水溶性,即铵化木质素解决了纯木质素难溶于水的问题,又解决了碱木质素与柴油乳化后对柴油发动机汽缸内的损坏和长期使用会存在积炭的风险。这说明铵化木质素与木质素和碱木质素相比更适于同柴油乳化混合,实现传统化石能源的添加剂,铵化木质素为我国林木废弃生物质资源化利用和替代能源开发提供了一条潜在的途径。     

Analysis of the effect of backward masking by means of a complex model of a net of neuron-like elements

According to the experiments with a projective-associative model of the neuronal net, the phenomenon of “backward masking” of the first stimulus of a pair of stimuli at a small time gap between the stimuli is caused by two events: (1) pre-excitation inhibition of the first stimulus-induced activation by the second stimulus and (2) disturbance of information processing connected with the deficiency of time needed to match the recalled symbol in memory to the symbol presented to the input subsystem and also to name it. Identification of the second stimulus may be impaired with a decreasing time interval due to: (1) superposition of the second (2) recurrent inhibition occurring in the neuronal net upon recognition of the first stimulus. It was found that in conditions of activity of neuron-like elements of the neuronal net, simulating the states of somnolence or slow-wave sleep, corresponding subsystems failed to learn, while time needed to identify already “learned” symbols substantially increased. The data obtained are in agreement with the hypothesis concerning the causes of backward masking and also with the facts on optimal conditions of learning and reproducing its results in living nervous system. It seems reasonable that discussed disturbances of information processing should be kept in mind in designing computers of a new generation, based on the use of principles of brain functioning, in order to increase the reliability and operation speed of technical systems.     

Significance of phosphorylation of phosphofructokinase

In order to understand the effect of phosphorylation on phosphofructokinase, the allosteric kinetic behavior, ligand binding at various pHs, and pH-dependent cold inactivation of phosphofructokinase phosphorylated to different extents were studied. A subtilisin-digested phosphofructokinase from which a COOH-terminal peptide containing a phosphorylation site has been cleaved (Riquelme, P. T., and Kemp, R. G. (1980) J. Biol. Chem. 255, 4367-4371) was also included in these studies in order to investigate the possible role of this region of the molecule. Allosteric kinetics and direct binding experiments have shown that increasing phosphorylation of phosphofructokinase results in increased sensitivity to ATP inhibition and stronger binding of ATP to the inhibitory site of the enzyme. Ths subtilisin-cleaved phosphofructokinase is the least sensitive to the inhibition and shows the weakest binding of ATP. The opposite effect is observed with the binding isotherms of fructose-6-P. There is no difference in the binding of fructose-2,6-P2 among these enzymes. Binding of ATP to the inhibitory site of these enzymes as determined by fluorescence quenching (Pettigrew, D. W., and Frieden, C. (1979) J. Biol. Chem. 254, 1887-1895) is affected by pH; the binding is greatly enhanced at lower pH. Moreover, there is little difference in the binding among the modified enzymes at pH 8, but at lower pHs the binding to the phosphorylated enzyme is much more enhanced than the dephosphoenzyme. A pH-dependent cold inactivation study has shown that the phosphorylation of the enzyme causes an increase in the pK value for the inactivation, and the extent of the pK shift depends upon the degree of phosphorylation. Based on these results, a model originally proposed by Frieden et al. (Frieden, C., Gilbert, H. R., and Bock, P. E. (1976) J. Biol. Chem. 251, 5644-5647) can be applied to explain a possible role for the phosphorylation and the peptide portion of phosphofructokinase in its complex allosteric kinetic behavior.     

输卵管通水术268例临床分析

目的:探讨输卵管炎性不孕症通水试验的诊断及治疗的临床意义。方法:回顾分析对268例输卵管炎性不孕患者行输卵管通水术后的疗效。结果:来我院进行通水试验治疗的268例输卵管炎性不孕症患者,其中原发性不孕症67例,占发病总数的25%;继发性不孕201例,占75%。经通水反复局部药物治疗,严重者加全身治疗后,输卵管完全通畅者244例,成功率91.04%,术后随访宫内妊娠238例,有效治愈率达88.81%;发生异位妊娠3例,占1.12%。仅有24例经通水治疗无效后行输卵管碘油造影,术后宫内妊娠4例。输卵管通水治疗当月受孕占14.2%。结论:输卵管通水术是诊断和治疗输卵管炎性不孕症的有效方法,早期性生活是否有利于输卵管功能的恢复,有待进一步探讨。     

Observation of two families of folding pathways of BBL

BBL is an independent folding domain of a large multienzyme complex, 2-oxoglutarate dehydrogenase. The folding mechanism of BBL is under debate between the views of noncooperative downhill-type and classical two-state. Extensive replica exchange molecular dynamics simulations of BBL in explicit solvent have shown some non-two-state behaviors despite no definitive evidence of downhill folding. In this work, we postprocess the replica exchange data using our roadmap-based MaxFlux reaction path algorithm to reveal atomically detailed folding pathways. A connected graph is used to organize and visualize the folding pathways initiated from random coils. High structural and transition heterogeneity is seen in the early stage of folding. Two main parallel folding pathways emerge in the later stage; one path shows that tertiary contact and helix formation develop at different stages of folding, whereas the other path exhibits concurrence of secondary and tertiary structure formation to some extent. Because the native state of BBL is sensitive to experimental conditions, we speculate that the relative predominance of the two pathways may vary with the protein construct and solvent conditions, possibly leading to the seeming discrepancy of experimental results. Our roadmap-based reaction path algorithm is a general tool to extract path information from replica exchange.     

Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs

Fine-tuning of insulin secretion from pancreatic beta-cells participates in blood glucose homeostasis. Defects in this process can lead to chronic hyperglycemia and diabetes mellitus. Several proteins controlling insulin exocytosis have been identified, but the mechanisms regulating their expression remain poorly understood. Here, we show that two non-coding microRNAs, miR124a and miR96, modulate the expression of proteins involved in insulin exocytosis and affect secretion of the beta-cell line MIN6B1. miR124a increases the levels of SNAP25, Rab3A and synapsin-1A and decreases those of Rab27A and Noc2. Inhibition of Rab27A expression is mediated by direct binding to the 3'-untranslated region of Rab27A mRNA. The effect on the other genes is indirect and linked to changes in mRNA levels. Over-expression of miR124a leads to exaggerated hormone release under basal conditions and a reduction in glucose-induced secretion. miR96 increases mRNA and protein levels of granuphilin, a negative modulator of insulin exocytosis, and decreases the expression of Noc2, resulting in lower capacity of MIN6B1 cells to respond to secretagogues. Our data identify miR124a and miR96 as novel regulators of the expression of proteins playing a critical role in insulin exocytosis and in the release of other hormones and neurotransmitters.     

Mechanisms of loss of latency of lysosomal enzymes. Effects of incubation on the properties of lysosomal membranes.

1. The effects of sucrose and KCl on the loss of latency of lysosomal enzymes caused by incubation at 37 degrees C, pH 7.4, were examined by using Triton-filled lysosomes from rat liver and two fractions from livers of rats not injected with Triton. 2. After incubation, the percentage free activity of lysosomal enzymes was measured before and after cooling to 0 degrees C in order to determine the amount of latency lost at 37 degrees C without cooling and the additional amount lost on cooling the incubated lysosomes to 0 degrees C. 3. The latency that is lost without cooling is first decreased and then increased by increasing the osmotic strength of the incubation medium with KCl, or with sucrose in the presence of KCl. However, if the osmotic strength is increased with sucrose alone, loss of latency is decreased up to 0.25M-sucrose, but is increased only slightly at higher sucrose concentrations. Apparently the lysosome is permeated by hyperosmolar KCl but not by sucrose during incubation. 4. If the osmotic strength of the assay medium is increased with KCl, the loss of latency caused by incubation for 60 min in hyperosmolar KCl is repressed. Thus it appears that a KCl-permeated lysosome can be obtained which is relatively stable until exposure to lower osmolarities. 5. The loss of latency caused by cooling incubated lysosomes to 0 degrees C is largely eliminated if the osmotic strength of the medium in which the lysosomes are cooled is raised sufficiently with either sucrose or KCl. 6. Osmotic-fragility curves were obtained after incubation for 1 and 60 min at iso-osmoticity (0.2M-KCl or 0.25 M-sucrose). Although little loss of latency occurs at iso-osmoticity, lysosomes incubated for 60 min display greatly increased fragility on exposure to hypo-osmolar KCl, hypo-osmolar sucrose or hyperosmolar KCl. 7. It is suggested that permeability to KCl at 37 degrees C and the increase in fragility on exposure to hypo-osmolar conditions are both consequences of injury, probably from enzymic action, sustained by the lysosomal membrane during incubation at 37 degrees C.     

Specificity of the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase and to a series of other calcium-binding proteins

Trifluoperazine inhibits the activation of phosphodiesterase by binding to the calcium-dependent activator. To determine further the specificity by which trifluoperazine binds to activator, we compared the binding of trifluoperazine to activator prepared from several species and tissues and to a number of other calcium-binding proteins devoid of activator activity.Trifluoperazine binds to activator prepared from human, bovine, rat and rabbit brain and from chick embryo fibroblasts. In each case, the binding of trifluoperazine to activator was qualitatively similar and related quantitatively to the ability of the preparation to activate phosphodiesterase.Of the other calcium-binding proteins examined, namely, troponin-C, S-100 protein, phospholipase A, phospholipase B and myosin light chain, only troponin-C displayed any significant calcium-specific binding of trifluoperazine. The binding to troponin-C, however, appeared to be different from the binding to activator; whereas the binding of trifluoperazine to actovator showed no cooperativity, the binding to troponin-C showed positive cooperatively.These results and earlier data showing that trifluoperazine fails to bind to a variety of other proteins, indicate that the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase is selective and suggest that this binding may explain some of the biochemical and pharmacological actions of this antipsychotic agent.     

Designation of Pathotypes of Plant Pathogens

For evaluation and communication of data on populations of plant pathogens a sensible code to name pathotypes can be extremely helpful. Starting from a coding system proposed by Habgood in 1970, a system, called “coded triplets” is developed which has the same advantages but is easier to understand and to use. This is especially useful as, in the meantime, pathotypes did become increasingly complex due to the increased number of genes conferring race specific resistance in the host. An important advantage of the coded triplets is that codes change only at one digit if, for example, a new differentia) is added or if the pathotype changes from avirulence to virulence or vice versa on a single differential. In this way evoluationary patterns and changes in the pathogen population can be visualized easily. The system is used to describe complex data on haplotypes of the barley mildew pathogen, but it is suited equally well for designation of pathotypes of other pathogens. Some basic principles of coded triplets are similar to octal notation, described by Gilmour in 1973, which has, however, not become widely known. Reasons for this are discussed. – There is a fourth system belonging to the same group of mathematical, condensing codes. As there is reason to believe that the evolution of condensing codes is drawing to an end, the systems are compared extensively, and the benefits of a generally accepted designation are outlined.