The Gene Construction Kit: a new computer program for manipulating and presenting DNA constructs

The Gene Construction Kit is a new tool for manipulating and displaying DNA sequence information. Constructs can be displayed either graphically or as formatted sequence. Segments of DNA can be cut out with restriction enzymes and pasted into other sites. The program keeps track of staggered ends and notifies the user of incompatibilities and offers a choice of ligation options. Each segment of a construct can have its own defined thickness, pattern, direction and color. The sequence listing can be displayed in any font and style in user defined grouping. Nucleotide positions can be displayed as can restriction sites and protein sequences. The DNA can be displayed as either single- or double-stranded. Restriction sites can be readily marked. Alternative views of the DNA can be maintained and the history of the construct automatically stored. Gel electrophoresis patterns can be generated and can be used in cloning project design. Extensive comments can be stored with the construct and can be searched rapidly for key words. High quality illustrations showing multiple editable constructs with added graphics and text information can be generated for slides, posters or publication.     

Modification of commerical and custom-built slab gel electrophoresis units for two-dimensional polyacrylamide gel electrophoresis

Many commercial and custom-built slab gel electrophoresis units can be modified to function as two-dimensional polyacrylamide gel electrophoresis units with the insertion of Plexiglas adapters. These adapters can be made for about $50 a pair and can be used for either temporary or permanent modification of the slab gel units. The physical dimensions of the adapters can be varied to permit great flexibility in the diameter of cylinder gels and the thickness of slab gels that can be run together. For example, proteins from 6-mm cylinder gels can be easily separated on 1-mm slab gels, which can then be dried for autoradiography.     

基于血流多普勒原理的血压测量系统设计

血流信号的采集可基于超声多普勒技术。利用多普勒超声探头在肢体主动脉脉搏处采集到血流多普勒频移信号,对信号电压进行放大,一方面直接输入扬声器转变为音频信号,得到多普勒音;同时用频率/电压变换器LM331变换多普勒频移信号,得到脉搏波信号。基于此原理,设计了使用无创、直观的方法获得肢体血流参数,并经PC机处理,最终在显示器上显示脉搏波形和血压数值的方法。     

Marine yeasts as biocontrol agents and producers of bio-products

As some species of marine yeasts can colonize intestine of marine animals, they can be used as probiotics. It has been reported that β-glucans from marine yeast cells can be utilized as immuno-stimulants in marine animals. Some siderophores or killer toxins produced by marine yeasts have ability to inhibit growth of pathogenic bacteria or kill pathogenic yeasts in marine animals. The virulent factors from marine pathogens can be genetically displayed on marine yeast cells, and the yeast cells displaying the virulent factors can stimulate marine animals to produce specific antibody against the pathogens. Some marine yeast cells are rich in proteins and essential amino acids and can be used in nutrition for marine animals. The marine yeast cells rich in lipid can be used for biodiesel production. Recently, it has been reported that some strains of Yarrowia lipolytica isolated from marine environments can produce nanoparticles. Because many marine yeasts can remove organic pollutants and heavy metals, they can be applied to remediation of marine environments. It has been shown that the enzymes produced by some marine yeasts have many unique properties and many potential applications.     

甲壳质,壳聚糖在农业上的应用

本文综述了甲壳质、壳聚糖作为降解性地膜、植物生长调节剂、肥料和土壤改良剂、农药、食物保鲜剂及饲料、饵料添加剂等在农业方面的应用。     

Protein φ and ψ dihedral restraints determined from multidimensional hypersurface correlations of backbone chemical shifts and their use in the determination of protein tertiary structures

The chemical shifts of the backbone atoms of proteins can be used to obtainrestraints that can be incorporated into structure determination methods. Eachchemical shift can be used to define a restraint and these restraints can besimultaneously used to define the local, secondary structure features. Theglobal fold can be determined by a combined use of the chemical shift basedrestraints along with the long-range information present in the NOEs ofpartially deuterated proteins or the amide–amide NOEs but not from suchlimited NOE data sets alone. This approach has been demonstrated to be capableof determining the overall folding pattern of four proteins. This suggeststhat solution-state NMR methods can be extended to the structure determinationof larger proteins by using the information present in the chemical shifts ofthe backbone atoms along with the data that can be obtained on a small numberof labeled forms.     

Interactions of liposomes with serum proteins

The interactions of serum proteins are diverse, complex and can lead to dramatic effects on liposome stability and in vivo behavior; conversely lipids can modify the biological activities of serum proteins. Serum lipoproteins can potentially destabilize bilayer membranes leading to vesicle disruption and loss of contents; irregularities in the lipid bilayer, such as those which exist at phase boundaries, promote the destabilizing effects of lipoproteins. Other serum components such as fibronectin, immunoglobulins and C reactive protein can modify the biological properties of liposomes by promoting interactions with reticuloendothelial cells and/or activation of the complement system. Liposomes can avidly bind certain serum clotting factors, a process which can lead to dramatic effects on the clotting cascade. Thus the interactions of liposomes with serum proteins can reciprocally effect both components involved.     

荧光标记的染色体原位杂交及其在人类基因组研究中的应用

FISH技术是80年代开始发展起来的一种新的定位技术.在人类基因组研究中得到了广泛的应用.通过中期染色体的FISH可以进行SCP,Cosmid和YAC的染色体定位,嵌合克隆的鉴别;通过间期核的FISH可以在50kb的分辨率下进行基因作图;最新的研究进展已可以进行伸展的染色质丝(chromatin fibre)的FISH,直接测量基因的长度,从而达到高精度基因作图的目的.总之,随着FISH技术本身的发展,它将在人类基因组研究中发挥更大的作用.     

The logical repertoire of ligand-binding proteins

Proteins whose conformation can be altered by the equilibrium binding of a regulatory ligand are one of the main building blocks of signal-processing networks in cells. Typically, such proteins switch between an 'inactive' and an 'active' state, as the concentration of the regulator varies. We investigate the properties of proteins that can bind two different ligands and show that these proteins can individually act as logical elements: their 'output', quantified by their average level of activity, depends on the two 'inputs', the concentrations of both regulators. In the case where the two ligands can bind simultaneously, we show that all of the elementary logical functions can be implemented by appropriate tuning of the ligand-binding energies. If the ligands bind exclusively, the logical repertoire is more limited. When such proteins cluster together, cooperative interactions can greatly enhance the sharpness of the response. Protein clusters can therefore act as digital logical elements whose activity can be abruptly switched from fully inactive to fully active, as the concentrations of the regulators pass threshold values. We discuss a particular instance in which this type of protein logic appears to be used in signal transduction-the chemotaxis receptors of E. coli.     

Interactive robots in experimental biology

Interactive robots have the potential to revolutionise the study of social behaviour because they provide several methodological advances. In interactions with live animals, the behaviour of robots can be standardised, morphology and behaviour can be decoupled (so that different morphologies and behavioural strategies can be combined), behaviour can be manipulated in complex interaction sequences and models of behaviour can be embodied by the robot and thereby be tested. Furthermore, robots can be used as demonstrators in experiments on social learning. As we discuss here, the opportunities that robots create for new experimental approaches have far-reaching consequences for research in fields such as mate choice, cooperation, social learning, personality studies and collective behaviour.     

黑河流域生态经济带分异协调规律与耦合发展模式

在西北干旱地区建设黑河流域生态经济带,是从根本上高效配置流域水资源,彻底化解流域上,下游利益冲突,实现利益共享,保护流域生态环境,推进流域可持续发展,全面实施国务院黑河流域分水方案的重要途径,通过对黑河流域生态经济带上－中－下游投入产出效益的比较分析和流域上、中、下游生态－生产、生活系统发展分异及互动协调关系的分析,提出了黑河流域生态经济带上－中－下游多维互动的协调耦合发展模式,进而提出了黑河流域生态经济带建设与发展的主要途径,包括推进黑河流域经济发展一体化和集成管理公司化,大力推行全流域水资源的差异化有偿使用制度,实施流动上、中、下游的水权转让贸易,实行规范的流域财政转移支付制度,建立流域资源与生态环境和经济的整合帐户体系,实行跨行政区域河流边界水量水质达标交接制度,等等。     

Allochthonous inputs: integrating population changes and food-web dynamics

Most ecosystems are recipients of allochthonous materials that enhance in situ productivity. Recent theoretical and empirical studies suggest that low to moderate inputs can stabilize food webs. However, depending on the trophic levels that use the resource, food webs can become unstable as inputs increase. Where large amounts of agricultural resources are transferred to natural habitats, trophic dynamics change: trophic cascades can occur and rare or uncommon species can become invasive. Rates of change in species abundances can also be amplified by the effects of changes in legislation and management practices on subsidized consumers.     

Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins

There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1–2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life. Most mAbs display target mediated drug disposition (TMDD), which can have significant consequences on the study designs of preclinical and clinical studies. The PK of mAb can also be influenced by anti-drug antibody (ADA) response and off-target binding, which require careful consideration during the discovery stage. mAbs are primarily absorbed through the lymphatics via convection and can be conveniently administered by the subcutaneous (sc) route in large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb can be reasonably estimated using cynomolgus monkey data and allometric scaling methods.     

Measurement of free radical oxygen generation by cytochrome c reduction requirement for cytochrome c oxidase blockade

Data is presented showing that one commercial preparation of cytochrome c, used to trap and measure free radical superoxide anion, can be contaminated with cytochrome c oxidase activity. This activity can vary from lot to lot, can introduce variability into the measurement of superoxide anion and can result in falsely low estimations of free radical formation. This cytochrome c oxidase activity can be inhibited by low (0.2 mM) concentrations of KCN. Blockade of the cytochrome c oxidase activity allows reproducible measurement of superoxide anion formation at low levels by red cells.     

Artificial cardiac stimulation: a current view of physiologic pacemakers.

Artificial pacing of the heart has evolved rapidly over the last 20 years; the physician can now implant "physiologic" pacemakers that preserve the natural order of atrial and ventricular systole. The commonly used pacemakers that pace only the ventricle can induce dizziness, fatigue and syncope and increase congestive heart failure. Physiologic pacemakers can eliminate many of these side effects, but they are more expensive, can be less durable and may induce arrhythmias. Physiologic pacing can provide the greatest benefit and cost-effectiveness when the particular functions of the device are matched to the specific needs of the patient.     

Rapid multivariate analysis and display of cross-reacting antibodies on human leukocytes.

We present an application which can rapidly determine the binding patterns of monoclonal antibodies on mixed populations of cells simultaneously in a single rapid analysis. It is an application of the tube identifier parameter (TIP) system which can provide fully correlated list-mode data of the entire patient phenotype in a single file. Using the phenogram analytical display, we are able to determine the cross-reacting antibodies for an entire antibody panel for each cell type. This information can be displayed in a single plot. Using light scatter gating to select different populations of lymphocytes, monocytes, and neutrophils, phenograms can be simultaneously generated. This provides a directly comparable means of displaying the positive and negative binding characteristics of each antibody on each cell population. Any marker combination that is abnormal will be identifiable in the phenogram. Additionally, by plotting the fluorescence distributions of each marker beside one another (termed overview), quantifiable differences in intensity can be determined. There are 3 major benefits of the proposed analysis. By using the TIP concept, several sets of antibodies can be compared simultaneously. Any light scatter gate can be used and this gate can be changed on one histogram or plot, yet apply to the total analysis. Data analysis is particularly rapid since the entire phenotype of a patient can be evaluated by performing a single rapid analysis.     

VISUALIZING MULTIVARIATE SELECTION

Recent developments in quantitative-genetic theory have shown that natural selection can be viewed as the multivariate relationship between fitness and phenotype. This relationship can be described by a multidimensional surface depicting fitness as a function of phenotypic traits. We examine the connection between this surface and the coefficients of phenotypic selection that can be estimated by multiple regression and show how the interpretation of multivariate selection can be facilitated through the use of the method of canonical analysis. The results from this analysis can be used to visualize the surface implied by a set of selection coefficients. Such a visualization provides a compact summary of selection coefficients, can aid in the comparison of selection surfaces, and can help generate testable hypotheses as to the adaptive significance of the traits under study. Further, we discuss traditional definitions of directional, stabilizing, and disruptive selection and conclude that selection may be more usefully classified into two general modes, directional and nonlinear selection, with stabilizing and disruptive selection as special cases of nonlinear selection.     

Environmental forcing, invasion and control of ecological and epidemiological systems

Destabilising a biological system through periodic or stochastic forcing can lead to significant changes in system behaviour. Forcing can bring about coexistence when previously there was exclusion; it can excite massive system response through resonance, it can offset the negative effect of apparent competition and it can change the conditions under which the system can be invaded. Our main focus is on the invasion properties of continuous time models under periodic forcing. We show that invasion is highly sensitive to the strength, period, phase, shape and configuration of the forcing components. This complexity can be of great advantage if some of the forcing components are anthropogenic in origin. They can be turned into instruments of control to achieve specific objectives in ecology and disease management, for example. Culling, vaccination and resource regulation are considered. A general analysis is presented, based on the leading Lyapunov exponent criterion for invasion. For unstructured invaders, a formula for this exponent can typically be written down from the model equations. Whether forcing hinders or encourages invasion depends on two factors: the covariances between invader parameters and resident populations and the shifts in average resident population levels brought about by the forcing. The invasion dynamics of a structured invader are much more complicated but an analytic solution can be obtained in quadratic approximation for moderate forcing strength. The general theory is illustrated by a range of models drawn from ecology and epidemiology. The relationship between periodic and stochastic forcing is also considered.     

一氧化氮对家榆种子老化的影响及其作用机制研究

以家榆种子为试材,采用种子活力检测技术、激光共聚焦显微镜技术、蛋白质S-亚硝基化检测技术,结合多种相关抑制剂的使用,研究了NO对种子老化的影响及其作用机制。结果表明:(1)外源NO可显著提升老化处理后种子的活力,NO清除剂cPTIO可降低老化处理后种子的活力,且此影响可被NO供体硝普钠所恢复。(2)硝酸还原酶底物亚硝酸钠、类一氧化氮合酶底物L-精氨酸(L-Arg)均可提高老化处理后种子的活力,2种酶的抑制剂可降低种子活力,且此影响可被NO供体硝普钠所恢复,即硝酸还原酶与类一氧化氮合酶可参与种子老化过程中NO的产生。(3)种子老化过程中NO首先在子叶中合成,随后在胚根尖部、生长点与下胚轴等部位出现,蛋白质S-亚硝基化水平与NO在种子中产生的时间特点一致。研究认为,NO可提高种子抗老化能力,种子内NO可通过硝酸还原酶途径和类一氧化氮合酶途径产生,且与种子蛋白质S-亚硝基化水平相关。     

Modern problems of biodosimetry

Humans have different radiosensitivity. Besides, many factors which are not under control can change significantly biological effects of radiation. Some of substances are present in our food--residual amounts of fertilizers or herbicides can be mutagenic or influence mutagenic action of radiation. In the last case synergetic or antagonistic effects can be observed. At the same time many food products contain radioprotectors or antimutagens. Some drugs, stress, virus diseases and so on can change biological effects of radiation too. Radioadaptive response is one of the most significant factors which can be responsible for incorrect radiation dose evaluation. All these uncontrolled factors may be responsible for significant mistakes of evaluating radiation dose by biological methods. That is why biological methods can be used for bioindication but not for biodosimetry.