The origin of the alkaline inactivation of pepsinogen.

Above pH 8.5, pepsinogen is converted into a form which cannot be activated to pepsin on exposure to low pH. Intermediate exposure to neutral pH, however, returns the protein to a form which can be activated. Evidence is presented for a reversible, small conformational change in the molecule, distinct from the unfolding of the protein. At the same time, the molecule is converted to a form of limited solubility, which is precipitated at low pH, where activation is normally seen. The results are interpreted in terms of the peculiar structure of the pepsinogen molecule. Titration of the basic NH2-terminal region produced an open form, which can return to the native form at neutral pH, but which is maintained at low pH by neutralization of carboxylate groups in the pepsin portion.     

Parallel recognition of idealised line characters

Summary The aim is to design a machine which is able to learn a number of idealised characters and to recognise them, irrespective of their size, position and context on an infinite retina. If the number of characters which such a machine can possibly learn to recognise is astronomical, it is not practical to use separate templates for every possible character. It is more economical to use, instead, templates for various parts, called features, of characters. In recognising a number of characters simultaneously, without scanning, the question arises of how to tell which feature belongs to which character of figure on the retina. In particular, if a given character is not present but all its features are included in nonsense figures simultaneously present on the retina then the machine must not indicate the presence of the given character. The technique which overcomes this difficulty employs overlapping features which must be mutually consistent for recognition. This consistency technique is assessed by comparison with a more conventional technique, and the work is restricted to closed line characters which are not subject to deformations or mutilations.     

Isoelectric points of multi-domain proteins

Although the distribution of protein isoelectric points is multi-modal, large proteins show isoelectric points less variable than small proteins and their isoelectric points tend to converge to a unique value, close to the pH of the milieu in which the proteins are functional, as far as the protein dimension increases. This study demonstrates that large proteins, which contain more than a single domain, do have isoelectric points less variable than small proteins, which contains a single domain. However, the distribution of the isoelectric points of the single domains, contained in large proteins, resembles that of small proteins, which contain a single domain. Thus, large proteins can be soluble even if their pI is very close to the pH of the milieu, in which they perform their function, since they can contain several domains, the electrostatic properties of each of which mirror those of small proteins.     

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).     

Diversity of antimicrobial peptides and their mechanisms of action

Antimicrobial peptides encompass a wide variety of structural motifs. Many peptides have alpha-helical structures. The majority of these peptides are cationic and amphipathic but there are also hydrophobic alpha-helical peptides which possess antimicrobial activity. In addition, some beta-sheet peptides have antimicrobial activity and even antimicrobial alpha-helical peptides which have been modified to possess a beta-structure retain part of their antimicrobial activity. There are also antimicrobial peptides which are rich in a certain specific amino acid such as Trp or His. In addition, antimicrobial peptides exist with thio-ether rings, which are lipopeptides or which have macrocyclic Cys knots. In spite of the structural diversity, a common feature of the cationic antimicrobial peptides is that they all have an amphipathic structure which allows them to bind to the membrane interface. Indeed, most antimicrobial peptides interact with membranes and may be cytotoxic as a result of disturbance of the bacterial inner or outer membranes. Alternatively, a necessary but not sufficient property of these peptides may be to be able to pass through the membrane to reach a target inside the cell. The interaction of these peptides with biological membranes is not just a function of the peptide but is also modulated by the lipid components of the membrane. It is not likely that this diverse group of peptides has a single mechanism of action, but interaction of the peptides with membranes is an important requirement for most, if not all, antimicrobial peptides.     

Importance of phoresy in the transmission of Acarina

Dispersal capacity plays a central role in the radiation of animals, facilitating the exploitation of habitats variously distributed in space or in time or both. Many living species are unable to leave a host, crawl around, and find a new host, so they must rely on external factors to be transmitted. Biotical factors may be important in passive transport and the process, by means of which an animal is passively transported by a selected carrier of different species, is known as "phoresy". Phoresy is a phenomenon in which one animal (the phoretic) seeks out and attaches to an animal of another species, with which it does not share any phase of the life cycle, for dispersal, during which time the phoretic animal becomes quiescent, stopping feeding and development. Activity starts again beginning with detachment, induced by stimuli originating from its carrier or the microhabitat. The adaptive traits of phoresy may be categorized as follow: host surface, quiescence, recognition of signals to abandon the carrier and, if needed, synchronization with the host life cycle. Phoresy is exploited by many Arthropods. In Acarina, there are basically four main types of phoresy. First, there is a type in which adult females are the only forms becoming phoretic and attachment is by means of chelicerae, palpal hooks and ambulacral claws, which grasp a seta or a fold of the integument of carrier-host. The second type is represented by mites, in which deutonymphs are phoretic; there is generally no cheliceral or sucker attachment in this group, mites instead hanging on by their ambulacral claws. The third type is similar to the second in that deutonymphs are phoretic; however, in this case, attachment to the host is by means of an anal pedicel formed by a substance, extruded through the anus, which hardens upon coming in contact with air and literally glues the mite to its host. In the fourth type there is a very highly modified deutonymph stage, called hypope, which only occurs at certain times, presumably when environmental conditions are no longer appropriate for the mite. Hypope is simplified morphologically, may have many sucker-like discs or claspers for efficient attachment, and is much more resistant to desiccation than are other stages of the life cycle.     

Mathematical theory of motivation interactions of two individuals: II

The behavior of two individuals, consisting of effort which results in output, is considered to be determined by a satisfaction function which depends on remuneration (receiving part of the output) and on the effort expended. The total output of the two individuals is not additive, that is, together they produce in general more than separately. Each individual behaves in a way which he considers will maximize his satisfaction function. Conditions are deduced for a certain relative equilibrium and for the stability of this equilibrium, i.e., conditions under which it will not “pay” the individual to decrease his efforts. In the absence of such conditions “exploitation” occurs which may or may not lead to total parasitism. Some forms of the inverse problem are considered, where the form of behavior is given and forms of the satisfaction function are deduced which lead to it.     

Preliminary Classification of Viruses Based on Quantitative Comparisons of Viral Nucleic Acids

It is proposed that classifications used in science are of two main types; those which are designed to solve practical problems and which are based on conventions, and those which are designed to solve theoretical problems, based on theories, and in which the classes are tested by experiment. An attempt has been made to construct a preliminary classification of viruses which is of the second type. It is based on the theories of molecular biology, with the use of computer-based comparisons of the molecular weights and base ratios of viral nucleic acids to assign the viruses to clusters which show a high degree of correlation with groupings based on nucleic acid hybridization, serological cross-reactions, and phenotypic properties.     

Bootstrapping model of the origin of life

The origin of life is analyzed in terms of the self-facilitating aspect of evolution. According to the self-facilitation (or bootstrap) principle the structure of biological systems becomes increasingly suited to effective evolutionary search through the process of evolution. The principle may be extended to primitive collections of polymers with catalytic properties. The origin of the code may be based on a form of bootstrapping evolution. Once a primitive code appeared it could become more sophisticated through a multi-coding mechanism together with classical Darwinian mechanisms. The bootstrapping principle is also formulated in terms of the fluctuation-instability framework of Prigogine, Nicolis, and Babloyantz. Primitive collections of polymers accumulate evolution-enhancing redundancies which tend to reduce the extent to which they change when destabilized by fluctuation, but which increase the chances that these changes will lead to new predominant regimes. We show that the bootstrapping of evolutionary amenability is accompanied by the accumulation of a thermodynamic load, that is, a free energy cost which reduces the mechanistic efficiency. The bootstrapping effect suggests that the origin of life is most fruitfully approached as a long process during which the capacity to evolve facilitates itself in a step by step fashion rather than as a series of low probability events.     

Apparent bisexual behavior of yeast strains obtained from hybridization of industrial yeasts of the genusSaccharomyces with auxotrophic diploids

During a genetic study of some hybrids of brewer's and distiller's yeast strains with impaired sporulation characteristics and genetically marked auxotrophic aa and alpha alpha diploids, strains which showed positive mating reactions with both a and alpha haploid tester strains were observed. These strains proved to be homothallic and sporulated freely. The original hybrids, which appeared to be tetraploid, usually yielded sporulating single-spore clones on dissection of asci formed from them, with few or no mating strains among them. Dissection of asci from these clones yielded some single-spore clones which showed mating reactions with one or the other or both haploid tester strains, and further selection produced strains which on sporulation and dissection yielded single-spore clones which were apparently bisexual and sporulated freely. These strains proved to be homothallic, yielding single-spore clones which were all of the a mating type, and in which the mating reaction and, possibly, the action of the genes for homothallism were impaired, so that sporulating, non-mating diploids and haploids of both mating types were present in cultures originally obtained as single-spore clones.     

Effect of non-histone proteins on thermal transition of chromatin and of DNA.

The effect of chromatin non-histone protein on DNA and chromatin stability is investigated by differential thermal denaturation method. 1) Chromatin (rat liver) yields a multiphasic melting profile. The major part of the melting curve of this chromatin is situated at temperatures higher than pure DNA, with a distinct contribution due to nucleosomes melting. A minor part melts at temperatures lower than DNA which may be assigned to chromatin non-histone protein-DNA complex which destabilized DNA structure. 2) Heparin which extracts histones lowers the melting profile of chromatin and one observes also a contribution with a Tm lower that of pure DNA. In contrast, extraction on non-histone proteins by urea supresses the low Tm peak. 3) Reconstitution of chromatin non-histone protein-DNA complexes confirms the existence of a fraction of chromatin non-histone protein which lowers the melting temperature when compared to pure DNA. It is concluded that chromatin non-histone proteins contain different fractions of proteins which are causing stabilizing and destabilizing effect on DNA structure.     

Molecular weights of aggregation states of Busycon hemocyanin.

Molecular weights of all hemocyanin aggregates which can be homogeneously isolated have been measured by sedimentation equilibrium. The larger aggregates, which are the ones present under physiological conditions, are, to a very close approximation, integral multiples of a 4.4 x 10(6)-dalton, 60 S species. Dissociation of the 60 S species at high pH gives heterogeneous samples in which the smallest species has a molecular weight of 300,000. The smallest subunit which can be produced in denaturing solvents also has a molecular weight of 300,000.     

PCR指纹图谱分析在念珠菌性阴道炎、龟头炎流行病学研究中的应用

目的 建立一种鉴别念珠菌性阴道炎和龟头炎传染、复发及再感染的分子生物学方法.方法 对实验菌株进行微卫星PCR扩增,对所获得的PCR指纹图谱多态性进行分析,比较两次感染或夫妻同时感染的病原菌株的亲缘性关系.结果 22株实验菌株中,8株来自4例患者前后两次感染的两株,图谱相似系数大于0.8,可以认为是复发,3对夫妻间感染的6株菌株相似系数大于0.8,可以认定是性传染,其余8株菌的相似系数小于0.8,可以认为是再感染.结论 微卫星PCR指纹图谱能在一定程度上说明念珠菌阴道炎、龟头炎发病及复发的原因,在鉴别感染是由传染、复发还是再感染所致时中有一定的参考价值,可为临床治疗提供参考.     

Radioiodination of nonionic detergents of the alkyl-phenol class: Triton X-100

A method is described by which nonionic detergents of the alkyl-phenol class can be labeled with ¹²⁵I. The detergent is labeled to a high specific activity, which provides a sensitive method for the detection of detergent molecules bound to proteins, and, in addition, may provide a method by which proteins may be labeled indirectly.     

Optimization over a class of tree shape statistics

Tree shape statistics quantify some aspect of the shape of a phylogenetic tree. They are commonly used to compare reconstructed trees to evolutionary models and to find evidence of tree reconstruction bias. Historically, to find a useful tree shape statistic, formulas have been invented by hand and then evaluated for utility. This paper presents the first method which is capable of optimizing over a class of tree shape statistics, called binary recursive tree shape statistics (BRTSS). After defining the BRTSS class, a set of algebraic expressions is defined which can be used in the recursions. The set of tree shape statistics definable using these expressions in the BRTSS is very general and includes many of the statistics with which phylogenetic researchers are already familiar. We then present a practical genetic algorithm which is capable of performing optimization over BRTSS given any objective function. The chapter concludes with a successful application of the methods to find a new statistic which indicates a significant difference between two distributions on trees which were previously postulated to have similar properties.     

Determination of dependence of binding parameters on receptor occupancy

Measurements of the binding of ligand to receptors that are macromolecules, either free or components of biomembranes, often show deviation from what is expected of a simple reaction described by an association and a dissociation rate constant. A more versatile model and more discriminating experiments are required for a satisfactory explanation. This paper is based on a general model of the binding reaction in which the rate constants and equilibrium constant are dependent upon occupancy of receptors. The analysis of the model leads to three kinds of experiments: (1) equilibrium measurements which permit quantitative determination of a dissociation equilibrium parameter as a function of receptor occupancy; (2) measurements prior to equilibrium which yield the same information; and (3) measurements prior to equilibrium which reveal quantitatively the dependence of both association and dissociation rate parameters separately, on occupancy.     

Ecological-economic modelling of the conservation of threatened habitats: heather moorland in the Northern Isles of Scotland

This paper describes the results of an ecological-economic modelling exercise of the management of a scarce habitat, namely heather moorland. The Orkney Islands of Scotland are used to illustrate a modelling approach which could be easily applied elsewhere, and to other habitats. We describe the evolution and present condition of heather moorland on Orkney, then quantify the extent of over-grazing (leading to ecological damage) on a spatial basis. This is accomplished using a model of heather utilization and heather productivity. Critical grazing limits are then used as constraints in an economic model of farm production decisions, which enables us to quantify the minimum necessary compensation payments which farmers should be offered to offset income losses due to grazing restrictions. Such a policy is in line with European Union and UK agri-environmental policy, which typically uses payments for income forgone as a means of persuading farmers to protect environmental quality.     

Synthesis of bioprocesses using physical properties data

The aim of this article is to illustrate and evaluate a synthesis procedure which has been extended to tackle bioprocesses. Physical property information is used to screen candidate units thereby reducing the size of the synthesis problem. In this way, only units which exploit large property differences between components in a stream are selected. This is important for bioprocesses because of the large number of components and wide range of unit operations which are available. The screening technique and bioprocess-unit-design methodologies have been incorporated within an implicit enumeration algorithm which was developed for chemical process synthesis and is implemented in Java programming language. An important advantage is the ability of the bioprocess synthesis software to generate a ranked list of flowsheets which may subsequently be analyzed in more detail. Two case studies are used to evaluate the bioprocess-synthesis technique. The first system involves a product which is secreted from the host organism. The second has significantly different characteristics in that the product is intracellular and forms inclusion bodies. The latter case study, in particular, is a large synthesis problem with 12 unit operations and 20 contaminant compounds. The results show that the synthesis methodology identifies a set of economically optimal flowsheets in a reasonable computational time which demonstrates its ability to deal with large synthesis problems. Using the synthesis methodology we can generate bioprocesses which are optimal in a system-wide, rather than unit-by-unit, sense.     

The inactivation of tet genes on a plasmid by the duplication of one inverted repeat of a transposon-like structure which itself mediates tetracycline resistance

Derivatives of a naturally occurring IncFII tetracycline resistance plasmid (pUB889) which are unable to confer resistance to tetracycline, and which were isolated from both partners of a married couple, have been examined. The tet genes are part of a transposon-like structure which is closely related to, but distinct from, Tn10. The lesions in the two plasmids examined are identical and involve the insertion of a nucleotide sequence of 0.9 × 10⁶ within the region encoding tetracycline resistance, expression of which is lost as a consequence. The extra DNA is homologous with the nucleotide sequence, a pair of which form the inverted repeats of the Tn10-like structure. We conclude that this nucleotide sequence comprises an IS element. The epidemiological implications arising from the origin of these plasmids are discussed.