Adaptive noise

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.     

Optimizing combination chemotherapy by controlling drug ratios

Cancer chemotherapy treatments typically employ drug combinations in which the dose of each agent is pushed to the brink of unacceptable toxicity; however, emerging evidence indicates that this approach may not be providing optimal efficacy due to the manner in which drugs interact. Specifically, whereas certain ratios of combined drugs can be synergistic, other ratios of the same agents may be antagonistic, implying that the most efficacious combinations may be those that utilize certain agents at reduced doses. Advances in nano-scale drug delivery vehicles now enable the translation of in vitro information on synergistic drug ratios into improved anticancer combination therapies in which the desired drug ratio can be controlled and maintained following administration in vivo, so that synergistic effects can be exploited. This "ratiometric" approach to combination chemotherapy opens new opportunities to enhance the effectiveness of existing and future treatment regimens across a spectrum of human diseases.     

Chronic hypoplastic marrow failure and residual injury.

An experimental model of chronic marrow failure can be produced in mice by treatment with a short course of busulphan. This results in permanent partial marrow failure which may later progress and become complete. The underlying lesion appears to be stem cell damage which leads to failure of proliferation of stem cells and their progeny. Other drugs can produce the same lesion and alkylation of DNA may be the mechanism.     

ELBOW AND WRIST INJURIES IN SPORTS

Any disabling injury of the elbow or wrist should be studied roentgenographically for evidence of fracture which may not be otherwise evident but which may cause permanent disability unless the joint is immobilized for healing.“Tennis elbow” may be treated with physical therapy and analgesic injection but may require splinting or tendon stripping. Elbow sprain can occur in the growing epiphysis but is rare in adults. A jarring fall on the hand may cause fracture or dislocation at the elbow.Full extension of the joint should be restored gradually by active exercise rather than passive or forcible stretching.Fracture at the head of the radius may cause joint hemorrhage with severe pain which can be relieved by aspiration. A displacing fracture at the head of the radius requires removal of the head to prevent arthritic changes. Myositis ossificans contraindicates operation until after it has cleared.Healing of wrist fractures may be facilitated by exercise of the shoulder and elbow while the wrist is still in a cast. Fractures of the navicular bone are difficult to detect even roentgenographically and splinting may have to be done on clinical evidence alone.     

Phylogenetic inference based on matrix representation of trees.

Rooted phylogenetic trees can be represented as matrices in which the rows correspond to termini, and columns correspond to internal nodes (elements of the n-tree). Parsimony analysis of such a matrix will fully recover the topology of the original tree. The maximum size of the represented matrix depends only on the number of termini in the tree; for a tree derived from molecular sequences, the represented matrix may be orders of magnitude smaller than the original data matrix. Representations of multiple trees (which may or may not have identical termini) can readily be combined into a single matrix; columns of discrete-character-state data can be added and, if desired, weighted differentially. Parsimony analysis of the resulting composite matrix yields a hybrid supertree which typically provides greater resolution than conventional consensus trees. Use of this method is illustrated with examples involving multiple tRNA genes in organelles and multiple protein-coding genes in eukaryotes.     

Human and mouse monoclonal antibodies by repertoire cloning.

Antibody repertoires, the wide range of antibody molecules produced by animals, can now be established in bacteria by cloning and expression of antibody genes. Beginning with immunized animals, antigen can be used to select, from the repertoire, clones which secrete specific monoclonal antibody. In the future, immunization may become unnecessary. The method may provide a general route, which has so far eluded biotechnologists, to human monoclonal antibodies.     

CORRECTION OF COLLAPSED NASAL ALAE—A Simple Surgical Procedure

Collapse of the nasal alae against the septum brings about a serious obstruction to the airway. Collapse may be overlooked on routine examination because the speculum may prevent it.In most cases alar collapse can be corrected by a simple surgical procedure, herein described, which can be readily done at the same time as operation on the caudal portion of the septum.     

Correction of collapsed nasal alae; a simple surgical procedure

Collapse of the nasal alae against the septum brings about a serious obstruction to the airway. Collapse may be overlooked on routine examination because the speculum may prevent it. In most cases alar collapse can be corrected by a simple surgical procedure, herein described, which can be readily done at the same time as operation on the caudal portion of the septum.     

Infiltrating and Embedding Tissues with Mixtures of Polyethylene Glycols and Polyvinylacetate Resins

The use of water-soluble polyethylene glycol polymers (Carbowax, Hydrowax) as embedding media can be extended and facilitated by incorporating a water insoluble polyvinylacetate resin, AYAF (Union Carbide Co.). A combination of 7.5% resin added by heating to a 3:1 mixture of polyethylene glycols 1540 and 4000 gives blocks which may be cut at 2-3 μ. Sections can be floated and properly expanded on an ordinary water bath in a manner which may be impossible with Carbowax alone because of section fragility. This may require judicious adjustment of surface tension by the prior addition of minute quantities of the wax. On water, polyethylene glycol dissolves out of tissues, which remain supported by the resin. After attachment to albumen-coated slides, residual resin may, at option, be removed by a 1-2 min immersion in methyl alcohol without visible impairment of fat content. Abopon is used for mounting. The method appears suitable for the study of intracellular lipids, particularly in tissues which cannot be conveniently handled after Carbowax alone.     

Plasmid screening at high colony density

A procedure is described for screening bacterial colonies containing recombinant plasmids by nucleic acid hybridization at high density i.e., at 100000 colonies per 150 mm diameter plate. Small colonies are established on nitrocellulose filters from which they can be faithfully replicated to additional filters. Chloramphenicol amplification may be carried out in situ before screening. The filters may be kept frozen for long-term storage of colonies which may be further replicated after thawing.     

Synaptic competition in structural plasticity and cognitive function

Connections between neurons can undergo long-lasting changes in synaptic strength correlating with changes in structure. These events require the synthesis of new proteins, the availability of which can lead to cooperative and competitive interactions between synapses for the expression of plasticity. These processes can occur over limited spatial distances and temporal periods, defining dendritic regions over which activity may be integrated and could lead to the physical rewiring of synapses into functional groups. Such clustering of inputs may increase the computational power of neurons by allowing information to be combined in a greater than additive manner. The availability of new proteins may be a key modulatory step towards activity-dependent, long-term growth or elimination of spines necessary for remodelling of connections. Thus, the aberrant growth or shrinkage of dendritic spines could occur if protein levels are misregulated. Indeed, such perturbations can be seen in several mental retardation disorders, wherein either too much or too little protein translation exists, matching an observed increase or decrease in spine density, respectively. Cellular events which alter protein availability could relieve a constraint on synaptic competition and disturb synaptic clustering mechanisms. These changes may be detrimental to modifications in neural circuitry following activity.     

Estimating the Dilution Effect Due to Unreliability of Dichotomous Outcome Variables From Kappa

If category-specific reliabilities are constant across groups, the difference in group-specific "success" probabilities estimated from an unreliable dichotomous outcome variable can be shown to be diluted. Thus, although an intervention may truly have a sizable effect, this effect may not be detectable because of unreliability of the outcome variable. This article explores the dilution effect in a latent class analysis framework in which reliability is defined as the probability with which the manifest measure and the true state correspond. The size of the dilution effect will be related to the popular kappa coefficient, which is often used to assess the reliability of dichotomous variables. Conditions will be specified under which the magnitude of the dilution effect can be estimated from kappa.     

Theory of time-resolved somatic complementation and its use to explore the sporulation control network in Physarum polycephalum

Mutants of Physarum polycephalum can be complemented by fusion of plasmodial cells followed by cytoplasmic mixing. Complementation between strains carrying different mutational defects in the sporulation control network may depend on the signaling state of the network components. We have previously suggested that time-resolved somatic complementation (TRSC) analysis with such mutants may be used to probe network architecture and dynamics. By computer simulation it is now shown how and under which conditions the regulatory hierarchy of genes can be determined experimentally. A kinetic model of the sporulation control network is developed, which is then used to demonstrate how the mechanisms of TRSC can be understood and simulated at the kinetic level. On the basis of theoretical considerations, experimental parameters that determine whether functional complementation of two mutations will occur are identified. It is also shown how gene dosage-effect relationships can be employed for network analysis. The theoretical framework provided may be used to systematically analyze network structure and dynamics through time-resolved somatic complementation studies. The conclusions drawn are of general relevance in that they do not depend on the validity of the model from which they were derived.     

Prorenin in plasma and kidney

Circulating prorenin is an enzymatically inactive form of renin, also present in kidney, which can be activated in vitro. Its biochemical properties and physiological behavior suggest that it may be a biosynthetic precursor of active renin. However, in contrast to typical prohormones, the normal plasma concentrations of prorenin are much higher than the active hormone. The purposes and functions of prorenin are unclear. It may have no further role after its secretion into the circulation. On the other hand, it may be a transport form of renin that can enter or exit cells more easily than the active form. It is also possible that the activity of the renin-angiotensin system may be regulated by the conversion of prorenin to renin in the kidney (which may be under beta-adrenergic control) or at other possible sites. Irreversible activation of prorenin appears to be a proteolytic process. In addition, acidification causes reversible activation, perhaps through a change in molecular conformation. Such reversible activation might occur in vivo by unknown mechanisms. Future studies are needed to define the biochemical processes by which increased physiological demand for renin is translated into the production of more active enzyme.     

Linkage Modification with Mixed Random Mating and Selfing: A Numerical Study

Although recombination cannot increase under conditions of random mating or complete selfing in regimes of constant selection, with mixed random mating and selfing, selection for increased recombination can occur. For some fitness regimes there may be selection for reduced recombination with both low and high degrees of selfing but selection for increased recombination with moderate degrees of selfing. With some fitness regimes there is a historical effect: depending on which equilibrium a population starts from, there may be selection for either increased or decreased recombination. In other cases the direction of selection may be determined by the present state of individuals within the population. If recombination is already fairly limited, there may be selection for further reduction. If recombination is already fairly frequent, there may be selection for increased recombination. For certain symmetric viability systems there may be an intermediate value of the recombination fraction between 0 and 0.5 toward which the population will evolve. Although it is not yet possible to classify precisely those fitness matrices that can exhibit selection for increased recombination, it does appear that selection for increased recombination can occur only if at least two of the double homozygotes are less fit than would be expected on the basis of a comparison of the fitnesses of the single and double heterozygotes on an additive scale.     

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.     

Genetical ESS-models. II. Multi-strategy models and multiple alleles

The problem of evolutionarily stable strategies (ESS) in sexual populations can be investigated by means of genetical ESS-models which link common sense, phenotypic ESS-models to an underlying genetical system. Thorough results are obtained for multi-strategy models in diploid, panmictic populations on the basis of multi-allelic, one-locus systems. A sexual population will be maintained at a phenotypic ESS if this can possibly be produced by the genotypes currently existing. If there is enough allelic variation, the corresponding gene pool may either be an ESS itself, or belong to an attracting, continuous set of states, which all determine the same evolutionarily stable population. The latter case allows new alleles to enter and spread in the gene pool without disturbing the phenotypic ESS. If a phenotypic ESS cannot be established, ESSs of the genetical model may be found which give rise to stable populations alternatively. Since these depend on the phenotypes determined by the currently existing genotypes, they may be destabilized by the occurrence of new mutations. In this sense, they are less durable than populations maintained at a phenotypic ESS and can be expected to evolve, in the long run, towards a phenotypic ESS.     

On the analysis of linear binding effects associated with curved Scatchard plots.

First the question is examined as to which binding data, especially if given as Scatchard plots, can be described in terms of a basic model mechanism. This referes to a linear lattice of equivalent binding sites (as for example located on a linear biopolymer) which can exert cooperative interaction between nearest neighbors. It is shown that the effect of overlapping of potential site (so-called "multiple-contact"binding), as may occur with larger ligands, will largely be compensated by a higher degree of cooperativity. Therefore, in practice such properties can scarcely be separated by means of oridnary binding experiments. A pronounced inflection point in the Scatchard plot turns out to be clearly indicating a more complex mechanism involving at least two rather antagonistic cooperative interactions which may, however, occur even between equivalent binding sites. Finally some consequences of different classes of bindings sites are considered. In particular a simple approach is introduced by which the binding to mutually exclusive classes of sites may be described. Such a model is of interest for multiple-mode binding of ionic ligands to oppositely charged polymers.     

An analysis of DNA cytophotometry on tissue sections in a rat liver model

Since the nuclear DNA content of neoplastic cells may be of predictive value, it is important that a reliable approach to cytophotometric DNA estimation in tissue sections be available by which cases can be assessed retrospectively and correlated with a recorded clinical course. Studies on a rat liver model indicate that the additional problems involved in using sections can be overcome. Selection of an appropriate section thickness has shown that spindle-shaped nuclei can be used reliably as an internal control for a test population with spherical nuclei. The location of higher ploidy peaks may then be predicted once the diploid absorbance has been found.     

微生物在生物能源生产中的应用(英文)

生物可再生能源是最有前景的石油替代品之一.生物能源的生产原料包括:植物、有机废弃物和微生物.微生物在生物能源生产上有着广泛的应用,利用微生物制备的主要生物能源包括:生物柴油、生物乙醇、生物甲烷等.某些微生物如微藻和真菌可以生产大量油脂,这些油脂可以转化为生物柴油;有些微生物如酵母可以将糖类、淀粉以及纤维素转化为燃料乙醇,添加乙醇的汽油或柴油燃烧排放明显降低;还有些厌氧微生物可以将有机废弃物转化为甲烷,可用做家用燃气、车用燃气或发电.除此之外微生物还具有在生产能源的同时治理环境污染的优势.总之研究开发微生物在生物能源生产中的应用有利于世界可持续发展.