“Induced-fit”-type complex formation of the model enzyme α-cyclodextrin

On the basis of X-ray and neutron data for several α-cyclodextrin·substrate complexes it is shown that basically two different structures for α-cyclodextrin exist, one “tense”, the other “relaxed”. An “induced-fit”-like mechanism for α-cyclodextrin complex formation is proposed.     

Anhydrobiosis: the model worm as a model?

New work now shows that the dauer larvae of Caenorhabditis elegans can survive anhydrobiotically. The genetic tractability of this model organism may be useful in studying how organisms survive when losing most or all of their water.     

A comparison of sodium channel kinetics in the squid axon,the frog node and the frog node with BTX using the “silent gate” model

In this paper it is shown that the very different kinetics measured for the rise of the sodium current which follows a depolarization of the membrane in the squid giant axon, the frog node and the frog node treated with Batrachotoxin may be accurately predicted using only the measured equilibrium and static characteristics for the three preparations and the kinetics measured for the gating charge transfer.The kinetic predictions follow the use of the silent gate model for ion channel gating. The model is electrostatic and its chief assumptions are that the channel gate, called here the N-system, has fast kinetics and responds to the gating charge that transfers but not directly to the trans-membrane voltage applied. Because channel gating, corresponding here to the motion of the N-system, does not change its energy in the trans-membrane applied electric field the gating is electrically silent as far as gating charge transfer measurement is concerned. However the probability of gating rises with the quantity of gating charge that transfers due to the electrostatic interaction between the N-system and the gating charge, redistributed under the influence of the applied trans-membrane electric field. With these assumptions the kinetics of sodium channel gating are predictable using only the static and equilibrium characteristics of gating charge and channel activation measured as a function of membrane voltage, and the kinetics of the gating charge transfer. Because of the fast kinetics assumed for the N-system the predicted kinetics are the same for channels with any number of equivalent and independent N-systems or gates acting in parallel.The model predictions for sodium permeability kinetics are compared in detail with those recently measured for the frog node treated with Batrachotoxin and excellent agreement is obtained.     

General base-catalyzed ester hydrolysis as a model of the “charge-relay” system

The validity of the “charge-relay” system in serine esterases was examined by use of the general base-catalyzed hydrolysis of ethyl chloroacetate (I) as a model system. The general base catalytic rate for 2-benzimidazoleacetic acid (II) exhibited an eightfold positive deviation from the Brønsted plot including benzimidazole, imidazole, N-methylimidazole (V), and acetate ion, though in nucleophilic catalysis of the hydrolysis of p-nitrophenyl acetate, the point for II conformed to the Brønsted relationship together with imidazole and benzimidazole derivatives. The positive deviation of II from the Brønsted plot for the general base-catalysis was attributed to the cooperativity of the carboxyl group of II, the imidazolyl group of II, and the hydroxyl group of water. The present result provides support for the “charge-relay” system. Furthermore, the (essentially) total loss of the enzymatic activity due to N-3 methylation of histidine-57 in α-chymotrypsin is discussed in comparison to the general base-catalysis of V in the hydrolysis of I, which is also favorable for the “charge-relay” system.     

Comparative Study of the Absorption,Plasma Levels,and Urinary Excretion of the “New” and the “Old” Lanoxin

A comparative study was performed of the absorption, the plasma level at equilibrium, and the urinary excretion of digoxin using two types of Lanoxin tablets, those produced before and after the 1972 alteration of the tablet manufacture.After a single dose the absorption rate of the new tablets was about twice as great as the old, both in young subjects and in the elderly patients. There were no significant differences in the plasma levels of digoxin for the two tablets 15 hours after the last administration in patients on an equal maintenance dose. The urinary excretion of digoxin increased about 40% when the “old” Lanoxin was replaced by the “new.” In elderly patients a daily dose of 0·125 mg twice daily of the new tablets should be sufficient to reach the therapeutic range. Young people need a higher dosage. If the kidney function is reduced by as much as 50% the dose should be reduced.     

The “sugar” coarse-grained DNA model

More than 20 coarse-grained (CG) DNA models have been developed for simulating the behavior of this molecule under various conditions, including those required for nanotechnology. However, none of these models reproduces the DNA polymorphism associated with conformational changes in the ribose rings of the DNA backbone. These changes make an essential contribution to the DNA local deformability and provide the possibility of the transition of the DNA double helix from the B-form to the A-form during interactions with biological molecules. We propose a CG representation of the ribose conformational flexibility. We substantiate the choice of the CG sites (six per nucleotide) needed for the ”sugar” GC DNA model, and obtain the potentials of the CG interactions between the sites by the ”bottom-up” approach using the all-atom AMBER force field. We show that the representation of the ribose flexibility requires one non-harmonic and one three-particle potential, the forms of both the potentials being different from the ones generally used. The model also includes (i) explicit representation of ions (in an implicit solvent) and (ii) sequence dependence. With these features, the sugar CG DNA model reproduces (with the same parameters) both the B- and A- stable forms under corresponding conditions and demonstrates both the A to B and the B to A phase transitions.

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Graphical Abstract The proposed coarse-grained DNA model allows to reproduce both the B- and A- DNA forms and the transitions between them under corresponding conditions.

     

Comments on “distinctions among reciprocal altruism,kin selection,and cooperation and a model for the initial evolution of beneficent behavior”

For two reasons, by-product beneficence may sometimes become fixed in an unstructured population even more easily than Rothstein and Pierotti's (1988) analyses indicate. Also, contrary to their disclaimer, Rothstein and Pierotti's analyses do imply the existence of alleles specifically for beneficent behaviors.     

A model for the lateral diffusion of “stiff” chains in a lipid bilayer

We present random walk models for the diffusive motion of lipid probe molecules in a lipid bilayer and calculate the diffusion constants for probes spanning the entire bilayer and for probes extending through one lipid layer only. The stiffness of such molecules can explain the observed value of 2/3 for the ratio of these diffusion constants.     

Using the shifted multiplicative model to search for “separability” in crop cultivar trials

Summary The shifted multiplicative model (SHMM) is used in an exploratory step-down method for identifying subsets of environments in which genotypic effects are separable from environmental effects. Subsets of environments are chosen on the basis of a SHMM analysis of the entire data set. SHMM analyses of the subsets may indicate a need for further subdivision and/or suggest that a different subdivision at the previous stage should be tried. The process continues until SHMM analysis indicates that a SHMM with only one multiplicative term and its point of concurrence outside (left or right) of the cluster of data points adequately fits the data in all subsets. The method is first illustrated with a simple example using a small data set from the statistical literature. Then results obtained in an international maize (Zea mays L.) yield trial with 20 sites and nine cultivars is presented and discussed.Journal Article No. 91-3-171 of the Kentucky Agricultural Experiment Station published with the approval of the Director     

Ultrastructure of the endocrine cell types in the adenohypophysis of the teleost,Poecilia latipinna — a morphometric model

Summary A morphometric model providing detailed quantitative information on the ultrastructure of the adenohypophysial endocrine cells has been developed for Poecilia latipinna. The model consists of various morphological components quantified in terms of volumes, surfaces or numbers. For prolactin and growth hormone cells, appropriate results are expressed relative to the average volume of that cell type. The difficulties of quantifying EM data on pituitary glands, together with the various sources of error to which the data are clearly open, have been discussed. Some practical applications of quantitative EM to problems in fish pituitary research are outlined.I thank Dr. J.N. Ball for supplying the fish and Mr. L. Ethridge for technical assistance.     

A numerical model of cellular blebbing: A volume-conserving,fluid–structure interaction model of the entire cell

In animal cells, blebs are smooth, quasi-hemispherical protrusions of the plasma membrane that form when a section of the membrane detaches from the underlying actin cytoskeleton and is inflated by flowing cytosol. The mechanics behind this common cellular activity are not yet clear. As a first step in the development of a full computational framework, we present a numerical model of overall cell behavior based upon the interaction between a background Newtonian-fluid cytosol and elastic structures modeling the membrane and filaments. The detailed micromechanics of the cytoskeletal network are the subject of future work. Here, the myosin-driven contraction of the actin network is modeled through stressed elastic filaments. Quantitative models of cytoskeletal micromechanics and biochemistry require accurate estimates of local stress and flow conditions. The main contribution of this paper is the development of a computationally efficient fluid–structure interaction model based on operator splitting, to furnish this data. Cytosol volume conservation (as supported by experimental evidence) is enforced through an intermediate energy minimization step. Realistic bleb formation and retraction is observed from this model, offering an alternative formulation to positing complex continuum behavior of the cytoplasm (e.g. poroelastic model of Charras et al., 2008).     

Identification Keys,the “Natural Method,” and the Development of Plant Identification Manuals

The origins of field guides and other plant identification manuals have been poorly understood until now because little attention has been paid to 18th century botanical identification guides. Identification manuals came to have the format we continue to use today when botanical instructors in post-Revolutionary France combined identification keys (step-wise analyses focusing on distinctions between plants) with the “natural method” (clustering of similar plants, allowing for identification by gestalt) and alphabetical indexes. Botanical works featuring multiple but linked techniques to enable plant identification became very popular in France by the first decade of the 19th century. British botanists, however, continued to use Linnaeus’s sexual system almost exclusively for another two decades. Their reluctance to use other methods or systems of classification can be attributed to a culture suspicious of innovation, anti-French sentiment and the association of all things Linnaean with English national pride, fostered in particular by the President of the Linnean Society of London, Sir James Edward Smith. The British aversion to using multiple plant identification technologies in one text also helps explain why it took so long for English botanists to adopt the natural method, even after several Englishmen had tried to introduce it to their country. Historians of ornithology emphasize that the popularity of ornithological guides in the 19th and 20th centuries stems from their illustrations, illustrations made possible by printing technologies that improved illustration quality and reduced costs. Though illustrations are the most obvious features of late 19th century and 20th century guides, the organizational principles that make them functional as identification devices come from techniques developed in botanical works in the 18th century.     

Examination of the “null” model of connor and simberloff for species co-occurrences on Islands

Summary Among birds of the Bismarck Archipelago, only certain combinations of the species in a guild coexist on islands, and some species that are very similar ecologically have mutually exclusive distributions. Diamond (1975) interpreted these patterns as biologically significant, involving effects such as competition. Connor and Simberloff (1979) claimed such patterns to be not recognizably different from random, because they were scarcely distinguishable from those generated by a null distribution supposedly not incorporating competition.On examining the analysis by Connor and Simberloff, we find that it actually yields the opposite conclusion: three faunas tested have grossly non-random structures, while their test is unworkable for the fourth fauna. The method of Connor and Simberloff for generating a null distribution has many fatal weaknesses: dilution of relevant data from guilds with irrelevant data from the whole species pool; hidden incorporation of effects of competition into the constraints; inability to recognize a checkerboard, the extreme example of a distribution produced by competition; reliance on inefficient Monte Carlo simulations; severe constraints that sometimes make generation of a null distribution impossible; failure to weight species combinations; and failure to identify the direction of non-randomness or the species combinations most responsible.Finally, we use other recent studies by Simberloff and coleagues to examine the value of constructing null hypotheses in community ecology.     

A model of direction-selective “simple” cells in the visual cortex based on inhibition asymmetry

Direction selectivity is a prominent feature of single units in the central visual pathway of cat and monkey. Various mechanisms have been proposed for the generation of this property. Experimental evidence suggests that intracortical inhibition is a major factor contributing to direction selectivity.We have developed a one-dimensional computer model for direction selective simple cells in the visual cortex under two basic assumptions: 1) Inhibition is exerted upon a cortical cell by neighboring cells from either side within a retinotopic array, 2) The relative strength of inhibition from both neighbors can be varied, interneurons always having larger time constants than the simple cells. Summation in the model is linear, but is followed by an essential non-linearity. ON- and/or OFF-center cells of the sustained type (X-cells) are used as an input to the simple cells.The computer simulation demonstrates that various subtypes of direction-selective simple cells in area 17, as described by Schiller et al. (1976), can be generated by different amounts of inhibition asymmertry, different delays and by different spatial arrangements of the input. Only one type of input (ON or OFF) is required to generate direction selectivity, but a greater variety of cell subtypes is created by combining both. Length-summation, contributing to orientation selectivity, was not considered in this one-dimensional model.