The Human Obesity Gene Map: The 1996 Update

An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single-gene mutation rodent models, quantitative trait loci uncovered in crossbreeding experiments with mouse, rat, and pig models, association and case-control studies with candidate genes, and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed.     

Global stability of an SIR epidemic model with time delays

An SIR disease transmission model is formulated under the assumption that the force of infection at the present time depends on the number of infectives at the past. It is shown that a disease free equilibrium point is globally stable if no endemic equilibrium point exists. Further the endemic point (if it exists) is globally stable with respect to the whole state space except the neighborhood of the disease free state.Research partly supported by the Ministry of Education, Science and Culture, Japan, Grant 05640256     

Optimal local propensities for model proteins

Lattice models of proteins were used to examine the role of local propensities in stabilizing the native state of a protein, using techniques drawn from spin-glass theory to characterize the free-energy landscapes. In the strong evolutionary limit, optimal conditions for folding are achieved when the contributions from local interactions to the stability of the native state is small. Further increasing the local interactions rapidly decreases the foldability. © 1995 Wiley-Liss, Inc.     

Brief overview of control of genetic expression by antisense oligonucleotides and in vivo applications

Over the past several years, the use of synthetic oligonucleotides and functional analogs thereof as a possibly general means of controlling genetic expression has received widespread attention. Following a brief overview of some of the basic principles and strategies for this approach, attention is focused here on summarizing some recent reports of in vitro and, in particular, in vivo investigations in various animal models using phosphorothioate analogs of 2′-deoxyoligo-nucleotides. In view of these findings, which include studies related to neurobiology, this field should find significant utility in applications of the antisense method for controlling genetic expression.     

Exhaustive enumeration of protein conformations using experimental restraints.

We present an efficient new algorithm that enumerates all possible conformations of a protein that satisfy a given set of distance restraints. Rapid growth of all possible self-avoiding conformations on the diamond lattice provides construction of alpha-carbon representations of a protein fold. We investigated the dependence of the number of conformations on pairwise distance restraints for the proteins crambin, pancreatic trypsin inhibitor, and ubiquitin. Knowledge of between one and two contacts per monomer is shown to be sufficient to restrict the number of candidate structures to approximately 1,000 conformations. Pairwise RMS deviations of atomic position comparisons between pairs of these 1,000 structures revealed that these conformations can be grouped into about 25 families of structures. These results suggest a new approach to assessing alternative protein folds given a very limited number of distance restraints. Such restraints are available from several experimental techniques such as NMR, NOESY, energy transfer fluorescence spectroscopy, and crosslinking experiments. This work focuses on exhaustive enumeration of protein structures with emphasis on the possible use of NOESY-determined distance restraints.     

Interactions between two sheets of a bilayer membrane and its internal lateral pressure

We have modelled a phospholipid bilayer as two monolayer sheets which interact with each other by a coupling which depends upon the states of the lipid hydrocarbon chains in each sheet. We make use of a model (Georgallas and Pink 1982a) and its parameters, already used to study monolayer phase changes at the LC-LE transition, in order to study the lipid main transition. Although the monolayer coexistence curve can be calculated exactly, we have made use of high-temperature series expansions to calculate the critical point of the bilayer. We also present the results of computer simulations on triangular lattices for the pressure-area isotherms. We find: (i) the interaction between the sheets of a DPPC bilayer is about 1.5–2% of the maximum interaction within the plane of each sheet; (ii) the internal lateral pressure of a DPPC bilayer is about 30.5 dyne/cm; (iii) the bilayer transition enthalpy depends sensitively upon the coupling between the sheets. Should this coupling vary from sample to sample (due, possibly, to its preparation) then very different values of transition enthalpy may be measured. (iv) We present a rough rule-of-thumb for estimating the internal lateral pressure of a bilayer from a knowledge of the corresponding monolayer pressure-area isotherms.Abbreviations LC-LE liquid condensed — liquid expanded - DPPC dipalmitoylphosphatidylcholine - Q transition enthalpy Work supported in part by the Natural Sciences and Engineering Research Council of Canada     

Diversity concept in ecology

Hierarchy of systems organization is used as a framework in advancing methodological guidelines for posing correct questions related to ecological diversity.Diversity if defined in general terms as a property of a set of elements dependent on and determines: by the epistemological perspective. Ontological diversity, because it is indefinite, is regarded as unmeasurable.Ecological diversity — be it species, spatial, reproductive or trophic, is a particular case of diversity of matter and must be precisely defined on the studied level of system organization.Diversity measurements combining more than one level of organization are information-void, for data become irretrievable as a result of such a treatment.Hypotheses explaining diversity sources are briefly surveyed. An integrated model interrelating them is constructed as a result of some basic views on the structure of matter coupled with the empirical knowledge of involved factors. The model reflects hierarchies of systems, their dynamics, and the complexities of factors affecting diversity. The model's properties suggest that it is conceptually related to an imaginary model of organization of ecological systems. Parameters recognized as invariant components of this complexity are: habitat differentiation, ecological specialization of species, ambiental changes, and integration of this system.Finally, it is shown that the peculiar shape of the species abundances curve is a necessary consequence of stratification of the system structure, which is an intrinsic attribute of hierarchical organization.     

The significance of specific distributions and functions in models of quantitative inheritance

The main purpose of this paper is to attract attention to the fact that a mathematical model of quantitative inheritance can lead to qualitatively different results, if distributions and functions which in the model represent biological processes are assumed to take analytically different (even though qualitatively similar) forms. A simple model of the effect of environmental variation on the post-selection genotypic variance in a population under phenotypic stabilizing selection is considered. It is demonstrated that this model leads to qualitatively different conclusions depending on whether the phenotypic fitness function is assumed in a Gaussian or in a quadratic form.     

Photoperiodic time measurement in the spider mite Tetranychus urticae: A novel concept

To explain photoperiodic induction of diapause in the spider mite Tetranychus urticae a new theoretical model was developed which took into account both the hourglass and rhythmic elements shown to be present in the photoperiodic reaction of these mites. It is emphasized that photoperiodic induction is the result of time measurement as well as the summation and integration of a number of successive photoperiodic cycles: the model, therefore, consists of separate ‘clock’ and ‘counter’ mechanisms. In current views involvement of the circadian system in photoperiodism is interpreted in terms of the hypothesis that the photoperiodic clock itself is based on one or more circadian oscillators. Here a different approach has been chosen as regards the role of the circadian system in photoperiodism: the possibility, previously put forward by other authors, that some aspect of the photoperiodic induction mechanism other than the clock is controlled by the circadian system was investigated by assuming a circadian influence on the photoperiodic counter mechanism. The derivation of this ‘hourglass timer oscillator counter’ model of photoperiodic induction in T. urticae is described and its operation demonstrated on the basis of a number of diel and nondiel photoperiods, with and without light interruptions.     

MIXED MODEL APPROACHES FOR ESTIMATING GENETIC VARIANCES AND COVARIANCES

The limitations of methods for analysis of variance(ANOVA)in estimating genetic variances are discussed. Among the three methods(maximum likelihood ML, restricted maximum likelihood REML, and minimum norm quadratic unbiased estimation MINQUE)for mixed linear models, MINQUE method is presented with formulae for estimating variance components and covariances components and for predicting genetic effects. Several genetic models, which cannot be appropriately analyzed by ANOVA methods, are introduced in forms of mixed linear models. Genetic models with independent random effects can be analyzed by MINQUE(1)method whieh is a MINQUE method with all prior values setting 1. MINQUE(1)method can give unbiased estimation for variance components and covariance components, and linear unbiased prediction (LUP) for genetic effects. There are more complicate genetic models for plant seeds which involve correlated random effects. MINQUE(0/1)method, which is a MINQUE method with all prior covariances setting 0 and all prior variances setting 1, is suitable for estimating variance and covariance components in these models. Mixed model approaches have advantage over ANOVA methods for the capacity of analyzing unbalanced data and complicated models. Some problems about estimation and hypothesis test by MINQUE method are discussed.