Ecological determinants of divorce: a structural approach to the explanation of Japanese divorce.

This paper examines the ecological determinants of contemporary Japanese divorce rates on the prefectural level. LISREL and computer-generated graphics are the analytic methods used. The aggregate level of analysis demands the use of the ecological model which posits that demographic changes, economic activities, migration patterns, and the level of urbanization are significant predictors of divorce rate. Our analysis demonstrates that sex ratio, female labor force participation, female in-migration patterns, population increase, and net household income all play a significant role in affecting the divorce rate. Our findings also confirm the well-supported hypothesis that both population density and modernization positively influence modern Japan's divorce rates. The residual analysis also points out that in order to account for the large proportion of the unexplained variance of Japanese divorce, behavioral-related variables and island- or prefecture-specific dimensions need to be included in the ecological model of divorce.     

Ecological determinants of the behavior and social structure of Japanese monkeys: A synthesis

A review is presented of the results of the various studies in this volume and an attempt is made to establish connections among several features of the ecology, behavior, and social structure of Japanese monkeys. Several studies in this volume suggest that intergroup direct feeding competition has been much more severe in Yakushima, in the warm-temperate region, than in Kinkazan, in the cool-temperate region of Japan. This result is consistent with the predictions that moderate abundance and clumped distribution of food incur more severe intergroup direct competition. However, the number of adult females within a group in Yakushima was smaller than that in Kinkazan even though severe intergroup direct competition should favor large groups. This contradiction can be mainly explained by the less severe intergroup indirect competition in Kinkazan than in Yakushima. By contrast, some studies in this volume also indicate that adult male to female ratio within a group has been higher in Yakushima than in Kinkazan. This result can be explained in two ways: the females in Yakushima might have recruited more males to increase the competitive ability of the group under conditions of severe intergroup direct feeding competition; alternatively, it might be profitable that the males in Yakushima defend females cooperatively as group males against the males in other groups at a moderate density of females. Some studies in this volume suggest that grooming frequency was higher in Yakushima than in Kinkazan. The higher grooming frequency in Yakushima might have been partly due to a constant increase in engaging in social behavior from a decrease in feeding time. Another reason might be that there is a stronger effect of grooming on promotion of formation of coalitions among adults under conditions of severe intergroup direct and intragroup direct competition.     

A design approach to the structural analysis of interleukin-2

A semi-synthetic protein design approach has been employed for the structural investigation of a putative helical region at the C-terminus of Interleukin-2. With crystallographic or NMR derived conformational data as yet unavailable, we have relied only on primary sequence information and computer-assisted modelling to direct the analysis. By employing both chemical peptide synthesis and recombinant DNA methods, the C-terminus of IL-2 was modified according to a strategy designed to stabilize helical secondary structure. A semi-synthetic protein incorporating 12 simultaneous amino acid replacements was constructed, which possessed potentiated biological activity and displayed a far UV circular dichroism spectrum comparable to a hybrid protein with the authentic sequence. By comparison, another hybrid protein containing a C-terminal region designed to contain helix breaking residues was totally devoid of bioactivity. These findings provide evidence that the modelling method correctly identified a helix necessary for the formation of a bioactive tertiary fold. Moreover, by employing semi-synthesis it was possible to circumvent the difficulties associated with the preparation, purification and analysis of multiple recombinant proteins, and also to avoid the unreliability of total chemical synthesis for proteins greater than 100 residues.     

A molecular dynamics approach to the structural characterization of amyloid aggregation

A novel computational approach to the structural analysis of ordered beta-aggregation is presented and validated on three known amyloidogenic polypeptides. The strategy is based on the decomposition of the sequence into overlapping stretches and equilibrium implicit solvent molecular dynamics (MD) simulations of an oligomeric system for each stretch. The structural stability of the in-register parallel aggregates sampled in the implicit solvent runs is further evaluated using explicit water simulations for a subset of the stretches. The beta-aggregation propensity along the sequence of the Alzheimer's amyloid-beta peptide (Abeta(42)) is found to be highly heterogeneous with a maximum in the segment V(12)HHQKLVFFAE(22) and minima at S(8)G(9), G(25)S(26), G(29)A(30), and G(38)V(39), which are turn-like segments. The simulation results suggest that these sites may play a crucial role in determining the aggregation tendency and the fibrillar structure of Abeta(42). Similar findings are obtained for the human amylin, a 37-residue peptide that displays a maximal beta-aggregation propensity at Q(10)RLANFLVHSSNN(22) and two turn-like sites at G(24)A(25) and G(33)S(34). In the third application, the MD approach is used to identify beta-aggregation "hot-spots" within the N-terminal domain of the yeast prion Ure2p (Ure2p(1-94)) and to design a double-point mutant (Ure2p-N4748S(1-94)) with lower beta-aggregation propensity. The change in the aggregation propensity of Ure2p-N4748S(1-94) is verified in vitro using the thioflavin T binding assay.     

Dynamic structure theory: A structural approach to social and biological systems

The relationships that define the structure of a given ecosystem, social system, or even a physiological function can only exist if certain parameters are confined to a certain range of values. As the values change and exceed this given range the relationships are forced to change, and so produce a new pattern of relationships. The concept of a dynamic structure captures this potential for structural change in relation to a set of parameters. The precise definition of structure and allowable transformation constitutes the definition of a category. The total range of parameters associated with all the relevant structures provides a parameter space which is assumed to be a manifold. Maps with extra structure from the manifold to the category define dynamic structures. The domain of differential dynamic systems is the manifold, and a flow or movement across the manifold is associated with a series of structural transformations in the category. In some cases a structure outruns its parameter range, to be faced with an obstruction—an absence of possible transformations. Ways of studying such “obstructions” are considered along with the related problem of extending a dynamic structure beyond a previously given set of parameters. The cost or resistance of transformations is also studied. The concepts of dynamic structures are illustrated by the structural change of food webs and they are used in a necessarily qualitative fashion to study dominance structures of social orders and finally to speculate on the qualitative nature of evolutionary change of functional aspects of organisms.     

Ensemble approach to predict specificity determinants: benchmarking and validation

Background  

It is extremely important and challenging to identify the sites that are responsible for functional specification or diversification in protein families. In this study, a rigorous comparative benchmarking protocol was employed to provide a reliable evaluation of methods which predict the specificity determining sites. Subsequently, three best performing methods were applied to identify new potential specificity determining sites through ensemble approach and common agreement of their prediction results.     

Limited tendency of alpha-helical residues to form disulfide bridges: a structural explanation.

Disulfide bridges have an enormous impact on the structure of a large number of proteins and polypeptides. Understanding the structural basis that regulates their formation may be important for the design of novel peptide-based molecules with a specific fold and stability. Here we report a statistical analysis of the relationships between secondary structure and disulfide bond formation, carried out using a large database of protein structures. Our analyses confirm the observation sporadically reported in previous investigations that cysteine residues located in alpha-helices display a limited tendency to form disulfide bridges. The very low occurrence of the disulfide bond in all alpha-chains compared to all beta-chains indicates that this property is also evident when proteins with different topologies are investigated. Taking advantage of the large database that endorsed the analysis on relatively rare motifs, we demonstrate that cysteine residues embedded in 3(10) helices present a good tendency to form disulfide bonds. This result is somewhat surprising since 3(10) helices are commonly assimilated into alpha-helices. A plausible structural explanation for the observed data has been derived combining analyses of disulfide bond sequence separation and of the length of the different secondary structure elements.     

A crystallographic approach to structural transitions in icosahedral viruses

Viruses with icosahedral capsids, which form the largest class of all viruses and contain a number of important human pathogens, can be modelled via suitable icosahedrally invariant finite subsets of icosahedral 3D quasicrystals. We combine concepts from the theory of 3D quasicrystals, and from the theory of structural phase transformations in crystalline solids, to give a framework for the study of the structural transitions occurring in icosahedral viral capsids during maturation or infection. As 3D quasicrystals are in a one-to-one correspondence with suitable subsets of 6D icosahedral Bravais lattices, we study systematically the 6D-analogs of the classical Bain deformations in 3D, characterized by minimal symmetry loss at intermediate configurations, and use this information to infer putative viral-capsid transition paths in 3D via the cut-and-project method used for the construction of quasicrystals. We apply our approach to the Cowpea Chlorotic Mottle virus (CCMV) and show that the putative transition path between the experimentally observed initial and final CCMV structures is most likely to preserve one threefold axis. Our procedure suggests a general method for the investigation and prediction of symmetry constraints on the capsids of icosahedral viruses during structural transitions, and thus provides insights into the mechanisms underlying structural transitions of these pathogens.     

Using multiple biomarkers and determinants to obtain a better measurement of oxidative stress: a latent variable structural equation model approach

Purpose: Since oxidative stress involves a variety of cellular changes, no single biomarker can serve as a complete measure of this complex biological process. The analytic technique of structural equation modeling (SEM) provides a possible solution to this problem by modelling a latent (unobserved) variable constructed from the covariance of multiple biomarkers.

Methods: Using three pooled datasets, we modelled a latent oxidative stress variable from five biomarkers related to oxidative stress: F₂-isoprostanes (FIP), fluorescent oxidation products, mitochondrial DNA copy number, γ-tocopherol (Gtoc) and C-reactive protein (CRP, an inflammation marker closely linked to oxidative stress). We validated the latent variable by assessing its relation to pro- and anti-oxidant exposures.

Results: FIP, Gtoc and CRP characterized the latent oxidative stress variable. Obesity, smoking, aspirin use and β-carotene were statistically significantly associated with oxidative stress in the theorized directions; the same exposures were weakly and inconsistently associated with the individual biomarkers.

Conclusions: Our results suggest that using SEM with latent variables decreases the biomarker-specific variability, and may produce a better measure of oxidative stress than do single variables. This methodology can be applied to similar areas of research in which a single biomarker is not sufficient to fully describe a complex biological phenomenon.     

A structural screening approach to ketoamide-based inhibitors of cathepsin K

Several novel ketoamide-based inhibitors of cathepsin K have been identified. Starting from a modestly potent inhibitor, structural screening of P2 elements led to 100-fold enhancements in inhibitory activity. Modifications to one of these leads resulted in an orally bioavailable cathepsin K inhibitor.     

Characterization of antibodies to the structural polypeptides of HGSAg: evidence for subtype-specific determinants.

Antisera prepared in guinea pigs to the structural polypeptides of HBAAg/adw and HBSAg/ayw were examined by a modified passive hemagglutination assay for antibodies to the subtype-specific d and y determinants. All of the isolated polypeptide fractions stimulated antibodies to both group specific and subtype-specific antigens of the native HBSAg particle from which they were derived. These data indicate that the polypeptides have similarities in their immunochemical structure.     

Teenage childbearing: structural determinants in developing countries

Data for a sample of 50 developing countries are analysed to investigate the social correlates of the teenage birth rate. Of five major factors considered as predictors of national birth rates (socioeconomic development, family planning programmes, women's status, the sex ratio, and marriage patterns), regression analyses reveal that only the average age at marriage for women has a significant effect on the teenage birth rate. In contrast, all variables except the sex ratio and the average age at marriage for women have a significant effect on the total fertility rate.     

Sarcoplasmic reticulum: structural determinants and protein dynamics

The sarcoplasmic reticulum is a unique organelle found in muscle cells that is dedicated to the regulation of Ca(2+) homeostasis and activation of myofilament contraction. The functional requirement for an efficient and synchronous activation of Ca(2+) release from the SR, following the depolarization of the plasma membrane, accounts for the complex three-dimensional organization of internal membranes observed in muscle cells and for the localization of proteins at specific sites of the SR. Recent advancements in understanding the molecular basis of SR structure and function have greatly increased our understanding of muscle cellular physiology and biology. Parallel work has revealed that several human diseases affecting skeletal and cardiac tissues are linked to either mutations or altered post-translational modifications of SR proteins.     

Biological glass: structural determinants of eye lens transparency

The purpose of the lens is to project a sharply focused, undistorted image of the visual surround onto the neural retina. The first pre-requisite, therefore, is that the tissue should be transparent. Despite the presence of remarkably high levels of protein, the lens cytosol remains transparent as a result of short-range-order interactions between the proteins. At a cellular level, the programmed elimination of nuclei and other light-scattering organelles from cells located within the pupillary space contributes directly to tissue transparency. Scattering at the cell borders is minimized by the close apposition of lens fibre cells facilitated by a plethora of adhesive proteins, some expressed only in the lens. Similarly, refractive index matching between lens membranes and cytosol is believed to minimize scatter. Refractive index matching between the cytoplasm of adjacent cells is achieved through the formation of cellular fusions that allow the intermingling of proteins. Together, these structural adaptations serve to minimize light scatter and enable this living, cellular structure to function as 'biological glass'.     

Family fingerprints: a global approach to structural classification

Protein domain classification is a useful tool to deduce functional properties of proteins. Many software to classify domains according to available databases have been proposed so far. This paper introduces the notion of "fingerprint" as an easy and readable digest of the similarities between a protein fragment and an entire set of sequences. This concept offers us a rationale for building an automatic SCOP classifier which assigns a query sequence to the most likely family. Fingerprint-based analysis has been implemented in a software tool and we report some experimental validations for it.