Double-stranded DNA organization in bacteriophage heads: an alternative toroid-based model.

Studies of the organization of double-stranded DNA within bacteriophage heads during the past four decades have produced a wealth of data. However, despite the presentation of numerous models, the true organization of DNA within phage heads remains unresolved. The observations of toroidal DNA structures in electron micrographs of phage lysates have long been cited as support for the organization of DNA in a spool-like fashion. This particular model, like all other models, has not been found to be consistent will all available data. Recently we proposed that DNA within toroidal condensates produced in vitro is organized in a manner significantly different from that suggested by the spool model. This new toroid model has allowed the development of an alternative model for DNA organization within bacteriophage heads that is consistent with a wide range of biophysical data. Here we propose that bacteriophage DNA is packaged in a toroid that is folded into a highly compact structure.     

The genetic implications of biological and cultural structuring processes during hominid evolution

Human populations are genetically structured through biological reproduction but reproduction is socially structured through culturally expressed systems of marriage, hence the need to take into account the cultural dimension of human societies when considering the genetic structure of modern human populations. The interplay between these two structuring processes is examined through the implications of a biologically based primate form of social organization versus a culturally based foraging form of social organization for an anomaly between the genetic differentiation implied by micro-evolutionary genetic models versus the species-wide pattern of morphological change implied by hominid fossil evidence. Simulation is used to derive the pattern for genetic differentiation at the level of the living group for both forms of social organization and a competition model is added to the genetic model as a way to resolve the anomaly. The importance of the competition model for the transition from a biologically based to a culturally based form of social organization is discussed.     

A mechanistic model for the organization of microtubule asters by motor and non-motor proteins in a mammalian mitotic extract

We used computer simulation to understand the functional relationships between motor (dynein, HSET, and Eg5) and non-motor (NuMA) proteins involved in microtubule aster organization. The simulation accurately predicted microtubule organization under all combinations of motor and non-motor proteins, provided that microtubule cross-links at minus-ends were dynamic, and dynein and HSET were restricted to cross-linking microtubules in parallel orientation only. A mechanistic model was derived from these data in which a combination of two aggregate properties, Net Minus-end-directed Force and microtubule Cross-linking Orientation Bias, determine microtubule organization. This model uses motor and non-motor proteins, accounts for motor antagonism, and predicts that alterations in microtubule Cross-linking Orientation Bias should compensate for imbalances in motor force during microtubule aster formation. We tested this prediction in the mammalian mitotic extract and, consistent with the model, found that increasing the contribution of microtubule cross-linking by NuMA compensated for the loss of Eg5 motor activity. Thus, this model proposes a precise mechanism of action of each noncentrosomal protein during microtubule aster organization and suggests that microtubule organization in spindles involves both motile forces from motors and static forces from non-motor cross-linking proteins.     

N-3 fatty acids and membrane microdomains: From model membranes to lymphocyte function

This article summarizes the author's research on fish oil derived n-3 fatty acids, plasma membrane organization and B cell function. We first cover basic model membrane studies that investigated how docosahexaenoic acid (DHA) targeted the organization of sphingolipid-cholesterol enriched lipid microdomains. A key finding here was that DHA had a relatively poor affinity for cholesterol. This work led to a model that predicted DHA acyl chains in cells would manipulate lipid-protein microdomain organization and thereby function. We then review how the predictions of the model were tested with B cells in vitro followed by experiments using mice fed fish oil. These studies reveal a highly complex picture on how n-3 fatty acids target lipid-protein organization and B cell function. Key findings are as follows: (1) n-3 fatty acids target not just the plasma membrane but also endomembrane organization; (2) DHA, but not eicosapentaenoic acid (EPA), disrupts microdomain spatial distribution (i.e. clustering), (3) DHA alters protein lateral organization and (4) changes in membrane organization are accompanied by functional effects on both innate and adaptive B cell function. Altogether, the research over the past 10 years has led to an evolution of the original model on how DHA reorganizes membrane microdomains. The work raises the intriguing possibility of testing the model at the human level to target health and disease.     

Allogrooming and social status: An assessment of the contributions of female behavior to the social organization of hamadryas baboons (Papio hamadryas)

Three isosexual social groups, each containing ten subadult female hamadryas monkeys (Papio hamadryas) were studied for seven months to test three hypotheses dealing with the assumptions underlyingSeyfarth's (1977) model of allogrooming and social organization. Aggression, avoid and allogrooming behaviors were used as criteria for studying the social organization of the groups. UsingLandau's (1951) index and discriminant analyses, we found that each of the three isosexual female social units conformed to a model of social organization having a non-linear hierarchy and only two major strata: a dominant animal and subordinates who were largely undifferentiated. This aspect of social organization is similar to the normal one-male unit leader harem form of social organization that is typical of hamadryas. However, since no male was present, the role of unit leader was filled by a female. The length of allogrooming bouts and the amount of allogroom received was affected by the social status of the recipient, with high status individuals receiving more than low status individuals. Social peers were not observed competing for access to high status individuals and did not exchange most of their grooming among themselves. We found that the assumptions underlyingSeyfarth's (1977) model were not appropriate for the type of social organization typically found in hamadryas monkeys, thus suggesting the need for further modification of the model so that it fits available data.     

Phase organization of circadian oscillators in extended gate and oscillator models

The suprachiasmatic nuclei (SCN) control daily oscillations in physiology and behavior. The gate-oscillator model captures functional heterogeneity in SCN and has been successful in reproducing many features of SCN. This paper investigates the mechanism of phase organization in the gate-oscillator model and finds that only stable fixed points of the phase transition function are essential to phase organization. This obvious finding forms the basis for understanding the complex phase distribution in the gate-oscillator scheme. Extending the model with a dead zone of the phase transition function and the propagation delay of the gate signal which may represent the spatial structure of SCN, the author discusses how some features of experimentally reported phase distribution, such as the existence of anti-phase neurons and fixed phase difference between neurons, could be understood in the framework of the gate-oscillator model. The extended model shows clearly the way in which the interplay between the single-cell property and the property of the network organization influence the phase distribution of SCN neurons.     

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.     

A Lamin-Associated Chromatin Model for Chromosome Organization

We propose a simple model for chromatin organization based on the interaction of the chromatin fibers with lamin proteins along the nuclear membrane. Lamin proteins are known to be a major factor that influences chromatin organization and hence gene expression in the cells. We provide a quantitative understanding of lamin-associated chromatin organization in a crowded macromolecular environment by systematically varying the heteropolymer segment distribution and the strength of the lamin-chromatin attractive interaction. Our minimal polymer model reproduces the formation of lamin-associated-domains and provides an in silico tool for quantifying domain length distributions for different distributions of heteropolymer segments. We show that a Gaussian distribution of heteropolymer segments, coupled with strong lamin-chromatin interactions, can qualitatively reproduce observed length distributions of lamin-associated-domains. Further, lamin-mediated interaction can enhance the formation of chromosome territories as well as the organization of chromatin into tightly packed heterochromatin and the loosely packed gene-rich euchromatin regions.     

Homology modeling and consensus protein disorder prediction of human filamin

Filamins are dimeric actin-binding proteins participating in the organization of the actin-based cytoskeleton. Their modular domain organization is made up of an N-terminal actin-binding domain composed of two CH domains followed by flexible rod regions that consist of 24 Ig-like domains. Homology modeling was used to model human filamin using Modeller 9v5. The resulting model assessed by Verify 3D and PROCHECK showed that the final model is reliable. The conformational disorder prediction of human filamin residues were also mapped on the validated structure of human filamin. Prediction of protein disorder in filamin structures will help structural biologists to find suitable targets to be analyzed and for understanding protein function.     

Rat hepatoma cells nucleolar DNA. II. A possible model of nucleolar DNA organisation.

A model of nucleolar DNA organization has been established. Three clearly defined main components are found in ascites hepatoma cell nucleolar DNA by CsCl gradient analysis. A linear arrangement for nucleolar DNA and a model of DNA organization in the neighbourhood of a set of ribosomal genes, which may play a fundamental role in the elaboration of nucleolar chromatin tertiary structure, are presented.     

Autopoiesis: The organization of living systems,its characterization and a model

We formulate the organization of living organisms through the characterization of the class of autopoietic systems to which living things belong. This general characterization is seen at work in a computer simulated model of a minimal case satisfying the conditions for autopoietic organization.     

A Three-Dimensional Computer Simulation Model Reveals the Mechanisms for Self-Organization of Plant Cortical Microtubules into Oblique Arrays

The noncentrosomal cortical microtubules (CMTs) of plant cells self-organize into a parallel three-dimensional (3D) array that is oriented transverse to the cell elongation axis in wild-type plants and is oblique in some of the mutants that show twisted growth. To study the mechanisms of CMT array organization, we developed a 3D computer simulation model based on experimentally observed properties of CMTs. Our computer model accurately mimics transverse array organization and other fundamental properties of CMTs observed in rapidly elongating wild-type cells as well as the defective CMT phenotypes observed in the Arabidopsis mor1-1 and fra2 mutants. We found that CMT interactions, boundary conditions, and the bundling cutoff angle impact the rate and extent of CMT organization, whereas branch-form CMT nucleation did not significantly impact the rate of CMT organization but was necessary to generate polarity during CMT organization. We also found that the dynamic instability parameters from twisted growth mutants were not sufficient to generate oblique CMT arrays. Instead, we found that parameters regulating branch-form CMT nucleation and boundary conditions at the end walls are important for forming oblique CMT arrays. Together, our computer model provides new mechanistic insights into how plant CMTs self-organize into specific 3D arrangements.     

Predicting chromatin organization using histone marks

Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these features across datasets and cell types. Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries. Our predictions provide a useful guide for the exploration of chromatin organization.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0740-z) contains supplementary material, which is available to authorized users.     

Reprogramming of three-dimensional chromatin organization in the early embryo

Chromatin organization within the three-dimensional (3D) nuclear space is important for proper gene expression and developmental programming. This organization is established during the dramatic reprogramming that occurs in early embryonic development. Thus, the early embryo is an ideal model for examining the formation and dynamics of 3D chromatin structure. Advances in high-resolution microscopy and single-nucleus genomic analyses have provided fundamental insights into the mechanisms driving genome organization in the early embryo. Here, we highlight recent findings describing the dynamics and driving mechanisms for establishing 3D chromatin organization and discuss the role such organization has on gene regulation in early embryonic development.     

The mitochondrial genome. The nucleoid

Mitochondrial DNA (mtDNA) in cells is organized in nucleoids containing DNA and various proteins. This review discusses questions of organization and structural dynamics of nucleoids as well as their protein components. The structures of mt-nucleoid from different organisms are compared. The currently accepted model of nucleoid organization is described and questions needing answers for better understanding of the fine mechanisms of the mitochondrial genetic apparatus functioning are discussed.     

The contribution of signaling pathways to olfactory organization and development

The exquisite specificity in the organization of the mammalian olfactory system underlies its remarkable sensitivity and precision in odorant detection. The contribution of olfactory receptor proteins to the initial patterning of connections between the sensory epithelium and the bulb is widely appreciated. The application of genetic model systems has revealed additional roles for odorant-evoked activity in the development, organization and dynamic turnover of cells in this regenerating sensory organ.     

Quantitative aspects of metabolic organization: a discussion of concepts

Metabolic organization of individual organisms follows simple quantitative rules that can be understood from basic physical chemical principles. Dynamic energy budget (DEB) theory identifies these rules, which quantify how individuals acquire and use energy and nutrients. The theory provides constraints on the metabolic organization of subcellular processes. Together with rules for interaction between individuals, it also provides a basis to understand population and ecosystem dynamics. The theory, therefore, links various levels of biological organization. It applies to all species of organisms and offers explanations for body-size scaling relationships of natural history parameters that are otherwise difficult to understand. A considerable number of popular empirical models turn out to be special cases of the DEB model, or very close numerical approximations. Strong and weak homeostasis and the partitionability of reserve kinetics are cornerstones of the theory and essential for understanding the evolution of metabolic organization.     

The impact of entropy on the spatial organization of synaptonemal complexes within the cell nucleus

We employ 4Pi-microscopy to study SC organization in mouse spermatocyte nuclei allowing for the three-dimensional reconstruction of the SC's backbone arrangement. Additionally, we model the SCs in the cell nucleus by confined, self-avoiding polymers, whose chain ends are attached to the envelope of the confining cavity and diffuse along it. This work helps to elucidate the role of entropy in shaping pachytene SC organization. The framework provided by the complex interplay between SC polymer rigidity, tethering and confinement is able to qualitatively explain features of SC organization, such as mean squared end-to-end distances, mean squared center-of-mass distances, or SC density distributions. However, it fails in correctly assessing SC entanglement within the nucleus. In fact, our analysis of the 4Pi-microscopy images reveals a higher ordering of SCs within the nuclear volume than what is expected by our numerical model. This suggests that while effects of entropy impact SC organization, the dedicated action of proteins or actin cables is required to fine-tune the spatial ordering of SCs within the cell nucleus.     

Self-organization of treadmilling microtubules into a polar array

The centrosome is normally thought to determine the cell center and to dictate the formation of a radial array of microtubules that defines the spatial organization of cytoplasm. However, experiments indicate the existence of a mechanism for organization of a centered microtubule array that is independent of the centrosome. Here, we formulate a model of treadmilling dynamics of non-centrosomal microtubules that predicts a spontaneously established, polarized distribution of microtubule orientation. Based on this model, we propose that the autonomous ability of non-centrosomal microtubules to form a polarized array arises from their treadmilling within the space constrained by the cell boundary.