Functional contribution of the parafascicular complex of the thalamus to complex forms of behavior in cats

The role of the thalamic parafascicular complex in cognitive processes was studied in free behaviour of cats on an original model of alternative choice with generalization of different signals systems by the principle of formation of preverbal concept "more-less". It is shown that the lateral part of the complex is involved in the mechanisms of generalization and abstraction, and the medial one--in conditioned activity. Biological bases of thalamic dementia are discussed.     

How radiation influences atherosclerotic plaque development: a biophysical approach in ApoE ¯/¯ mice

Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE\(^{{-/-}}\) mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors’ knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development.     

Reliability of enzyme systems and molecular mechanisms of aging

A stochastic model of animal mortality and ageing is proposed. In a living being there is a "biological clock", constructed from Q kinds of functional elements (genes), The reliability of functioning of these genes determines the biological age of the being. Oxidative processes in the cells are accompanied by random failures of electron transfer enzyme systems, which result in appearance of free superoxide radicals. Failures of electron transfer enzymes and of defence enzymes lead to accumulation of functional damages in the genes of the "clock". In terms of the model experimental data of gerontology (Gompertz's law, Strehler-Mildvan's compensation effect, etc) are easily explained. The value of Q for the man is estimated to be of the order of 10. Some possible mechanisms of action of "geroprotectors" have been discussed.     

Mechanisms of neovasculogenesis and its regulation in the adult organism

Under regeneration of organs, wound healing, tumour growth, inflammatory processes, under many compensatory and adaptive reactions in the organism of mature persons and animals, an inevitable formation of new blood vessels (neovasculogenesis) takes place. Modern notions on mechanisms of neovasculogenesis are based on the fact that new formation of vessels in a mature organism includes processes of migration and replication of endothelial cells according to the principle: "endothelium from endothelium". The literature data on neovasculogenesis in the mature organism are summarized and compared with the authors' investigations. Characterization of new blood vessels growth is presented; ultrastructural organization of endotheliocytes in growing capillaries, formation of barrier-transport properties in the newly formed vessels, role of inductors and inhibitors of neovasculogenesis in creation of new vascular formations are considered.     

The continuous Sir Philip Sidney game: a simple model of biological signalling.

An analysis of Maynard Smith's two-player, ESS model of biological signalling, the "Sir Philip Sidney game", is presented. The stable strategies of the players in this game are shown to satisfy the conditions of Zahavi's handicap principle. At equilibrium, signals are honest, costly, and costly in a way that is related to the true quality revealed. Further analysis reveals that the level of cost required to maintain stability is inversely related to the degree of relatedness between the players. It therefore seems likely that stable biological signalling systems will feature lower signalling costs when communication occurs between relatives. A three-player, extended version of the model is investigated, in which signals are passed via an intermediate, or "messenger". It is shown that this destabilizes the signalling system, and leads to increased signalling costs. This result suggests that "kin conflict" theories of the evolution of the endosperm in flowering plants require further refinement. The introduction of a novel resource acquisition tissue, which mediates parent-offspring interaction during development, cannot be assumed to limit parent-offspring conflict simply because it carries an extra copy of the maternally inherited genes. The ability to add such complications to the Sir Philip Sidney game and still obtain solutions makes it a very useful modelling tool.     

The possible use of PKZh-type devices (liquid purity control devices) in the analysis of cell suspensions

PKZh means "device for liquid purity control". A possibility is considered to use the native PKZh type device for carrying out quantitative analyses of cellular suspension components, for routine bacterial suspension, agglutinated bacterial suspension and erythrocyte suspension. The flowing photometric principle of particle recording, used in the device, allows to analyse biological suspensions with small amounts of components. The device provides a differential count of some cells and their conglomerates in six dimensional ranges, within the frames of 1-25 micron or higher. The time consumption for one sample analysis is 10-15 seconds.     

Three phase model of the processive motor protein kinesin

Kinesin is a stepping motor that successively produces forward and backward 8-nm steps along microtubules. Under physiological conditions, the steps powering kinesin's motility are biased in one direction and drive various biological motile processes. So far, the physical mechanism underlying the unidirectional bias of the kinesin is not fully understood. Recently, Martin Bier have provided a stepper model [Martin Bier, 2003, Processive motor protein as an overdamped Brownian stepper, Phys. Rev. Lett. 91, 148104], in which the stepping cycle of kinesin includes two distinguished phases: (i) a power stroke phase and (ii) a ratcheted diffusion phase which is characterized as a "random diffusional search". At saturating ATP level, this model can fit the experimental results accurately. In this paper, we'll provide a modified Brownian stepper model, in which the dependence of ATP concentration is considered. In our model, the stepping cycle of kinesin is distinguished into three phases: an ATP-binding phase, a power stroke phase and a ratcheted diffusion phase. This modified model can reconstruct most of the experimental results accurately.     

Inorganic radicals of relevance to biological systems

There is little doubt that the most important inorganic radicals involved in biological systems are those which are intermediates in the oxygen-water redox cycle, i.e. OH., O_2, and HO.2. Aspects of the structure and reactivities of these radicals are considered, together with methods of detection. In particular, the use of e.s.r. spectroscopy is outlined, including rapid-freeze and spin-trapping techniques. Attention is called to comparisons and contrasts between these radicals and corresponding sulphur-centered radicals, although these are not strictly "inorganic". The oxygen-centred radicals are usually generated in vivo by redox reactions, but they are also of importance in radiolytic processes because they are formed from water. Other radicals formed in this way whose structures and reactivities are considered include solvated electrons and hydrogen atoms.     

A "lookup table" schema for synthetic biological patterning

A schema is proposed by which the three-dimensional structure and temporal development of a biological organism might be encoded and implemented via a genetic "lookup table". In the schema, diffusive morphogen gradients and/or the global concentration of a quickly diffusing signal index sets of kinase genes having promoters with logarithmically diminished affinity for the signal. Specificity of indexing is enhanced via concomitant expression of phosphatases undoing phosphorylation by "neighboring" kinases of greater affinity. Combinations of thus-selected kinases in turn jointly activate, via multiple phosphorylation, a particular enzyme from a virtual, multi-dimensional array thereof, at locations and times specified within the "lookup table". In principle, such a scheme could be employed to specify arbitrary gross anatomy, surface pigmentation, and/or developmental sequencing, extending the burgeoning toolset of the nascent field of synthetic morphology. A model of two-dimensional surface coloration using this scheme is specified, and LabVIEW software for its exploration is described and made available.     

Estimating developmental states of tumors and normal tissues using a linear time-ordered model

Background  

Tumor cells are considered to have an aberrant cell state, and some evidence indicates different development states appearing in the tumorigenesis. Embryonic development and stem cell differentiation are ordered processes in which the sequence of events over time is highly conserved. The "cancer attractor" concept integrates normal developmental processes and tumorigenesis into a high-dimensional "cell state space", and provides a reasonable explanation of the relationship between these two biological processes from theoretical viewpoint. However, it is hard to describe such relationship by using existed experimental data; moreover, the measurement of different development states is also difficult.     

Allee effects in stochastic populations

The Allee effect, or inverse density dependence at low population sizes, could seriously impact preservation and management of biological populations. The mounting evidence for widespread Allee effects has lately inspired theoretical studies of how Allee effects alter population dynamics. However, the recent mathematical models of Allee effects have been missing another important force prevalent at low population sizes: stochasticity. In this paper, the combination of Allee effects and stochasticity is studied using diffusion processes, a type of general stochastic population model that accommodates both demographic and environmental stochastic fluctuations. Including an Allee effect in a conventional deterministic population model typically produces an unstable equilibrium at a low population size, a critical population level below which extinction is certain. In a stochastic version of such a model, the probability of reaching a lower size a before reaching an upper size b , when considered as a function of initial population size, has an inflection point at the underlying deterministic unstable equilibrium. The inflection point represents a threshold in the probabilistic prospects for the population and is independent of the type of stochastic fluctuations in the model. In particular, models containing demographic noise alone (absent Allee effects) do not display this threshold behavior, even though demographic noise is considered an "extinction vortex". The results in this paper provide a new understanding of the interplay of stochastic and deterministic forces in ecological populations.     

What is the subject of science "bioinformatics"?

The paper is concerned with some problems of terminology, in particular the term "bioinformatics". In the last few years, the term "bioinformatics" has been intensively used among molecular biologists to indicate a subject that is only a constituent of genomics and is considered to involve a computer-assisted analysis of all data on nucleotide sequences of DNA. However, a wide circle of scientists, including biologists, physicists, mathematicians, and specialists in the field of cybernetics, informatics, and other disciplines have accepted and accept, as a rule, the "bioinformatics" as a synonym of science cybernetics and as a successor of this science. In this case, the subject of science "bioinformatics" should embrace not only genomics but practically all sections of the biological science. It should involve a study of information processes (storage, transfer, and processing of information, etc.) participating in the regulation and control at all levels of living systems, from macromolecules to the brain of higher animals and human.     

The treatment of pulp and paper mill effluent: a review

The manufacture of paper generates significant quantities of wastewater; as high as 60 m3/tonne of paper produced. The raw wastewaters from paper and board mills can be potentially very polluting. Indeed, a recent survey within the UK industry has found that their chemical oxygen demands can be as high as 11000 mg/l. This paper reviews the processes involved in paper making and examines the effects which they could have on the environment. It also evaluates the treatment processes which are used to minimise these effects. In line with the majority of UK practice, it focuses mainly on aerobic biological treatment and, in particular, on the activated sludge process. This means that there is an in-depth discussion about the problems associated with filamentous bacteria and sludge "bulking". The paper also discusses the way in which anaerobic digestion can be applied to the treatment of liquid wastes from the manufacture of paper.     

On the processivity of DNA replication

In this paper we describe the nature and importance of processive enzymatic reactions in biological processes. A model is set up to describe the processive synthetic process in DNA replication, and experiments are presented to define and test the model, using the components of the T4 phage-coded five-protein (in vitro) DNA replication system of Alberts. Nossal and coworkers. These experiments are performed either with a homogeneous oligo dT-poly dA primer-template system, or with a natural primer-template system using phage M13 DNA. The results are used to define some molecular aspects of the microscopic "processivity cycle".     

Cell behaviour as a dynamic attractor in the intracellular signalling system

We present a model of the cell signalling network based on the generic properties of interactions between protein kinases (PKs) and protein phosphatases (PPs) inside cells. The model is designed to examine the global properties and intrinsic dynamics of the phosphorylation system. A genetic algorithm (GA) is used to evolve populations of "cells". The GA selects cells and ranks them based on an analysis of the dynamics of the proteins within the networks from a series of different random starting conditions. The fittest cells are taken to be those which can generate a variety of different "behaviours" from a series of different initial conditions. During the GA, intracellular protein interactions evolve via mutation and an analogue of domain shuffling between protein types that is thought to occur during biological evolution. The dynamics of the simulated networks are presented and we discuss the hypothesis that changes in the behaviour of a cell may be interpretable as a switch between attractor basins in the intracellular signalling network.     

Saccharomyces cerevisiae as a model organism: a comparative study

Background

Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking.

Methodology/Principal Findings

In this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes.

Conclusions/Significance

The method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.     

The three-state model for the elementary process of energy conversion in muscle.

A three-state model for the elementary process of energy conversion in striated muscle is analysed; in two of the three states, the crossbridge is attached to an actin site, while the third is a detached state. This model accounts for the mechanical properties of steady shortening and lengthening processes as well as those of isometric and isotonic transient processes in a quantitative way. Moreover, qualitative agreement is obtained for the total energy liberation from muscle. Biochemical properties are also computed for transient processes. Comparisions are made with other models with "three states".     

Dances with data

Conclusion: Medical decisions concerning the end of life are a difficult matter and they evoke much emotional response. What is needed, however, is an open debate in order to improve the moral quality of decision making, not "dances with data". The central question in this debate should be, as Callahan aptly notes, whether medicine should involve itself only in that kind of "suffering which is brought on by illness and dying as biological phenomena" (emphasis added) or whether it should concern itself with the wellbeing of the patient. Apart from the fundamental question as to what types of suffering are to be considered as, at least in part biological phenomena, in The Netherlands most doctors, ourselves included, think the medical profession should do the latter.     

Modularity: a new perspective in biology

Several decades of research in biochemistry and molecular biology have been devoted for studies on isolated enzymes and proteins. Recent high throughput technologies in genomics and proteomics have resulted in avalanche of information about several genes, proteins and enzymes in variety of living systems. Though these efforts have greatly contributed to the detailed understanding of a large number of individual genes and proteins, this explosion of information has simultaneously brought out the limitations of reductionism in understanding complex biological processes. The genes or gene products do not function in isolation in vivo. A delicate and dynamic molecular architecture is required for precision of the chemical reactions associated with "life". In future, a paradigm shift is, therefore, envisaged, in biology leading to exploration of molecular organizations in physical and genomic context, a subtle transition from conventional molecular biology to modular biology. A module can be defined as an organization of macromolecules performing a synchronous function in a given metabolic pathway. In modular biology, the biological processes of interest are explored as complex systems of functionally interacting macromolecules. The present article describes the perceptions of the concept of modularity, in terms of associations among genes and proteins, presenting a link between reductionist approach and system biology.