A Geometro-mechanical model for pulsatile morphogenesis

A model is proposed which imitates the morphogenesis of several species of the lower invertebrate animals, the hydroid polyps and permits the derivation of the geometry (surface curvature) of each developmental stage from that of the preceding stage. The model is based upon two experimentally verified assumptions. First, neighbouring cells are assumed to compress each other laterally in a regular and species-specific pulsatile manner. It is this pressure, and/or an active cell reaction to it, which changes the curvature of a cell layer. Secondly, cell layers are assumed to have quasi-elastic properties tending to smooth out their curvature. With our model, the different pulsatile patterns of cell-cell pressure are reproduced and the elasticity parameters are modulated. As a result, within a large zone of parameter values (a so-called "morphogenetic zone", MZ) realistic shapes of the rudiments are reproduced. The main principles of the model can also be used for interpreting the morphogenesis of other groups of animals. A suggested model emphasizes the self-organizing properties of a "stressed geometry" of embryonic rudiments.     

A turbulence model for pulsatile arterial flows

Difficulties in predicting the behavior of some high Reynolds number flows in the circulatory system stem in part from the severe requirements placed on the turbulence model chosen to close the time-averaged equations of fluid motion. In particular, the successful turbulence model is required to (a) correctly capture the "nonequilibrium" effects wrought by the interactions of the organized mean-flow unsteadiness with the random turbulence, (b) correctly reproduce the effects of the laminar-turbulent transitional behavior that occurs at various phases of the cardiac cycle, and (c) yield good predictions of the near-wall flow behavior in conditions where the universal logarithmic law of the wall is known to be not valid. These requirements are not immediately met by standard models of turbulence that have been developed largely with reference to data from steady, fully turbulent flows in approximate local equilibrium. The purpose of this paper is to report on the development of a turbulence model suited for use in arterial flows. The model is of the two-equation eddy-viscosity variety with dependent variables that are zero-valued at a solid wall and vary linearly with distance from it. The effects of transition are introduced by coupling this model to the local value of the intermittency and obtaining the latter from the solution of a modeled transport equation. Comparisons with measurements obtained in oscillatory transitional flows in circular tubes show that the model produces substantial improvements over existing closures. Further pulsatile-flow predictions, driven by a mean-flow wave form obtained in a diseased human carotid artery, indicate that the intermittency-modified model yields much reduced levels of wall shear stress compared to the original, unmodified model. This result, which is attributed to the rapid growth in the thickness of the viscous sublayer arising from the severe acceleration of systole, argues in favor of the use of the model for the prediction of arterial flows.     

Molecular basis for constructing artificial immunogens

The molecular and cellular mechanisms of the effect of synthetic polyions on immunogenesis are discussed in the paper. The data on the basic properties of polyion immune stimulants and on the mechanisms of cellular reactions to these stimulants were used for constructing artificial antigen-polyion complexes having enhanced immunogenic properties. The vaccinating properties of a number of macromolecular complexes conjugated to bacterial and viral antigens are analyzed.     

The synthesis of artificial genome as the basis of synthetic biology

Recent achievements in the whole-genome sequencing especially viral and bacterial ones together with the development of methods of bioinformatics and molecular biology, have created preconditions for transition from synthesis of genes to assembly of the whole genomes based on chemically synthesized blocks, oligonucleotides. The creation of artificial genomes and artificial cells will undoubtedly render huge influence on a deepening of knowledge on mechanisms of functioning of living systems at a cellular level, on a way of origin and evolution of life, and also on biotechnology of the future, and will generate preconditions for the further development of synthetic biology and nanobiotechnology.     

Structural basis for the autoinhibition of talin in regulating integrin activation

Activation of heterodimeric (alpha/beta) integrin transmembrane receptors by the 270 kDa cytoskeletal protein talin is essential for many important cell adhesive and physiological responses. A key step in this process involves interaction of phosphotyrosine-binding (PTB) domain in the N-terminal head of talin (talin-H) with integrin beta membrane-proximal cytoplasmic tails (beta-MP-CTs). Compared to talin-H, intact talin exhibits low potency in inducing integrin activation. Using NMR spectroscopy, we show that the large C-terminal rod domain of talin (talin-R) interacts with talin-H and allosterically restrains talin in a closed conformation. We further demonstrate that talin-R specifically masks a region in talin-PTB where integrin beta-MP-CT binds and competes with it for binding to talin-PTB. The inhibitory interaction is disrupted by a constitutively activating mutation (M319A) or by phosphatidylinositol 4,5-bisphosphate, a known talin activator. These data define a distinct autoinhibition mechanism for talin and suggest how it controls integrin activation and cell adhesion.     

Plant cell suspension cultures as model systems for investigating growth regulating compounds

Several plant growth regulators were investigated for their activity in cell suspension cultures of Glycine max, Gossypium hirsutum and Zea mays. The effect on the growth of the cell cultures was traced by means of cell counting and determining packed cell volume and turbidity of the suspensions. The growth retardant 5-(4-chlorophenyl)-3,4,5,9,10-pentaaza-tetracyclo-5,4,10^2,6 ,0^8,11-dodeca-3,9-diene (NDA) and, to a slightly lesser extent, ancymidol proved to be the compounds with the greatest inhibitory action on cell division growth of all three cell cultures. In the case of cotton this effect was accompanied by increased synthesis and secretion of cell-wall material. Staining methods showed that, especially in the case of NDA, a high percentage of cells could be considered as viable, and showed thus that NDA inhibits the cell division process while the cells remain metabolically active. The effects of 1,1-Dimethyl-piperidiniumchloride (DPC), a genuine growth retardant of cell propagation, and, with less efficiency, N-trimethyl-(-chloroethyl)-ammoniumchloride (CCC) in cotton, the triazole LAB 117 682 in soybean and maize, and, to a lesser extent, (2-isopropyl-5-methyl-4-trimethyl-ammoniumchloride)-phenyl-l-piperidiniumcarboxylate (AM0-1618) in soybean can be regarded as species-specific. Otherwise, CCC and particularly daminozide exhibited no action at the concentrations used. A comparison of the data from hydroculture studies with soybean and maize seedlings showed considerable agreement with the effectiveness of the substances in the corresponding cell cultures. Thus, cell cultures can be used to identify and screen substances with growth-influencing activity, and may also offer new ways to elucidate the mode of action of plant growth regulators.     

A non-linear model for the synaptic basis of neuronal memory.

We propose a mathematical model for the synaptic basis of neuronal memory. The model incorporates non-linear effects in analogy with population growth problems of human beings, animals, biological species, crystal growth, etc., and provides a mechanism whereby the excitatory and inhibitory inputs produce alterations in a neurone which result in a long-lasting increase in transmitter release at a synapse.     

The cellular basis for enhanced volume-modulated cardiac output in fish hearts

During vertebrate evolution there has been a shift in the way in which the heart varies cardiac output (the product of heart rate and stroke volume). While mammals, birds, and amphibians increase cardiac output through large increases in heart rate and only modest increases (approximately 30%) in stroke volume, fish and some reptiles use modest increases in heart rate and very large increases in stroke volume (up to 300%). The cellular mechanisms underlying these fundamentally different approaches to cardiac output modulation are unknown. We hypothesized that the divergence between volume modulation and frequency modulation lies in the response of different vertebrate myocardium to stretch. We tested this by progressively stretching individual cardiac myocytes from the fish heart while measuring sarcomere length (SL), developed tension, and intracellular Ca2+ ([Ca2+]i) transients. We show that in fish cardiac myocytes, active tension increases at SLs greater than those previously demonstrated for intact mammalian myocytes, representing a twofold increase in the functional ascending limb of the length-tension relationship. The mechanism of action is a length-dependent increase in myofilament Ca2+ sensitivity, rather than changes in the [Ca2+]i transient or actin filament length in the fish cell. The capacity for greater sarcomere extension in fish myocardium may be linked to the low resting tension that is developed during stretch. These adaptations allow the fish heart to volume modulate and thus underpin the fundamental difference between the way fish and higher vertebrates vary cardiac output.     

A reduced-dimensional model for near-wall transport in cardiovascular flows

Near-wall mass transport plays an important role in many cardiovascular processes, including the initiation of atherosclerosis, endothelial cell vasoregulation, and thrombogenesis. These problems are characterized by large Péclet and Schmidt numbers as well as a wide range of spatial and temporal scales, all of which impose computational difficulties. In this work, we develop an analytical relationship between the flow field and near-wall mass transport for high-Schmidt-number flows. This allows for the development of a wall-shear-stress-driven transport equation that lies on a codimension-one vessel-wall surface, significantly reducing computational cost in solving the transport problem. Separate versions of this equation are developed for the reaction-rate-limited and transport-limited cases, and numerical results in an idealized abdominal aortic aneurysm are compared to those obtained by solving the full transport equations over the entire domain. The reaction-rate-limited model matches the expected results well. The transport-limited model is accurate in the developed flow regions, but overpredicts wall flux at entry regions and reattachment points in the flow.     

Analysis of the scientific-methodologic basis for vaccine standardization using cholerogen-toxoid as a model]

The author discusses methodical principles of the vaccine standardization on the basis of experience in the standardization of the cholerogen-toxoid, a principally new vaccine preparation for the immunoprophylaxis of cholera. The author substantiated the statement according to which the following should serve as the task of primary importance in the program of investigations: elaboration of a system laboratory-immunological methods for the measurement of properties and quality of preparation, and primarily of its efficacy, strictly adequate to the biological nature of the vaccine (correct), highly-reproducable and of a high informative value. Data are presented proving the fact that without solving the problem of standardization of the vaccine it is practically impossible to lay scientific foundation under the choice of the optimal vaccination doses, under the immunization scheme, and introduction into the association with other preparations etc. At the same time it is emphasized that the absence of the system of measurement of the properties responsible for the biological activity of the vaccine also excludes a possibility of successive improvement of the technology of its production.     

Environmental capacity of receiving water as basis for regulating intensity of milkfish (Chanos chanos Forsskal) culture

This paper presents the results of the assessment of the environmental condition of a receiving water and demonstrates how the environmental capacity of the system can be estimated based on effluent discharge from milkfish ponds and water criteria from scientific literature and other studies. An estuary (average volume, 295 333 m³; average depth, 1.9 m) in Punta Pulao, Dumangas, Iloilo, Philippines served as discharge and irrigation system for commercial milkfish ponds and experimental/verification ponds owned by the Southeast Asian Fisheries Development Center. Total ammonia nitrogen, nitrite, nitrate, phosphate, and chlorophyll a (chl a) were determined monthly (during spring tide) for 4 months. Samples were taken at low and high tides that coincided with the draining and flooding of ponds, respectively. Monthly concentrations of these water quality variables generally increased from the first to fourth month of sampling (April–July 2001) during low tide. Very slight increases were observed during high tide. The magnitude of changes in the diurnal patterns of phosphate, chl a, and dissolved oxygen appeared to be higher at spring tide than at neap tide. This indicates that the inflowing river at low tide (during spring tide) brought effluents containing high amounts of nutrients from ponds located upstream. The water, salt, dissolved inorganic nitrogen (DIN), and phosphate (DIP) budgets of the entire estuary were determined following the one‐box model by LOICZ‐IGBP (2000, LOICZ biochemical budgeting procedure: a tutorial pamphlet. L. T. David, M. L. San Diego‐McGlone, C. J. Crossland and S. V. Smith (Eds). Publ. for LOICZ International Project Office, the Netherlands, 29 pp.). The budgets indicate that the system is net heterotrophic and nitrogen (N) fixing during the dry months, but that there could be no environmental impact during the rainy months because of short water exchange time. Results further suggest that the system is a source of N and phosphorus (P) during the dry and rainy months; the condition is largely influenced by the high amount of nutrient inputs in to the river. Linear regression analysis was performed to determine relationship between nutrient concentrations in the system and total DIN or DIP input to the system at low tide. Environmental capacity in terms of the maximum amount of DIN or DIP input to the system was predicted using regression analysis and following set criteria for nutrients, i.e. nitrite, nitrate, and phosphate. At present, the estuarine water quality has already reached its environmental capacity during the dry months. About 945 ha of commercial milkfish ponds are operating upstream, mostly as extensive systems. If these ponds are converted to semi‐intensive or intensive systems, it is recommended that the pond area be reduced to 122 ha if the DIP criterion is to be followed so as not to exceed the environmental capacity. Exceeding this environmental capacity may affect production through reduction of fish growth, occurrence of diseases, and fish mortalities.     

Patterns in air pollution as model for the physical basis for olfactory navigation in pigeon homing

Spatial distribution and temporal variability of air pollution were used as a model to describe the stability and predictability of the distribution of airborne substances, postulated by some to be used by homing pigeons to navigate. If the man-made substances reflect the distributional characteristics of natural airborne substances, navigation based on airborne substances is unlikely to be possible.     

Microcontinuum model for pulsatile blood flow through a stenosed tube

The effects of polar nature of blood and pulsatility on flow through a stenosed tube have been analysed by assuming blood as a micropolar fluid. Linearized solutions of basic equations are obtained through consecutive applications of finite Hankel and Laplace transforms. The analytical expressions for axial and particle angular velocities, wall shear stress, resistance to flow and apparent viscosity have been obtained. The axial velocity profiles for Newtonian and micropolar fluids have been compared. The interesting observation of this analysis is velocity, in certain parts of cycle, for micropolar fluid is higher than Newtonain fluid. Variation of apparent viscosity eta a with tube radius shows both inverse Fahraeus-Lindqvist and Fahraeus-Lindqvist effects. Finally, the resistance to flow and wall shear stress for normal and diseased blood have been computed and compared.     

A model of pulsatile flow in a uniform deformable vessel.

Simulations of blood flow in natural and artificial conduits usually require large computers for numerical solution of the Navier-Stokes equations. Often, physical insight into the fluid dynamics is lost when the solution is purely numerical. An alternative to solving the most general form of the Navier-Stokes equations is described here, wherein a functional form of the solution is assumed in order to simplify the required computations. The assumed forms for the axial pressure gradient and velocity profile are chosen such that conservation of mass is satisfied for fully established pulsatile flow in a straight, deformable vessel. The resulting equations are cast in finite-difference form and solved explicitly. Results for the limiting cases of rigid wall and zero applied pressure are found to be in good agreement with analytical solutions. Comparison with the experimental results of Klanchar et al. [Circ. Res. 66, 1624-1635 (1990]) also shows good agreement. Application of the model to realistic physiological parameter values provides insight as to the influence of the pulsatile nature of the flow field on wall shear development in the presence of a moving wall boundary. Specifically, the model illustrates the dependence of flow rate and shear rate on the amplitude of the vessel wall motion and the phase difference between the applied pressure difference and the oscillations of the vessel radius. The present model can serve as a useful tool for experimentalists interested in quantifying the magnitude and character of velocity profiles and shearing forces in natural and artificial biologic conduits.     

Admixture as the basis for genetic mapping

Genetic mapping in natural populations is increasing rapidly in feasibility and accessibility. As with many areas in genetics, advances in molecular techniques and statistics are drastically altering how we can investigate inheritance in wild organisms. For ecology and evolution, this is particularly significant and promising, because many of the organisms of interest are not amenable to conventional genetic approaches. Admixture mapping falls within a family of statistical approaches that use natural recombination and linkage disequilibrium between genetic markers and phenotypes as the basis for mapping. Our aim in this review is to provide a snapshot of previous and ongoing research, existing methods and challenges, the nature of questions that can be investigated and prospects for the future of admixture mapping.