On Some Application of Non-Homogeneous Semi-Markov Processes

In this paper a non-homogeneous semi-Markov process is applied to a study of the behaviour of a cell after irradiation. The definition and main properties of the non-homogeneous semi-Markov process are reminded. Moreover one assumes that the cell may stay in one of four states namely, normal state, damaged state 1, damaged state 2, state of death, which are defined. Using the results of the theory of non-homogeneous semi-Markov processes and Markov renewal theory the characteristics of interest pertaining to the cell behaviour are studied.     

A two compartment model for cell survival after irradiation with ionizing radiation

A theory of cell survival after irradiation has been developed, considering the cell as composed of two compartments with different sensitivities and taking into account recovery phenomena. Expressions are obtained for the probabilities that the cell will be in a survival state or damaged state or will function with reduced efficiency.     

Alginate Hydrogels as Scaffolds and Delivery Systems to Repair the Damaged Spinal Cord

Alginate (ALG) is a lineal hydrophilic polysaccharide present in brown algae cell walls, which turns into a gel state when hydrated. Gelation readily produces a series of three dimensional (3D) architectures like fibers, capillaries, and microspheres, used as biosensors and bio‐actuators in a plethora of biomedical applications like drug delivery and wound healing. Hydrogels have made a great impact on regenerative medicine and tissue engineering because they are able to mimic the mechanical properties of natural tissues due to their high water content. Recent advances in neurosciences have led to promising strategies for repairing and/or regenerating the damaged nervous system. Spinal cord injury (SCI) is particularly challenging, owing to its devastating medical, human, and social consequences. Although effective therapies to repair the damaged spinal cord (SC) are still lacking, multiple pharmacological, genetic, and cell‐based therapies are currently under study. In this framework, ALG hydrogels constitute a source of potential tools for the development of implants capable of promoting axonal growth and/or delivering cells or drugs at specific damaged sites, which may result in therapeutic strategies for SCI. In this mini‐review, the current state of the art of ALG applications in neural tissues for repairing the damaged spinal cord is discussed.     

An active-medium model of organic substance transformation in soil and its dynamic properties

An analysis of the behaviour of the soil system considered as an active medium with distributed energy sources was undertaken. This approach enabled the authors to build a heuristic model of soil which accounts for processes of organic substance production, migration and utilisation. The soil body is presented as a spatially distributed trophic chain with non-linear interactions of adjacent links. The level of this non-linearity appears to be the key parameter determining the dynamic behaviour of the model system in one-, two- and three-dimensional cases. The conditions for the existence of pulse-generating and autowave modes in this system were determined by computer simulations. Of particular interest is the behaviour of damaged soil, especially its self-regeneration potential. Inoculation autowave was proven to restore the initial state of the soil if two adjacent or separated trophic links fall out. Possible ways of the further development of the proposed model are also discussed.     

Pathology of structured water and associated cations in cells (ther tissue damage syndrome) and its medical treatment

Modern experimental evidence indicates that the cell should be regarded as analogous to an ion exchanger resin granule with structured water in the interstices and with potassium and sodium ions associated with fixed negative charges on the protein matrix. In tissues damaged by disease or trauma, a similar set of changes in properties of cell cations and water is to be expected, for which a similar set of therapies is appropriate. Tissue damage causes a configurational change of the protein matrix from the normal to the damaged state. This leads to loss of association preference for potassium vs. sodium ions and to loss of water structuring, resulting in replacement of cell potassium by sodium and abnormal uptake of water by the cell. Appropriate therapies for reestablishment of the normal configurational state of the proteins of the cell are reestablishment of normal cell ATP production, for which prostaglandin PGBx is the rational approach, plus diets or drugs that decrease sodium and/or increase potassium concentrations in the body. Partial normalization of cell protein configuration by digitalis compounds may also be possible.     

Executing cell senescence

Senescence is a permanent form of cell cycle arrest that limits the proliferation of damaged cells and may contribute to tumor suppression and aging. We recently demonstrated that some senescent cell types undergo dramatic changes in chromatin organization that are dependent on the retinoblastoma protein and are associated with the stable repression of some E2F target genes. Here we show how these changes might contribute to the stability of the senescent state.     

Bacillus cereus cell and spore properties as influenced by the micro-structure of the medium

Aim:  To investigate the effect of different growth conditions on Bacillus cereus cell and spore properties.
Methods and Results:  Bacillus cereus was grown on agar plates with different surface water conditions (wet and dry) or viscosity. Cell populations displayed different types of behaviour, and heterogeneity was manifested in cell motility and dimension. Spore populations were heterogeneous regarding their properties, namely size and thermal resistance. The smallest spores were produced from flagellated cells, which also displayed jet-motility, growing on the wettest agar. Cytometric analysis also revealed within the smallest spores a sub-population labelled by propidium iodide (PI), indicating that spore populations were partly damaged. Nonmotile cells grown on diffusion-limiting media were elongated and produced the least thermal-resistant spores.
Conclusions:  The micro-structural properties of the media were found to influence cell and spore properties. Abundant surface water enabled flagellar motility and resulted in a heterogeneous cell and spore population, the latter including small and damaged spores. High viscosity gave rise to filamentous cells and more heat-sensitive spores.
Significance and Impact of the Study:  This study provides useful information on conditions resulting in heterogeneous populations of damaged and heat-sensitive spores.     

Probability of survival of a cell in a complex system when irradiated with ionizing radiations

Theoretical expressions for the probability of survival of an irradiated cell have been obtained in a simple form. An attempt has been made to calculate the probability that a cell will remain in normal condition or in damaged state at a given instant of time. The important assumption which makes this possible is that once the cell is repaired it will behave like a normal cell for further irradiation.     

Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres

When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression.     

Molecular mechanisms of cardiomyogenesis and the prospects for cardiomyocyte regeneration in cardiac failure

The review briefs the current state of research in molecular biological and cell aspects of cardiac development and the prospects of applying the corresponding results to treating heart failure by cardiomyocyte regeneration in damaged myocardium.     

Modelling of congenital nystagmus waveforms produced by saccadic system abnormalities

 Models of the mechanisms of normal eye movements are typically described in terms of the block diagrams which are used in control theory. An alternative approach to understanding the mechanisms of normal eye movements involves describing the eye movement behaviour in terms of smooth changes in state variables. The latter approach captures the burst cell firing against motor error (difference between target gaze angle and current gaze angle) phase plane behaviour which is found experimentally and facilitates the modelling of variations in burst cell behaviour. A novel explanation of several types of congenital nystagmus waveforms is given in terms of a saccadic termination abnormality. Received: 12 May 1999 / Accepted in revised form: 19 November 1999     

The decisive role of the Saccharomyces cerevisiae cell cycle behaviour for dynamic growth characterization.

The dynamic behaviour of the cell cycle and the physiology of Saccharomyces cerevisiae was monitored in transient experiments. Frequent flow cytometric analyses of the DNA (nuclear phase state) and the cell size enabled us to characterize the proliferation properties of yeast cells under well controlled and undisturbed cultivation conditions. Preliminarily, the correlation between flow cytometric light scattering measurements and the cell size was attested for yeasts. These flow cytometric results are compared with the physiological behaviour of the culture that was detected by high resolution on-line analyses and off-line measurements. The presented results focus on the importance of the yeast cell cycle behaviour for the dynamic growth characterization. Any kind of transients in yeast cultures induced partial synchronization. The characteristics and the time course of the yeast cell cycle were found to be strongly dependent on the physiological environment.     

Tales of biomaterials, molecules, and cells for repairing and treating brain dysfunction

Current therapies have limited or no capacity to restore lost function, slow ongoing neurodegeneration, or promote regeneration following damage to the brain. Biomaterials are playing an increasingly important role in the development of novel, potentially efficacious approaches to brain treatment and repair. Programmable biomaterials enable and augment the targeted delivery of drugs into the brain and allow cell/tissue transplants to be effectively delivered and integrate into the brain, to serve as delivery vehicles for therapeutic proteins, and rebuild damaged circuits. Similarly, biomaterials are being increasingly used to recapitulate specific aspects of brain niches to promote regeneration and/or repair damaged neuronal pathways with stem cell therapies. Many of these approaches are gaining momentum because nanotechnology allows greater control over material-cell interactions that induce specific developmental processes and cellular responses including differentiation, migration, and outgrowth. This review discusses the state of the art and new directions in the convergence of biomaterial science, drug delivery, and stem cell biology in the treatment of degenerative and malignant brain diseases.     

The role of growth factors in gastrointestinal cell proliferation.

The epithelial lining of the gastrointestinal (GI) tract is in a state of continuous cell renewal, and the proliferating and differentiating/differentiated cell populations are spatially clearly demarcated. Members of the epidermal growth factor (EGF) family of peptides, the trefoil peptides and enteroglucagon appear to be the most important enterotrophic molecules for both normal cell renewal and healing after cell damage. Transforming growth factor-a (TGF-a) appears to be the primary physiological ligand for the EGF receptor (EGFR), promoting normal cell renewal, and TGF-a/EGFR are part of an autocrine loop in many intestinal cancers. In response to damage, a differentiating cell lineage arises from adjacent epithelium secreting EGF, TGF-a and trefoil peptides; this may be viewed as part of a ‘repair kit’ in damaged endodermally-derived tissue.     

The role of volatiles from cruciferous plants and pre-flight experience in the foraging behaviour of the specialist parasitoid Cotesia plutellae

The braconid Cotesia plutellae is an important larval parasitoid of the diamondback moth (Plutella xylostella), a major pest of crucifers in the tropics and sub-tropics. The in-flight searching behaviour of C. plutellae was investigated in a wind tunnel and the close-range attack behaviour observed in cages. The relative importance of volatile stimuli emanating from the plant-host-complex, oilseed rape (Brassica napus) – P. xylostella, in the long-range attraction of C. plutellae was investigated. Plants that were mechanically damaged, or damaged by P. xylostella larvae, were attractive to the parasitoid. Host-damaged leaves remained attractive to the parasitoid after removal of the host larvae. These results indicate that C. plutellae predominantly uses plant derived stimuli in its in-flight searching behaviour. An oviposition experience or contact with a host-damaged leaf prior to the bioassay significantly increased the response to these volatile cues. The foraging behaviour of C. plutellae is compared with other braconid larval parasitoids attacking lepidopteran hosts on crucifers.     

Structural correlates of imbibitional injury in Typha pollen

The ultrastructure of Typha latifolia pollen was examined as a function of pollen moisture content and incubation temperature, in order to identify possible lesions induced by imbibitional chilling. A syndrome of structural traits was found which characterizes damaged grains. Compared to viable grains, the protoplast of damaged pollen has a higher proportion of its volume occupied by vesicles, and less volume occupied by cytoplasm. Damaged grains also tend to have dilated cisternae of endoplasmic reticulum, larger starch grains and lipid bodies, poorly preserved mitochondria and membranes, and, sometimes, numerous electron-dense globules associated with membranes. The percentage of grains exhibiting this damage syndrome correlates closely with the number of ungerminated grains in most samples, regardless of moisture content or incubation temperature. Injury due to rapid imbibition from the dry state or to imbibitional chilling appear to be similar structurally, regardless of whether the stresses are imposed singly or together. The injury is not confined to one cell component (e.g., mitochondria), but may involve a generalized disruption of membranes. These results suggest that similar stress responses are elicited by imbibition from the dry state and by imbibitional chilling.     

Mathematical modelling of immobilized living yeast cell reactor for sugar bioconversion to ethanol

In the present work, a mathematical model was developed regarding the immobilized living yeast cell reactor for sugar bioconversion to ethanol. The model, composed of a system of ordinary differential equations (ODEs) enables the computation of the paramters involved in the steady state reactor behaviour. Comparing the values computed through the integration of this mathematical model with the experimental data, it has been shown its capacity to describe sufficiently accurate the steady state behaviour of the continuous fixed film bioconversion reactor.     

Osmotic behaviour of Acholeplasma laidlawii B cells with membrane lipids in liquid-crystalline and gel state.

The osmotic behaviour of Acholeplasma laidlawii B cells was investigated with combined spectrophotometric and enzymatic measurements. The conclusion could be drawn that this osmotic behaviour depends largely on the physical state of the membrane lipids. When part of the membrane lipids is in the liquid-crystalline phase the cell is able to swell and behaves as a good osmometer. However, when the membrane lipid is in the gel phase, the cell is unable to swell and the change in absorbance of the cell suspension is then completely due to lysis.     

Ways to test stochastic dynamic programming models empirically

Stochastic dynamic programming (SDP) models are widely used to predict optimal behavioural and life history strategies. We discuss a diversity of ways to test SDP models empirically, taking as our main illustration a model of the daily singing routine of birds. One approach to verification is to quantify model parameters, but most SDP models are schematic. Because predictions are therefore qualitative, testing several predictions is desirable. How state determines behaviour (the policy) is a central prediction that should be examined directly if both state and behaviour are measurable. Complementary predictions concern how behaviour and state change through time, but information is discarded by considering behaviour rather than state, by looking only at average state rather than its distribution, and by not following individuals. We identify the various circumstances in which an individual's state/behaviour at one time is correlated with its state/behaviour at a later time. When there are several state variables the relationships between them may be informative. Often model parameters represent environmental conditions that can also be viewed as state variables. Experimental manipulation of the environment has several advantages as a test, but a problem is uncertainty over how much the organism's policy will adjust. As an example we allow birds to use different assumptions about how well past weather predicts future weather. We advocate mirroring planned empirical investigations on the computer to investigate which manipulations and predictions will best test a model. Copyright 2000 The Association for the Study of Animal Behaviour.