Modelling cellular senescence as a result of telomere state

Telomeres in mammalian cells end in large duplex T loops. These loops protect the single-strand overhangs from degradation and/or interactions with signalling proteins. This protection is sometimes referred to as capping. At each cell division, telomeres shorten and there is a general consensus that telomere shortening triggers cell cycle exit. However, the exact mechanism by which telomere shortening causes cell cycle arrest is not known. Mathematical models of telomere shortening have been developed to help us understand the processes involved. Until now most models have assumed that the trigger for cell cycle arrest is the first telomere or a group of telomeres reaching a critically short length. However, there is evidence that cells stop cycling over a wide range of telomere lengths. This suggests that telomere length per se may not in fact be the trigger for cellular senescence. In this paper we develop a model which examines the hypothesis that uncapping of a telomere is the main trigger. By letting the probability of uncapping depend upon telomere length, we show that the hypothesized model provides a good fit to experimental data.     

Occupational performance of a paced secondary task under conditions of sensory deprivation. I. Heart rate changes in train drivers as a result of monotony

Twelve experienced train drivers were asked to operate the train function safety circuit (SIFA)--a paced secondary motor task which is expected to guarantee the driver's fitness for service on engines of the German Federal Railway--under laboratory conditions of extreme monotony. In spite of massive decreases in vigilance as shown by theta-activity in the EEG, all subjects were able to operate the device without major errors. A prerequisite for adequate performance is an EEG-defined arousal reaction, which is synchronized with the SIFA cycles. For 7 subjects the time-related cross-correlation coefficients between SIFA operation, alpha-activity (indicative of alertness), theta-activity (indicative of reduced vigilance), and heart rate were calculated. The central-nervous arousal found in the EEG corresponded to distinct increases in heart rate. The moments of SIFA operation after phases of light sleep correlated significantly and positively with increases in heart rate. These increases constituted a physiological overcompensation as far as the physical readiness was concerned which reached its peak after the task had been performed satisfactorily, constituting additional and superfluous occupational stress. The results of this study indicate clearly that monotony stress is not a result of occupational monotony itself, but the result of the physiological effort which is required in order to regain a level of alterness which allows adequate performance under monotonous conditions.     

Relationship between pycnotic indec Qp as a result of oxygen supply and similar indices as a result of in vitro offer of cytochrome c and NADP in psychiatry.

The authors follow up on their previous studies of morphological changes in the properties of white blood cells represented by the oxygen pycnotic index Qp in patients with the schizophrenic syndrome. Several years of research made it obvious to them that this index remains generally unaffected by drugs administered during the treatment although the patient does show a pronounced clinical change. They decided to substitute the offer of oxygen by adding a supply of cytochrome c and NADP, i.e. by substances that give a boost to the oxidoreduction processes within the cell. They found the pycnotic quotient, based on cytochrome c, and - to an even greater degree - the NADP-based quotient to be more responsive to differences in the seriousness of the disease than the oxygen quotient.     

The general laws of formation of a condition monotony

In article results of research of spectral characteristics and a level of coherence basic rhythms EEG being under inspection of 19 with use are of resulted multifactorial dispersive analyses surveyed. On the basis of the received material an assumption comes out, that realization of base conditions of wakefulness is provided by own "built-in" regulating with mechanisms. Absence of such "built-in" mechanisms for a condition of monotonous causes "search" character of activity of regulating systems which results in the expressed periodicity in changes both a functional condition of a brain, and quality of activity carried out by the person.     

Parkinson's disease as a result of aging

It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field.     

The whole as a result of self-organization

On the basis of the experimental discovery of characteristic eigenfrequencies of the human body, the living organism is considered as a quantum system and a dissipative structure, the long-range coherence of which is provided by electromagnetic interaction.Among dissipative structures a special class is discerned for stable intact systems. Included along with living objects in this class are other fundamental structural material units with discrete characteristic frequencies of single-particle type (the nucleus, atom, molecule).     

Coexistence in the chemostat as a result of metabolic by-products

Classical chemostat models assume that competition is purely exploitative and mediated via a common, limiting and single resource. However, in laboratory experiments with pathogens related to the genetic disease Cystic Fibrosis, species specific properties of production, inhibition and consumption of a metabolic by-product, acetate, were found. These assumptions were implemented into a mathematical chemostat model which consists of four nonlinear ordinary differential equations describing two species competing for one limiting nutrient in an open system. We derive classical chemostat results and find that our basic model supports the competitive exclusion principle, the bistability of the system as well as stable coexistence. The analytical results are illustrated by numerical simulations performed with experimentally measured parameter values. As a variant of our basic model, mimicking testing of antibiotics for therapeutic treatments in mixed cultures instead of pure ones, we consider the introduction of a lethal inhibitor, which cannot be eliminated by one of the species and is selective for the stronger competitor. We discuss our theoretical results in relation to our experimental model system and find that simulations coincide with the qualitative behavior of the experimental result in the case where the metabolic by-product serves as a second carbon source for one of the species, but not the producer.     

Stabilization of energy charge, generation of oscillations and multiple steady states in energy metabolism as a result of purely stoichiometric regulation.

A simple kinetic model of cell energy metabolism with autocatalytic reaction sequences has beepn analysed. The model accounts for the fact that part of energy produced in the form of ATP, or any other equivalent form, is utilized in "sparking" reactions to activate initial substrates. Analysis of the model shows that energy metabolism, in the absen-e of all non-stoichiometric (i.e. isosteric, cooperative, and allosteric) regulations, is capable of (a) stabilizing, to a high degree of accuracy, the relative concentration of the "charged form" of the energy-transferring cofactor (ATP); (b) alternating between two stable stationary states by means of hysteretic transitions; (c) generating self-oscillations in energy production. It is proposed that energy metabolism can be a source of very slow, in particular circadian (of about a one-day period), oscillations which may serve as the basis for temporal organization of the cell.     

Plant teratologies as a result of phytoplasma infections

The direct correlation between teratological cases and phytoplasma infections was ascertained in spontaneous and cultivated plant species. Plants, belonging to 31 species and 12 families, showing symptoms of growth abnormalities were collected and analysed. Attempted detection of Rhodococcus fascians by isolation, PCR indexing and 16S rRNA sequencing from fasciated tissues allowed to exclude its presence. Nested PCR by universal primers and 16S rRNA sequence analyses indicated the presence of phytoplasmas, belonging to six groups, in the 44% of symptomatic samples. Among the infected species, Austrocylindropuntia exaltata, Opuntia subulata, Euphorbia characias, Euphorbia dendroides, Euphorbia linifolia, Euphorbia myrsinites, Rumex buchephalophorus, Linaria multicaulis and Fedia cornucopiae represent new phytoplasma hosts world-wide. Moreover this is the first report of phytoplasma belonging to subgroup 16SrRNA II-I in Italy. These findings together with the known erratic distribution in plant tissues of these phloem-restricted prokaryotes indicate a close correlation between fasciation and similar growth disorders and phytoplasma infections.     

Clonal exhaustion as a result of immune deviation

An overwhelming virus infection that spreads within a few days throughout the host can cause deletion of the specific cytotoxic T lymphocytes (CTL). This phenomenon is known as ‘clonal exhaustion’. Current explanations for this phenomenon are ‘clonal’, and consider either the terminal differentiation of the virus-specific CTL to an effector phenotype, or the lack of help and antigen presentation for a specific CTL clone. The virus remains controlled by some other form of immunity in the exhausted state. Candidates are innate immunity (especially NK cells andmacrophages) and a T helper type 2 based immune response. Surprisingly, the role of this other form of immunity in causing exhaustion has been ignored so far. Developing a mathematical model, we here investigate the possibility that this inter-clonal immunity is responsible for exhaustion by down regulating the CTL response. The model is based on previously published exhaustion data for Lymphocytic choriomeningitis virus as an in vivo model. We demonstrate that several complicated experiments on clonal exhaustion are consistentwith inter-clonal regulation. By interpreting the available data with a mathematical model, we compare this novel mechanism with the mechanisms suggested previously.     

Mortality of geese as a result of collision with the ground

Two incidents are reported in which groups of migrating wild geese were found dead in agricultural fields in southern Manitoba during spring. In each case, the birds died overnight and poisoning was suspected; however, the birds had lesions of severe traumatic injury. The first incident, in 1985, involved about 150 lesser snow geese (Anser caerulescens caerulescens); the second, in 2003, involved 62 Canada geese (Branta canadensis). Both incidents occurred on dark, moonless nights. One possible explanation is that the birds became disoriented in a manner analogous to spatial disorientation described in aircraft pilots and flew as a flock directly into the earth. In the first incident, geese might have been frightened by sonic booms from aircraft; in the second, there was a thunderstorm with strong gusty winds in the area.     

Changes in the blood-testis barrier as a result of streptococcal sensitization

Permeability of the histo-hematic barrier in the guinea pig and mouse testes immunized with streptococci has been studied radiometrically and luminescent microscopically with application of labelled bovine serum albumin, human gamma-globulin and blue dye preparations. The permeability of the hemato-testicular barrier increases on the 7th--30th day after immunization. Test-preparations penetrate from the vessels of the intercanalicular connective tissue layers through the membrane of the convoluted tubules. The testicular autoantigen is revealed in blood. The disturbance in permeability of the hemato-testicular barrier precedes or coincides in time with the developing destruction of the testicular spermatogenic elements.