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arXiv2009

Generalized Voronoi Tessellation as a Model of Two-dimensional Cell Tissue Dynamics

Voronoi tessellations have been used to model the geometric arrangement of cells in morphogenetic or cancerous tissues, however so far only with flat hypersurfaces as cell-cell contact borders. In order to reproduce the experimentally observed piecewise spherical boundary shapes, we develop a consistent theoretical framework of multiplicatively weighted distance functions, defining generalized finite Voronoi neighborhoods around cell bodies of varying radius, which serve as heterogeneous generators of the resulting model tissue. The interactions between cells are represented by adhesive and repelling force densities on the cell contact borders. In addition, protrusive locomotion forces are implemented along the cell boundaries at the tissue margin, and stochastic perturbations allow for non-deterministic motility effects. Simulations of the emerging system of stochastic differential equations for position and velocity of cell centers show the feasibility of this Voronoi method generating realistic cell shapes. In the limiting case of a single cell pair in brief contact, the dynamical nonlinear Ornstein-Uhlenbeck process is analytically investigated. In general, topologically distinct tissue conformations are observed, exhibiting stability on different time scales, and tissue coherence is quantified by suitable characteristics. Finally, an argument is derived pointing to a tradeoff in natural tissues between cell size heterogeneity and the extension of cellular lamellae.

physics.bio-ph↗

arXiv2009

Tracking tumor evolution via the prostate marker PSA: An individual post-operative study

The progress of the prostate-specific antigen after radical prostatectomy is observed for a patient in order to extract information on the growth mode of the tumor cells. An initial fast-growth mode goes over to a slower power-law regime within two years of surgery. We argue that such studies may help determine the appropriate time window for subsequent therapies in order to increase the life expectancy of the patient.

q-bio.QM↗

arXiv2011

Aging as a consequence of misrepair -- a novel theory of aging

It is now increasingly realized that the underlying mechanism which governs aging (ageing) is a complex interplay of genetic regulation and damage-accumulation. "Aging as a result of accumulation of 'faults' on cellular and molecular levels", has been proposed in the damage (fault)-accumulation theory. However, this theory fails to explain some aging phenotypes such as fibrosis and premature aging, since terms such as 'damage' and 'fault' are not specified. Therefore we introduce some crucial modifications of this theory and arrive at a novel theory: aging of the body is the result of accumulation of Misrepair of tissue. It emphasizes: a) it is Misrepair, not the original damage, that accumulates and leads to aging; and b) aging can occur at different levels, however aging of the body takes place necessarily on the tissue level, but not requiring the aging of cells/molecules. The Misrepair-accumulation theory introduced in the present paper unifies the understanding of the roles of environmental damage, repair, gene regulation, and multicellular structure in the aging process. This theory gives explanations for the aging phenotypes, premature aging, the difference of longevity in different species, and it is consistent with the physical view on complex systems.

q-bio.TO↗

arXiv2009

Global Asymptotic Stability and Hopf Bifurcation for a Blood Cell Production Model

We analyze the asymptotic stability of a nonlinear system of two differential equations with delay describing the dynamics of blood cell production. This process takes place in the bone marrow where stem cells differentiate throughout divisions in blood cells. Taking into account an explicit role of the total population of hematopoietic stem cells on the introduction of cells in cycle, we are lead to study a characteristic equation with delay-dependent coefficients. We determine a necessary and sufficient condition for the global stability of the first steady state of our model, which describes the population's dying out, and we obtain the existence of a Hopf bifurcation for the only nontrivial positive steady state, leading to the existence of periodic solutions. These latter are related to dynamical diseases affecting blood cells known for their cyclic nature.

math.AP↗

arXiv2009

On Pattern and Evolution

A model of pattern formation in living systems is presented. The pattern is achieved by the sequential interaction of two signaling pathways. The coupling of the pattern to the (thick) epithelial sheet changes is given, when the Gauss curvature'K'enters. The model suggests a novel point-like placement for organs such as eyes, antennae, limbs, and wings. In the case of plant patterns, 'leaf' outgrowths from a stem are predicted to be under the control of a yet to be discovered "master regulatiory gene", analogous to the animal case, when various outgrowths from the animal body are generally accompanied by activation of the 'distal-less' (Dll) gene.

q-bio.TO↗

arXiv2009

Similar in vivo killing efficacy of polyoma virus-specific CD8 T cells during acute and chronic phases of the infection

Viral infections can be broadly divided into infections that are cleared from the host (acute) and those that persist (chronic). Why some viruses establish chronic infections while other do not is poorly understood. One possibility is that the host's immune response is impaired during chronic infections and is unable to clear the virus from the host. In this report we use a recently proposed framework to estimate the per capita killing efficacy of CD8$^+$ T cells, specific for the MT389 epitope of polyoma virus (PyV), which establishes a chronic infection in mice. Surprisingly, the estimated per cell killing efficacy of MT389-specific effector CD8$^+$ T cells during the acute phase of the infection was very similar to the previously estimated efficacy of effector CD8$^+$ T cells specific to lymphocytic choriomeningitis virus (LCMV-Armstrong), which is cleared from the host. We also find that during the chronic phase of the infection the killing efficacy of PyV-specific CD8$^+$ T cells was only half of that of cells in the acute phase. This decrease in the killing efficacy is again surprisingly similar to the change in the killing efficacy of LCMV-specific CD8$^+$ T cells from the peak of the response to the memory phase. Interestingly, we also find that PyV-specific CD8$^+$ T cells in the chronic phase of the infection require lower doses of antigen to kill a target cell. In summary, we find little support for the hypothesis that persistence of infections is caused by inability of the host to mount an efficient immune response, and that even in the presence of an efficient CD8$^+$ T cell response, some viruses can still establish a persistent infection.

q-bio.PE↗

arXiv2009

Isoprenaline increases Excursive Restitution Slope in the Conscious Rabbit with Ischaemic Heart Failure

Background: An increased QT/RR slope is hypothesized to be predictive of sudden cardiac death after myocardial infarction. Previous studies have shown that beta-adrenergic stimulation increases QT/RR slope, but the effects of beta-adrenergic stimulation on QT/RR slope in heart failure are unknown. Methods: New Zealand White rabbits underwent coronary ligation (n=15) or sham surgery (n=11), and implantation of a pediatric pacemaker lead in the right ventricle for chronic ECG recording. Eight weeks after surgery, unsedated rabbits were given intravenous administrations of 0.25 to 2.0 ml of 1 micromol/l isoprenaline, while peak QRS to QRS (RR) and Q to T peak (QT) intervals were measured. Results: Ligated rabbits (n=6) had lower LVEF than sham rabbits (n=7, p<.0001), but similar baseline RR (269 +/- 15 vs 292 +/- 23 ms, p=.07), QT (104 +/- 17 vs 91 +/- 9 ms, p=.1) and minimum RR (204 +/- 11 vs 208 +/- 6 ms, p=.4) intervals induced by isoprenaline (0.79 +/- 0.18 vs 0.73 +/- 0.14 ml, p=.6). Hysteresis in QT vs TQ interval plots displayed biphasic restitution and regions of negative slope. The slope of the positive slope region was >1 in ligated rabbits (1.27 +/- 0.66) and <1 in sham rabbits (0.35 +/- 0.14, p=.004). Absolute value of the negative slope was greater in ligated rabbits (-0.81 +/- 0.52 vs -0.35 +/- 0.14, p=.04). Conclusion: Ischaemic heart failure produces steeper restitution slopes during beta-adrenergically induced QT/TQ hysteresis. This could underlie the propensity of failing hearts to arrhythmias.

q-bio.TO↗

arXiv2009

Phyllotaxis, a model

A model of the regular arrangement of leaves on a plant stem (phyllotactic patterns) is proposed, based on a new plant pattern algorithm. Tripartite patterning is proposed to occur by the interaction of two signaling pathways. Each pathway produces stimulated extracellular emission of like ligand upon activation of its respective receptor, as well as inhibiting such emission from the other pathway. Patterns arise spontaneously from zero density of activated receptor. All known phyllotactic patterns are reproduced, Fibonacci, distichous, decussate, and whorls, as well as the rare monostichy, with only one leaf directly above the previous.

q-bio.TO↗

arXiv2009

Spectral region optimization for Raman-based optical diagnosis of inflammatory lesions

FT-Raman Spectroscopy was applied to identify biochemical alterations existing between inflammatory fibrous hyperplasia (IFH) and normal tissues of buccal mucosa. One important implication of this study is related to the cancer lesion border. In fact, the cancerous normal border line is characterized by the presence of inflammation and its correct discrimination would increase the accuracy in delimiting the lesion frontier. Seventy spectra of IFH from 14 patients were compared to 30 spectra of normal tissue from 6 patients. The statistical analysis was performed with Principal Components Analysis and Soft Independent Modeling Class Analogy methodologies. After studying several spectral ranges it was concluded that the best discrimination capability (sensibility of 95% and specificity of 100%) was found using the 530 to 580 cm$^{-1}$ wavenumbers. The bands in this region are related to vibrational modes of Collagen aminoacids Cistine, Cysteine, and Proline and their relevant contribution to the classification probably relies on the extracellular matrix degeneration process occurring in the inflammatory tissues.

q-bio.TO↗

arXiv2009

Distribution Principle of Bone Tissue

Using the analytic and experimental techniques we present an exploratory study of the mass distribution features of the high coincidence of centre of mass of heterogeneous bone tissue in vivo and its centroid of geometry position. A geometric concept of the average distribution radius of bone issue is proposed and functional relation of this geometric distribution feature between the partition density and its relative tissue average distribution radius is observed. Based upon the mass distribution feature, our results suggest a relative distance assessment index between the center of mass of cortical bone and the bone center of mass and establish a bone strength equation. Analysing the data of human foot in vivo, we notice that the mass and geometric distribution laws have expanded the connotation of Wolff's law, which implies a leap towards the quantitative description of bone strength. We finally conclude that this will not only make a positive contribution to help assess osteoporosis, but will also provide guidance to exercise prescription to the osteoporosis patients.

physics.bio-ph↗

arXiv2009

Generalized calculus in radiobiology: Physical implications

Non-extensive statistical physics has allowed to generalize mathematical functions such as exponential and logarithms. The same framework is used to generalize sum and product so that the operations allow a more fluid way to work with mathematical expressions emerging from non-additive formulation of statistical physics. In this work we employ the generalization of the exponential, logarithm and product to obtain a formula for the survival fraction corresponding to the application of several radiation doses on a living tissue. Also we provide experimental recommendations to determine the universal characteristics of living tissues in interaction with radiation. These results have a potential application in radiobiology and radiation oncology.

physics.bio-ph↗

arXiv2010

Asymptotics of conduction velocity restitution in models of electrical excitation in the heart

We extend a non-Tikhonov asymptotic embedding, proposed earlier, for calculation of conduction velocity restitution curves in ionic models of cardiac excitability. Conduction velocity restitution is the simplest nontrivial spatially extended problem in excitable media, and in the case of cardiac tissue it is an important tool for prediction of cardiac arrhythmias and fibrillation. An idealized conduction velocity restitution curve requires solving a nonlinear eigenvalue problem with periodic boundary conditions, which in the cardiac case is very stiff and calls for the use of asymptotic methods. We compare asymptotics of restitution curves in four examples, two generic excitable media models, and two ionic cardiac models. The generic models include the classical FitzHugh-Nagumo model and its variation by Barkley. They are treated with standard singular perturbation techniques. The ionic models include a simplified "caricature" of the Noble (1962) model and the Beeler and Reuter (1977) model, which lead to non-Tikhonov problems where known asymptotic results do not apply. The Caricature Noble model is considered with particular care to demonstrate the well-posedness of the corresponding boundary-value problem. The developed method for calculation of conduction velocity restitution is then applied to the Beeler-Reuter model. We discuss new mathematical features appearing in cardiac ionic models and possible applications of the developed method.

q-bio.TO↗

arXiv2009

A Simpler Explanation to BAK1 Gene Variation in Aortic and Blood Tissues

The explanation is that in aortic tissue (both diseased and nondiseased) a BAK1 pseudogene is expressed; while in the matching blood samples the actual BAK1 gene is expressed. This explanation was reached after we realized that BAK1 has two edited copies in human genome. These copies are probably BAK1 pseudogenes. One copy belongs to chromosome 11 (NG_005599.3) and the other to chromosome 20 (NC_000850.5). The first copy has frameshifts which means that probably it does not express any functional protein; by other hand, the chromosome 20 copy has no frameshifts and what is more important contains all the reported polymorphisms.

q-bio.GN↗

arXiv2009

New Universal Theory of Injury Prediction and Prevention

The prediction and prevention of traumatic brain injury, spinal injury and general musculo-skeletal injury is a very important aspect of preventive medical science. Recently, in a series of papers, I have proposed a new coupled loading-rate hypothesis as a unique cause of all above injuries. This new hypothesis states that the main cause of all mechanical injuries is a Euclidean Jolt, which is an impulsive loading that strikes any part of the human body (head, spine or any bone/joint) - in several coupled degrees-of-freedom simultaneously. It never goes in a single direction only. Also, it is never a static force. It is always an impulsive translational and/or rotational force, coupled to some human mass eccentricity. Keywords: traumatic brain injury, spinal injury, musculo-skeletal injury, coupled loading-rate hypothesis, Euclidean jolt

q-bio.TO↗

arXiv2009

Supramolecular Stacking of Doxorubicin on Carbon Nanotubes for in vivo Cancer Therapy

Many therapeutic advantages such as prolonged circulation in the blood, increased tumor drug uptake, enhanced therapeutic efficacy, and markedly reduced toxic side effects are provided by a carbon nanotube based chemotherapeutic formulation. In this system, doxorubicin (DOX) is loaded onto the sidewalls of functionalized single-walled carbon nanotubes by supramolecular pi-pi stacking.

cond-mat.mtrl-sci↗

arXiv2009

Pixel multiplexing for high-speed multi-resolution fluorescence imaging

We introduce a imaging modality that works by transiently masking image-subregions during a single exposure of a CCD frame. By offsetting subregion exposure time, temporal information is embedded within each stored frame, allowing simultaneous acquisition of a full high spatial resolution image and a high-speed image sequence without increasing bandwidth. The technique is demonstrated by imaging calcium transients in heart cells at 250 Hz with a 10 Hz megapixel camera.

q-bio.QM↗

arXiv2009

Living Tissue Self-Regulation as a Self-Organization Phenomenon

Self-regulation of living tissue as an example of self-organization phenomena in hierarchical systems of biological, ecological, and social nature is under consideration. The characteristic feature of these systems is the absence of any governing center and, thereby, their self-regulation is based on a cooperative interaction of all the elements. The work develops a mathematical theory of a vascular network response to local effects on scales of individual units of peripheral circulation.

physics.med-ph↗

arXiv2009

Variant assumptions made in deriving equilibrium solutions to Little et al (PLoS Comput Biol 2009 5(10) e1000539)

The paper of Little et al. (PloS Comput Biol 2009 5(10) e1000539) outlined a system of reaction-diffusion equations that were used to describe induction of atherosclerotic disease. These were solved by considering an equilibrium solution and small perturbations around this equilibrium. Here we consider slight variant sets of assumptions that could be used to derive equilibrium solutions. In general they do not imply any change in the numerical results relating to monocyte chemo-attractant protein-1 (MCP-1) presented in that paper.

q-bio.TO↗