http://www.tbiomed.com The latest research articles published by Theoretical Biology and Medical Modelling 2012-05-15T00:00:00Z Background: Consensus exists that several bariatric surgery procedures produce a rapid improvement of glucose homeostasis in obese diabetic patients, improvement apparently uncorrelated with the degree of eventual weight loss after surgery. Several hypotheses have been suggested to account for these results: among these, the anti-incretin, the ghrelin and the lower-intestinal dumping hypotheses have been discussed in the literature. Since no clear-cut experimental results are so far available to confirm or disprove any of these hypotheses, in the present work a mathematical model of the glucose-insulin-incretin system has been built, capable of expressing these three postulated mechanisms. The model has been populated with critically evaluated parameter values from the literature, and simulations under the three scenarios have been compared. Results: The modeling results seem to indicate that the suppression of ghrelin release is unlikely to determine major changes in short-term glucose control. The possible existence of an anti-incretin hormone would be supported if an experimental increase of GIP concentrations were evident post-surgery. Given that, on the contrary, collected evidence suggests that GIP concentrations decrease postsurgery, the lower-intestinal dumping hypothesis would seem to describe the mechanism most likely to produce the observed normalization of Type 2 Diabetes Mellitus (T2DM) after bariatric surgery. Conclusions: The proposed model can help discriminate among competing hypotheses in a context where definitive data are not available and mechanisms are still not clear. http://www.tbiomed.com/content/9/1/16 Puntip Toghaw Alice Matone Yongwimon Lenbury Andrea De Gaetano Theoretical Biology and Medical Modelling 2012, null:16 2012-05-15T00:00:00Z doi:10.1186/1742-4682-9-16 /content/figures/1742-4682-9-16-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 16 2012-05-15T00:00:00Z PDF Background: An allometric relationship between different electrocardiogram (ECG) parameters and infarcted ventricular mass was assessed in ten New Zealand rabbits. Methods: Animals underwent left anterior descending coronary artery ligation to provoke infarction (7-35% area). Myocardial infarction (MI) evolved and stabilized during a three month-period, after which, rabbits were sacrificed and the injured area was histologically confirmed. Right before sacrifice, ECGs were obtained to correlate several of its parameters to the infarcted mass. The latter was normalized after combining data from planimetry measurements and heart weight. The following ECG parameters were studied: RR (RR) and PR intervals (PR), P-wave duration (PD), QRS complex duration (QRSD) and amplitude (QRSA), Q-wave (QA), R-wave (RA) and S-wave (SA) amplitudes, T-wave peak amplitude (TA), the interval from the peak to the end of the T-wave (TPE), ST segment deviation (STA), QT interval (QT), corrected QT and JT (JT) intervals. Corrected QT was analyzed with different QT correction formulae (Bazett (QTB), Framingham (QTFRA), Fridericia (QTFRI), Hodge (QTHO) and Matsunaga (QTMA)) and compared thereafter. The former variables and infarcted ventricular mass were also fitted to the allometric equation. Results: Six variables (JT, QTB, QA, SA, TA and STA) presented statistical differences among leads. QA showed the best allometric fit (r=0.83), followed by the STA (r=0.73), SA (r=0.71) and TPE (r=0.68). Corrected QT's and the uncorrected counterpart performed alike (QT, QTFRA and QTFRI), scaling allometrically with similar goodness of fits. Conclusions: QA could possibly be used to assess infarction extent in an old MI event as a first approach. http://www.tbiomed.com/content/9/1/15 Maria Bonomini Maximo Valentinuzzi Pedro Arini Germán Gonzalez Bruno Buchholz Theoretical Biology and Medical Modelling 2012, null:15 2012-05-11T00:00:00Z doi:10.1186/1742-4682-9-15 /content/figures/1742-4682-9-15-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 15 2012-05-11T00:00:00Z PDF This article proposes a model of bone remodeling that encompasses mechanical and electrical stimuli. The remodeling formulation proposed by Weinans and collaborators was used as the basis of this research, with a literature review allowing a constitutive model evaluating the permittivity of bone tissue to be developed. This allowed the mass distribution that depends on mechanical and electrical stimuli to be obtained. The remaining constants were established through numerical experimentation. The results demonstrate that mass distribution is alteredunder electrical stimulation, generally resulting in a greater deposition of mass. In addition, the frequency of application of an electric field can affect the distribution of mass; at a lower frequency there is more mass in the domain. These numerical experiments open up discussion concerning the importance of the electric field in the remodeling process and propose the quantification of their effects. http://www.tbiomed.com/content/9/1/14 Diego Garzón Alvarado Angélica Ramírez-Martínez Carmen Cardozo de Martínez Theoretical Biology and Medical Modelling 2012, null:14 2012-05-11T00:00:00Z doi:10.1186/1742-4682-9-14 /content/figures/1742-4682-9-14-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 14 2012-05-11T00:00:00Z PDF Background: Lordosis is the bending of the lumbar spine that gives the vertebral column of humans its characteristic ventrally convex curvature. Infants develop lordosis around the time when they acquire bipedal locomotion. Even macaques develop a lordosis when they are trained to walk bipedally. The aim of this study was to investigate why humans and some animals develop a lumbar lordosis while learning to walk bipedally. Results: We developed a musculoskeletal model of the lumbar spine, that includes an asymmetric, dorsally shifted location of the spinal column in the body, realistic moment arms, and physiological cross-sectional areas (PCSA) of the muscles as well as realistic force-length and force-velocity relationships. The model was used to analyze the stability of an upright body posture. According to our results, lordosis reduces the local joint torques necessary for an equilibrium of the vertebral column during an erect posture. At the same time lordosis increases the demands on the global muscles to provide stability. Conclusions: We conclude that the development of a spinal lordosis is a compromise between the stability requirements of an erect posture and the necessity of torque equilibria at each spinal segment. http://www.tbiomed.com/content/9/1/13 Heiko Wagner Anne Liebetrau David Schinowski Thomas Wulf Marc de Lussanet Theoretical Biology and Medical Modelling 2012, null:13 2012-04-16T00:00:00Z doi:10.1186/1742-4682-9-13 /content/figures/1742-4682-9-13-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 13 2012-04-16T00:00:00Z XML The X-level Approach Reaction Noise Estimator (XARNES) method has been developed previously to study reaction noise in well mixed reaction volumes. The method is a typical moment closure method and it works by closing the infinite hierarchy of equations that describe moments of the particle number distribution function. This is done by using correlation forms which describe correlation effects in a strict mathematical way. The variable X is used to specify which correlation effects (forms) are included in the description. Previously, it was argued, in a rather informal way, that the method should work well in situations where the particle number distribution function is Poisson-like. Numerical tests confirmed this. It was shown that the predictive power of the method increases, i.e. the agreement between the theory and simulations improves, if X is increased. In here, these features of the method are explained by using rigorous mathematical reasoning. Three derivative matching theoremsare proven which show that the observed numerical behavior is generic to the method. http://www.tbiomed.com/content/9/1/12 Zoran Konkoli Theoretical Biology and Medical Modelling 2012, null:12 2012-04-13T00:00:00Z doi:10.1186/1742-4682-9-12 /content/figures/1742-4682-9-12-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 12 2012-04-13T00:00:00Z PDF Background: An accepted hypothesis states that coronary atherosclerosis (CA) is initiated by endothelial dysfunction due to inflammation and high levels of LDL-C, followed by deposition of lipids and macrophages from the luminal blood into the arterial intima, resulting in plaque formation. The success of statins in preventing CA promised much for extended protection and effective therapeutics. However, stalled progress in pharmaceutical treatment gives a good reason to review logical properties of the hypothesis underlining our efforts, and to reconsider whether our perception of CA is consistent with facts about the normal and diseased coronary artery.AnalysisTo begin with, it must be noted that the normal coronary intima is not a single-layer endothelium covering a thin acellular compartment, as claimed in most publications, but always appears as a multi-layer cellular compartment, or diffuse intimal thickening (DIT), in which cells are arranged in many layers. If low density lipoprotein cholesterol (LDL-C) invades the DIT from the coronary lumen, the initial depositions ought to be most proximal to blood, i.e. in the inner DIT. The facts show that the opposite is true, and lipids are initially deposited in the outer DIT. This contradiction is resolved by observing that the normal DIT is always avascular, receiving nutrients by diffusion from the lumen, whereas in CA the outer DIT is always neovascularized from adventitial vasa vasorum. The proteoglycan biglycan, confined to the outer DIT in both normal and diseased coronary arteries, has high binding capacity for LDL-C. However, the normal DIT is avascular and biglycan-LDL-C interactions are prevented by diffusion distance and LDL-C size (20 nm), whereas in CA, biglycan in the outer DIT can extract lipoproteins by direct contact with the blood. These facts lead to the single simplest explanation of all observations: (1) lipid deposition is initially localized in the outer DIT; (2) CA often develops at high blood LDL-C levels; (3) apparent CA can develop at lowered blood LDL-C levels. This mechanism is not unique to the coronary artery: for instance, the normally avascular cornea accumulates lipoproteins after neovascularization, resulting in lipid keratopathy.HypothesisNeovascularization of the normally avascular coronary DIT by permeable vasculature from the adventitial vasa vasorum is the cause of LDL deposition and CA. DIT enlargement, seen in early CA and aging, causes hypoxia of the outer DIT and induces neovascularization. According to this alternative proposal, coronary atherosclerosis is not related to inflammation and can occur in individuals with normal circulating levels of LDL, consistent with research findings. http://www.tbiomed.com/content/9/1/11 Vladimir Subbotin Theoretical Biology and Medical Modelling 2012, null:11 2012-04-10T00:00:00Z doi:10.1186/1742-4682-9-11 /content/figures/1742-4682-9-11-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 11 2012-04-10T00:00:00Z PDF We suggest that tRNA actively participates in the transfer of 3D information from mRNA to peptides - in addition to its well-known, "classical" role of translating the 3-letter RNA codes into the one letter protein code. The tRNA molecule displays a series of thermodynamically favored configurations during translation, a movement which places the codon and coded amino acids in proximity to each other and make physical contact between some amino acids and their codons possible. This specific codon-amino acid interaction of some selected amino acids is necessary for the transfer of spatial information from mRNA to coded proteins, and is known as RNA-assisted protein folding. http://www.tbiomed.com/content/9/1/10 Jan Biro Theoretical Biology and Medical Modelling 2012, null:10 2012-04-02T00:00:00Z doi:10.1186/1742-4682-9-10 /content/figures/1742-4682-9-10-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 10 2012-04-02T00:00:00Z PDF Background: Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals. Methods: We developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface. Results: Our within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased. Conclusion: Our results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection. http://www.tbiomed.com/content/9/1/9 Diego Cuadros Gisela Garcia-Ramos Theoretical Biology and Medical Modelling 2012, null:9 2012-03-19T00:00:00Z doi:10.1186/1742-4682-9-9 /content/figures/1742-4682-9-9-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 9 2012-03-19T00:00:00Z XML The fields of molecular biology and computer science have cooperated over recent years to create a synergy between the cybernetic and biosemiotic relationship found in cellular genomics to that of information and language found in computational systems. Biological information frequently manifests its "meaning" through instruction or actual production of formal bio-function. Such information is called Prescriptive Information (PI). PI programs organize and execute a prescribed set of choices. Closer examination of this term in cellular systems has led to a dichotomy in its definition suggesting both prescribed data and prescribed algorithms are constituents of PI. This paper looks at this dichotomy as expressed in both the genetic code and in the central dogma of protein synthesis. An example of a genetic algorithm is modeled after the ribosome, and an examination of the protein synthesis process is used to differentiate PI data from PI algorithms. http://www.tbiomed.com/content/9/1/8 David D'Onofrio David Abel Donald Johnson Theoretical Biology and Medical Modelling 2012, null:8 2012-03-14T00:00:00Z doi:10.1186/1742-4682-9-8 /content/figures/1742-4682-9-8-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 8 2012-03-14T00:00:00Z XML Background: Based on a literature review, the current study aimed to construct mathematical models of lactate production and removal in both muscles and blood during steady state and at varying intensities during whole-body exercise. In order to experimentally test the models in dynamic situations, a cross-country skier performed laboratory tests while treadmill roller skiing, from where work rate, aerobic power and blood lactate concentration were measured. A two-compartment simulation model for blood lactate production and removal was constructed. Results: The simulated and experimental data differed less than 0.5 mmol/L both during steady state and varying sub-maximal intensities. However, the simulation model for lactate removal after high exercise intensities seems to require further examination. Conclusions: Overall, the simulation models of lactate production and removal provide useful insight into the parameters that affect blood lactate response, and specifically how blood lactate concentration during practical training and testing in dynamical situations should be interpreted. http://www.tbiomed.com/content/9/1/7 John Moxnes Oyvind Sandbakk Theoretical Biology and Medical Modelling 2012, null:7 2012-03-13T00:00:00Z doi:10.1186/1742-4682-9-7 /content/figures/1742-4682-9-7-toc.gif Theoretical Biology and Medical Modelling 1742-4682 ${item.volume} 7 2012-03-13T00:00:00Z XML