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Geometric interpretation of phyllotaxis transition

The original problem of phyllotaxis was focused on the regular arrangements of leaves on mature stems represented by common fractions such as 1/2, 1/3, 2/5, 3/8, 5/13, etc. The phyllotaxis fraction is not fixed for each plant but it may undergo stepwise transitions during ontogeny, despite contrasting observation that the arrangement of leaf primordia at shoot apical meristems changes continuously. No explanation has been given so far for the mechanism of the phyllotaxis transition, excepting suggestion resorting to genetic programs operating at some specific stages. Here it is pointed out that varying length of the leaf trace acts as an important factor to control the transition by analyzing Larson's diagram of the procambial system of young cottonwood plants. The transition is interpreted as a necessary consequence of geometric constraints that the leaf traces cannot be fitted into a fractional pattern unless their length is shorter than the denominator times the internode.

physics.bio-ph↗

Large variability in dynamical transitions in biological systems with quenched disorder

Coherent oscillatory activity can arise spontaneously as a result of increased coupling in a system of excitable and passive cells, each being quiescent in isolation. This can potentially explain the appearance of spontaneous rhythmic contractions in the pregnant uterus close to term. We investigate the transition to periodic activity using a model system comprising a lattice of excitable cells, each being coupled to a variable number of passive cells whose distribution defines a quenched realization (replica) of spatial disorder. Close to the transition between quiescent state and sustained oscillations in the system we observe large fluctuations between different replicas induced by variations in the local density of passive cells around an excitable cell. We demonstrate that the disorder-induced fluctuations can be described in terms of a simple scaling relation which involves the strength of coupling between excitable cells, the mean passive cell density, as well as the logarithm of the system size. Our results can be interpreted as suggesting that larger organs will have greater variability in the onset of persistent activity.

cond-mat.dis-nn↗

Physics of Wound Healing I: Energy Considerations

Wound healing is a complex process with many components and interrelated processes on a microscopic level. This paper addresses a macroscopic view on wound healing based on an energy conservation argument coupled with a general scaling of the metabolic rate with body mass M as M^γ where 0 <γ<1. Our three main findings are 1) the wound healing rate peaks at a value determined by γ alone, suggesting a concept of wound acceleration to monitor the status of a wound. 2) We find that the time-scale for wound healing is a factor 1/(1 -γ) longer than the average internal timescale for producing new material filling the wound cavity in corresondence with that it usually takes weeks rather than days to heal a wound. 3) The model gives a prediction for the maximum wound mass which can be generated in terms of measurable quantities related to wound status. We compare our model predictions to experimental results for a range of different wound conditions (healthy, lean, diabetic and obsese rats) in order to delineate the most important factors for a positive wound development trajectory. On this general level our model has the potential of yielding insights both into the question of local metabolic rates as well as possible diagnostic and therapeutic aspects.

physics.med-ph↗

Sodium Magnetic Resonance Imaging: Biomedical Applications

In this article, we present an up-to-date overview of the potential biomedical applications of sodium MRI in vivo. Sodium MRI is a subject of increasing interest in translational research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most of human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: (1) the role of sodium in biological tissues, (2) a short review on sodium magnetic resonance, and (3) a review of some studies on sodium MRI on different organs/diseases to date.

physics.med-ph↗

Omni-tomography: Next-generation Biomedical Imaging

Omni-tomography is enabled by interior tomography that has been developed over the past five years. By omni-tomography, we envision that the next stage of biomedical imaging will be the grand fusion of many tomographic modalities into a single gantry (all in one) for simultaneous data acquisition of numerous complementary features (all at once). This integration has great synergistic potential for development of systems biology, personalized and preventive medicine, because many physiological processes are dynamic and complicated, and must be observed promptly, comprehensively, sensitively, specifically, and non-invasively. In this perspective, we first present the background for and power of omni-tomography, then discuss its important applications in vulnerable plaque characterization and intratumor heterogeneity evaluation, review its enabling theory and technology, explain for the first time the feasibility of the CT-MRI scanner as an example, and finally suggest exciting research opportunities.

physics.med-ph↗

Multifractal age? Multifractal analysis of cardiac interbeat intervals in assessing of healthy aging

24-hour Holter recordings of 124 healthy people at different age are studied. The nocturnal signals of young people reveal the presence of the multiplicative structure. This structure is significantly weaker in diurnal signals and becomes less evident for elderly people. Multifractal analysis allows us to propose qualitative and quantitative methods to estimate the advancement of the aging process for healthy humans.

physics.data-an↗

In vitro investigation of the effects of X- rays carried by a photon beam upon the cell cycle progression in Vero cells

The effects of the X-rays carried out in a photon beam produced by a medical linear particle accelerator on the progression of the cell cycle in normal cells Vero were evaluated by flow cytometric mean. The evaluation of the consequences of 1 and 3 Gy irradiation upon cell cycle development was performed after 96 and 120 hours from the exposure moment, in order to register the late effects of irradiation. As compared with the control group (sham exposed) the treated cells with the dose of 1 Gy have shown an increase of the frequency of cells blocked in S and G2/M stages and also of the apoptotic cells at 96 hours from the treatment. After another 24 hours, the frequency of the blocked cells in S and G2/M has decreased. The response of the 96 hours cell cultures to 3 Gy treatment was faster, as suggested by the increased number of apoptotic cells and by reduced frequency of the arrested cells in S and G2/M. The blockage of Vero cells in different phases of the cell-cycle and the presence of active repairing systems reveals the reduced risk of the malignant transformation of the exposed normal cells and could offer an enhanced cell protection to another damaging agents.

q-bio.TO↗

Intrinsic cell factors that influence tumourigenicity in cancer stem cells - towards hallmarks of cancer stem cells

Since the discovery of a cancer initiating side population in solid tumours, studies focussing on the role of so-called cancer stem cells in cancer initiation and progression have abounded. The biological interrogation of these cells has yielded volumes of information about their behaviour, but there has, as of yet, not been many actionable generalised theoretical conclusions. To address this point, we have created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue and explored the phenotypic traits inherent in the inciting cell and the resultant tissue growth. We identify the regions in phenotype parameter space where these initiating cells are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour formation. As our parameters and model are non-specific, they could apply to any tissue cancer stem-cell and do not assume specific genetic mutations. In this way, our model suggests that targeting these phenotypic traits could represent generalizable strategies across cancer types and represents a first attempt to identify the hallmarks of cancer stem cells.

q-bio.TO↗

Comparative study of non-invasive force and stress inference methods in tissue

In the course of animal development, the shape of tissue emerges in part from mechanical and biochemical interactions between cells. Measuring stress in tissue is essential for studying morphogenesis and its physical constraints. Experimental measurements of stress reported thus far have been invasive, indirect, or local. One theoretical approach is force inference from cell shapes and connectivity, which is non-invasive, can provide a space-time map of stress and relies on prefactors. Here, to validate force- inference methods, we performed a comparative study of them. Three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces, were tested by using two artificial and two experimental data sets. Our results using different datasets consistently indicate that our Bayesian force inference, by which cell-junction tensions and cell pressures are simultaneously estimated, performs best in terms of accuracy and robustness. Moreover, by measuring the stress anisotropy and relaxation, we cross-validated the force inference and the global annular ablation of tissue, each of which relies on different prefactors. A practical choice of force-inference methods in distinct systems of interest is discussed.

q-bio.QM↗

Microscopic and thermodynamic evaluation of vesicles shed by erythrocytes at elevated temperatures

Erythrocytes and vesicles shed by erythrocytes from human and rat blood were collected and analyzed after temperature was elevated by physical exercise or by exposure to external heat. The images of erythrocytes and vesicles were analyzed by the light microscopy system with spatial resolution of better than 90 nm. The samples were observed in an aqueous environment and required no freezing, dehydration, staining, shadowing, marking or any other manipulation. Temperature elevation, whether passive or through exercise, resulted in significant concentration increase of structurally transformed erythrocytes (echinocytes) and vesicles in blood. At temperature of 37 oC, mean vesicle concentrations and diameters in human and rat blood were (1.50+-0.35)x10^6 and (1.4+-0.2)x10^6 vesicles/μL, and 0.365+-0.065 and 0.436+-0.03 μm, respectively. It was estimated that 80% of all vesicles found in human blood are smaller than 0.4 μm. Thermodynamic analysis of experimental and literature data showed that erythrocyte transformation, vesicle release and other associated processes are driven by entropy with enthalpy-entropy compensation. It is suggested that physical state of hydrated cell membrane is responsible for the compensation. The increase of vesicle number related to elevated temperatures may be indicative of the heat stress level and serve as diagnostic of erythrocyte stability and human performance.

q-bio.TO↗

The Invalidity of the Laplace Law for Biological Vessels and of Estimating Elastic Modulus from Total Stress vs. Strain: a New Practical Method

The quantification of the stiffness of tubular biological structures is often obtained, both in vivo and in vitro, as the slope of total transmural hoop stress plotted against hoop strain. Total hoop stress is typically estimated using the "Laplace law." We show that this procedure is fundamentally flawed for two reasons: Firstly, the Laplace law predicts total stress incorrectly for biological vessels. Furthermore, because muscle and other biological tissue are closely volume-preserving, quantifications of elastic modulus require the removal of the contribution to total stress from incompressibility. We show that this hydrostatic contribution to total stress has a strong material-dependent nonlinear response to deformation that is difficult to predict or measure. To address this difficulty, we propose a new practical method to estimate a mechanically viable modulus of elasticity that can be applied both in vivo and in vitro using the same measurements as current methods, with care taken to record the reference state. To be insensitive to incompressibility, our method is based on shear stress rather than hoop stress, and provides a true measure of the elastic response without application of the Laplace law. We demonstrate the accuracy of our method using a mathematical model of tube inflation with multiple constitutive models. We also re-analyze an in vivo study from the gastro-intestinal literature that applied the standard approach and concluded that a drug-induced change in elastic modulus depended on the protocol used to distend the esophageal lumen. Our new method removes this protocol-dependent inconsistency in the previous result.

cond-mat.soft↗

Postcranial pneumaticity in dinosaurs and the origin of the avian lung

In birds, diverticula of the lungs and air sacs pneumatize specific regions of the postcranial skeleton. Relationships among pulmonary components and skeletal regions they pneumatize allow inferences about pulmonary anatomy in non-avian dinosaurs. Fossae, foramina and chambers in the postcranial skeletons of pterosaurs and saurischian dinosaurs are diagnostic for pneumaticity. In basal saurischians only the cervical skeleton is pneumatized, by cervical air sacs. In more derived saurischians pneumatization of posterior dorsal, sacral, and caudal vertebrae indicates abdominal air sacs. Abdominal air sacs in sauropods are also indicated by a pneumatic hiatus (a gap in vertebral pneumatization) in Haplocanthosaurus. Minimally, saurischians had dorsally attached diverticular lungs plus anterior and posterior air sacs, and all the pulmonary prerequisites for flow-through lung ventilation like that of birds. Pneumaticity reduced skeletal mass in saurischians. I propose the Air Space Proportion (ASP) as a measure of proportional volume of air in pneumatic bones. The mean ASP of a sample of sauropod and theropod vertebrae is 0.61, so on average, air occupied more than half the volume of these vertebrae. In Diplodocus, pneumatization lightened the living animal by 7-10 percent, and that does not include extraskeletal diverticula, air sacs, lungs, or trachea. If all these air reservoirs included, the specific gravity of Diplodocus is 0.80, higher than published values for birds but lower than those for squamates and crocodilians. Pneumatization of cervical vertebrae facilitated evolution of long necks in sauropods. Necks longer than nine meters evolved at least four times, in mamenchisaurs, diplodocids, brachiosaurids, and titanosaurs. Increases in the number of cervical vertebrae, their proportional lengths, and their internal complexity occurred in parallel in most of these lineages.

q-bio.TO↗

The Flexibility and Musculature of the Ostrich Neck: Implications for the Feeding Ecology and Reconstruction of the Sauropoda (Dinosauria:Saurischia)

The Sauropoda were the largest terrestrial animals ever to have lived on this planet. As their nutritional requirements were so huge, their diet holds sway over the ecology of many Mesozoic herbivores. The diet of the sauropods is limited by their feeding envelope, which in turn is governed by the posture and flexibility of their elongate necks. Yet the exact nature of the flexibility and posture of the neck has been a contentious issue. Previous studies have utilised computer models of dry bone, mechanical principles or the flexibility of the necks of extant animals. However, the effect of the musculature of the neck has yet to be investigated. Through measurements of the flexibility of the ostrich neck after cumulative tissue removal, analyses of the muscle attachment sites of the ostrich and sauropods, and testing of the Osteological Neutral Pose model, this study attempts to rectify this situation. The ostrich neck was shown to have three sections of flexibility; a slightly flexible anterior section, a very flexible middle section and a stiff posterior section. The Osteological Neutral Pose did not show these sections, and was shown to potentially overestimate and underestimate flexibility. It was also found that the inter-vertebral space could account for varying estimates of flexibility, and that sauropods would have proportionally more muscle mass at the base of the neck in relation to the ostrich. Ultimately, it was shown that the tissues of the neck place the limits of flexibility, and that zygapophyseal overlap does not indicate the flexibility of the neck. Should the Osteological Neutral Pose affect sauropod flexibility estimates in the same manner as that of the ostrich (a general overestimate), then the sauropods would have a more limited feeding envelope than previously thought, allowing for greater niche partitioning between groups.

q-bio.TO↗

Aspects of the history, anatomy, taxonomy and palaeobiology of sauropod dinosaurs

Although the sauropod dinosaurs have been recognised for more than a hundred and sixty years, much remains to be discovered and understood about their functional anatomy and palaeobiology. Older taxa require revision and new taxa await description. The characteristic long necks of sauropods are mechanically perplexing and their evolution is obscure. All these issues are addressed herein. The genus Brachiosaurus is represented by the American type species B. altithorax and the better known African species B. brancai. However, examination of the overlapping material shows 26 differences between the species. B. brancai must be removed from Brachiosaurus and referred to the genus Giraffatitan, which has been previously proposed for it. Xenoposeidon proneneukos is a new neosauropod from the Lower Cretaceous Hastings Bed Group, known from a single partial dorsal vertebra. The excellent preservation of the Xenoposeidon holotype reveals six unique characters. The distinctive morphology suggests that Xenoposeidon may represent a new sauropod family, extending sauropod disparity as well as bringing to four the number of sauropod families known from the Wealden. A second new Early Cretaceous genus is also described, a titanosauriform from the Ruby Ranch Member of the Cedar Mountain Formation, in Utah. This taxon is known from at least two individuals, an adult and a juvenile, which together provide vertebrae, ribs, a scapula, sternal plates and an ilium. The ilium is particularly unusual, exhibiting five unique features. The longest sauropod necks were five times as long as those of the next longest terrestrial animals, and four separate lineages evolved necks exceeding 10 m. Elongation was enabled by sheer size, vertebral pneumaticity and the relative smallness of sauropod heads, despite aspects of cervical osteology that are difficult to understand on mechanical first principles.

q-bio.TO↗

Warburg Effect due to Exposure to Different Types of Radiation

Cancer cells maintain a high level of aerobic glycolysis (the Warburg effect), which is associated with their rapid proliferation. Many studies have reported that the suppression of glycolysis and activation of oxidative phosphorylation can repress the growth of cancer cells through regulation of key regulators. Whether Warburg effect of cancer cells could be switched by some other environmental stimulus? Herein, we report an interesting phenomenon in which cells alternated between glycolysis and mitochondrial respiration depending on the type of radiation they were exposed to. We observed enhanced glycolysis and mitochondrial respiration in HeLa cells exposed to 2-Gy X-ray and 2-Gy carbon ion radiation, respectively. This discovery may provide novel insights for tumor therapy.

q-bio.TO↗

Imaging of non tumorous and tumorous human brain tissue with full-field optical coherence tomography

A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\mum resolution in 3D with a typical 200\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low- grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a real-time manner as a label-free non-invasive imaging technique in an intra-operative neurosurgical clinical setting to assess tumorous glial and epileptic margins.

physics.med-ph↗