Cell-center-based model for simulating three-dimensional monolayer tissue deformation

The shape of the epithelial monolayer can be depicted as a curved tissue in three-dimensional (3D) space, where individual cells are tightly adhered to one another. The 3D morphogenesis of these tissues is governed by cell dynamics, and a variety of mathematical modeling and simulation studies have been conducted to investigate this process. One promising approach is the cell-center model, which can account for the discreteness of cells. The cell nucleus, which is considered to correspond to the cell center, can be observed experimentally. However, there has been a shortage of cell-center models specifically tailored for simulating 3D monolayer tissue deformation. In this study, we developed a mathematical model based on the cell-center model to simulate 3D monolayer tissue deformation. Our model was confirmed by simulating the in-plane deformation, out-of-plane deformation, and invagination due to apical constriction

Impact of environmental asymmetry on epithelial morphogenesis

Epithelial folding is a universal biological phenomenon in morphogenesis, typical examples being brain gyri, villi of the intestinal tract, and imaginal discs in invertebrates. During epithelial morphogenesis, the physical constraints imposed by the surrounding microenvironment on epithelial tissue play critical roles in folding morphology. In this study, we focused on the asymmetry of the environmental constraints sandwiching the epithelial sheet and introduced the degree of asymmetry, which indicates whether the basal or apical side of the epithelium is closer to the constraint wall. Then, we investigated the relationship between the degree of asymmetry and epithelial folding morphology using three-dimensional vertex simulations. The results show that the folding patterns of the epithelial sheets change from spot patterns to labyrinth patterns and then to hole patterns as the degree of asymmetry changes. Furthermore, we examined the pattern formation in terms of the equation of out-of-plane displacement of the sheet derived from the mechanical energy functional

An energy landscape approach to understanding variety and robustness in tissue morphogenesis

During morphogenesis in development, multicellular tissues deform by mechanical forces induced by spatiotemporally regulated cellular activities, such as cell proliferation and constriction. Various morphologies are formed because of various spatiotemporal combinations and sequences of multicellular activities. Despite its potential to variations, morphogenesis is a surprisingly robust process, in which qualitatively similar morphologies are reproducibly formed even under spatiotemporal fluctuation of multicellular activities. To understand these essential characteristics of tissue morphogenesis, which involves the coexistence of various morphologies and robustness of the morphogenetic process, in this study, we propose a novel approach to capture the overall view of morphogenesis from mechanical viewpoints. This approach will enable visualization of the energy landscape, which includes morphogenetic processes induced by admissible histories of cellular activities. This approach was applied to investigate the morphogenesis of a sheet-like tissue with curvature, where it deformed to a concave or convex morphology depending on the history of growth and constriction. Qualitatively different morphologies were produced by bifurcation of the valley in the energy landscape. The depth and steepness of the valley near the stable states represented the degree of robustness to fluctuations of multicellular activities. Furthermore, as a realistic example, we showed an application of this approach to luminal folding observed in the initial stage of intestinal villus formation. This approach will be helpful to understand the mechanism of how various morphologies are formed and how tissues reproducibly achieve specific morphologies

Evaluation of extensional and torsional stiffness of single actin filaments by molecular dynamics analysis.

It is essential to investigate the mechanical behaviour of cytoskeletal actin filaments in order to understand their critical role as mechanical components in various cellular functional activities. These actin filaments consisting of monomeric molecules function in the thermal fluctuations. Hence, it is important to understand their mechanical behaviour on the microscopic scale by comparing the stiffness based on thermal fluctuations with the one experimentally measured on the macroscopic scale. In this study, we perform a large-scale molecular dynamics (MD) simulation for a half-turn structure of an actin filament. We analyse its longitudinal and twisting Brownian motions in equilibrium and evaluated its apparent extensional and torsional stiffness on the nanosecond scale. Upon increasing the sampling-window durations for analysis, the apparent stiffness gradually decreases and exhibits a trend to converge to a value that is close to the experimental value. This suggests that by extrapolating the data obtained in the MD analysis, we can estimate the experimentally determined stiffness on the microsecond to millisecond scales. For shorter temporal scales, the apparent stiffness is larger than experimental values, indicating that fast, local motions of the molecular structure are dominant. To quantify the local structural changes within the filament on the nanosecond scale and investigate the molecular mechanisms, such as the binding of the actin-regulatory proteins to the filaments, it is preferable to analyse the mechanical behaviour on the nanometre and nanosecond scales using MD simulation

Three-dimensional-printed soft kidney model for surgical simulation of robot-assisted partial nephrectomy: A proof-of-concept study.

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Capillary Architecture in the Skeletal Muscles in the Rat Hind Limb

We observed differences in the capillary architecture of the skeletal muscles that have different fiber metabolism. The soleus, the vastus intermedius and the tibialis anterior muscles of adult Wistar rats were prepared using two different techniques. Samples for adenosine triphosphatase (ATPase) staining were prepared following Dubovitz's method, and the distributions of fiber type, Types 1, 2A and 2B, were analyzed. Then, corrosion casts of capillary architecture of these muscles prepared following Murakami's method were observed with a scanning electron microscope (SEM) and compared with the fiber distribution. The fiber type composition of the soleus muscle showed Type 1 (slow-twitch) dominance and that of the vastus intermedius and the tibialis anterior muscle showed Type 2 (fast-twitch) dominance. The capillaries of the soleus muscle were tortuous, and this was thought to be advantageous for blood supply. In contrast, the capillaries of the vastus intermedius and tibialis anterior muscles had a relatively parallel pattern. Additionally, two different patterns of capillary architecture that appeared to correspond to certain metabolic characteristic of different muscle fiber types were preserved with corrosion casting. In conclusion, comparative studies on capillary architecture of the skeletal muscles are useful for analyses of its function. </p

Absence of the PsbQ protein results in destabilization of the PsbV protein and decreased oxygen evolution activity in cyanobacterial photosystem II

We have previously reported that cyanobacterial photosystem II (PS II) contains a protein homologous to PsbQ, the extrinsic 17-kDa protein found in higher plant and green algal PS II (Kashino, Y., Lauber, W. M., Carroll, J. A., Wang, Q., Whitmarsh, J., Satoh, K., and Pakrasi, H. B. (2002) Biochemistry 41, 8004-8012) and that it has regulatory role(s) on the water oxidation machinery (Thornton, L. E., Ohkawa, H., Roose, J. L., Kashino, Y., Keren, N., and Pakrasi, H. B. (2004) Plant Cell 16, 2164-2175). In this work, the localization and the function of PsbQ were assessed using the cyanobacterium Synechocystis sp. PCC 6803. From the predicted sequence, cyanobacterial PsbQ is expected to be a lipoprotein on the luminal side of the thylakoid membrane. Indeed, experiments in this work show that upon Triton X-114 fractionation of thylakoid membranes, PsbQ partitioned in the hydrophobic phase, and trypsin digestion revealed that PsbQ was highly exposed to the luminal space of thylakoid membranes. Detailed functional assays were conducted on the psbQ deletion mutant (ΔpsbQ) to analyze its water oxidation machinery. PS II complexes purified from ΔpsbQ mutant cells had impaired oxygen evolution activity and were remarkably sensitive to NH2OH, which indicates destabilization of the water oxidation machinery. Additionally, the cytochrome c550 (PsbV) protein partially dissociated from purified ΔpsbQ PS II complexes, suggesting that PsbQ contributes to the stability of PsbV in cyanobacterial PS II. Therefore, we conclude that the major function of PsbQ is to stabilize the PsbV protein, thereby contributing to the protection of the catalytic Mn 4-Ca1-Clx cluster of the water oxidation machinery. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc

Nonequilibrium Kondo Effect in a Quantum Dot Coupled to Ferromagnetic Leads

We study the Kondo effect in the electron transport through a quantum dot coupled to ferromagnetic leads, using a real-time diagrammatic technique which provides a systematic description of the nonequilibrium dynamics of a system with strong local electron correlations. We evaluate the theory in an extension of the `resonant tunneling approximation', introduced earlier, by introducing the self-energy of the off-diagonal component of the reduced propagator in spin space. In this way we develop a charge and spin conserving approximation that accounts not only for Kondo correlations but also for the spin splitting and spin accumulation out of equilibrium. We show that the Kondo resonances, split by the applied bias voltage, may be spin polarized. A left-right asymmetry in the coupling strength and/or spin polarization of the electrodes significantly affects both the spin accumulation and the weight of the split Kondo resonances out of equilibrium. The effects are observable in the nonlinear differential conductance. We also discuss the influence of decoherence on the Kondo resonance in the frame of the real-time formulation.Comment: 13 pages, 13 figure

日本人血液透析患者におけるProtein-Energy Wasting（PEW）と高リン血症が予後に及ぼす影響 : 5年間の観察研究

Background & aims: In dialysis patients, malnutrition is a poor prognostic factor. In patients with chronic kidney disease (CKD), malnutrition is qualitatively different from general malnutrition, which is defined as “Protein-Energy Wasting (PEW).” Dietary therapy for the enhancement of PEW requires the aggressive intake of protein. Conversely, as protein intake and phosphorus intake correlate positively, increasing the protein intake increases the phosphorus intake, which is a poor prognostic factor in dialysis patients. One of the treatments for hyperphosphatemia in dialysis patients is the intake restriction of phosphorus by dietary counseling. However, protein uptake to maintain and augment the nutritional status and the protein intake restriction to correct hyperphosphatemia are contradictory treatments. Hence, this study aims to investigate the effects of PEW and hyperphosphatemia on the prognosis in hemodialysis patients. Methods: We enrolled 60 outpatients who underwent maintenance hemodialysis for 6 months (May–November 2012) at Iga City General Hospital (Mie, Japan). In November 2012, we assessed the presence or absence of PEW and hyperphosphatemia in patients and evaluated the survival rate over the next 5 years. Results: Overall, 10 patients (17%) were diagnosed as PEW. While 17 patients (28%) exhibited average phosphorus level >6.0 mg/dL (hyperphosphatemia). The 5-year survival rate was 30% in the PEW group, 66% in the non-PEW group, 57% in the hyperphosphatemia group, and 61% in the non-hyperphosphatemia group. A statistically significant difference existed between the PEW and non-PEW groups (P = 0.021). However, we observed no significant difference between the hyperphosphatemia and non-hyperphosphatemia groups. Conclusions: This study suggests that PEW affects the prognosis more than hyperphosphatemia in maintenance hemodialysis patients. The normalization of the serum phosphorus level by the protein intake restriction could prevent secondary hyperparathyroidism and vascular calcification. Conversely, restricting the protein intake poses a risk of malnutrition. In fact, early death occurred in patients with PEW in this study. Perhaps, patients with PEW should prioritize improving their nutritional status rather than controlling the serum phosphorus level