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1.
The mixing performance of gastric contents during digestion is expected to have a major role on the rate and final bioavailability of nutrients within the body. The aim of this study was to characterize the ability of the human stomach to advect gastric contents with different rheological properties. The flow behavior of two Newtonian fluids (10−3 Pa s, 1 Pa s) and a pseudoplastic solution (K=0.223 Pa s0.59) during gastric digestion were numerically characterized within a simplified 3D model of the stomach geometry and motility during the process (ANSYS-FLUENT). The advective performances of each of these gastric flows were determined by analyzing the spatial distribution and temporal history of their stretching abilities (Lagrangian analysis). Results illustrate the limited influence that large retropulsive and vortex structures have on the overall dynamics of gastric flows. Even within the distal region, more than 50% of the flow experienced velocity and shear values lower than 10% of their respective maximums. While chaotic, gastric advection was always relatively poor (with Lyapunov exponents an order of magnitude lower than those of a laminar stirred tank). Contrary to expectations, gastric rheology had only a minor role on the advective properties of the flow (particularly within the distal region). As viscosity increased above 1 St, the role of fluid viscosity became largely negligible. By characterizing the fluid dynamic and mixing conditions that develop during digestion, this work will inform the design of novel in vitro systems of enhanced biomechanical performance and facilitate a more accurate diagnosis of gastric digestion processes.  相似文献   
2.
Designed retroaldolases have utilized a nucleophilic lysine to promote carbon–carbon bond cleavage of β-hydroxy-ketones via a covalent Schiff base intermediate. Previous computational designs have incorporated a water molecule to facilitate formation and breakdown of the carbinolamine intermediate to give the Schiff base and to function as a general acid/base. Here we investigate an alternative active-site design in which the catalytic water molecule was replaced by the side chain of a glutamic acid. Five out of seven designs expressed solubly and exhibited catalytic efficiencies similar to previously designed retroaldolases for the conversion of 4-hydroxy-4-(6-methoxy-2-naphthyl)-2-butanone to 6-methoxy-2-naphthaldehyde and acetone. After one round of site-directed saturation mutagenesis, improved variants of the two best designs, RA114 and RA117, exhibited among the highest kcat (> 10− 3 s− 1) and kcat/KM (11–25 M− 1 s− 1) values observed for retroaldolase designs prior to comprehensive directed evolution. In both cases, the > 105-fold rate accelerations that were achieved are within 1–3 orders of magnitude of the rate enhancements reported for the best catalysts for related reactions, including catalytic antibodies (kcat/kuncat = 106 to 108) and an extensively evolved computational design (kcat/kuncat > 107). The catalytic sites, revealed by X-ray structures of optimized versions of the two active designs, are in close agreement with the design models except for the catalytic lysine in RA114. We further improved the variants by computational remodeling of the loops and yeast display selection for reactivity of the catalytic lysine with a diketone probe, obtaining an additional order of magnitude enhancement in activity with both approaches.  相似文献   
3.
Differential seed dispersal, in which selfed and outcrossed seeds possess different dispersal propensities, represents a potentially important individual‐level association. A variety of traits can mediate differential seed dispersal, including inflorescence and seed size variation. However, how natural selection shapes such associations is poorly known. Here, we developed theoretical models for the evolution of mating system and differential seed dispersal in metapopulations, incorporating heterogeneous pollination, dispersal cost, cost of outcrossing and environment‐dependent inbreeding depression. We considered three models. In the ‘fixed dispersal model’, only selfing rate is allowed to evolve. In the ‘fixed selfing model’, in which selfing is fixed but differential seed dispersal can evolve, we showed that natural selection favours a higher, equal or lower dispersal rate for selfed seeds to that for outcrossed seeds. However, in the ‘joint evolution model’, in which selfing and dispersal can evolve together, evolution necessarily leads to higher or equal dispersal rate for selfed seeds compared to that for outcrossed. Further comparison revealed that outcrossed seed dispersal is selected against by the evolution of mixed mating or selfing, whereas the evolution of selfed seed dispersal undergoes independent processes. We discuss the adaptive significance and constraints for mating system/dispersal association.  相似文献   
4.
The regulation of intracellular Ca2 + triggers a multitude of vital processes in biological cells. Ca2 + permeable ryanodine receptors (RyRs) are the biggest known ion channels and play a key role in the regulation of intracellular calcium concentrations, particularly in muscle cells. In this study, we construct a computational model of the pore region of the skeletal RyR and perform molecular dynamics (MD) simulations. The dynamics and distribution of Ca2 + around the luminal pore entry of the RyR suggest that Ca2 + ions are channeled to the pore entry due to the arrangement of (acidic) amino acids at the extramembrane surface of the protein. This efficient mechanism of Ca2 + supply is thought to be part of the mechanism of Ca2 + conductance of RyRs. Viral myocarditis is predominantly caused by coxsackie viruses that induce the expression of the protein 2B which is known to affect intracellular Ca2 + homeostasis in infected cells. From our sequence comparison, it is hypothesized, that modulation of RyR could be due to replacement of its transmembrane domains (TMDs) by those domains of the viral channel forming protein 2B of coxsackie virus. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.  相似文献   
5.
The insulin receptor (IR) binds insulin and plays important roles in glucose homeostasis by regulating the tyrosine kinase activity at its C-terminus. Its transmembrane domain (TMD) is shown to be important for transferring conformational changes induced by insulin across the cell membrane to regulate kinase activity. In this study, a construct IR940–988 containing the TMD was expressed and purified for structural studies. Its solution structure in dodecylphosphocholine (DPC) micelles was determined. The sequence containing residues L962 to Y976 of the TMD of the IR in micelles adopts a well-defined helical structure with a kink formed by glycine and proline residues present at its N-terminus, which might be important for its function. Paramagnetic relaxation enhancement (PRE) and relaxation experimental results suggest that residues following the TMD are flexible and expose to aqueous solution. Although purified IR940–988 in micelles existed mainly as a monomeric form verified by gel filtration and relaxation analysis, cross-linking study suggests that it may form a dimer or oligomers under micelle conditions.  相似文献   
6.
We recently published two papers detailing the structures of fluid phase phosphatidylglycerol (PG) lipid bilayers (Ku?erka et al., 2012 J. Phys. Chem. B 116: 232–239; Pan et al., 2012 Biochim. Biophys. Acta Biomembr. 1818: 2135–2148), which were determined using the scattering density profile model. This hybrid experimental/computational technique utilizes molecular dynamics simulations to parse a lipid bilayer into components whose volume probabilities follow simple analytical functional forms. Given the appropriate scattering densities, these volume probabilities are then translated into neutron scattering length density (NSLD) and electron density (ED) profiles, which are used to jointly refine experimentally obtained small angle neutron and X-ray scattering data. However, accurate NSLD and ED profiles can only be obtained if the bilayer's chemical composition is known. Specifically, in the case of neutron scattering, the lipid's exchangeable hydrogens with aqueous D2O must be accounted for, as they can have a measureable effect on the resultant lipid bilayer structures. This was not done in our above-mentioned papers. Here we report on the molecular structures of PG lipid bilayers by appropriately taking into account the exchangeable hydrogens. Analysis indicates that the temperature-averaged PG lipid areas decrease by 1.5 to 3.8 Å2, depending on the lipid's acyl chain length and unsaturation, compared to PG areas when hydrogen exchange was not taken into account.  相似文献   
7.
A new software package, RASPA, for simulating adsorption and diffusion of molecules in flexible nanoporous materials is presented. The code implements the latest state-of-the-art algorithms for molecular dynamics and Monte Carlo (MC) in various ensembles including symplectic/measure-preserving integrators, Ewald summation, configurational-bias MC, continuous fractional component MC, reactive MC and Baker's minimisation. We show example applications of RASPA in computing coexistence properties, adsorption isotherms for single and multiple components, self- and collective diffusivities, reaction systems and visualisation. The software is released under the GNU General Public License.  相似文献   
8.
Geert van Wirdum 《Hydrobiologia》1993,265(1-3):129-153
A survey of base-rich wetlands in The Netherlands is presented. The main area of their occurrence is the low-lying Holocene part of the country, until some thousand years ago a large and coherent wetland landscape: the Holland wetland. The development of various parts of the Holland wetland into marshes, fens and bogs can be understood from hydrological relations in mire basins, as recognized in the distinction of primary, secondary and tertiary mire basin stages. Presently, the remnants of the Holland wetland are separate base-rich wetlands. The succession of their vegetation reflects various abiotic conditions and human influences. Three main developmental periods are distinguished as regards these factors. The first, geological period of mire development is seen as a post-glacial relaxation, with the inertia due to the considerable mass of wetland as a stabilizing factor. Biological “grazing” influences, as an aspect of utilization by humans, converted base-rich wetlands to whole new types in the second, historical period. Presently, mass and harvesting have decreased in importance, and actual successions in terrestrializing turbaries seem to reflect rapidly changing environmental conditions. Human control could well become the most important factor in the future development of wetland nature. The present value of open fen vegetation strongly depends on the continuation of the historical harvesting. The development of wooded fen may help to increase the mass of wetland in the future. Best results in terms of biodiversity are expected when their base state is maintained through water management. The vegetation and hydrology of floating fens in terrestrializing turbaries is treated in some more detail. Various lines and phases in the succession are distinguished. Open fen vegetation at base-rich, yet nutrient-poor sites is very rich in species threatened elsewhere. The fast acidification of certain such fens is attributed to hydrological and management factors. This acidification is illustrated in the profile of a floating raft sample. At the scale of these small fens, the elemental structure comprising base-rich fen, transitional fen and bog vegetation, is not as stable as it was in the large Holland wetland. A critical role seems to be played by the supply of bases with the water influx. The changing base state is supposed to change the nutrient cycling to such an extent that it would be correct to call this trophic excitation of the ecosystem, rather than just eutrophication. Eutrophication indicates a quantitative reaction to an increased nutrient supply, the internal system being unaltered. The drainage of fens, resulting in an increased productivity of the vegetation, provides another example of excitation, to the effect that the functional system is dramatically changed internally.  相似文献   
9.
We explore the relationship between transition probabilities in the Leslie model and those derived from experimental cumulative distributions. The nature of the two kinds of probabilities are discussed, and a formula derived for converting from one to the other. A numerical example is given to illustrate the differences.  相似文献   
10.
茶园冬季乔木落叶的分解和矿质元素释放   总被引:1,自引:0,他引:1  
在我国南方存在着一种传统植茶方式——茶林复合生态系统,近年来人们已逐步认识到它在维持土壤肥力,抗御自然灾害和保证茶叶内质特性等方面的作用,然而对冬季乔木落叶分解和矿质元素释放的作用尚无报道。本文是对安徽省黄山市休宁县茶树-乌桕复合园和茶树-板栗复合园的冬季乔木落叶分解的研究,为全面认识茶林复合生态系统的性质提供依据。  相似文献   
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