A mathematical model of the pathological functional state of the oxygen transport system

Based on the principle of minimum power, a mathematical model of the pathological functional state of the oxygen transport system is presented. The model is used to determine the optimal functional parameters of the oxygen transport system in hyperthyroidism, anemia and hypertension. Theoretical results are compared with clinical data.     

A mathematical model of the functional state of the oxygen transport system

Based on the principle of minimum power, a mathematical model of the functional state of the oxygen transport system is presented. The optimization model minimizes the power expenditure of the heart, bone marrow, lung and other tissues. The model is used to determine the functional parameters of the oxygen transport system in man under both normal and varying barometric pressures. Theoretical results are compared with experimental data.     

A mathematical model of the exercise functional state of the oxygen transport system

Based on the principle of minimum power, a mathematical model of the exercise functional state of the oxygen transport system is presented. Aerobic and anaerobic muscular efficiencies are considered. The energetically optimal arteriovenous oxygen content difference, cardiac output and ventilation during exercise in man are determined depending on mechanical power. Theoretical results are compared with experimental data.     

Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems.

The livR locus, which leads to a trans-recessive derepression of branched-chain amino acid transport and periplasmic branched-chain amino acid-binding proteins, is responsible for greatly increased sensitivity toward growth inhibition by leucine, valine, and serine and, as shown previously, for increased sensitivity toward toxicity by branched-chain amino acid analogues, such as 4-azaleucine or 5',5',5'-trifluoroleucine. These phenotypes are similar to those of relA mutants; however, the livR mutants retain the stringent response of ribonucleic acid synthesis. However, an increase in the rate of transport or in the steady-state intracellular level of amino acids in the livR strain cannot completely account for this sensitivity. The ability of the LIV-I transport system to carry out exchange of pool amino acids for extracellular leucine is a major factor in leucine sensitivity. The previous finding that inhibition of threonine deaminase by leucine contributes to growth inhibition is confirmed by simulating the in vivo conditions using a toluene-treated cell preparation with added amino acids at levels corresponding to the internal pool. The relationship between transport systems and corresponding biosynthetic pathways is discussed and the general principle of a coordination in the regulation of transport and biosynthetic pathways is forwarded. The finding that the LIV-I transport system functions well for amino acid exchange in contrast to the LIV-II system provides another feature that distinguishes these systems in addition to previously described differences in regulation and energetics.     

COPI-mediated protein and lipid sorting in the early secretory pathway

Summary The major function of the secretory pathway of eukaryotes is to maintain the compartmental organization of the endomembrane system and organelle-associated functions by proper distribution of newly synthesized molecules. Protein and lipid transport is mediated by vesicular intermediates that connect the various organelles throughout this pathway. This principle enables the eukaryotic cell to actively sort proteins and lipids at every level of this route, in both the anterograde and the retrograde direction. Here, we discuss the molecular mechanisms of nonclathrin (COPI and COPII)-coated-vesicle biogenesis and how transport vesicle formation is linked to protein and lipid sorting in the early secretory pathway.     

On the extent of localization of the energized membrane state in chromatophores from Rhodopseudomonas capsulata N22.

1. The principle of the double-inhibitor titration method for assessing competing models of electron transport phosphorylation is expounded. 2. This principle is applied to photophosphorylation by chromatophores from Rhodopseudomonas capsulata N22. 3. It is found that, in contrast to the predictions of the chemiosmotic coupling model, free energy transfer is confined to individual electron transport chain and ATP synthase complexes. 4. This conclusion is not weakened by arguments concerning, the degree of uncoupling in the native chromatophore preparation or the relative number of electron transport chain and ATP synthase complexes present. 5. Photophosphorylation is completely inhibited by the uncoupler SF 6847 at a concentration corresponding to 0.31 molecules per electron transport chain. 6. The apparent paradox is solved by the proposal, consistent with the available evidence on the mode of action of uncouplers, that uncoupler binding causes a co-operative conformation transition in the chromatophore membrane, which leads to uncoupling and which is not present in the absence of uncoupler.     

An improved flame ionization detector for high performance liquid chromatography

A flame ionization detector and associated transport device of high sensitivity for liquid chromatography are described. The system is based on the moving chain principle and employs a stainless steel belt of perforated structure that confers on it superior surface properties for collection and transport of column eluent. After evaporation of the solvent, the solute is converted to hydrocarbons in a stainless steel reactor of sandwich construction and is combusted in a hydrogen flame. The universality of the system is demonstrated with albumin and glucose, as well as with lipids. Sensitivity and reproducibility of the system are demonstrated also with a standard mixture of neutral lipids.     

Model of Active Transport of Ions in Archaea Cells

A mathematical model of the active transport of main ions in cells of archaebacteria has been constructed. A set of equations has been developed and solved for ion fluxes through the bacterium membrane. The model is based on the principle “one ion—one transport system.” Considering experimental data, the major transport mechanism was determined for each ion and the balance equation was written on the basis of this mechanism in the stationary state. This allowed calculating values of the membrane potential and intracellular concentrations of the ions independently. The calculated values of the intracellular concentrations and resting potential are in qualitative agreement with the corresponding experimental values for cells of extremely halophilic archaea.     

Escherichia coli K-12 mutants that allow transport of maltose via the beta-galactoside transport system.

We have isolated mutants of Escherichia coli that have an altered beta-galactoside transport system. This altered transport system is able to transport a sugar, maltose, that the wild-type beta-galactoside transport system is unable to transport. The mutation that alters the specificity of the transport system is in the lacY gene, and we refer to the allele as lacYmal. The lacYmal allele was detected originally in strains in which the lac genes were fused to the malF gene. Thus, as a result of gene fusion and isolation of the lacYmal mutation, a new transport system was evolved with regulatory properties and specificity similar to those of the original maltose transport system. Maltose transport via the lacYmal gene product is independent of all of the normal maltose transport system components. The altered transport system shows a higher affinity than the wild-type transport system for two normal substrates of the beta-galactoside transport system, thiomethyl-beta-D-galactoside and o-nitrophenyl-beta-D-galactoside.     

A Novel Two-Tag System for Monitoring Transport and Cleavage through the Classical Secretory Pathway – Adaptation to HIV Envelope Processing

The classical secretory pathway is essential for the transport of a host of proteins to the cell surface and/or extracellular matrix. While the pathway is well-established, many factors still remain to be elucidated. One of the most relevant biological processes that occur during transport involves the cleavage of pro-proteins by enzymes residing in the endoplasmic reticulum/Golgi/TransGolgi Network compartment. Teasing out the requirements involved in the classical secretory pathway and cleavage during transport would shed new light into mis-regulation leading to disease. Current methodologies fail to link transport and cleavage at the single cell level. Here, we describe a cell-based assay that relies on an engineered protein scaffold that can discriminate between transport to the cell surface, in the absence or presence of cleavage. Our novel two-tag system works in a robust and quantitative manner and distinguishes between cleaved and non-cleaved events based on cell surface expression of one or two epitope tags, respectively. Here, we have used the HIV-1 envelope as a substrate, which is cleaved during transport, as proof of principle. Importantly, this assay can be easily coupled to existing siRNA-based screens to identify novel regulators and effectors involved in transport and/or cleavage of cell surface proteins. In addition, unlike other in vivo based assays, the assay described here can also be easily adapted to drug discovery purposes.     

Approaches used to examine the mechanism and regulation of hexose transport in rat myoblasts

This review discusses some of the approaches and general criteria that we have used to examine the properties of the hexose transport system in undifferentiated L6 rat myoblasts. These approaches include studying the kinetics of hexose transport in whole cells and plasma membrane vesicles, the effects of various inhibitors on hexose transport, the isolation and characterization of hexose transport mutants, and the use of cytochalasin B (CB) to identify the transport component(s). Transport kinetics indicated that two transport systems are present in these cells. 2-Deoxy-D-glucose is transported primarily by the high affinity system, whereas 3-O-methyl-D-glucose is transported by the low affinity system. Furthermore, these two transport systems are inactivated to different extents by CB. CB has a higher binding affinity for the low affinity hexose transport system. The inhibitory effect of various hexose analogues also revealed the presence of two hexose transport systems. The effects of various ionophores and energy uncouplers on hexose transport suggest that the high affinity system is an active transport process, whereas the low affinity system is of the facilitated diffusion type. The high affinity system is also sensitive to sulfhydryl reagents, whereas the low affinity system is not. Further evidence for the presence of two transport systems comes from the characterization of hexose transport mutants. Two of the mutants isolated are shown to be defective in the high affinity transport system, but not in the low affinity transport system. These mutants are also defective in the CB low affinity binding site. Based on our results a tentative working model for hexose transport in L6 rat myoblasts is presented.     

The interpretation of mean transit time measurements for multiphase tissue systems

A model-independent proof of the central-volume principle for multiphase tissue systems is presented. This derivation emphasizes the transport processes which occur within the system, and the physical constraints which the system must satisfy for valid application of the principle. These constraints include: (i) the fluid flowing into the system must be equivalentlylabelled; (ii) the system under study must be part of a larger system which has no diffusive inlets or outlets. The derivation shows that the definition of the volume of distribution and the choice of appropriate partition coefficients for evaluation of this quantity, are independent of any assumption concerning tracer equilibrium between phases as a whole. A less restrictive definition of equivalent labelling also results from the proof.The relationship between the mean transit times measured by global residue detection and by “snapshot” outflow detection is derived. If diffusion of tracer across the boundaries of the monitored system is significant compared to convective transport, then these two transit times will not have identical values.The conditions under which valid measurements of regional, i.e. local, physiological variables can be performed by residue detection are also discussed, and it is shown that regional residue-detection measurements may be used to assess variations in anatomical structure throughout a larger region. However, the use of the height/area method for calculating regional perfusion can lead to error when tracer enters the detector field by diffusion, as opposed to convection, or when a significant amount of diffusion occurs before tracer enters the observed region.     

Biomechanical model of the xylem vessels in vascular plants

BACKGROUND AND AIMS: The xylem, or water transport system, in vascular plants adopts different morphologies that appear sequentially during growth phases. This paper proposes an explanation of these morphologies based on engineering design principles. METHODS: Using microscopic observations of the different growth stages, an engineering analysis of the xylem vessels as a closed cylinder under internal pressure is carried out adopting pressure vessel design concepts. KEY RESULTS: The analysis suggests that the xylem vessel structural morphology follows the 'constant strength' design principle, i.e. all of the material within the wall of the xylem is loaded equally to its maximum allowable stress capacity, and the amount of material used is therefore systematically minimized. The analysis shows that the different structural designs of the xylem vessel walls (annular, helical, reticulate and pitted) all quantitatively follow the constant strength design principle. CONCLUSIONS: The results are discussed with respect to growth and differentiation. It is concluded that the morphology of the xylem vessel through the different phases of growth seems to follow optimal engineering design principles.     

Optimal arterial blood pressure

Based on the principle of minimum power, a mathematical model of the functional state of the circulatory system is presented. The optimization model minimizes the power expenditure of the heart, bone marrow and the power expended in carrying blood. Mean arterial blood pressure is determined depending on oxygen transport parameters and locomotor activity. Theoretical results are compared with experimental data for man.     

SNAREs and the specificity of membrane fusion

A major problem of intracellular membrane traffic concerns the way in which transport vesicles find and fuse with their target organelles. SNARE proteins are involved in fusion, and their mutual recognition could in principle provide the necessary specificity. Alternatively, the preliminary tethering of vesicles, mediated by peripheral membrane proteins, could hold the key. Previous studies of SNARE complex assembly in solution have suggested little specificity, but recent experiments with yeast SNAREs anchored in liposomes show that their interactions can be highly selective. It is likely that both tethering and SNARE engagement contribute to the accuracy of membrane transport.     

Use of a genetic variant to study the hexose transport properties of human skin fibroblasts.

Human skin fibroblasts from 'normal' subjects were found to possess at least two hexose transport systems. One system was responsible for the uptake of 2-deoxy-D-glucose (dGlc), D-glucose and D-galactose, whereas the other was responsible primarily for the uptake of 3-O-methyl-D-glucose (MeGlc). The transport of dGlc was the rate-limiting step in the uptake process; over 97% of the internalized dGlc was phosphorylated and the specific activity of hexokinase was several times higher than that for dGlc transport. The dGlc transport system was activated by glucose starvation, and was very sensitive to inhibition by cytochalasin B and energy uncouplers. Fibroblasts isolated from a patient with symptoms of hypoglycaemia were found to differ from their normal counterparts in the dGlc transport system. They exhibited a much higher transport affinity for dGlc, D-glucose and D-galactose, with no change in the respective transport capacity. Transport was not the rate-limiting step in dGlc uptake by these cells. Moreover, the patient's dGlc transport system was no longer sensitive to inhibition by cytochalasin B and energy uncouplers. This suggested that the intrinsic properties of the patient's dGlc transport system were altered. It should be noted that the patient's dGlc transport system could still be activated by glucose starvation. Despite the changes in the dGlc transport system, the MeGlc transport system in the patient's fibroblasts remained unaltered. The observed difference in the properties of the two hexose transport systems in the 'normal' and the patient's fibroblasts strongly suggests that the two transport systems may be coded or regulated by different genes. The present finding provides the first genetic evidence from naturally occurring fibroblasts indicating the presence of two different hexose transport systems.     

Research approaches to study the functioning of vesicular-arbuscular mycorrhizas in the field

Approaches suitable for the study on the functioning of vesicular-arbuscular mycorrhizas (VAM) in the field are discussed, with emphasis on those VAM-specific processes which may influence P nutrition of crops. These processes are related to hyphal P transport in particular, and conventional techniques based on comparisons between VAM-colonized plants and uncolonized controls are therefore of limited value in such studies. Novel methods are described, which make use of a two-compartment principle and isotopes to directly measure the P transport by the VAM mycelium under controlled conditions and in the field. The principle of isotopic equilibrium may be used for indirectly quantifying the relative amounts of P supplied by hyphae and by roots of VAM plants. The hyphal contribution to P uptake may also be assessed by comparing hyphal uptake of ³²P from a hyphal compartment with uptake of ³³P from a corresponding compartment containing both roots and hyphae. These methods are suitable for a functional characterization of VAM fungi and for identifying constraints to the functioning of VAM.     

Imino acid transport across the brush-border membrane of the guinea-pig small intestine

The transport of imino and non-alpha-amino acids across the brush-border membrane of the guinea-pig small intestine has been examined. It was found that the guinea pig is without a transport system for non-alpha-amino acids. The transport of imino acids was characterized using methylaminoisobutyrate (MeAIB) as a substrate. This choice was validated by lack of kinetic evidence that more than one transport system was involved in the transport of MeAIB, by the identical values of the estimates of the passive permeability of MeAIB, the magnitude of its proline-resistant transport, and the permeability of mannitol. The transport system for MeAIB is moderately stereospecific. It does not accept cationic amino acids. It accepts alpha-amino-monocarboxylic acids but N-methylation increases the affinities of these amino acids by an order of magnitude. The length of the side-chain of the aliphatic imino acids seems of little importance for the affinity for the transport system, but the data on inhibition of the transport of MeAIB by proline and piperidine-2-carboxylic acid indicate that it is sharply increased by ring formation.     

革兰氏阴性菌亚铁离子转运系统的组成及作用机制

几乎所有细菌的生长都离不开铁元素。在有氧的环境中,三价铁离子几乎无法被细菌直接利用。但是在宿主胃肠道中,铁元素主要以可溶性的亚铁离子形式存在,它们可通过革兰氏阴性菌外膜直接进入胞周质,在周质通过亚铁离子转运系统,将铁离子转运至胞浆供细菌利用。绝大多数阴性菌主要是通过Feo转运系统利用亚铁离子,大肠杆菌的Feo转运系统由feoA、feoB和feoC3个基因组成。除Feo转运系统外,还发现Yfe转运系统、Efe转运系统、Sit转运系统等。本文重点介绍革兰氏阴性菌Feo转运系统的组成及作用机制,以期为进一步研究细菌亚铁离子的转运机制提供参考。     

Controlling the ratchet effect through the symmetries of the systems: application to molecular motors

We discuss a novel generic mechanism for controlling the ratchet effect through the breaking of relevant symmetries. We review previous works on ratchets where directed transport is induced by the breaking of standard temporal symmetries f(t)=-f(t+T/2) and f(t)=f(-t) (or f(t)=-f(-t)). We find that in seemingly unrelated systems the average velocity (or the current) of particles (or solitons) exhibits common features. We show that, as a consequence of Curie's symmetry principle, the average velocity (or the current) is related to the breaking of the symmetries of the system. This relationship allows us to control the transport in a systematic way. The qualitative agreement between the present analytical predictions and previous experimental, numerical, and theoretical results leads us to suggest that for the given breaking of the temporal symmetries there is an optimal wave form for a given time-periodic force. Also, we comment on how this mechanism can be applied to the case where a ratchet effect is induced by breaking of spatial symmetries. Finally, we conjecture that the ratchet potential underlying biological motor proteins might be optimized according to the breaking of the relevant symmetries.