Ecological correlates of population density and behavior in the circumtropical black triggerfish Melichthys niger (Balistidae)

The remarkable swarming of black triggerfish Melichthys niger (Balistidae) on oceanic islands led us to undertake a comparative ecological study of high-density and low-density populations of this unusual circumtropical species. Abundance, distribution, and aggressive encounters were recorded in the field from the high-density Johnston Atoll (JA) population, the low-density Belize (BE) population, and a local high-density aggregation from Puerto Rico (PR). JA and PR populations of M. niger occurred at significantly higher densities and were more aggregated than in BE. Intraspecific aggression (chases/min/fish) was an order of magnitude higher in BE than in JA, while interspecific aggression was similar among sites. Size frequency, growth rate, diet composition, body condition (liver-somatic index LSI) were assessed from collected specimens. JA grew more slowly than BE as determined by back-calculations from dorsal spine rings, suggesting density-dependent growth limitation. Size frequency analysis reflected this difference with significantly more large fish in the BE sample. Maximum age of triggerfish in both populations was estimated at 11 years, and 35–40% of growth occurred in the first year. Diet composition was similar in all three locations and indicated broad omnivory. Percent organic composition of gut contents (food quality measure) and LSI (body condition assay) were both significantly higher in the PR population, but no difference was detected between JA and BE. An increase in consumption of algae on the degraded PR reef may explain this pattern.     

Equality of average and steady-state levels in some nonlinear models of biological oscillations

Nonlinear oscillatory systems, playing a major role in biology, do not exhibit harmonic oscillations. Therefore, one might assume that the average value of any of their oscillating variables is unequal to the steady-state value. For a number of mathematical models of calcium oscillations (e.g. the Somogyi–Stucki model and several models developed by Goldbeter and co-workers), the average value of the cytosolic calcium concentration (not, however, of the concentration in the intracellular store) does equal its value at the corresponding unstable steady state at the same parameter values. The average value for parameter values in the unstable region is even equal to the level at the stable steady state for other parameter values, which allow stability. This holds for all parameters except those involved in the net flux across the cell membrane. We compare these properties with a similar property of the Higgins–Selkov model of glycolytic oscillations and two-dimensional Lotka–Volterra equations. Here, we show that this equality property is critically dependent on the following conditions: There must exist a net flux across the model boundaries that is linearly dependent on the concentration variable for which the equality property holds plus an additive constant, while being independent of all others. A number of models satisfy these conditions or can be transformed such that they do so. We discuss our results in view of the question which advantages oscillations may have in biology. For example, the implications of the findings for the decoding of calcium oscillations are outlined. Moreover, we elucidate interrelations with metabolic control analysis. This paper is dedicated to the memory of the late Reinhart Heinrich, who was the academic teacher of S.S. and, to a great extent, also of M.M.     

Modulation of cell surface iron transferrin receptors by cellular density and state of activation

This report describes investigations of plasma membrane transferrin receptors on a variety of lymphoid cell lines and normal peripheral blood lymphocytes during activation and cell growth cycles. Transformed lymphoid cell lines have as many as 1,000 times the number of receptors found on normal resting lymphocytes. The number of iron transferrin receptors on continuous cell lines as well as normal human fibroblasts is down-regulated during the transition from log-phase growth to stationary plateau growth. When normal lymphocytes are transformed by mixed lymphocyte culture or mitogens, they rapidly express a 50-fold increase in the number of transferrin binding sites. This appearance of iron transferrin receptors anticipates nuclear changes during cell activation and subsequent mitosis of normal cells.     

The influence of cellular and lipoprotein cholesterol contents on the flux of cholesterol between fibroblasts and high density lipoprotein

Previous studies indicate that free cholesterol moves passively between high density lipoprotein (HDL) and cell plasma membranes by uncatalyzed diffusion of cholesterol molecules in the extracellular aqueous phase. By this mechanism, the rate constants for free cholesterol influx (Cli) and efflux (ke) should not be very sensitive to the free cholesterol content of cells or HDL. Thus, at a given HDL concentration, the unidirectional influx and efflux of cholesterol mass (Fi, Fe) should be proportional to the cholesterol content of HDL and cells, respectively, and net efflux of cholesterol mass (Fe-Fi greater than 0) should occur when either cells are enriched with cholesterol or HDL is depleted of cholesterol. We have examined the influence of cell and HDL free cholesterol contents on the bidirectional flux of free cholesterol between HDL and human fibroblasts and also attempted to detect some dependence of flux on the binding of HDL to the cells. In the range of HDL concentrations from 1 to 1000 micrograms of protein/ml, ke for cell free cholesterol approximately doubled for every 10-fold increase in HDL concentration, reaching 0.04 h-1 at 1000 micrograms of HDL/ml. ke and Cli were not influenced by the doubling of fibroblast free cholesterol content (from 31 +/- 5 to 62 +/- 13 micrograms of cholesterol/mg of protein). There was an approximate exchange of cholesterol between HDL and the unenriched fibroblasts (e.g. at [HDL] = 100 micrograms/ml, Fe and Fi = 3.2 and 3.0 micrograms of cholesterol/[4 h.mg of cell protein], respectively). In contrast, there was substantial net efflux from the enriched cells (at [HDL] = 100 micrograms/ml, Fe and Fi = 5.5 and 3.1 micrograms of cholesterol/[4 h.mg of cell protein], respectively). The rate constants for cholesterol flux were not influenced by changing the free cholesterol content of HDL, so that there was net efflux of cell cholesterol in the presence of cholesterol-depleted HDL and net influx from cholesterol-rich HDL. The Kd of HDL binding to fibroblasts was reduced from 1.7 to 0.9 micrograms/ml by the enrichment of the cells with free cholesterol; this increase in affinity for HDL was not reflected in enhanced rate constants for cholesterol flux. The inhibition of specific HDL binding by treatment of the lipoprotein with dimethyl suberimidate did not affect cholesterol flux using either control or cholesterol-rich cells at any HDL concentration in the range 1-1000 micrograms/ml. The above results are consistent with the concept that net movement of free cholesterol between cells and HDL occurs by passive, mass-action effects.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of density-dependent dispersal in source-sink dynamics

I investigate two aspects of source-sink theory that have hitherto received little attention: density-dependent dispersal and the cost of dispersal to sources. The cost arises because emigration reduces the per capita growth rate of sources, thus predisposing them to extinction. I show that source-sink persistence depends critically on the interplay between these two factors. When the emigration rate increases with abundance at an accelerating rate, dispersal costs to sources is the lowest and risk of source-sink extinction the least. When the emigration rate increases with abundance at a decelerating rate, dispersal costs to sources is the highest and the risk of source-sink extinction the greatest. Density-independent emigration has an intermediate effect. Thus, density-dependent dispersal per se does not increase or decrease source-sink persistence relative to density-independent dispersal. The exact mode of dispersal is crucial. A key point to appreciate is that these effects of dispersal on source-sink extinction arise from the temporal density-dependence that dispersal induces in the per capita growth rates of source and sink populations. Temporal density-dependence due to dispersal is beneficial at low abundances because it rescues sinks from extinction, and detrimental at high abundances because it drives otherwise viable sources to extinction. These results are robust to the nature of population dynamics in the sink, whether exponential or logistic. They provide a means of assessing the relative costs and benefits of preserving sink habitats given three biological parameters.     

ODE,RDE and SDE models of cell cycle dynamics and clustering in yeast

Biologists have long observed periodic-like oxygen consumption oscillations in yeast populations under certain conditions, and several unsatisfactory explanations for this phenomenon have been proposed. These ‘autonomous oscillations’ have often appeared with periods that are nearly integer divisors of the calculated doubling time of the culture. We hypothesize that these oscillations could be caused by a form of cell cycle synchronization that we call clustering. We develop some novel ordinary differential equation models of the cell cycle. For these models, and for random and stochastic perturbations, we give both rigorous proofs and simulations showing that both positive and negative growth rate feedback within the cell cycle are possible agents that can cause clustering of populations within the cell cycle. It occurs for a variety of models and for a broad selection of parameter values. These results suggest that the clustering phenomenon is robust and is likely to be observed in nature. Since there are necessarily an integer number of clusters, clustering would lead to periodic-like behaviour with periods that are nearly integer divisors of the period of the cell cycle. Related experiments have shown conclusively that cell cycle clustering occurs in some oscillating yeast cultures.     

The effects of EGF-receptor density on multiscale tumor growth patterns

We studied the effects of epidermal growth factor receptor (EGFR) density on tumor growth dynamics, both on the sub- and the multi-cellular level using our previously developed model. This algorithm simulates the growth of a brain tumor using a multi-scale two-dimensional agent-based approach with an integrated transforming growth factor alpha (TGFalpha) induced EGFR-gene-protein interaction network. The results confirm that increasing cell receptor density correlates with an acceleration of the tumor system's spatio-temporal expansion dynamics. This multicellular behavior cannot be explained solely on the basis of spatial sub-cellular dynamics, which remain qualitatively similar amongst the three glioma cell lines investigated here in silico. Rather, we find that cells with higher EGFR density show an early increase in the phenotypic switching activity between proliferative and migratory traits, linked to a higher level of initial auto-stimulation by the PLCgamma-mediated TGFalpha-EGFR autocrine network. This indicates a more active protein level interaction in these chemotactically acting tumor systems and supports the role of post-translational regulation for the implemented EGFR pathway. Implications of these results for experimental cancer research are discussed.     

Optimal cytoplasmatic density and flux balance model under macromolecular crowding effects

Macromolecules occupy between 34% and 44% of the cell cytoplasm, about half the maximum packing density of spheres in three dimension. Yet, there is no clear understanding of what is special about this value. To address this fundamental question we investigate the effect of macromolecular crowding on cell metabolism. We develop a cell scale flux balance model capturing the main features of cell metabolism at different nutrient uptakes and macromolecular densities. Using this model we show there are two metabolic regimes at low and high nutrient uptakes. The latter regime is characterized by an optimal cytoplasmatic density where the increase of reaction rates by confinement and the decrease by diffusion slow-down balance. More important, the predicted optimal density is in the range of the experimentally determined density of Escherichia coli.     

Kinetic isotope effects significantly influence intracellular metabolite 13C labeling patterns and flux determination

Rigorous mathematical modeling of carbon-labeling experiments allows estimation of fluxes through the pathways of central carbon metabolism, yielding powerful information for basic scientific studies as well as for a wide range of applications. However, the mathematical models that have been developed for flux determination from ¹³C labeling data have commonly neglected the influence of kinetic isotope effects on the distribution of ¹³C label in intracellular metabolites, as these effects have often been assumed to be inconsequential. We have used measurements of the ¹³C isotope effects on the pyruvate dehydrogenase enzyme from the literature to model isotopic fractionation at the pyruvate node and quantify the modeling errors expected to result from the assumption that isotope effects are negligible. We show that under some conditions kinetic isotope effects have a significant impact on the ¹³C labeling patterns of intracellular metabolites, and the errors associated with neglecting isotope effects in ¹³C-metabolic flux analysis models can be comparable in size to measurement errors associated with GC–MS. Thus, kinetic isotope effects must be considered in any rigorous assessment of errors in ¹³C labeling data, goodness-of-fit between model and data, confidence intervals of estimated metabolic fluxes, and statistical significance of differences between estimated metabolic flux distributions.     

Combining Gompertzian growth and cell population dynamics

A two-compartment model of cancer cells population dynamics proposed by Gyllenberg and Webb includes transition rates between proliferating and quiescent cells as non-specified functions of the total population, N. We define the net inter-compartmental transition rate function: Phi(N). We assume that the total cell population follows the Gompertz growth model, as it is most often empirically found and derive Phi(N). The Gyllenberg-Webb transition functions are shown to be characteristically related through Phi(N). Effectively, this leads to a hybrid model for which we find the explicit analytical solutions for proliferating and quiescent cell populations, and the relations among model parameters. Several classes of solutions are examined. Our model predicts that the number of proliferating cells may increase along with the total number of cells, but the proliferating fraction appears to be a continuously decreasing function. The net transition rate of cells is shown to retain direction from the proliferating into the quiescent compartment. The death rate parameter for quiescent cell population is shown to be a factor in determining the proliferation level for a particular Gompertz growth curve.     

视觉和嗅觉密度信号对布氏田鼠社会应激的影响

鼠类具有密度依赖的行为—内分泌反馈调节机制:当其种群密度升高时,会产生社会应激,增加紧张焦虑、攻击等行为,同时其神经内分泌也产生相应变化.然而,密度升高引起的社会应激可能涉及到视觉、嗅觉、触觉、听觉、味觉等不同感官,而不同感官对社会应激反应产生的独特作用尚不清楚.我们以前的研究发现,高密度饲养可导致雄性布氏田鼠脑部催产...     

The effects of phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin on cellular glucose transport

Glucose is the principal fuel for brain metabolism and its movement across the blood-brain barrier depends on Glut1. Impaired glucose transport to the brain may have deleterious consequences. For example, Glut1 deficiency syndrome (Glut1DS) is the result of heterozygous loss of function Glut1 mutation leading to energy failure of the brain and subsequently, epileptic encephalopathy. To preserve the integrity of the energy supply to the brain in patients with compromised glucose transport function, consumption of compounds with glucose transport inhibiting properties should be avoided. Phenytoin is a widely used anticonvulsant that affects carbohydrate metabolism. In this study, the hypothesis that phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) affect cellular glucose transport was tested. With a focus on Glut1, the effects of phenytoin and HPPH on cellular glucose transport were studied. Glucose uptake assay measuring the zero-trans influx of radioactive-labeled glucose analogues showed that phenytoin and HPPH did not exert immediate effects on erythrocyte Glut1 activity or glucose transport in Hs68 control fibroblasts, Glut1DS primary fibroblasts isolated from two patients, or in rat primary astrocytes. Prolonged exposure to the two compounds could stimulate glucose transport by up to 30-60% over the control level (p <0.05) in Hs68 and Glut1DS fibroblasts as well as in rat astrocytes. The stimulation of glucose transport by HPPH was dose-dependent and accompanied by an up-regulation of GLUT1 mRNA expression (p <0.05). In conclusion, phenytoin and HPPH do not compromise cellular glucose transport. Prolonged exposure to these compounds can modify carbohydrate homeostasis by up-regulating glucose transport in both normal and Glut1DS conditions in vitro.     

黄土丘陵半干旱区柠条林密度对土壤水分和柠条生长的影响

研究密度对土壤水分和植物生长的影响对森林植被恢复和生态建设具有重要的意义。以黄土丘陵半干旱区人工柠条为研究对象,对相同立地条件下不同密度柠条林生长与林地土壤水分进行了长期定位观测和分析。研究表明,1—5年生柠条不同密度林地土壤水资源量差异显著,从第3年开始,土壤水资源量随着密度增加而增加;10—12年生柠条密度越低土壤水资源量越高(Treatment4除外,T4),不同密度之间水资源量差异不显著。1—3年生柠条密度越高会促进其株高生长;从第四年开始,柠条密度过高会抑制其株高生长;1—5年生柠条密度越高基径生长越快,不同密度生长差异不显著;10—12年生密度过高(Treatment1,T1)或过低(T4)均会抑制柠条株高与基径生长。在柠条播种后第5年,高密度试验小区(T1和Treatment2,T2)柠条林地最大入渗深度土壤水资源量降到水资源利用限度,此时需要依据土壤水分植被承载力通过平茬来降低林分密度,以达到减少土壤水分消耗和可持续利用土壤水资源之目的。     

Continuous photoautotrophic cultures of the eukaryotic alga Chlorella vulgaris can exhibit stable oscillatory dynamics

Sustained oscillations in cell concentration, average per cell DNA content, and average cell size were found in continuous photoautotrophic cultures of Chlorella vulgaris at low dilution rates (0.1/day). The period of oscillation was approximately 10 days. DNA histograms determined by flow cytometry exhibited reproducible pattern through consecutive oscillations. At the maximum cell concentration during an oscillation, the DNA histograms showed that the majority of the cells were not replicating their chromosomes, and most of the culture was comprised of single cells in G0/G1 phase. The cells then initiated DNA replication; however, because of the long generation time, the cell concentration decreased to a minimum, and at the same time the average per cell DNA content reached its maximum value. At this point the cells began to divide, and the cell concentration increased until it reached its maximum value at the beginning of the next oscillation. Calculations based on the supplied nutrients and comparison to biomass generation showed that the oscillatory behavior in continuous photoautotrophic cultures of C. vulgaris was not due to nutrient limitation, but most likely was due to the secretion of compounds that alter cell cycle kinetics. The oscillatory behavior disappeared when the dilution rate was increased to 0.3/day and the culture reached a stable steady state.     

The effects of cell density and starvation on early developmental events in Dictyostelium discoideum

We show that removal of yeast extract and trypticase from growth medium is sufficient for induction of several key events which occur during the early stages of Dictyostelium differentiation: run-off of polysomes, the earliest known change in macromolecular metabolism; appearance of the cell surface cAMP receptor; and aggregation itself. Starvation of glucose has little effect on these parameters. These results are consistent with those of other investigators who showed that starvation only of amino acids will induce other activities associated with cAMP-mediated cell signaling and cell-cell adhesion. We show, in contrast, that other factors are involved in the increase in the relative rates of synthesis of three polypeptides very early in differentiation: actin, and two proteins (“45-min” proteins) which are synthesized only during the period of 45–90 min. The induction of synthesis of these three proteins and presumably, of their mRNAs, is not the result of starvation for glucose or amino acids but is the result of plating cells at high density. The increases in the synthesis of these proteins are dependent on the density at which cells are plated and do not occur at a density 75-fold lower than the density used in standard experiments. Cells growing at high density or near stationary phase do not show the induction of increased synthesis of actin or the “45-min” proteins. These experiments suggest that these early developmental changes may be dependent on a threshold level of a diffusible factor excreted early in development.     

FTIR spectra signatures reveal different cellular effects of EGFR inhibitors on nonsmall cell lung cancer cells

ATP‐analogue inhibitors, Gefitinib (Iressa) and Erlotinib (Tarceva) had been approved for advanced and metastatic nonsmall cell lung cancer (NSCLC) cells against tyrosine kinase domain of epidermal growth factor receptor (EGFR). Many techniques have been developed to better understand the drug mechanism which is multistep, time‐consuming and expensive. Herein, we performed Fourier‐transform infrared (FTIR) microscopy for evaluating the biochemical change on NSCLC (A549) cells after treatment. At levels that produced equivalent effects, Gefitinib dramatically induced cell apoptosis via impaired mitochondrial transmembrane potential. Whereas, Erlotinib had a slight effect on A549. Principal component analysis was performed to distinguish the effect of EGFR inhibitors on A549. FTIR spectra regions were divided into three regions: lipids (3000‐2800 cm^?1), proteins (1700‐1500 cm^?1) and carbohydrates and nuclei acids (1200‐1000 cm^?1). Biochemical changes can be evaluated by these spectral regions. This work may be a novel concept for utilizing FTIR spectroscopy for high‐throughput discriminative effects of a drug or compound and its derivatives on cells.     

细胞生长因子对冠状动脉内皮细胞增殖与迁移的影响

目的 :观察肝细胞生长因子 (HGF)和血管内皮细胞生长因子 (VEGF)对体外培养牛冠状动脉内皮细胞(BCAEC)增殖、迁移的影响。方法 :分离和培养BCAEC ,设对照组、VEGF组、HGF组。采用四甲基偶氮唑蓝法(MTT)观察细胞增殖 ;倒置显微镜观察培养的血管内皮细胞的迁移。结果 :对照组、VEGF组、HGF组的OD值分别为 0 .2 2± 0 .0 1、0 .40± 0 .1 4、0 .44± 0 .1 5 ;VEGF组、HGF组BCAEC的增殖率分别为 81 .8%± 1 6 .9%、1 0 0 %±2 1 .1 % ;对照组BCAEC迁移不明显 ,而VEGF组和HGF组BCAEC迁移明显。结论 :VEGF、HGF能促进BCAEC增殖、迁移 ,HGF作用强度不亚于VEGF。     

Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy

B cell immunotherapy has emerged as a mainstay in the treatment of lymphomas and autoimmune diseases. Although the microenvironment has recently been demonstrated to play critical roles in B cell homeostasis, its contribution to immunotherapy is unknown. To analyze the in vivo factors that regulate mechanisms involved in B cell immunotherapy, we used a murine model for human CD20 (hCD20) expression in which treatment of hCD20(+) mice with anti-hCD20 mAbs mimics B cell depletion observed in humans. We demonstrate in this study that factors derived from the microenvironment, including signals from the B cell-activating factor belonging to the TNF family/BLyS survival factor, integrin-regulated homeostasis, and circulatory dynamics of B cells define distinct in vivo mechanism(s) and sensitivities of cells in anti-hCD20 mAb-directed therapies. These findings provide new insights into the mechanisms of immunotherapy and define new opportunities in the treatment of cancers and autoimmune diseases.     

Prohibitin对非小细胞肺癌细胞增殖和凋亡的影响

目的:研究Prohibitin对非小细胞肺癌株A549和NCI-H460细胞增殖和凋亡的影响.方法:将针对Prohibitin的特异性的干扰片段瞬时转染非小细胞肺癌A549和NCI-H460细胞株,以瞬时转染与Prohibitin没有同源性的干扰片段的细胞作为阴性对照,通过免疫蛋白印迹检测各组细胞Prohibitin和Survivin蛋白的表达情况,通过MTT法检测各组细胞的增殖情况,通过流式仪检测各组细胞的凋亡率.结果:针对Prohibitin基因设计的siRNA片段特异性地沉默该基因的表达,与对照组相比较,干扰组的细胞的增殖活性明显增强.同时与凋亡密切相关的Survivin的表达在沉默掉prohibitin后,在A549和NCI-H460中分别降低了46.3%和54.5%.而干扰prohibitin后导致A549细胞的凋亡率上升了约2%.结论:Prohibitin能显著抑制非小细胞肺癌A549和NCI-H460细胞的增殖,而对凋亡的影响可能并不是通过survivin介导的.     

The effects of cell population density on the plasma membrane of Acanthamoeba castellanii

Plasma membranes were isolated from both exponential and stationary phase cells and their properties compared, to determine whether alterations are sustained coincident with the transition to plateau phase growth. Polyacrylamide gel electrophoresis revealed no significant differences in macromolecular composition between the two types of membrane. However, the specific activity of alkaline phosphatase (EC 3.1.3.1), an enzyme which shows enrichments in purified plasma membrane fractions relative to homogenates, was markedly reduced in preparations from stationary as compared with exponentially growing cells. The total activity per cell did not change, but in cell fractionation experiments the stationary phase cells yielded a higher proportion of the enzyme in microsomal fractions than did exponentially growing cells. This indicates that once plateau phase is attained, a greater proportion of the membrane bearing alkaline phosphatase activity is internalized as opposed to being associated with the plasmalemma.Alkaline phosphatase is known to be present on the contractile vacuole membrane. During discharge this vacuole becomes associated with the plasmalemma, an event which presumably accounts for at least part of the alkaline phosphatase in plasma membrane preparations. Thus one interpretation of the decreased levels of alkaline phosphatase in plasma membrane fractions from stationary phase cells is that they reflect a decline in the rate of water expulsion. This in turn suggests that the plasmalemma of stationary phase cells may have undergone changes leading to a decreased rate of water influx.