Autogenous Formation of Spiral Waves by Coupled Chaotic Attractors

When large arrays of strange attractors are coupled diffusively through one of the variables, chaotic systems become periodic and form large archimedean spirals or concentric bands. This observation may have importance for many applications in the field of deterministic chaos and seems particularly relevant to the question of the formal temporal structure of the biological clock in metazoan organisms. In particular, although individual cellular oscillators, as manifested in the cell cycle, may have deep basins of attraction and appear to be more or less periodic, we suggest that cells oscillate with chaotic dynamics in the ultradian domain. Only when large aggregates of these cells are tightly coupled can a precise circadian clock emerge. For changing coupling strength or parameter values, period increase occurs through quantal or integral multiple increments of the fundamental. All calculations were implemented on a 386AT, using a Mercury MC6400 floating point processor.     

Autogenous Formation of Spiral Waves by Coupled Chaotic Attractors

When large arrays of strange attractors are coupled diffusively through one of the variables, chaotic systems become periodic and form large archimedean spirals or concentric bands. This observation may have importance for many applications in the field of deterministic chaos and seems particularly relevant to the question of the formal temporal structure of the biological clock in metazoan organisms. In particular, although individual cellular oscillators, as manifested in the cell cycle, may have deep basins of attraction and appear to be more or less periodic, we suggest that cells oscillate with chaotic dynamics in the ultradian domain. Only when large aggregates of these cells are tightly coupled can a precise circadian clock emerge. For changing coupling strength or parameter values, period increase occurs through quantal or integral multiple increments of the fundamental. All calculations were implemented on a 386AT, using a Mercury MC6400 floating point processor.     

Spontaneous behaviour,training and discrimination training in goldfish using chemosensory stimuli

The present behavioural experimental paradigm made use of the responsiveness of goldfish to natural and non-familiar chemosensory stimuli in the context of feeding. With the exception of Tubifex food extract, which was spontaneously preferred, goldfish exhibited no spontaneously recordable response to low concentrations of the stimuli tested. Training experiments using non-familiar stimuli (amyl acetate, -ionone, -phenylethanol, 10^-6, 10^-7 M) required 2–3 months of daily training prior to the animals reaching a 70% positive response level for discrimination. This discrimination was dependent upon a functioning olfactory system as no responses were recorded after bilateral exclusion of olfaction, e.g. dissection of olfactory nerve or olfactory tracts. Amino acids (Ala, Arg, Gln, Gly, Lys), more natural stimuli than those listed above, were preferred when applied at concentrations < 10^-5 M. Goldfish were able to discriminate amino acid odours applied at 10^-6 or 10^-7 M, but these stimuli elicited no spontaneous response below 10^-5 M. Ten to twenty reinforcements were sufficient to achieve discrimination between amino acids, which again was eliminated after bilateral exclusion of olfactory pathways. In contrast to the 4-week period for long-term memory to non-familiar odours, long-term memory for amino acids lasted at least 3 months.Abbreviations FB funnel biting - FO funnel orientation     

Orderly inactivation of the key checkpoint protein mitotic arrest deficient 2 (MAD2) during mitotic progression

Anaphase is promoted by the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) only when all the chromosomes have achieved bipolar attachment to the mitotic spindles. Unattached kinetochores or the absence of tension between the paired kinetochores activates a surveillance mechanism termed the spindle-assembly checkpoint. A fundamental principle of the checkpoint is the activation of mitotic arrest deficient 2 (MAD2). MAD2 then forms a diffusible complex called mitotic checkpoint complex (designated as MAD2(MCC)) before it is recruited to APC/C (designated as MAD2(APC/C)). Large gaps in our knowledge remain on how MAD2 is inactivated after the checkpoint is satisfied. In this study, we have investigated the regulation of MAD2-containing complexes during mitotic progression. Using selective immunoprecipitation of checkpoint components and gel filtration chromatography, we found that MAD2(MCC) and MAD2(APC/C) were regulated very differently during mitotic exit. Temporally, MAD2(MCC) was broken down ahead of MAD2(APC/C). The inactivation of the two complexes also displayed different requirements of proteolysis; although APC/C and proteasome activities were dispensable for MAD2(MCC) inactivation, they are required for MAD2(APC/C) inactivation. In fact, the degradation of CDC20 is inextricably linked to the breakdown of MAD2(APC/C). These data extended our understanding of the checkpoint complexes during checkpoint silencing.     

RED, a spindle pole-associated protein, is required for kinetochore localization of MAD1, mitotic progression, and activation of the spindle assembly checkpoint

The spindle assembly checkpoint (SAC) is essential for ensuring the proper attachment of kinetochores to the spindle and, thus, the precise separation of paired sister chromatids during mitosis. The SAC proteins are recruited to the unattached kinetochores for activation of the SAC in prometaphase. However, it has been less studied whether activation of the SAC also requires the proteins that do not localize to the kinetochores. Here, we show that the nuclear protein RED, also called IK, a down-regulator of human leukocyte antigen (HLA) II, interacts with the human SAC protein MAD1. Two RED-interacting regions identified in MAD1 are from amino acid residues 301-340 and 439-480, designated as MAD1(301-340) and MAD1(439-480), respectively. Our observations reveal that RED is a spindle pole-associated protein that colocalizes with MAD1 at the spindle poles in metaphase and anaphase. Depletion of RED can cause a shorter mitotic timing, a failure in the kinetochore localization of MAD1 in prometaphase, and a defect in the SAC. Furthermore, the RED-interacting peptides MAD1(301-340) and MAD1(439-480), fused to enhanced green fluorescence protein, can colocalize with RED at the spindle poles in prometaphase, and their expression can abrogate the SAC. Taken together, we conclude that RED is required for kinetochore localization of MAD1, mitotic progression, and activation of the SAC.     

Solvent toxicity in organic-aqueous systems analysed by multivariate analysis

The effect of several solvents present in a biphasic reaction system on cells of Rhodococcus erythropolis DCL14, Xanthobacter Py2, Arthrobacter simplex and Mycobacterium sp. NRRL B-3805 was evaluated. These four strains have been widely exploited, from bioremediation to the production of fine chemicals, in two-phase reaction media. The solvents tested were ethyl butyrate, n-hexane, cyclohexane, iso-octane, n-dodecane, DMSO, bis(2-ethylhexyl) phthalate and fluorinert FC-70. The cell population was monitored by fluorescence microscopy and analysis of the images captured provided single-cell-level information on cell viability, morphological factors of both viable and non-viable cells, and on the number of viable cells in clusters. These data, and those concerning the initial carveol concentration, the carbon source used during growth, the adaptation time to the solvent prior to substrate addition, and the properties of the organic solvent, were interpreted using principal components analysis (PCA). For R. erythropolis, X. Py2, and A. simplex, between 70.1 and 80.4% of the variability of the data could be explained by six principal components, while 86.7% of the variance in the results obtained with Mycobacterium sp. could be represented by seven principal components. In all cases, solvent toxicity could explain over a third of the variability in the data. R. erythropolis cells were able to maintain their viability under harsh conditions. A period of contact between cells and solvent, prior to the addition of substrate, was prejudicial for R. erythropolis and A. simplex cells, at least for the most toxic solvents, but was beneficial for X. Py2 cells. The number of Mycobacterium sp. cells in clusters was lower after an adaptation period compared to the number of cells in aggregates when the substrate was added at time zero. The substrates transformed by R. erythropolis and A. simplex cells increased the toxicity of the system by decreasing the log P of the reaction mixture. Hydrocortisone was responsible for a reduction in the ability of A. simplex to respond to stress conditions. Mycobacterium sp. cells were apparently unaffected by -sitosterol. The results obtained are useful for the design of more efficient two-phase reaction systems where solvent toxicity may be overcome in order to increase cell productivity.Paper presented at the International Conference on Trends in Monitoring and Control of Life Science Applications, 7–8 October 2002, Lyngby, Denmark.     

Analysis and description of the evolution of alginate immobilised cells systems

Different immobilised cells models, including very simple ones, can be useful in the fitting of experimental results. However, goodness or the ability to extrapolate results needs to be in accordance with basic observations and these will also suggest models to be proposed. In this paper, observations of calcium alginate/bacteria systems are used to show the ability of basic models to fit classic observations, as well as how new observations, in this case from electronic microscopy, oblige us to think about more complex mechanisms and mathematical treatments. Nevertheless it is not only important to discuss the model type, but also the type of kinetics assumed in the interior of the beads, as well as the internal structure, the boundary conditions related to bead shredding and cell escape and finally, geometrical effects.     

Monocyte cytokine synthesis in response to extracellular cell stress proteins suggests these proteins exhibit network behaviour

Human peripheral blood monocytes were exposed to single or pairs of cell stress proteins (CSPs), specifically Hsp10, Hsp27, Hsp60 and Hsp70—the former two having anti-inflammatory actions while the latter pair being assumed to be pro-inflammatory in activity. This study was to test if these proteins exhibited any network behaviour. To control for possible lipopolysaccharide contamination, polymyxin B was used. Surprisingly, at concentrations higher than 1 μg/ml, polymyxin B itself could induce cytokine synthesis. A number of commercial sources of the molecular chaperones were tested, and marked variations in monocyte cytokine synthesis were found. All four CSPs stimulated the same profile of IL-1/IL-6 synthesis and IL-10/TNF-α synthesis although the kinetics of production of these two pairs of cytokines were very different. A key question was whether extracellular molecular chaperones exhibited network behaviour. To test this, monocytes were cultured with suboptimal concentrations of single CSP and pairs of CSP to look for additive, synergistic or antagonistic cell responses. The major finding was that pairs of molecular chaperones, including chaperones thought to stimulate monocyte cytokine synthesis, could produce significant antagonistic cellular responses. This demonstrates that extracellular CSPs constitute an additional potent layer within the complex cytokine network and furthermore suggests that monocytes have evolved to dampen their immune responses upon exposure to extracellular networks of CSPs—perhaps as a mechanism for protecting cells against detrimental cellular stress responses.     

Cell behaviour in tubes

The motile behaviour, growth and reactions of osteoblasts, chondrocytes, epitenal cells and endothelia to culture on extended concave surfaces inside tubes is reported. Time-lapse video observations show that these cells can be successfully grown in quartz tubes for up to 21days. The cells would attach to the concave surfaces even when the radius of curvature was as low as 25 μm. The cells attached to the walls were not oriented. As culturing progressed the chondrocytes, osteoblasts and epitenon cells tended to detach from the walls of the tubes, forming long cords of cells attached to the walls at a few points only. Endothelial cells did not detach. These cords showed extensive lamellipodial activity at their points of attachment to the tube wall. The cells in these cords do not show contact inhibition of movement.Electronic supplementary material Electronic supplementary material is available for this article at and accessible for authorised users.     

G418抗性HEK293细胞的培育

目的　培育具有G418抗性的HEK2 93细胞 ,用于建立猪内源性反转录病毒感染人HEK2 93细胞的模型。方法　通过脂质体转染的方法 ,将含有neo基因的质粒pIRESneo导入HEK2 93细胞中 ,利用G418的选择特性 ,对转染细胞进行压力筛选 ,并对其进行了PCR鉴定。结果　经 6 0 0 μg ml的G418压力筛选后 ,获得了抗性细胞克隆。抗性细胞的形态和生长速度与筛选前细胞没有差异 ,特异性核苷酸引物检测抗性细胞基因组DNA ,可以扩增出对应的核苷酸片段。结论　成功地培育了G418抗性HEK2 93细胞 ,为建立猪内源性反转录病毒感染人HEK2 93细胞的模型奠定了基础。     

The joy of sex pheromones

Sex pheromones provide an important means of communication to unite individuals for successful reproduction. Although sex pheromones are highly diverse across animals, these signals fulfil common fundamental roles in enabling identification of a mating partner of the opposite sex, the appropriate species and of optimal fecundity. In this review, we synthesize both classic and recent investigations on sex pheromones in a range of species, spanning nematode worms, insects and mammals. These studies reveal comparable strategies in how these chemical signals are produced, detected and processed in the brain to regulate sexual behaviours. Elucidation of sex pheromone communication mechanisms both defines outstanding models to understand the molecular and neuronal basis of chemosensory behaviours, and reveals how similar evolutionary selection pressures yield convergent solutions in distinct animal nervous systems.EMBO reports advance online publication 13 September 2013; doi:10.1038/embor.2013.140     

Ataxia Telangiectasia-mutated- and Rad3-related Protein Regulates the DNA Damage-induced G2/M Checkpoint through the Aurora A Cofactor Bora Protein

Polo-like kinase1 (Plk1) activation is inhibited in response to DNA damage, and this inhibition contributes to the activation of the G₂/M checkpoint, although the molecular mechanism by which Plk1 is inhibited is not clear. Here we report that the DNA damage signaling pathway inhibits Plk1 activity through Bora. Following UV irradiation, ataxia telangiectasia-mutated- and Rad3-related protein phosphorylates Bora at Thr-501. The phosphorylated Thr-501 is subsequently recognized by the E3 ubiquitin ligase SCF-β-TRCP, which targets Bora for degradation. The degradation of Bora compromises Plk1 activation and contributes to DNA damage-induced G₂ arrest. These findings shed new light on Plk1 regulation by the DNA damage response pathway.     

A note on a quantitative genetic approach for modelling of differentiation tasks

Learning capacities and cognitive abilities of farm animals will become more important and they will have an impact on animal welfare and productivity. Scientific examinations of these aspects presuppose genetic models. This paper presents an approach for modelling differentiation tasks in animal learning on a quantitative genetic basis. The approach links the likelihood function, to make a correct decision, with the two-dimensional density function, capable to be to decide right. The proposed model is able to depict several situations in learning processes of populations. Its parameters characterize the theoretical course of the learning process and also the stage of learning which a population has reached. The approach can be used to estimate parameters of a learning process and of the genetic disposition to learn, to estimate breeding values of learning capacity and to fit models on population's learning capability under selection.     

Do lipids shape the eukaryotic cell cycle?

Successful passage through the cell cycle presents a number of structural challenges to the cell. Inceptive studies carried out in the last five years have produced clear evidence of modulations in the lipid profile (sometimes referred to as the lipidome) of eukaryotes as a function of the cell cycle. This mounting body of evidence indicates that lipids play key roles in the structural transformations seen across the cycle. The accumulation of this evidence coincides with a revolution in our understanding of how lipid composition regulates a plethora of biological processes ranging from protein activity through to cellular signalling and membrane compartmentalisation. In this review, we discuss evidence from biological, chemical and physical studies of the lipid fraction across the cell cycle that demonstrate that lipids are well-developed cellular components at the heart of the biological machinery responsible for managing progress through the cell cycle. Furthermore, we discuss the mechanisms by which this careful control is exercised.     

An in silico investigation into the causes of telomere length heterogeneity and its implications for the Hayflick limit

In telomerase-negative cell populations the mean telomere length (TL) decreases with increasing population doubling number (PD). A critically small TL is believed to stop cell proliferation at a cell-, age- and species-specific PD thus defining the Hayflick limit. However, positively skewed TL distributions are broad compared to differences between initial and final mean TL and strongly overlap at middle and late PD, which is inconsistent with a limiting role of TL. We used computer-assisted modelling to define what set of premises may account for the above. Our model incorporates the following concepts. DNA end replication problem: telomeres loose 1 shortening unit (SU) upon each cell division. Free radical-caused TL decrease: telomeres experience random events resulting in the loss of a random SU number within a remaining TL. Stochasticity of gene expression and cell differentiation: cells experience random events inducing mitoses or committing cells to proliferation arrest, the latter option requiring a specified number of mitoses to be passed. Cells whose TL reaches 1SU cannot divide. The proliferation kinetics of such virtual cells conforms to the transition probability model of cell cycle. When no committing events occur and at realistic SU estimates of the initial TL, maximal PD values far exceed the Hayflick limit observed in normal cells and are consistent with the crisis stage entered by transformed cells that have surpassed the Hayflick limit. At intermediate PD, symmetrical TL distributions are yielded. Upon introduction of committing events making the ratio of the rates of proliferating and committing events (P/C) range from 1.10 to 1.25, TL distributions at intermediate PD become positively skewed, and virtual cell clones show bimodal size distributions. At P/C as high as 1.25 the majority of virtual cells at maximal PD contain telomeres with TL>1SU. A 10% increase in P/C within the 1.10-1.25 range produces a two-fold increase in the maximal PD, which can reach values of up to 25 observed in rodent and some human cells. Increasing the number of committed mitoses from 0 to 10 can increases PD to about 50 observed in human fibroblasts. Introduction of the random TL breakage makes the shapes of TL distributions quite dissimilar from those observed in real cells. CONCLUSIONS: Telomere length decrease is a correlate of cell proliferation that cannot alone account for the Hayflick limit, which primarily depends on parameters of cell population kinetics. Free radical damage influences the Hayflick limit not through TL but rather by affecting the ratio of the rates of events that commit cells to mitoses or to proliferation arrest.     

Upgrading of low-boiling fraction of bio-oil in supercritical methanol and reaction network

In this work, the low-boiling fraction (LBF) of bio-oil was used as feed stock. LBF is a very complex mixture, and the three groups in LBF: acids, aldehydes and phenols, are primarily responsible for deterioration in the quality. The upgrading reactions were carried out over Pt/Al₂(SiO₃)₃, Pt/C or Pt/MgO in supercritical methanol. It is demonstrated that supercritical condition can greatly facilitate the esterification process, and after 6 h reaction, all the acids can be converted into esters even without adding any catalyst. The total amount of the three groups left in products was much less exhibited on Pt supported on active carbon and MgO in the presence of hydrogen. By investigating the model reactions, the relations between the representative compounds and major products were identified, and the conversion scheme of the upgrading reactions is proposed.     

The hard cell: from proteomics to a whole cell model

Proteomics has provided a wealth of data related to the nature of the proteome, including subcellular location, copy number, interaction partners and protein complexes. This raises the question of whether it is feasible to combine these data, together with other data related to overall cellular structure, to construct a static picture of the cell. In this minireview, we discuss these data, and the issues of turning them into whole cell models.     

细胞离子在振荡电磁场作用下的受力模型分析

本文通过生物细胞模型,研究振荡电场、振荡磁场以及振荡磁场产生的感应电场对细胞离子的作用机理。模型分析结果表明,电场力和罗仑兹力对细胞膜两侧的自由离子将产生加速度,振荡离子将产生周期性电位移。该模型同时也解释了脉冲电磁场比同参教的连续场产生更多的生物效应,以及连续场在开始施加和切除时的效应最大。