视觉细胞反应中方向选择性和取向选择性成分的分离

运动的光刺激常被用于研究视觉神经细胞的方向和取向选择性.但是,在细胞的反应中,两种因素同时存在且混杂在一起; 以往的各种分析方法均因未能有效地解决这一问题而不够准确,对此我们给出了理论和实例证明.本工作引入正余弦函数系对实验数据作最优回归分析.拟合程度好于以往的方法.并且从根本上分离了反应中的方向和取向选择性成分.使对这两种性质的准确定量成为可能.本文对此方法的内在含义作出了解释,并提出了对方向、取向选择性及最优方向、取向的理解.     

How to unconfound the directional and orientational information in visual neuron's response

When drifting bars or gratings are used as visual stimuli, information about orientation specificity (which has a period of 180°) and direction specificity (which has a period of 360°) is inherently confounded in the response of visual cortical neurons, which have long been known to be selective for both the orientation of the stimulus and the direction of its movement. It is essential to unconfound or separate these two components of the response as they may respectively contribute to form and motion perception, two of the main streams of information processing in the mammalian brain. Wörgötter and Eysel (1987) recently proposed the Fourier transform technique as a method of unconfounding the two components, but their analysis was incomplete. Here we formally develop the mathematical tools for this method to calculate the peak angles, bandwidths, and relative strengths, the three most important elements of a tuning curve, of both the orientational and the directional components, based on the experimentally-recorded neuron's response polar-plot. It will be shown that, in the 1-D Fourier decomposition of the polar-plot along its angular dimension, (1) the odd harmonics contain only the directional component, while the even harmonics are contributed to by both the orientational and the directional components; (2) the phases and the amplitudes of all the harmonics are related, respectively, to the peak angle and the bandwidth of the individual component. The basic assumption used here is that the two components are linearly additive; this in turn is immediately testable by the method itself.     

猫视皮层细胞对运动光棒刺激的反应特性的定量分析

数据分析方法的不完善影响了关于细胞视觉反应特性研究结果的可靠性.本工作在分离视觉反应中方向和取向选择性因素的基础上.采用“积分平均”的手段.且将取向选择性理解为“强度随取向的变化率”,得到一种较为准确全面地表现细胞有关反应特性的定量分析法,可以体现出一些以往各方法无法反映出的差别,我们用此方法分析了猫视皮层细胞对运动光棒刺激的反应特性及其相关性.发现取向选择性因素对总反应的贡献较方向选择性大;反应强度,方向选择性和取向选择性三者间存在着弱相关.最优方向、最优取向及方向选择性最强的方向三者间有一定的偏离.     

Maximum likelihood method for the analysis of time-resolved fluorescence decay curves

The usefulness of fluorescence techniques for the study of macromolecular structure and dynamics depends on the accuracy and sensitivity of the methods used for data analysis. Many methods for data analysis have been proposed and used, but little attention has been paid to the maximum likelihood method, generally known as the most powerful statistical method for parameter estimation. In this paper we study the properties and behavior of maximum likelihood estimates by using simulated fluorescence intensity decay data. We show that the maximum likelihood method provides generally more accurate estimates of lifetimes and fractions than does the standard least-squares approach especially when the lifetime ratios between individual components are small. Three novelties to the field of fluorescence decay analysis are also introduced and studied in this paper: a) discretization of the convolution integral based on the generalized integral mean value theorem: b) the likelihood ratio test as a tool to determine the number of exponential decay components in a given decay profile; and c) separability and detectability indices which provide measures on how accurately, a particular decay component can be detected. Based on the experience gained from this and from our previous study of the Padé-Laplace method, we make some recommendations on how the complex problem of deconvolution and parameter estimation of multiexponential functions might be approached in an experimental setting. Offprint requests to: F. G. Prendergast     

A Statistical Method for Comparison of Two Structures and Its Biological Applications

Some experimental methods applied to biological investigations allow to find a number q of homogeneous discrete components that determine a structure of the object in the study and the to establish the presence of some components from these q in compositions of other n objects. Such data form a nXq incidence matrix. In this paper a statistical approach is suggested for revealing the associated components in two different structures of the object. The procedure is based on joint consideration of two sampling incidence matrices. An application of this method is demonstrated by analysis of relationships between antigens and proteins of one strain of cyanobacteria. The method may be useful in different scientific areas, e.g. psychology, when direct experimental comparison of components from two structures is difficult.     

Genomewide computational analysis of nitrate response elements in rice and Arabidopsis

Nitrate response element (NRE) was originally reported to be comprised of an Ag/cTCA core sequence motif preceded by a 7-bp AT rich region, based on promoter deletion analyses in nitrate and nitrite reductases from Arabidopsis thaliana and birch. In view of hundreds of new nitrate responsive genes discovered recently, we sought to computationally verify whether the above motif indeed qualifies to be the cis-acting NRE for all the responsive genes. We searched for the specific occurrence of at least two copies of the above motif in and around the nitrate responsive genes and elsewhere in the Arabidopsis and rice (Oryza sativa) genomes, with respect to their positional, orientational and strand-specific bias. This is the first comprehensive analysis of NREs for 625 nitrate responsive genes of Arabidopsis and their rice homologs, representing dicots and monocots, respectively. We report that the above motifs are present almost randomly throughout these genomes and do not reveal any specificity or bias towards nitrate responsive genes. This also seems to be true for smaller subsets of nitrate responsive genes in Arabidopsis, such as the 21 early responsive genes, 261 and 90 genes for root-specific and shoot-specific response, respectively, and 25 housekeeping genes. This necessitates a fresh search for candidate sequences that qualify to be NREs in these and other plants. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Use of skin biopsies for assessing levels of organochlorines in walruses (Odobenus rosmarus)

Skin and blubber samples of ten adult male Pacific walruses (Odobenus rosmarus divergens) from Alaska were used to investigate the relationship between organochlorine (OC) levels in skin and blubber of individuals. For analyses we selected 11 components that were quantified in the blubber of all individuals: hexachlorocyclohexanes (αHCH and βHCH), the DDT (dichlorodiphenyltrichloroethane) metabolite p,p′DDE, oxychlordane, and 7 individual PCB congeners, 28, 99, 105, 118, 138, 153 and 180. The correlation between the levels in the two types of tissues was significant and the relation was isometric for all components. The regression coefficient between levels in blubber (dependent variable) and levels in skin (independent variable) was different from 1 for only four of the components. The mean levels in the two types of tissues were significantly different for 3 of the 11 chemical components (βHCH, oxychlordane, and PCB28). Although this analysis is based on only ten individuals, we propose that skin samples taken by biopsy darts can be used to monitor OC levels in walruses. In August 1993 skin biopsies were collected from 25 adult male Atlantic walruses (O. r. rosmarus) at haul-out sites in southeastern Svalbard in the Norwegian Arctic and from 28 walruses of different sex and age at haul-out sites at Franz Josef Land in the Russian Arctic. The mean levels of OCs were 2–10 times higher at Svalbard than at Franz Josef Land. The dominant OC component was PCB153 in both areas. A principal component analysis detected differences between areas in OC levels but not in patterns. Since the Franz Josef Land samples were mainly taken from females and young individuals and the Svalbard samples were taken largely from adult males, we believe the differences in tissue OC levels observed from these areas can be explained by differences in sex and age of the walrus sampled. Comparable organochlorine levels in skin samples from walruses from other areas are not available. However, compared to the corresponding OC levels found in walrus blubber in other areas, the OC levels from Svalbard and Franz Josef Land are higher. The high levels of OCs in walruses from Svalbard and Franz Josef Land may be a combined effect of high pollution level in the environment and seal-eating habits. In the present study we show that it is possible to use skin biopsies taken by a non-destructive method to assess OC levels in walruses. Accepted: 24 October 1999     

The contribution of olfactory receptor neurons to the perception of pheromone component ratios in male redbanded leafroller moths

Summary (Z)-11-tetradecenyl acetate (Z-11, 14:AC) must be in a 1009 ratio with (E)-11-tetradecenyl acetate (E-11,14:AC) to produce maximal wing fanning and attraction in male redbanded leafrollers. Earlier electrophysiological studies had indicated that mixtures of these pheromone components elicited responses from olfactory receptor neurons that appeared to differ from those expected on the basis of the responses to the individual components. Here we evaluate whether the behavioral sensitivity to particular ratios of Z- and E-11,14:AC has a correlate in the response properties of olfactory receptor neurons.The stimuli included the ratios of Z- and E-11, 14:AC used in earlier behavioral work plus several different mixtures of the seven components found in the pheromone blend, and equivalent amounts of the individual components. These stimuli were presented over a range of intensities to individual trichoid sensilla on the male antenna. In common with earlier results, the receptor neuron with the larger amplitude action potential responded most strongly to Z-11,14:AC, whereas the companion receptor neuron in the sensillum responded most strongly to E-11,14:AC. In contrast with earlier results, each receptor neuron responded exclusively to its own most effective stimulus, without regard to the presence of any other compound. They failed to respond uniquely to any of the other five compounds in the female pheromone blend, or to any of the tested combinations of these compounds. These minor components also failed to modulate the responses elicited in receptor neurons by appropriate ratios of Z- and E-11,14:AC. Thus, the responses of the two types of olfactory receptor neurons found in trichoid sensilla failed to show an optimum at the pheromone ratio known to elicit peak behavioral activity.Abbreviation RBLR redbanded leafroller moth     

Dimensionality Reduction of Bistable Biological Systems

Time hierarchies, arising as a result of interactions between system’s components, represent a ubiquitous property of dynamical biological systems. In addition, biological systems have been attributed switch-like properties modulating the response to various stimuli across different organisms and environmental conditions. Therefore, establishing the interplay between these features of system dynamics renders itself a challenging question of practical interest in biology. Existing methods are suitable for systems with one stable steady state employed as a well-defined reference. In such systems, the characterization of the time hierarchies has already been used for determining the components that contribute to the dynamics of biological systems. However, the application of these methods to bistable nonlinear systems is impeded due to their inherent dependence on the reference state, which in this case is no longer unique. Here, we extend the applicability of the reference-state analysis by proposing, analyzing, and applying a novel method, which allows investigation of the time hierarchies in systems exhibiting bistability. The proposed method is in turn used in identifying the components, other than reactions, which determine the systemic dynamical properties. We demonstrate that in biological systems of varying levels of complexity and spanning different biological levels, the method can be effectively employed for model simplification while ensuring preservation of qualitative dynamical properties (i.e., bistability). Finally, by establishing a connection between techniques from nonlinear dynamics and multivariate statistics, the proposed approach provides the basis for extending reference-based analysis to bistable systems.     

Computer-Aided Topological Analysis of the Faujasite Lattice I: Exact Solution for Zeolite-X

Abstract

In order to study the possible configurations of Aluminum and Silicon atoms on a Faujasite lattice, two different methods of analysis are presented. The first method is based on the study of the physical properties of different lattice structures: the energy and the dipolar moment. The second one examines the topological properties of the configurations in order to count the inequivalent lattice structures. An original algorithm selects the configurations to be generated and compared in order to keep the computer time required at an acceptable level. The results from the two methods are compared and found to be in agreement.

In this paper we specialize our study to zeolite-X but the methods are general and can be applied to other types of lattices.     

A New Quantitative Method for Analysing Unreplicated Factorial Designs

The paper proposes a new method for the analysis of unreplicated factorial designs. The new method does not use an estimate of the error variance and has the potential to identify up to m – 1 active contrasts, where m is the number of contrasts in the study. It can be shown that the proposed test statistic, called MaxU_r, is a function of the generalized likelihood ratio test statistic under normality, which was also used by Al‐Shiha and Yang (1999). Our strategy to identify active contrasts using MaxU_r, however, is different from the multistage procedure proposed by Al‐Shiha and Yang (1999). Additionally, our simulation study seems to show that the new method is superior to Al‐Shiha and Yang's (1999) method. In order to test the performance of the new method, we did an extensive simulation study based on 10,000 samples to compare the new method with 12 other methods from the literature. To reasonably compare these methods, some of the 12 existing methods had to be slightly modified, such that the probability of falsely rejecting the global null hypothesis of no active factors was 0.05 for all methods. Two types of evaluation standard were used, the empirical power and the loss of decision. The results show that the new method performs very well, especially for large number of active contrasts (say more than 3 out of 15). A second purpose of the simulation study was to compare the performance of two well‐known estimates for the variance. One is the PSE introduced by Lenth (1989), the other the ASE introduced by Dong (1993). The simulation study confirmed the approximations of Kunert (1997) which indicate that Dong's (1993) estimate should perform better for small numbers of active factors. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

CotG controls spore surface formation in response to the temperature of growth in Bacillus subtilis

Bacterial spores of the Bacillus genus are ubiquitous in nature and are commonly isolated from a variety of diverse environments. Such wide distribution mainly reflects the spore resistance properties but some Bacillus species can grow/sporulate in at least some of the environments where they have been originally isolated. Growing and sporulating at different conditions is known to affect the structure and the resistance properties of the produced spore. In B. subtilis the temperature of growth and sporulation has been shown to influence the structure of the spore surface throughout the action of a sporulation-specific and heat-labile kinase CotH. Here we report that CotG, an abundant component of the B. subtilis spore surface and a substrate of the CotH kinase, assembles around the forming spore but also accumulates in the mother cell cytoplasm where it forms aggregates with at least two other coat components. Our data suggest that the thermo-regulator CotH contributes to the switch between the coat of 25°C and that of 42°C spores by controlling the phosphorylation levels of CotG that, in turn, regulates the assembly of at least two other coat components.     

Antibacterial properties of nine pure metals: a laboratory study using Staphylococcus aureus and Escherichia coli

Bacterial attachment and growth on material surfaces are considered to be the primary steps leading to the formation of biofilm. Biofilms in hospital and food processing settings can result in bacterial infection and food contamination, respectively. Prevention of bacterial attachment, therefore, is considered to be the best strategy for abating these menaces and therefore the development of antibacterial metals becomes important. In this study, nine pure metals, viz. titanium, cobalt, nickel, copper, zinc, zirconium, molybdenum, tin, and lead have been tested for their antibacterial properties against two bacterial strains, Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. This was accomplished using two assay methods, the film contact method and the shaking flask method. The results show that the antibacterial properties varied significantly with different metals and the effectiveness of metals to resist bacterial attachment varied with the bacterial strain. Among the metals tested, titanium and tin did not exhibit antibacterial properties. TEM images showed that metal accumulation resulted in the disruption of the bacterial cell wall and other cellular components.     

Synthetic conversion of a graded receptor signal into a tunable,reversible switch

The ability to engineer an all‐or‐none cellular response to a given signaling ligand is important in applications ranging from biosensing to tissue engineering. However, synthetic gene network ‘switches’ have been limited in their applicability and tunability due to their reliance on specific components to function. Here, we present a strategy for reversible switch design that instead relies only on a robust, easily constructed network topology with two positive feedback loops and we apply the method to create highly ultrasensitive (n_H>20), bistable cellular responses to a synthetic ligand/receptor complex. Independent modulation of the two feedback strengths enables rational tuning and some decoupling of steady‐state (ultrasensitivity, signal amplitude, switching threshold, and bistability) and kinetic (rates of system activation and deactivation) response properties. Our integrated computational and synthetic biology approach elucidates design rules for building cellular switches with desired properties, which may be of utility in engineering signal‐transduction pathways.     

Padé-Laplace method for the analysis of time-resolved fluorescence decay curves

The interpretation of fluorescence intensity decay times in terms of protein structure and dynamics depends on the accuracy and sensitivity of the methods used for data analysis. The are many methods available for the analysis of fluorescence decay data, but justification for choosing any one of them is unclear. In this paper we generalize the recently proposed Padé-Laplace method [45] to include deconvolution with respect to the instrument response function. In this form the method can be readily applied to the analysis of time-correlated single photon counting data. By extensive simulations we have shown that the Padé-Laplace method provides more accurate results than the standard least squares method with iterative reconvolution under the condition of closely spaced lifetimes. The application of the Padé-Laplace method to several experimental data sets yielded results consistent with those obtained by use of the least squares analysis. Offprint requests to: F. G. Prendergast     

Model-independent analysis of the orientation of fluorescent probes with restricted mobility in muscle fibers

The orientation of proteins in ordered biological samples can be investigated using steady-state polarized fluorescence from probes conjugated to the protein. A general limitation of this approach is that the probes typically exhibit rapid orientational motion ("wobble") with respect to the protein backbone. Here we present a method for characterizing the extent of this wobble and for removing its effects from the available information about the static orientational distribution of the probes. The analysis depends on four assumptions: 1) the probe wobble is fast compared with the nanosecond time scale of its excited-state decay; 2) the orientational distributions of the absorption and emission transition dipole moments are cylindrically symmetrical about a common axis c fixed in the protein; 3) protein motions are negligible during the excited-state decay; 4) the distribution of c is cylindrically symmetrical about the director of the experimental sample. In a muscle fiber, the director is the fiber axis, F. All of the information on the orientational order of the probe that is available from measurements of linearly polarized fluorescence is contained in five independent polarized fluorescence intensities measured with excitation and emission polarizers parallel or perpendicular to F and with the propagation axis of the detected fluorescence parallel or perpendicular to that of the excitation. The analysis then yields the average second-rank and fourth-rank order parameters ( and ) of the angular distribution of c relative to F, and and , the average second-rank order parameters of the angular distribution for wobble of the absorption and emission transition dipole moments relative to c. The method can also be applied to other cylindrically ordered systems such as oriented lipid bilayer membranes and to processes slower than fluorescence that may be observed using longer-lived optically excited states.     

Elimination of response latency variability in neuronal spike trains

 Neuronal activity in the mammalian cortex exhibits a considerable amount of trial-by-trial variability. This may be reflected by the magnitude of the activity as well as by the response latency with respect to an external event, such as the onset of a sensory stimulus, or a behavioral event. Here we present a novel nonparametric method for estimating trial-by-trial differences in response latency from neuronal spike trains. The method makes use of the dynamic rate profile for each single trial and maximizes their total pairwise correlation by appropriately shifting all trials in time. The result is a new alignment of trials that largely eliminates the variability in response latency and provides a new internal trigger that is independent of experiment time. To calibrate the method, we simulated spike trains based on stochastic point processes using a parametric model for phasic response profiles. We illustrate the method by an application to simultaneous recordings from a pair of neurons in the motor cortex of a behaving monkey. It is demonstrated how the method can be used to study the temporal relation of the neuronal response to the experiment, to investigate whether neurons share the same dynamics, and to improve spike correlation analysis. Differences between this and other previously published methods are discussed. Received: 8 April 2002 / Accepted: 26 November 2002 / Published online: 7 April 2003 Correspondence to: Stefan Rotter (e-mail: rotter@biologie.uni-freiburg.de), Tel.: +49-761-2032862, Fax: +49-761-2032860 Acknowledgements. We are grateful to Alexa Riehle for providing us with the monkey data and for valuable discussions. We also thank Felix Kümmell, Hiroyuki Nakahara, and Shun-ichi Amari for helpful discussions. Partial funding was received by the Deutsche Forschungsgemeinschaft (DFG, SFB 505) and the German-Israeli Foundation (GIF). Additional support was provided by the RIKEN Brain Science Institute.     

Quantification of emotion by nonlinear analysis of the chaotic dynamics of electroencephalograms during perception of 1/f music

The goal of this study is to quantify and determine the way in which the emotional response to music is reflected in the electrical activities of the brain. When the power spectrum of sequences of musical notes is inversely proportional to the frequency on a log-log plot, we call it 1/f music. According to previous research, most listeners agree that 1/f music is much more pleasing than white (1/f ⁰) or brown (1/f ²) music. Based on these studies, we used nonlinear methods to investigate the chaotic dynamics of electroencephalograms (EEGs) elicited by computer-generated 1/f music, white music, and brown music. In this analysis, we used the correlation dimension and the largest Lyapunov exponent as measures of complexity and chaos. We developed a new method that is strikingly faster and more accurate than other algorithms for calculating the nonlinear invariant measures from limited noisy data. At the right temporal lobe, 1/f music elicited lower values of both the correlation dimension and the largest Lyapunov exponent than white or brown music. We observed that brains which feel more pleased show decreased chaotic electrophysiological behavior. By observing that the nonlinear invariant measures for the 1/f distribution of the rhythm with the melody kept constant are lower than those for the 1/f distribution of melody with the rhythm kept constant, we could conclude that the rhythm variations contribute much more to a pleasing response to music than the melody variations do. These results support the assumption that chaos plays an important role in brain function, especially emotion. Received: 30 December 1996 / Accepted in revised form: 18 December 1997     

Bifurcation analysis of an orientational aggregation model

 We consider an integro-differential equation for the evolution of a function f on the circle, describing an orientational aggregation process. In the first part we analyze generic bifurcations of steady-state solutions when a single eigenvalue changes sign. Lyapunov-Schmidt reduction leads to the bifurcation equation which is solved explicitly by formal power series. We prove that these series have positive radius of convergence. Two examples exhibit forward and backward bifurcations, respectively. In the second part we assume that the first and second eigenvalues become positive. Again we use Lyapunov-Schmidt reduction to arrive at the reduced bifurcation system from which we get the bifurcating branches as power series. We calculate the two most important parameters of the reduced system for two examples; one of them has interesting mode interactions which lead to various kinds of time-periodic solutions. Received: 23 April 2001 / Revised version: 29 October 2002 / Published online: 28 February 2003 Key words or phrases: Actin – Cytoskeleton – Orientational Aggregation – Bifurcation Analysis – Mode Interaction – Power Series Expansion     

A study on the influence of molecular properties in the psychoactivity of cannabinoid compounds

Several molecular properties are calculated for a set of 26 cannabinoid compounds with the goal of connecting the psychoactivity of the compounds with an appropriate set of calculated properties. For this purpose we used quantum chemical (the AM1 semi-empirical method) and chemometric methods. The AM1 method was employed to calculate the set of quantum chemical molecular properties and the chemometric methods were employed with the aim of selecting the most relevant properties to be correlated with psychoactivity. The chemometric methods used were Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA) and the K-Nearest Neighbor (KNN) method. The chemometric analysis showed that an electronic property (energy of LUMO), a hydrophobic property (log P), a steric property (volume of the substituent at the C4 position) and a topological property (Lovasz–Pelikan index) were the most important variables for the separation between the psychoactive and psychoinactive compounds. In order to validate our PCA, HCA and KNN results, eight new cannabinoid compounds (with known psychoactivity) were used in a prediction study and were classified correctly by the methods used in this work, indicating that our PCA, HCA and KNN models are able to predict reliable psychoactivity of cannabinoid compounds. Figure: ⁹-THC This revised version was published online in June 2005 with corrections to Table 1.