The psoriatic epidermal lesion and anagen hair growth may share the same "switch-on" mechanism

Based on striking parallels between the cell kinetics in the epidermal lesion of psoriasis and the proliferation of hair matrix keratinocytes during the anagen phase of the hair growth cycle, the hypothesis is proposed that both phenomena may share the same "switch-on" mechanism. Particular emphasis is placed on a comparison between the Koebner phenomenon in psoriasis and wounding-induced anagen hair growth. In discussing alternative theoretical models for the proposed common "switch-on" mechanism, some useful experimental tools are suggested. Research into the mechanisms which control epithelial proliferation in psoriasis and hair growth may provide new insights into other growth processes, such as embryonic organogenesis and neoplasia, in which similar epithelial-mesenchymal interactions play a pivotal role.     

The Bio-Logic and machinery of plant morphogenesis

Morphogenesis (the development of organic form) requires signal-trafficking and cross-talking across all levels of organization to coordinate the operation of metabolic and genomic networked systems. Many biologists are currently converging on the pictorial conventions of computer scientists to render biological signaling as logic circuits supervising the operation of one or more signal-activated metabolic or gene networks. This approach can redact and simplify complex morphogenetic phenomena and allows for their aggregation into diagrams of larger, more "global" networked systems. This conceptualization is discussed in terms of how logic circuits and signal-activated subsystems work, and it is illustrated for examples of increasingly more complex morphogenetic phenomena, e.g., auxin-mediated cell expansion, entry into the mitotic cell cycle phases, and polar/lateral intercellular auxin transport. For each of these phenomena, a posited circuit/subsystem diagram draws rapid attention to missing components, either in the logic circuit or in the subsystem it supervises. These components must be identified experimentally if each of these basic phenomena is to be fully understood. Importantly, the power of the circuit/subsystem approach to modeling developmental phenomena resides not in its pictorial appeal but in the mathematical tools that are sufficiently strong to reveal and quantify the synergistics of networked systems and thus foster a better understanding of morphogenesis.     

From theory to data: Representing neurons in the 1940s

Recent literature on the role of pictorial representation in the life sciences has focused on the relationship between detailed representations of empirical data and more abstract, formal representations of theory. The standard argument is that in both a historical and epistemic sense, this relationship is a directional one: beginning with raw, unmediated images and moving towards diagrams that are more interpreted and more theoretically rich. Using the neural network diagrams of Warren McCulloch and Walter Pitts as a case study, I argue that while in the empirical sciences, pictorial representation tends to move from data to theory, in areas of the life sciences that are predominantly theoretical, when abstraction occurs at the outset, the relationship between detail and abstraction in pictorial representations can be of a different character.     

VennDIS: A JavaFX‐based Venn and Euler diagram software to generate publication quality figures

Venn diagrams are graphical representations of the relationships among multiple sets of objects and are often used to illustrate similarities and differences among genomic and proteomic datasets. All currently existing tools for producing Venn diagrams evince one of two traits; they require expertise in specific statistical software packages (such as R), or lack the flexibility required to produce publication‐quality figures. We describe a simple tool that addresses both shortcomings, Venn Diagram Interactive Software (VennDIS), a JavaFX‐based solution for producing highly customizable, publication‐quality Venn, and Euler diagrams of up to five sets. The strengths of VennDIS are its simple graphical user interface and its large array of customization options, including the ability to modify attributes such as font, style and position of the labels, background color, size of the circle/ellipse, and outline color. It is platform independent and provides real‐time visualization of figure modifications. The created figures can be saved as XML files for future modification or exported as high‐resolution images for direct use in publications.     

Dynamical and integrative cell signaling: challenges for the new biology

Years of careful experimental analysis have revealed that signaling molecules are organized into complex networks of biochemical reactions exquisitely regulated in time and space to provide a cell with high-fidelity information about an extremely noisy and volatile environment. A new view of signaling networks as systems consisting of multiple complex elements interacting in a multifarious fashion is emerging, a view that conflicts with the single-gene or protein-centric approach common in biological research. The postgenomic era has brought about a different, network-centric methodology of analysis, suddenly forcing researchers toward the opposite extreme of complexity, where the networks being explored are, to a certain extent, intractable and uninterpretable. Both the cartoons of simple pathways and the very large "hair-ball" diagrams of large intracellular networks are also representations of static worlds, superficially devoid of dynamics and chemistry. These representations are often viewed as being analogous to stably linked computer and neural networks rather than dynamically changing networks of chemical interactions, where the notions of concentration, compartmentalization, and diffusion may be the primary determinants of connectivity. Arguably, the systems biology approach, relying on computational modeling coupled with various experimental techniques and methodologies, will be an essential component of analysis of the behavior of signal transduction pathways. Combining the dynamical view of rapidly evolving responses and the structural view arising from high-throughput analyses of the interacting species will be the best approach toward efforts toward greater understanding of intracellular signaling processes.     

Computational models of spatial updating in peri-saccadic perception

Perceptual phenomena that occur around the time of a saccade, such as peri-saccadic mislocalization or saccadic suppression of displacement, have often been linked to mechanisms of spatial stability. These phenomena are usually regarded as errors in processes of trans-saccadic spatial transformations and they provide important tools to study these processes. However, a true understanding of the underlying brain processes that participate in the preparation for a saccade and in the transfer of information across it requires a closer, more quantitative approach that links different perceptual phenomena with each other and with the functional requirements of ensuring spatial stability. We review a number of computational models of peri-saccadic spatial perception that provide steps in that direction. Although most models are concerned with only specific phenomena, some generalization and interconnection between them can be obtained from a comparison. Our analysis shows how different perceptual effects can coherently be brought together and linked back to neuronal mechanisms on the way to explaining vision across saccades.     

Stages in the development of a model organism as a platform for mechanistic models in developmental biology: Zebrafish, 1970-2000

Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the main focus was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena - structures, processes or the mechanisms that explain them - through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes.     

shinyChromosome:An R/Shiny Application for Interactive Creation of Non-circular Plots of Whole Genomes

Non-circular plots of whole genomes are natural representations of genomic data aligned along all chromosomes.Currently,there is no specialized graphical user interface(GUI) designed to produce non-circular whole genome diagrams,and the use of existing tools requires considerable coding effort from users.Moreover,such tools also require improvement,including the addition of new functionalities.To address these issues,we developed a new R/Shiny application,named shiny Chromosome,as a GUI for the interactive creation of non-circular whole genome diagrams.shiny Chromosome can be easily installed on personal computers for own use as well as on local or public servers for community use.Publication-quality images can be readily generated and annotated from user input using diverse widgets.shiny Chromosome is deployed at http://150.109.59.144:3838/shiny Chromosome/,http://shiny Chromosome.ncpgr.cn,and https://yimingyu.shinyapps.io/shiny Chromosome for online use.The source code and manual of shiny Chromosome are freely available at https://github.com/venyao/shiny Chromosome.     

Ruthless reductionism and social cognition

Social cognition appears to present phenomena that "ruthlessly reductive" molecular and cellular neuroscience cannot fruitfully investigate or explain. This is because the causes of such phenomena are distal and external not only to the molecular machinery of individual neurons, but to individual brains. However, the "reductionist's epiphany" insists that to the extent that we understand the specific molecular mechanisms that underlie phenomena upon which most or all social cognition depends, we can be sure that molecular mechanisms for the broader phenomena can be found using standard experimental methods from molecular and cellular cognition. Furthermore, social recognition memory consolidation is required for virtually all types of social cognition, and its specific molecular mechanisms have now been uncovered experimentally. These same molecular mechanisms obtain across a wide variety of divergent species (from invertebrates to vertebrates). Thus we can expect to find the molecular mechanisms of the broader social cognitive functions that must "plug into" these specific molecular mechanisms, despite these functions' typically distal, external initial causes. This conclusion rests on explicit scientific facts, not just on some vague philosophical commitment to physicalism about mind.     

What we talk about when we talk about access deficits

Semantic impairments have been divided into storage deficits, in which the semantic representations themselves are damaged, and access deficits, in which the representations are intact but access to them is impaired. The behavioural phenomena that have been associated with access deficits include sensitivity to cueing, sensitivity to presentation rate, performance inconsistency, negative serial position effects, sensitivity to number and strength of competitors, semantic blocking effects, disordered selection between strong and weak competitors, correlation between semantic deficits and executive function deficits and reduced word frequency effects. Four general accounts have been proposed for different subsets of these phenomena: abnormal refractoriness, too much activation, impaired competitive selection and deficits of semantic control. A combination of abnormal refractoriness and impaired competitive selection can account for most of the behavioural phenomena, but there remain several open questions. In particular, it remains unclear whether access deficits represent a single syndrome, a syndrome with multiple subtypes or a variable collection of phenomena, whether the underlying deficit is domain-general or domain-specific, whether it is owing to disorders of inhibition, activation or selection, and the nature of the connection (if any) between access phenomena in aphasia and in neurologically intact controls. Computational models offer a promising approach to answering these questions.     

Batch mode generation of residue-based diagrams of proteins

SUMMARY: Residue-based diagrams of proteins are graphical representations that can be used in protein information systems. These diagrams make it possible to visually integrate different types of biological information. The approach has been used successfully for membrane proteins. We developed the Residue-based diagram generator to (i) make it possible to generate residue-based diagrams of proteins in a batch mode that is compatible with the needs of information system curators, (ii) allow the generation of residue-based diagrams for families of soluble proteins or domains. AVAILABILITY: Licensed. Royalty free licenses are granted to non-profit institutions for educational and research purposes. http://icb.mssm.edu/crt/RbDg/index.xml     

听觉皮层信号处理

听觉系统和视觉系统的不同之处在于：听觉系统在外周感受器和听皮层间具有更长的皮层下通路和更多的突触联系。该特殊结构反应了听觉系统从复杂听觉环境中提取与行为相关信号的机制与其他感觉系统不同。听皮层神经信号处理包括两种重要的转换机制,声音信号的非同构转换以及从声音感受到知觉层面的转换。听觉皮层神经编码机制同时也受到听觉反馈和语言或发声过程中发声信号的调控。听觉神经科学家和生物医学工程师所面临的挑战便是如何去理解大脑中这些转换的编码机制。我将会用我实验室最近的一些发现来阐述听觉信号是如何在原听皮层中进行处理的,并讨论其对于言语和音乐在大脑中的处理机制以及设计神经替代装置诸如电子耳蜗的意义。我们使用了结合神经电生理技术和量化工程学的方法来研究这些问题。     

What’s the matter with technology? Long (and short) yams,materialisation and technology in Nyamikum village,Maprik district,Papua New Guinea

Things are not just consumable, they are made so. They acquire their ‘materiality’ not only through engagements with them as finished products, but also through processes that make them material, i.e. technical activities. This field of study in anthropology, rejected by dominant trends because of its deterministic connotations, is a useful way to explore processes of materialisation and to investigate the ‘inbuilt’ relationality of things and activities. This paper focuses on yam gardening in Nyamikum, an Abelam village of the East Sepik. Once harvested, long (and short) yams emerge not solely as phallic symbols, but also as artefacts, representations, living beings, ancestors, artworks, valuables and, mostly, food. Starting observations at the beginning of the operational sequences (‘chaînes opératoire’, Lemonnier 1992 ) within gardening techniques, a combination of gestures, body, materials, energy, tools, knowledge and behaviours takes us across domains of experience (embodiments, transformations, sociality, narratives) to illuminate how yams are made into ‘relational’ entities. They demonstrate that techniques create a web that materialises social and cultural values, condensing networks of relations into things. As the results of these (known or imagined) processes, things can demonstrate the material validities of representational—or ideological—components of technological phenomena and may be used to generate sociality.     

Resonance modulation,annihilation and generation of anti-resonance and anti-phasonance in 3D neuronal systems: interplay of resonant and amplifying currents with slow dynamics

Subthreshold (membrane potential) resonance and phasonance (preferred amplitude and zero-phase responses to oscillatory inputs) in single neurons arise from the interaction between positive and negative feedback effects provided by relatively fast amplifying currents and slower resonant currents. In 2D neuronal systems, amplifying currents are required to be slave to voltage (instantaneously fast) for these phenomena to occur. In higher dimensional systems, additional currents operating at various effective time scales may modulate and annihilate existing resonances and generate antiresonance (minimum amplitude response) and antiphasonance (zero-phase response with phase monotonic properties opposite to phasonance). We use mathematical modeling, numerical simulations and dynamical systems tools to investigate the mechanisms underlying these phenomena in 3D linear models, which are obtained as the linearization of biophysical (conductance-based) models. We characterize the parameter regimes for which the system exhibits the various types of behavior mentioned above in the rather general case in which the underlying 2D system exhibits resonance. We consider two cases: (i) the interplay of two resonant gating variables, and (ii) the interplay of one resonant and one amplifying gating variables. Increasing levels of an amplifying current cause (i) a response amplification if the amplifying current is faster than the resonant current, (ii) resonance and phasonance attenuation and annihilation if the amplifying and resonant currents have identical dynamics, and (iii) antiresonance and antiphasonance if the amplifying current is slower than the resonant current. We investigate the underlying mechanisms by extending the envelope-plane diagram approach developed in previous work (for 2D systems) to three dimensions to include the additional gating variable, and constructing the corresponding envelope curves in these envelope-space diagrams. We find that antiresonance and antiphasonance emerge as the result of an asymptotic boundary layer problem in the frequency domain created by the different balances between the intrinsic time constants of the cell and the input frequency f as it changes. For large enough values of f the envelope curves are quasi-2D and the impedance profile decreases with the input frequency. In contrast, for f ? 1 the dynamics are quasi-1D and the impedance profile increases above the limiting value in the other regime. Antiresonance is created because the continuity of the solution requires the impedance profile to connect the portions belonging to the two regimes. If in doing so the phase profile crosses the zero value, then antiphasonance is also generated.     

jvenn: an interactive Venn diagram viewer

Background

Venn diagrams are commonly used to display list comparison. In biology, they are widely used to show the differences between gene lists originating from different differential analyses, for instance. They thus allow the comparison between different experimental conditions or between different methods. However, when the number of input lists exceeds four, the diagram becomes difficult to read. Alternative layouts and dynamic display features can improve its use and its readability.

Results

jvenn is a new JavaScript library. It processes lists and produces Venn diagrams. It handles up to six input lists and presents results using classical or Edwards-Venn layouts. User interactions can be controlled and customized. Finally, jvenn can easily be embeded in a web page, allowing to have dynamic Venn diagrams.

Conclusions

jvenn is an open source component for web environments helping scientists to analyze their data. The library package, which comes with full documentation and an example, is freely available at http://bioinfo.genotoul.fr/jvenn.     

Mixture models with multiple levels, with application to the analysis of multifactor gene expression data

Model-based clustering is a popular tool for summarizing high-dimensional data. With the number of high-throughput large-scale gene expression studies still on the rise, the need for effective data- summarizing tools has never been greater. By grouping genes according to a common experimental expression profile, we may gain new insight into the biological pathways that steer biological processes of interest. Clustering of gene profiles can also assist in assigning functions to genes that have not yet been functionally annotated. In this paper, we propose 2 model selection procedures for model-based clustering. Model selection in model-based clustering has to date focused on the identification of data dimensions that are relevant for clustering. However, in more complex data structures, with multiple experimental factors, such an approach does not provide easily interpreted clustering outcomes. We propose a mixture model with multiple levels, , that provides sparse representations both "within" and "between" cluster profiles. We explore various flexible "within-cluster" parameterizations and discuss how efficient parameterizations can greatly enhance the objective interpretability of the generated clusters. Moreover, we allow for a sparse "between-cluster" representation with a different number of clusters at different levels of an experimental factor of interest. This enhances interpretability of clusters generated in multiple-factor contexts. Interpretable cluster profiles can assist in detecting biologically relevant groups of genes that may be missed with less efficient parameterizations. We use our multilevel mixture model to mine a proliferating cell line expression data set for annotational context and regulatory motifs. We also investigate the performance of the multilevel clustering approach on several simulated data sets.     

中国旧石器文化的“西方元素”与早期人类文化进化格局

本文回顾和分析中国旧石器研究史上有关"西方元素"即西方旧石器文化标志性技术和工具问题的争论,得出三点结论:1)"西方元素"在中国旧石器文化中是与西方同类技术和工具大体同步出现的客观现象,两者无本质差别;2)和西方一样,中国旧石器的"西方元素"也有重叠与穿时性.这使得旧大陆两侧的旧石器文化连成一体,难分东西;3)基于以上事实,本文作者倾向于认为:迄今已知的旧大陆旧石器文化是过去200多万年间早期人类在进化过程中应对全球气候波动引起的生态环境变迁而反复进行的横贯大陆的双向迁移、交流与融合的结果.     

Diagrammatic Icons and Historical Processes in Belau

In this paper I analyze the relationship between diagrammatic representations of social relations and historical processes in Belau (formerly Palau), Micronesia. Four diagrams, linear paths, balanced sides, quadripartition, and graded series, are discussed in terms of their lexical labels, schematic arrangements, prototypical embodiments, and semantic fields. Ethnographic and historical examples presented reveal the differential historical vulnerability of social institutions modeled by these diagrams. The use of Peirce's typology of signs is demonstrated to be an important corrective to the structuralist notion of transformation.