Validation of theoretical framework explaining active solute uptake in dynamically loaded porous media

Solute transport in biological tissues is a fundamental process necessary for cell metabolism. In connective soft tissues, such as articular cartilage, cells are embedded within a dense extracellular matrix that hinders the transport of solutes. However, according to a recent theoretical study (Mauck et al., 2003, J. Biomech. Eng. 125, 602–614), the convective motion of a dynamically loaded porous solid matrix can also impart momentum to solutes, pumping them into the tissue and giving rise to concentrations which exceed those achived under passive diffusion alone. In this study, the theoretical predictions of this model are verified against experimental measurements. The mechanical and transport properties of an agarose–dextran model system were characterized from independent measurements and substituted into the theory to predict solute uptake or desorption under dynamic mechanical loading for various agarose concentrations and dextran molecular weights, as well as different boundary and initial conditions. In every tested case, agreement was observed between experiments and theoretical predictions as assessed by coefficients of determination ranging from R²=0.61 to 0.95. These results provide strong support for the hypothesis that dynamic loading of a deformable porous tissue can produce active transport of solutes via a pumping mechanisms mediated by momentum exchange between the solute and solid matrix.     

Biodiversity and climate change use scenarios framework for the GEOSS interoperability pilot process

Climate change threatens to commit 15–37% of species to extinction by 2050. There is a clear need to support policy-makers analyzing and assessing the impact of climate change along with land use changes. This requires a megascience infrastructure that is capable of discovering and integrating enormous volumes of multi-disciplinary data, i.e. data from biodiversity, earth observation, and climatic archives. Metadata and services interoperability is necessary. The Global Earth Observation System of Systems (GEOSS) works to realize such an interoperability infrastructure based on systems architecture standardization. In this paper we describe the results of linking the infrastructures of Climate Change research and Biodiversity research together using the approach envisioned by GEOSS. In fact, we present and discuss a service-oriented framework which was applied to implement and demonstrate the Climate Change and Biodiversity use scenario of the GEOSS Interoperability Process Pilot Project (IP3). This interoperability is done for the purpose of enabling scientists to do large-scale ecological analysis. We describe a generic use scenario and related modelling workbench that implement an environment for studying the impacts of climate change on biodiversity. The Service Oriented Architecture framework, which realizes this environment, is described. Its standard-based components and services, according to GEOSS requirements, are discussed. This framework was successfully demonstrated at the GEO IV Ministerial Meeting in Cape Town, South Africa November 2007.     

气候变化和土地利用变化驱动下的生物多样性系统分析新框架

尽管目前已有大量关于生物多样性评估的研究,但同时考虑生物多样性多维评估、多驱动因素对生物多样性变化的影响评估及生物多样性变化中长期动态模拟预测等研究仍相对缺乏,这会引起对生物多样性不同维度变化水平的片面理解,导致生物多样性保护工程管理决策失误。基于此,综述现有生物多样性评估维度、驱动因素及历史评估的研究进展,并基于现有研究存在的局限性提出生物多样性多维评估方法与人地耦合系统下生物多样性模拟模型构建思路,基于此提出气候变化和土地利用变化驱动下的生物多样性系统分析新框架。该框架包括:①生物多样性"潜力-贡献-重要性"多维评估理论与方法构建;②人地耦合系统下生物多样性模拟模型构建;③人地耦合系统下生物多样性预测及生物多样性保护工程效果仿真与管理。该框架可为生物多样性保护工程管理及可持续开展提供科学建议。     

Land use for animal production in global change studies: Defining and characterizing a framework

Land use for animal production influences the earth system in a variety of ways, including local‐scale modification to biodiversity, soils, and nutrient cycling; regional changes in albedo and hydrology; and global‐scale changes in greenhouse gas and aerosol concentrations. Pasture is furthermore the single most extensive form of land cover, currently comprising about 22–26% of the earth's ice‐free land surface. Despite the importance and variable expressions of animal production, distinctions among different systems are effectively absent from studies of land use and land cover change. This deficiency is improving; however, livestock production system classifications are rarely applied in this context, and the most popular global land cover inventories still present only a single, usually poorly defined category of “pasture” or “rangeland” with no characterization of land use. There is a marked lack of bottom‐up, evidence‐based methodology, creating a pressing need to incorporate cross‐disciplinary evidence of past and present animal production systems into global change studies. Here, we present a framework, modified from existing livestock production systems, that is rooted in sociocultural, socioeconomic, and ecological contexts. The framework defines and characterizes the range of land usage pertaining to animal production, and is suitable for application in land use inventories and scenarios, land cover modeling, and studies on sustainable land use in the past, present, and future.     

基于生态系统服务供需的城市群生态安全格局构建框架

近年来,生态系统服务供需失调引发了一系列问题,诸如城市热岛、生态用地流失、环境污染、生物多样性减少等生态风险问题,已成为威胁生态安全、制约社会经济可持续发展的重要因素,因此维持生态系统服务供需平衡是生态安全健康发展的保障和关键。梳理了生态系统服务评价、生态安全格局构建的研究现状,指出了存在的不足,同时构建了基于生态系统服务的城市群生态安全格局基本框架,并提出了生态安全格局未来的研究重点:城市群区域和城市内部生态系统服务的多尺度综合评价、城市功能区的划分及对生态安全的胁迫作用、生态过程与生态系统服务与生态安全的耦合、基于生态系统服务流的生态安全格局构建、模拟和优化。通过耦合社会经济数据、卫星遥感数据、城市地图大数据,评价城市内部和外部不同尺度的生态系统服务,保障城市群生态系统服务流畅通传输,实现城市群生态安全格局评价和优化。     

A framework for models of biological behaviour

Modelling is most clearly understood as a adjunct in the process of deriving predictions from hypotheses. By representing a hypothesised mechanism in a model we hope by manipulating the model to understand the hypotheses' consequences. Eight dimensions on which models of biological behaviour can vary are described: the degree of realism with which they apply to biology; the level of biology they represent; the generality or range of systems the model is supposed to cover; the abstraction or amount of biological detail represented; the accuracy of representation of the mechanisms; the medium in which the model is built; the match of the model behaviour to biological behaviour; and the utility of the model in providing biological understanding and/or technical insight. It is hoped this framework will help to clarify debates over different approaches to modelling, particularly by pointing out how the above dimensions are relatively independent and should not be conflated.     

A framework for the study of genetic variation in migratory behaviour

Evolutionary change results from selection acting on genetic variation. For migration to be successful, many different aspects of an animal’s physiology and behaviour need to function in a co-coordinated way. Changes in one migratory trait are therefore likely to be accompanied by changes in other migratory and life-history traits. At present, we have some knowledge of the pressures that operate at the various stages of migration, but we know very little about the extent of genetic variation in various aspects of the migratory syndrome. As a consequence, our ability to predict which species is capable of what kind of evolutionary change, and at which rate, is limited. Here, we review how our evolutionary understanding of migration may benefit from taking a quantitative-genetic approach and present a framework for studying the causes of phenotypic variation. We review past research, that has mainly studied single migratory traits in captive birds, and discuss how this work could be extended to study genetic variation in the wild and to account for genetic correlations and correlated selection. In the future, reaction-norm approaches may become very important, as they allow the study of genetic and environmental effects on phenotypic expression within a single framework, as well as of their interactions. We advocate making more use of repeated measurements on single individuals to study the causes of among-individual variation in the wild, as they are easier to obtain than data on relatives and can provide valuable information for identifying and selecting traits. This approach will be particularly informative if it involves systematic testing of individuals under different environmental conditions. We propose extending this research agenda by using optimality models to predict levels of variation and covariation among traits and constraints. This may help us to select traits in which we might expect genetic variation, and to identify the most informative environmental axes. We also recommend an expansion of the passerine model, as this model does not apply to birds, like geese, where cultural transmission of spatio-temporal information is an important determinant of migration patterns and their variation.     

Killing the competition: a theoretical framework for liver-stage malaria

The first stage of malaria infections takes place inside the host''s hepatocytes. Remarkably, Plasmodium parasites do not infect hepatocytes immediately after reaching the liver. Instead, they migrate through several hepatocytes before infecting their definitive host cells, thus increasing their chances of immune destruction. Considering that malaria can proceed normally without cell traversal, this is indeed a puzzling behaviour. In fact, the role of hepatocyte traversal remains unknown to date, implying that the current understanding of malaria is incomplete. In this work, we hypothesize that the parasites traverse hepatocytes to actively trigger an immune response in the host. This behaviour would be part of a strategy of superinfection exclusion aimed to reduce intraspecific competition during the blood stage of the infection. Based on this hypothesis, we formulate a comprehensive theory of liver-stage malaria that integrates all the available knowledge about the infection. The interest of this new paradigm is not merely theoretical. It highlights major issues in the current empirical approach to the study of Plasmodium and suggests new strategies to fight malaria.     

A theoretical framework for defining some concepts in evolution.

We present a theoretical framework for biological evolution with the intention of giving precise mathematical definitions of some concepts in evolutionary biology such as fitness, evolutionary pressure, specialization and natural selection. In this framework, such concepts are identified with well-known mathematical terms within the theory of dynamical systems. We also discuss some more general implications in evolution; for instance, the fact that our model naturally exhibits a frequency spectrum of the type 1/f for low frequencies of evolutionary events.     

A theoretical framework for strain-related trabecular bone maintenance and adaptation

It is assumed that density and morphology of trabecular bone is partially controlled by mechanical forces. How these effects are expressed in the local metabolic functions of osteoclast resorption and osteoblast formation is not known. In order to investigate possible mechano-biological pathways for these mechanisms we have proposed a mathematical theory (Nature 405 (2000) 704). This theory is based on hypothetical osteocyte stimulation of osteoblast bone formation, as an effect of elevated strain in the bone matrix, and a role for microcracks and disuse in promoting osteoclast resorption. Applied in a 2-D Finite Element Analysis model, the theory explained the formation of trabecular patterns. In this article we present a 3-D FEA model based on the same theory and investigated its potential morphological predictability of metabolic reactions to mechanical loads. The computations simulated the development of trabecular morphological details during growth, relative to measurements in growing pigs, reasonably realistic. They confirmed that the proposed mechanisms also inherently lead to optimal stress transfer. Alternative loading directions produced new trabecular orientations. Reduction of load reduced trabecular thickness, connectivity and mass in the simulation, as is seen in disuse osteoporosis. Simulating the effects of estrogen deficiency through increased osteoclast resorption frequencies produced osteoporotic morphologies as well, as seen in post-menopausal osteoporosis. We conclude that the theory provides a suitable computational framework to investigate hypothetical relationships between bone loading and metabolic expressions.     

A theoretical framework for quantitative analysis of the molecular basis of costimulation

We present a theoretical framework for simulating the synaptic accumulation of the costimulatory molecules CD28, CTLA-4, B7-1, and B7-2, based on a system of mean-field, ordinary differential equations, and rigorous biophysical and expression data. The simulations show that binding affinity, stoichiometric properties, expression levels, and, in particular, competition effects all profoundly influence complex formation at cellular interfaces. B7-2 engages 33-fold more CD28 than CTLA-4 at the synapse in contrast to B7-1, which ligates approximately 7-fold more CTLA-4 than CD28. Although B7-1 completely dominates interactions with CTLA-4, forming linear arrays of 7-18 receptor-ligand pairs, CTLA-4 is fully engaged by B7-2 when B7-1 is absent. Additional simulations reveal the sensitivity of CD28 interactions to modeled transport processes. The results support the concept that B7-2 and B7-1 are the dominant ligands of CD28 and CTLA-4, respectively, and indicate that the inability of B7-2 to recruit CTLA-4 to the synapse cannot be due to the differential binding properties of B7-1 and B7-2 only. We discuss the apparent redundancy of B7-1 in the context of a potentially dynamic synaptic microenvironment, and in light of functions other than the direct enhancement of T cell inhibition by CTLA-4.     

The behaviour of nuclear domains in the course of apoptosis

Programmed cell death is activated, by different stimuli and in many cell types, to regulate cell population balance during tissue proliferation and embryogenesis. Its initial event seems to be, in most cases, the activation of a Ca²⁺-dependent endonuclease, causing DNA cleavage into nucleosomic fragments. Its morphological expression is characterized by deep nuclear changes, consisting of typical cap-shaped chromatin marginations, followed by nuclear fragmentation and final formation of numerous micronuclei. Cytoplasmic damage appears in a very late stage of the process and the greatest part of the phenomenon appears to take place despite good preservation of the plasma membrane and organellar component. In the present study we analyzed apoptosis in camptothecin-treated HL60 leukaemia cells, and in freshly isolated mouse thymocytes treated with dexamethasone. The process was first quantified and time monitored by flow cytometry. Subsequently the specimens were processed for morphological examination in order to investigate the behaviour of the different nuclear domains. To follow DNA and RNA localization, we utilized osmium ammine and DNase-colloidal gold cytochemical reactions. The concentration of most DNA in the cap-shaped structures was demonstrated by these reactions. Confocal microscopy of cells processed by in situ nick-translation suggested that DNA was firstly cleaved and subsequently condensed in cup-shaped structures. Despite the strong nuclear modifications, nucleoli could be clearly recognized until the late apoptotic stages.     

Validation of a new system for the automatic registration of behaviour in mice and rats

A newly developed behaviour registration system, Laboratory Animal Behaviour Observation, Registration and Analysis System (LABORAS) for the automatic registration of different behavioural elements of mice and rats was validated. The LABORAS sensor platform records vibrations evoked by animal movements and the LABORAS software translates these into the corresponding behaviours. Data obtained by using LABORAS were compared with data from conventional observation methods (observations of videotapes by human observers). The results indicate that LABORAS is a reliable system for the automated registration of eating, drinking, grooming, climbing, resting and locomotion of mice during a prolonged period of time. In rats, grooming, locomotion and resting also met the pre-defined validation criteria. The system can reduce observation labour and time considerably.     

On the theoretical and empirical framework for studying genetic interactions within and among species

We present a quantitative genetic (QG) interpretation of the Bateson-Dobzhansky-Muller (BDM) genetic model of speciation in order to unify the theoretical framework for understanding how the genetic differentiation of populations is associated with the process of speciation. Specifically, we compare the QG theory of joint scaling with the Turelli-Orr mathematical formulation of the BDM model. By formally linking the two models, we show that a wealth of empirical methods from QG can be brought to bear on the study of the genetic architecture of hybrid phenotypes to better understand the connections, if any, between microevolution within populations and macroevolution in the origin of species. By integrating the two theories, we make additional novel predictions that enrich the opportunities for empirically testing speciation genetic theory or facets of it, such as Haldane's rule. We show that the connection between the two theories is simple and straightforward for autosomal genes but not for sex-linked genes. Differences between the two approaches highlight key conceptual issues concerning the relevance of epistasis to evolution within and among lineages and to differences in the process of speciation in hermaphrodites and in organisms with separate sexes.     

Validation of the Boussinesq equation for use in traction field determination

Cell traction force plays an important role in many biological processes. Several traction force microscopy methods have been developed to determine cell traction forces based on the Boussinesq solution. This approach, however, is rooted in a half-space assumption. The purpose of this study was to determine the error induced in the half-space assumption using a finite element method (FEM). It demonstrates that displacement error between the FEM and the Boussinesq equation can be used to measure the accuracy of the Boussinesq equation, although singularity exists in the loading point. For one concentrated force, significant difference between the FEM and the Boussinesq equation occurs in the whole field; this difference decreases with an increase in the plate thickness. However, in the case of the balanced forces, the offset of the balanced forces decreases the errors in the middle area. Overall, this study demonstrates that increasing the thickness of the polyacrylamide gel is important for reducing the error of the Boussinesq equation when determining the displacement field of the gel under loads.     

A novel theoretical framework for simultaneous measurement of excitatory and inhibitory conductances

The firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs, and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Future experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.