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Toward integration of biological and physiological functions at multiple levels.

ABSTRACT: An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.

SUBMITTER: Nomura T

PROVIDER: S-EPMC3059937 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Toward integration of biological and physiological functions at multiple levels.

Nomura Taishin T

Frontiers in physiology 20101229

An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowl ...[more]

PMID: 21423399

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Project description:BackgroundCurrently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project's requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation.ResultsWe present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale.ConclusionsThis report demonstrates the feasibility of PMMs and their usefulness across multiple model use cases. The pharmacodynamic response module developed here is robust to changes in model context and flexible in its ability to achieve validation targets in the face of considerable experimental uncertainty. Adopting the modularization methods presented here is expected to facilitate model reuse and integration, thereby accelerating the pace of biomedical research.

Project description:Turbidity can influence trophic levels by altering species composition and can potentially affect fish feeding strategies and predator-prey interactions. The estuarine turbidity maximum, described as an area of increased suspended particles, phytoplankton and zooplankton, generally represents a zone with higher turbidity and enhanced food sources important for successful feeding and growth in many fish species. The delta smelt (Hypomesus transpacificus) is an endangered, pelagic fish species endemic to the San Francisco Estuary and Sacramento-San Joaquin River Delta, USA, where it is associated with turbid waters. Turbidity is known to play an important role for the completion of the species' life cycle; however, turbidity ranges in the Delta are broad, and specific requirements for this fish species are still unknown. To evaluate turbidity requirements for early life stages, late-larval delta smelt were maintained at environmentally relevant turbidity levels ranging from 5 to 250?nephelometric turbidity units (NTU) for 24?h, after which a combination of physiological endpoints (molecular biomarkers and cortisol), behavioural indices (feeding) and whole-organism measures (survival) were determined. All endpoints delivered consistent results and identified turbidities between 25 and 80?NTU as preferential. Delta smelt survival rates were highest between 12 and 80?NTU and feeding rates were highest between 25 and 80?NTU. Cortisol levels indicated minimal stress between 35 and 80?NTU and were elevated at low turbidities (5, 12 and 25?NTU). Expression of stress-related genes indicated significant responses for gst, hsp70 and glut2 in high turbidities (250?NTU), and principal component analysis on all measured genes revealed a clustering of 25, 35, 50 and 80?NTU separating the medium-turbidity treatments from low- and high-turbidity treatments. Taken together, these data demonstrate that turbidity levels that are either too low or too high affect delta smelt physiological performance, causing significant effects on overall stress, food intake and mortality. They also highlight the need for turbidity to be considered in habitat and water management decisions.

Dataset Information

Toward integration of biological and physiological functions at multiple levels.

Publications

Toward integration of biological and physiological functions at multiple levels.

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