WorldWideScience

Sample records for modeling cell biology

  1. Spatial Modeling Tools for Cell Biology

    National Research Council Canada - National Science Library

    Przekwas, Andrzej; Friend, Tom; Teixeira, Rodrigo; Chen, Z. J; Wilkerson, Patrick

    2006-01-01

    .... Scientific potentials and military relevance of computational biology and bioinformatics have inspired DARPA/IPTO's visionary BioSPICE project to develop computational framework and modeling tools for cell biology...

  2. Models to Study NK Cell Biology and Possible Clinical Application.

    Science.gov (United States)

    Zamora, Anthony E; Grossenbacher, Steven K; Aguilar, Ethan G; Murphy, William J

    2015-08-03

    Natural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. NK cells rapidly recognize and respond to abnormal cells in the absence of prior sensitization due to their wide array of germline-encoded inhibitory and activating receptors, which differs from the receptor diversity found in B and T lymphocytes that is due to the use of recombination-activation gene (RAG) enzymes. Although NK cells have traditionally been described as natural killers that provide a first line of defense prior to the induction of adaptive immunity, a more complex view of NK cells is beginning to emerge, indicating they may also function in various immunoregulatory roles and have the capacity to shape adaptive immune responses. With the growing appreciation for the diverse functions of NK cells, and recent technological advancements that allow for a more in-depth understanding of NK cell biology, we can now begin to explore new ways to manipulate NK cells to increase their clinical utility. In this overview unit, we introduce the reader to various aspects of NK cell biology by reviewing topics ranging from NK cell diversity and function, mouse models, and the roles of NK cells in health and disease, to potential clinical applications. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

  3. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

    Full Text Available Abstract Background Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.. A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells. Results We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a

  4. Chimeric animal models in human stem cell biology.

    Science.gov (United States)

    Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

    2009-01-01

    The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

  5. Modeling cell-in-cell structure into its biological significance

    OpenAIRE

    He, M-f; Wang, S; Wang, Y; Wang, X-n

    2013-01-01

    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of ?entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...

  6. Human pluripotent stem cells: an emerging model in developmental biology.

    Science.gov (United States)

    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

  7. Evolving cell models for systems and synthetic biology.

    Science.gov (United States)

    Cao, Hongqing; Romero-Campero, Francisco J; Heeb, Stephan; Cámara, Miguel; Krasnogor, Natalio

    2010-03-01

    This paper proposes a new methodology for the automated design of cell models for systems and synthetic biology. Our modelling framework is based on P systems, a discrete, stochastic and modular formal modelling language. The automated design of biological models comprising the optimization of the model structure and its stochastic kinetic constants is performed using an evolutionary algorithm. The evolutionary algorithm evolves model structures by combining different modules taken from a predefined module library and then it fine-tunes the associated stochastic kinetic constants. We investigate four alternative objective functions for the fitness calculation within the evolutionary algorithm: (1) equally weighted sum method, (2) normalization method, (3) randomly weighted sum method, and (4) equally weighted product method. The effectiveness of the methodology is tested on four case studies of increasing complexity including negative and positive autoregulation as well as two gene networks implementing a pulse generator and a bandwidth detector. We provide a systematic analysis of the evolutionary algorithm's results as well as of the resulting evolved cell models.

  8. Theories and models on the biological of cells in space

    Science.gov (United States)

    Todd, P.; Klaus, D. M.

    1996-01-01

    A wide variety of observations on cells in space, admittedly made under constraining and unnatural conditions in may cases, have led to experimental results that were surprising or unexpected. Reproducibility, freedom from artifacts, and plausibility must be considered in all cases, even when results are not surprising. The papers in symposium on 'Theories and Models on the Biology of Cells in Space' are dedicated to the subject of the plausibility of cellular responses to gravity -- inertial accelerations between 0 and 9.8 m/sq s and higher. The mechanical phenomena inside the cell, the gravitactic locomotion of single eukaryotic and prokaryotic cells, and the effects of inertial unloading on cellular physiology are addressed in theoretical and experimental studies.

  9. Micrasterias as a model system in plant cell biology

    Directory of Open Access Journals (Sweden)

    Ursula Luetz-Meindl

    2016-07-01

    Full Text Available The unicellular freshwater alga Micrasterias denticulata is an exceptional organism due to its extraordinary star-shaped, highly symmetric morphology and has thus attracted the interest of researchers for many decades. As a member of the Streptophyta, Micrasterias is not only genetically closely related to higher land plants but shares common features with them in many physiological and cell biological aspects. These facts, together with its considerable cell size of about 200 µm, its modest cultivation conditions and the uncomplicated accessibility particularly to any microscopic techniques, make Micrasterias a very well suited cell biological plant model system. The review focuses particularly on cell wall formation and composition, dictyosomal structure and function, cytoskeleton control of growth and morphogenesis as well as on ionic regulation and signal transduction. It has been also shown in the recent years that Micrasterias is a highly sensitive indicator for environmental stress impact such as heavy metals, high salinity, oxidative stress or starvation. Stress induced organelle degradation, autophagy, adaption and detoxification mechanisms have moved in the center of interest and have been investigated with modern microscopic techniques such as 3-D- and analytical electron microscopy as well as with biochemical, physiological and molecular approaches. This review is intended to summarize and discuss the most important results obtained in Micrasterias in the last 20 years and to compare the results to similar processes in higher plant cells.

  10. Mobile Applications in Cell Biology Present New Approaches for Cell Modelling

    Science.gov (United States)

    de Oliveira, Mayara Lustosa; Galembeck, Eduardo

    2016-01-01

    Cell biology apps were surveyed in order to identify whether there are new approaches for modelling cells allowed by the new technologies implemented in tablets and smartphones. A total of 97 apps were identified in 3 stores surveyed (Apple, Google Play and Amazon), they are presented as: education 48.4%, games 26.8% and medicine 15.4%. The apps…

  11. Artificial cell mimics as simplified models for the study of cell biology.

    Science.gov (United States)

    Salehi-Reyhani, Ali; Ces, Oscar; Elani, Yuval

    2017-07-01

    Living cells are hugely complex chemical systems composed of a milieu of distinct chemical species (including DNA, proteins, lipids, and metabolites) interconnected with one another through a vast web of interactions: this complexity renders the study of cell biology in a quantitative and systematic manner a difficult task. There has been an increasing drive towards the utilization of artificial cells as cell mimics to alleviate this, a development that has been aided by recent advances in artificial cell construction. Cell mimics are simplified cell-like structures, composed from the bottom-up with precisely defined and tunable compositions. They allow specific facets of cell biology to be studied in isolation, in a simplified environment where control of variables can be achieved without interference from a living and responsive cell. This mini-review outlines the core principles of this approach and surveys recent key investigations that use cell mimics to address a wide range of biological questions. It will also place the field in the context of emerging trends, discuss the associated limitations, and outline future directions of the field. Impact statement Recent years have seen an increasing drive to construct cell mimics and use them as simplified experimental models to replicate and understand biological phenomena in a well-defined and controlled system. By summarizing the advances in this burgeoning field, and using case studies as a basis for discussion on the limitations and future directions of this approach, it is hoped that this minireview will spur others in the experimental biology community to use artificial cells as simplified models with which to probe biological systems.

  12. cellPACK: a virtual mesoscope to model and visualize structural systems biology.

    Science.gov (United States)

    Johnson, Graham T; Autin, Ludovic; Al-Alusi, Mostafa; Goodsell, David S; Sanner, Michel F; Olson, Arthur J

    2015-01-01

    cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10-100 nm) between molecular and cellular biology scales. cellPACK's modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive three-dimensional models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is available as open-source code, with tools for validation of models and with 'recipes' and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org/.

  13. Fluid models and simulations of biological cell phenomena

    Science.gov (United States)

    Greenspan, H. P.

    1982-01-01

    The dynamics of coated droplets are examined within the context of biofluids. Of specific interest is the manner in which the shape of a droplet, the motion within it as well as that of aggregates of droplets can be controlled by the modulation of surface properties and the extent to which such fluid phenomena are an intrinsic part of cellular processes. From the standpoint of biology, an objective is to elucidate some of the general dynamical features that affect the disposition of an entire cell, cell colonies and tissues. Conventionally averaged field variables of continuum mechanics are used to describe the overall global effects which result from the myriad of small scale molecular interactions. An attempt is made to establish cause and effect relationships from correct dynamical laws of motion rather than by what may have been unnecessary invocation of metabolic or life processes. Several topics are discussed where there are strong analogies droplets and cells including: encapsulated droplets/cell membranes; droplet shape/cell shape; adhesion and spread of a droplet/cell motility and adhesion; and oams and multiphase flows/cell aggregates and tissues. Evidence is presented to show that certain concepts of continuum theory such as suface tension, surface free energy, contact angle, bending moments, etc. are relevant and applicable to the study of cell biology.

  14. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  15. METABOLIC MODELLING IN THE DEVELOPMENT OF CELL FACTORIES BY SYNTHETIC BIOLOGY

    Directory of Open Access Journals (Sweden)

    Paula Jouhten

    2012-10-01

    Full Text Available Cell factories are commonly microbial organisms utilized for bioconversion of renewable resources to bulk or high value chemicals. Introduction of novel production pathways in chassis strains is the core of the development of cell factories by synthetic biology. Synthetic biology aims to create novel biological functions and systems not found in nature by combining biology with engineering. The workflow of the development of novel cell factories with synthetic biology is ideally linear which will be attainable with the quantitative engineering approach, high-quality predictive models, and libraries of well-characterized parts. Different types of metabolic models, mathematical representations of metabolism and its components, enzymes and metabolites, are useful in particular phases of the synthetic biology workflow. In this minireview, the role of metabolic modelling in synthetic biology will be discussed with a review of current status of compatible methods and models for the in silico design and quantitative evaluation of a cell factory.

  16. Bayesian parameter estimation for stochastic models of biological cell migration

    Science.gov (United States)

    Dieterich, Peter; Preuss, Roland

    2013-08-01

    Cell migration plays an essential role under many physiological and patho-physiological conditions. It is of major importance during embryonic development and wound healing. In contrast, it also generates negative effects during inflammation processes, the transmigration of tumors or the formation of metastases. Thus, a reliable quantification and characterization of cell paths could give insight into the dynamics of these processes. Typically stochastic models are applied where parameters are extracted by fitting models to the so-called mean square displacement of the observed cell group. We show that this approach has several disadvantages and problems. Therefore, we propose a simple procedure directly relying on the positions of the cell's trajectory and the covariance matrix of the positions. It is shown that the covariance is identical with the spatial aging correlation function for the supposed linear Gaussian models of Brownian motion with drift and fractional Brownian motion. The technique is applied and illustrated with simulated data showing a reliable parameter estimation from single cell paths.

  17. Systems Modelling and the Development of Coherent Understanding of Cell Biology

    Science.gov (United States)

    Verhoeff, Roald P.; Waarlo, Arend Jan; Boersma, Kerst Th.

    2008-01-01

    This article reports on educational design research concerning a learning and teaching strategy for cell biology in upper-secondary education introducing "systems modelling" as a key competence. The strategy consists of four modelling phases in which students subsequently develop models of free-living cells, a general two-dimensional model of…

  18. Modeling human risk: Cell & molecular biology in context

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.

  19. Modeling human risk: Cell ampersand molecular biology in context

    International Nuclear Information System (INIS)

    1997-06-01

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response

  20. A data integration approach for cell cycle analysis oriented to model simulation in systems biology

    Directory of Open Access Journals (Sweden)

    Mosca Ettore

    2007-08-01

    Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

  1. After the Greeting: Realizing the Potential of Physical Models in Cell Biology.

    Science.gov (United States)

    Paluch, Ewa K

    2015-12-01

    Biophysics is increasingly taking center stage in cell biology as the tools for precise quantifications of cellular behaviors expand. Interdisciplinary approaches, combining quantitative physical modeling with cell biology, are of growing interest to journal editors, funding agencies, and hiring committees. However, despite an ever-increasing emphasis on the importance of interdisciplinary research, the student trained in biology may still be at a loss as to what it actually means. I discuss here some considerations on how to achieve meaningful and high-quality interdisciplinary work. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Unleashing the potential of the root hair cell as a single plant cell type model in root systems biology

    Directory of Open Access Journals (Sweden)

    Zhenzhen eQiao

    2013-11-01

    Full Text Available Plant root is an organ composed of multiple cell types with different functions. This multicellular complexity limits our understanding of root biology because –omics studies performed at the level of the entire root reflect the average responses of all cells composing the organ. To overcome this difficulty and allow a more comprehensive understanding of root cell biology, an approach is needed that would focus on one single cell type in the plant root. Because of its biological functions (i.e. uptake of water and various nutrients; primary site of infection by nitrogen-fixing bacteria in legumes, the root hair cell is an attractive single cell model to study root cell response to various stresses and treatments. To fully study their biology, we have recently optimized procedures in obtaining root hair cell samples. We culture the plants using an ultrasound aeroponic system maximizing root hair cell density on the entire root systems and allowing the homogeneous treatment of the root system. We then isolate the root hair cells in liquid nitrogen. Isolated root hair yields could be up to 800 to 1000 mg of plant cells from 60 root systems. Using soybean as a model, the purity of the root hair was assessed by comparing the expression level of genes previously identified as soybean root hair specific between preparations of isolated root hair cells and stripped roots, roots devoid in root hairs. Enlarging our tests to include other plant species, our results support the isolation of large quantities of highly purified root hair cells which is compatible with a systems biology approach.

  3. Biological effects of desert dust in respiratory epithelial cells and a murine model.

    Science.gov (United States)

    Abstract As a result of the challenge of recent dust storms to public health, we tested the postulate that desert dust collected in the southwestern United States could impact a biological effect in respiratory epithelial cells and an animal model. Two samples of surface sedime...

  4. The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration

    Directory of Open Access Journals (Sweden)

    Luca Gentile

    2011-01-01

    Full Text Available Planarian flatworms are an exception among bilaterians in that they possess a large pool of adult stem cells that enables them to promptly regenerate any part of their body, including the brain. Although known for two centuries for their remarkable regenerative capabilities, planarians have only recently emerged as an attractive model for studying regeneration and stem cell biology. This revival is due in part to the availability of a sequenced genome and the development of new technologies, such as RNA interference and next-generation sequencing, which facilitate studies of planarian regeneration at the molecular level. Here, we highlight why planarians are an exciting tool in the study of regeneration and its underlying stem cell biology in vivo, and discuss the potential promises and current limitations of this model organism for stem cell research and regenerative medicine.

  5. Modelling effective dielectric properties of materials containing diverse types of biological cells

    International Nuclear Information System (INIS)

    Huclova, Sonja; Froehlich, Juerg; Erni, Daniel

    2010-01-01

    An efficient and versatile numerical method for the generation of different realistically shaped biological cells is developed. This framework is used to calculate the dielectric spectra of materials containing specific types of biological cells. For the generation of the numerical models of the cells a flexible parametrization method based on the so-called superformula is applied including the option of obtaining non-axisymmetric shapes such as box-shaped cells and even shapes corresponding to echinocytes. The dielectric spectra of effective media containing various cell morphologies are calculated focusing on the dependence of the spectral features on the cell shape. The numerical method is validated by comparing a model of spherical inclusions at a low volume fraction with the analytical solution obtained by the Maxwell-Garnett mixing formula, resulting in good agreement. Our simulation data for different cell shapes suggest that around 1MHz the effective dielectric properties of different cell shapes at different volume fractions significantly deviate from the spherical case. The most pronounced change exhibits ε eff between 0.1 and 1 MHz with a deviation of up to 35% for a box-shaped cell and 15% for an echinocyte compared with the sphere at a volume fraction of 0.4. This hampers the unique interpretation of changes in cellular features measured by dielectric spectroscopy when simplified material models are used.

  6. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    Science.gov (United States)

    Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

    1991-01-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

  7. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    International Nuclear Information System (INIS)

    Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Nealy, J.E.; Shinn, J.L.

    1991-02-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space

  8. A MODELING AND SIMULATION LANGUAGE FOR BIOLOGICAL CELLS WITH COUPLED MECHANICAL AND CHEMICAL PROCESSES.

    Science.gov (United States)

    Somogyi, Endre; Glazier, James A

    2017-04-01

    Biological cells are the prototypical example of active matter. Cells sense and respond to mechanical, chemical and electrical environmental stimuli with a range of behaviors, including dynamic changes in morphology and mechanical properties, chemical uptake and secretion, cell differentiation, proliferation, death, and migration. Modeling and simulation of such dynamic phenomena poses a number of computational challenges. A modeling language describing cellular dynamics must naturally represent complex intra and extra-cellular spatial structures and coupled mechanical, chemical and electrical processes. Domain experts will find a modeling language most useful when it is based on concepts, terms and principles native to the problem domain. A compiler must then be able to generate an executable model from this physically motivated description. Finally, an executable model must efficiently calculate the time evolution of such dynamic and inhomogeneous phenomena. We present a spatial hybrid systems modeling language, compiler and mesh-free Lagrangian based simulation engine which will enable domain experts to define models using natural, biologically motivated constructs and to simulate time evolution of coupled cellular, mechanical and chemical processes acting on a time varying number of cells and their environment.

  9. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    Science.gov (United States)

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  10. The female gametophyte: an emerging model for cell type-specific systems biology in plant development

    Directory of Open Access Journals (Sweden)

    Marc William Schmid

    2015-11-01

    Full Text Available Systems biology, a holistic approach describing a system emerging from the interactions of its molecular components, critically depends on accurate qualitative determination and quantitative measurements of these components. Development and improvement of large-scale profiling methods (omics now facilitates comprehensive measurements of many relevant molecules. For multicellular organisms, such as animals, fungi, algae, and plants, the complexity of the system is augmented by the presence of specialized cell types and organs, and a complex interplay within and between them. Cell type-specific analyses are therefore crucial for the understanding of developmental processes and environmental responses. This review first gives an overview of current methods used for large-scale profiling of specific cell types exemplified by recent advances in plant biology. The focus then lies on suitable model systems to study plant development and cell type specification. We introduce the female gametophyte of flowering plants as an ideal model to study fundamental developmental processes. Moreover, the female reproductive lineage is of importance for the emergence of evolutionary novelties such as an unequal parental contribution to the tissue nurturing the embryo or the clonal production of seeds by asexual reproduction (apomixis. Understanding these processes is not only interesting from a developmental or evolutionary perspective, but bears great potential for further crop improvement and the simplification of breeding efforts. We finally highlight novel methods, which are already available or which will likely soon facilitate large-scale profiling of the specific cell types of the female gametophyte in both model and non-model species. We conclude that it may take only few years until an evolutionary systems biology approach toward female gametogenesis may decipher some of its biologically most interesting and economically most valuable processes.

  11. Predicting spiral wave patterns from cell properties in a model of biological self-organization.

    Science.gov (United States)

    Geberth, Daniel; Hütt, Marc-Thorsten

    2008-09-01

    In many biological systems, biological variability (i.e., systematic differences between the system components) can be expected to outrank statistical fluctuations in the shaping of self-organized patterns. In principle, the distribution of single-element properties should thus allow predicting features of such patterns. For a mathematical model of a paradigmatic and well-studied pattern formation process, spiral waves of cAMP signaling in colonies of the slime mold Dictyostelium discoideum, we explore this possibility and observe a pronounced anticorrelation between spiral waves and cell properties (namely, the firing rate) and particularly a clustering of spiral wave tips in regions devoid of spontaneously firing (pacemaker) cells. Furthermore, we observe local inhomogeneities in the distribution of spiral chiralities, again induced by the pacemaker distribution. We show that these findings can be explained by a simple geometrical model of spiral wave generation.

  12. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  13. Sialoglycoconjugates in Trypanosoma cruzi-host cell interaction: possible biological model - a review

    Directory of Open Access Journals (Sweden)

    Alane Beatriz Vermelho

    1994-03-01

    Full Text Available A number of glycoconjugates, including glycolipids and glycoproteins, participate in the process of host-cell invasion by Trypanosoma cruzi and one of the most important carbohydrates involved on this interaction is sialic acid. It is known that parasite trans-sialidase participates with sialic acid in a coordinated fashion in the initial stages of invasion. Given the importance of these sialogycoconjugates, this review sets out various possible biological models for the interaction between the parasite and mammalian cells that possess a sialylated receptor/ligand system.

  14. Dose rate effect models for biological reaction to ionizing radiation in human cell lines

    International Nuclear Information System (INIS)

    Magae, Junji; Ogata, Hiromitsu

    2008-01-01

    Full text: Because of biological responses to ionizing radiation are dependent on irradiation time or dose rate as well as dose, simultaneous inclusion of dose and dose rate is required to evaluate the risk of long term irradiation at low dose rates. We previously published a novel statistical model for dose rate effect, modified exponential (MOE) model, which predicts irradiation time-dependent biological response to low dose rate ionizing radiation, by analyzing micronucleus formation and growth inhibition in a human osteosarcoma cell line, exposed to wide range of doses and dose rates of gamma-rays. MOE model demonstrates that logarithm of median effective dose exponentially increases in low dose rates, and thus suggests that the risk approaches to zero at infinitely low dose rate. In this paper, we extend the analysis in various kinds of human cell lines exposed to ionizing radiation for more than a year. We measured micronucleus formation and [ 3 H]thymidine uptake in human cell lines including an osteosarcoma, a DNA-dependent protein kinase-deficient glioma, a SV40-transformed fibroblast derived from an ataxia telangiectasia patient, a normal fibroblast, and leukemia cell lines. Cells were exposed to gamma-rays in irradiation room bearing 50,000 Ci of cobalt-60. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide. The number of binuclear cells bearing a micronucleus was counted under a fluorescence microscope. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [ 3 H] thymidine was pulsed for 4 h before harvesting. We statistically analyzed the data for quantitative evaluation of radiation risk. While dose and dose rate relationship cultured within one month followed MOE model in cell lines holding wild-type DNA repair system, dose rate effect was greatly impaired in DNA repair-deficient cell lines

  15. Workshop Introduction: Systems Biology and Biological Models

    Science.gov (United States)

    As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

  16. Light scattering of a Bessel beam by a nucleated biological cell: An eccentric sphere model

    Science.gov (United States)

    Wang, Jia Jie; Han, Yi Ping; Chang, Jiao Yong; Chen, Zhu Yang

    2018-02-01

    Within the framework of generalized Lorenz-Mie theory (GLMT), an eccentrically stratified dielectric sphere model illuminated by an arbitrarily incident Bessel beam is applied to investigate the scattering characteristics of a single nucleated biological cell. The Bessel beam propagating in an arbitrary direction is expanded in terms of vector spherical wave functions (VSWFs), where the beam shape coefficients (BSCs) are calculated rigorously in a closed analytical form. The effects of the half-cone angle of Bessel beam, the location of the particle in the beam, the size ratio of nucleus to cell, and the location of the nucleus inside the cell on the scattering properties of a nucleated cell are analyzed. The results provide useful references for optical diagnostic and imaging of particle having nucleated structure.

  17. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  18. Networks in Cell Biology

    Science.gov (United States)

    Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, Michele

    2010-05-01

    Introduction; 1. Network views of the cell Paolo De Los Rios and Michele Vendruscolo; 2. Transcriptional regulatory networks Sarath Chandra Janga and M. Madan Babu; 3. Transcription factors and gene regulatory networks Matteo Brilli, Elissa Calistri and Pietro Lió; 4. Experimental methods for protein interaction identification Peter Uetz, Björn Titz, Seesandra V. Rajagopala and Gerard Cagney; 5. Modeling protein interaction networks Francesco Rao; 6. Dynamics and evolution of metabolic networks Daniel Segré; 7. Hierarchical modularity in biological networks: the case of metabolic networks Erzsébet Ravasz Regan; 8. Signalling networks Gian Paolo Rossini; Appendix 1. Complex networks: from local to global properties D. Garlaschelli and G. Caldarelli; Appendix 2. Modelling the local structure of networks D. Garlaschelli and G. Caldarelli; Appendix 3. Higher-order topological properties S. Ahnert, T. Fink and G. Caldarelli; Appendix 4. Elementary mathematical concepts A. Gabrielli and G. Caldarelli; References.

  19. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.

    Science.gov (United States)

    Nickerson, M L; Witte, N; Im, K M; Turan, S; Owens, C; Misner, K; Tsang, S X; Cai, Z; Wu, S; Dean, M; Costello, J C; Theodorescu, D

    2017-01-05

    The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study

  20. Translational environmental biology: cell biology informing conservation.

    Science.gov (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Tactile Models and Games as Learning Tools for Topics of Molecular and Cell Biology

    Directory of Open Access Journals (Sweden)

    Nelma Regina Segnini Bossolan

    2017-07-01

    Full Text Available The cell structure and the dynamics of its functioning are basic topics for the understanding of phenomena on a larger scale in living organisms and for which research in science teaching has suggested several strategies based on the use of images, games, computational simulations and tactile models, among other types of external representations. Our science education research group, over the last 17 years, has developed and evaluated educational materials for teaching these topics, aimed at all levels of school. Among these materials, we highlight the tactile models for the assembly of nucleic acid, amino acids and proteins molecules, as well as a board game that deals with the process of protein synthesis. These materials were evaluated with students from the final grades of elementary and high school, in the context of the Natural Sciences Curriculum of the State of São Paulo, as well as students from two higher level courses, one of them Licentiate’s program in Exact Sciences. Activities were planned with a problem-solving approach and carried out in small groups. Tactile models of nucleic acid aided elementary students in understanding the role of these molecules in the transmission of hereditary traits. The game of protein synthesis, which depicts this process in a schematic eukaryotic cell where the participants aim to synthesize a particular protein, promoted the development of skills such as “decision making” and “making anticipations” among high school students, in addition of expanding their knowledge about the biological functions of these molecules. The tactile models of amino acids and proteins used by students of higher education promoted their spatial perception of these molecules, allowing the prediction of intra- and intermolecular interactions. It is important to emphasize the importance of these educational resources in the construction of more functional mental models of cells and of intracellular processes.

  2. Biology of Schwann cells.

    Science.gov (United States)

    Kidd, Grahame J; Ohno, Nobuhiko; Trapp, Bruce D

    2013-01-01

    The fundamental roles of Schwann cells during peripheral nerve formation and regeneration have been recognized for more than 100 years, but the cellular and molecular mechanisms that integrate Schwann cell and axonal functions continue to be elucidated. Derived from the embryonic neural crest, Schwann cells differentiate into myelinating cells or bundle multiple unmyelinated axons into Remak fibers. Axons dictate which differentiation path Schwann cells follow, and recent studies have established that axonal neuregulin1 signaling via ErbB2/B3 receptors on Schwann cells is essential for Schwann cell myelination. Extracellular matrix production and interactions mediated by specific integrin and dystroglycan complexes are also critical requisites for Schwann cell-axon interactions. Myelination entails expansion and specialization of the Schwann cell plasma membrane over millimeter distances. Many of the myelin-specific proteins have been identified, and transgenic manipulation of myelin genes have provided novel insights into myelin protein function, including maintenance of axonal integrity and survival. Cellular events that facilitate myelination, including microtubule-based protein and mRNA targeting, and actin based locomotion, have also begun to be understood. Arguably, the most remarkable facet of Schwann cell biology, however, is their vigorous response to axonal damage. Degradation of myelin, dedifferentiation, division, production of axonotrophic factors, and remyelination all underpin the substantial regenerative capacity of the Schwann cells and peripheral nerves. Many of these properties are not shared by CNS fibers, which are myelinated by oligodendrocytes. Dissecting the molecular mechanisms responsible for the complex biology of Schwann cells continues to have practical benefits in identifying novel therapeutic targets not only for Schwann cell-specific diseases but other disorders in which axons degenerate. Copyright © 2013 Elsevier B.V. All rights

  3. Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory

    Science.gov (United States)

    Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

    2010-01-01

    A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

  4. Artificial vesicles as an animal cell model for the study of biological application of non-thermal plasma

    International Nuclear Information System (INIS)

    Ki, S H; Park, J K; Sung, C; Lee, C B; Uhm, H; Choi, E H; Baik, K Y

    2016-01-01

    Artificial cell-like model systems can provide information which is hard to obtain with real biological cells. Giant unilamellar vesicles (GUV) containing intra-membrane DNA or OH radical-binding molecules are used to visualize the cytolytic activity of OH radicals. Changes in the GUV membrane are observed by microscopy or flow cytometry as performed for animal cells after non-thermal plasma treatment. The experimental data shows that OH radicals can be detected inside the membrane, although the biological effects are not as significant as for H 2 O 2 . This artificial model system can provide a systemic means to elucidate the complex interactions between biological materials and non-thermal plasma. (paper)

  5. Mesangial cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Abboud, Hanna E., E-mail: Abboud@uthscsa.edu

    2012-05-15

    Mesangial cells originate from the metanephric mesenchyme and maintain structural integrity of the glomerular microvascular bed and mesangial matrix homeostasis. In response to metabolic, immunologic or hemodynamic injury, these cells undergo apoptosis or acquire an activated phenotype and undergo hypertrophy, proliferation with excessive production of matrix proteins, growth factors, chemokines and cytokines. These soluble factors exert autocrine and paracrine effects on the cells or on other glomerular cells, respectively. MCs are primary targets of immune-mediated glomerular diseases such as IGA nephropathy or metabolic diseases such as diabetes. MCs may also respond to injury that primarily involves podocytes and endothelial cells or to structural and genetic abnormalities of the glomerular basement membrane. Signal transduction and oxidant stress pathways are activated in MCs and likely represent integrated input from multiple mediators. Such responses are convenient targets for therapeutic intervention. Studies in cultured MCs should be supplemented with in vivo studies as well as examination of freshly isolated cells from normal and diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex, cells should be studied in their natural environment, isolated glomeruli or even tissue slices. Identification of a specific marker of MCs should help genetic manipulation as well as selective therapeutic targeting of these cells. Identification of biological responses of MCs that are not mediated by the renin–angiotensin system should help development of novel and effective therapeutic strategies to treat diseases characterized by MC pathology.

  6. Mesangial cell biology

    International Nuclear Information System (INIS)

    Abboud, Hanna E.

    2012-01-01

    Mesangial cells originate from the metanephric mesenchyme and maintain structural integrity of the glomerular microvascular bed and mesangial matrix homeostasis. In response to metabolic, immunologic or hemodynamic injury, these cells undergo apoptosis or acquire an activated phenotype and undergo hypertrophy, proliferation with excessive production of matrix proteins, growth factors, chemokines and cytokines. These soluble factors exert autocrine and paracrine effects on the cells or on other glomerular cells, respectively. MCs are primary targets of immune-mediated glomerular diseases such as IGA nephropathy or metabolic diseases such as diabetes. MCs may also respond to injury that primarily involves podocytes and endothelial cells or to structural and genetic abnormalities of the glomerular basement membrane. Signal transduction and oxidant stress pathways are activated in MCs and likely represent integrated input from multiple mediators. Such responses are convenient targets for therapeutic intervention. Studies in cultured MCs should be supplemented with in vivo studies as well as examination of freshly isolated cells from normal and diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex, cells should be studied in their natural environment, isolated glomeruli or even tissue slices. Identification of a specific marker of MCs should help genetic manipulation as well as selective therapeutic targeting of these cells. Identification of biological responses of MCs that are not mediated by the renin–angiotensin system should help development of novel and effective therapeutic strategies to treat diseases characterized by MC pathology.

  7. Model system for plant cell biology: GFP imaging in living onion epidermal cells

    Science.gov (United States)

    Scott, A.; Wyatt, S.; Tsou, P. L.; Robertson, D.; Allen, N. S.

    1999-01-01

    The ability to visualize organelle localization and dynamics is very useful in studying cellular physiological events. Until recently, this has been accomplished using a variety of staining methods. However, staining can give inaccurate information due to nonspecific staining, diffusion of the stain or through toxic effects. The ability to target green fluorescent protein (GFP) to various organelles allows for specific labeling of organelles in vivo. The disadvantages of GFP thus far have been the time and money involved in developing stable transformants or maintaining cell cultures for transient expression. In this paper, we present a rapid transient expression system using onion epidermal peels. We have localized GFP to various cellular compartments (including the cell wall) to illustrate the utility of this method and to visualize dynamics of these compartments. The onion epidermis has large, living, transparent cells in a monolayer, making them ideal for visualizing GFP. This method is easy and inexpensive, and it allows for testing of new GFP fusion proteins in a living tissue to determine deleterious effects and the ability to express before stable transformants are attempted.

  8. Models for synthetic biology.

    Science.gov (United States)

    Kaznessis, Yiannis N

    2007-11-06

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

  9. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D

    2015-08-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  10. Multiscale models and stochastic simulation methods for computing rare but key binding events in cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Guerrier, C. [Applied Mathematics and Computational Biology, IBENS, Ecole Normale Supérieure, 46 rue d' Ulm, 75005 Paris (France); Holcman, D., E-mail: david.holcman@ens.fr [Applied Mathematics and Computational Biology, IBENS, Ecole Normale Supérieure, 46 rue d' Ulm, 75005 Paris (France); Mathematical Institute, Oxford OX2 6GG, Newton Institute (United Kingdom)

    2017-07-01

    The main difficulty in simulating diffusion processes at a molecular level in cell microdomains is due to the multiple scales involving nano- to micrometers. Few to many particles have to be simulated and simultaneously tracked while there are exploring a large portion of the space for binding small targets, such as buffers or active sites. Bridging the small and large spatial scales is achieved by rare events representing Brownian particles finding small targets and characterized by long-time distribution. These rare events are the bottleneck of numerical simulations. A naive stochastic simulation requires running many Brownian particles together, which is computationally greedy and inefficient. Solving the associated partial differential equations is also difficult due to the time dependent boundary conditions, narrow passages and mixed boundary conditions at small windows. We present here two reduced modeling approaches for a fast computation of diffusing fluxes in microdomains. The first approach is based on a Markov mass-action law equations coupled to a Markov chain. The second is a Gillespie's method based on the narrow escape theory for coarse-graining the geometry of the domain into Poissonian rates. The main application concerns diffusion in cellular biology, where we compute as an example the distribution of arrival times of calcium ions to small hidden targets to trigger vesicular release.

  11. Multiscale models and stochastic simulation methods for computing rare but key binding events in cell biology

    International Nuclear Information System (INIS)

    Guerrier, C.; Holcman, D.

    2017-01-01

    The main difficulty in simulating diffusion processes at a molecular level in cell microdomains is due to the multiple scales involving nano- to micrometers. Few to many particles have to be simulated and simultaneously tracked while there are exploring a large portion of the space for binding small targets, such as buffers or active sites. Bridging the small and large spatial scales is achieved by rare events representing Brownian particles finding small targets and characterized by long-time distribution. These rare events are the bottleneck of numerical simulations. A naive stochastic simulation requires running many Brownian particles together, which is computationally greedy and inefficient. Solving the associated partial differential equations is also difficult due to the time dependent boundary conditions, narrow passages and mixed boundary conditions at small windows. We present here two reduced modeling approaches for a fast computation of diffusing fluxes in microdomains. The first approach is based on a Markov mass-action law equations coupled to a Markov chain. The second is a Gillespie's method based on the narrow escape theory for coarse-graining the geometry of the domain into Poissonian rates. The main application concerns diffusion in cellular biology, where we compute as an example the distribution of arrival times of calcium ions to small hidden targets to trigger vesicular release.

  12. Illuminating Cell Biology

    Science.gov (United States)

    2002-01-01

    NASA's Ames Research Center awarded Ciencia, Inc., a Small Business Innovation Research contract to develop the Cell Fluorescence Analysis System (CFAS) to address the size, mass, and power constraints of using fluorescence spectroscopy in the International Space Station's Life Science Research Facility. The system will play an important role in studying biological specimen's long-term adaptation to microgravity. Commercial applications for the technology include diverse markets such as food safety, in situ environmental monitoring, online process analysis, genomics and DNA chips, and non-invasive diagnostics. Ciencia has already sold the system to the private sector for biosensor applications.

  13. Laboratory of Biological Modeling

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to a...

  14. Mammalian cell biology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival

  15. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  16. Unicellular eukaryotes as models in cell and molecular biology: critical appraisal of their past and future value.

    Science.gov (United States)

    Simon, Martin; Plattner, Helmut

    2014-01-01

    Unicellular eukaryotes have been appreciated as model systems for the analysis of crucial questions in cell and molecular biology. This includes Dictyostelium (chemotaxis, amoeboid movement, phagocytosis), Tetrahymena (telomere structure, telomerase function), Paramecium (variant surface antigens, exocytosis, phagocytosis cycle) or both ciliates (ciliary beat regulation, surface pattern formation), Chlamydomonas (flagellar biogenesis and beat), and yeast (S. cerevisiae) for innumerable aspects. Nowadays many problems may be tackled with "higher" eukaryotic/metazoan cells for which full genomic information as well as domain databases, etc., were available long before protozoa. Established molecular tools, commercial antibodies, and established pharmacology are additional advantages available for higher eukaryotic cells. Moreover, an increasing number of inherited genetic disturbances in humans have become elucidated and can serve as new models. Among lower eukaryotes, yeast will remain a standard model because of its peculiarities, including its reduced genome and availability in the haploid form. But do protists still have a future as models? This touches not only the basic understanding of biology but also practical aspects of research, such as fund raising. As we try to scrutinize, due to specific advantages some protozoa should and will remain favorable models for analyzing novel genes or specific aspects of cell structure and function. Outstanding examples are epigenetic phenomena-a field of rising interest. © 2014 Elsevier Inc. All rights reserved.

  17. Three-dimensional models of cancer for pharmacology and cancer cell biology: capturing tumor complexity in vitro/ex vivo.

    Science.gov (United States)

    Hickman, John A; Graeser, Ralph; de Hoogt, Ronald; Vidic, Suzana; Brito, Catarina; Gutekunst, Matthias; van der Kuip, Heiko

    2014-09-01

    Cancers are complex and heterogeneous pathological "organs" in a dynamic interplay with their host. Models of human cancer in vitro, used in cancer biology and drug discovery, are generally highly reductionist. These cancer models do not incorporate complexity or heterogeneity. This raises the question as to whether the cancer models' biochemical circuitry (not their genome) represents, with sufficient fidelity, a tumor in situ. Around 95% of new anticancer drugs eventually fail in clinical trial, despite robust indications of activity in existing in vitro pre-clinical models. Innovative models are required that better capture tumor biology. An important feature of all tissues, and tumors, is that cells grow in three dimensions. Advances in generating and characterizing simple and complex (with added stromal components) three-dimensional in vitro models (3D models) are reviewed in this article. The application of stirred bioreactors to permit both scale-up/scale-down of these cancer models and, importantly, methods to permit controlled changes in environment (pH, nutrients, and oxygen) are also described. The challenges of generating thin tumor slices, their utility, and potential advantages and disadvantages are discussed. These in vitro/ex vivo models represent a distinct move to capture the realities of tumor biology in situ, but significant characterization work still remains to be done in order to show that their biochemical circuitry accurately reflects that of a tumor. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Numerical Approach to Spatial Deterministic-Stochastic Models Arising in Cell Biology.

    Science.gov (United States)

    Schaff, James C; Gao, Fei; Li, Ye; Novak, Igor L; Slepchenko, Boris M

    2016-12-01

    Hybrid deterministic-stochastic methods provide an efficient alternative to a fully stochastic treatment of models which include components with disparate levels of stochasticity. However, general-purpose hybrid solvers for spatially resolved simulations of reaction-diffusion systems are not widely available. Here we describe fundamentals of a general-purpose spatial hybrid method. The method generates realizations of a spatially inhomogeneous hybrid system by appropriately integrating capabilities of a deterministic partial differential equation solver with a popular particle-based stochastic simulator, Smoldyn. Rigorous validation of the algorithm is detailed, using a simple model of calcium 'sparks' as a testbed. The solver is then applied to a deterministic-stochastic model of spontaneous emergence of cell polarity. The approach is general enough to be implemented within biologist-friendly software frameworks such as Virtual Cell.

  19. An in vivo model to assess magnesium alloys and their biological effect on human bone marrow stromal cells.

    Science.gov (United States)

    Yoshizawa, Sayuri; Chaya, Amy; Verdelis, Kostas; Bilodeau, Elizabeth A; Sfeir, Charles

    2015-12-01

    Magnesium (Mg) alloys have many unique qualities which make them ideal candidates for bone fixation devices, including biocompatibility and degradation in vivo. Despite a rise in Mg alloy production and research, there remains no standardized system to assess their degradation or biological effect on human stem cells in vivo. In this study, we developed a novel in vivo model to assess Mg alloys for craniofacial and orthopedic applications. Our model consists of a collagen sponge seeded with human bone marrow stromal cells (hBMSCs) around a central Mg alloy rod. These scaffolds were implanted subcutaneously in mice and analyzed after eight weeks. Alloy degradation and biological effect were determined by microcomputed tomography (microCT), histological staining, and immunohistochemistry (IHC). MicroCT showed greater volume loss for pure Mg compared to AZ31 after eight weeks in vivo. Histological analysis showed that hBMSCs were retained around the Mg implants after 8 weeks. Furthermore, immunohistochemistry showed the expression of dentin matrix protein 1 and osteopontin around both pure Mg and AZ31 with implanted hBMSCs. In addition, histological sections showed a thin mineral layer around all degrading alloys at the alloy-tissue interface. In conclusion, our data show that degrading pure Mg and AZ31 implants are cytocompatible and do not inhibit the osteogenic property of hBMSCs in vivo. These results demonstrate that this model can be used to efficiently assess the biological effect of corroding Mg alloys in vivo. Importantly, this model may be modified to accommodate additional cell types and clinical applications. Magnesium (Mg) alloys have been investigated as ideal candidates for bone fixation devices due to high biocompatibility and degradation in vivo, and there is a growing need of establishing an efficient in vivo material screening system. In this study, we assessed degradation rate and biological effect of Mg alloys by transplanting Mg alloy rod with

  20. Tactile Models and Games as Learning Tools for Topics of Molecular and Cell Biology

    OpenAIRE

    Nelma Regina Segnini Bossolan

    2017-01-01

    The cell structure and the dynamics of its functioning are basic topics for the understanding of phenomena on a larger scale in living organisms and for which research in science teaching has suggested several strategies based on the use of images, games, computational simulations and tactile models, among other types of external representations. Our science education research group, over the last 17 years, has developed and evaluated educational materials for teaching these topics, aimed at ...

  1. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Progress is reported on the following research projects: the effects of N-ethyl-maleimide and hydroxyurea on hamster cells in culture; sensitization of synchronized human cells to x rays by N-ethylmaleimide; sensitization of hypoxic mammalian cells with a sulfhydryl inhibitor; damage interaction due to ionizing and nonionizing radiation in mammalian cells; DNA damage relative to radioinduced cell killing; spurious photolability of DNA labeled with methyl- 14 C-thymidine; radioinduced malignant transformation of cultured mouse cells; a comparison of properties of uv and near uv light relative to cell function and DNA damage; Monte Carlo simulation of DNA damage and repair mechanisms; and radiobiology of fast neutrons

  2. Studying cell biology in the skin.

    Science.gov (United States)

    Morrow, Angel; Lechler, Terry

    2015-11-15

    Advances in cell biology have often been driven by studies in diverse organisms and cell types. Although there are technical reasons for why different cell types are used, there are also important physiological reasons. For example, ultrastructural studies of vesicle transport were aided by the use of professional secretory cell types. The use of tissues/primary cells has the advantage not only of using cells that are adapted to the use of certain cell biological machinery, but also of highlighting the physiological roles of this machinery. Here we discuss advantages of the skin as a model system. We discuss both advances in cell biology that used the skin as a driving force and future prospects for use of the skin to understand basic cell biology. A unique combination of characteristics and tools makes the skin a useful in vivo model system for many cell biologists. © 2015 Morrow and Lechler. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  4. Mechanics rules cell biology

    Directory of Open Access Journals (Sweden)

    Wang James HC

    2010-07-01

    Full Text Available Abstract Cells in the musculoskeletal system are subjected to various mechanical forces in vivo. Years of research have shown that these mechanical forces, including tension and compression, greatly influence various cellular functions such as gene expression, cell proliferation and differentiation, and secretion of matrix proteins. Cells also use mechanotransduction mechanisms to convert mechanical signals into a cascade of cellular and molecular events. This mini-review provides an overview of cell mechanobiology to highlight the notion that mechanics, mainly in the form of mechanical forces, dictates cell behaviors in terms of both cellular mechanobiological responses and mechanotransduction.

  5. Interaction of Clostridium perfringens epsilon-toxin with biological and model membranes: A putative protein receptor in cells.

    Science.gov (United States)

    Manni, Marco M; Sot, Jesús; Goñi, Félix M

    2015-03-01

    Epsilon-toxin (ETX) is a powerful toxin produced by some strains of Clostridium perfringens (classified as types B and D) that is responsible for enterotoxemia in animals. ETX forms pores through the plasma membrane of eukaryotic cells, consisting of a β-barrel of 14 amphipathic β-strands. ETX shows a high specificity for certain cell lines, of which Madin-Darby canine kidney (MDCK) is the first sensitive cell line identified and the most studied one. The aim of this study was to establish the role of lipids in the toxicity caused by ETX and the correlation of its activity in model and biological membranes. In MDCK cells, using cell counting and confocal microscopy, we have observed that the toxin causes cell death mediated by toxin binding to plasma membrane. Moreover, ETX binds and permeabilizes the membranes of giant plasma membrane vesicles (GPMV). However, little effect is observed on protein-free vesicles. The data suggest the essential role of a protein receptor for the toxin in cell membranes. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Molecular biology of the cell

    National Research Council Canada - National Science Library

    Alberts, Bruce; Walter, Peter; Raff, Martin; Roberts, Keith; Lewis, Julian; Johnson, Alexander

    2007-01-01

    .... By extracting fundamental concepts and meaning from this enormous and ever-growing field, the authors tell the story of cell biology, and create a coherent framework through which non-expert readers...

  7. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)

  8. The Virtual Cell: a software environment for computational cell biology.

    Science.gov (United States)

    Loew, L M; Schaff, J C

    2001-10-01

    The newly emerging field of computational cell biology requires software tools that address the needs of a broad community of scientists. Cell biological processes are controlled by an interacting set of biochemical and electrophysiological events that are distributed within complex cellular structures. Computational modeling is familiar to researchers in fields such as molecular structure, neurobiology and metabolic pathway engineering, and is rapidly emerging in the area of gene expression. Although some of these established modeling approaches can be adapted to address problems of interest to cell biologists, relatively few software development efforts have been directed at the field as a whole. The Virtual Cell is a computational environment designed for cell biologists as well as for mathematical biologists and bioengineers. It serves to aid the construction of cell biological models and the generation of simulations from them. The system enables the formulation of both compartmental and spatial models, the latter with either idealized or experimentally derived geometries of one, two or three dimensions.

  9. Molecular biology of the cell

    CERN Document Server

    Alberts, Bruce; Lewis, Julian

    2000-01-01

    Molecular Biology of the Cell is the classic in-dept text reference in cell biology. By extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and create a coherent framework through which non-expert readers may approach the subject. Written in clear and concise language, and beautifully illustrated, the book is enjoyable to read, and it provides a clear sense of the excitement of modern biology. Molecular Biology of the Cell sets forth the current understanding of cell biology (completely updated as of Autumn 2001), and it explores the intriguing implications and possibilities of the great deal that remains unknown. The hallmark features of previous editions continue in the Fourth Edition. The book is designed with a clean and open, single-column layout. The art program maintains a completely consistent format and style, and includes over 1,600 photographs, electron micrographs, and original drawings by the authors. Clear and concise concept...

  10. Teaching Real Data Interpretation with Models (TRIM): Analysis of Student Dialogue in a Large-Enrollment Cell and Developmental Biology Course

    Science.gov (United States)

    Zagallo, Patricia; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    We present our design for a cell biology course to integrate content with scientific practices, specifically data interpretation and model-based reasoning. A 2-year research project within this course allowed us to understand how students interpret authentic biological data in this setting. Through analysis of written work, we measured the extent…

  11. Developmental biology, the stem cell of biological disciplines

    OpenAIRE

    Gilbert, Scott F.

    2017-01-01

    Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines.” Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, ...

  12. The central dogma of cell biology.

    Science.gov (United States)

    Cooper, S

    1981-06-01

    The Continuum Model proposes that preparations for DNA synthesis occur continuously during all phases of the division cycle. Various stimuli activate cell proliferation by changing the rate of initiator (protein) synthesis. Cell division does not initiate any process regulating cell proliferation. Cell division is the end of a process and the beginning of nothing. The alternative model which has cell proliferation regulated in the G1 phase of the division cycle is reexamined and the two types of evidence for this model, G1-variability and G1-arrest are shown to be compatible with the Continuum Model. Here, the Continuum Model is generalized to produce a new look at the logic of the division cycle in prokaryotes and eukaryotes. This new view, the Central Dogma of Cell Biology, is presented and two predictions are made. I propose that (i) cell division does not have any regulatory function, and (ii) that DNA synthesis may, indeed, have some affect on the synthesis of initiator.

  13. Computational Tools for Stem Cell Biology.

    Science.gov (United States)

    Bian, Qin; Cahan, Patrick

    2016-12-01

    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Teaching Cell Biology in Primary Schools

    Directory of Open Access Journals (Sweden)

    Francele de Abreu Carlan

    2014-01-01

    Full Text Available Basic concepts of cell biology are essential for scientific literacy. However, because many aspects of cell theory and cell functioning are quite abstract, students experience difficulties understanding them. In this study, we investigated whether diverse teaching resources such as the use of replicas of Leeuwenhoek’s microscope, visualization of cells using an optical microscope, construction of three-dimensional cell models, and reading of a comic book about cells could mitigate the difficulties encountered when teaching cell biology to 8th-grade primary school students. The results suggest that these didactic activities improve students’ ability to learn concrete concepts about cell biology, such as the composition of living beings, growth, and cicatrization. Also, the development of skills was observed, as, for example, the notion of cell size. However, no significant improvements were observed in students’ ability to learn about abstract topics, such as the structures of subcellular organelles and their functions. These results suggest that many students in this age have not yet concluded Piaget’s concrete operational stage, indicating that the concepts required for the significant learning of abstract subjects need to be explored more thoroughly in the process of designing programs that introduce primary school students to cell biology.

  15. Developmental biology, the stem cell of biological disciplines.

    Science.gov (United States)

    Gilbert, Scott F

    2017-12-01

    Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

  16. Theories and models of the biology of the cell in space--an introduction

    Science.gov (United States)

    Cogoli, A.; Cogoli-Greuter, M.

    1994-01-01

    The World Space Congress 1992 took place after two Spacelab flights with important biological payloads on board, the SLS-1 (June 1991) and IML-1 (January 1992) missions respectively. Interesting experiments were carried out in 1991 also on the Shuttle middeck and on the sounding rocket MASER 4. The highlights of the investigations on these missions together with the results of relevant ground-based research were presented at the symposium.

  17. Cell biology experiments conducted in space

    Science.gov (United States)

    Taylor, G. R.

    1977-01-01

    A review of cell biology experiments conducted during the first two decades of space flight is provided. References are tabulated for work done with six types of living test system: isolated viruses, bacteriophage-host, bacteria, yeasts and filamentous fungi, protozoans, and small groups of cells (such as hamster cell tissue and fertilized frog eggs). The general results of studies involving the survival of cells in space, the effect of space flight on growing cultures, the biological effects of multicharged high-energy particles, and the effects of space flight on the genetic apparatus of microorganisms are summarized. It is concluded that cell systems remain sufficiently stable during space flight to permit experimentation with models requiring a fixed cell line during the space shuttle era.

  18. Surface functionalization of a polymeric lipid bilayer for coupling a model biological membrane with molecules, cells, and microstructures.

    Science.gov (United States)

    Morigaki, Kenichi; Mizutani, Kazuyuki; Saito, Makoto; Okazaki, Takashi; Nakajima, Yoshihiro; Tatsu, Yoshiro; Imaishi, Hiromasa

    2013-02-26

    We describe a stable and functional model biological membrane based on a polymerized lipid bilayer with a chemically modified surface. A polymerized lipid bilayer was formed from a mixture of two diacetylene-containing phospholipids, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC) and 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (DiynePE). DiynePC formed a stable bilayer structure, whereas the ethanolamine headgroup of DiynePE enabled functional molecules to be grafted onto the membrane surface. Copolymerization of DiynePC and DiynePE resulted in a robust bilayer. Functionalization of the polymeric bilayer provided a route to a robust and biomimetic surface that can be linked with biomolecules, cells, and three-dimensional (3D) microstructures. Biotin and peptides were grafted onto the polymeric bilayer for attaching streptavidin and cultured mammalian cells by molecular recognition, respectively. Nonspecific adsorption of proteins and cells on polymeric bilayers was minimum. DiynePE was also used to attach a microstructure made of an elastomer (polydimethylsiloxan: PDMS) onto the membrane, forming a confined aqueous solution between the two surfaces. The microcompartment enabled us to assay the activity of a membrane-bound enzyme (cyochrome P450). Natural (fluid) lipid bilayers were incorporated together with membrane-bound proteins by lithographically polymerizing DiynePC/DiynePE bilayers. The hybrid membrane of functionalized polymeric bilayers and fluid bilayers offers a novel platform for a wide range of biomedical applications including biosensor, bioassay, cell culture, and cell-based assay.

  19. Soft x-ray-controlled dose deposition in yeast cells: techniques, model, and biological assessment

    Science.gov (United States)

    Milani, Marziale; Batani, Dimitri; Conti, Aldo; Masini, Alessandra; Costato, Michele; Pozzi, Achille; Turcu, I. C. Edmond

    1996-12-01

    A procedure is presented to release soft x-rays onto yeast cell membrane allegedly damaging the resident enzymatic processes connected with fermentation. The damage is expected to be restricted to regulating fermentation processes without interference with respiration. By this technique fermentation is followed leading to CO2 production, and respiration resulting in global pressure measurements. A solid state pressure sensor system has been developed linked to a data acquisition system. Yeast cells cultures have been investigated at different concentrations and with different nutrients. A non-monotone response in CO2 production as a function of the delivered x-ray dose is observed.

  20. Integrating interactive computational modeling in biology curricula.

    Directory of Open Access Journals (Sweden)

    Tomáš Helikar

    2015-03-01

    Full Text Available While the use of computer tools to simulate complex processes such as computer circuits is normal practice in fields like engineering, the majority of life sciences/biological sciences courses continue to rely on the traditional textbook and memorization approach. To address this issue, we explored the use of the Cell Collective platform as a novel, interactive, and evolving pedagogical tool to foster student engagement, creativity, and higher-level thinking. Cell Collective is a Web-based platform used to create and simulate dynamical models of various biological processes. Students can create models of cells, diseases, or pathways themselves or explore existing models. This technology was implemented in both undergraduate and graduate courses as a pilot study to determine the feasibility of such software at the university level. First, a new (In Silico Biology class was developed to enable students to learn biology by "building and breaking it" via computer models and their simulations. This class and technology also provide a non-intimidating way to incorporate mathematical and computational concepts into a class with students who have a limited mathematical background. Second, we used the technology to mediate the use of simulations and modeling modules as a learning tool for traditional biological concepts, such as T cell differentiation or cell cycle regulation, in existing biology courses. Results of this pilot application suggest that there is promise in the use of computational modeling and software tools such as Cell Collective to provide new teaching methods in biology and contribute to the implementation of the "Vision and Change" call to action in undergraduate biology education by providing a hands-on approach to biology.

  1. Integrating interactive computational modeling in biology curricula.

    Science.gov (United States)

    Helikar, Tomáš; Cutucache, Christine E; Dahlquist, Lauren M; Herek, Tyler A; Larson, Joshua J; Rogers, Jim A

    2015-03-01

    While the use of computer tools to simulate complex processes such as computer circuits is normal practice in fields like engineering, the majority of life sciences/biological sciences courses continue to rely on the traditional textbook and memorization approach. To address this issue, we explored the use of the Cell Collective platform as a novel, interactive, and evolving pedagogical tool to foster student engagement, creativity, and higher-level thinking. Cell Collective is a Web-based platform used to create and simulate dynamical models of various biological processes. Students can create models of cells, diseases, or pathways themselves or explore existing models. This technology was implemented in both undergraduate and graduate courses as a pilot study to determine the feasibility of such software at the university level. First, a new (In Silico Biology) class was developed to enable students to learn biology by "building and breaking it" via computer models and their simulations. This class and technology also provide a non-intimidating way to incorporate mathematical and computational concepts into a class with students who have a limited mathematical background. Second, we used the technology to mediate the use of simulations and modeling modules as a learning tool for traditional biological concepts, such as T cell differentiation or cell cycle regulation, in existing biology courses. Results of this pilot application suggest that there is promise in the use of computational modeling and software tools such as Cell Collective to provide new teaching methods in biology and contribute to the implementation of the "Vision and Change" call to action in undergraduate biology education by providing a hands-on approach to biology.

  2. Stem cell biology meets systems biology

    OpenAIRE

    Roeder, I.; Radtke, F.

    2009-01-01

    Stem cells and their descendents are the building blocks of life. How stem cell populations guarantee their maintenance and/or self-renewal, and how individual stem cells decide to transit from one cell stage to another to generate different cell types are long-standing and fascinating questions in the field. Here, we review the discussions that took place at a recent EMBO conference in Cambridge, UK, in which these questions were placed in the context of the latest advances in stem cell biol...

  3. Biological fuel cells and their applications

    OpenAIRE

    Shukla, AK; Suresh, P; Berchmans, S; Rajendran, A

    2004-01-01

    One type of genuine fuel cell that does hold promise in the long-term is the biological fuel cell. Unlike conventional fuel cells, which employ hydrogen, ethanol and methanol as fuel, biological fuel cells use organic products produced by metabolic processes or use organic electron donors utilized in the growth processes as fuels for current generation. A distinctive feature of biological fuel cells is that the electrode reactions are controlled by biocatalysts, i.e. the biological redox-reac...

  4. Stochastic processes in cell biology

    CERN Document Server

    Bressloff, Paul C

    2014-01-01

    This book develops the theory of continuous and discrete stochastic processes within the context of cell biology.  A wide range of biological topics are covered including normal and anomalous diffusion in complex cellular environments, stochastic ion channels and excitable systems, stochastic calcium signaling, molecular motors, intracellular transport, signal transduction, bacterial chemotaxis, robustness in gene networks, genetic switches and oscillators, cell polarization, polymerization, cellular length control, and branching processes. The book also provides a pedagogical introduction to the theory of stochastic process – Fokker Planck equations, stochastic differential equations, master equations and jump Markov processes, diffusion approximations and the system size expansion, first passage time problems, stochastic hybrid systems, reaction-diffusion equations, exclusion processes, WKB methods, martingales and branching processes, stochastic calculus, and numerical methods.   This text is primarily...

  5. Electromagnetic effects - From cell biology to medicine.

    Science.gov (United States)

    Funk, Richard H W; Monsees, Thomas; Ozkucur, Nurdan

    2009-01-01

    In this review we compile and discuss the published plethora of cell biological effects which are ascribed to electric fields (EF), magnetic fields (MF) and electromagnetic fields (EMF). In recent years, a change in paradigm took place concerning the endogenously produced static EF of cells and tissues. Here, modern molecular biology could link the action of ion transporters and ion channels to the "electric" action of cells and tissues. Also, sensing of these mainly EF could be demonstrated in studies of cell migration and wound healing. The triggers exerted by ion concentrations and concomitant electric field gradients have been traced along signaling cascades till gene expression changes in the nucleus. Far more enigmatic is the way of action of static MF which come in most cases from outside (e.g. earth magnetic field). All systems in an organism from the molecular to the organ level are more or less in motion. Thus, in living tissue we mostly find alternating fields as well as combination of EF and MF normally in the range of extremely low-frequency EMF. Because a bewildering array of model systems and clinical devices exits in the EMF field we concentrate on cell biological findings and look for basic principles in the EF, MF and EMF action. As an outlook for future research topics, this review tries to link areas of EF, MF and EMF research to thermodynamics and quantum physics, approaches that will produce novel insights into cell biology.

  6. Issues in Biological Shape Modelling

    DEFF Research Database (Denmark)

    Hilger, Klaus Baggesen

    This talk reflects parts of the current research at informatics and Mathematical Modelling at the Technical University of Denmark within biological shape modelling. We illustrate a series of generalizations, modifications, and applications of the elements of constructing models of shape or appear......This talk reflects parts of the current research at informatics and Mathematical Modelling at the Technical University of Denmark within biological shape modelling. We illustrate a series of generalizations, modifications, and applications of the elements of constructing models of shape...

  7. Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhou

    Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

  8. Feedback dynamics and cell function: Why systems biology is called Systems Biology.

    Science.gov (United States)

    Wolkenhauer, Olaf; Mesarovic, Mihajlo

    2005-05-01

    A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

  9. Laboratory of Cell and Molecular Biology

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Cell and Molecular Biology investigates the organization, compartmentalization, and biochemistry of eukaryotic cells and the pathology associated...

  10. Automatic detection of biological cells

    International Nuclear Information System (INIS)

    Alves Da Costa, Caiuby

    1983-01-01

    The present research work has dealt with the analysis of biological cell images in general, and more specially with the cervical cells. This work was carried out in order to develop an automaton leading to a better prevention of cancer through automated mass screening. The device has been implemented on Motorola 68.000 microprocessor system. The automaton carries out cell nucleus analysis in several steps. The main steps are: - First: the automaton focuses on an individual cell nucleus among the smear's cell (about 10.000), - Second: it process each nucleus image. The digital processing yields geometrical of the nucleus (area and perimeter) for each cell. These data are stored in a local memory for further discriminant analysis by a microcomputer. In this way smears are classed in two groups: hale smears and uncertain smears. The automaton uses a wired logic for image acquisition and its software algorithms provide image reconstruction. The reconstruction algorithms are general purpose. Tests have proved that they can reconstruct any two dimensional images independently of its geometrical form. Moreover they can make the reconstruction of any image among the several images present in observation field. The processing times registered during the tests (for different cases) were situated, all of them, below three minutes for 10,000 images (each of them formed by an average of 450 pixels). The interest of the method is generality and speed. The only restriction is the primary device sensor (CCD linear array) length. Thus the automaton application can be extended beyond the biological image field. (author) [fr

  11. Mathematical modeling of biological processes

    CERN Document Server

    Friedman, Avner

    2014-01-01

    This book on mathematical modeling of biological processes includes a wide selection of biological topics that demonstrate the power of mathematics and computational codes in setting up biological processes with a rigorous and predictive framework. Topics include: enzyme dynamics, spread of disease, harvesting bacteria, competition among live species, neuronal oscillations, transport of neurofilaments in axon, cancer and cancer therapy, and granulomas. Complete with a description of the biological background and biological question that requires the use of mathematics, this book is developed for graduate students and advanced undergraduate students with only basic knowledge of ordinary differential equations and partial differential equations; background in biology is not required. Students will gain knowledge on how to program with MATLAB without previous programming experience and how to use codes in order to test biological hypothesis.

  12. Track structure in biological models.

    Science.gov (United States)

    Curtis, S B

    1986-01-01

    High-energy heavy ions in the galactic cosmic radiation (HZE particles) may pose a special risk during long term manned space flights outside the sheltering confines of the earth's geomagnetic field. These particles are highly ionizing, and they and their nuclear secondaries can penetrate many centimeters of body tissue. The three dimensional patterns of ionizations they create as they lose energy are referred to as their track structure. Several models of biological action on mammalian cells attempt to treat track structure or related quantities in their formulation. The methods by which they do this are reviewed. The proximity function is introduced in connection with the theory of Dual Radiation Action (DRA). The ion-gamma kill (IGK) model introduces the radial energy-density distribution, which is a smooth function characterizing both the magnitude and extension of a charged particle track. The lethal, potentially lethal (LPL) model introduces lambda, the mean distance between relevant ion clusters or biochemical species along the track. Since very localized energy depositions (within approximately 10 nm) are emphasized, the proximity function as defined in the DRA model is not of utility in characterizing track structure in the LPL formulation.

  13. Laser interaction with biological material mathematical modeling

    CERN Document Server

    Kulikov, Kirill

    2014-01-01

    This book covers the principles of laser interaction with biological cells and tissues of varying degrees of organization. The problems of biomedical diagnostics are considered. Scattering of laser irradiation of blood cells is modeled for biological structures (dermis, epidermis, vascular plexus). An analytic theory is provided which is based on solving the wave equation for the electromagnetic field. It allows the accurate analysis of interference effects arising from the partial superposition of scattered waves. Treated topics of mathematical modeling are: optical characterization of biological tissue with large-scale and small-scale inhomogeneities in the layers, heating blood vessel under laser irradiation incident on the outer surface of the skin and thermo-chemical denaturation of biological structures at the example of human skin.

  14. Mesoscopic models of biological membranes

    DEFF Research Database (Denmark)

    Venturoli, M.; Sperotto, Maria Maddalena; Kranenburg, M.

    2006-01-01

    Phospholipids are the main components of biological membranes and dissolved in water these molecules self-assemble into closed structures, of which bilayers are the most relevant from a biological point of view. Lipid bilayers are often used, both in experimental and by theoretical investigations...... to coarse grain a biological membrane. The conclusion of this comparison is that there can be many valid different strategies, but that the results obtained by the various mesoscopic models are surprisingly consistent. A second objective of this review is to illustrate how mesoscopic models can be used...

  15. Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology.

    Science.gov (United States)

    Pavon, Lorena Favaro; Sibov, Tatiana Tais; Caminada de Toledo, Silvia Regina; Mara de Oliveira, Daniela; Cabral, Francisco Romero; Gabriel de Souza, Jean; Boufleur, Pamela; Marti, Luciana C; Malheiros, Jackeline Moraes; Ferreira da Cruz, Edgar; Paiva, Fernando F; Malheiros, Suzana M F; de Paiva Neto, Manoel A; Tannús, Alberto; Mascarenhas de Oliveira, Sérgio; Silva, Nasjla Saba; Cappellano, Andrea Maria; Petrilli, Antonio Sérgio; Chudzinski-Tavassi, Ana Marisa; Cavalheiro, Sérgio

    2018-04-24

    Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients ( n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model.

  16. Toward synthesizing executable models in biology.

    Science.gov (United States)

    Fisher, Jasmin; Piterman, Nir; Bodik, Rastislav

    2014-01-01

    Over the last decade, executable models of biological behaviors have repeatedly provided new scientific discoveries, uncovered novel insights, and directed new experimental avenues. These models are computer programs whose execution mechanistically simulates aspects of the cell's behaviors. If the observed behavior of the program agrees with the observed biological behavior, then the program explains the phenomena. This approach has proven beneficial for gaining new biological insights and directing new experimental avenues. One advantage of this approach is that techniques for analysis of computer programs can be applied to the analysis of executable models. For example, one can confirm that a model agrees with experiments for all possible executions of the model (corresponding to all environmental conditions), even if there are a huge number of executions. Various formal methods have been adapted for this context, for example, model checking or symbolic analysis of state spaces. To avoid manual construction of executable models, one can apply synthesis, a method to produce programs automatically from high-level specifications. In the context of biological modeling, synthesis would correspond to extracting executable models from experimental data. We survey recent results about the usage of the techniques underlying synthesis of computer programs for the inference of biological models from experimental data. We describe synthesis of biological models from curated mutation experiment data, inferring network connectivity models from phosphoproteomic data, and synthesis of Boolean networks from gene expression data. While much work has been done on automated analysis of similar datasets using machine learning and artificial intelligence, using synthesis techniques provides new opportunities such as efficient computation of disambiguating experiments, as well as the ability to produce different kinds of models automatically from biological data.

  17. Evolutionary cell biology: two origins, one objective.

    Science.gov (United States)

    Lynch, Michael; Field, Mark C; Goodson, Holly V; Malik, Harmit S; Pereira-Leal, José B; Roos, David S; Turkewitz, Aaron P; Sazer, Shelley

    2014-12-02

    All aspects of biological diversification ultimately trace to evolutionary modifications at the cellular level. This central role of cells frames the basic questions as to how cells work and how cells come to be the way they are. Although these two lines of inquiry lie respectively within the traditional provenance of cell biology and evolutionary biology, a comprehensive synthesis of evolutionary and cell-biological thinking is lacking. We define evolutionary cell biology as the fusion of these two eponymous fields with the theoretical and quantitative branches of biochemistry, biophysics, and population genetics. The key goals are to develop a mechanistic understanding of general evolutionary processes, while specifically infusing cell biology with an evolutionary perspective. The full development of this interdisciplinary field has the potential to solve numerous problems in diverse areas of biology, including the degree to which selection, effectively neutral processes, historical contingencies, and/or constraints at the chemical and biophysical levels dictate patterns of variation for intracellular features. These problems can now be examined at both the within- and among-species levels, with single-cell methodologies even allowing quantification of variation within genotypes. Some results from this emerging field have already had a substantial impact on cell biology, and future findings will significantly influence applications in agriculture, medicine, environmental science, and synthetic biology.

  18. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

    Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

    2016-08-04

    Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.

  19. MIAMI cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease

    Science.gov (United States)

    Grau-Monge, Cristina; Delcroix, Gaëtan J.-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F.; Armour, Maxime R.; Montero, Ramon B.; Schiller, Paul C.; Andreopoulos, Fotios M.; D’Ippolito, Gianluca

    2017-01-01

    Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of 2 layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration. PMID:28211362

  20. Mast cells: potential positive and negative roles in tumor biology.

    Science.gov (United States)

    Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

    2013-11-01

    Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. ©2013 AACR.

  1. Mathematical models in biological discovery

    CERN Document Server

    Walter, Charles

    1977-01-01

    When I was asked to help organize an American Association for the Advancement of Science symposium about how mathematical models have con­ tributed to biology, I agreed immediately. The subject is of immense importance and wide-spread interest. However, too often it is discussed in biologically sterile environments by "mutual admiration society" groups of "theoreticians", many of whom have never seen, and most of whom have never done, an original scientific experiment with the biolog­ ical materials they attempt to describe in abstract (and often prejudiced) terms. The opportunity to address the topic during an annual meeting of the AAAS was irresistable. In order to try to maintain the integrity ;,f the original intent of the symposium, it was entitled, "Contributions of Mathematical Models to Biological Discovery". This symposium was organized by Daniel Solomon and myself, held during the 141st annual meeting of the AAAS in New York during January, 1975, sponsored by sections G and N (Biological and Medic...

  2. Radiobilogical cell survival models

    International Nuclear Information System (INIS)

    Zackrisson, B.

    1992-01-01

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose-response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data depend on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowlegde of biological, physical, and chemical mechanisms is reflected in the formulation of new models. The present overview shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell surivival models ought to be complemented by models of stochastic energy deposition processes and repair processes at the intracellular level. (orig.)

  3. Industrial systems biology and its impact on synthetic biology of yeast cell factories.

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  4. Toward computational cumulative biology by combining models of biological datasets.

    Science.gov (United States)

    Faisal, Ali; Peltonen, Jaakko; Georgii, Elisabeth; Rung, Johan; Kaski, Samuel

    2014-01-01

    A main challenge of data-driven sciences is how to make maximal use of the progressively expanding databases of experimental datasets in order to keep research cumulative. We introduce the idea of a modeling-based dataset retrieval engine designed for relating a researcher's experimental dataset to earlier work in the field. The search is (i) data-driven to enable new findings, going beyond the state of the art of keyword searches in annotations, (ii) modeling-driven, to include both biological knowledge and insights learned from data, and (iii) scalable, as it is accomplished without building one unified grand model of all data. Assuming each dataset has been modeled beforehand, by the researchers or automatically by database managers, we apply a rapidly computable and optimizable combination model to decompose a new dataset into contributions from earlier relevant models. By using the data-driven decomposition, we identify a network of interrelated datasets from a large annotated human gene expression atlas. While tissue type and disease were major driving forces for determining relevant datasets, the found relationships were richer, and the model-based search was more accurate than the keyword search; moreover, it recovered biologically meaningful relationships that are not straightforwardly visible from annotations-for instance, between cells in different developmental stages such as thymocytes and T-cells. Data-driven links and citations matched to a large extent; the data-driven links even uncovered corrections to the publication data, as two of the most linked datasets were not highly cited and turned out to have wrong publication entries in the database.

  5. Agent-based modelling in synthetic biology.

    Science.gov (United States)

    Gorochowski, Thomas E

    2016-11-30

    Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

  6. BIOLOGICALLY INSPIRED HARDWARE CELL ARCHITECTURE

    DEFF Research Database (Denmark)

    2010-01-01

    Disclosed is a system comprising: - a reconfigurable hardware platform; - a plurality of hardware units defined as cells adapted to be programmed to provide self-organization and self-maintenance of the system by means of implementing a program expressed in a programming language defined as DNA...... language, where each cell is adapted to communicate with one or more other cells in the system, and where the system further comprises a converter program adapted to convert keywords from the DNA language to a binary DNA code; where the self-organisation comprises that the DNA code is transmitted to one...... or more of the cells, and each of the one or more cells is adapted to determine its function in the system; where if a fault occurs in a first cell and the first cell ceases to perform its function, self-maintenance is performed by that the system transmits information to the cells that the first cell has...

  7. Synthetic biology approaches to engineer T cells.

    Science.gov (United States)

    Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

    2015-08-01

    There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis.

    Science.gov (United States)

    MacLean, Adam L; Lo Celso, Cristina; Stumpf, Michael P H

    2017-01-01

    Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe. The application of population dynamics to biology is amongst the oldest applications of mathematics to biology, and the population dynamics perspective continues to offer much today. Here we describe the impact that such a perspective has made in the field of stem cell biology. Using hematopoietic stem cells as our model system, we discuss the approaches that have been used to study their key properties, such as capacity for self-renewal, differentiation, and cell fate lineage choice. We will also discuss the relevance of population dynamics in models of stem cells and cancer, where competition naturally emerges as an influential factor on the temporal evolution of cell populations. Stem Cells 2017;35:80-88. © 2016 AlphaMed Press.

  9. Industrial systems biology and its impact on synthetic biology of yeast cell factories

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools......, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex...... regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal...

  10. Streptococcus dysgalactiae subsp. dysgalactiae isolated from milk of the bovine udder as emerging pathogens: In vitro and in vivo infection of human cells and zebrafish as biological models.

    Science.gov (United States)

    Alves-Barroco, Cinthia; Roma-Rodrigues, Catarina; Raposo, Luís R; Brás, Catarina; Diniz, Mário; Caço, João; Costa, Pedro M; Santos-Sanches, Ilda; Fernandes, Alexandra R

    2018-03-25

    Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  11. Revealing the Functions of Tenascin-C in 3-D Breast Cancer Models Using Cell Biological and In Silico Approaches

    National Research Council Canada - National Science Library

    Taraseviciute, Agne; Jones, Peter L

    2007-01-01

    ...) organotypic cultures of human mammary epithelial cells by focusing on cell-cell junctions, adherens junctions in particular, as well as activation of receptor tyrosine kinases, namely EGFR and c-met...

  12. Bioengineering thermodynamics of biological cells.

    Science.gov (United States)

    Lucia, Umberto

    2015-12-01

    Cells are open complex thermodynamic systems. They can be also regarded as complex engines that execute a series of chemical reactions. Energy transformations, thermo-electro-chemical processes and transports phenomena can occur across the cells membranes. Moreover, cells can also actively modify their behaviours in relation to changes in their environment. Different thermo-electro-biochemical behaviours occur between health and disease states. But, all the living systems waste heat, which is no more than the result of their internal irreversibility. This heat is dissipated into the environment. But, this wasted heat represent also a sort of information, which outflows from the cell toward its environment, completely accessible to any observer. The analysis of irreversibility related to this wasted heat can represent a new approach to study the behaviour of the cells themselves and to control their behaviours. So, this approach allows us to consider the living systems as black boxes and analyze only the inflows and outflows and their changes in relation to the modification of the environment. Therefore, information on the systems can be obtained by analyzing the changes in the cell heat wasted in relation to external perturbations. The bioengineering thermodynamics bases are summarized and used to analyse possible controls of the calls behaviours based on the control of the ions fluxes across the cells membranes.

  13. Time lags in biological models

    CERN Document Server

    MacDonald, Norman

    1978-01-01

    In many biological models it is necessary to allow the rates of change of the variables to depend on the past history, rather than only the current values, of the variables. The models may require discrete lags, with the use of delay-differential equations, or distributed lags, with the use of integro-differential equations. In these lecture notes I discuss the reasons for including lags, especially distributed lags, in biological models. These reasons may be inherent in the system studied, or may be the result of simplifying assumptions made in the model used. I examine some of the techniques available for studying the solution of the equations. A large proportion of the material presented relates to a special method that can be applied to a particular class of distributed lags. This method uses an extended set of ordinary differential equations. I examine the local stability of equilibrium points, and the existence and frequency of periodic solutions. I discuss the qualitative effects of lags, and how these...

  14. Interfacing nanostructures to biological cells

    Science.gov (United States)

    Chen, Xing; Bertozzi, Carolyn R.; Zettl, Alexander K.

    2012-09-04

    Disclosed herein are methods and materials by which nanostructures such as carbon nanotubes, nanorods, etc. are bound to lectins and/or polysaccharides and prepared for administration to cells. Also disclosed are complexes comprising glycosylated nanostructures, which bind selectively to cells expressing glycosylated surface molecules recognized by the lectin. Exemplified is a complex comprising a carbon nanotube functionalized with a lipid-like alkane, linked to a polymer bearing repeated .alpha.-N-acetylgalactosamine sugar groups. This complex is shown to selectively adhere to the surface of living cells, without toxicity. In the exemplified embodiment, adherence is mediated by a multivalent lectin, which binds both to the cells and the .alpha.-N-acetylgalactosamine groups on the nanostructure.

  15. The cell biology of aging.

    Science.gov (United States)

    Hayflick, L

    1985-02-01

    It is only within the past ten years that biogerontology has become attractive to a sufficient number of biologists so that the field can be regarded as a seriously studied discipline. Cytogerontology, or the study of aging at the cellular level, had its genesis about 20 years ago when the dogma that maintained that cultured normal cells could replicate forever was overturned. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Only abnormal somatic cells are capable of immortality. In recent years it has been found that the number of population doublings of which cultured normal cells are capable is inversely proportional to donor age. There is also good evidence that the number of population doublings of cultured normal fibroblasts is directly proportional to the maximum lifespan of ten species that have been studied. Cultures prepared from patients with accelerated aging syndromes (progeria and Werner's syndrome) undergo far fewer doublings than do those of age-matched controls. The normal human fibroblast cell strain WI-38 was established in 1962 from fetal lung, and several hundred ampules of these cells were frozen in liquid nitrogen at that time. These ampules have been reconstituted periodically and shown to be capable of replication. This represents the longest period of time that a normal human cell has ever been frozen. Normal human fetal cell strains such as WI-38 have the capacity to double only about 50 times. If cultures are frozen at various population doublings, the number of doublings remaining after reconstitution is equal to 50 minus the number of doublings that occurred prior to freezing. The memory of the cells has been found to be accurate after 23 years of preservation in liquid nitrogen. Normal human cells incur many physiologic decrements that herald the approach of their

  16. Neural crest cells: from developmental biology to clinical interventions.

    Science.gov (United States)

    Noisa, Parinya; Raivio, Taneli

    2014-09-01

    Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

  17. Reaction of long-lived radicals and vitamin C in γ-irradiated mammalian cells and their model system at 295 K. Tunneling reaction in biological system

    International Nuclear Information System (INIS)

    Matsumoto, Takuro; Miyazaki, Tetsuo; Kosugi, Yoshio; Kumada, Takayuki; Koyama, Sinji; Kodama, Seiji; Watanabe, Masami.

    1996-01-01

    When golden hamster embryo (GHE) cells or concentrated albumin solution (0.1 kg dm -3 ) that is a model system of cells is irradiated with γ-rays at 295 K, organic radicals produced can be observed by ESR. The organic radicals survive at both 295 K and 310 K for such a long time as 20 hr. The long-lived radicals in GHE cells and the albumin solution react with vitamin C by the rate constants of 0.007 dm 3 mol -1 s -1 and 0.014 dm 3 mol -1 s -1 , respectively. The long-lived radicals in human cells cause gene mutation, which is suppressed by addition of vitamin C. The isotope effect on the rate constant (k) for the reaction of the long-lived radicals and vitamin C has been studied in the albumin solution by use of protonated vitamin C and deuterated vitamin C. The isotope effect (k H /k D ) was more than 20-50 and was interpreted in terms of tunneling reaction. When GHE cells or the aqueous albumin solution (0.1 kg dm -3 ) is irradiated with γ-rays at 295 K, organic radicals produced survive for more than 24 hr at room temperature. Very recently we have found that vitamin C reacts with the long-lived organic radicals in the γ-irradiated albumin solution at high concentration of 0.1 kg dm -3 by the rate constant of 0.014 dm 3 mol -1 s -1 . Since most of reactions in biological systems including the reaction of vitamin C are a transfer of a hydrogen atom or a proton that has a large wave character, it is generally expected that the tunneling reaction may play an important role in biological systems at room temperature. The studies of isotope effects on reactions will give an information on the contribution of tunneling reaction. (J.P.N.)

  18. Glycoengineering in CHO cells: Advances in systems biology

    DEFF Research Database (Denmark)

    Tejwani, Vijay; Andersen, Mikael Rørdam; Nam, Jong Hyun

    2018-01-01

    are not well understood. A systems biology approach combining different technologies is needed for complete understanding of the molecular processes accounting for this variability and to open up new venues in cell line development. In this review, we describe several advances in genetic manipulation, modeling......For several decades, glycoprotein biologics have been successfully produced from Chinese hamster ovary (CHO) cells. The therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis....... Recently, CHO cells have also been explored for production of therapeutic glycosaminoglycans (e.g. heparin), which presents similar challenges as producing glycoproteins biologics. Approaches to controlling heterogeneity in CHO cells and directing the biosynthetic process toward desired glycoforms...

  19. Spherical Cancer Models in Tumor Biology

    Directory of Open Access Journals (Sweden)

    Louis-Bastien Weiswald

    2015-01-01

    Full Text Available Three-dimensional (3D in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.

  20. Biological transportation networks: Modeling and simulation

    KAUST Repository

    Albi, Giacomo; Artina, Marco; Foransier, Massimo; Markowich, Peter A.

    2015-01-01

    We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation

  1. Cell biology of mitotic recombination

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2015-01-01

    Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as w...

  2. Cell Science and Cell Biology Research at MSFC: Summary

    Science.gov (United States)

    2003-01-01

    The common theme of these research programs is that they investigate regulation of gene expression in cells, and ultimately gene expression is controlled by the macromolecular interactions between regulatory proteins and DNA. The NASA Critical Path Roadmap identifies Muscle Alterations and Atrophy and Radiation Effects as Very Serious Risks and Severe Risks, respectively, in long term space flights. The specific problem addressed by Dr. Young's research ("Skeletal Muscle Atrophy and Muscle Cell Signaling") is that skeletal muscle loss in space cannot be prevented by vigorous exercise. Aerobic skeletal muscles (i.e., red muscles) undergo the most extensive atrophy during long-term space flight. Of the many different potential avenues for preventing muscle atrophy, Dr. Young has chosen to study the beta-adrenergic receptor (betaAR) pathway. The reason for this choice is that a family of compounds called betaAR agonists will preferentially cause an increase in muscle mass of aerobic muscles (i.e., red muscle) in animals, potentially providing a specific pharmacological solution to muscle loss in microgravity. In addition, muscle atrophy is a widespread medical problem in neuromuscular diseases, spinal cord injury, lack of exercise, aging, and any disease requiring prolonged bedridden status. Skeletal muscle cells in cell culture are utilized as a model system to study this problem. Dr. Richmond's research ("Radiation & Cancer Biology of Mammary Cells in Culture") is directed toward developing a laboratory model for use in risk assessment of cancer caused by space radiation. This research is unique because a human model will be developed utilizing human mammary cells that are highly susceptible to tumor development. This approach is preferential over using animal cells because of problems in comparing radiation-induced cancers between humans and animals.

  3. Genome-scale biological models for industrial microbial systems.

    Science.gov (United States)

    Xu, Nan; Ye, Chao; Liu, Liming

    2018-04-01

    The primary aims and challenges associated with microbial fermentation include achieving faster cell growth, higher productivity, and more robust production processes. Genome-scale biological models, predicting the formation of an interaction among genetic materials, enzymes, and metabolites, constitute a systematic and comprehensive platform to analyze and optimize the microbial growth and production of biological products. Genome-scale biological models can help optimize microbial growth-associated traits by simulating biomass formation, predicting growth rates, and identifying the requirements for cell growth. With regard to microbial product biosynthesis, genome-scale biological models can be used to design product biosynthetic pathways, accelerate production efficiency, and reduce metabolic side effects, leading to improved production performance. The present review discusses the development of microbial genome-scale biological models since their emergence and emphasizes their pertinent application in improving industrial microbial fermentation of biological products.

  4. Halomonas desiderata as a bacterial model to predict the possible biological nitrate reduction in concrete cells of nuclear waste disposals.

    Science.gov (United States)

    Alquier, Marjorie; Kassim, Caroline; Bertron, Alexandra; Sablayrolles, Caroline; Rafrafi, Yan; Albrecht, Achim; Erable, Benjamin

    2014-01-01

    After closure of a waste disposal cell in a repository for radioactive waste, resaturation is likely to cause the release of soluble species contained in cement and bituminous matrices, such as ionic species (nitrates, sulfates, calcium and alkaline ions, etc.), organic matter (mainly organic acids), or gases (from steel containers and reinforced concrete structures as well as from radiolysis within the waste packages). However, in the presence of nitrates in the near-field of waste, the waste cell can initiate oxidative conditions leading to enhanced mobility of redox-sensitive radionuclides (RN). In biotic conditions and in the presence of organic matter and/or hydrogen as electron donors, nitrates may be microbiologically reduced, allowing a return to reducing conditions that promote the safety of storage. Our work aims to analyze the possible microbial reactivity of nitrates at the bitumen - concrete interface in conditions as close as possible to radioactive waste storage conditions in order (i) to evaluate the nitrate reaction kinetics; (ii) to identify the by-products (NO2(-), NH4(+), N2, N2O, etc.); and (iii) to discriminate between the roles of planktonic bacteria and those adhering as a biofilm structure in the denitrifying activity. Leaching experiments on solid matrices (bitumen and cement pastes) were first implemented to define the physicochemical conditions that microorganisms are likely to meet at the bitumen-concrete interface, e.g. highly alkaline pH conditions (10 < pH < 11) imposed by the cement matrix. The screening of a range of anaerobic denitrifying bacterial strains led us to select Halomonas desiderata as a model bacterium capable of catalyzing the reaction of nitrate reduction in these particular conditions of pH. The denitrifying activity of H. desiderata was quantified in a batch bioreactor in the presence of solid matrices and/or leachate from bitumen and cement matrices. Denitrification was relatively fast in the presence of cement

  5. TinkerCell: modular CAD tool for synthetic biology

    Science.gov (United States)

    Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

    2009-01-01

    Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at . Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily

  6. TinkerCell: modular CAD tool for synthetic biology

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T

    2009-10-01

    Full Text Available Abstract Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API. TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com. Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled

  7. Prion potency in stem cells biology.

    Science.gov (United States)

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  8. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...... in the context of stem cell tracking in vivo. This review concludes with a section on the unexpected potential of bone marrow-derived stem cells to contribute to the repair of damaged tissues. The contribution of cell fusion to explain the latter phenomenon is discussed. SUMMARY: Because of exciting discoveries...

  9. Quantitative stem cell biology: the threat and the glory.

    Science.gov (United States)

    Pollard, Steven M

    2016-11-15

    Major technological innovations over the past decade have transformed our ability to extract quantitative data from biological systems at an unprecedented scale and resolution. These quantitative methods and associated large datasets should lead to an exciting new phase of discovery across many areas of biology. However, there is a clear threat: will we drown in these rivers of data? On 18th July 2016, stem cell biologists gathered in Cambridge for the 5th annual Cambridge Stem Cell Symposium to discuss 'Quantitative stem cell biology: from molecules to models'. This Meeting Review provides a summary of the data presented by each speaker, with a focus on quantitative techniques and the new biological insights that are emerging. © 2016. Published by The Company of Biologists Ltd.

  10. Integrating systems biology models and biomedical ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Dumontier, Michel; Gennari, John H; Wimalaratne, Sarala; de Bono, Bernard; Cook, Daniel L; Gkoutos, Georgios V

    2011-08-11

    Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

  11. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    Science.gov (United States)

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Biologically based multistage modeling of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

  13. Countercurrent distribution of biological cells

    Science.gov (United States)

    Brooks, D. E.

    1979-01-01

    A neutral polymer phase system consisting of 7.5 percent dextran 40/4.5 percent PEG 6, 0.11 M Na phosphate, 5 percent fetal bovine serum (FBS), pH 7.5, was developed which has a high phase droplet electrophoretic mobility and retains cell viability over many hours. In this and related systems, the drop mobility was a linear function of drop size, at least in the range 4-30 micron diameter. Applications of and electric field of 4.5 v/cm to a system containing 10 percent v/v bottom phase cleared the system more than two orders of magnitude faster than in the absence of the field. At higher bottom phase concentrations a secondary phenomenon intervened in the field driven separations which resulted in an increase in turbidity after clearing had commenced. The increase was associated with a dilution of the phase system in the chamber. The effect depended on the presence of the electric field. It may be due to electroosmotic flow of buffer through the Amicon membranes into the sample chamber and flow of phase system out into the rinse stream. Strategies to eliminate this problem are proposed.

  14. The cell biology of bone growth.

    Science.gov (United States)

    Price, J S; Oyajobi, B O; Russell, R G

    1994-02-01

    The field of bone cell biology is clearly of relevance to the problem of stunting in children, as in the final analysis the cells of the growing long bone are the ultimate 'regulators'. It is the alterations in the functions of these cells that manifests as a reduction in height. Normal longitudinal growth is achieved by the coordinated recruitment, proliferation, differentiation, maturation and eventual death of the cells of growth plate and bone. Cellular activity is closely regulated by endocrine factors acting directly or indirectly, with factors produced locally and stored within the bone and cartilage microenvironment having a critical role in intercellular communication. Disruption of any of these processes can lead to growth disturbances, since it only requires a defect in a single gene to have profound effects. Studies in recent years have shed light on the biochemical and molecular effects of cytokines and growth factors and have shown that these regulatory molecules may mediate the effects of certain hormones important in controlling growth. However, the complex interrelationship of these molecules is still not clear. Notwithstanding, understanding of the mechanisms involved in bone remodelling is increasing, as this area attracts much research because of the high incidence of metabolic bone disease in Western society. Although studies of adult bone remodelling are of relevance, there is a requirement for increased research directed specifically at the mechanisms of endochondral ossification and its regulation. Longitudinal bone growth is a challenge to the cell biologist, since it is an accelerated cycle of cellular division and differentiation, within which it is not easy to separate events temporally and spatially. In addition, different regulatory mechanisms are probably important at different stages of growth. Another difficulty impeding progress in this field is the lack of appropriate animal models for research. Much information has come from

  15. Three-factor models versus time series models: quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data.

    Science.gov (United States)

    Frank, Till D; Kiyatkin, Anatoly; Cheong, Alex; Kholodenko, Boris N

    2017-06-01

    Signal integration determines cell fate on the cellular level, affects cognitive processes and affective responses on the behavioural level, and is likely to be involved in psychoneurobiological processes underlying mood disorders. Interactions between stimuli may subjected to time effects. Time-dependencies of interactions between stimuli typically lead to complex cell responses and complex responses on the behavioural level. We show that both three-factor models and time series models can be used to uncover such time-dependencies. However, we argue that for short longitudinal data the three factor modelling approach is more suitable. In order to illustrate both approaches, we re-analysed previously published short longitudinal data sets. We found that in human embryonic kidney 293 cells cells the interaction effect in the regulation of extracellular signal-regulated kinase (ERK) 1 signalling activation by insulin and epidermal growth factor is subjected to a time effect and dramatically decays at peak values of ERK activation. In contrast, we found that the interaction effect induced by hypoxia and tumour necrosis factor-alpha for the transcriptional activity of the human cyclo-oxygenase-2 promoter in HEK293 cells is time invariant at least in the first 12-h time window after stimulation. Furthermore, we applied the three-factor model to previously reported animal studies. In these studies, memory storage was found to be subjected to an interaction effect of the beta-adrenoceptor agonist clenbuterol and certain antagonists acting on the alpha-1-adrenoceptor / glucocorticoid-receptor system. Our model-based analysis suggests that only if the antagonist drug is administer in a critical time window, then the interaction effect is relevant. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  16. More on Grandmother Cells and the Biological Implausibility of PDP Models of Cognition: A Reply to Plaut and McClelland (2010) and Quian Quiroga and Kreiman (2010)

    Science.gov (United States)

    Bowers, Jeffrey S.

    2010-01-01

    Plaut and McClelland (2010) and Quian Quiroga and Kreiman both challenged my characterization of localist and distributed representations. They also challenged the biological plausibility of grandmother cells on conceptual and empirical grounds. This reply addresses these issues in turn. The premise of my argument is that grandmother cells in…

  17. Amylase and blood cell-count hematological radiation-injury biomarkers in a rhesus monkey radiation model-use of multiparameter and integrated biological dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, W.F. [Uniformed Services University, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: blakely@afrri.usuhs.mil; Ossetrova, N.I.; Manglapus, G.L.; Salter, C.A.; Levine, I.H.; Jackson, W.E.; Grace, M.B.; Prasanna, P.G.S.; Sandgren, D.J.; Ledney, G.D. [Uniformed Services University, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    Effective medical management of suspected radiation exposure incidents requires the recording of dynamic medical data (clinical signs and symptoms), biological assessments of radiation exposure, and physical dosimetry in order to provide diagnostic information to the treating physician and dose assessment for personnel radiation protection records. The need to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios prompted an evaluation of suitable biomarkers that can provide early diagnostic information after exposure. We investigated the utility of serum amylase and hematological blood-cell count biomarkers to provide early assessment of severe radiation exposures in a non-human primate model (i.e., rhesus macaques; n=8) exposed to whole-body radiation of {sup 60}Co-gamma rays (6.5 Gy, 40cGymin{sup -1}). Serum amylase activity was significantly elevated (12.3{+-}3.27- and 2.6{+-}0.058-fold of day zero samples) at 1 and 2-days, respectively, after radiation. Lymphocyte cell counts decreased ({<=}15% of day zero samples) 1 and 2 days after radiation exposure. Neutrophil cell counts increased at day one by 1.9({+-}0.38)-fold compared with levels before irradiation. The ratios of neutrophil to lymphocyte cell counts increased by 13({+-}2.66)- and 4.23({+-}0.95)-fold at 1 and 2 days, respectively, after irradiation. These results demonstrate that increases in serum amylase activity along with decreases of lymphocyte counts, increases in neutrophil cell counts, and increases in the ratio of neutrophil to lymphocyte counts 1 day after irradiation can provide enhanced early triage discrimination of individuals with severe radiation exposure and injury. Use of the biodosimetry assessment tool (BAT) application is encouraged to permit dynamic recording of medical data in the management of a suspected radiological casualty.

  18. CellNet: Network Biology Applied to Stem Cell Engineering

    Science.gov (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

    2014-01-01

    SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793

  19. Biologic Constraints on Modelling Virus Assembly

    Directory of Open Access Journals (Sweden)

    Robert L. Garcea

    2008-01-01

    Full Text Available The mathematic modelling of icosahedral virus assembly has drawn increasing interest because of the symmetric geometry of the outer shell structures. Many models involve equilibrium expressions of subunit binding, with reversible subunit additions forming various intermediate structures. The underlying assumption is that a final lowest energy state drives the equilibrium toward assembly. In their simplest forms, these models have explained why high subunit protein concentrations and strong subunit association constants can result in kinetic traps forming off pathway partial and aberrant structures. However, the cell biology of virus assembly is exceedingly complex. The biochemistry and biology of polyoma and papillomavirus assembly described here illustrates many of these specific issues. Variables include the use of cellular ‘chaperone’ proteins as mediators of assembly fidelity, the coupling of assembly to encapsidation of a specific nucleic acid genome, the use of cellular structures as ‘workbenches’ upon which assembly occurs, and the underlying problem of making a capsid structure that is metastable and capable of rapid disassembly upon infection. Although formidable to model, incorporating these considerations could advance the relevance of mathematical models of virus assembly to the real world.

  20. Evaluation of biological models using Spacelab

    Science.gov (United States)

    Tollinger, D.; Williams, B. A.

    1980-01-01

    Biological models of hypogravity effects are described, including the cardiovascular-fluid shift, musculoskeletal, embryological and space sickness models. These models predict such effects as loss of extracellular fluid and electrolytes, decrease in red blood cell mass, and the loss of muscle and bone mass in weight-bearing portions of the body. Experimentation in Spacelab by the use of implanted electromagnetic flow probes, by fertilizing frog eggs in hypogravity and fixing the eggs at various stages of early development and by assessing the role of the vestibulocular reflex arc in space sickness is suggested. It is concluded that the use of small animals eliminates the uncertainties caused by corrective or preventive measures employed with human subjects.

  1. Stochastic models of cell motility

    DEFF Research Database (Denmark)

    Gradinaru, Cristian

    2012-01-01

    Cell motility and migration are central to the development and maintenance of multicellular organisms, and errors during this process can lead to major diseases. Consequently, the mechanisms and phenomenology of cell motility are currently under intense study. In recent years, a new...... interdisciplinary field focusing on the study of biological processes at the nanoscale level, with a range of technological applications in medicine and biological research, has emerged. The work presented in this thesis is at the interface of cell biology, image processing, and stochastic modeling. The stochastic...... models introduced here are based on persistent random motion, which I apply to real-life studies of cell motility on flat and nanostructured surfaces. These models aim to predict the time-dependent position of cell centroids in a stochastic manner, and conversely determine directly from experimental...

  2. The cell biology of T-dependent B cell activation

    DEFF Research Database (Denmark)

    Owens, T; Zeine, R

    1989-01-01

    The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...... includes multipoint intermolecular interactions that probably involve aggregation of both polymorphic and monomorphic T cell surface molecules. Such aggregations have been shown in vitro to markedly enhance and, in some cases, induce T cell activation. The production of T-derived lymphokines that have been...... implicated in B cell activation is dependent on the T cell receptor for antigen and its associated CD3 signalling complex. T-dependent help for B cell activation is therefore similarly MHC-restricted and involves T-B intercellular interaction. Recent reports that describe antigen-independent B cell...

  3. New frontiers in human cell biology and medicine: can pluripotent stem cells deliver?

    Science.gov (United States)

    Goldstein, Lawrence S B

    2012-11-12

    Human pluripotent stem cells provide enormous opportunities to treat disease using cell therapy. But human stem cells can also drive biomedical and cell biological discoveries in a human model system, which can be directly linked to understanding disease or developing new therapies. Finally, rigorous scientific studies of these cells can and should inform the many science and medical policy issues that confront the translation of these technologies to medicine. In this paper, I discuss these issues using amyotrophic lateral sclerosis as an example.

  4. Nonlinear Rheology in a Model Biological Tissue

    Science.gov (United States)

    Matoz-Fernandez, D. A.; Agoritsas, Elisabeth; Barrat, Jean-Louis; Bertin, Eric; Martens, Kirsten

    2017-04-01

    The rheological response of dense active matter is a topic of fundamental importance for many processes in nature such as the mechanics of biological tissues. One prominent way to probe mechanical properties of tissues is to study their response to externally applied forces. Using a particle-based model featuring random apoptosis and environment-dependent division rates, we evidence a crossover from linear flow to a shear-thinning regime with an increasing shear rate. To rationalize this nonlinear flow we derive a theoretical mean-field scenario that accounts for the interplay of mechanical and active noise in local stresses. These noises are, respectively, generated by the elastic response of the cell matrix to cell rearrangements and by the internal activity.

  5. Multidisciplinary approaches to understanding collective cell migration in developmental biology.

    Science.gov (United States)

    Schumacher, Linus J; Kulesa, Paul M; McLennan, Rebecca; Baker, Ruth E; Maini, Philip K

    2016-06-01

    Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. © 2016 The Authors.

  6. ML-Space: Hybrid Spatial Gillespie and Particle Simulation of Multi-Level Rule-Based Models in Cell Biology.

    Science.gov (United States)

    Bittig, Arne T; Uhrmacher, Adelinde M

    2017-01-01

    Spatio-temporal dynamics of cellular processes can be simulated at different levels of detail, from (deterministic) partial differential equations via the spatial Stochastic Simulation algorithm to tracking Brownian trajectories of individual particles. We present a spatial simulation approach for multi-level rule-based models, which includes dynamically hierarchically nested cellular compartments and entities. Our approach ML-Space combines discrete compartmental dynamics, stochastic spatial approaches in discrete space, and particles moving in continuous space. The rule-based specification language of ML-Space supports concise and compact descriptions of models and to adapt the spatial resolution of models easily.

  7. Analysis of undergraduate cell biology contents in Brazilian public universities.

    Science.gov (United States)

    Mermelstein, Claudia; Costa, Manoel Luis

    2017-04-01

    The enormous amount of information available in cell biology has created a challenge in selecting the core concepts we should be teaching our undergraduates. One way to define a set of essential core ideas in cell biology is to analyze what a specific cell biology community is teaching their students. Our main objective was to analyze the cell biology content currently being taught in Brazilian universities. We collected the syllabi of cell biology courses from public universities in Brazil and analyzed the frequency of cell biology topics in each course. We also compared the Brazilian data with the contents of a major cell biology textbook. Our analysis showed that while some cell biology topics such as plasma membrane and cytoskeleton was present in ∼100% of the Brazilian curricula analyzed others such as cell signaling and cell differentiation were present in only ∼35%. The average cell biology content taught in the Brazilian universities is quite different from what is presented in the textbook. We discuss several possible explanations for these observations. We also suggest a list with essential cell biology topics for any biological or biomedical undergraduate course. The comparative discussion of cell biology topics presented here could be valuable in other educational contexts. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  8. AFM Nanotools for Surgery of Biological Cells

    Energy Technology Data Exchange (ETDEWEB)

    Beard, J D; Gordeev, S N [Department of Physics, Claverton Down, University of Bath, Bath, BA2 7AY (United Kingdom); Guy, R H, E-mail: jdb28@bath.ac.uk [Department of Pharmacy and Pharmacology, Claverton Down, University of Bath, Bath, BA2 7AY (United Kingdom)

    2011-03-01

    Using a method of electron-beam induced deposition, we have been able to fabricate specialized AFM probes with application as 'nanotools' for the manipulation of biological structures ('nanosurgery'). We describe several such tools, including a 'nanoscalpel', 'nanoneedles' for probing intracellular structures, and a 'nanotome' which can separate surface layers from a biological structure. These applications are demonstrated by performing nanomanipulation on corneocyte cells from the outer layer of human skin.

  9. Implications of Big Data for cell biology

    OpenAIRE

    Dolinski, Kara; Troyanskaya, Olga G.

    2015-01-01

    “Big Data” has surpassed “systems biology” and “omics” as the hottest buzzword in the biological sciences, but is there any substance behind the hype? Certainly, we have learned about various aspects of cell and molecular biology from the many individual high-throughput data sets that have been published in the past 15–20 years. These data, although useful as individual data sets, can provide much more knowledge when interrogated with Big Data approaches, such as applying integrative methods ...

  10. Alternative Educational Approach to Introducing Cell Biology

    Directory of Open Access Journals (Sweden)

    Rosilane T. Silva

    2005-07-01

    Full Text Available First year medical students usually have a great  difficulty to visualize a three  dimensional  cell. They also present a series of misconceptions  related to cell biology that seems to begin in the high school. An alternative educational approach  is being tested  with high school students in order to minimize these misconceptions,  and also increase the pupils interest in the subject.  The approach  combines theoretical classes with experimental activities, the  use of models, games, discussions,  and oral presentations by the students at the end of the educational module.  In short,  the experimental activities  are low-cost, easy-to-follow experiments that basically show a few properties  of the living cells, such as membrane transport, enzyme action  as well as the  importance of the  membrane  integrity for life.  A card  game relates  the  functions  of the organnels  by matching  pairs  of cards.  This  game has one card without a matching  pair  that explains  apoptosis;  the  player  that ends up with  this  card  loses the game.   The pupils learn while they play the game.  A 3D model of the membrane  shows the major components  and allows the observation of membrane  assimetry.   After comparing  some panels of photomicrographs of cells and organnels, the students are presented  to a 3D model of a cell as the teacher  tries to relate the panels  with  a three  dimensional  visualization.  They  also have the  opportunity to present their  own models.  The opinion of high school teachers  about  the different activities  will be shown.  The aim of this educational module is to promote  learning while different abilities, according to Gardners  Multiple Intelligences  Theory,  such as the visual-spatial, bodily-kinesthetic, interpersonal, and naturalistic are being developed.  We believe that the diversity  of approaches  is one of the most important

  11. Lipid Cell Biology: A Focus on Lipids in Cell Division.

    Science.gov (United States)

    Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

    2018-06-20

    Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

  12. A three-dimensional cell culture model to study the mechano-biological behavior in periodontal ligament regeneration

    NARCIS (Netherlands)

    Oortgiesen, D.A.W.; Yu, N.; Bronckers, A.L.J.J.; Yang, F.; Walboomers, X.F.; Jansen, J.A.

    2012-01-01

    Periodontitis is a disease affecting the supporting structures of the teeth, which can eventually result in tooth loss. A three-dimensional (3D) tissue culture model was developed that may serve to grow a 3D construct that not only transplants into defective periodontal sites, but also allows to

  13. Biological cell controllable patch-clamp microchip

    Science.gov (United States)

    Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

    2010-12-01

    A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

  14. Modeling biological pathway dynamics with timed automata.

    Science.gov (United States)

    Schivo, Stefano; Scholma, Jetse; Wanders, Brend; Urquidi Camacho, Ricardo A; van der Vet, Paul E; Karperien, Marcel; Langerak, Rom; van de Pol, Jaco; Post, Janine N

    2014-05-01

    Living cells are constantly subjected to a plethora of environmental stimuli that require integration into an appropriate cellular response. This integration takes place through signal transduction events that form tightly interconnected networks. The understanding of these networks requires capturing their dynamics through computational support and models. ANIMO (analysis of Networks with Interactive Modeling) is a tool that enables the construction and exploration of executable models of biological networks, helping to derive hypotheses and to plan wet-lab experiments. The tool is based on the formalism of Timed Automata, which can be analyzed via the UPPAAL model checker. Thanks to Timed Automata, we can provide a formal semantics for the domain-specific language used to represent signaling networks. This enforces precision and uniformity in the definition of signaling pathways, contributing to the integration of isolated signaling events into complex network models. We propose an approach to discretization of reaction kinetics that allows us to efficiently use UPPAAL as the computational engine to explore the dynamic behavior of the network of interest. A user-friendly interface hides the use of Timed Automata from the user, while keeping the expressive power intact. Abstraction to single-parameter kinetics speeds up construction of models that remain faithful enough to provide meaningful insight. The resulting dynamic behavior of the network components is displayed graphically, allowing for an intuitive and interactive modeling experience.

  15. A biological compression model and its applications.

    Science.gov (United States)

    Cao, Minh Duc; Dix, Trevor I; Allison, Lloyd

    2011-01-01

    A biological compression model, expert model, is presented which is superior to existing compression algorithms in both compression performance and speed. The model is able to compress whole eukaryotic genomes. Most importantly, the model provides a framework for knowledge discovery from biological data. It can be used for repeat element discovery, sequence alignment and phylogenetic analysis. We demonstrate that the model can handle statistically biased sequences and distantly related sequences where conventional knowledge discovery tools often fail.

  16. The changing world of modern cell biology.

    Science.gov (United States)

    Misteli, Tom

    2009-01-12

    Change is always ambiguous. There is the enticing prospect of novelty and better times ahead, but at the same time the concern of losing the good of the past. It is with these sentiments that I take over as the Editor-in-Chief from Ira Mellman who for a decade has cleverly and effectively lead the JCB. During this time he directed and oversaw an extensive modernization of the journal and guided it through dramatic changes in the publishing world. Ira lead the journal with unyielding dedication and enthusiasm and we in the cell biology community must thank him profoundly for his service. It is his work, together with the invaluable contribution of the best editorial board and the most dedicated professional editorial staff in the scientific publishing business, that allows me to now take over the stewardship of the JCB with a tremendous sense of excitement and determination to continue and expand the JCB's role as the leading journal in the cell biology community and as a trendsetter in the rapidly changing world of modern cell biology.

  17. Continuum Modeling of Biological Network Formation

    KAUST Repository

    Albi, Giacomo; Burger, Martin; Haskovec, Jan; Markowich, Peter A.; Schlottbom, Matthias

    2017-01-01

    We present an overview of recent analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transportation networks. The model describes

  18. Cellular potts models multiscale extensions and biological applications

    CERN Document Server

    Scianna, Marco

    2013-01-01

    A flexible, cell-level, and lattice-based technique, the cellular Potts model accurately describes the phenomenological mechanisms involved in many biological processes. Cellular Potts Models: Multiscale Extensions and Biological Applications gives an interdisciplinary, accessible treatment of these models, from the original methodologies to the latest developments. The book first explains the biophysical bases, main merits, and limitations of the cellular Potts model. It then proposes several innovative extensions, focusing on ways to integrate and interface the basic cellular Potts model at the mesoscopic scale with approaches that accurately model microscopic dynamics. These extensions are designed to create a nested and hybrid environment, where the evolution of a biological system is realistically driven by the constant interplay and flux of information between the different levels of description. Through several biological examples, the authors demonstrate a qualitative and quantitative agreement with t...

  19. Cell-free synthetic biology for in vitro prototype engineering.

    Science.gov (United States)

    Moore, Simon J; MacDonald, James T; Freemont, Paul S

    2017-06-15

    Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

  20. Noninvasive Assessment of Cell Fate and Biology in Transplanted Mesenchymal Stem Cells.

    Science.gov (United States)

    Franchi, Federico; Rodriguez-Porcel, Martin

    2017-01-01

    Recently, molecular imaging has become a conditio sine qua non for cell-based regenerative medicine. Developments in molecular imaging techniques, such as reporter gene technology, have increasingly enabled the noninvasive assessment of the fate and biology of cells after cardiovascular applications. In this context, bioluminescence imaging is the most commonly used imaging modality in small animal models of preclinical studies. Here, we present a detailed protocol of a reporter gene imaging approach for monitoring the viability and biology of Mesenchymal Stem Cells transplanted in a mouse model of myocardial ischemia reperfusion injury.

  1. Advances in Retinal Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2013-01-01

    Full Text Available Tremendous progress has been made in recent years to generate retinal cells from pluripotent cell sources. These advances provide hope for those suffering from blindness due to lost retinal cells. Understanding the intrinsic genetic network in model organisms, like fly and frog, has led to a better understanding of the extrinsic signaling pathways necessary for retinal progenitor cell formation in mouse and human cell cultures. This review focuses on the culture methods used by different groups, which has culminated in the generation of laminated retinal tissue from both embryonic and induced pluripotent cells. The review also briefly describes advances made in transplantation studies using donor retinal progenitor and cultured retinal cells.

  2. Tensegrity I. Cell structure and hierarchical systems biology

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

    In 1993, a Commentary in this journal described how a simple mechanical model of cell structure based on tensegrity architecture can help to explain how cell shape, movement and cytoskeletal mechanics are controlled, as well as how cells sense and respond to mechanical forces (J. Cell Sci. 104, 613-627). The cellular tensegrity model can now be revisited and placed in context of new advances in our understanding of cell structure, biological networks and mechanoregulation that have been made over the past decade. Recent work provides strong evidence to support the use of tensegrity by cells, and mathematical formulations of the model predict many aspects of cell behavior. In addition, development of the tensegrity theory and its translation into mathematical terms are beginning to allow us to define the relationship between mechanics and biochemistry at the molecular level and to attack the larger problem of biological complexity. Part I of this two-part article covers the evidence for cellular tensegrity at the molecular level and describes how this building system may provide a structural basis for the hierarchical organization of living systems--from molecule to organism. Part II, which focuses on how these structural networks influence information processing networks, appears in the next issue.

  3. Potentials of single-cell biology in identification and validation of disease biomarkers.

    Science.gov (United States)

    Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

    2016-09-01

    Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  4. Proteomics in studying cancer stem cell biology.

    Science.gov (United States)

    Kranenburg, Onno; Emmink, Benjamin L; Knol, Jaco; van Houdt, Winan J; Rinkes, Inne H M Borel; Jimenez, Connie R

    2012-06-01

    Normal multipotent tissue stem cells (SCs) are the driving force behind tissue turnover and repair. The cancer stem cell theory holds that tumors also contain stem-like cells that drive tumor growth and metastasis formation. However, very little is known about the regulation of SC maintenance pathways in cancer and how these are affected by cancer-specific genetic alterations and by treatment. Proteomics is emerging as a powerful tool to identify the signaling complexes and pathways that control multi- and pluri-potency and SC differentiation. Here, the authors review the novel insights that these studies have provided and present a comprehensive strategy for the use of proteomics in studying cancer SC biology.

  5. The biologic effects of cigarette smoke on cancer cells.

    Science.gov (United States)

    Sobus, Samantha L; Warren, Graham W

    2014-12-01

    Smoking is one of the largest preventable risk factors for developing cancer, and continued smoking by cancer patients is associated with increased toxicity, recurrence, risk of second primary cancer, and mortality. Cigarette smoke (CS) contains thousands of chemicals, including many known carcinogens. The carcinogenic effects of CS are well established, but relatively little work has been done to evaluate the effects of CS on cancer cells. In this review of the literature, the authors demonstrate that CS induces a more malignant tumor phenotype by increasing proliferation, migration, invasion, and angiogenesis and by activating prosurvival cellular pathways. Significant work is needed to understand the biologic effect of CS on cancer biology, including the development of model systems and the identification of critical biologic mediators of CS-induced changes in cancer cell physiology. © 2014 American Cancer Society.

  6. Molecular biology of mycoplasmas: from the minimum cell concept to the artificial cell.

    Science.gov (United States)

    Cordova, Caio M M; Hoeltgebaum, Daniela L; Machado, Laís D P N; Santos, Larissa Dos

    2016-01-01

    Mycoplasmas are a large group of bacteria, sorted into different genera in the Mollicutes class, whose main characteristic in common, besides the small genome, is the absence of cell wall. They are considered cellular and molecular biology study models. We present an updated review of the molecular biology of these model microorganisms and the development of replicative vectors for the transformation of mycoplasmas. Synthetic biology studies inspired by these pioneering works became possible and won the attention of the mainstream media. For the first time, an artificial genome was synthesized (a minimal genome produced from consensus sequences obtained from mycoplasmas). For the first time, a functional artificial cell has been constructed by introducing a genome completely synthesized within a cell envelope of a mycoplasma obtained by transformation techniques. Therefore, this article offers an updated insight to the state of the art of these peculiar organisms' molecular biology.

  7. 100 years after Smoluchowski: stochastic processes in cell biology

    International Nuclear Information System (INIS)

    Holcman, D; Schuss, Z

    2017-01-01

    100 years after Smoluchowski introduced his approach to stochastic processes, they are now at the basis of mathematical and physical modeling in cellular biology: they are used for example to analyse and to extract features from a large number (tens of thousands) of single molecular trajectories or to study the diffusive motion of molecules, proteins or receptors. Stochastic modeling is a new step in large data analysis that serves extracting cell biology concepts. We review here Smoluchowski’s approach to stochastic processes and provide several applications for coarse-graining diffusion, studying polymer models for understanding nuclear organization and finally, we discuss the stochastic jump dynamics of telomeres across cell division and stochastic gene regulation. (topical review)

  8. Simulating biological processes: stochastic physics from whole cells to colonies

    Science.gov (United States)

    Earnest, Tyler M.; Cole, John A.; Luthey-Schulten, Zaida

    2018-05-01

    The last few decades have revealed the living cell to be a crowded spatially heterogeneous space teeming with biomolecules whose concentrations and activities are governed by intrinsically random forces. It is from this randomness, however, that a vast array of precisely timed and intricately coordinated biological functions emerge that give rise to the complex forms and behaviors we see in the biosphere around us. This seemingly paradoxical nature of life has drawn the interest of an increasing number of physicists, and recent years have seen stochastic modeling grow into a major subdiscipline within biological physics. Here we review some of the major advances that have shaped our understanding of stochasticity in biology. We begin with some historical context, outlining a string of important experimental results that motivated the development of stochastic modeling. We then embark upon a fairly rigorous treatment of the simulation methods that are currently available for the treatment of stochastic biological models, with an eye toward comparing and contrasting their realms of applicability, and the care that must be taken when parameterizing them. Following that, we describe how stochasticity impacts several key biological functions, including transcription, translation, ribosome biogenesis, chromosome replication, and metabolism, before considering how the functions may be coupled into a comprehensive model of a ‘minimal cell’. Finally, we close with our expectation for the future of the field, focusing on how mesoscopic stochastic methods may be augmented with atomic-scale molecular modeling approaches in order to understand life across a range of length and time scales.

  9. Building executable biological pathway models automatically from BioPAX

    NARCIS (Netherlands)

    Willemsen, Timo; Feenstra, Anton; Groth, Paul

    2013-01-01

    The amount of biological data exposed in semantic formats is steadily increasing. In particular, pathway information (a model of how molecules interact within a cell) from databases such as KEGG and WikiPathways are available in a standard RDF-based format BioPAX. However, these models are

  10. Biology and relevance of human acute myeloid leukemia stem cells.

    Science.gov (United States)

    Thomas, Daniel; Majeti, Ravindra

    2017-03-23

    Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

  11. CellNet: network biology applied to stem cell engineering.

    Science.gov (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

    2014-08-14

    Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Cell-free synthetic biology: thinking outside the cell.

    Science.gov (United States)

    Hodgman, C Eric; Jewett, Michael C

    2012-05-01

    Cell-free synthetic biology is emerging as a powerful approach aimed to understand, harness, and expand the capabilities of natural biological systems without using intact cells. Cell-free systems bypass cell walls and remove genetic regulation to enable direct access to the inner workings of the cell. The unprecedented level of control and freedom of design, relative to in vivo systems, has inspired the rapid development of engineering foundations for cell-free systems in recent years. These efforts have led to programmed circuits, spatially organized pathways, co-activated catalytic ensembles, rational optimization of synthetic multi-enzyme pathways, and linear scalability from the micro-liter to the 100-liter scale. It is now clear that cell-free systems offer a versatile test-bed for understanding why nature's designs work the way they do and also for enabling biosynthetic routes to novel chemicals, sustainable fuels, and new classes of tunable materials. While challenges remain, the emergence of cell-free systems is poised to open the way to novel products that until now have been impractical, if not impossible, to produce by other means. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Biophysical mechanisms complementing "classical" cell biology.

    Science.gov (United States)

    Funk, Richard H W

    2018-01-01

    This overview addresses phenomena in cell- and molecular biology which are puzzling by their fast and highly coordinated way of organization. Generally, it appears that informative processes probably involved are more on the biophysical than on the classical biochemical side. The coordination problem is explained within the first part of the review by the topic of endogenous electrical phenomena. These are found e.g. in fast tissue organization and reorganization processes like development, wound healing and regeneration. Here, coupling into classical biochemical signaling and reactions can be shown by modern microscopy, electronics and bioinformatics. Further, one can follow the triggered reactions seamlessly via molecular biology till into genetics. Direct observation of intracellular electric processes is very difficult because of e.g. shielding through the cell membrane and damping by other structures. Therefore, we have to rely on photonic and photon - phonon coupling phenomena like molecular vibrations, which are addressed within the second part. Molecules normally possess different charge moieties and thus small electromagnetic (EMF) patterns arise during molecular vibration. These patterns can now be measured best within the optical part of the spectrum - much less in the lower terahertz till kHz and lower Hz part (third part of this review). Finally, EMFs facilitate quantum informative processes in coherent domains of molecular, charge and electron spin motion. This helps to coordinate such manifold and intertwined processes going on within cells, tissues and organs (part 4). Because the phenomena described in part 3 and 4 of the review still await really hard proofs we need concerted efforts and a combination of biophysics, molecular biology and informatics to unravel the described mysteries in "physics of life".

  14. Piecewise deterministic processes in biological models

    CERN Document Server

    Rudnicki, Ryszard

    2017-01-01

    This book presents a concise introduction to piecewise deterministic Markov processes (PDMPs), with particular emphasis on their applications to biological models. Further, it presents examples of biological phenomena, such as gene activity and population growth, where different types of PDMPs appear: continuous time Markov chains, deterministic processes with jumps, processes with switching dynamics, and point processes. Subsequent chapters present the necessary tools from the theory of stochastic processes and semigroups of linear operators, as well as theoretical results concerning the long-time behaviour of stochastic semigroups induced by PDMPs and their applications to biological models. As such, the book offers a valuable resource for mathematicians and biologists alike. The first group will find new biological models that lead to interesting and often new mathematical questions, while the second can observe how to include seemingly disparate biological processes into a unified mathematical theory, and...

  15. Nanobodies and recombinant binders in cell biology

    Science.gov (United States)

    Helma, Jonas; Cardoso, M. Cristina; Muyldermans, Serge

    2015-01-01

    Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. PMID:26056137

  16. Nanobodies and recombinant binders in cell biology.

    Science.gov (United States)

    Helma, Jonas; Cardoso, M Cristina; Muyldermans, Serge; Leonhardt, Heinrich

    2015-06-08

    Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. © 2015 Helma et al.

  17. Towards Synthesizing Executable Models in Biology

    Directory of Open Access Journals (Sweden)

    Jasmin eFisher

    2014-12-01

    Full Text Available Over the last decade, executable models of biological behaviors have repeatedly provided new scientific discoveries, uncovered novel insights, and directed new experimental avenues. These models are computer programs whose execution mechanistically simulates aspects of the cell’s behaviors. If the observed behavior of the program agrees with the observed biological behavior, then the program explains the phenomena. This approach has proven beneficial for gaining new biological insights and directing new experimental avenues. One advantage of this approach is that techniques for analysis of computer programs can be applied to the analysis of executable models. For example, one can confirm that a model agrees with experiments for all possible executions of the model (corresponding to all environmental conditions, even if there are a huge number of executions. Various formal methods have been adapted for this context, for example, model checking or symbolic analysis of state spaces. To avoid manual construction of executable models, one can apply synthesis, a method to produce programs automatically from high-level specifications. In the context of biological modelling, synthesis would correspond to extracting executable models from experimental data. We survey recent results about the usage of the techniques underlying synthesis of computer programs for the inference of biological models from experimental data. We describe synthesis of biological models from curated mutation experiment data, inferring network connectivity models from phosphoproteomic data, and synthesis of Boolean networks from gene expression data. While much work has been done on automated analysis of similar datasets using machine learning and artificial intelligence, using synthesis techniques provides new opportunities such as efficient computation of disambiguating experiments, as well as the ability to produce different kinds of models automatically from biological data.

  18. Stem cell biology and cell transplantation therapy in the retina.

    Science.gov (United States)

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

    2010-01-01

    Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells is an important treatment strategy. Although adult neurogenesis occurs in restricted regions, the CNS has poor potential for regeneration to compensate for cell loss. Thus, cell transplantation into damaged or diseased CNS tissues is a promising approach to treating various neurodegenerative disorders. Transplantation of photoreceptors or retinal pigment epithelium cells derived from human ES cells can restore some visual function. Patient-specific iPS cells may lead to customized cell therapy. However, regeneration of retinal function will require a detailed understanding of eye development, visual system circuitry, and retinal degeneration pathology. Here, we review the current progress in retinal regeneration, focusing on the therapeutic potential of pluripotent stem cells.

  19. The Emerging Cell Biology of Thyroid Stem Cells

    Science.gov (United States)

    Latif, Rauf; Minsky, Noga C.; Ma, Risheng

    2011-01-01

    Context: Stem cells are undifferentiated cells with the property of self-renewal and give rise to highly specialized cells under appropriate local conditions. The use of stem cells in regenerative medicine holds great promise for the treatment of many diseases, including those of the thyroid gland. Evidence Acquisition: This review focuses on the progress that has been made in thyroid stem cell research including an overview of cellular and molecular events (most of which were drawn from the period 1990–2011) and discusses the remaining problems encountered in their differentiation. Evidence Synthesis: Protocols for the in vitro differentiation of embryonic stem cells, based on normal developmental processes, have generated thyroid-like cells but without full thyrocyte function. However, agents have been identified, including activin A, insulin, and IGF-I, which are able to stimulate the generation of thyroid-like cells in vitro. In addition, thyroid stem/progenitor cells have been identified within the normal thyroid gland and within thyroid cancers. Conclusions: Advances in thyroid stem cell biology are providing not only insight into thyroid development but may offer therapeutic potential in thyroid cancer and future thyroid cell replacement therapy. PMID:21778219

  20. Can molecular cell biology explain chromosome motions?

    Directory of Open Access Journals (Sweden)

    Gagliardi L

    2011-05-01

    Full Text Available Abstract Background Mitotic chromosome motions have recently been correlated with electrostatic forces, but a lingering "molecular cell biology" paradigm persists, proposing binding and release proteins or molecular geometries for force generation. Results Pole-facing kinetochore plates manifest positive charges and interact with negatively charged microtubule ends providing the motive force for poleward chromosome motions by classical electrostatics. This conceptual scheme explains dynamic tracking/coupling of kinetochores to microtubules and the simultaneous depolymerization of kinetochore microtubules as poleward force is generated. Conclusion We question here why cells would prefer complex molecular mechanisms to move chromosomes when direct electrostatic interactions between known bound charge distributions can accomplish the same task much more simply.

  1. Cell Biology of Astrocyte-Synapse Interactions.

    Science.gov (United States)

    Allen, Nicola J; Eroglu, Cagla

    2017-11-01

    Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the establishment and maintenance of proper synaptic connectivity, our understanding of their role in brain function is still in its infancy. We propose that this is at least in part due to large gaps in our knowledge of the cell biology of astrocytes and the mechanisms they use to interact with synapses. In this review, we summarize some of the seminal findings that yield important insight into the cellular and molecular basis of astrocyte-neuron communication, focusing on the role of astrocytes in the development and remodeling of synapses. Furthermore, we pose some pressing questions that need to be addressed to advance our mechanistic understanding of the role of astrocytes in regulating synaptic development. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Biocellion: accelerating computer simulation of multicellular biological system models.

    Science.gov (United States)

    Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

    2014-11-01

    Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Cells, targets, and molecules in radiation biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    Cellular damage and repair are discussed with regard to inactivation models, dose-effect curves and cancer research, repair relative to damage accumulation, potentially lethal damage, repair of potentially lethal vs. sublethal damage, cell killing and DNA damage due to nonionizing radiation, and anisotonicity vs. lethality due to nonionizing radiation. Other topics discussed are DNA damage and repair in cells exposed to ionizing radiation, kinetics of repair of single-strand DNA breaks, effects of actinomycin D on x-ray survival curve of hamster cells, misrepair and lethality, and perspective and prospects

  4. Cellular and molecular biology of the prostate: stem cell biology.

    NARCIS (Netherlands)

    Schalken, J.A.; Leenders, G.J.L.H. van

    2003-01-01

    The normal prostate shows a high degree of cellular organization. The basal layer is populated by prostate epithelial stem cells and a population of transiently proliferating/amplifying (TP/A) cells intermediate to the stem cells and fully differentiated cells. The luminal layer is composed of fully

  5. Setting Parameters for Biological Models With ANIMO

    NARCIS (Netherlands)

    Schivo, Stefano; Scholma, Jetse; Karperien, Hermanus Bernardus Johannes; Post, Janine Nicole; van de Pol, Jan Cornelis; Langerak, Romanus; André, Étienne; Frehse, Goran

    2014-01-01

    ANIMO (Analysis of Networks with Interactive MOdeling) is a software for modeling biological networks, such as e.g. signaling, metabolic or gene networks. An ANIMO model is essentially the sum of a network topology and a number of interaction parameters. The topology describes the interactions

  6. Seeing Cells: Teaching the Visual/Verbal Rhetoric of Biology

    Science.gov (United States)

    Dinolfo, John; Heifferon, Barbara; Temesvari, Lesly A.

    2007-01-01

    This pilot study obtained baseline information on verbal and visual rhetorics to teach microscopy techniques to college biology majors. We presented cell images to students in cell biology and biology writing classes and then asked them to identify textual, verbal, and visual cues that support microscopy learning. Survey responses suggest that…

  7. Biological transportation networks: Modeling and simulation

    KAUST Repository

    Albi, Giacomo

    2015-09-15

    We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation and angiogenesis) and ion transportation networks (e.g., neural networks) is explained in detail and basic analytical features like the gradient flow structure of the fluid transportation network model and the impact of the model parameters on the geometry and topology of network formation are analyzed. We also present a numerical finite-element based discretization scheme and discuss sample cases of network formation simulations.

  8. Modeling biology using relational databases.

    Science.gov (United States)

    Peitzsch, Robert M

    2003-02-01

    There are several different methodologies that can be used for designing a database schema; no one is the best for all occasions. This unit demonstrates two different techniques for designing relational tables and discusses when each should be used. These two techniques presented are (1) traditional Entity-Relationship (E-R) modeling and (2) a hybrid method that combines aspects of data warehousing and E-R modeling. The method of choice depends on (1) how well the information and all its inherent relationships are understood, (2) what types of questions will be asked, (3) how many different types of data will be included, and (4) how much data exists.

  9. Structured population models in biology and epidemiology

    CERN Document Server

    Ruan, Shigui

    2008-01-01

    This book consists of six chapters written by leading researchers in mathematical biology. These chapters present recent and important developments in the study of structured population models in biology and epidemiology. Topics include population models structured by age, size, and spatial position; size-structured models for metapopulations, macroparasitc diseases, and prion proliferation; models for transmission of microparasites between host populations living on non-coincident spatial domains; spatiotemporal patterns of disease spread; method of aggregation of variables in population dynamics; and biofilm models. It is suitable as a textbook for a mathematical biology course or a summer school at the advanced undergraduate and graduate level. It can also serve as a reference book for researchers looking for either interesting and specific problems to work on or useful techniques and discussions of some particular problems.

  10. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Daniel D. [Integrative Genetics and Genomics, University of California Davis, Davis, CA (United States); Department of Biomedical Engineering, University of California Davis, Davis, CA (United States); Villarreal, Fernando D.; Wu, Fan; Tan, Cheemeng, E-mail: cmtan@ucdavis.edu [Department of Biomedical Engineering, University of California Davis, Davis, CA (United States)

    2014-12-09

    As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  11. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    International Nuclear Information System (INIS)

    Lewis, Daniel D.; Villarreal, Fernando D.; Wu, Fan; Tan, Cheemeng

    2014-01-01

    As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  12. Cell biology apps for Apple devices.

    Science.gov (United States)

    Stark, Louisa A

    2012-01-01

    Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score.

  13. Unified data model for biological data

    International Nuclear Information System (INIS)

    Idrees, M.

    2014-01-01

    A data model empowers us to store, retrieve and manipulate data in a unified way. We consider the biological data consists of DNA (De-Oxyribonucleic Acid), RNA (Ribonucleic Acid) and protein structures. In our Bioinformatics Lab (Bioinformatics Lab, Alkhawarizmi Institute of Computer Science, University of Engineering and Technology, Lahore, Pakistan), we have already proposed two data models for DNA and protein structures individually. In this paper, we propose a unified data model by using the data models of TOS (Temporal Object Oriented System) after making some necessary modifications to this data model and our already proposed the two data models. This proposed unified data model can be used for the modeling and maintaining the biological data (i.e. DNA, RNA and protein structures), in a single unified way. (author)

  14. SYSTEMS BIOLOGY AND METABOLIC ENGINEERING OF ARTHROSPIRA CELL FACTORIES

    Directory of Open Access Journals (Sweden)

    Amornpan Klanchui

    2012-10-01

    Full Text Available Arthrospira are attractive candidates to serve as cell factories for production of many valuable compounds useful for food, feed, fuel and pharmaceutical industries. In connection with the development of sustainable bioprocessing, it is a challenge to design and develop efficient Arthrospira cell factories which can certify effective conversion from the raw materials (i.e. CO2 and sun light into desired products. With the current availability of the genome sequences and metabolic models of Arthrospira, the development of Arthrospira factories can now be accelerated by means of systems biology and the metabolic engineering approach. Here, we review recent research involving the use of Arthrospira cell factories for industrial applications, as well as the exploitation of systems biology and the metabolic engineering approach for studying Arthrospira. The current status of genomics and proteomics through the development of the genome-scale metabolic model of Arthrospira, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies are discussed. At the end, the perspective and future direction on Arthrospira cell factories for industrial biotechnology are presented.

  15. Ranked retrieval of Computational Biology models.

    Science.gov (United States)

    Henkel, Ron; Endler, Lukas; Peters, Andre; Le Novère, Nicolas; Waltemath, Dagmar

    2010-08-11

    The study of biological systems demands computational support. If targeting a biological problem, the reuse of existing computational models can save time and effort. Deciding for potentially suitable models, however, becomes more challenging with the increasing number of computational models available, and even more when considering the models' growing complexity. Firstly, among a set of potential model candidates it is difficult to decide for the model that best suits ones needs. Secondly, it is hard to grasp the nature of an unknown model listed in a search result set, and to judge how well it fits for the particular problem one has in mind. Here we present an improved search approach for computational models of biological processes. It is based on existing retrieval and ranking methods from Information Retrieval. The approach incorporates annotations suggested by MIRIAM, and additional meta-information. It is now part of the search engine of BioModels Database, a standard repository for computational models. The introduced concept and implementation are, to our knowledge, the first application of Information Retrieval techniques on model search in Computational Systems Biology. Using the example of BioModels Database, it was shown that the approach is feasible and extends the current possibilities to search for relevant models. The advantages of our system over existing solutions are that we incorporate a rich set of meta-information, and that we provide the user with a relevance ranking of the models found for a query. Better search capabilities in model databases are expected to have a positive effect on the reuse of existing models.

  16. The emerging age of cell-free synthetic biology.

    Science.gov (United States)

    Smith, Mark Thomas; Wilding, Kristen M; Hunt, Jeremy M; Bennett, Anthony M; Bundy, Bradley C

    2014-08-25

    The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. The Strategies of Modeling in Biology Education

    Science.gov (United States)

    Svoboda, Julia; Passmore, Cynthia

    2013-01-01

    Modeling, like inquiry more generally, is not a single method, but rather a complex suite of strategies. Philosophers of biology, citing the diverse aims, interests, and disciplinary cultures of biologists, argue that modeling is best understood in the context of its epistemic aims and cognitive payoffs. In the science education literature,…

  18. Introduction to stochastic models in biology

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Samson, Adeline

    2013-01-01

    This chapter is concerned with continuous time processes, which are often modeled as a system of ordinary differential equations (ODEs). These models assume that the observed dynamics are driven exclusively by internal, deterministic mechanisms. However, real biological systems will always be exp...

  19. Notions of similarity for computational biology models

    KAUST Repository

    Waltemath, Dagmar

    2016-03-21

    Computational models used in biology are rapidly increasing in complexity, size, and numbers. To build such large models, researchers need to rely on software tools for model retrieval, model combination, and version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of similarity may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here, we introduce a general notion of quantitative model similarities, survey the use of existing model comparison methods in model building and management, and discuss potential applications of model comparison. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on different model aspects. Potentially relevant aspects of a model comprise its references to biological entities, network structure, mathematical equations and parameters, and dynamic behaviour. Future similarity measures could combine these model aspects in flexible, problem-specific ways in order to mimic users\\' intuition about model similarity, and to support complex model searches in databases.

  20. Notions of similarity for computational biology models

    KAUST Repository

    Waltemath, Dagmar; Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knuepfer, Christian; Liebermeister, Wolfram

    2016-01-01

    Computational models used in biology are rapidly increasing in complexity, size, and numbers. To build such large models, researchers need to rely on software tools for model retrieval, model combination, and version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of similarity may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here, we introduce a general notion of quantitative model similarities, survey the use of existing model comparison methods in model building and management, and discuss potential applications of model comparison. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on different model aspects. Potentially relevant aspects of a model comprise its references to biological entities, network structure, mathematical equations and parameters, and dynamic behaviour. Future similarity measures could combine these model aspects in flexible, problem-specific ways in order to mimic users' intuition about model similarity, and to support complex model searches in databases.

  1. Integrating cell biology and proteomic approaches in plants.

    Science.gov (United States)

    Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef

    2017-10-03

    Significant improvements of protein extraction, separation, mass spectrometry and bioinformatics nurtured advancements of proteomics during the past years. The usefulness of proteomics in the investigation of biological problems can be enhanced by integration with other experimental methods from cell biology, genetics, biochemistry, pharmacology, molecular biology and other omics approaches including transcriptomics and metabolomics. This review aims to summarize current trends integrating cell biology and proteomics in plant science. Cell biology approaches are most frequently used in proteomic studies investigating subcellular and developmental proteomes, however, they were also employed in proteomic studies exploring abiotic and biotic stress responses, vesicular transport, cytoskeleton and protein posttranslational modifications. They are used either for detailed cellular or ultrastructural characterization of the object subjected to proteomic study, validation of proteomic results or to expand proteomic data. In this respect, a broad spectrum of methods is employed to support proteomic studies including ultrastructural electron microscopy studies, histochemical staining, immunochemical localization, in vivo imaging of fluorescently tagged proteins and visualization of protein-protein interactions. Thus, cell biological observations on fixed or living cell compartments, cells, tissues and organs are feasible, and in some cases fundamental for the validation and complementation of proteomic data. Validation of proteomic data by independent experimental methods requires development of new complementary approaches. Benefits of cell biology methods and techniques are not sufficiently highlighted in current proteomic studies. This encouraged us to review most popular cell biology methods used in proteomic studies and to evaluate their relevance and potential for proteomic data validation and enrichment of purely proteomic analyses. We also provide examples of

  2. Functional model of biological neural networks.

    Science.gov (United States)

    Lo, James Ting-Ho

    2010-12-01

    A functional model of biological neural networks, called temporal hierarchical probabilistic associative memory (THPAM), is proposed in this paper. THPAM comprises functional models of dendritic trees for encoding inputs to neurons, a first type of neuron for generating spike trains, a second type of neuron for generating graded signals to modulate neurons of the first type, supervised and unsupervised Hebbian learning mechanisms for easy learning and retrieving, an arrangement of dendritic trees for maximizing generalization, hardwiring for rotation-translation-scaling invariance, and feedback connections with different delay durations for neurons to make full use of present and past informations generated by neurons in the same and higher layers. These functional models and their processing operations have many functions of biological neural networks that have not been achieved by other models in the open literature and provide logically coherent answers to many long-standing neuroscientific questions. However, biological justifications of these functional models and their processing operations are required for THPAM to qualify as a macroscopic model (or low-order approximate) of biological neural networks.

  3. Alkali-treated titanium selectively regulating biological behaviors of bacteria, cancer cells and mesenchymal stem cells.

    Science.gov (United States)

    Li, Jinhua; Wang, Guifang; Wang, Donghui; Wu, Qianju; Jiang, Xinquan; Liu, Xuanyong

    2014-12-15

    Many attentions have been paid to the beneficial effect of alkali-treated titanium to bioactivity and osteogenic activity, but few to the other biological effect. In this work, hierarchical micro/nanopore films were prepared on titanium surface by acid etching and alkali treatment and their biological effects on bacteria, cancer cells and mesenchymal stem cells were investigated. Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and human cholangiocarcinoma cell line RBE were used to investigate whether alkali-treated titanium can influence behaviors of bacteria and cancer cells. Responses of bone marrow mesenchymal stem cells (BMMSCs) to alkali-treated titanium were also subsequently investigated. The alkali-treated titanium can potently reduce bacterial adhesion, inhibit RBE and BMMSCs proliferation, while can better promote BMMSCs osteogenesis and angiogenesis than acid-etched titanium. The bacteriostatic ability of the alkali-treated titanium is proposed to result from the joint effect of micro/nanotopography and local pH increase at bacterium/material interface due to the hydrolysis of alkali (earth) metal titanate salts. The inhibitory action of cell proliferation is thought to be the effect of local pH increase at cell/material interface which causes the alkalosis of cells. This alkalosis model reported in this work will help to understand the biologic behaviors of various cells on alkali-treated titanium surface and design the intended biomedical applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease.

    Science.gov (United States)

    Grau-Monge, Cristina; Delcroix, Gaëtan J-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F; Armour, Maxime R; Montero, Ramon B; Schiller, Paul C; Andreopoulos, Fotios M; D'Ippolito, Gianluca

    2017-02-17

    Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of two layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration.

  5. An online model composition tool for system biology models.

    Science.gov (United States)

    Coskun, Sarp A; Cicek, A Ercument; Lai, Nicola; Dash, Ranjan K; Ozsoyoglu, Z Meral; Ozsoyoglu, Gultekin

    2013-09-05

    There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, querying, and browsing computational models. We present the design and implementation of the Model Composition Tool (Interface) within the PathCase-SB (PathCase Systems Biology) web portal. The tool helps users compose systems biology models to facilitate the complex process of merging systems biology models. We also present three tools that support the model composition tool, namely, (1) Model Simulation Interface that generates a visual plot of the simulation according to user's input, (2) iModel Tool as a platform for users to upload their own models to compose, and (3) SimCom Tool that provides a side by side comparison of models being composed in the same pathway. Finally, we provide a web site that hosts BioModels Database models and a separate web site that hosts SBML Test Suite models. Model composition tool (and the other three tools) can be used with little or no knowledge of the SBML document structure. For this reason, students or anyone who wants to learn about systems biology will benefit from the described functionalities. SBML Test Suite models will be a nice starting point for beginners. And, for more advanced purposes, users will able to access and employ models of the BioModels Database as well.

  6. Notions of similarity for systems biology models.

    Science.gov (United States)

    Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knüpfer, Christian; Liebermeister, Wolfram; Waltemath, Dagmar

    2018-01-01

    Systems biology models are rapidly increasing in complexity, size and numbers. When building large models, researchers rely on software tools for the retrieval, comparison, combination and merging of models, as well as for version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of 'similarity' may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here we survey existing methods for the comparison of models, introduce quantitative measures for model similarity, and discuss potential applications of combined similarity measures. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on a combination of different model aspects. The six aspects that we define as potentially relevant for similarity are underlying encoding, references to biological entities, quantitative behaviour, qualitative behaviour, mathematical equations and parameters and network structure. We argue that future similarity measures will benefit from combining these model aspects in flexible, problem-specific ways to mimic users' intuition about model similarity, and to support complex model searches in databases. © The Author 2016. Published by Oxford University Press.

  7. Structure, function, and behaviour of computational models in systems biology.

    Science.gov (United States)

    Knüpfer, Christian; Beckstein, Clemens; Dittrich, Peter; Le Novère, Nicolas

    2013-05-31

    Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such "bio-models" necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language. We present a conceptual framework - the meaning facets - which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model's components (structure), the meaning of the model's intended use (function), and the meaning of the model's dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces. The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research.

  8. Obstructive renal injury: from fluid mechanics to molecular cell biology.

    Science.gov (United States)

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

    2010-04-22

    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

  9. Advancing cell biology through proteomics in space and time (PROSPECTS)

    DEFF Research Database (Denmark)

    Lamond, A.I.; Uhlen, M.; Horning, S.

    2012-01-01

    a range of sensitive and quantitative approaches for measuring protein structures and dynamics that promise to revolutionize our understanding of cell biology and molecular mechanisms in both human cells and model organisms. The Proteomics Specification in Time and Space (PROSPECTS) Network is a unique EU......-funded project that brings together leading European research groups, spanning from instrumentation to biomedicine, in a collaborative five year initiative to develop new methods and applications for the functional analysis of cellular proteins. This special issue of Molecular and Cellular Proteomics presents 16...... quantification of protein levels. Manuscripts in this issue exemplify approaches for performing quantitative measurements of cell proteomes and for studying their dynamic responses to perturbation, both during normal cellular responses and in disease mechanisms. Here we present a perspective on how...

  10. Cell Biology of Cnidarian-Dinoflagellate Symbiosis

    Science.gov (United States)

    Allemand, Denis; Weis, Virginia M.

    2012-01-01

    Summary: The symbiosis between cnidarians (e.g., corals or sea anemones) and intracellular dinoflagellate algae of the genus Symbiodinium is of immense ecological importance. In particular, this symbiosis promotes the growth and survival of reef corals in nutrient-poor tropical waters; indeed, coral reefs could not exist without this symbiosis. However, our fundamental understanding of the cnidarian-dinoflagellate symbiosis and of its links to coral calcification remains poor. Here we review what we currently know about the cell biology of cnidarian-dinoflagellate symbiosis. In doing so, we aim to refocus attention on fundamental cellular aspects that have been somewhat neglected since the early to mid-1980s, when a more ecological approach began to dominate. We review the four major processes that we believe underlie the various phases of establishment and persistence in the cnidarian/coral-dinoflagellate symbiosis: (i) recognition and phagocytosis, (ii) regulation of host-symbiont biomass, (iii) metabolic exchange and nutrient trafficking, and (iv) calcification. Where appropriate, we draw upon examples from a range of cnidarian-alga symbioses, including the symbiosis between green Hydra and its intracellular chlorophyte symbiont, which has considerable potential to inform our understanding of the cnidarian-dinoflagellate symbiosis. Ultimately, we provide a comprehensive overview of the history of the field, its current status, and where it should be going in the future. PMID:22688813

  11. Genome Annotation in a Community College Cell Biology Lab

    Science.gov (United States)

    Beagley, C. Timothy

    2013-01-01

    The Biology Department at Salt Lake Community College has used the IMG-ACT toolbox to introduce a genome mapping and annotation exercise into the laboratory portion of its Cell Biology course. This project provides students with an authentic inquiry-based learning experience while introducing them to computational biology and contemporary learning…

  12. Ultrafast spectroscopy of model biological membranes

    NARCIS (Netherlands)

    Ghosh, Avishek

    2009-01-01

    In this PhD thesis, I have described the novel time-resolved sum-frequency generation (TR-SFG) spectroscopic technique that I developed during the course of my PhD research and used it study the ultrafast vibrational, structural and orientational dynamics of water molecules at model biological

  13. Dynamics of mathematical models in biology bringing mathematics to life

    CERN Document Server

    Zazzu, Valeria; Guarracino, Mario

    2016-01-01

    This volume focuses on contributions from both the mathematics and life science community surrounding the concepts of time and dynamicity of nature, two significant elements which are often overlooked in modeling process to avoid exponential computations. The book is divided into three distinct parts: dynamics of genomes and genetic variation, dynamics of motifs, and dynamics of biological networks. Chapters included in dynamics of genomes and genetic variation analyze the molecular mechanisms and evolutionary processes that shape the structure and function of genomes and those that govern genome dynamics. The dynamics of motifs portion of the volume provides an overview of current methods for motif searching in DNA, RNA and proteins, a key process to discover emergent properties of cells, tissues, and organisms. The part devoted to the dynamics of biological networks covers networks aptly discusses networks in complex biological functions and activities that interpret processes in cells. Moreover, chapters i...

  14. Prospective Tests on Biological Models of Acupuncture

    Directory of Open Access Journals (Sweden)

    Charles Shang

    2009-01-01

    Full Text Available The biological effects of acupuncture include the regulation of a variety of neurohumoral factors and growth control factors. In science, models or hypotheses with confirmed predictions are considered more convincing than models solely based on retrospective explanations. Literature review showed that two biological models of acupuncture have been prospectively tested with independently confirmed predictions: The neurophysiology model on the long-term effects of acupuncture emphasizes the trophic and anti-inflammatory effects of acupuncture. Its prediction on the peripheral effect of endorphin in acupuncture has been confirmed. The growth control model encompasses the neurophysiology model and suggests that a macroscopic growth control system originates from a network of organizers in embryogenesis. The activity of the growth control system is important in the formation, maintenance and regulation of all the physiological systems. Several phenomena of acupuncture such as the distribution of auricular acupuncture points, the long-term effects of acupuncture and the effect of multimodal non-specific stimulation at acupuncture points are consistent with the growth control model. The following predictions of the growth control model have been independently confirmed by research results in both acupuncture and conventional biomedical sciences: (i Acupuncture has extensive growth control effects. (ii Singular point and separatrix exist in morphogenesis. (iii Organizers have high electric conductance, high current density and high density of gap junctions. (iv A high density of gap junctions is distributed as separatrices or boundaries at body surface after early embryogenesis. (v Many acupuncture points are located at transition points or boundaries between different body domains or muscles, coinciding with the connective tissue planes. (vi Some morphogens and organizers continue to function after embryogenesis. Current acupuncture research suggests a

  15. Multi-level and hybrid modelling approaches for systems biology.

    Science.gov (United States)

    Bardini, R; Politano, G; Benso, A; Di Carlo, S

    2017-01-01

    During the last decades, high-throughput techniques allowed for the extraction of a huge amount of data from biological systems, unveiling more of their underling complexity. Biological systems encompass a wide range of space and time scales, functioning according to flexible hierarchies of mechanisms making an intertwined and dynamic interplay of regulations. This becomes particularly evident in processes such as ontogenesis, where regulative assets change according to process context and timing, making structural phenotype and architectural complexities emerge from a single cell, through local interactions. The information collected from biological systems are naturally organized according to the functional levels composing the system itself. In systems biology, biological information often comes from overlapping but different scientific domains, each one having its own way of representing phenomena under study. That is, the different parts of the system to be modelled may be described with different formalisms. For a model to have improved accuracy and capability for making a good knowledge base, it is good to comprise different system levels, suitably handling the relative formalisms. Models which are both multi-level and hybrid satisfy both these requirements, making a very useful tool in computational systems biology. This paper reviews some of the main contributions in this field.

  16. From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

    Science.gov (United States)

    Chiel, Hillel J.; McManus, Jeffrey M.; Shaw, Kendrick M.

    2010-01-01

    We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge…

  17. Effect of amino acid supplementation on titer and glycosylation distribution in hybridoma cell cultures-Systems biology-based interpretation using genome-scale metabolic flux balance model and multivariate data analysis.

    Science.gov (United States)

    Reimonn, Thomas M; Park, Seo-Young; Agarabi, Cyrus D; Brorson, Kurt A; Yoon, Seongkyu

    2016-09-01

    Genome-scale flux balance analysis (FBA) is a powerful systems biology tool to characterize intracellular reaction fluxes during cell cultures. FBA estimates intracellular reaction rates by optimizing an objective function, subject to the constraints of a metabolic model and media uptake/excretion rates. A dynamic extension to FBA, dynamic flux balance analysis (DFBA), can calculate intracellular reaction fluxes as they change during cell cultures. In a previous study by Read et al. (2013), a series of informed amino acid supplementation experiments were performed on twelve parallel murine hybridoma cell cultures, and this data was leveraged for further analysis (Read et al., Biotechnol Prog. 2013;29:745-753). In order to understand the effects of media changes on the model murine hybridoma cell line, a systems biology approach is applied in the current study. Dynamic flux balance analysis was performed using a genome-scale mouse metabolic model, and multivariate data analysis was used for interpretation. The calculated reaction fluxes were examined using partial least squares and partial least squares discriminant analysis. The results indicate media supplementation increases product yield because it raises nutrient levels extending the growth phase, and the increased cell density allows for greater culture performance. At the same time, the directed supplementation does not change the overall metabolism of the cells. This supports the conclusion that product quality, as measured by glycoform assays, remains unchanged because the metabolism remains in a similar state. Additionally, the DFBA shows that metabolic state varies more at the beginning of the culture but less by the middle of the growth phase, possibly due to stress on the cells during inoculation. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1163-1173, 2016. © 2016 American Institute of Chemical Engineers.

  18. Synthetic biology: programming cells for biomedical applications.

    Science.gov (United States)

    Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

    2012-01-01

    The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

  19. Plant Systems Biology at the Single-Cell Level.

    Science.gov (United States)

    Libault, Marc; Pingault, Lise; Zogli, Prince; Schiefelbein, John

    2017-11-01

    Our understanding of plant biology is increasingly being built upon studies using 'omics and system biology approaches performed at the level of the entire plant, organ, or tissue. Although these approaches open new avenues to better understand plant biology, they suffer from the cellular complexity of the analyzed sample. Recent methodological advances now allow plant scientists to overcome this limitation and enable biological analyses of single-cells or single-cell-types. Coupled with the development of bioinformatics and functional genomics resources, these studies provide opportunities for high-resolution systems analyses of plant phenomena. In this review, we describe the recent advances, current challenges, and future directions in exploring the biology of single-cells and single-cell-types to enhance our understanding of plant biology as a system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Boolean Models of Biological Processes Explain Cascade-Like Behavior.

    Science.gov (United States)

    Chen, Hao; Wang, Guanyu; Simha, Rahul; Du, Chenghang; Zeng, Chen

    2016-01-29

    Biological networks play a key role in determining biological function and therefore, an understanding of their structure and dynamics is of central interest in systems biology. In Boolean models of such networks, the status of each molecule is either "on" or "off" and along with the molecules interact with each other, their individual status changes from "on" to "off" or vice-versa and the system of molecules in the network collectively go through a sequence of changes in state. This sequence of changes is termed a biological process. In this paper, we examine the common perception that events in biomolecular networks occur sequentially, in a cascade-like manner, and ask whether this is likely to be an inherent property. In further investigations of the budding and fission yeast cell-cycle, we identify two generic dynamical rules. A Boolean system that complies with these rules will automatically have a certain robustness. By considering the biological requirements in robustness and designability, we show that those Boolean dynamical systems, compared to an arbitrary dynamical system, statistically present the characteristics of cascadeness and sequentiality, as observed in the budding and fission yeast cell- cycle. These results suggest that cascade-like behavior might be an intrinsic property of biological processes.

  1. Physical models of cell motility

    CERN Document Server

    2016-01-01

    This book surveys the most recent advances in physics-inspired cell movement models. This synergetic, cross-disciplinary effort to increase the fidelity of computational algorithms will lead to a better understanding of the complex biomechanics of cell movement, and stimulate progress in research on related active matter systems, from suspensions of bacteria and synthetic swimmers to cell tissues and cytoskeleton.Cell motility and collective motion are among the most important themes in biology and statistical physics of out-of-equilibrium systems, and crucial for morphogenesis, wound healing, and immune response in eukaryotic organisms. It is also relevant for the development of effective treatment strategies for diseases such as cancer, and for the design of bioactive surfaces for cell sorting and manipulation. Substrate-based cell motility is, however, a very complex process as regulatory pathways and physical force generation mechanisms are intertwined. To understand the interplay between adhesion, force ...

  2. A Diagnostic Assessment for Introductory Molecular and Cell Biology

    Science.gov (United States)

    Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

    2010-01-01

    We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

  3. Determining the bacterial cell biology of Planctomycetes.

    Science.gov (United States)

    Boedeker, Christian; Schüler, Margarete; Reintjes, Greta; Jeske, Olga; van Teeseling, Muriel C F; Jogler, Mareike; Rast, Patrick; Borchert, Daniela; Devos, Damien P; Kucklick, Martin; Schaffer, Miroslava; Kolter, Roberto; van Niftrik, Laura; Engelmann, Susanne; Amann, Rudolf; Rohde, Manfred; Engelhardt, Harald; Jogler, Christian

    2017-04-10

    Bacteria of the phylum Planctomycetes have been previously reported to possess several features that are typical of eukaryotes, such as cytosolic compartmentalization and endocytosis-like macromolecule uptake. However, recent evidence points towards a Gram-negative cell plan for Planctomycetes, although in-depth experimental analysis has been hampered by insufficient genetic tools. Here we develop methods for expression of fluorescent proteins and for gene deletion in a model planctomycete, Planctopirus limnophila, to analyse its cell organization in detail. Super-resolution light microscopy of mutants, cryo-electron tomography, bioinformatic predictions and proteomic analyses support an altered Gram-negative cell plan for Planctomycetes, including a defined outer membrane, a periplasmic space that can be greatly enlarged and convoluted, and an energized cytoplasmic membrane. These conclusions are further supported by experiments performed with two other Planctomycetes, Gemmata obscuriglobus and Rhodopirellula baltica. We also provide experimental evidence that is inconsistent with endocytosis-like macromolecule uptake; instead, extracellular macromolecules can be taken up and accumulate in the periplasmic space through unclear mechanisms.

  4. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    Directory of Open Access Journals (Sweden)

    Daniel eLewis

    2014-12-01

    Full Text Available As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo systems, with only a few examples of prominent work done on predicting the dynamics of cell-free systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  5. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  6. Structural Identifiability of Dynamic Systems Biology Models.

    Science.gov (United States)

    Villaverde, Alejandro F; Barreiro, Antonio; Papachristodoulou, Antonis

    2016-10-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas.

  7. The genome of the Hi5 germ cell line from Trichoplusia ni, an agricultural pest and novel model for small RNA biology.

    Science.gov (United States)

    Fu, Yu; Yang, Yujing; Zhang, Han; Farley, Gwen; Wang, Junling; Quarles, Kaycee A; Weng, Zhiping; Zamore, Phillip D

    2018-01-29

    We report a draft assembly of the genome of Hi5 cells from the lepidopteran insect pest, Trichoplusia ni , assigning 90.6% of bases to one of 28 chromosomes and predicting 14,037 protein-coding genes. Chemoreception and detoxification gene families reveal T. ni -specific gene expansions that may explain its widespread distribution and rapid adaptation to insecticides. Transcriptome and small RNA data from thorax, ovary, testis, and the germline-derived Hi5 cell line show distinct expression profiles for 295 microRNA- and >393 piRNA-producing loci, as well as 39 genes encoding small RNA pathway proteins. Nearly all of the W chromosome is devoted to piRNA production, and T. ni siRNAs are not 2´- O -methylated. To enable use of Hi5 cells as a model system, we have established genome editing and single-cell cloning protocols. The T. ni genome provides insights into pest control and allows Hi5 cells to become a new tool for studying small RNAs ex vivo. © 2018, Fu et al.

  8. Biologically based modelling and simulation of carcinogenesis at low doses

    International Nuclear Information System (INIS)

    Ouchi, Noriyuki B.

    2003-01-01

    The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

  9. Institute for Multiscale Modeling of Biological Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Paulaitis, Michael E; Garcia-Moreno, Bertrand; Lenhoff, Abraham

    2009-12-26

    The Institute for Multiscale Modeling of Biological Interactions (IMMBI) has two primary goals: Foster interdisciplinary collaborations among faculty and their research laboratories that will lead to novel applications of multiscale simulation and modeling methods in the biological sciences and engineering; and Building on the unique biophysical/biology-based engineering foundations of the participating faculty, train scientists and engineers to apply computational methods that collectively span multiple time and length scales of biological organization. The success of IMMBI will be defined by the following: Size and quality of the applicant pool for pre-doctoral and post-doctoral fellows; Academic performance; Quality of the pre-doctoral and post-doctoral research; Impact of the research broadly and to the DOE (ASCR program) mission; Distinction of the next career step for pre-doctoral and post-doctoral fellows; and Faculty collaborations that result from IMMBI activities. Specific details about accomplishments during the three years of DOE support for IMMBI have been documented in Annual Progress Reports (April 2005, June 2006, and March 2007) and a Report for a National Academy of Sciences Review (October 2005) that were submitted to DOE on the dates indicated. An overview of these accomplishments is provided.

  10. Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology

    Science.gov (United States)

    Wright, Robin; Boggs, James

    2002-01-01

    To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular…

  11. The use of biologically based cancer risk models in radiation epidemiology

    International Nuclear Information System (INIS)

    Krewski, D.; Zielinski, J.M.; Hazelton, W.D.; Garner, M.J.; Moolgavkar, S.H.

    2003-01-01

    Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article, biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiologic datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada. (author)

  12. Guidelines for Reproducibly Building and Simulating Systems Biology Models.

    Science.gov (United States)

    Medley, J Kyle; Goldberg, Arthur P; Karr, Jonathan R

    2016-10-01

    Reproducibility is the cornerstone of the scientific method. However, currently, many systems biology models cannot easily be reproduced. This paper presents methods that address this problem. We analyzed the recent Mycoplasma genitalium whole-cell (WC) model to determine the requirements for reproducible modeling. We determined that reproducible modeling requires both repeatable model building and repeatable simulation. New standards and simulation software tools are needed to enhance and verify the reproducibility of modeling. New standards are needed to explicitly document every data source and assumption, and new deterministic parallel simulation tools are needed to quickly simulate large, complex models. We anticipate that these new standards and software will enable researchers to reproducibly build and simulate more complex models, including WC models.

  13. Multispectral optical tweezers for molecular diagnostics of single biological cells

    Science.gov (United States)

    Butler, Corey; Fardad, Shima; Sincore, Alex; Vangheluwe, Marie; Baudelet, Matthieu; Richardson, Martin

    2012-03-01

    Optical trapping of single biological cells has become an established technique for controlling and studying fundamental behavior of single cells with their environment without having "many-body" interference. The development of such an instrument for optical diagnostics (including Raman and fluorescence for molecular diagnostics) via laser spectroscopy with either the "trapping" beam or secondary beams is still in progress. This paper shows the development of modular multi-spectral imaging optical tweezers combining Raman and Fluorescence diagnostics of biological cells.

  14. The cell biology of Tobacco mosaic virus replication and movement

    Directory of Open Access Journals (Sweden)

    Chengke eLiu

    2013-02-01

    Full Text Available Successful systemic infection of a plant by Tobacco mosaic virus (TMV requires three processes that repeat over time: initial establishment and accumulation in invaded cells, intercellular movement and systemic transport. Accumulation and intercellular movement of TMV necessarily involves intracellular transport by complexes containing virus and host proteins and virus RNA during a dynamic process that can be visualized. Multiple membranes appear to assist TMV accumulation, while membranes, microfilaments and microtubules appear to assist TMV movement. Here we review cell biological studies that describe TMV-membrane, -cytoskeleton and -other host protein interactions which influence virus accumulation and movement in leaves and callus tissue. The importance of understanding the developmental phase of the infection in relationship to the observed virus-membrane or -host protein interaction is emphasized. Utilizing the latest observations of TMV-membrane and -host protein interactions within our evolving understanding of the infection ontogeny, a model for TMV accumulation and intracellular spread in a cell biological context is provided.

  15. Evaluation of radiobiological effects in 3 distinct biological models

    International Nuclear Information System (INIS)

    Lemos, J.; Costa, P.; Cunha, L.; Metello, L.F.; Carvalho, A.P.; Vasconcelos, V.; Genesio, P.; Ponte, F.; Costa, P.S.; Crespo, P.

    2015-01-01

    Full text of publication follows. The present work aims at sharing the process of development of advanced biological models to study radiobiological effects. Recognizing several known limitations and difficulties of the current monolayer cellular models, as well as the increasing difficulties to use advanced biological models, our group has been developing advanced biological alternative models, namely three-dimensional cell cultures and a less explored animal model (the Zebra fish - Danio rerio - which allows the access to inter-generational data, while characterized by a great genetic homology towards the humans). These 3 models (monolayer cellular model, three-dimensional cell cultures and zebra fish) were externally irradiated with 100 mGy, 500 mGy or 1 Gy. The consequences of that irradiation were studied using cellular and molecular tests. Our previous experimental studies with 100 mGy external gamma irradiation of HepG2 monolayer cells showed a slight increase in the proliferation rate 24 h, 48 h and 72 h post irradiation. These results also pointed into the presence of certain bystander effects 72 h post irradiation, constituting the starting point for the need of a more accurate analysis realized with this work. At this stage, we continue focused on the acute biological effects. Obtained results, namely MTT and clonogenic assays for evaluating cellular metabolic activity and proliferation in the in vitro models, as well as proteomics for the evaluation of in vivo effects will be presented, discussed and explained. Several hypotheses will be presented and defended based on the facts previously demonstrated. This work aims at sharing the actual state and the results already available from this medium-term project, building the proof of the added value on applying these advanced models, while demonstrating the strongest and weakest points from all of them (so allowing the comparison between them and to base the subsequent choice for research groups starting

  16. The biology of innate lymphoid cells

    NARCIS (Netherlands)

    Artis, David; Spits, Hergen

    2015-01-01

    The innate immune system is composed of a diverse array of evolutionarily ancient haematopoietic cell types, including dendritic cells, monocytes, macrophages and granulocytes. These cell populations collaborate with each other, with the adaptive immune system and with non-haematopoietic cells to

  17. Reaction of long-lived radicals and vitamin C in γ-irradiated mammalian cells and their model system at 295 K. Tunneling reaction in biological system

    International Nuclear Information System (INIS)

    Matsumoto, Takuro; Kumada, Takayuki; Kodama, Seiji; Watanabe, Masami

    1997-01-01

    When golden hamster embryo (GHE) cells or concentrated albumin solution (0.1 kg dm -3 ), that is a model system of cells, is irradiated with γ-rays at 295 K, organic radicals produced can be observed by ESR. The organic radicals survive at both 295 and 310 K for as long as 20 h. The long-lived radicals in GHE cells and the albumin solution react with vitamin C by the rate constants of 0.007 dm 3 mol -1 s -1 and 0.014 dm 3 mol -1 s -1 , respectively. The long-lived radicals in human cells cause gene mutation, which is suppressed by the addition of vitamin C. The isotope effect on the rate constant (κ) for the reaction of the long-lived radicals and vitamin C has been studied in the albumin solution by use of protonated vitamin C and deuterated vitamin C. The isotope effect (κ H /κ D ) was more than 20 ∼ 50 and was interpreted in terms of tunnelling reaction. (author)

  18. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  19. Systems biology perspectives on minimal and simpler cells.

    Science.gov (United States)

    Xavier, Joana C; Patil, Kiran Raosaheb; Rocha, Isabel

    2014-09-01

    The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  20. Systems Biology Perspectives on Minimal and Simpler Cells

    Science.gov (United States)

    Xavier, Joana C.; Patil, Kiran Raosaheb

    2014-01-01

    SUMMARY The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells. PMID:25184563

  1. From biology to mathematical models and back: teaching modeling to biology students, and biology to math and engineering students.

    Science.gov (United States)

    Chiel, Hillel J; McManus, Jeffrey M; Shaw, Kendrick M

    2010-01-01

    We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a "live" textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology.

  2. From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

    Science.gov (United States)

    McManus, Jeffrey M.; Shaw, Kendrick M.

    2010-01-01

    We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a “live” textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology. PMID:20810957

  3. Cell-free synthetic biology for environmental sensing and remediation.

    Science.gov (United States)

    Karig, David K

    2017-06-01

    The fields of biosensing and bioremediation leverage the phenomenal array of sensing and metabolic capabilities offered by natural microbes. Synthetic biology provides tools for transforming these fields through complex integration of natural and novel biological components to achieve sophisticated sensing, regulation, and metabolic function. However, the majority of synthetic biology efforts are conducted in living cells, and concerns over releasing genetically modified organisms constitute a key barrier to environmental applications. Cell-free protein expression systems offer a path towards leveraging synthetic biology, while preventing the spread of engineered organisms in nature. Recent efforts in the areas of cell-free approaches for sensing, regulation, and metabolic pathway implementation, as well as for preserving and deploying cell-free expression components, embody key steps towards realizing the potential of cell-free systems for environmental sensing and remediation. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  4. Modeling the Biological Diversity of Pig Carcasses

    DEFF Research Database (Denmark)

    Erbou, Søren Gylling Hemmingsen

    This thesis applies methods from medical image analysis for modeling the biological diversity of pig carcasses. The Danish meat industry is very focused on improving product quality and productivity by optimizing the use of the carcasses and increasing productivity in the abattoirs. In order...... equipment is investigated, without the need for a calibration against a less accurate manual dissection. The rest of the contributions regard the construction and use of point distribution models (PDM). PDM’s are able to capture the shape variation of a population of shapes, in this case a 3D surface...

  5. Stem cells: a plant biology perspective

    NARCIS (Netherlands)

    Scheres, B.J.G.

    2005-01-01

    A recent meeting at the Juan March Foundation in Madrid, Spain brought together plant biologists to discuss the characteristics of plant stem cells that are unique and those that are shared by stem cells from the animal kingdom

  6. Biology at a single cell level

    CSIR Research Space (South Africa)

    Mthunzi, P

    2012-10-01

    Full Text Available ://www.regenexx.com/wp-content/uploads/2011/05/IPS-cell-problems.jpg Induced pluripotent stem cells differentiated in culture http://www.youtube.com/watch?v=ECllrIzTKbA&feature=related Transfecting neuroblastomas Neuroblastoma ? Brain cells ? 80 ? 120 billion neurons in human... brain ? Non- renewing cell type ? Neurons difficult to transfect with established protocols ? Susceptible to degenerative disorders: - Parkinson?s disease - Multiple sclerosis - Alzheimer's disease http...

  7. iPS-Cinderella Story in Cell Biology

    Directory of Open Access Journals (Sweden)

    Editorial

    2010-01-01

    Full Text Available As we step through the frontiers of modern Science, we are all witnesses to the Cinderella story repeating itself in the form of the iPS. The process of re-programming adult somatic cells to derive Induced Pluripotent stem cells (iPS with the wand of transcription factors and then differentiating them back to adult somatic cells resembles the transformation of Cinderella from a Cinder girl to princess and back to a Cinder girl after the ball; but the iPS-Cinderella is the most fascinating thing ever in cell biology!From the day iPS first made its headlines when it was first produced by Shinya Yamanaka at Kyoto University in Japan, Stem Cell scientists all over the world are re- doing their experiments so far done using other sources like embryonic and adult Stem cells with the iPS cells exploring their potential to the fullest. A Stem Cell science news page without this magic word of iPS is difficult to imagine these days and Scientists have been successful in growing most of the adult Cell types from iPS cells.iPS cells was the key to solve the problems of Immune rejection and Immunosupression required when using other allogeneic Stem cell types which had baffled scientists previously. But the issues raised by scientists about the use of viruses and Oncogenes in producing iPS cells were made groundless when scientists in February 2008 published the discovery of a technique that could remove oncogenes after the induction of pluripotency and now it is possible to induce pluripotency using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. The word of the day is pIPS which are protein-induced Pluripotent stem cells which are iPS cells that were generated without any genetic alteration of the adult cell. This research by the group of Sheng Ding in La Jolla, California made public in April 2009 showed that the generation of poly-arginine anchors was sufficient to induce

  8. Progenitor cells in the kidney: biology and therapeutic perspectives

    NARCIS (Netherlands)

    Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.

    2004-01-01

    Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of

  9. Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics.

    Science.gov (United States)

    Melton, Douglas A

    2016-01-01

    Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes. © 2016 Elsevier Inc. All rights reserved.

  10. Mathematical modeling in biology: A critical assessment

    Energy Technology Data Exchange (ETDEWEB)

    Buiatti, M. [Florence, Univ. (Italy). Dipt. di Biologia Animale e Genetica

    1998-01-01

    The molecular revolution and the development of biology-derived industry have led in the last fifty years to an unprecedented `lead forward` of life sciences in terms of experimental data. Less success has been achieved in the organisation of such data and in the consequent development of adequate explanatory and predictive theories and models. After a brief historical excursus inborn difficulties of mathematisation of biological objects and processes derived from the complex dynamics of life are discussed along with the logical tools (simplifications, choice of observation points etc.) used to overcome them. `Autistic`, monodisciplinary attitudes towards biological modeling of mathematicians, physicists, biologists aimed in each case at the use of the tools of other disciplines to solve `selfish` problems are also taken into account and a warning against derived dangers (reification of mono disciplinary metaphors, lack of falsification etc.) is given. Finally `top.down` (deductive) and `bottom up` (inductive) heuristic interactive approaches to mathematisation are critically discussed with the help of serie of examples.

  11. Mathematical modeling in biology: A critical assessment

    International Nuclear Information System (INIS)

    Buiatti, M.

    1998-01-01

    The molecular revolution and the development of biology-derived industry have led in the last fifty years to an unprecedented 'lead forward' of life sciences in terms of experimental data. Less success has been achieved in the organisation of such data and in the consequent development of adequate explanatory and predictive theories and models. After a brief historical excursus inborn difficulties of mathematisation of biological objects and processes derived from the complex dynamics of life are discussed along with the logical tools (simplifications, choice of observation points etc.) used to overcome them. 'Autistic', monodisciplinary attitudes towards biological modeling of mathematicians, physicists, biologists aimed in each case at the use of the tools of other disciplines to solve 'selfish' problems are also taken into account and a warning against derived dangers (reification of mono disciplinary metaphors, lack of falsification etc.) is given. Finally 'top.down' (deductive) and 'bottom up' (inductive) heuristic interactive approaches to mathematisation are critically discussed with the help of serie of examples

  12. Biological parameters for lung cancer in mathematical models of carcinogenesis

    International Nuclear Information System (INIS)

    Jacob, P.; Jacob, V.

    2003-01-01

    Applications of the two-step model of carcinogenesis with clonal expansion (TSCE) to lung cancer data are reviewed, including those on atomic bomb survivors from Hiroshima and Nagasaki, British doctors, Colorado Plateau miners, and Chinese tin miners. Different sets of identifiable model parameters are used in the literature. The parameter set which could be determined with the lowest uncertainty consists of the net proliferation rate gamma of intermediate cells, the hazard h 55 at an intermediate age, and the hazard H? at an asymptotically large age. Also, the values of these three parameters obtained in the various studies are more consistent than other identifiable combinations of the biological parameters. Based on representative results for these three parameters, implications for the biological parameters in the TSCE model are derived. (author)

  13. Continuum Modeling of Biological Network Formation

    KAUST Repository

    Albi, Giacomo

    2017-04-10

    We present an overview of recent analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transportation networks. The model describes the pressure field using a Darcy type equation and the dynamics of the conductance network under pressure force effects. Randomness in the material structure is represented by a linear diffusion term and conductance relaxation by an algebraic decay term. We first introduce micro- and mesoscopic models and show how they are connected to the macroscopic PDE system. Then, we provide an overview of analytical results for the PDE model, focusing mainly on the existence of weak and mild solutions and analysis of the steady states. The analytical part is complemented by extensive numerical simulations. We propose a discretization based on finite elements and study the qualitative properties of network structures for various parameter values.

  14. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  15. Unit testing, model validation, and biological simulation.

    Science.gov (United States)

    Sarma, Gopal P; Jacobs, Travis W; Watts, Mark D; Ghayoomie, S Vahid; Larson, Stephen D; Gerkin, Richard C

    2016-01-01

    The growth of the software industry has gone hand in hand with the development of tools and cultural practices for ensuring the reliability of complex pieces of software. These tools and practices are now acknowledged to be essential to the management of modern software. As computational models and methods have become increasingly common in the biological sciences, it is important to examine how these practices can accelerate biological software development and improve research quality. In this article, we give a focused case study of our experience with the practices of unit testing and test-driven development in OpenWorm, an open-science project aimed at modeling Caenorhabditis elegans. We identify and discuss the challenges of incorporating test-driven development into a heterogeneous, data-driven project, as well as the role of model validation tests, a category of tests unique to software which expresses scientific models.

  16. Modelling biological invasions: Individual to population scales at interfaces

    KAUST Repository

    Belmonte-Beitia, J.

    2013-10-01

    Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility. © 2013 Elsevier Ltd.

  17. Modelling biological invasions: Individual to population scales at interfaces

    KAUST Repository

    Belmonte-Beitia, J.; Woolley, T.E.; Scott, J.G.; Maini, P.K.; Gaffney, E.A.

    2013-01-01

    Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility. © 2013 Elsevier Ltd.

  18. Evaluation of the Redesign of an Undergraduate Cell Biology Course

    Science.gov (United States)

    McEwen, Laura April; Harris, dik; Schmid, Richard F.; Vogel, Jackie; Western, Tamara; Harrison, Paul

    2009-01-01

    This article offers a case study of the evaluation of a redesigned and redeveloped laboratory-based cell biology course. The course was a compulsory element of the biology program, but the laboratory had become outdated and was inadequately equipped. With the support of a faculty-based teaching improvement project, the teaching team redesigned the…

  19. Special Issue: International Congress of Cell Biology 2016, Prague

    Czech Academy of Sciences Publication Activity Database

    Stick, R.; Dráber, Pavel

    2017-01-01

    Roč. 254, č. 3 (2017), s. 1141-1142 ISSN 0033-183X R&D Projects: GA ČR GA16-25159S Institutional support: RVO:68378050 Keywords : cellular structures and functions, ,, , * tubulin isotypes * actin * transcription regulation * signaling pathways Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 2.870, year: 2016

  20. Cell Division and Evolution of Biological Tissues

    Science.gov (United States)

    Rivier, Nicolas; Arcenegui-Siemens, Xavier; Schliecker, Gudrun

    A tissue is a geometrical, space-filling, random cellular network; it remains in this steady state while individual cells divide. Cell division (fragmentation) is a local, elementary topological transformation which establishes statistical equilibrium of the structure. Statistical equilibrium is characterized by observable relations (Lewis, Aboav) between cell shapes, sizes and those of their neighbours, obtained through maximum entropy and topological correlation extending to nearest neighbours only, i.e. maximal randomness. For a two-dimensional tissue (epithelium), the distribution of cell shapes and that of mother and daughter cells can be obtained from elementary geometrical and physical arguments, except for an exponential factor favouring division of larger cells, and exponential and combinatorial factors encouraging a most symmetric division. The resulting distributions are very narrow, and stationarity severely restricts the range of an adjustable structural parameter

  1. Modeling biological tissue growth: discrete to continuum representations.

    Science.gov (United States)

    Hywood, Jack D; Hackett-Jones, Emily J; Landman, Kerry A

    2013-09-01

    There is much interest in building deterministic continuum models from discrete agent-based models governed by local stochastic rules where an agent represents a biological cell. In developmental biology, cells are able to move and undergo cell division on and within growing tissues. A growing tissue is itself made up of cells which undergo cell division, thereby providing a significant transport mechanism for other cells within it. We develop a discrete agent-based model where domain agents represent tissue cells. Each agent has the ability to undergo a proliferation event whereby an additional domain agent is incorporated into the lattice. If a probability distribution describes the waiting times between proliferation events for an individual agent, then the total length of the domain is a random variable. The average behavior of these stochastically proliferating agents defining the growing lattice is determined in terms of a Fokker-Planck equation, with an advection and diffusion term. The diffusion term differs from the one obtained Landman and Binder [J. Theor. Biol. 259, 541 (2009)] when the rate of growth of the domain is specified, but the choice of agents is random. This discrepancy is reconciled by determining a discrete-time master equation for this process and an associated asymmetric nonexclusion random walk, together with consideration of synchronous and asynchronous updating schemes. All theoretical results are confirmed with numerical simulations. This study furthers our understanding of the relationship between agent-based rules, their implementation, and their associated partial differential equations. Since tissue growth is a significant cellular transport mechanism during embryonic growth, it is important to use the correct partial differential equation description when combining with other cellular functions.

  2. Glial cell biology in the Great Lakes region.

    Science.gov (United States)

    Feinstein, Douglas L; Skoff, Robert P

    2016-03-31

    We report on the tenth bi-annual Great Lakes Glial meeting, held in Traverse City, Michigan, USA, September 27-29 2015. The GLG meeting is a small conference that focuses on current research in glial cell biology. The array of functions that glial cells (astrocytes, microglia, oligodendrocytes, Schwann cells) play in health and disease is constantly increasing. Despite this diversity, GLG meetings bring together scientists with common interests, leading to a better understanding of these cells. This year's meeting included two keynote speakers who presented talks on the regulation of CNS myelination and the consequences of stress on Schwann cell biology. Twenty-two other talks were presented along with two poster sessions. Sessions covered recent findings in the areas of microglial and astrocyte activation; age-dependent changes to glial cells, Schwann cell development and pathology, and the role of stem cells in glioma and neural regeneration.

  3. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  4. Dendritic cells: biology of the skin

    NARCIS (Netherlands)

    Toebak, M.J.; Gibbs, S.; Bruynzeel, D.P.; Scheper, R.J.; Rustemeyer, T.

    2009-01-01

    Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo

  5. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

    Science.gov (United States)

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com © The Author(s) 2015. Published by Oxford University Press.

  6. Compact Electro-Permeabilization System for Controlled Treatment of Biological Cells and Cell Medium Conductivity Change Measurement

    Directory of Open Access Journals (Sweden)

    Novickij Vitalij

    2014-10-01

    Full Text Available Subjection of biological cells to high intensity pulsed electric field results in the permeabilization of the cell membrane. Measurement of the electrical conductivity change allows an analysis of the dynamics of the process, determination of the permeabilization thresholds, and ion efflux influence. In this work a compact electro-permeabilization system for controlled treatment of biological cells is presented. The system is capable of delivering 5 μs - 5 ms repetitive square wave electric field pulses with amplitude up to 1 kV. Evaluation of the cell medium conductivity change is implemented in the setup, allowing indirect measurement of the ion concentration changes occurring due to the cell membrane permeabilization. The simulation model using SPICE and the experimental data of the proposed system are presented in this work. Experimental data with biological cells is also overviewed

  7. Micro/nano-fabrication technologies for cell biology.

    Science.gov (United States)

    Qian, Tongcheng; Wang, Yingxiao

    2010-10-01

    Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade. Due to the low costs and simple procedures, these techniques have become important and popular for biological studies. In this review, we focus on the studies integrating micro/nano-fabrication work to elucidate the molecular mechanism of signaling transduction in cell biology. We first describe different micro/nano-fabrication technologies, including techniques generating three-dimensional scaffolds for tissue engineering. We then introduce the application of these technologies in manipulating the physical or chemical micro/nano-environment to regulate the cellular behavior and response, such as cell life and death, differentiation, proliferation, and cell migration. Recent advancement in integrating the micro/nano-technologies and live cell imaging are also discussed. Finally, potential schemes in cell biology involving micro/nano-fabrication technologies are proposed to provide perspectives on the future research activities.

  8. Computer-aided design of biological circuits using TinkerCell.

    Science.gov (United States)

    Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

    2010-01-01

    Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. © 2010 Landes Bioscience

  9. Model cell membranes

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Nylander, Tommy; Cardenas Gomez, Marite

    2014-01-01

    The high complexity of biological membranes has motivated the development and application of a wide range of model membrane systems to study biochemical and biophysical aspects of membranes in situ under well defined conditions. The aim is to provide fundamental understanding of processes control...

  10. Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands.

    Science.gov (United States)

    Santosa, Munirah Mohamad; Low, Blaise Su Jun; Pek, Nicole Min Qian; Teo, Adrian Kee Keong

    2015-01-01

    In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic β cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1(+) pancreatic progenitors, much less is known about the transition toward Ngn3(+) pancreatic endocrine progenitors. Essentially, the later steps of pancreatic β cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic β cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic β cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini-review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic β cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments.

  11. A methodology to annotate systems biology markup language models with the synthetic biology open language.

    Science.gov (United States)

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

    Recently, we have begun to witness the potential of synthetic biology, noted here in the form of bacteria and yeast that have been genetically engineered to produce biofuels, manufacture drug precursors, and even invade tumor cells. The success of these projects, however, has often failed in translation and application to new projects, a problem exacerbated by a lack of engineering standards that combine descriptions of the structure and function of DNA. To address this need, this paper describes a methodology to connect the systems biology markup language (SBML) to the synthetic biology open language (SBOL), existing standards that describe biochemical models and DNA components, respectively. Our methodology involves first annotating SBML model elements such as species and reactions with SBOL DNA components. A graph is then constructed from the model, with vertices corresponding to elements within the model and edges corresponding to the cause-and-effect relationships between these elements. Lastly, the graph is traversed to assemble the annotating DNA components into a composite DNA component, which is used to annotate the model itself and can be referenced by other composite models and DNA components. In this way, our methodology can be used to build up a hierarchical library of models annotated with DNA components. Such a library is a useful input to any future genetic technology mapping algorithm that would automate the process of composing DNA components to satisfy a behavioral specification. Our methodology for SBML-to-SBOL annotation is implemented in the latest version of our genetic design automation (GDA) software tool, iBioSim.

  12. A Checklist for Successful Quantitative Live Cell Imaging in Systems Biology

    Science.gov (United States)

    Sung, Myong-Hee

    2013-01-01

    Mathematical modeling of signaling and gene regulatory networks has provided unique insights about systems behaviors for many cell biological problems of medical importance. Quantitative single cell monitoring has a crucial role in advancing systems modeling of molecular networks. However, due to the multidisciplinary techniques that are necessary for adaptation of such systems biology approaches, dissemination to a wide research community has been relatively slow. In this essay, I focus on some technical aspects that are often under-appreciated, yet critical in harnessing live cell imaging methods to achieve single-cell-level understanding and quantitative modeling of molecular networks. The importance of these technical considerations will be elaborated with examples of successes and shortcomings. Future efforts will benefit by avoiding some pitfalls and by utilizing the lessons collectively learned from recent applications of imaging in systems biology. PMID:24709701

  13. ACTIVE AND PARTICIPATORY METHODS IN BIOLOGY: MODELING

    Directory of Open Access Journals (Sweden)

    Brînduşa-Antonela SBÎRCEA

    2011-01-01

    Full Text Available By using active and participatory methods it is hoped that pupils will not only come to a deeper understanding of the issues involved, but also that their motivation will be heightened. Pupil involvement in their learning is essential. Moreover, by using a variety of teaching techniques, we can help students make sense of the world in different ways, increasing the likelihood that they will develop a conceptual understanding. The teacher must be a good facilitator, monitoring and supporting group dynamics. Modeling is an instructional strategy in which the teacher demonstrates a new concept or approach to learning and pupils learn by observing. In the teaching of biology the didactic materials are fundamental tools in the teaching-learning process. Reading about scientific concepts or having a teacher explain them is not enough. Research has shown that modeling can be used across disciplines and in all grade and ability level classrooms. Using this type of instruction, teachers encourage learning.

  14. Documentation of TRU biological transport model (BIOTRAN)

    Energy Technology Data Exchange (ETDEWEB)

    Gallegos, A.F.; Garcia, B.J.; Sutton, C.M.

    1980-01-01

    Inclusive of Appendices, this document describes the purpose, rationale, construction, and operation of a biological transport model (BIOTRAN). This model is used to predict the flow of transuranic elements (TRU) through specified plant and animal environments using biomass as a vector. The appendices are: (A) Flows of moisture, biomass, and TRU; (B) Intermediate variables affecting flows; (C) Mnemonic equivalents (code) for variables; (D) Variable library (code); (E) BIOTRAN code (Fortran); (F) Plants simulated; (G) BIOTRAN code documentation; (H) Operating instructions for BIOTRAN code. The main text is presented with a specific format which uses a minimum of space, yet is adequate for tracking most relationships from their first appearance to their formulation in the code. Because relationships are treated individually in this manner, and rely heavily on Appendix material for understanding, it is advised that the reader familiarize himself with these materials before proceeding with the main text.

  15. Documentation of TRU biological transport model (BIOTRAN)

    International Nuclear Information System (INIS)

    Gallegos, A.F.; Garcia, B.J.; Sutton, C.M.

    1980-01-01

    Inclusive of Appendices, this document describes the purpose, rationale, construction, and operation of a biological transport model (BIOTRAN). This model is used to predict the flow of transuranic elements (TRU) through specified plant and animal environments using biomass as a vector. The appendices are: (A) Flows of moisture, biomass, and TRU; (B) Intermediate variables affecting flows; (C) Mnemonic equivalents (code) for variables; (D) Variable library (code); (E) BIOTRAN code (Fortran); (F) Plants simulated; (G) BIOTRAN code documentation; (H) Operating instructions for BIOTRAN code. The main text is presented with a specific format which uses a minimum of space, yet is adequate for tracking most relationships from their first appearance to their formulation in the code. Because relationships are treated individually in this manner, and rely heavily on Appendix material for understanding, it is advised that the reader familiarize himself with these materials before proceeding with the main text

  16. Echinococcus as a model system: biology and epidemiology.

    Science.gov (United States)

    Thompson, R C A; Jenkins, D J

    2014-10-15

    The introduction of Echinococcus to Australia over 200 years ago and its establishment in sheep rearing areas of the country inflicted a serious medical and economic burden on the country. This resulted in an investment in both basic and applied research aimed at learning more about the biology and life cycle of Echinococcus. This research served to illustrate the uniqueness of the parasite in terms of developmental biology and ecology, and the value of Echinococcus as a model system in a broad range of research, from fundamental biology to theoretical control systems. These studies formed the foundation for an international, diverse and ongoing research effort on the hydatid organisms encompassing stem cell biology, gene regulation, strain variation, wildlife diseases and models of transmission dynamics. We describe the development, nature and diversity of this research, and how it was initiated in Australia but subsequently has stimulated much international and collaborative research on Echinococcus. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  17. At the biological modeling and simulation frontier.

    Science.gov (United States)

    Hunt, C Anthony; Ropella, Glen E P; Lam, Tai Ning; Tang, Jonathan; Kim, Sean H J; Engelberg, Jesse A; Sheikh-Bahaei, Shahab

    2009-11-01

    We provide a rationale for and describe examples of synthetic modeling and simulation (M&S) of biological systems. We explain how synthetic methods are distinct from familiar inductive methods. Synthetic M&S is a means to better understand the mechanisms that generate normal and disease-related phenomena observed in research, and how compounds of interest interact with them to alter phenomena. An objective is to build better, working hypotheses of plausible mechanisms. A synthetic model is an extant hypothesis: execution produces an observable mechanism and phenomena. Mobile objects representing compounds carry information enabling components to distinguish between them and react accordingly when different compounds are studied simultaneously. We argue that the familiar inductive approaches contribute to the general inefficiencies being experienced by pharmaceutical R&D, and that use of synthetic approaches accelerates and improves R&D decision-making and thus the drug development process. A reason is that synthetic models encourage and facilitate abductive scientific reasoning, a primary means of knowledge creation and creative cognition. When synthetic models are executed, we observe different aspects of knowledge in action from different perspectives. These models can be tuned to reflect differences in experimental conditions and individuals, making translational research more concrete while moving us closer to personalized medicine.

  18. A Color-Opponency Based Biological Model for Color Constancy

    Directory of Open Access Journals (Sweden)

    Yongjie Li

    2011-05-01

    Full Text Available Color constancy is the ability of the human visual system to adaptively correct color-biased scenes under different illuminants. Most of the existing color constancy models are nonphysiologically plausible. Among the limited biological models, the great majority is Retinex and its variations, and only two or three models directly simulate the feature of color-opponency, but only of the very earliest stages of visual pathway, i.e., the single-opponent mechanisms involved at the levels of retinal ganglion cells and lateral geniculate nucleus (LGN neurons. Considering the extensive physiological evidences supporting that both the single-opponent cells in retina and LGN and the double-opponent neurons in primary visual cortex (V1 are the building blocks for color constancy, in this study we construct a color-opponency based color constancy model by simulating the opponent fashions of both the single-opponent and double-opponent cells in a forward manner. As for the spatial structure of the receptive fields (RF, both the classical RF (CRF center and the nonclassical RF (nCRF surround are taken into account for all the cells. The proposed model was tested on several typical image databases commonly used for performance evaluation of color constancy methods, and exciting results were achieved.

  19. Bioinformatics approaches to single-cell analysis in developmental biology.

    Science.gov (United States)

    Yalcin, Dicle; Hakguder, Zeynep M; Otu, Hasan H

    2016-03-01

    Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology. © The Author 2015. Published by Oxford University Press on behalf of the European

  20. Editorial Introduction [to Female Germ Cells: Biology and Genetic Risk

    Science.gov (United States)

    This is an editorial introduction to the special issue of utation Research, titled, emale Germ Cells: Biology and Genetic isk, which is an attempt to present a collection of papers that emphasize the distinct properties of female germ cells and their characteristic response to mu...

  1. Single-cell sequencing in stem cell biology.

    Science.gov (United States)

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  2. Cell Culture in Microgravity: Opening the Door to Space Cell Biology

    Science.gov (United States)

    Pellis, Neal R.; Dawson, David L. (Technical Monitor)

    1999-01-01

    Adaptational response of human cell populations to microgravity is investigated using simulation, short-term Shuttle experiments, and long-term microgravity. Simulation consists of a clinostatically-rotated cell culture system. The system is a horizontally-rotated cylinder completely filled with culture medium. Low speed rotation results in continuous-fall of the cells through the fluid medium. In this setting, cells: 1) aggregate, 2) propagate in three dimensions, 3) synthesize matrix, 4) differentiate, and 5) form sinusoids that facilitate mass transfer. Space cell culture is conducted in flight bioreactors and in static incubators. Cells grown in microgravity are: bovine cartilage, promyelocytic leukemia, kidney proximal tubule cells, adrenal medulla, breast and colon cancer, and endothelium. Cells were cultured in space to test specific hypotheses. Cartilage cells were used to determine structural differences in cartilage grown in space compared to ground-based bioreactors. Results from a 130-day experiment on Mir revealed that cartilage grown in space was substantially more compressible due to insufficient glycosaminoglycan in the matrix. Interestingly, earth-grown cartilage conformed better to the dimensions of the scaffolding material, while the Mir specimens were spherical. The other cell populations are currently being analyzed for cell surface properties, gene expression, and differentiation. Results suggest that some cells spontaneously differentiate in microgravity. Additionally, vast changes in gene expression may occur in response to microgravity. In conclusion, the transition to microgravity may constitute a physical perturbation in cells resulting in unique gene expressions, the consequences of which may be useful in tissue engineering, disease modeling, and space cell biology.

  3. Micro and nano-platforms for biological cell analysis

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Castillo, Jaime; Moresco, Jacob Lange

    2011-01-01

    In this paper some technological platforms developed for biological cell analysis will be presented and compared to existing systems. In brief, we present a novel micro cell culture chamber based on diffusion feeding of cells, into which cells can be introduced and extracted after culturing using...... from the cells, while passive modifications involve the presence of a peptide nanotube based scaffold for the cell culturing that mimics the in vivo environment. Two applications involving fluorescent in situ hybridization (FISH) analysis and cancer cell sorting are presented, as examples of further...... analysis that can be done after cell culturing. A platform able to automate the entire process from cell culturing to cell analysis by means of simple plug and play of various self-contained, individually fabricated modules is finally described....

  4. Muscle Satellite Cells: Exploring the Basic Biology to Rule Them.

    Science.gov (United States)

    Almeida, Camila F; Fernandes, Stephanie A; Ribeiro Junior, Antonio F; Keith Okamoto, Oswaldo; Vainzof, Mariz

    2016-01-01

    Adult skeletal muscle is a postmitotic tissue with an enormous capacity to regenerate upon injury. This is accomplished by resident stem cells, named satellite cells, which were identified more than 50 years ago. Since their discovery, many researchers have been concentrating efforts to answer questions about their origin and role in muscle development, the way they contribute to muscle regeneration, and their potential to cell-based therapies. Satellite cells are maintained in a quiescent state and upon requirement are activated, proliferating, and fusing with other cells to form or repair myofibers. In addition, they are able to self-renew and replenish the stem pool. Every phase of satellite cell activity is highly regulated and orchestrated by many molecules and signaling pathways; the elucidation of players and mechanisms involved in satellite cell biology is of extreme importance, being the first step to expose the crucial points that could be modulated to extract the optimal response from these cells in therapeutic strategies. Here, we review the basic aspects about satellite cells biology and briefly discuss recent findings about therapeutic attempts, trying to raise questions about how basic biology could provide a solid scaffold to more successful use of these cells in clinics.

  5. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...... are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent...... studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells...

  6. Synthetic biology of cyanobacterial cell factories

    NARCIS (Netherlands)

    Angermayr, S.A.

    2014-01-01

    In the field of microbial biotechnology rational design approaches are employed for the generation of microbial cells with desired functions, such as the ability to produce precursor molecules for biofuels or bioplastics. In essence, that is the introduction of a (new) biosynthetic pathway into a

  7. Cell biology of homologous recombination in yeast

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine Valerie; Rothstein, Rodney; Lisby, Michael

    2011-01-01

    Homologous recombination is an important pathway for error-free repair of DNA lesions, such as single- and double-strand breaks, and for rescue of collapsed replication forks. Here, we describe protocols for live cell imaging of single-lesion recombination events in the yeast Saccharomyces...

  8. Wnt Signaling in Cancer Stem Cell Biology

    NARCIS (Netherlands)

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells

  9. High-dimensional single-cell cancer biology.

    Science.gov (United States)

    Irish, Jonathan M; Doxie, Deon B

    2014-01-01

    Cancer cells are distinguished from each other and from healthy cells by features that drive clonal evolution and therapy resistance. New advances in high-dimensional flow cytometry make it possible to systematically measure mechanisms of tumor initiation, progression, and therapy resistance on millions of cells from human tumors. Here we describe flow cytometry techniques that enable a "single-cell " view of cancer. High-dimensional techniques like mass cytometry enable multiplexed single-cell analysis of cell identity, clinical biomarkers, signaling network phospho-proteins, transcription factors, and functional readouts of proliferation, cell cycle status, and apoptosis. This capability pairs well with a signaling profiles approach that dissects mechanism by systematically perturbing and measuring many nodes in a signaling network. Single-cell approaches enable study of cellular heterogeneity of primary tissues and turn cell subsets into experimental controls or opportunities for new discovery. Rare populations of stem cells or therapy-resistant cancer cells can be identified and compared to other types of cells within the same sample. In the long term, these techniques will enable tracking of minimal residual disease (MRD) and disease progression. By better understanding biological systems that control development and cell-cell interactions in healthy and diseased contexts, we can learn to program cells to become therapeutic agents or target malignant signaling events to specifically kill cancer cells. Single-cell approaches that provide deep insight into cell signaling and fate decisions will be critical to optimizing the next generation of cancer treatments combining targeted approaches and immunotherapy.

  10. Biological Influence of Deuterium on Procariotic and Eukaryotic Cells

    OpenAIRE

    Oleg Mosin; Ignat Ignatov

    2014-01-01

    Biologic influence of deuterium (D) on cells of various taxonomic groups of prokaryotic and eukaryotic microorganisms realizing methylotrophic, chemoheterotrophic, photo-organotrophic, and photosynthetic ways of assimilation of carbon substrates are investigated at growth on media with heavy water (D2О). The method of step by step adaptation technique of cells to D2О was developed, consisting in plating of cells on 2 % agarose nutrient media containing increasing gradient of concentration of ...

  11. Virtual Reconstruction and Three-Dimensional Printing of Blood Cells as a Tool in Cell Biology Education.

    Science.gov (United States)

    Augusto, Ingrid; Monteiro, Douglas; Girard-Dias, Wendell; Dos Santos, Thaisa Oliveira; Rosa Belmonte, Simone Letícia; Pinto de Oliveira, Jairo; Mauad, Helder; da Silva Pacheco, Marcos; Lenz, Dominik; Stefanon Bittencourt, Athelson; Valentim Nogueira, Breno; Lopes Dos Santos, Jorge Roberto; Miranda, Kildare; Guimarães, Marco Cesar Cunegundes

    2016-01-01

    The cell biology discipline constitutes a highly dynamic field whose concepts take a long time to be incorporated into the educational system, especially in developing countries. Amongst the main obstacles to the introduction of new cell biology concepts to students is their general lack of identification with most teaching methods. The introduction of elaborated figures, movies and animations to textbooks has given a tremendous contribution to the learning process and the search for novel teaching methods has been a central goal in cell biology education. Some specialized tools, however, are usually only available in advanced research centers or in institutions that are traditionally involved with the development of novel teaching/learning processes, and are far from becoming reality in the majority of life sciences schools. When combined with the known declining interest in science among young people, a critical scenario may result. This is especially important in the field of electron microscopy and associated techniques, methods that have greatly contributed to the current knowledge on the structure and function of different cell biology models but are rarely made accessible to most students. In this work, we propose a strategy to increase the engagement of students into the world of cell and structural biology by combining 3D electron microscopy techniques and 3D prototyping technology (3D printing) to generate 3D physical models that accurately and realistically reproduce a close-to-the native structure of the cell and serve as a tool for students and teachers outside the main centers. We introduce three strategies for 3D imaging, modeling and prototyping of cells and propose the establishment of a virtual platform where different digital models can be deposited by EM groups and subsequently downloaded and printed in different schools, universities, research centers and museums, thereby modernizing teaching of cell biology and increasing the accessibility to

  12. SulfoSYS (Sulfolobus Systems Biology): towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

    NARCIS (Netherlands)

    Albers, S.V.; Birkeland, N.K.; Driessen, A.J.M.; Gertig, S.; Haferkamp, P.; Klenk, H.P.; Kouril, T.; Manica, A.; Pham, T.K.; Ruoff, P.; Schleper, C.; Schomburg, D.; Sharkey, K.; Siebers, B.; Sierocinski, P.; Steur, R.; Oost, van der J.; Westerhoff, H.V.; Wieloch, P.; Wright, P.C.; Zaparty, M.

    2009-01-01

    SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. In Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

  13. Sulfosys (Sulfolobus Systems Biology): towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation.

    NARCIS (Netherlands)

    Albers, S.V.; Birkeland, N.K.; Driessen, A.J.; Gertig, S.; Haferkamp, P.; Klenk, H.P.; Kouril, T.; Manica, A.; Pham, T.K.; Ruoff, P.; Schleper, C.; Schomburg, D.; Sharkey, K.J.; Siebers, B.; Sierocinski, P.; Steuer, R.; van der Oost, J.; Westerhoff, H.V.; Wieloch, P.; Wright, P.C.; Zaparty, M.

    2009-01-01

    SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. In Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

  14. SulfoSYS (Sulfolobus Systems Biology) : towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

    NARCIS (Netherlands)

    Albers, Sonja-Verena; Birkeland, Nils-Kare; Driessen, Arnold J. M.; Gertig, Susanne; Haferkamp, Patrick; Klenk, Hans-Peter; Kouril, Theresa; Manica, Andrea; Pham, Trong K.; Ruoff, Peter; Schleper, Christa; Schomburg, Dietmar; Sharkey, Kieran J.; Siebers, Bettina; Sierocinski, Pawel; Steuer, Ralf; van der Oost, John; Westerhoff, Hans V.; Wieloch, Patricia; Wright, Phillip C.; Zaparty, Melanie; Birkeland, Nils-Kåre

    SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. in Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

  15. Molecular biological features of male germ cell differentiation

    Science.gov (United States)

    HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

    2007-01-01

    Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

  16. Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.

    Science.gov (United States)

    Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal

    2015-01-01

    During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.

  17. Introducing Mammalian Cell Culture and Cell Viability Techniques in the Undergraduate Biology Laboratory.

    Science.gov (United States)

    Bowey-Dellinger, Kristen; Dixon, Luke; Ackerman, Kristin; Vigueira, Cynthia; Suh, Yewseok K; Lyda, Todd; Sapp, Kelli; Grider, Michael; Crater, Dinene; Russell, Travis; Elias, Michael; Coffield, V McNeil; Segarra, Verónica A

    2017-01-01

    Undergraduate students learn about mammalian cell culture applications in introductory biology courses. However, laboratory modules are rarely designed to provide hands-on experience with mammalian cells or teach cell culture techniques, such as trypsinization and cell counting. Students are more likely to learn about cell culture using bacteria or yeast, as they are typically easier to grow, culture, and manipulate given the equipment, tools, and environment of most undergraduate biology laboratories. In contrast, the utilization of mammalian cells requires a dedicated biological safety cabinet and rigorous antiseptic techniques. For this reason, we have devised a laboratory module and method herein that familiarizes students with common cell culture procedures, without the use of a sterile hood or large cell culture facility. Students design and perform a time-efficient inquiry-based cell viability experiment using HeLa cells and tools that are readily available in an undergraduate biology laboratory. Students will become familiar with common techniques such as trypsinizing cells, cell counting with a hemocytometer, performing serial dilutions, and determining cell viability using trypan blue dye. Additionally, students will work with graphing software to analyze their data and think critically about the mechanism of death on a cellular level. Two different adaptations of this inquiry-based lab are presented-one for non-biology majors and one for biology majors. Overall, these laboratories aim to expose students to mammalian cell culture and basic techniques and help them to conceptualize their application in scientific research.

  18. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

    Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

  19. Using synthetic biology to make cells tomorrow's test tubes.

    Science.gov (United States)

    Garcia, Hernan G; Brewster, Robert C; Phillips, Rob

    2016-04-18

    The main tenet of physical biology is that biological phenomena can be subject to the same quantitative and predictive understanding that physics has afforded in the context of inanimate matter. However, the inherent complexity of many of these biological processes often leads to the derivation of complex theoretical descriptions containing a plethora of unknown parameters. Such complex descriptions pose a conceptual challenge to the establishment of a solid basis for predictive biology. In this article, we present various exciting examples of how synthetic biology can be used to simplify biological systems and distill these phenomena down to their essential features as a means to enable their theoretical description. Here, synthetic biology goes beyond previous efforts to engineer nature and becomes a tool to bend nature to understand it. We discuss various recent and classic experiments featuring applications of this synthetic approach to the elucidation of problems ranging from bacteriophage infection, to transcriptional regulation in bacteria and in developing embryos, to evolution. In all of these examples, synthetic biology provides the opportunity to turn cells into the equivalent of a test tube, where biological phenomena can be reconstituted and our theoretical understanding put to test with the same ease that these same phenomena can be studied in the in vitro setting.

  20. Basic science through engineering? Synthetic modeling and the idea of biology-inspired engineering.

    Science.gov (United States)

    Knuuttila, Tarja; Loettgers, Andrea

    2013-06-01

    Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more "biology inspired." Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Primary culture of glial cells from mouse sympathetic cervical ganglion: a valuable tool for studying glial cell biology.

    Science.gov (United States)

    de Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2010-12-15

    Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Differentiation of RPE cells from integration-free iPS cells and their cell biological characterization.

    Science.gov (United States)

    Hazim, Roni A; Karumbayaram, Saravanan; Jiang, Mei; Dimashkie, Anupama; Lopes, Vanda S; Li, Douran; Burgess, Barry L; Vijayaraj, Preethi; Alva-Ornelas, Jackelyn A; Zack, Jerome A; Kohn, Donald B; Gomperts, Brigitte N; Pyle, April D; Lowry, William E; Williams, David S

    2017-10-02

    Dysfunction of the retinal pigment epithelium (RPE) is implicated in numerous forms of retinal degeneration. The readily accessible environment of the eye makes it particularly suitable for the transplantation of RPE cells, which can now be derived from autologous induced pluripotent stem cells (iPSCs), to treat retinal degeneration. For RPE transplantation to become feasible in the clinic, patient-specific somatic cells should be reprogrammed to iPSCs without the introduction of reprogramming genes into the genome of the host cell, and then subsequently differentiated into RPE cells that are well characterized for safety and functionality prior to transplantation. We have reprogrammed human dermal fibroblasts to iPSCs using nonintegrating RNA, and differentiated the iPSCs toward an RPE fate (iPSC-RPE), under Good Manufacturing Practice (GMP)-compatible conditions. Using highly sensitive assays for cell polarity, structure, organelle trafficking, and function, we found that iPSC-RPE cells in culture exhibited key characteristics of native RPE. Importantly, we demonstrate for the first time with any stem cell-derived RPE cell that live cells are able to support dynamic organelle transport. This highly sensitive test is critical for RPE cells intended for transplantation, since defects in intracellular motility have been shown to promote RPE pathogenesis akin to that found in macular degeneration. To test their capabilities for in-vivo transplantation, we injected the iPSC-RPE cells into the subretinal space of a mouse model of retinal degeneration, and demonstrated that the transplanted cells are capable of rescuing lost RPE function. This report documents the successful generation, under GMP-compatible conditions, of human iPSC-RPE cells that possess specific characteristics of healthy RPE. The report adds to a growing literature on the utility of human iPSC-RPE cells for cell culture investigations on pathogenicity and for therapeutic transplantation, by

  3. Systems-biology dissection of eukaryotic cell growth

    Directory of Open Access Journals (Sweden)

    Andrews Justen

    2010-05-01

    Full Text Available Abstract A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth. See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68

  4. Heavy ion induced DNA transfer in biological cells

    International Nuclear Information System (INIS)

    Vilaithong, T.; Yu, L.D.; Apavatjrut, P.; Phanchaisri, B.; Sangyuenyongpipat, S.; Anuntalabhochai, S.; Brown, I.G.

    2004-01-01

    Low-energy ion beam bombardment of biological materials for genetic modification purposes has experienced rapid growth in the last decade, particularly for the direct DNA transfer into living organisms including both plants and bacteria. Attempts have been made to understand the mechanisms involved in ion-bombardment-induced direct gene transfer into biological cells. Here we summarize the present status of the application of low-energy ions for genetic modification of living sample materials

  5. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  6. Genome annotation in a community college cell biology lab.

    Science.gov (United States)

    Beagley, C Timothy

    2013-01-01

    The Biology Department at Salt Lake Community College has used the IMG-ACT toolbox to introduce a genome mapping and annotation exercise into the laboratory portion of its Cell Biology course. This project provides students with an authentic inquiry-based learning experience while introducing them to computational biology and contemporary learning skills. Additionally, the project strengthens student understanding of the scientific method and contributes to student learning gains in curricular objectives centered around basic molecular biology, specifically, the Central Dogma. Importantly, inclusion of this project in the laboratory course provides students with a positive learning environment and allows for the use of cooperative learning strategies to increase overall student success. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  7. On the limitations of standard statistical modeling in biological systems: a full Bayesian approach for biology.

    Science.gov (United States)

    Gomez-Ramirez, Jaime; Sanz, Ricardo

    2013-09-01

    One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Canine osteosarcoma cell lines contain stem-like cancer cells: biological and pharmacological characterization.

    Science.gov (United States)

    Gatti, Monica; Wurth, Roberto; Vito, Guendalina; Pattarozzi, Alessandra; Campanella, Chiara; Thellung, Stefano; Maniscalco, Lorella; De Maria, Raffaella; Villa, Valentina; Corsaro, Alessandro; Nizzari, Mario; Bajetto, Adriana; Ratto, Alessandra; Ferrari, Angelo; Barbieri, Federica; Florio, Tullio

    2016-05-01

    Cancer stem cells (CSCs) represent a small subpopulation of cells responsible for tumor formation and progression, drug resistance, tumor recurrence and metastasization. CSCs have been identified in many human tumors including osteosarcoma (OSA). CSC distinctive properties are the expression of stem cell markers, sustained growth, self-renewal and tumorigenicity. Here we report the isolation of stem-like cells from two canine OSA cultures, characterized by self-renewal, evaluated by sphere formation ability, differential marker expression, and in vitro proliferation when cultured in a medium containing EGF and bFGF. Current therapies for OSA increased survival time, but prognosis remains poor, due to the development of drug resistance and metastases. Chemotherapy shrinks the tumor mass but CSCs remain unaffected, leading to tumor recurrence. Metformin, a drug for type 2 diabetes, has been shown to possess antitumor properties affecting CSC survival in different human and animal cancers. Here we show that metformin has a significant antiproliferative effect on canine OSA stem-like cells, validating this in vitro model for further pre-clinical drug evaluations. In conclusion, our results demonstrate the feasibility of obtaining CSC-enriched cultures from primary canine OSA cells as a promising model for biological and pharmacological studies of canine and human OSAs.

  9. Model checking biological systems described using ambient calculus

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Priami, Corrado; Qualia, Paola

    2005-01-01

    Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005.......Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005....

  10. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  11. Cell biological study on ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Ohta, Shigeru; Katsura, Tadahiko; Shimada, Morimi; Shima, Akihiro; Chishiro, Hiroko; Kasahara, Yoshitaka.

    1985-01-01

    Diagnosis of ataxia-telangiectasia (AT) has largely been dependent on the clinical findings such as cerebellar ataxia, telangiectasia, and immunological deficiency. However, diagnosis of AT by these ordinary criteria is sometimes not sufficient because of the lack of immunological abnormalities. We examined three cases of AT by ordinary clinical criteria and also by X-ray sensitivity of cultured skin fibroblasts. Case 1, a 9-year-old boy, revealed typical clinical features of AT. However, he had no abnormality in serum IgA or IgE. Case 2, a 10-year-old boy, showed decreased serum IgA level. Case 3, a 19-year-old female, had typical clinical features of AT with normal serum IgA, and developed papillary adenocarcinoma of thyroid which was surgically removed. Fibroblast strains derived from these three cases of AT and from the parents of Case 3 were examined with regard to X-ray sensitivity. Three fibroblast strains derived from AT patients (AT homozygotes) showed remarkable hypersensitivity to X-ray. Fibroblast strains derived from the parents (AT heterozygotes) of Case 3, however, showed normal X-ray sensitivity. Recently, AT fibroblasts have been known to show hypersensitivity also to some mutagen like neocarzinostazin as reported by Shiloh et al. Fibroblasts from Case 3 revealed hypersensitivity to neocarzinostazin. However, the sensitivity of the strains from AT heterozygotes (the parents of Case 3) showed no apparent difference from that of control cells. The assay system for mutagen is quite unstable and proper conditioning of the seeding cell number is important for the carrier detection. However, the diagnosis of AT homozygotes was definitely established by X-ray irradiation to cultured fibroblasts from patients. (author)

  12. Biological Evaluation of Single Cell Protein

    International Nuclear Information System (INIS)

    Hasan, I.A.; Mohamed, N.E.; El-Sayed, E.A.; Younis, N.A.

    2011-01-01

    In this study, the nutritional value of single cell protein (SCP) was evaluated as a non conventional protein source produced by fermenting fungal local strains of Trichoderma longibrachiatum, Aspergillus niger, Aspergillus terreus and Penicillium funiculosum with alkali treated sugar cane bagasse. Amino acid analysis revealed that the produced SCP contains essential and non essential amino acids. Male mice were fed on normal (basal) diet which contains 18% conventional protein and served as control group. In the second (T1) and the third (T2) group, the animals were fed on a diet in which 15% and 30% of conventional protein source were replaced by SCP, respectively. At intervals of 15, 30, 45 and 60 days, mice were sacrificed and the blood samples were collected for the biochemical evaluation. The daily averages of body weight were significantly higher with group T2 than group T1. Where as, the kidney weights in groups (T1) and (T2) were significantly increased as compared with control. A non significant difference between the tested groups in the enzyme activities of AST, ALT and GSH content of liver tissue were recorded. While, cholesterol and triglycerides contents showed a significant decrease in both (T1) and (T2) groups as compared with control. The recorded values of the serum hormone (T4), ALP activities, albumin and A/G ratio did not changed by the previous treatments. Serum levels of total protein, urea, creatinine and uric acid were higher for groups (T1) and (T2) than the control group. In conclusion, partial substitution of soy bean protein in mice diet with single cell protein (15%) improved the mice growth without any adverse effects on some of the physiological functions tested

  13. Advancing Stem Cell Biology toward Stem Cell Therapeutics

    OpenAIRE

    Scadden, David; Srivastava, Alok

    2012-01-01

    Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of articles outlining the current status, opportunities, and challenges surrounding the clinical translation of stem cell therapeutics for specific medical conditions.

  14. Investigating the role of retinal Müller cells with approaches in genetics and cell biology.

    Science.gov (United States)

    Fu, Suhua; Zhu, Meili; Ash, John D; Wang, Yunchang; Le, Yun-Zheng

    2014-01-01

    Müller cells are major macroglia and play many essential roles as a supporting cell in the retina. As Müller cells only constitute a small portion of retinal cells, investigating the role of Müller glia in retinal biology and diseases is particularly challenging. To overcome this problem, we first generated a Cre/lox-based conditional gene targeting system that permits the genetic manipulation and functional dissection of gene of interests in Müller cells. To investigate diabetes-induced alteration of Müller cells, we recently adopted methods to analyze Müller cells survival/death in vitro and in vivo. We also used normal and genetically altered primary cell cultures to reveal the mechanistic insights for Müller cells in biological and disease processes. In this article, we will discuss the applications and limitations of these methodologies, which may be useful for research in retinal Müller cell biology and pathophysiology.

  15. Cell biology, biophysics, and mechanobiology: From the basics to Clinics.

    Science.gov (United States)

    Zeng, Y

    2017-04-29

    Cell biology, biomechanics and biophysics are the key subjects that guide our understanding in diverse areas of tissue growth, development, remodeling and homeostasis. Novel discoveries such as molecular mechanism, and mechanobiological mechanism in cell biology, biomechanics and biophysics play essential roles in our understanding of the pathogenesis of various human diseases, as well as in designing the treatment of these diseases. In addition, studies in these areas will also facilitate early diagnostics of human diseases, such as cardiovascular diseases and cancer. In this special issue, we collected 10 original research articles and 1 review...

  16. A decade of molecular cell biology: achievements and challenges.

    Science.gov (United States)

    Akhtar, Asifa; Fuchs, Elaine; Mitchison, Tim; Shaw, Reuben J; St Johnston, Daniel; Strasser, Andreas; Taylor, Susan; Walczak, Claire; Zerial, Marino

    2011-09-23

    Nature Reviews Molecular Cell Biology celebrated its 10-year anniversary during this past year with a series of specially commissioned articles. To complement this, here we have asked researchers from across the field for their insights into how molecular cell biology research has evolved during this past decade, the key concepts that have emerged and the most promising interfaces that have developed. Their comments highlight the broad impact that particular advances have had, some of the basic understanding that we still require, and the collaborative approaches that will be essential for driving the field forward.

  17. Modeling of nonlinear biological phenomena modeled by S-systems.

    Science.gov (United States)

    Mansouri, Majdi M; Nounou, Hazem N; Nounou, Mohamed N; Datta, Aniruddha A

    2014-03-01

    A central challenge in computational modeling of biological systems is the determination of the model parameters. In such cases, estimating these variables or parameters from other easily obtained measurements can be extremely useful. For example, time-series dynamic genomic data can be used to develop models representing dynamic genetic regulatory networks, which can be used to design intervention strategies to cure major diseases and to better understand the behavior of biological systems. Unfortunately, biological measurements are usually highly infected by errors that hide the important characteristics in the data. Therefore, these noisy measurements need to be filtered to enhance their usefulness in practice. This paper addresses the problem of state and parameter estimation of biological phenomena modeled by S-systems using Bayesian approaches, where the nonlinear observed system is assumed to progress according to a probabilistic state space model. The performances of various conventional and state-of-the-art state estimation techniques are compared. These techniques include the extended Kalman filter (EKF), unscented Kalman filter (UKF), particle filter (PF), and the developed variational Bayesian filter (VBF). Specifically, two comparative studies are performed. In the first comparative study, the state variables (the enzyme CadA, the model cadBA, the cadaverine Cadav and the lysine Lys for a model of the Cad System in Escherichia coli (CSEC)) are estimated from noisy measurements of these variables, and the various estimation techniques are compared by computing the estimation root mean square error (RMSE) with respect to the noise-free data. In the second comparative study, the state variables as well as the model parameters are simultaneously estimated. In this case, in addition to comparing the performances of the various state estimation techniques, the effect of the number of estimated model parameters on the accuracy and convergence of these

  18. Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

    Science.gov (United States)

    Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

    2015-08-21

    In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

  19. Biology and clinical application of CAR T cells for B cell malignancies.

    Science.gov (United States)

    Davila, Marco L; Sadelain, Michel

    2016-07-01

    Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

  20. "Known Unknowns": Current Questions in Muscle Satellite Cell Biology.

    Science.gov (United States)

    Cornelison, Ddw

    2018-01-01

    Our understanding of satellite cells, now known to be the obligate stem cells of skeletal muscle, has increased dramatically in recent years due to the introduction of new molecular, genetic, and technical resources. In addition to their role in acute repair of damaged muscle, satellite cells are of interest in the fields of aging, exercise, neuromuscular disease, and stem cell therapy, and all of these applications have driven a dramatic increase in our understanding of the activity and potential of satellite cells. However, many fundamental questions of satellite cell biology remain to be answered, including their emergence as a specific lineage, the degree and significance of heterogeneity within the satellite cell population, the roles of their interactions with other resident and infiltrating cell types during homeostasis and regeneration, and the relative roles of intrinsic vs extrinsic factors that may contribute to satellite cell dysfunction in the context of aging or disease. This review will address the current state of these open questions in satellite cell biology. © 2018 Elsevier Inc. All rights reserved.

  1. The Emerging Role of PEDF in Stem Cell Biology

    Science.gov (United States)

    Elahy, Mina; Baindur-Hudson, Swati; Dass, Crispin R.

    2012-01-01

    Encoded by a single gene, PEDF is a 50 kDa glycoprotein that is highly conserved and is widely expressed among many tissues. Most secreted PEDF deposits within the extracellular matrix, with cell-type-specific functions. While traditionally PEDF is known as a strong antiangiogenic factor, more recently, as this paper highlights, PEDF has been linked with stem cell biology, and there is now accumulating evidence demonstrating the effects of PEDF in a variety of stem cells, mainly in supporting stem cell survival and maintaining multipotency. PMID:22675247

  2. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

    Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

  3. Estimating confidence intervals in predicted responses for oscillatory biological models.

    Science.gov (United States)

    St John, Peter C; Doyle, Francis J

    2013-07-29

    The dynamics of gene regulation play a crucial role in a cellular control: allowing the cell to express the right proteins to meet changing needs. Some needs, such as correctly anticipating the day-night cycle, require complicated oscillatory features. In the analysis of gene regulatory networks, mathematical models are frequently used to understand how a network's structure enables it to respond appropriately to external inputs. These models typically consist of a set of ordinary differential equations, describing a network of biochemical reactions, and unknown kinetic parameters, chosen such that the model best captures experimental data. However, since a model's parameter values are uncertain, and since dynamic responses to inputs are highly parameter-dependent, it is difficult to assess the confidence associated with these in silico predictions. In particular, models with complex dynamics - such as oscillations - must be fit with computationally expensive global optimization routines, and cannot take advantage of existing measures of identifiability. Despite their difficulty to model mathematically, limit cycle oscillations play a key role in many biological processes, including cell cycling, metabolism, neuron firing, and circadian rhythms. In this study, we employ an efficient parameter estimation technique to enable a bootstrap uncertainty analysis for limit cycle models. Since the primary role of systems biology models is the insight they provide on responses to rate perturbations, we extend our uncertainty analysis to include first order sensitivity coefficients. Using a literature model of circadian rhythms, we show how predictive precision is degraded with decreasing sample points and increasing relative error. Additionally, we show how this method can be used for model discrimination by comparing the output identifiability of two candidate model structures to published literature data. Our method permits modellers of oscillatory systems to confidently

  4. Three-dimensional printing of human skeletal muscle cells: An interdisciplinary approach for studying biological systems.

    Science.gov (United States)

    Bagley, James R; Galpin, Andrew J

    2015-01-01

    Interdisciplinary exploration is vital to education in the 21st century. This manuscript outlines an innovative laboratory-based teaching method that combines elements of biochemistry/molecular biology, kinesiology/health science, computer science, and manufacturing engineering to give students the ability to better conceptualize complex biological systems. Here, we utilize technology available at most universities to print three-dimensional (3D) scale models of actual human muscle cells (myofibers) out of bioplastic materials. The same methodological approach could be applied to nearly any cell type or molecular structure. This advancement is significant because historically, two-dimensional (2D) myocellular images have proven insufficient for detailed analysis of organelle organization and morphology. 3D imaging fills this void by providing accurate and quantifiable myofiber structural data. Manipulating tangible 3D models combats 2D limitation and gives students new perspectives and alternative learning experiences that may assist their understanding. This approach also exposes learners to 1) human muscle cell extraction and isolation, 2) targeted fluorescence labeling, 3) confocal microscopy, 4) image processing (via open-source software), and 5) 3D printing bioplastic scale-models (×500 larger than the actual cells). Creating these physical models may further student's interest in the invisible world of molecular and cellular biology. Furthermore, this interdisciplinary laboratory project gives instructors of all biological disciplines a new teaching tool to foster integrative thinking. © 2015 The International Union of Biochemistry and Molecular Biology.

  5. Natural Killer T Cells: An Ecological Evolutionary Developmental Biology Perspective

    Science.gov (United States)

    Kumar, Amrendra; Suryadevara, Naveenchandra; Hill, Timothy M.; Bezbradica, Jelena S.; Van Kaer, Luc; Joyce, Sebastian

    2017-01-01

    Type I natural killer T (NKT) cells are innate-like T lymphocytes that recognize glycolipid antigens presented by the MHC class I-like protein CD1d. Agonistic activation of NKT cells leads to rapid pro-inflammatory and immune modulatory cytokine and chemokine responses. This property of NKT cells, in conjunction with their interactions with antigen-presenting cells, controls downstream innate and adaptive immune responses against cancers and infectious diseases, as well as in several inflammatory disorders. NKT cell properties are acquired during development in the thymus and by interactions with the host microbial consortium in the gut, the nature of which can be influenced by NKT cells. This latter property, together with the role of the host microbiota in cancer therapy, necessitates a new perspective. Hence, this review provides an initial approach to understanding NKT cells from an ecological evolutionary developmental biology (eco-evo-devo) perspective. PMID:29312339

  6. Natural Killer T Cells: An Ecological Evolutionary Developmental Biology Perspective.

    Science.gov (United States)

    Kumar, Amrendra; Suryadevara, Naveenchandra; Hill, Timothy M; Bezbradica, Jelena S; Van Kaer, Luc; Joyce, Sebastian

    2017-01-01

    Type I natural killer T (NKT) cells are innate-like T lymphocytes that recognize glycolipid antigens presented by the MHC class I-like protein CD1d. Agonistic activation of NKT cells leads to rapid pro-inflammatory and immune modulatory cytokine and chemokine responses. This property of NKT cells, in conjunction with their interactions with antigen-presenting cells, controls downstream innate and adaptive immune responses against cancers and infectious diseases, as well as in several inflammatory disorders. NKT cell properties are acquired during development in the thymus and by interactions with the host microbial consortium in the gut, the nature of which can be influenced by NKT cells. This latter property, together with the role of the host microbiota in cancer therapy, necessitates a new perspective. Hence, this review provides an initial approach to understanding NKT cells from an ecological evolutionary developmental biology (eco-evo-devo) perspective.

  7. Natural Killer T Cells: An Ecological Evolutionary Developmental Biology Perspective

    Directory of Open Access Journals (Sweden)

    Amrendra Kumar

    2017-12-01

    Full Text Available Type I natural killer T (NKT cells are innate-like T lymphocytes that recognize glycolipid antigens presented by the MHC class I-like protein CD1d. Agonistic activation of NKT cells leads to rapid pro-inflammatory and immune modulatory cytokine and chemokine responses. This property of NKT cells, in conjunction with their interactions with antigen-presenting cells, controls downstream innate and adaptive immune responses against cancers and infectious diseases, as well as in several inflammatory disorders. NKT cell properties are acquired during development in the thymus and by interactions with the host microbial consortium in the gut, the nature of which can be influenced by NKT cells. This latter property, together with the role of the host microbiota in cancer therapy, necessitates a new perspective. Hence, this review provides an initial approach to understanding NKT cells from an ecological evolutionary developmental biology (eco-evo-devo perspective.

  8. Modelling collective cell migration of neural crest.

    Science.gov (United States)

    Szabó, András; Mayor, Roberto

    2016-10-01

    Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Cell biology of the Koji mold Aspergillus oryzae.

    Science.gov (United States)

    Kitamoto, Katsuhiko

    2015-01-01

    Koji mold, Aspergillus oryzae, has been used for the production of sake, miso, and soy sauce for more than one thousand years in Japan. Due to the importance, A. oryzae has been designated as the national micro-organism of Japan (Koku-kin). A. oryzae has been intensively studied in the past century, with most investigations focusing on breeding techniques and developing methods for Koji making for sake brewing. However, the understanding of fundamental biology of A. oryzae remains relatively limited compared with the yeast Saccharomyces cerevisiae. Therefore, we have focused on studying the cell biology including live cell imaging of organelles, protein vesicular trafficking, autophagy, and Woronin body functions using the available genomic information. In this review, I describe essential findings of cell biology of A. oryzae obtained in our study for a quarter of century. Understanding of the basic biology will be critical for not its biotechnological application, but also for an understanding of the fundamental biology of other filamentous fungi.

  10. INTERVAL OBSERVER FOR A BIOLOGICAL REACTOR MODEL

    Directory of Open Access Journals (Sweden)

    T. A. Kharkovskaia

    2014-05-01

    Full Text Available The method of an interval observer design for nonlinear systems with parametric uncertainties is considered. The interval observer synthesis problem for systems with varying parameters consists in the following. If there is the uncertainty restraint for the state values of the system, limiting the initial conditions of the system and the set of admissible values for the vector of unknown parameters and inputs, the interval existence condition for the estimations of the system state variables, containing the actual state at a given time, needs to be held valid over the whole considered time segment as well. Conditions of the interval observers design for the considered class of systems are shown. They are: limitation of the input and state, the existence of a majorizing function defining the uncertainty vector for the system, Lipschitz continuity or finiteness of this function, the existence of an observer gain with the suitable Lyapunov matrix. The main condition for design of such a device is cooperativity of the interval estimation error dynamics. An individual observer gain matrix selection problem is considered. In order to ensure the property of cooperativity for interval estimation error dynamics, a static transformation of coordinates is proposed. The proposed algorithm is demonstrated by computer modeling of the biological reactor. Possible applications of these interval estimation systems are the spheres of robust control, where the presence of various types of uncertainties in the system dynamics is assumed, biotechnology and environmental systems and processes, mechatronics and robotics, etc.

  11. Toward University Modeling Instruction—Biology: Adapting Curricular Frameworks from Physics to Biology

    Science.gov (United States)

    Manthey, Seth; Brewe, Eric

    2013-01-01

    University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence. PMID:23737628

  12. Toward university modeling instruction--biology: adapting curricular frameworks from physics to biology.

    Science.gov (United States)

    Manthey, Seth; Brewe, Eric

    2013-06-01

    University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence.

  13. Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

    Science.gov (United States)

    Kurihara, Hidetake; Sakai, Tatsuo

    2017-03-01

    The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.

  14. Physical models of biological information and adaptation.

    Science.gov (United States)

    Stuart, C I

    1985-04-07

    The bio-informational equivalence asserts that biological processes reduce to processes of information transfer. In this paper, that equivalence is treated as a metaphor with deeply anthropomorphic content of a sort that resists constitutive-analytical definition, including formulation within mathematical theories of information. It is argued that continuance of the metaphor, as a quasi-theoretical perspective in biology, must entail a methodological dislocation between biological and physical science. It is proposed that a general class of functions, drawn from classical physics, can serve to eliminate the anthropomorphism. Further considerations indicate that the concept of biological adaptation is central to the general applicability of the informational idea in biology; a non-anthropomorphic treatment of adaptive phenomena is suggested in terms of variational principles.

  15. Teaching Cell and Molecular Biology for Gender Equity

    Science.gov (United States)

    Sible, Jill C.; Wilhelm, Dayna E.; Lederman, Muriel

    2006-01-01

    Science, technology, engineering, and math (STEM) fields, including cell biology, are characterized by the "leaky pipeline" syndrome in which, over time, women leave the discipline. The pipeline itself and the pond into which it empties may not be neutral. Explicating invisible norms, attitudes, and practices by integrating social…

  16. The time is right: proteome biology of stem cells.

    NARCIS (Netherlands)

    Whetton, A.D.; Williamson, A.J.K.; Krijgsveld, J.; Lee, B.H.; Lemischka, I.; Oh, S.; Pera, M.; Mummery, C.L.; Heck, A.J.R.

    2008-01-01

    In stem cell biology, there is a growing need for advanced technologies that may help to unravel the molecular mechanisms of self-renewal and differentiation. Proteomics, the comprehensive analysis of proteins, is such an emerging technique. To facilitate interactions between specialists in

  17. Human mesenchymal stromal cells : biological characterization and clinical application

    NARCIS (Netherlands)

    Bernardo, Maria Ester

    2010-01-01

    This thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has

  18. Oscillation and stability of delay models in biology

    CERN Document Server

    Agarwal, Ravi P; Saker, Samir H

    2014-01-01

    Environmental variation plays an important role in many biological and ecological dynamical systems. This monograph focuses on the study of oscillation and the stability of delay models occurring in biology. The book presents recent research results on the qualitative behavior of mathematical models under different physical and environmental conditions, covering dynamics including the distribution and consumption of food. Researchers in the fields of mathematical modeling, mathematical biology, and population dynamics will be particularly interested in this material.

  19. Bovine mammary stem cells: Cell biology meets production agriculture

    Science.gov (United States)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  20. Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yuhao Jiao

    2016-10-01

    Full Text Available Group 1 innate lymphoid cells (ILC comprise the natural killer (NK cells and ILC1 which reside within peripheral tissues. Several different ILC1 subsets have recently been characterised, however no unique markers to define these subsets have been identified. Whether ILC1 and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs, that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILC and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumour immunosurveillance. Here, we review the diversity in the Group 1 ILC subsets with regards to their transcriptional regulation, localization, mobility and receptor expression and highlight the challenges in unraveling the individual functions of these different populations of cells.

  1. Computerised modelling for developmental biology : an exploration with case studies

    NARCIS (Netherlands)

    Bertens, Laura M.F.

    2012-01-01

    Many studies in developmental biology rely on the construction and analysis of models. This research presents a broad view of modelling approaches for developmental biology, with a focus on computational methods. An overview of modelling techniques is given, followed by several case studies. Using

  2. Modeling the Shapes of Cells

    Science.gov (United States)

    Garimella, Umadevi I.; Robertson, Belinda M.

    2015-01-01

    A solid understanding of the structure and function of cells can help establish the foundation for learning advanced concepts in the biological sciences. The concept of the cell is introduced in middle school life science courses and is continued at the undergraduate level in college (NRC 2012; Reece et al. 2014). Cells are introduced to students…

  3. Morphogenesis and pattern formation in biological systems experiments and models

    CERN Document Server

    Noji, Sumihare; Ueno, Naoto; Maini, Philip

    2003-01-01

    A central goal of current biology is to decode the mechanisms that underlie the processes of morphogenesis and pattern formation. Concerned with the analysis of those phenomena, this book covers a broad range of research fields, including developmental biology, molecular biology, plant morphogenesis, ecology, epidemiology, medicine, paleontology, evolutionary biology, mathematical biology, and computational biology. In Morphogenesis and Pattern Formation in Biological Systems: Experiments and Models, experimental and theoretical aspects of biology are integrated for the construction and investigation of models of complex processes. This collection of articles on the latest advances by leading researchers not only brings together work from a wide spectrum of disciplines, but also provides a stepping-stone to the creation of new areas of discovery.

  4. Hydraulic fracturing in cells and tissues: fracking meets cell biology.

    Science.gov (United States)

    Arroyo, Marino; Trepat, Xavier

    2017-02-01

    The animal body is largely made of water. A small fraction of body water is freely flowing in blood and lymph, but most of it is trapped in hydrogels such as the extracellular matrix (ECM), the cytoskeleton, and chromatin. Besides providing a medium for biological molecules to diffuse, water trapped in hydrogels plays a fundamental mechanical role. This role is well captured by the theory of poroelasticity, which explains how any deformation applied to a hydrogel causes pressure gradients and water flows, much like compressing a sponge squeezes water out of it. Here we review recent evidence that poroelastic pressures and flows can fracture essential biological barriers such as the nuclear envelope, the cellular cortex, and epithelial layers. This type of fracture is known in engineering literature as hydraulic fracturing or 'fracking'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. In silico biology of bone modelling and remodelling: adaptation.

    Science.gov (United States)

    Gerhard, Friederike A; Webster, Duncan J; van Lenthe, G Harry; Müller, Ralph

    2009-05-28

    Modelling and remodelling are the processes by which bone adapts its shape and internal structure to external influences. However, the cellular mechanisms triggering osteoclastic resorption and osteoblastic formation are still unknown. In order to investigate current biological theories, in silico models can be applied. In the past, most of these models were based on the continuum assumption, but some questions related to bone adaptation can be addressed better by models incorporating the trabecular microstructure. In this paper, existing simulation models are reviewed and one of the microstructural models is extended to test the hypothesis that bone adaptation can be simulated without particular knowledge of the local strain distribution in the bone. Validation using an experimental murine loading model showed that this is possible. Furthermore, the experimental model revealed that bone formation cannot be attributed only to an increase in trabecular thickness but also to structural reorganization including the growth of new trabeculae. How these new trabeculae arise is still an unresolved issue and might be better addressed by incorporating other levels of hierarchy, especially the cellular level. The cellular level sheds light on the activity and interplay between the different cell types, leading to the effective change in the whole bone. For this reason, hierarchical multi-scale simulations might help in the future to better understand the biomathematical laws behind bone adaptation.

  6. Ovary and fimbrial stem cells: biology, niche and cancer origins.

    Science.gov (United States)

    Ng, Annie; Barker, Nick

    2015-10-01

    The mammalian ovary is covered by a single-layered epithelium that undergoes rupture and remodelling following each ovulation. Although resident stem cells are presumed to be crucial for this cyclic regeneration, their identity and mode of action have been elusive. Surrogate stemness assays and in vivo fate-mapping studies using recently discovered stem cell markers have identified stem cell pools in the ovary and fimbria that ensure epithelial homeostasis. Recent findings provide insights into intrinsic mechanisms and local extrinsic cues that govern the function of ovarian and fimbrial stem cells. These discoveries have advanced our understanding of stem cell biology in the ovary and fimbria, and lay the foundations for evaluating the contribution of resident stem cells to the initiation and progression of human epithelial ovarian cancer.

  7. Influence of cell printing on biological characters of chondrocytes.

    Science.gov (United States)

    Qu, Miao; Gao, Xiaoyan; Hou, Yikang; Shen, Congcong; Xu, Yourong; Zhu, Ming; Wang, Hengjian; Xu, Haisong; Chai, Gang; Zhang, Yan

    2015-01-01

    To establish a two-dimensional biological printing technique of chondrocytes and compare the difference of related biological characters between printed chondrocytes and unprinted cells so as to control the cell transfer process and keep cell viability after printing. Primary chondrocytes were obtained from human mature and fetal cartilage tissues and then were regularly sub-cultured to harvest cells at passage 2 (P2), which were adjusted to the single cell suspension at a density of 1×10(6)/mL. The experiment was divided into 2 groups: experimental group P2 chondrocytes were transferred by rapid prototype biological printer (driving voltage value 50 V, interval in x-axis 300 μm, interval in y-axis 1500 μm). Afterwards Live/Dead viability Kit and flow cytometry were respectively adopted to detect cell viability; CCK-8 Kit was adopted to detect cell proliferation viability; immunocytochemistry, immunofluorescence and RT-PCR was employed to identify related markers of chondrocytes; control group steps were the same as the printing group except that cell suspension received no printing. Fluorescence microscopy and flow cytometry analyses showed that there was no significant difference between experimental group and control group in terms of cell viability. After 7-day in vitro culture, control group exhibited higher O.D values than experimental group from 2nd day to 7th day but there was no distinct difference between these two groups (P>0.05). Inverted microscope observation demonstrated that the morphology of these two groups had no significant difference either. Similarly, Immunocytochemistry, immunofluorescence and RT-PCR assays also showed that there was no significant difference in the protein and gene expression of type II collagen and aggrecan between these two groups (P>0.05). Conclusion Cell printing has no distinctly negative effect on cell vitality, proliferation and phenotype of chondrocytes. Biological printing technique may provide a novel approach

  8. Tumor necrosis factor (TNF) biology and cell death.

    Science.gov (United States)

    Bertazza, Loris; Mocellin, Simone

    2008-01-01

    Tumor necrosis factor (TNF) was the first cytokine to be used in humans for cancer therapy. However, its role in the treatment of cancer patients is debated. Most uncertainties in this field stem from the knowledge that the pathways directly activated or indirectly affected upon TNF engagement with its receptors can ultimately lead to very different outcomes in terms of cell survival. In this article, we summarize the fundamental molecular biology aspects of this cytokine. Such a basis is a prerequisite to critically approach the sometimes conflicting preclinical and clinical findings regarding the relationship between TNF, tumor biology and anticancer therapy. Although the last decade has witnessed remarkable advances in this field, we still do not know in detail how cells choose between life and death after TNF stimulation. Understanding this mechanism will not only shed new light on the physiological significance of TNF-driven programmed cell death but also help investigators maximize the anticancer potential of this cytokine.

  9. Plasma cell leukemia: update on biology and therapy.

    Science.gov (United States)

    Mina, Roberto; D'Agostino, Mattia; Cerrato, Chiara; Gay, Francesca; Palumbo, Antonio

    2017-07-01

    Plasma cell leukemia (PCL) is a rare, but very aggressive, plasma cell dyscrasia, representing a distinct clinicopathological entity as compared to multiple myeloma (MM), with peculiar biological and clinical features. A hundred times rarer than MM, the disease course is characterized by short remissions and poor survival. PCL is defined by an increased percentage (>20%) and absolute number (>2 × 10 9 /l) of plasma cells in the peripheral blood. PCL is defined as 'primary' when peripheral plasmacytosis is detected at diagnosis, 'secondary' when leukemization occurs in a patient with preexisting MM. Novel agents have revolutionized the outcomes of MM patients and have been introduced also for the treatment of PCL. Here, we provide an update on biology and treatment options for PCL.

  10. Tomography studies of biological cells on polymer scaffolds

    International Nuclear Information System (INIS)

    Thurner, P; Mueller, B; Sennhauser, U; Hubbell, J; Mueller, R

    2004-01-01

    Advances in cell biology and tissue engineering rely heavily on performing 2D cell culture experiments. Analysis of these is conventionally done with 2D imaging techniques such as light (LM) or electron microscopy (SEM), since they are readily available. Cells, however, might act significantly differently when cultured in 2D or 3D environments. In order to analyse cells in a 3D arrangement, new imaging techniques are necessary not only in order to visualize the periphery of the cell culture in reflection mode but also to perform qualitative and quantitative investigations of the inner parts. Synchrotron radiation micro-computed tomography (SRμCT) using hard x-rays was shown to be a promising tool that can be used for 3D cell culture visualization. SRμCT allows not only visualization of cell cultures in their native 3D environment but also use of the volumetric nature of this imaging procedure to evaluate the cells quantitatively. In our approach, cells were seeded on polymer yarns, stained and measured with SRμCT in absorption and in differential absorption contrast mode. A new segmentation procedure was developed and the measured volumetric data were quantitatively assessed. Quantification parameters included total cell volume, total yarn volume, cell volume density, which is the ratio of cell to yarn volume, and the radial cell mass distribution. The applied variation of the staining parameter of gold enhancement incubation time was shown to have significant influence on the cell volume density. Differential absorption contrast mode was found to provide similar but no additional information on the investigated sample. Using novel approaches of hierarchical volumetric imaging allows closure of the gap between imaging of whole organs and single cells and might be expanded to even higher resolutions, offering investigation of the cell machinery in closer detail

  11. Revision history aware repositories of computational models of biological systems.

    Science.gov (United States)

    Miller, Andrew K; Yu, Tommy; Britten, Randall; Cooling, Mike T; Lawson, James; Cowan, Dougal; Garny, Alan; Halstead, Matt D B; Hunter, Peter J; Nickerson, David P; Nunns, Geo; Wimalaratne, Sarala M; Nielsen, Poul M F

    2011-01-14

    Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs) for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. We have extended the Physiome Model Repository software to be fully revision history aware

  12. Revision history aware repositories of computational models of biological systems

    Directory of Open Access Journals (Sweden)

    Nickerson David P

    2011-01-01

    Full Text Available Abstract Background Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. Results We have extended the Physiome Model

  13. Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

    Science.gov (United States)

    Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

    2010-11-01

    Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

  14. Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    De Domenico, Manlio

    2018-03-01

    Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

  15. Cystitis: From Urothelial Cell Biology to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Gilho Lee

    2014-01-01

    Full Text Available Cystitis is a urinary bladder disease with many causes and symptoms. The severity of cystitis ranges from mild lower abdominal discomfort to life-threatening haemorrhagic cystitis. The course of disease is often chronic or recurrent. Although cystitis represents huge economical and medical burden throughout the world and in many cases treatments are ineffective, the mechanisms of its origin and development as well as measures for effective treatment are still poorly understood. However, many studies have demonstrated that urothelial dysfunction plays a crucial role. In the present review we first discuss fundamental issues of urothelial cell biology, which is the core for comprehension of cystitis. Then we focus on many forms of cystitis, its current treatments, and advances in its research. Additionally we review haemorrhagic cystitis with one of the leading causative agents being chemotherapeutic drug cyclophosphamide and summarise its management strategies. At the end we describe an excellent and widely used animal model of cyclophosphamide induced cystitis, which gives researches the opportunity to get a better insight into the mechanisms involved and possibility to develop new therapy approaches.

  16. OFFl Models: Novel Schema for Dynamical Modeling of Biological Systems.

    Science.gov (United States)

    Ogbunugafor, C Brandon; Robinson, Sean P

    2016-01-01

    Flow diagrams are a common tool used to help build and interpret models of dynamical systems, often in biological contexts such as consumer-resource models and similar compartmental models. Typically, their usage is intuitive and informal. Here, we present a formalized version of flow diagrams as a kind of weighted directed graph which follow a strict grammar, which translate into a system of ordinary differential equations (ODEs) by a single unambiguous rule, and which have an equivalent representation as a relational database. (We abbreviate this schema of "ODEs and formalized flow diagrams" as OFFL.) Drawing a diagram within this strict grammar encourages a mental discipline on the part of the modeler in which all dynamical processes of a system are thought of as interactions between dynamical species that draw parcels from one or more source species and deposit them into target species according to a set of transformation rules. From these rules, the net rate of change for each species can be derived. The modeling schema can therefore be understood as both an epistemic and practical heuristic for modeling, serving both as an organizational framework for the model building process and as a mechanism for deriving ODEs. All steps of the schema beyond the initial scientific (intuitive, creative) abstraction of natural observations into model variables are algorithmic and easily carried out by a computer, thus enabling the future development of a dedicated software implementation. Such tools would empower the modeler to consider significantly more complex models than practical limitations might have otherwise proscribed, since the modeling framework itself manages that complexity on the modeler's behalf. In this report, we describe the chief motivations for OFFL, carefully outline its implementation, and utilize a range of classic examples from ecology and epidemiology to showcase its features.

  17. OFFl Models: Novel Schema for Dynamical Modeling of Biological Systems.

    Directory of Open Access Journals (Sweden)

    C Brandon Ogbunugafor

    Full Text Available Flow diagrams are a common tool used to help build and interpret models of dynamical systems, often in biological contexts such as consumer-resource models and similar compartmental models. Typically, their usage is intuitive and informal. Here, we present a formalized version of flow diagrams as a kind of weighted directed graph which follow a strict grammar, which translate into a system of ordinary differential equations (ODEs by a single unambiguous rule, and which have an equivalent representation as a relational database. (We abbreviate this schema of "ODEs and formalized flow diagrams" as OFFL. Drawing a diagram within this strict grammar encourages a mental discipline on the part of the modeler in which all dynamical processes of a system are thought of as interactions between dynamical species that draw parcels from one or more source species and deposit them into target species according to a set of transformation rules. From these rules, the net rate of change for each species can be derived. The modeling schema can therefore be understood as both an epistemic and practical heuristic for modeling, serving both as an organizational framework for the model building process and as a mechanism for deriving ODEs. All steps of the schema beyond the initial scientific (intuitive, creative abstraction of natural observations into model variables are algorithmic and easily carried out by a computer, thus enabling the future development of a dedicated software implementation. Such tools would empower the modeler to consider significantly more complex models than practical limitations might have otherwise proscribed, since the modeling framework itself manages that complexity on the modeler's behalf. In this report, we describe the chief motivations for OFFL, carefully outline its implementation, and utilize a range of classic examples from ecology and epidemiology to showcase its features.

  18. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    Science.gov (United States)

    Randolph, Matthew E.; Pavlath, Grace K.

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

  19. Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

    Science.gov (United States)

    Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

    2017-01-24

    Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

  20. At the cutting edge: applications and perspectives of laser nanosurgery in cell biology.

    Science.gov (United States)

    Ronchi, Paolo; Terjung, Stefan; Pepperkok, Rainer

    2012-04-01

    Laser-mediated nanosurgery has become popular in the last decade because of the previously unexplored possibility of ablating biological material inside living cells with sub-micrometer precision. A number of publications have shown the potential applications of this technique, ranging from the dissection of sub-cellular structures to surgical ablations of whole cells or tissues in model systems such as Drosophila melanogaster or Danio rerio . In parallel, the recent development of micropatterning techniques has given cell biologists the possibility to shape cells and reproducibly organize the intracellular space. The integration of these two techniques has only recently started yet their combination has proven to be very interesting. The aim of this review is to present recent applications of laser nanosurgery in cell biology and to discuss the possible developments of this approach, particularly in combination with micropattern-mediated endomembrane organization.

  1. Cellular automaton modeling of biological pattern formation characterization, examples, and analysis

    CERN Document Server

    Deutsch, Andreas

    2017-01-01

    This text explores the use of cellular automata in modeling pattern formation in biological systems. It describes several mathematical modeling approaches utilizing cellular automata that can be used to study the dynamics of interacting cell systems both in simulation and in practice. New in this edition are chapters covering cell migration, tissue development, and cancer dynamics, as well as updated references and new research topic suggestions that reflect the rapid development of the field. The book begins with an introduction to pattern-forming principles in biology and the various mathematical modeling techniques that can be used to analyze them. Cellular automaton models are then discussed in detail for different types of cellular processes and interactions, including random movement, cell migration, adhesive cell interaction, alignment and cellular swarming, growth processes, pigment cell pattern formation, tissue development, tumor growth and invasion, and Turing-type patterns and excitable media. In ...

  2. Skeletal muscle stem cells from animals I. Basic cell biology

    Science.gov (United States)

    Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

  3. Preservice Biology Teachers' Conceptions about the Tentative Nature of Theories and Models in Biology

    Science.gov (United States)

    Reinisch, Bianca; Krüger, Dirk

    2018-01-01

    In research on the nature of science, there is a need to investigate the role and status of different scientific knowledge forms. Theories and models are two of the most important knowledge forms within biology and are the focus of this study. During interviews, preservice biology teachers (N = 10) were asked about their understanding of theories…

  4. Biochemical Space: A Framework for Systemic Annotation of Biological Models

    Czech Academy of Sciences Publication Activity Database

    Klement, M.; Děd, T.; Šafránek, D.; Červený, Jan; Müller, Stefan; Steuer, Ralf

    2014-01-01

    Roč. 306, JUL (2014), s. 31-44 ISSN 1571-0661 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : biological models * model annotation * systems biology * cyanobacteria Subject RIV: EH - Ecology, Behaviour

  5. Review of "Stochastic Modelling for Systems Biology" by Darren Wilkinson

    Directory of Open Access Journals (Sweden)

    Bullinger Eric

    2006-12-01

    Full Text Available Abstract "Stochastic Modelling for Systems Biology" by Darren Wilkinson introduces the peculiarities of stochastic modelling in biology. This book is particularly suited to as a textbook or for self-study, and for readers with a theoretical background.

  6. Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module.

    Science.gov (United States)

    McIlrath, Victoria; Trye, Alice; Aguanno, Ann

    2015-06-18

    Undergraduate biology students are required to learn, understand and apply a variety of cellular and molecular biology concepts and techniques in preparation for biomedical, graduate and professional programs or careers in science. To address this, a simple laboratory module was devised to teach the concepts of cell division, cellular communication and cancer through the application of animal cell culture techniques. Here the mouse mammary tumor (MMT) cell line is used to model for breast cancer. Students learn to grow and characterize these animal cells in culture and test the effects of traditional and non-traditional chemotherapy agents on cell proliferation. Specifically, students determine the optimal cell concentration for plating and growing cells, learn how to prepare and dilute drug solutions, identify the best dosage and treatment time course of the antiproliferative agents, and ascertain the rate of cell death in response to various treatments. The module employs both a standard cell counting technique using a hemocytometer and a novel cell counting method using microscopy software. The experimental procedure lends to open-ended inquiry as students can modify critical steps of the protocol, including testing homeopathic agents and over-the-counter drugs. In short, this lab module requires students to use the scientific process to apply their knowledge of the cell cycle, cellular signaling pathways, cancer and modes of treatment, all while developing an array of laboratory skills including cell culture and analysis of experimental data not routinely taught in the undergraduate classroom.

  7. Emerging concepts and future challenges in innate lymphoid cell biology

    Science.gov (United States)

    Artis, David

    2016-01-01

    Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053

  8. Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms

    Directory of Open Access Journals (Sweden)

    Christley Scott

    2010-08-01

    Full Text Available Abstract Background Simulation of sophisticated biological models requires considerable computational power. These models typically integrate together numerous biological phenomena such as spatially-explicit heterogeneous cells, cell-cell interactions, cell-environment interactions and intracellular gene networks. The recent advent of programming for graphical processing units (GPU opens up the possibility of developing more integrative, detailed and predictive biological models while at the same time decreasing the computational cost to simulate those models. Results We construct a 3D model of epidermal development and provide a set of GPU algorithms that executes significantly faster than sequential central processing unit (CPU code. We provide a parallel implementation of the subcellular element method for individual cells residing in a lattice-free spatial environment. Each cell in our epidermal model includes an internal gene network, which integrates cellular interaction of Notch signaling together with environmental interaction of basement membrane adhesion, to specify cellular state and behaviors such as growth and division. We take a pedagogical approach to describing how modeling methods are efficiently implemented on the GPU including memory layout of data structures and functional decomposition. We discuss various programmatic issues and provide a set of design guidelines for GPU programming that are instructive to avoid common pitfalls as well as to extract performance from the GPU architecture. Conclusions We demonstrate that GPU algorithms represent a significant technological advance for the simulation of complex biological models. We further demonstrate with our epidermal model that the integration of multiple complex modeling methods for heterogeneous multicellular biological processes is both feasible and computationally tractable using this new technology. We hope that the provided algorithms and source code will be a

  9. A model of engineering materials inspired by biological tissues

    Directory of Open Access Journals (Sweden)

    Holeček M.

    2009-12-01

    Full Text Available The perfect ability of living tissues to control and adapt their mechanical properties to varying external conditions may be an inspiration for designing engineering materials. An interesting example is the smooth muscle tissue since this "material" is able to change its global mechanical properties considerably by a subtle mechanism within individual muscle cells. Multi-scale continuum models may be useful in designing essentially simpler engineering materials having similar properties. As an illustration we present the model of an incompressible material whose microscopic structure is formed by flexible, soft but incompressible balls connected mutually by linear springs. This simple model, however, shows a nontrivial nonlinear behavior caused by the incompressibility of balls and is very sensitive on some microscopic parameters. It may elucidate the way by which "small" changes in biopolymer networks within individual muscular cells may control the stiffness of the biological tissue, which outlines a way of designing similar engineering materials. The 'balls and springs' material presents also prestress-induced stiffening and allows elucidating a contribution of extracellular fluids into the tissue’s viscous properties.

  10. Computational local stiffness analysis of biological cell: High aspect ratio single wall carbon nanotube tip

    Energy Technology Data Exchange (ETDEWEB)

    TermehYousefi, Amin, E-mail: at.tyousefi@gmail.com [Department of Human Intelligence Systems, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology (Kyutech) (Japan); Bagheri, Samira; Shahnazar, Sheida [Nanotechnology & Catalysis Research Centre (NANOCAT), IPS Building, University Malaya, 50603 Kuala Lumpur (Malaysia); Rahman, Md. Habibur [Department of Computer Science and Engineering, University of Asia Pacific, Green Road, Dhaka-1215 (Bangladesh); Kadri, Nahrizul Adib [Department of Biomedical Engineering, Faculty of Engineering, University Malaya, 50603 Kuala Lumpur (Malaysia)

    2016-02-01

    Carbon nanotubes (CNTs) are potentially ideal tips for atomic force microscopy (AFM) due to the robust mechanical properties, nanoscale diameter and also their ability to be functionalized by chemical and biological components at the tip ends. This contribution develops the idea of using CNTs as an AFM tip in computational analysis of the biological cells. The proposed software was ABAQUS 6.13 CAE/CEL provided by Dassault Systems, which is a powerful finite element (FE) tool to perform the numerical analysis and visualize the interactions between proposed tip and membrane of the cell. Finite element analysis employed for each section and displacement of the nodes located in the contact area was monitored by using an output database (ODB). Mooney–Rivlin hyperelastic model of the cell allows the simulation to obtain a new method for estimating the stiffness and spring constant of the cell. Stress and strain curve indicates the yield stress point which defines as a vertical stress and plan stress. Spring constant of the cell and the local stiffness was measured as well as the applied force of CNT-AFM tip on the contact area of the cell. This reliable integration of CNT-AFM tip process provides a new class of high performance nanoprobes for single biological cell analysis. - Graphical abstract: This contribution develops the idea of using CNTs as an AFM tip in computational analysis of the biological cells. The proposed software was ABAQUS 6.13 CAE/CEL provided by Dassault Systems. Finite element analysis employed for each section and displacement of the nodes located in the contact area was monitored by using an output database (ODB). Mooney–Rivlin hyperelastic model of the cell allows the simulation to obtain a new method for estimating the stiffness and spring constant of the cell. Stress and strain curve indicates the yield stress point which defines as a vertical stress and plan stress. Spring constant of the cell and the local stiffness was measured as well

  11. Biological modelling of fuzzy target volumes in 3D radiotherapy

    International Nuclear Information System (INIS)

    Levegruen, S.; Kampen, M. van; Waschek, T.; Engenhart, R.; Schlegel, W.

    1995-01-01

    increase in NTCP is then calculated for a homogeneous dose distribution extending the boundaries of the volume considered towards the maximal PTV. Results: The behavior of the model and its dependence on the input parameters was investigated for the case of a brain tumor. Going from the minimal PTV towards the maximal PTV, the TCP increases show a sigmoidal shape. The increase in NTCP depends for each patient on the relative position of the organs at risk with respect to the region of uncertainty. We use the model as input into a computer assisted expert system based on Fuzzy Logic. Output of the Fuzzy system is the target volume which, for each individual patient, leads to the best compromise between high tumor control probability on one side and a low risk of complications on the other side. With this system the extent of the target volume towards noncritical structures is large, whereas the boundaries near an organ at risk within the region of uncertainty are strongly influenced by the partial volume of that organ at risk irradiated. Conclusion: At present biological models, in particular of TCP, suffer from a lack of data for the biological input parameters, especially for the density and distribution of clonogenic cells. The better these input parameters become established in the future, the more the model described here will serve as an important aid for the radiotherapist in the definition of the optimal target volume

  12. The quest for a new modelling framework in mathematical biology. Comment on "On the interplay between mathematics and biology: Hallmarks towards a new systems biology" by N. Bellomo et al.

    Science.gov (United States)

    Eftimie, Raluca

    2015-03-01

    One of the main unsolved problems of modern physics is finding a "theory of everything" - a theory that can explain, with the help of mathematics, all physical aspects of the universe. While the laws of physics could explain some aspects of the biology of living systems (e.g., the phenomenological interpretation of movement of cells and animals), there are other aspects specific to biology that cannot be captured by physics models. For example, it is generally accepted that the evolution of a cell-based system is influenced by the activation state of cells (e.g., only activated and functional immune cells can fight diseases); on the other hand, the evolution of an animal-based system can be influenced by the psychological state (e.g., distress) of animals. Therefore, the last 10-20 years have seen also a quest for a "theory of everything"-approach extended to biology, with researchers trying to propose mathematical modelling frameworks that can explain various biological phenomena ranging from ecology to developmental biology and medicine [1,2,6]. The basic idea behind this approach can be found in a few reviews on ecology and cell biology [6,7,9-11], where researchers suggested that due to the parallel between the micro-scale dynamics and the emerging macro-scale phenomena in both cell biology and in ecology, many mathematical methods used for ecological processes could be adapted to cancer modelling [7,9] or to modelling in immunology [11]. However, this approach generally involved the use of different models to describe different biological aspects (e.g., models for cell and animal movement, models for competition between cells or animals, etc.).

  13. Metastasis in renal cell carcinoma: Biology and implications for therapy

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

    Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

  14. Computational brain models: Advances from system biology and future challenges

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-02-01

    Full Text Available Computational brain models focused on the interactions between neurons and astrocytes, modeled via metabolic reconstructions, are reviewed. The large source of experimental data provided by the -omics techniques and the advance/application of computational and data-management tools are being fundamental. For instance, in the understanding of the crosstalk between these cells, the key neuroprotective mechanisms mediated by astrocytes in specific metabolic scenarios (1 and the identification of biomarkers for neurodegenerative diseases (2,3. However, the modeling of these interactions demands a clear view of the metabolic and signaling pathways implicated, but most of them are controversial and are still under evaluation (4. Hence, to gain insight into the complexity of these interactions a current view of the main pathways implicated in the neuron-astrocyte communication processes have been made from recent experimental reports and reviews. Furthermore, target problems, limitations and main conclusions have been identified from metabolic models of the brain reported from 2010. Finally, key aspects to take into account into the development of a computational model of the brain and topics that could be approached from a systems biology perspective in future research are highlighted.

  15. Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications

    Science.gov (United States)

    Castro-Manrreza, Marta E.; Montesinos, Juan J.

    2015-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD). PMID:25961059

  16. Synthetic biology in cell-based cancer immunotherapy.

    Science.gov (United States)

    Chakravarti, Deboki; Wong, Wilson W

    2015-08-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. We first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Recent advances in the cell biology of aging.

    Science.gov (United States)

    Hayflick, L

    1980-01-01

    Cultured normal human and animal cells are predestined to undergo irreversible functional decrements that mimic age changes in the whole organism. When normal human embryonic fibroblasts are cultured in vitro, 50 +/- 10 population doublings occur. This maximum potential is diminished in cells derived from older donors and appears to be inversely proportional to their age. The 50 population doubling limit can account for all cells produced during a lifetime. The limitation on doubling potential of cultured normal cells is also expressed in vivo when serial transplants are made. There may be a direct correlation between the mean maximum life spans of several species and the population doubling potential of their cultured cells. A plethora of functional decrements occurs in cultured normal cells as they approach their maximum division capability. Many of these decrements are similar to those occurring in intact animals as they age. We have concluded that these functional decrements expressed in vitro, rather than cessation of cell division, are the essential contributors to age changes in intact animals. Thus, the study of events leading to functional losses in cultured normal cells may provide useful insights into the biology of aging.

  18. On a poroviscoelastic model for cell crawling

    KAUST Repository

    Kimpton, L. S.

    2014-02-08

    In this paper a minimal, one-dimensional, two-phase, viscoelastic, reactive, flow model for a crawling cell is presented. Two-phase models are used with a variety of constitutive assumptions in the literature to model cell motility. We use an upper-convected Maxwell model and demonstrate that even the simplest of two-phase, viscoelastic models displays features relevant to cell motility. We also show care must be exercised in choosing parameters for such models as a poor choice can lead to an ill-posed problem. A stability analysis reveals that the initially stationary, spatially uniform strip of cytoplasm starts to crawl in response to a perturbation which breaks the symmetry of the network volume fraction or network stress. We also demonstrate numerically that there is a steady travelling-wave solution in which the crawling velocity has a bell-shaped dependence on adhesion strength, in agreement with biological observation.

  19. Computer Models and Automata Theory in Biology and Medicine

    CERN Document Server

    Baianu, I C

    2004-01-01

    The applications of computers to biological and biomedical problem solving goes back to the very beginnings of computer science, automata theory [1], and mathematical biology [2]. With the advent of more versatile and powerful computers, biological and biomedical applications of computers have proliferated so rapidly that it would be virtually impossible to compile a comprehensive review of all developments in this field. Limitations of computer simulations in biology have also come under close scrutiny, and claims have been made that biological systems have limited information processing power [3]. Such general conjectures do not, however, deter biologists and biomedical researchers from developing new computer applications in biology and medicine. Microprocessors are being widely employed in biological laboratories both for automatic data acquisition/processing and modeling; one particular area, which is of great biomedical interest, involves fast digital image processing and is already established for rout...

  20. Sensitivity analysis approaches applied to systems biology models.

    Science.gov (United States)

    Zi, Z

    2011-11-01

    With the rising application of systems biology, sensitivity analysis methods have been widely applied to study the biological systems, including metabolic networks, signalling pathways and genetic circuits. Sensitivity analysis can provide valuable insights about how robust the biological responses are with respect to the changes of biological parameters and which model inputs are the key factors that affect the model outputs. In addition, sensitivity analysis is valuable for guiding experimental analysis, model reduction and parameter estimation. Local and global sensitivity analysis approaches are the two types of sensitivity analysis that are commonly applied in systems biology. Local sensitivity analysis is a classic method that studies the impact of small perturbations on the model outputs. On the other hand, global sensitivity analysis approaches have been applied to understand how the model outputs are affected by large variations of the model input parameters. In this review, the author introduces the basic concepts of sensitivity analysis approaches applied to systems biology models. Moreover, the author discusses the advantages and disadvantages of different sensitivity analysis methods, how to choose a proper sensitivity analysis approach, the available sensitivity analysis tools for systems biology models and the caveats in the interpretation of sensitivity analysis results.

  1. Learning (from) the errors of a systems biology model.

    Science.gov (United States)

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-11

    Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a data driven mathematical method which automatically detects such model errors in ordinary differential equation (ODE) models. We demonstrate for real and simulated data, how the dynamic elastic-net approach can be used to automatically (i) reconstruct the error signal, (ii) identify the target variables of model error, and (iii) reconstruct the true system state even for incomplete or preliminary models. Our work provides a systematic computational method facilitating modelling of open biological systems under uncertain knowledge.

  2. Thematic minireview series: cell biology of G protein signaling.

    Science.gov (United States)

    Dohlman, Henrik G

    2015-03-13

    This thematic series is on the topic of cell signaling from a cell biology perspective, with a particular focus on G proteins. G protein-coupled receptors (GPCRs, also known as seven-transmembrane receptors) are typically found at the cell surface. Upon agonist binding, these receptors will activate a GTP-binding G protein at the cytoplasmic face of the plasma membrane. Additionally, there is growing evidence that G proteins can also be activated by non-receptor binding partners, and they can signal from non-plasma membrane compartments. The production of second messengers at multiple, spatially distinct locations represents a type of signal encoding that has been largely neglected. The first minireview in the series describes biosensors that are being used to monitor G protein signaling events in live cells. The second describes the implementation of antibody-based biosensors to dissect endosome signaling by G proteins and their receptors. The third describes the function of a non-receptor, cytoplasmic activator of G protein signaling, called GIV (Girdin). Collectively, the advances described in these articles provide a deeper understanding and emerging opportunities for new pharmacology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Nanoscopical dissection of ancestral nucleoli in Archaea: a case of study in Evolutionary Cell Biology

    KAUST Repository

    Islas Morales, Parsifal

    2018-01-01

    Evolutionary cell biology (ECB) has raised increasing attention in the last decades. Is this a new discipline and an historical opportunity to combine functional and evolutionary biology towards the insight that cell

  4. Spatial Modeling Tools for Cell Biology

    Science.gov (United States)

    2006-10-01

    1 +⎯→⎯+ − Demethylation 41 r,r −− K p2 k p3 BTBT 1 +⎯→⎯+ − Ligand binding 765765 r,r,r;r,r,r −−− 2 5 5 2 LT k k L_T − ⇔ Autophosphorylation 138...r,,r K p2 k 2 TT 8⎯→⎯ Phosphotransfer tr p2 k p2 BTBT b⎯→⎯+ p2 k p2 YTYT y +⎯→⎯+ Dephosphorylation BB bkp ⎯⎯→⎯ − ZYZY y k p

  5. In search of mitochondrial mechanisms: interfield excursions between cell biology and biochemistry.

    Science.gov (United States)

    Bechtel, William; Abrahamsen, Adele

    2007-01-01

    Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration.

  6. Uncertainty in biology a computational modeling approach

    CERN Document Server

    Gomez-Cabrero, David

    2016-01-01

    Computational modeling of biomedical processes is gaining more and more weight in the current research into the etiology of biomedical problems and potential treatment strategies.  Computational modeling allows to reduce, refine and replace animal experimentation as well as to translate findings obtained in these experiments to the human background. However these biomedical problems are inherently complex with a myriad of influencing factors, which strongly complicates the model building and validation process.  This book wants to address four main issues related to the building and validation of computational models of biomedical processes: Modeling establishment under uncertainty Model selection and parameter fitting Sensitivity analysis and model adaptation Model predictions under uncertainty In each of the abovementioned areas, the book discusses a number of key-techniques by means of a general theoretical description followed by one or more practical examples.  This book is intended for graduate stude...

  7. Mathematical manipulative models: in defense of "beanbag biology".

    Science.gov (United States)

    Jungck, John R; Gaff, Holly; Weisstein, Anton E

    2010-01-01

    Mathematical manipulative models have had a long history of influence in biological research and in secondary school education, but they are frequently neglected in undergraduate biology education. By linking mathematical manipulative models in a four-step process-1) use of physical manipulatives, 2) interactive exploration of computer simulations, 3) derivation of mathematical relationships from core principles, and 4) analysis of real data sets-we demonstrate a process that we have shared in biological faculty development workshops led by staff from the BioQUEST Curriculum Consortium over the past 24 yr. We built this approach based upon a broad survey of literature in mathematical educational research that has convincingly demonstrated the utility of multiple models that involve physical, kinesthetic learning to actual data and interactive simulations. Two projects that use this approach are introduced: The Biological Excel Simulations and Tools in Exploratory, Experiential Mathematics (ESTEEM) Project (http://bioquest.org/esteem) and Numerical Undergraduate Mathematical Biology Education (NUMB3R5 COUNT; http://bioquest.org/numberscount). Examples here emphasize genetics, ecology, population biology, photosynthesis, cancer, and epidemiology. Mathematical manipulative models help learners break through prior fears to develop an appreciation for how mathematical reasoning informs problem solving, inference, and precise communication in biology and enhance the diversity of quantitative biology education.

  8. Development of a Value Inquiry Model in Biology Education.

    Science.gov (United States)

    Jeong, Eun-Young; Kim, Young-Soo

    2000-01-01

    Points out the rapid advances in biology, increasing bioethical issues, and how students need to make rational decisions. Introduces a value inquiry model development that includes identifying and clarifying value problems; understanding biological knowledge related to conflict situations; considering, selecting, and evaluating each alternative;…

  9. SEEK: a systems biology data and model management platform.

    NARCIS (Netherlands)

    Wolstencroft, K.J.; Owen, S.; Krebs, O.; Nguyen, Q.; Stanford, N.J.; Golebiewski, M.; Weidemann, A.; Bittkowski, M.; An, L.; Shockley, D.; Snoep, J.L.; Mueller, W.; Goble, C.

    2015-01-01

    Background: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems

  10. An overview of bioinformatics methods for modeling biological pathways in yeast.

    Science.gov (United States)

    Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

    2016-03-01

    The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. Computer support for physiological cell modelling using an ontology on cell physiology.

    Science.gov (United States)

    Takao, Shimayoshi; Kazuhiro, Komurasaki; Akira, Amano; Takeshi, Iwashita; Masanori, Kanazawa; Tetsuya, Matsuda

    2006-01-01

    The development of electrophysiological whole cell models to support the understanding of biological mechanisms is increasing rapidly. Due to the complexity of biological systems, comprehensive cell models, which are composed of many imported sub-models of functional elements, can get quite complicated as well, making computer modification difficult. Here, we propose a computer support to enhance structural changes of cell models, employing the markup languages CellML and our original PMSML (physiological model structure markup language), in addition to a new ontology for cell physiological modelling. In particular, a method to make references from CellML files to the ontology and a method to assist manipulation of model structures using markup languages together with the ontology are reported. Using these methods three software utilities, including a graphical model editor, are implemented. Experimental results proved that these methods are effective for the modification of electrophysiological models.

  12. Systems biology of stored blood cells: can it help to extend the expiration date?

    Science.gov (United States)

    Paglia, Giuseppe; Palsson, Bernhard Ø; Sigurjonsson, Olafur E

    2012-12-05

    With increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Unified Deep Learning Architecture for Modeling Biology Sequence.

    Science.gov (United States)

    Wu, Hongjie; Cao, Chengyuan; Xia, Xiaoyan; Lu, Qiang

    2017-10-09

    Prediction of the spatial structure or function of biological macromolecules based on their sequence remains an important challenge in bioinformatics. When modeling biological sequences using traditional sequencing models, characteristics, such as long-range interactions between basic units, the complicated and variable output of labeled structures, and the variable length of biological sequences, usually lead to different solutions on a case-by-case basis. This study proposed the use of bidirectional recurrent neural networks based on long short-term memory or a gated recurrent unit to capture long-range interactions by designing the optional reshape operator to adapt to the diversity of the output labels and implementing a training algorithm to support the training of sequence models capable of processing variable-length sequences. Additionally, the merge and pooling operators enhanced the ability to capture short-range interactions between basic units of biological sequences. The proposed deep-learning model and its training algorithm might be capable of solving currently known biological sequence-modeling problems through the use of a unified framework. We validated our model on one of the most difficult biological sequence-modeling problems currently known, with our results indicating the ability of the model to obtain predictions of protein residue interactions that exceeded the accuracy of current popular approaches by 10% based on multiple benchmarks.

  14. Stochastic processes, multiscale modeling, and numerical methods for computational cellular biology

    CERN Document Server

    2017-01-01

    This book focuses on the modeling and mathematical analysis of stochastic dynamical systems along with their simulations. The collected chapters will review fundamental and current topics and approaches to dynamical systems in cellular biology. This text aims to develop improved mathematical and computational methods with which to study biological processes. At the scale of a single cell, stochasticity becomes important due to low copy numbers of biological molecules, such as mRNA and proteins that take part in biochemical reactions driving cellular processes. When trying to describe such biological processes, the traditional deterministic models are often inadequate, precisely because of these low copy numbers. This book presents stochastic models, which are necessary to account for small particle numbers and extrinsic noise sources. The complexity of these models depend upon whether the biochemical reactions are diffusion-limited or reaction-limited. In the former case, one needs to adopt the framework of s...

  15. SBR-Blood: systems biology repository for hematopoietic cells.

    Science.gov (United States)

    Lichtenberg, Jens; Heuston, Elisabeth F; Mishra, Tejaswini; Keller, Cheryl A; Hardison, Ross C; Bodine, David M

    2016-01-04

    Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array- and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Biological response of cancer cells to radiation treatment

    Directory of Open Access Journals (Sweden)

    Rajamanickam eBaskar

    2014-11-01

    Full Text Available Cancer is a class of diseases characterized by uncontrolled cell growth and has the ability to spread or metastasize throughout the body. In recent years, remarkable progress has been made towards the understanding of proposed hallmarks of cancer development, care and treatment modalities. Radiation therapy or radiotherapy is an important and integral component of cancer management, mostly conferring a survival benefit. Radiation therapy destroys cancer by depositing high-energy radiation on the cancer tissues. Over the years, radiation therapy has been driven by constant technological advances and approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease. In radiation oncology, research and development in the last three decades has led to considerable improvement in our understanding of the differential responses of normal and cancer cells. The biological effectiveness of radiation depends on the linear energy transfer (LET, total dose, number of fractions and radiosensitivity of the targeted cells or tissues. Radiation can either directly or indirectly (by producing free radicals damages the genome of the cell. This has been challenged in recent years by a newly identified phenomenon known as radiation induced bystander effect (RIBE. In RIBE, the non-irradiated cells adjacent to or located far from the irradiated cells/tissues demonstrate similar responses to that of the directly irradiated cells. Understanding the cancer cell responses during the fractions or after the course of irradiation will lead to improvements in therapeutic efficacy and potentially, benefitting a significant proportion of cancer patients. In this review, the clinical implications of radiation induced direct and bystander effects on the cancer cell are discussed.

  17. Biological behaviour of buccal cells exposed to blue light

    International Nuclear Information System (INIS)

    Gritsch, Kerstin; Ponsonnet, Laurence; Schembri, Catherine; Farge, Pierre; Pourreyron, Laurence; Grosgogeat, Brigitte

    2008-01-01

    Blue light is used in dental practise to cure resin-based materials, but the path of the light often includes oral tissues such as gingival tissues. While adverse effects of blue light exposure on cells - such as retina cells - are well known, few studies have investigated the impact of blue light exposure on oral cells. The aim of the present in vitro study was to assess the biological effects of blue light emitted by two dental curing devices (a plasma-arc and a light-emitting diode curing unit) on human gingival fibroblasts. Light intensities and light-induced temperature rise were respectively measured with a radiometer and a thermocouple. Cellular response to blue light exposure was assessed by the observation of cell morphology (scanning electron microscopy) and the estimation of cell mitochondrial activity (MTT assay). Light intensities measured at the clinical distance were 488 ± 42 mW/cm 2 for the plasma-arc unit and ranged from 61 ± 5 to 140 ± 16 mW/cm 2 for the light-emitting diodes unit, according to the curing program used. The highest temperature rise was 0.5 and 3.5 deg. C for exposure to the plasma-arc light and to the light-emitting diodes light, respectively. Results showed no differences between exposed- and non-exposed cells in regards to cell morphology. However, cells exposed to blue light presented an increased mitochondrial activity compared to control cells (non-exposed), and mostly those exposed to plasma-arc light

  18. Genome Scale Modeling in Systems Biology: Algorithms and Resources

    Science.gov (United States)

    Najafi, Ali; Bidkhori, Gholamreza; Bozorgmehr, Joseph H.; Koch, Ina; Masoudi-Nejad, Ali

    2014-01-01

    In recent years, in silico studies and trial simulations have complemented experimental procedures. A model is a description of a system, and a system is any collection of interrelated objects; an object, moreover, is some elemental unit upon which observations can be made but whose internal structure either does not exist or is ignored. Therefore, any network analysis approach is critical for successful quantitative modeling of biological systems. This review highlights some of most popular and important modeling algorithms, tools, and emerging standards for representing, simulating and analyzing cellular networks in five sections. Also, we try to show these concepts by means of simple example and proper images and graphs. Overall, systems biology aims for a holistic description and understanding of biological processes by an integration of analytical experimental approaches along with synthetic computational models. In fact, biological networks have been developed as a platform for integrating information from high to low-throughput experiments for the analysis of biological systems. We provide an overview of all processes used in modeling and simulating biological networks in such a way that they can become easily understandable for researchers with both biological and mathematical backgrounds. Consequently, given the complexity of generated experimental data and cellular networks, it is no surprise that researchers have turned to computer simulation and the development of more theory-based approaches to augment and assist in the development of a fully quantitative understanding of cellular dynamics. PMID:24822031

  19. A hybrid mammalian cell cycle model

    Directory of Open Access Journals (Sweden)

    Vincent Noël

    2013-08-01

    Full Text Available Hybrid modeling provides an effective solution to cope with multiple time scales dynamics in systems biology. Among the applications of this method, one of the most important is the cell cycle regulation. The machinery of the cell cycle, leading to cell division and proliferation, combines slow growth, spatio-temporal re-organisation of the cell, and rapid changes of regulatory proteins concentrations induced by post-translational modifications. The advancement through the cell cycle comprises a well defined sequence of stages, separated by checkpoint transitions. The combination of continuous and discrete changes justifies hybrid modelling approaches to cell cycle dynamics. We present a piecewise-smooth version of a mammalian cell cycle model, obtained by hybridization from a smooth biochemical model. The approximate hybridization scheme, leading to simplified reaction rates and binary event location functions, is based on learning from a training set of trajectories of the smooth model. We discuss several learning strategies for the parameters of the hybrid model.

  20. Theoretical Biology and Medical Modelling: ensuring continued growth and future leadership.

    Science.gov (United States)

    Nishiura, Hiroshi; Rietman, Edward A; Wu, Rongling

    2013-07-11

    Theoretical biology encompasses a broad range of biological disciplines ranging from mathematical biology and biomathematics to philosophy of biology. Adopting a broad definition of "biology", Theoretical Biology and Medical Modelling, an open access journal, considers original research studies that focus on theoretical ideas and models associated with developments in biology and medicine.

  1. Development of a kinetic model for biological sulphate reduction ...

    African Journals Online (AJOL)

    A two-phase (aqueous/gas) physical, biological and chemical processes ... Additionally, the background weak acid/base chemistry for water, carbonate, ... in the UCTADM1 model, and hence the physical gas exchange for sulphide is included.

  2. Mathematical models in biology bringing mathematics to life

    CERN Document Server

    Ferraro, Maria; Guarracino, Mario

    2015-01-01

    This book presents an exciting collection of contributions based on the workshop “Bringing Maths to Life” held October 27-29, 2014 in Naples, Italy.  The state-of-the art research in biology and the statistical and analytical challenges facing huge masses of data collection are treated in this Work. Specific topics explored in depth surround the sessions and special invited sessions of the workshop and include genetic variability via differential expression, molecular dynamics and modeling, complex biological systems viewed from quantitative models, and microscopy images processing, to name several. In depth discussions of the mathematical analysis required to extract insights from complex bodies of biological datasets, to aid development in the field novel algorithms, methods and software tools for genetic variability, molecular dynamics, and complex biological systems are presented in this book. Researchers and graduate students in biology, life science, and mathematics/statistics will find the content...

  3. Modeling dynamics of biological and chemical components of aquatic ecosystems

    International Nuclear Information System (INIS)

    Lassiter, R.R.

    1975-05-01

    To provide capability to model aquatic ecosystems or their subsystems as needed for particular research goals, a modeling strategy was developed. Submodels of several processes common to aquatic ecosystems were developed or adapted from previously existing ones. Included are submodels for photosynthesis as a function of light and depth, biological growth rates as a function of temperature, dynamic chemical equilibrium, feeding and growth, and various types of losses to biological populations. These submodels may be used as modules in the construction of models of subsystems or ecosystems. A preliminary model for the nitrogen cycle subsystem was developed using the modeling strategy and applicable submodels. (U.S.)

  4. Systematic integration of experimental data and models in systems biology.

    Science.gov (United States)

    Li, Peter; Dada, Joseph O; Jameson, Daniel; Spasic, Irena; Swainston, Neil; Carroll, Kathleen; Dunn, Warwick; Khan, Farid; Malys, Naglis; Messiha, Hanan L; Simeonidis, Evangelos; Weichart, Dieter; Winder, Catherine; Wishart, Jill; Broomhead, David S; Goble, Carole A; Gaskell, Simon J; Kell, Douglas B; Westerhoff, Hans V; Mendes, Pedro; Paton, Norman W

    2010-11-29

    The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

  5. Radiobiological modelling with MarCell software

    International Nuclear Information System (INIS)

    Hasan, J.S.; Jones, T.D.

    1996-01-01

    Jones introduced a bone marrow radiation cell kinetics model with great potential for application in the fields of health physics, radiation research, and medicine. However, until recently, only the model developers have been able to apply it because of the complex array of biological and physical assignments needed for evaluation of a particular radiation exposure protocol. The purpose of this article is to illustrate the use of MarCell (MARrow CELL Kinetics) software for MS-DOS, a user-friendly computer implementation of that mathematical model that allows almost anyone with an elementary knowledge of radiation physics and/or medical procedures to apply the model. A hands-on demonstration of the software will be given by guiding the user through evaluation of a medical total body irradiation protocol and a nuclear fallout scenario. A brief overview of the software is given in the Appendix

  6. Cell illustrator 4.0: a computational platform for systems biology.

    Science.gov (United States)

    Nagasaki, Masao; Saito, Ayumu; Jeong, Euna; Li, Chen; Kojima, Kaname; Ikeda, Emi; Miyano, Satoru

    2011-01-01

    Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.

  7. Some Issues of Biological Shape Modelling with Applications

    DEFF Research Database (Denmark)

    Larsen, Rasmus; Hilger, Klaus Baggesen; Skoglund, Karl

    2003-01-01

    This paper illustrates current research at Informatics and Mathematical Modelling at the Technical University of Denmark within biological shape modelling. We illustrate a series of generalizations to, modifications to, and applications of the elements of constructing models of shape or appearance...

  8. The Cell Collective: Toward an open and collaborative approach to systems biology

    Directory of Open Access Journals (Sweden)

    Helikar Tomáš

    2012-08-01

    Full Text Available Abstract Background Despite decades of new discoveries in biomedical research, the overwhelming complexity of cells has been a significant barrier to a fundamental understanding of how cells work as a whole. As such, the holistic study of biochemical pathways requires computer modeling. Due to the complexity of cells, it is not feasible for one person or group to model the cell in its entirety. Results The Cell Collective is a platform that allows the world-wide scientific community to create these models collectively. Its interface enables users to build and use models without specifying any mathematical equations or computer code - addressing one of the major hurdles with computational research. In addition, this platform allows scientists to simulate and analyze the models in real-time on the web, including the ability to simulate loss/gain of function and test what-if scenarios in real time. Conclusions The Cell Collective is a web-based platform that enables laboratory scientists from across the globe to collaboratively build large-scale models of various biological processes, and simulate/analyze them in real time. In this manuscript, we show examples of its application to a large-scale model of signal transduction.

  9. Beware the tail that wags the dog: informal and formal models in biology.

    Science.gov (United States)

    Gunawardena, Jeremy

    2014-11-05

    Informal models have always been used in biology to guide thinking and devise experiments. In recent years, formal mathematical models have also been widely introduced. It is sometimes suggested that formal models are inherently superior to informal ones and that biology should develop along the lines of physics or economics by replacing the latter with the former. Here I suggest to the contrary that progress in biology requires a better integration of the formal with the informal. © 2014 Gunawardena. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. BioModels Database: a repository of mathematical models of biological processes.

    Science.gov (United States)

    Chelliah, Vijayalakshmi; Laibe, Camille; Le Novère, Nicolas

    2013-01-01

    BioModels Database is a public online resource that allows storing and sharing of published, peer-reviewed quantitative, dynamic models of biological processes. The model components and behaviour are thoroughly checked to correspond the original publication and manually curated to ensure reliability. Furthermore, the model elements are annotated with terms from controlled vocabularies as well as linked to relevant external data resources. This greatly helps in model interpretation and reuse. Models are stored in SBML format, accepted in SBML and CellML formats, and are available for download in various other common formats such as BioPAX, Octave, SciLab, VCML, XPP and PDF, in addition to SBML. The reaction network diagram of the models is also available in several formats. BioModels Database features a search engine, which provides simple and more advanced searches. Features such as online simulation and creation of smaller models (submodels) from the selected model elements of a larger one are provided. BioModels Database can be accessed both via a web interface and programmatically via web services. New models are available in BioModels Database at regular releases, about every 4 months.

  11. Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues

    KAUST Repository

    Davit, Y.; Osborne, J. M.; Byrne, H. M.; Gavaghan, D.; Pitt-Francis, J.

    2013-01-01

    The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to continuum methods based on partial differential equations, although formal relationships between

  12. Multiscale modeling of emergent materials: biological and soft matter

    DEFF Research Database (Denmark)

    Murtola, Teemu; Bunker, Alex; Vattulainen, Ilpo

    2009-01-01

    In this review, we focus on four current related issues in multiscale modeling of soft and biological matter. First, we discuss how to use structural information from detailed models (or experiments) to construct coarse-grained ones in a hierarchical and systematic way. This is discussed in the c......In this review, we focus on four current related issues in multiscale modeling of soft and biological matter. First, we discuss how to use structural information from detailed models (or experiments) to construct coarse-grained ones in a hierarchical and systematic way. This is discussed...

  13. Regenerative patterning in Swarm Robots: mutual benefits of research in robotics and stem cell biology

    Science.gov (United States)

    RUBENSTEIN, MICHAEL; SAI, YING; CHUONG, CHENG-MING; SHEN, WEI-MIN

    2010-01-01

    This paper presents a novel perspective of Robotic Stem Cells (RSCs), defined as the basic non-biological elements with stem cell like properties that can self-reorganize to repair damage to their swarming organization. “Self” here means that the elements can autonomously decide and execute their actions without requiring any preset triggers, commands, or help from external sources. We develop this concept for two purposes. One is to develop a new theory for self-organization and self-assembly of multi-robots systems that can detect and recover from unforeseen errors or attacks. This self-healing and self-regeneration is used to minimize the compromise of overall function for the robot team. The other is to decipher the basic algorithms of regenerative behaviors in multi-cellular animal models, so that we can understand the fundamental principles used in the regeneration of biological systems. RSCs are envisioned to be basic building elements for future systems that are capable of self-organization, self-assembly, self-healing and self-regeneration. We first discuss the essential features of biological stem cells for such a purpose, and then propose the functional requirements of robotic stem cells with properties equivalent to gene controller, program selector and executor. We show that RSCs are a novel robotic model for scalable self-organization and self-healing in computer simulations and physical implementation. As our understanding of stem cells advances, we expect that future robots will be more versatile, resilient and complex, and such new robotic systems may also demand and inspire new knowledge from stem cell biology and related fields, such as artificial intelligence and tissue engineering. PMID:19557691

  14. Regenerative patterning in Swarm Robots: mutual benefits of research in robotics and stem cell biology.

    Science.gov (United States)

    Rubenstein, Michael; Sai, Ying; Chuong, Cheng-Ming; Shen, Wei-Min

    2009-01-01

    This paper presents a novel perspective of Robotic Stem Cells (RSCs), defined as the basic non-biological elements with stem cell like properties that can self-reorganize to repair damage to their swarming organization. Self here means that the elements can autonomously decide and execute their actions without requiring any preset triggers, commands, or help from external sources. We develop this concept for two purposes. One is to develop a new theory for self-organization and self-assembly of multi-robots systems that can detect and recover from unforeseen errors or attacks. This self-healing and self-regeneration is used to minimize the compromise of overall function for the robot team. The other is to decipher the basic algorithms of regenerative behaviors in multi-cellular animal models, so that we can understand the fundamental principles used in the regeneration of biological systems. RSCs are envisioned to be basic building elements for future systems that are capable of self-organization, self-assembly, self-healing and self-regeneration. We first discuss the essential features of biological stem cells for such a purpose, and then propose the functional requirements of robotic stem cells with properties equivalent to gene controller, program selector and executor. We show that RSCs are a novel robotic model for scalable self-organization and self-healing in computer simulations and physical implementation. As our understanding of stem cells advances, we expect that future robots will be more versatile, resilient and complex, and such new robotic systems may also demand and inspire new knowledge from stem cell biology and related fields, such as artificial intelligence and tissue engineering.

  15. A minimal physical model for crawling cells

    Science.gov (United States)

    Tiribocchi, Adriano; Tjhung, Elsen; Marenduzzo, Davide; Cates, Michael E.

    Cell motility in higher organisms (eukaryotes) is fundamental to biological functions such as wound healing or immune response, and is also implicated in diseases such as cancer. For cells crawling on solid surfaces, considerable insights into motility have been gained from experiments replicating such motion in vitro. Such experiments show that crawling uses a combination of actin treadmilling (polymerization), which pushes the front of a cell forward, and myosin-induced stress (contractility), which retracts the rear. We present a simplified physical model of a crawling cell, consisting of a droplet of active polar fluid with contractility throughout, but treadmilling connected to a thin layer near the supporting wall. The model shows a variety of shapes and/or motility regimes, some closely resembling cases seen experimentally. Our work supports the view that cellular motility exploits autonomous physical mechanisms whose operation does not need continuous regulatory effort.

  16. Probing the biology of cell boundary conditions through confinement of Xenopus cell-free cytoplasmic extracts.

    Science.gov (United States)

    Bermudez, Jessica G; Chen, Hui; Einstein, Lily C; Good, Matthew C

    2017-01-01

    Cell-free cytoplasmic extracts prepared from Xenopus eggs and embryos have for decades provided a biochemical system with which to interrogate complex cell biological processes in vitro. Recently, the application of microfabrication and microfluidic strategies in biology has narrowed the gap between in vitro and in vivo studies by enabling formation of cell-size compartments containing functional cytoplasm. These approaches provide numerous advantages over traditional biochemical experiments performed in a test tube. Most notably, the cell-free cytoplasm is confined using a two- or three-dimensional boundary, which mimics the natural configuration of a cell. This strategy enables characterization of the spatial organization of a cell, and the role that boundaries play in regulating intracellular assembly and function. In this review, we describe the marriage of Xenopus cell-free cytoplasm and confinement technologies to generate synthetic cell-like systems, the recent biological insights they have enabled, and the promise they hold for future scientific discovery. © 2017 Wiley Periodicals, Inc.

  17. Statistical Model Checking for Biological Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Larsen, Kim Guldstrand; Legay, Axel

    2014-01-01

    Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfies a given linear temporal property. The technique has been applied to (discrete and continuous time) Markov chains, stochastic...

  18. Nematodes: Model Organisms in High School Biology

    Science.gov (United States)

    Bliss, TJ; Anderson, Margery; Dillman, Adler; Yourick, Debra; Jett, Marti; Adams, Byron J.; Russell, RevaBeth

    2007-01-01

    In a collaborative effort between university researchers and high school science teachers, an inquiry-based laboratory module was designed using two species of insecticidal nematodes to help students apply scientific inquiry and elements of thoughtful experimental design. The learning experience and model are described in this article. (Contains 4…

  19. Biological 2-Input Decoder Circuit in Human Cells

    Science.gov (United States)

    2015-01-01

    Decoders are combinational circuits that convert information from n inputs to a maximum of 2n outputs. This operation is of major importance in computing systems yet it is vastly underexplored in synthetic biology. Here, we present a synthetic gene network architecture that operates as a biological decoder in human cells, converting 2 inputs to 4 outputs. As a proof-of-principle, we use small molecules to emulate the two inputs and fluorescent reporters as the corresponding four outputs. The experiments are performed using transient transfections in human kidney embryonic cells and the characterization by fluorescence microscopy and flow cytometry. We show a clear separation between the ON and OFF mean fluorescent intensity states. Additionally, we adopt the integrated mean fluorescence intensity for the characterization of the circuit and show that this metric is more robust to transfection conditions when compared to the mean fluorescent intensity. To conclude, we present the first implementation of a genetic decoder. This combinational system can be valuable toward engineering higher-order circuits as well as accommodate a multiplexed interface with endogenous cellular functions. PMID:24694115

  20. Lessons learned about spaceflight and cell biology experiments

    Science.gov (United States)

    Hughes-Fulford, Millie

    2004-01-01

    Conducting cell biology experiments in microgravity can be among the most technically challenging events in a biologist's life. Conflicting events of spaceflight include waiting to get manifested, delays in manifest schedules, training astronauts to not shake your cultures and to add reagents slowly, as shaking or quick injection can activate signaling cascades and give you erroneous results. It is important to select good hardware that is reliable. Possible conflicting environments in flight include g-force and vibration of launch, exposure of cells to microgravity for extended periods until hardware is turned on, changes in cabin gases and cosmic radiation. One should have an on-board 1-g control centrifuge in order to eliminate environmental differences. Other obstacles include getting your funding in a timely manner (it is not uncommon for two to three years to pass between notification of grant approval for funding and actually getting funded). That said, it is important to note that microgravity research is worthwhile since all terrestrial life evolved in a gravity field and secrets of biological function may only be answered by removing the constant of gravity. Finally, spaceflight experiments are rewarding and worth your effort and patience.

  1. Biological 2-input decoder circuit in human cells.

    Science.gov (United States)

    Guinn, Michael; Bleris, Leonidas

    2014-08-15

    Decoders are combinational circuits that convert information from n inputs to a maximum of 2(n) outputs. This operation is of major importance in computing systems yet it is vastly underexplored in synthetic biology. Here, we present a synthetic gene network architecture that operates as a biological decoder in human cells, converting 2 inputs to 4 outputs. As a proof-of-principle, we use small molecules to emulate the two inputs and fluorescent reporters as the corresponding four outputs. The experiments are performed using transient transfections in human kidney embryonic cells and the characterization by fluorescence microscopy and flow cytometry. We show a clear separation between the ON and OFF mean fluorescent intensity states. Additionally, we adopt the integrated mean fluorescence intensity for the characterization of the circuit and show that this metric is more robust to transfection conditions when compared to the mean fluorescent intensity. To conclude, we present the first implementation of a genetic decoder. This combinational system can be valuable toward engineering higher-order circuits as well as accommodate a multiplexed interface with endogenous cellular functions.

  2. A bistable model of cell polarity.

    Directory of Open Access Journals (Sweden)

    Matteo Semplice

    Full Text Available Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems. It is not as well recognized that when ultrasensitivity and reinforcing feedback loops are present in a spatially distributed system such as the cell plasmamembrane, they may induce bistability and spatial separation of the system into distinct signaling phases. Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity. Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms. We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics. The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types.

  3. Track structure model of cell damage in space flight

    Science.gov (United States)

    Katz, Robert; Cucinotta, Francis A.; Wilson, John W.; Shinn, Judy L.; Ngo, Duc M.

    1992-01-01

    The phenomenological track-structure model of cell damage is discussed. A description of the application of the track-structure model with the NASA Langley transport code for laboratory and space radiation is given. Comparisons to experimental results for cell survival during exposure to monoenergetic, heavy-ion beams are made. The model is also applied to predict cell damage rates and relative biological effectiveness for deep-space exposures.

  4. Sub-terahertz resonance spectroscopy of biological macromolecules and cells

    Science.gov (United States)

    Globus, Tatiana; Moyer, Aaron; Gelmont, Boris; Khromova, Tatyana; Sizov, Igor; Ferrance, Jerome

    2013-05-01

    Recently we introduced a Sub-THz spectroscopic system for characterizing vibrational resonance features from biological materials. This new, continuous-wave, frequency-domain spectroscopic sensor operates at room temperature between 315 and 480 GHz with spectral resolution of at least 1 GHz and utilizes the source and detector components from Virginia Diode, Inc. In this work we present experimental results and interpretation of spectroscopic signatures from bacterial cells and their biological macromolecule structural components. Transmission and absorption spectra of the bacterial protein thioredoxin, DNA and lyophilized cells of Escherichia coli (E. coli), as well as spores of Bacillus subtillis and B. atrophaeus have been characterized. Experimental results for biomolecules are compared with absorption spectra calculated using molecular dynamics simulation, and confirm the underlying physics for resonance spectroscopy based on interactions between THz radiation and vibrational modes or groups of modes of atomic motions. Such interactions result in multiple intense and narrow specific resonances in transmission/absorption spectra from nano-gram samples with spectral line widths as small as 3 GHz. The results of this study indicate diverse relaxation dynamic mechanisms relevant to sub-THz vibrational spectroscopy, including long-lasting processes. We demonstrate that high sensitivity in resolved specific absorption fingerprints provides conditions for reliable detection, identification and discrimination capability, to the level of strains of the same bacteria, and for monitoring interactions between biomaterials and reagents in near real-time. Additionally, it creates the basis for the development of new types of advanced biological sensors through integrating the developed system with a microfluidic platform for biomaterial samples.

  5. High-Magnification In Vivo Imaging of Xenopus Embryos for Cell and Developmental Biology

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Esther K. Kieserman, Chanjae Lee, Ryan S. Gray, Tae Joo Park and John B. Wallingford Corresponding author ([]()). ### INTRODUCTION Embryos of the frog *Xenopus laevis* are an ideal model system for in vivo imaging of dynamic biological processes, from the inner workings of individual cells to the reshaping of tissues during embryogenesis. Their externally developing embryos are more amenable to in vivo analysis than in...

  6. Pectin: cell biology and prospects for functional analysis.

    Science.gov (United States)

    Willats, W G; McCartney, L; Mackie, W; Knox, J P

    2001-09-01

    Pectin is a major component of primary cell walls of all land plants and encompasses a range of galacturonic acid-rich polysaccharides. Three major pectic polysaccharides (homogalacturonan, rhamnogalacturonan-I and rhamnogalacturonan-II) are thought to occur in all primary cell walls. This review surveys what is known about the structure and function of these pectin domains. The high degree of structural complexity and heterogeneity of the pectic matrix is produced both during biosynthesis in the endomembrane system and as a result of the action of an array of wall-based pectin-modifying enzymes. Recent developments in analytical techniques and in the generation of anti-pectin probes have begun to place the structural complexity of pectin in cell biological and developmental contexts. The in muro de-methyl-esterification of homogalacturonan by pectin methyl esterases is emerging as a key process for the local modulation of matrix properties. Rhamnogalacturonan-I comprises a highly diverse population of spatially and developmentally regulated polymers, whereas rhamnogalacturonan-II appears to be a highly conserved and stable pectic domain. Current knowledge of biosynthetic enzymes, plant and microbial pectinases and the interactions of pectin with other cell wall components and the impact of molecular genetic approaches are reviewed in terms of the functional analysis of pectic polysaccharides in plant growth and development.

  7. Computational Biology Methods for Characterization of Pluripotent Cells.

    Science.gov (United States)

    Araúzo-Bravo, Marcos J

    2016-01-01

    Pluripotent cells are a powerful tool for regenerative medicine and drug discovery. Several techniques have been developed to induce pluripotency, or to extract pluripotent cells from different tissues and biological fluids. However, the characterization of pluripotency requires tedious, expensive, time-consuming, and not always reliable wet-lab experiments; thus, an easy, standard quality-control protocol of pluripotency assessment remains to be established. Here to help comes the use of high-throughput techniques, and in particular, the employment of gene expression microarrays, which has become a complementary technique for cellular characterization. Research has shown that the transcriptomics comparison with an Embryonic Stem Cell (ESC) of reference is a good approach to assess the pluripotency. Under the premise that the best protocol is a computer software source code, here I propose and explain line by line a software protocol coded in R-Bioconductor for pluripotency assessment based on the comparison of transcriptomics data of pluripotent cells with an ESC of reference. I provide advice for experimental design, warning about possible pitfalls, and guides for results interpretation.

  8. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  9. A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model.

    Science.gov (United States)

    Fu, Wei-Li; Zhou, Chun-Yan; Yu, Jia-Kuo

    2014-03-01

    Bone marrow (BM) has been considered as a major source of mesenchymal stem cells (MSCs), but it has many disadvantages in clinical application. However, MSCs from peripheral blood (PB) could be obtained by a less invasive method and be more beneficial for autologous transplantation than BM MSCs, which makes PB a promising source for articular cartilage repair in clinical use. To assess whether MSCs from mobilized PB of New Zealand White rabbits have similar biological characteristics in vitro and chondrogenesis in vivo as BM MSCs. Controlled laboratory study. A combined method of drug administration containing granulocyte colony stimulating factor (G-CSF) plus CXCR4 antagonist AMD3100 was adopted to mobilize the PB stem cells of adult New Zealand White rabbits in vitro. The isolated cells were identified as MSCs by morphological characteristics, surface markers, and differentiation potentials. A comparison between PB MSCs and BM MSCs was made in terms of biological characteristics in vitro and chondrogenesis in vivo. This issue was investigated from the aspects of morphology, immune phenotype, multiple differentiation capacity, expansion potential, antiapoptotic capacity, and ability to repair cartilage defects in vivo of PB MSCs compared with BM MSCs. Peripheral blood MSCs were successfully mobilized by the method of combined drug administration, then isolated, expanded, and identified in vitro. No significant difference was found concerning the morphology, immune phenotype, and antiapoptotic capacity between PB MSCs and BM MSCs. Significantly, MSCs from both sources compounded with decalcified bone matrix showed the same ability to repair cartilage defects in vivo. For multipluripotency, BM MSCs exhibited a more osteogenic potential and higher proliferation capacity than PB MSCs, whereas PB MSCs possessed a stronger adipogenic and chondrogenic differentiation potential than BM MSCs in vitro. Although there are some differences in the proliferation and

  10. Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.

    Science.gov (United States)

    Ham, Stephanie L; Joshi, Ramila; Luker, Gary D; Tavana, Hossein

    2016-11-01

    Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Cells from icons to symbols: molecularizing cell biology in the 1980s.

    Science.gov (United States)

    Serpente, Norberto

    2011-12-01

    Over centuries cells have been the target of optical and electronic microscopes as well as others technologies, with distinctive types of visual output. Whilst optical technologies produce images 'evident to the eye', the electronic and especially the molecular create images that are more elusive to conceptualization and assessment. My study applies the semiotic approach to the production of images in cell biology to capture the shift from microscopic images to non-traditional visual technologies around 1980. Here I argue that the visual shift that coincides with the growing dominance of molecular biology involves a change from iconic to symbolic forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Modeling and simulation of viscoelastic biological particles' 3D manipulation using atomic force microscopy

    Science.gov (United States)

    Korayem, M. H.; Habibi Sooha, Y.; Rastegar, Z.

    2018-05-01

    Manipulation of the biological particles by atomic force microscopy is used to transfer these particles inside body's cells, diagnosis and destruction of the cancer cells and drug delivery to damaged cells. According to the impossibility of simultaneous observation of this process, the importance of modeling and simulation can be realized. The contact of the tip with biological particle is important during manipulation, therefore, the first step of the modeling is choosing appropriate contact model. Most of the studies about contact between atomic force microscopy and biological particles, consider the biological particle as an elastic material. This is not an appropriate assumption because biological cells are basically soft and this assumption ignores loading history. In this paper, elastic and viscoelastic JKR theories were used in modeling and simulation of the 3D manipulation for three modes of tip-particle sliding, particle-substrate sliding and particle-substrate rolling. Results showed that critical force and time in motion modes (sliding and rolling) for two elastic and viscoelastic states are very close but these magnitudes were lower in the viscoelastic state. Then, three friction models, Coulomb, LuGre and HK, were used for tip-particle sliding mode in the first phase of manipulation to make results closer to reality. In both Coulomb and LuGre models, critical force and time are very close for elastic and viscoelastic states but in general critical force and time prediction of HK model was higher than LuGre and the LuGre model itself had higher prediction than Coulomb.

  13. Polynomial algebra of discrete models in systems biology.

    Science.gov (United States)

    Veliz-Cuba, Alan; Jarrah, Abdul Salam; Laubenbacher, Reinhard

    2010-07-01

    An increasing number of discrete mathematical models are being published in Systems Biology, ranging from Boolean network models to logical models and Petri nets. They are used to model a variety of biochemical networks, such as metabolic networks, gene regulatory networks and signal transduction networks. There is increasing evidence that such models can capture key dynamic features of biological networks and can be used successfully for hypothesis generation. This article provides a unified framework that can aid the mathematical analysis of Boolean network models, logical models and Petri nets. They can be represented as polynomial dynamical systems, which allows the use of a variety of mathematical tools from computer algebra for their analysis. Algorithms are presented for the translation into polynomial dynamical systems. Examples are given of how polynomial algebra can be used for the model analysis. alanavc@vt.edu Supplementary data are available at Bioinformatics online.

  14. SEEK: a systems biology data and model management platform.

    Science.gov (United States)

    Wolstencroft, Katherine; Owen, Stuart; Krebs, Olga; Nguyen, Quyen; Stanford, Natalie J; Golebiewski, Martin; Weidemann, Andreas; Bittkowski, Meik; An, Lihua; Shockley, David; Snoep, Jacky L; Mueller, Wolfgang; Goble, Carole

    2015-07-11

    Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems biology models. There are a large number of public repositories for storing biological data of a particular type, for example transcriptomics or proteomics, and there are several model repositories. However, this silo-type storage of data and models is not conducive to systems biology investigations. Interdependencies between multiple omics datasets and between datasets and models are essential. Researchers require an environment that will allow the management and sharing of heterogeneous data and models in the context of the experiments which created them. The SEEK is a suite of tools to support the management, sharing and exploration of data and models in systems biology. The SEEK platform provides an access-controlled, web-based environment for scientists to share and exchange data and models for day-to-day collaboration and for public dissemination. A plug-in architecture allows the linking of experiments, their protocols, data, models and results in a configurable system that is available 'off the shelf'. Tools to run model simulations, plot experimental data and assist with data annotation and standardisation combine to produce a collection of resources that support analysis as well as sharing. Underlying semantic web resources additionally extract and serve SEEK metadata in RDF (Resource Description Format). SEEK RDF enables rich semantic queries, both within SEEK and between related resources in the web of Linked Open Data. The SEEK platform has been adopted by many systems biology consortia across Europe. It is a data management environment that has a low barrier of uptake and provides rich resources for collaboration. This paper provides an update on the functions and

  15. Biological-Mathematical Modeling of Chronic Toxicity.

    Science.gov (United States)

    1981-07-22

    34Mathematical Model of Uptake and Distribution," Uptake and Distribution of Anesthetic Agents, E. M. Papper and R. J. Kitz (Editors, McGraw-Hill Book Co., Inc...distribution, In: Papper , E.M. and Kltz, R.J.(eds.) Uptake and distribution of anesthetic agents, McGraw- Hill, New York, p. 72 3. Plpleson, W.W...1963) Quantitative prediction of anesthetic concentrations. In: Papper , E.M. and Kitz, R.J. (eds.) Uptake and distribution of anesthetic agents, McGraw

  16. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy

    Science.gov (United States)

    Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J.; Rivière, Isabelle

    2009-01-01

    Summary Based on promising pre-clinical data demonstrating the eradication of systemic B cell malignancies by CD19-targeted T lymphocytes in vivo in SCID beige mouse models, we are launching Phase 1 clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). We present here the validation of the bioprocess we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads® CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semi-closed culture system using the Wave bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in SCID beige mice bearing disseminated tumors. The validation requirements in terms of T cell expansion, T cell transduction with the 1928z CAR, biological activity, quality control testing and release criteria were met for all four validation runs using apheresis products from patients with CLL. Additionally, following expansion of the T cells, the diversity of the skewed Vβ T cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemo-refractory CLL and in patients with relapsed ALL. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any chimeric antigen receptor or T cell receptor. PMID:19238016

  17. Coalescent models for developmental biology and the spatio-temporal dynamics of growing tissues.

    Science.gov (United States)

    Smadbeck, Patrick; Stumpf, Michael P H

    2016-04-01

    Development is a process that needs to be tightly coordinated in both space and time. Cell tracking and lineage tracing have become important experimental techniques in developmental biology and allow us to map the fate of cells and their progeny. A generic feature of developing and homeostatic tissues that these analyses have revealed is that relatively few cells give rise to the bulk of the cells in a tissue; the lineages of most cells come to an end quickly. Computational and theoretical biologists/physicists have, in response, developed a range of modelling approaches, most notably agent-based modelling. These models seem to capture features observed in experiments, but can also become computationally expensive. Here, we develop complementary genealogical models of tissue development that trace the ancestry of cells in a tissue back to their most recent common ancestors. We show that with both bounded and unbounded growth simple, but universal scaling relationships allow us to connect coalescent theory with the fractal growth models extensively used in developmental biology. Using our genealogical perspective, it is possible to study bulk statistical properties of the processes that give rise to tissues of cells, without the need for large-scale simulations. © 2016 The Authors.

  18. Modeling life the mathematics of biological systems

    CERN Document Server

    Garfinkel, Alan; Guo, Yina

    2017-01-01

    From predator-prey populations in an ecosystem, to hormone regulation within the body, the natural world abounds in dynamical systems that affect us profoundly. This book develops the mathematical tools essential for students in the life sciences to describe these interacting systems and to understand and predict their behavior. Complex feedback relations and counter-intuitive responses are common in dynamical systems in nature; this book develops the quantitative skills needed to explore these interactions. Differential equations are the natural mathematical tool for quantifying change, and are the driving force throughout this book. The use of Euler’s method makes nonlinear examples tractable and accessible to a broad spectrum of early-stage undergraduates, thus providing a practical alternative to the procedural approach of a traditional Calculus curriculum. Tools are developed within numerous, relevant examples, with an emphasis on the construction, evaluation, and interpretation of mathematical models ...

  19. Profiling the biological activity of oxide nanomaterials with mechanistic models

    NARCIS (Netherlands)

    Burello, E.

    2013-01-01

    In this study we present three mechanistic models for profiling the potential biological and toxicological effects of oxide nanomaterials. The models attempt to describe the reactivity, protein adsorption and membrane adhesion processes of a large range of oxide materials and are based on properties

  20. Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space

    Science.gov (United States)

    Gmunder, F. K.; Nordau, C. G.; Tschopp, A.; Huber, B.; Cogoli, A.

    1988-01-01

    The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 microliters. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 microliter h-1). The reservoir volume of culture medium is 230 microliters. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.

  1. Molecular infection biology : interactions between microorganisms and cells

    National Research Council Canada - National Science Library

    Hacker, Jörg (Jörg Hinrich); Heesemann, Jurgen

    2002-01-01

    ... and epidemiology of infectious diseases. Investigators, specialists, clinicians, and graduate students in biology, pharmacy, and medicine will find Molecular Infection Biology an invaluable addition to their professional libraries...

  2. Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm.

    Science.gov (United States)

    Stoll, Gautier; Viara, Eric; Barillot, Emmanuel; Calzone, Laurence

    2012-08-29

    Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time. There exist two major types of mathematical modeling approaches: (1) quantitative modeling, representing various chemical species concentrations by real numbers, mainly based on differential equations and chemical kinetics formalism; (2) and qualitative modeling, representing chemical species concentrations or activities by a finite set of discrete values. Both approaches answer particular (and often different) biological questions. Qualitative modeling approach permits a simple and less detailed description of the biological systems, efficiently describes stable state identification but remains inconvenient in describing the transient kinetics leading to these states. In this context, time is represented by discrete steps. Quantitative modeling, on the other hand, can describe more accurately the dynamical behavior of biological processes as it follows the evolution of concentration or activities of chemical species as a function of time, but requires an important amount of information on the parameters difficult to find in the literature. Here, we propose a modeling framework based on a qualitative approach that is intrinsically continuous in time. The algorithm presented in this article fills the gap between qualitative and quantitative modeling. It is based on continuous time Markov process applied on a Boolean state space. In order to describe the temporal evolution of the biological process we wish to model, we explicitly specify the transition rates for each node. For that purpose, we built a language that can be seen as a generalization of Boolean equations. Mathematically, this approach can be translated in a set of ordinary differential

  3. Predictive modelling of complex agronomic and biological systems.

    Science.gov (United States)

    Keurentjes, Joost J B; Molenaar, Jaap; Zwaan, Bas J

    2013-09-01

    Biological systems are tremendously complex in their functioning and regulation. Studying the multifaceted behaviour and describing the performance of such complexity has challenged the scientific community for years. The reduction of real-world intricacy into simple descriptive models has therefore convinced many researchers of the usefulness of introducing mathematics into biological sciences. Predictive modelling takes such an approach another step further in that it takes advantage of existing knowledge to project the performance of a system in alternating scenarios. The ever growing amounts of available data generated by assessing biological systems at increasingly higher detail provide unique opportunities for future modelling and experiment design. Here we aim to provide an overview of the progress made in modelling over time and the currently prevalent approaches for iterative modelling cycles in modern biology. We will further argue for the importance of versatility in modelling approaches, including parameter estimation, model reduction and network reconstruction. Finally, we will discuss the difficulties in overcoming the mathematical interpretation of in vivo complexity and address some of the future challenges lying ahead. © 2013 John Wiley & Sons Ltd.

  4. A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.

    Science.gov (United States)

    Pârvu, Ovidiu; Gilbert, David

    2016-01-01

    , the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems.

  5. Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research.

    Science.gov (United States)

    Kniss, Douglas A; Summerfield, Taryn L

    2014-08-01

    Continuous cell lines are used frequently in reproductive biology research to study problems in early pregnancy events and parturition. It has been recognized for 50 years that many mammalian cell lines contain inter- or intraspecies contaminations with other cells. However, most investigators do not routinely test their culture systems for cross-contamination. The most frequent contributor to cross-contamination of cell lines is the HeLa cell isolated from an aggressive cervical adenocarcinoma. We report on the discovery of HeLa cell contamination of the human endometrial epithelial cell line HES isolated in our laboratory. Short tandem repeat analysis of 9 unique genetic loci demonstrated molecular identity between HES and HeLa cells. In addition, we verified that WISH cells, isolated originally from human amnion epithelium, were also contaminated with HeLa cells. Inasmuch as our laboratory did not culture HeLa cells at the time of HES cell derivations, the source of contamination was the WISH cell line. These data highlight the need for continued diligence in authenticating cell lines used in reproductive biology research. © The Author(s) 2014.

  6. Complex Biological Systems Analysis of Cell Cycling Models in Carcinogenesis: I. The essential roles of modifications in the c-Myc, TP53/p53, p27 and hTERT modules in Cancer Initiation and Progression

    CERN Document Server

    Prisecaru, V I

    2004-01-01

    A new approach to the integration of results from a modular, complex biological systems analysis of nonlinear dynamics in cell cycling network transformations that are leading to carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. One such network module contains the cell cyclins whose functions are essential to cell cycling and division. Cyclins are proteins that also link to several critical pro-apoptotic and other cell cycling/division components, such as: c-Myc, p27, the tumor suppressor gene TP53 and its product-- the p53 protein with key roles in controlling DNA repair, inducing apoptosis and activating p21 (which can depress cell cyclins if activated), mdm2(with its biosynthesis activated by p53 and also, in its turn, inhibiting p53), p21, the Thomsen-Friedenreich antigen(T- antigen),Rb,Bax, Ba...

  7. Glucose Transport in Cultured Animal Cells: An Exercise for the Undergraduate Cell Biology Laboratory

    Science.gov (United States)

    Ledbetter, Mary Lee S.; Lippert, Malcolm J.

    2002-01-01

    Membrane transport is a fundamental concept that undergraduate students of cell biology understand better with laboratory experience. Formal teaching exercises commonly used to illustrate this concept are unbiological, qualitative, or intricate and time consuming to prepare. We have developed an exercise that uses uptake of radiolabeled nutrient…

  8. A distributed approach for parameters estimation in System Biology models

    International Nuclear Information System (INIS)

    Mosca, E.; Merelli, I.; Alfieri, R.; Milanesi, L.

    2009-01-01

    Due to the lack of experimental measurements, biological variability and experimental errors, the value of many parameters of the systems biology mathematical models is yet unknown or uncertain. A possible computational solution is the parameter estimation, that is the identification of the parameter values that determine the best model fitting respect to experimental data. We have developed an environment to distribute each run of the parameter estimation algorithm on a different computational resource. The key feature of the implementation is a relational database that allows the user to swap the candidate solutions among the working nodes during the computations. The comparison of the distributed implementation with the parallel one showed that the presented approach enables a faster and better parameter estimation of systems biology models.

  9. Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

    Science.gov (United States)

    Zhan, Han-Xiang; Zhou, Bin; Cheng, Yu-Gang; Xu, Jian-Wei; Wang, Lei; Zhang, Guang-Yong; Hu, San-Yuan

    2017-04-28

    Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Tiny cells meet big questions: a closer look at bacterial cell biology.

    Science.gov (United States)

    Goley, Erin D

    2013-04-01

    While studying actin assembly as a graduate student with Matt Welch at the University of California at Berkeley, my interest was piqued by reports of surprising observations in bacteria: the identification of numerous cytoskeletal proteins, actin homologues fulfilling spindle-like functions, and even the presence of membrane-bound organelles. Curiosity about these phenomena drew me to Lucy Shapiro's lab at Stanford University for my postdoctoral research. In the Shapiro lab, and now in my lab at Johns Hopkins, I have focused on investigating the mechanisms of bacterial cytokinesis. Spending time as both a eukaryotic cell biologist and a bacterial cell biologist has convinced me that bacterial cells present the same questions as eukaryotic cells: How are chromosomes organized and accurately segregated? How is force generated for cytokinesis? How is polarity established? How are signals transduced within and between cells? These problems are conceptually similar between eukaryotes and bacteria, although their solutions can differ significantly in specifics. In this Perspective, I provide a broad view of cell biological phenomena in bacteria, the technical challenges facing those of us who peer into bacterial cells, and areas of common ground as research in eukaryotic and bacterial cell biology moves forward.

  11. Preservice Biology Teachers' Conceptions About the Tentative Nature of Theories and Models in Biology

    Science.gov (United States)

    Reinisch, Bianca; Krüger, Dirk

    2018-02-01

    In research on the nature of science, there is a need to investigate the role and status of different scientific knowledge forms. Theories and models are two of the most important knowledge forms within biology and are the focus of this study. During interviews, preservice biology teachers ( N = 10) were asked about their understanding of theories and models. They were requested to give reasons why they see theories and models as either tentative or certain constructs. Their conceptions were then compared to philosophers' positions (e.g., Popper, Giere). A category system was developed from the qualitative content analysis of the interviews. These categories include 16 conceptions for theories ( n tentative = 11; n certai n = 5) and 18 conceptions for models ( n tentative = 10; n certain = 8). The analysis of the interviews showed that the preservice teachers gave reasons for the tentativeness or certainty of theories and models either due to their understanding of the terms or due to their understanding of the generation or evaluation of theories and models. Therefore, a variety of different terminology, from different sources, should be used in learning-teaching situations. Additionally, an understanding of which processes lead to the generation, evaluation, and refinement or rejection of theories and models should be discussed with preservice teachers. Within philosophy of science, there has been a shift from theories to models. This should be transferred to educational contexts by firstly highlighting the role of models and also their connections to theories.

  12. Cell-Oriented Modeling of Angiogenesis

    Directory of Open Access Journals (Sweden)

    Diego Guidolin

    2011-01-01

    Full Text Available Due to its significant involvement in various physiological and pathological conditions, angiogenesis (the development of new blood vessels from an existing vasculature represents an important area of the actual biological research and a field in which mathematical modeling proved particularly useful in supporting the experimental work. In this paper, we focus on a specific modeling strategy, known as “cell-centered” approach. This type of mathematical models work at a “mesoscopic scale,” assuming the cell as the natural level of abstraction for computational modeling of development. They treat cells phenomenologically, considering their essential behaviors to study how tissue structure and organization emerge from the collective dynamics of multiple cells. The main contributions of the cell-oriented approach to the study of the angiogenic process will be described. From one side, they have generated “basic science understanding” about the process of capillary assembly during development, growth, and pathology. On the other side, models were also developed supporting “applied biomedical research” for the purpose of identifying new therapeutic targets and clinically relevant approaches for either inhibiting or stimulating angiogenesis.

  13. Cell-oriented modeling of angiogenesis.

    Science.gov (United States)

    Guidolin, Diego; Rebuffat, Piera; Albertin, Giovanna

    2011-01-01

    Due to its significant involvement in various physiological and pathological conditions, angiogenesis (the development of new blood vessels from an existing vasculature) represents an important area of the actual biological research and a field in which mathematical modeling proved particularly useful in supporting the experimental work. In this paper, we focus on a specific modeling strategy, known as "cell-centered" approach. This type of mathematical models work at a "mesoscopic scale," assuming the cell as the natural level of abstraction for computational modeling of development. They treat cells phenomenologically, considering their essential behaviors to study how tissue structure and organization emerge from the collective dynamics of multiple cells. The main contributions of the cell-oriented approach to the study of the angiogenic process will be described. From one side, they have generated "basic science understanding" about the process of capillary assembly during development, growth, and pathology. On the other side, models were also developed supporting "applied biomedical research" for the purpose of identifying new therapeutic targets and clinically relevant approaches for either inhibiting or stimulating angiogenesis.

  14. Yeast as a Model System to Study Tau Biology

    Directory of Open Access Journals (Sweden)

    Ann De Vos

    2011-01-01

    Full Text Available Hyperphosphorylated and aggregated human protein tau constitutes a hallmark of a multitude of neurodegenerative diseases called tauopathies, exemplified by Alzheimer's disease. In spite of an enormous amount of research performed on tau biology, several crucial questions concerning the mechanisms of tau toxicity remain unanswered. In this paper we will highlight some of the processes involved in tau biology and pathology, focusing on tau phosphorylation and the interplay with oxidative stress. In addition, we will introduce the development of a human tau-expressing yeast model, and discuss some crucial results obtained in this model, highlighting its potential in the elucidation of cellular processes leading to tau toxicity.

  15. BayesMD: flexible biological modeling for motif discovery

    DEFF Research Database (Denmark)

    Tang, Man-Hung Eric; Krogh, Anders; Winther, Ole

    2008-01-01

    We present BayesMD, a Bayesian Motif Discovery model with several new features. Three different types of biological a priori knowledge are built into the framework in a modular fashion. A mixture of Dirichlets is used as prior over nucleotide probabilities in binding sites. It is trained on trans......We present BayesMD, a Bayesian Motif Discovery model with several new features. Three different types of biological a priori knowledge are built into the framework in a modular fashion. A mixture of Dirichlets is used as prior over nucleotide probabilities in binding sites. It is trained...

  16. Modeling fuel cell stack systems

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J H [Los Alamos National Lab., Los Alamos, NM (United States); Lalk, T R [Dept. of Mech. Eng., Texas A and M Univ., College Station, TX (United States)

    1998-06-15

    A technique for modeling fuel cell stacks is presented along with the results from an investigation designed to test the validity of the technique. The technique was specifically designed so that models developed using it can be used to determine the fundamental thermal-physical behavior of a fuel cell stack for any operating and design configuration. Such models would be useful tools for investigating fuel cell power system parameters. The modeling technique can be applied to any type of fuel cell stack for which performance data is available for a laboratory scale single cell. Use of the technique is demonstrated by generating sample results for a model of a Proton Exchange Membrane Fuel Cell (PEMFC) stack consisting of 125 cells each with an active area of 150 cm{sup 2}. A PEMFC stack was also used in the verification investigation. This stack consisted of four cells, each with an active area of 50 cm{sup 2}. Results from the verification investigation indicate that models developed using the technique are capable of accurately predicting fuel cell stack performance. (orig.)

  17. Student Perceptions of the Cell Biology Laboratory Learning Environment in Four Undergraduate Science Courses in Spain

    Science.gov (United States)

    De Juan, Joaquin; Pérez-Cañaveras, Rosa M.; Segovia, Yolanda; Girela, Jose Luis; Martínez-Ruiz, Noemi; Romero-Rameta, Alejandro; Gómez-Torres, Maria José; Vizcaya-Moreno, M. Flores

    2016-01-01

    Cell biology is an academic discipline that organises and coordinates the learning of the structure, function and molecular composition of cells in some undergraduate biomedical programs. Besides course content and teaching methodologies, the laboratory environment is considered a key element in the teaching of and learning of cell biology. The…

  18. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova

    2011-08-01

    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  19. Biology learning evaluation model in Senior High Schools

    Directory of Open Access Journals (Sweden)

    Sri Utari

    2017-06-01

    Full Text Available The study was to develop a Biology learning evaluation model in senior high schools that referred to the research and development model by Borg & Gall and the logic model. The evaluation model included the components of input, activities, output and outcomes. The developing procedures involved a preliminary study in the form of observation and theoretical review regarding the Biology learning evaluation in senior high schools. The product development was carried out by designing an evaluation model, designing an instrument, performing instrument experiment and performing implementation. The instrument experiment involved teachers and Students from Grade XII in senior high schools located in the City of Yogyakarta. For the data gathering technique and instrument, the researchers implemented observation sheet, questionnaire and test. The questionnaire was applied in order to attain information regarding teacher performance, learning performance, classroom atmosphere and scientific attitude; on the other hand, test was applied in order to attain information regarding Biology concept mastery. Then, for the analysis of instrument construct, the researchers performed confirmatory factor analysis by means of Lisrel 0.80 software and the results of this analysis showed that the evaluation instrument valid and reliable. The construct validity was between 0.43-0.79 while the reliability of measurement model was between 0.88-0.94. Last but not the least, the model feasibility test showed that the theoretical model had been supported by the empirical data.

  20. Modeling of biological intelligence for SCM system optimization.

    Science.gov (United States)

    Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

    2012-01-01

    This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  1. Modeling of Biological Intelligence for SCM System Optimization

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

    Full Text Available This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  2. Modeling of Biological Intelligence for SCM System Optimization

    Science.gov (United States)

    Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

    2012-01-01

    This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms. PMID:22162724

  3. Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime.

  4. Modelos experimentais em oncologia: O contributo da cultura de células para o conhecimento da biologia do cancro Experimental models in oncology: Contribution of cell culture on understanding the biology of cancer

    Directory of Open Access Journals (Sweden)

    Mariana Cruz

    2009-08-01

    Full Text Available A cultura de tecidos surgiu no século xx (Harrison, 1907 para estudar o comportamento das células animais em ambiente homeostático e em situações de stress. A capacidade de estudar as células a nível molecular relaciona-se com a forma como as células podem crescer e ser manipuladas em laboratório. A cultura de células in vitro permitiu estudar crescimento, diferenciação e morte celular e efectuar manipulações genéticas necessárias ao perfeito conhecimento da estrutura e funções dos genes. A cultura de células estaminais humanas veio colmatar algumas limitações inerentes aos restantes modelos de cultura. Ao que parece, as células estaminais cancerígenas mantêm-se quiescentes nos locais metastáticos até serem activadas por sinais apropriados do microambiente. Vários estudos revelaram que diferentes tipos de cancros podem surgir da transformação maligna de células estaminais. A eliminação destas células progenitoras tumorais é essencial para o desenvolvimento de novas abordagens terapêuticas mais eficazes em cancros agressivos. Por outro lado, a utilização de células dendríticas modificadas em cultura poderá contribuir para a produção de uma potencial vacina terapêutica eficaz para obter a regressão tumoral.In the beginning of the 20th century, tissue culture was started with the aim of studying the behaviour of animal cells in normal and stress conditions. The cell study at molecular level depends on their capacity of growing and how they can be manipulated in laboratory. In vitro cell culture allows us the possibility of studying biological key processes, such as growth, differentiation and cell death, and also to do genetic manipulations essential to the knowledge of structure and genes function. Human stem cells culture provides strategies to circumvent other models’ deficiencies. It seems that cancer stem cells remain quiescent until activation by appropriated micro-environmental stimulation

  5. Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

    Directory of Open Access Journals (Sweden)

    Matthew J Robertson

    Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

  6. Generative models versus underlying symmetries to explain biological pattern.

    Science.gov (United States)

    Frank, S A

    2014-06-01

    Mathematical models play an increasingly important role in the interpretation of biological experiments. Studies often present a model that generates the observations, connecting hypothesized process to an observed pattern. Such generative models confirm the plausibility of an explanation and make testable hypotheses for further experiments. However, studies rarely consider the broad family of alternative models that match the same observed pattern. The symmetries that define the broad class of matching models are in fact the only aspects of information truly revealed by observed pattern. Commonly observed patterns derive from simple underlying symmetries. This article illustrates the problem by showing the symmetry associated with the observed rate of increase in fitness in a constant environment. That underlying symmetry reveals how each particular generative model defines a single example within the broad class of matching models. Further progress on the relation between pattern and process requires deeper consideration of the underlying symmetries. © 2014 The Author. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  7. A framework to establish credibility of computational models in biology.

    Science.gov (United States)

    Patterson, Eann A; Whelan, Maurice P

    2017-10-01

    Computational models in biology and biomedical science are often constructed to aid people's understanding of phenomena or to inform decisions with socioeconomic consequences. Model credibility is the willingness of people to trust a model's predictions and is often difficult to establish for computational biology models. A 3 × 3 matrix has been proposed to allow such models to be categorised with respect to their testability and epistemic foundation in order to guide the selection of an appropriate process of validation to supply evidence to establish credibility. Three approaches to validation are identified that can be deployed depending on whether a model is deemed untestable, testable or lies somewhere in between. In the latter two cases, the validation process involves the quantification of uncertainty which is a key output. The issues arising due to the complexity and inherent variability of biological systems are discussed and the creation of 'digital twins' proposed as a means to alleviate the issues and provide a more robust, transparent and traceable route to model credibility and acceptance. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Natural crayfish clone as emerging model for various biological ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 36; Issue 2. Marmorkrebs: Natural crayfish clone as emerging model for various biological disciplines. Günter Vogt. Mini-review Volume 36 Issue 2 June 2011 pp 377-382. Fulltext. Click here to view fulltext PDF. Permanent link:

  9. Learning through Creating Robotic Models of Biological Systems

    Science.gov (United States)

    Cuperman, Dan; Verner, Igor M.

    2013-01-01

    This paper considers an approach to studying issues in technology and science, which integrates design and inquiry activities towards creating and exploring technological models of scientific phenomena. We implemented this approach in a context where the learner inquires into a biological phenomenon and develops its representation in the form of a…

  10. Model calculations of nuclear data for biologically-important elements

    International Nuclear Information System (INIS)

    Chadwick, M.B.; Blann, M.; Reffo, G.; Young, P.G.

    1994-05-01

    We describe calculations of neutron-induced reactions on carbon and oxygen for incident energies up to 70 MeV, the relevant clinical energy in radiation neutron therapy. Our calculations using the FKK-GNASH, GNASH, and ALICE codes are compared with experimental measurements, and their usefulness for modeling reactions on biologically-important elements is assessed

  11. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  12. Part 6: Modelling of simultaneous chemical-biological P removal ...

    African Journals Online (AJOL)

    drinie

    approaches taken in modelling the chemical P removal processes. In the literature .... to 2 mgP/l) for an iron dose of ~1 to 10 mg/l as Fe - refer to dashed line in Fig. 1). ...... systems exhibiting biological enhanced phosphate removal. Part 3:.

  13. Universally sloppy parameter sensitivities in systems biology models.

    Directory of Open Access Journals (Sweden)

    Ryan N Gutenkunst

    2007-10-01

    Full Text Available Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring in vivo biochemical parameters is difficult, and collectively fitting them to other experimental data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a "sloppy" spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our growth-factor-signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.

  14. Universally sloppy parameter sensitivities in systems biology models.

    Science.gov (United States)

    Gutenkunst, Ryan N; Waterfall, Joshua J; Casey, Fergal P; Brown, Kevin S; Myers, Christopher R; Sethna, James P

    2007-10-01

    Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring in vivo biochemical parameters is difficult, and collectively fitting them to other experimental data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a "sloppy" spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our growth-factor-signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.

  15. MEMFASILITASI HIGHER ORDER TIHINKING SKILLS DALAM PERKULIAHAN BIOLOGI SEL MELALUI MODEL INTEGRASI ATRIBUT ASESMEN FORMATIF

    Directory of Open Access Journals (Sweden)

    Sigit Saptono

    2017-10-01

    Full Text Available ABSTRACTHigher order thinking skills are needed to understand the problem and the essence of the lecture material Biology Sel. Study design Research and Development aims to develop reasoning skills and analytic thinking biology student teachers through the application of learning models Integration Attributes Formative Assessment (IAAF. Some 61 students of Biology Education Semarang State University who is doing his third semester courses Cell Biology is the subject of research. Analytical reasoning and  thinking ability of students is measured through individual assignments, group assignments concept map creation and preparation of the Review articles, and 30 items about the shape of the selected response and constructed response questions, validated questions. The result showed that the ability of reasoning and analytical thinking of students can be expanded significantly, although the development of the ability of argumentation, one category of analytic thinking skills, they need serious attention.

  16. Dielectric properties of biological tissues in which cells are connected by communicating junctions

    International Nuclear Information System (INIS)

    Asami, Koji

    2007-01-01

    The frequency dependence of the complex permittivity of biological tissues has been simulated using a simple model that is a cubic array of spherical cells in a parallel plate capacitor. The cells are connected by two types of communicating junctions: one is a membrane-lined channel for plasmodesmata in plant tissues, and the other is a conducting patch of adjoining plasma membranes for gap junctions in animal tissues. Both junctions provided similar effects on the dielectric properties of the tissue model. The model without junction showed a dielectric relaxation (called β-dispersion) that was expected from an interfacial polarization theory for a concentrated suspension of spherical cells. The dielectric relaxation was the same as that of the model in which neighbouring cells were connected by junctions perpendicular to the applied electric field. When neighbouring cells were connected by junctions parallel to the applied electric field or in all directions, a dielectric relaxation appeared at a lower frequency side in addition to the β-dispersion, corresponding to the so called α-dispersion. When junctions were randomly introduced at varied probabilities P j , the low-frequency (LF) relaxation curve became broader, especially at P j of 0.2-0.5, and its intensity was proportional to P j up to 0.7. The intensity and the characteristic frequency of the LF relaxation both decreased with decreasing junction conductance. The simulations indicate that communicating junctions are important for understanding the LF dielectric relaxation in tissues

  17. Dielectric properties of biological tissues in which cells are connected by communicating junctions

    Science.gov (United States)

    Asami, Koji

    2007-06-01

    The frequency dependence of the complex permittivity of biological tissues has been simulated using a simple model that is a cubic array of spherical cells in a parallel plate capacitor. The cells are connected by two types of communicating junctions: one is a membrane-lined channel for plasmodesmata in plant tissues, and the other is a conducting patch of adjoining plasma membranes for gap junctions in animal tissues. Both junctions provided similar effects on the dielectric properties of the tissue model. The model without junction showed a dielectric relaxation (called β-dispersion) that was expected from an interfacial polarization theory for a concentrated suspension of spherical cells. The dielectric relaxation was the same as that of the model in which neighbouring cells were connected by junctions perpendicular to the applied electric field. When neighbouring cells were connected by junctions parallel to the applied electric field or in all directions, a dielectric relaxation appeared at a lower frequency side in addition to the β-dispersion, corresponding to the so called α-dispersion. When junctions were randomly introduced at varied probabilities Pj, the low-frequency (LF) relaxation curve became broader, especially at Pj of 0.2-0.5, and its intensity was proportional to Pj up to 0.7. The intensity and the characteristic frequency of the LF relaxation both decreased with decreasing junction conductance. The simulations indicate that communicating junctions are important for understanding the LF dielectric relaxation in tissues.

  18. Computer modeling in developmental biology: growing today, essential tomorrow.

    Science.gov (United States)

    Sharpe, James

    2017-12-01

    D'Arcy Thompson was a true pioneer, applying mathematical concepts and analyses to the question of morphogenesis over 100 years ago. The centenary of his famous book, On Growth and Form , is therefore a great occasion on which to review the types of computer modeling now being pursued to understand the development of organs and organisms. Here, I present some of the latest modeling projects in the field, covering a wide range of developmental biology concepts, from molecular patterning to tissue morphogenesis. Rather than classifying them according to scientific question, or scale of problem, I focus instead on the different ways that modeling contributes to the scientific process and discuss the likely future of modeling in developmental biology. © 2017. Published by The Company of Biologists Ltd.

  19. Illuminating cell signaling: Using Vibrio harveyi in an introductory biology laboratory.

    Science.gov (United States)

    Hrizo, Stacy L; Kaufmann, Nancy

    2009-05-01

    Cell signaling is an essential cellular process that is performed by all living organisms. Bacteria communicate with each other using a chemical language in a signaling pathway that allows bacteria to evaluate the size of their population, determine when they have reached a critical mass (quorum sensing), and then change their behavior in unison to carry out processes that require many cells acting together to be effective. Here, we describe a laboratory exercise in which the students observe the induction of bioluminescence or light production as an output of the quorum sensing pathway in Vibrio harveyi. Using both wildtype and mutant bacterial strains they explore the induction of community behavior via cell-cell communication by determining whether there is a correlation between the density of the bacterial population and the production of light by the bacterial culture. Using data from a cross-feeding assay the students make predictions about the identity of their strains and directly test these predictions using conditioned media from various liquid cultures. This two part exercise is designed for an introductory biology course to begin familiarizing students with collecting data, making predictions based upon the data and directly testing their hypotheses using a model organism with a cell signaling pathway that has a simple visual output: light production. Copyright © 2009 International Union of Biochemistry and Molecular Biology, Inc.

  20. Estimation of relative biological effectiveness for low energy protons using cytogenetic end points in mammalian cells

    International Nuclear Information System (INIS)

    Bhat, N.N.; Nairy, Rajesh; Chaurasia, Rajesh; Desai, Utkarsha; Shirsath, K.B.; Anjaria, K.B.; Sreedevi, B.

    2013-01-01

    A facility has been designed and developed to facilitate irradiation of biological samples to proton beam using folded tandem ion accelerator (FOTIA) at BARC. The primary proton beam from the accelerator was diffused using gold foil and channelled through a drift tube. Scattered beam was monitored and calibrated. Uniformity and dosimetry studies were conducted to calibrate the setup for precise irradiation of mammalian cells. Irradiation conditions and geometry were optimized for mammalian cells and other biological samples in thin layer. The irradiation facility is housed in a clean air laminar flow to help exposure of samples in aseptic conditions. The set up has been used for studying various radiobiological endpoints in many biological model systems. CHO, MCF-7, A-549 and INT-407 cell lines were studied in the present investigation using micronucleus (MN) induction as an indicator of radiation damage. The mammalian cells grown on petri plates to about 40 % confluence (log phase) were exposed to proton beam of known doses in the range of 0.1 to 2 Gy. The dose estimation was done based on specific ionization in cell medium. Studies were also conducted using 60 Co gamma radiation to compare the results. Linear quadratic response was observed for all the cell lines when exposed to 60 Co gamma radiation. In contrast, linear response was observed for proton beam. In addition, very significant increase in the MN yield was observed for proton beam compared to 60 Co gamma radiation. Estimated α and β values for CHO cells is found to be 0.02±0.003 Gy-1 and 0.042±0.006 Gy-2 respectively for 60 Co gamma radiation. For proton beam, estimated α for linear fit is found to be 0.37±0.011 Gy-1. Estimated RBE was found to be in the range of 4-8 for all the cell lines and dose ranges studied. In conclusion, the proton irradiation facility developed for mammalian cells has helped to study various radiobiological endpoints. In this presentation, facility description, MN as

  1. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    Science.gov (United States)

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  2. Oral cancer cells with different potential of lymphatic metastasis displayed distinct biologic behaviors and gene expression profiles.

    Science.gov (United States)

    Zhuang, Zhang; Jian, Pan; Longjiang, Li; Bo, Han; Wenlin, Xiao

    2010-02-01

    Oral squamous cell carcinoma (OSCC) often spreads from the primary tumor to regional lymph nodes in the early stage. Better understanding of the biology of lymphatic spread of oral cancer cells is important for improving the survival rate of cancer patients. We established the cell line LNMTca8113 by repeated injections in foot pads of nude mice, which had a much higher lymphatic metastasis rate than its parental cell line Tca8113. Then, we compared the biologic behaviors of cancer cells between them. Moreover, microarray-based expression profiles between them were also compared, and a panel of differential genes was validated using real-time-PCR. In contrast to Tca8113 cells, LNMTca8113 cells were more proliferative and resistant to apoptosis in the absence of serum, and had enhanced ability of inducing capillary-like structures. Moreover, microarray-based expression profiles between them identified 1341 genes involved in cell cycle, cell adhesion, lymphangiogenesis, regulation of apoptosis, and so on. Some genes dedicating to the metastatic potential, including JAM2, TNC, CTSC, LAMB1, VEGFC, HAPLN1, ACPP, GDF9 and FGF11, were upregulated in LNMTca8113 cells. These results suggested that LNMTca8113 and Tca8113 cells were proper models for lymphatic metastasis study because there were differences in biologic behaviors and metastasis-related genes between them. Additionally, the differentially expressed gene profiles in cancer progression may be helpful in exploring therapeutic targets and provide the foundation for further functional validation of these specific candidate genes for OSCC.

  3. Simulations of living cell origins using a cellular automata model.

    Science.gov (United States)

    Ishida, Takeshi

    2014-04-01

    Understanding the generalized mechanisms of cell self-assembly is fundamental for applications in various fields, such as mass producing molecular machines in nanotechnology. Thus, the details of real cellular reaction networks and the necessary conditions for self-organized cells must be elucidated. We constructed a 2-dimensional cellular automata model to investigate the emergence of biological cell formation, which incorporated a looped membrane and a membrane-bound information system (akin to a genetic code and gene expression system). In particular, with an artificial reaction system coupled with a thermal system, the simultaneous formation of a looped membrane and an inner reaction process resulted in a more stable structure. These double structures inspired the primitive biological cell formation process from chemical evolution stage. With a model to simulate cellular self-organization in a 2-dimensional cellular automata model, 3 phenomena could be realized: (1) an inner reaction system developed as an information carrier precursor (akin to DNA); (2) a cell border emerged (akin to a cell membrane); and (3) these cell structures could divide into 2. This double-structured cell was considered to be a primary biological cell. The outer loop evolved toward a lipid bilayer membrane, and inner polymeric particles evolved toward precursor information carriers (evolved toward DNA). This model did not completely clarify all the necessary and sufficient conditions for biological cell self-organization. Further, our virtual cells remained unstable and fragile. However, the "garbage bag model" of Dyson proposed that the first living cells were deficient; thus, it would be reasonable that the earliest cells were more unstable and fragile than the simplest current unicellular organisms.

  4. When nano meets stem: the impact of nanotechnology in stem cell biology.

    Science.gov (United States)

    Kaur, Savneet; Singhal, Barkha

    2012-01-01

    Nanotechnology and biomedical treatments using stem cells are among the latest conduits of biotechnological research. Even more recently, scientists have begun finding ways to mate these two specialties of science. The advent of nanotechnology has paved the way for an explicit understanding of stem cell therapy in vivo and by recapitulation of such in vivo environments in the culture, this technology seems to accommodate a great potential in providing new vistas to stem cell research. Nanotechnology carries in its wake, the development of highly stable, efficient and specific gene delivery systems for both in vitro and in vivo genetic engineering of stem cells, use of nanoscale systems (such as microarrays) for investigation of gene expression in stem cells, creation of dynamic three-dimensional nano-environments for in vitro and in vivo maintenance and differentiation of stem cells and development of extremely sensitive in vivo detection systems to gain insights into the mechanisms of stem cell differentiation and apoptosis in different disease models. The present review presents an overview of the current applications and future prospects for the use of nanotechnology in stem cell biology. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  5. Redefining plant systems biology: from cell to ecosystem

    NARCIS (Netherlands)

    Keurentjes, J.J.B.; Angenent, G.C.; Dicke, M.; Martins Dos Santos, V.A.P.; Molenaar, J.; Van der Putten, W.H.; de Ruiter, P.C.; Struik, P.C.; Thomma, B.P.H.J.

    2011-01-01

    Molecular biologists typically restrict systems biology to cellular levels. By contrast, ecologists define biological systems as communities of interacting individuals at different trophic levels that process energy, nutrient and information flows. Modern plant breeding needs to increase

  6. Methods and models in mathematical biology deterministic and stochastic approaches

    CERN Document Server

    Müller, Johannes

    2015-01-01

    This book developed from classes in mathematical biology taught by the authors over several years at the Technische Universität München. The main themes are modeling principles, mathematical principles for the analysis of these models, and model-based analysis of data. The key topics of modern biomathematics are covered: ecology, epidemiology, biochemistry, regulatory networks, neuronal networks, and population genetics. A variety of mathematical methods are introduced, ranging from ordinary and partial differential equations to stochastic graph theory and  branching processes. A special emphasis is placed on the interplay between stochastic and deterministic models.

  7. Model fit versus biological relevance: Evaluating photosynthesis-temperature models for three tropical seagrass species

    OpenAIRE

    Matthew P. Adams; Catherine J. Collier; Sven Uthicke; Yan X. Ow; Lucas Langlois; Katherine R. O’Brien

    2017-01-01

    When several models can describe a biological process, the equation that best fits the data is typically considered the best. However, models are most useful when they also possess biologically-meaningful parameters. In particular, model parameters should be stable, physically interpretable, and transferable to other contexts, e.g. for direct indication of system state, or usage in other model types. As an example of implementing these recommended requirements for model parameters, we evaluat...

  8. Quantitative computational models of molecular self-assembly in systems biology.

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-05-23

    Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

  9. CelOWS: an ontology based framework for the provision of semantic web services related to biological models.

    Science.gov (United States)

    Matos, Ely Edison; Campos, Fernanda; Braga, Regina; Palazzi, Daniele

    2010-02-01

    The amount of information generated by biological research has lead to an intensive use of models. Mathematical and computational modeling needs accurate description to share, reuse and simulate models as formulated by original authors. In this paper, we introduce the Cell Component Ontology (CelO), expressed in OWL-DL. This ontology captures both the structure of a cell model and the properties of functional components. We use this ontology in a Web project (CelOWS) to describe, query and compose CellML models, using semantic web services. It aims to improve reuse and composition of existent components and allow semantic validation of new models.

  10. Differential biological effects of iodoacetate in mammalian cell lines; radio sensitization and radio protection

    International Nuclear Information System (INIS)

    Yadav, Usha; Anjaria, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Shirsath, K.B.; Bhat, Nagesh N.; Balakrishnan, Sreedevi; Sapra, B.K.; Nairy, Rajesha

    2014-01-01

    There are several studies where it has been shown that Iodoacetate (IA) possesses in vivo anti-tumor activity. The fact that it is a model glycolytic inhibitor makes it more interesting. As seen in recent trends, glycolytic inhibitors are emerging as new strategy for cancer therapeutic research taking advantage of glycolytic phenotype of cancerous tissues. IA has been reported to have radioprotective effects in yeast cells and human lymphocytes. Biological effects of IA in response to radiation in mammalian cell lines are not well documented. We screened IA for cytotoxicity using clonogenic assay at different concentrations ranging from 0.1 to 2.5 μg/ml using three different mammalian cell lines; A-549 (human lung carcinoma cell line), MCF-7 (human mammary cancer cell line) and a noncancerous CHO (Chinese hamster ovary cell line). For studying radioprotective/radio sensitizing efficacy, cells were exposed to 4 Gy of 60 Co-γ radiation using a teletherapy source at a dose rate of 1 Gy/min, following which IA post-treatment was carried out. Clonogenic and micronucleus assay were performed to assess radioprotection/sensitization. The results indicated that IA was highly cytotoxic in cancerous cell lines A-549 (IC 50 =1.25 μg/ml) and MCF-7 (IC 50 = 1.9 μg/ml). In contrast, it was totally non-toxic in non-cancerous cell line, viz. CHO, in the same concentration range. In addition, IA exhibited radio protective effect in CHO cell line, whereas in other two cancer cell lines, viz. A-549 and MCF-7, radio sensitizing effect was seen as judged by induction of cell killing and micronuclei. In conclusion, lA, a model glycolytic inhibitor, was found to be selectively cytotoxic in cancer cells as compared to normal cells. Further, it reduced radiation induced damage (micronuclei and cell killing) in normal cells but increased it in cancer cells indicating its potential use in cancer therapy. (author)

  11. Green Algae as Model Organisms for Biological Fluid Dynamics

    Science.gov (United States)

    Goldstein, Raymond E.

    2015-01-01

    In the past decade, the volvocine green algae, spanning from the unicellular Chlamydomonas to multicellular Volvox, have emerged as model organisms for a number of problems in biological fluid dynamics. These include flagellar propulsion, nutrient uptake by swimming organisms, hydrodynamic interactions mediated by walls, collective dynamics and transport within suspensions of microswimmers, the mechanism of phototaxis, and the stochastic dynamics of flagellar synchronization. Green algae are well suited to the study of such problems because of their range of sizes (from 10 μm to several millimeters), their geometric regularity, the ease with which they can be cultured, and the availability of many mutants that allow for connections between molecular details and organism-level behavior. This review summarizes these recent developments and highlights promising future directions in the study of biological fluid dynamics, especially in the context of evolutionary biology, that can take advantage of these remarkable organisms.

  12. Biological interaction of living cells with COSAN-based synthetic vesicles.

    Science.gov (United States)

    Tarrés, Màrius; Canetta, Elisabetta; Paul, Eleanor; Forbes, Jordan; Azzouni, Karima; Viñas, Clara; Teixidor, Francesc; Harwood, Adrian J

    2015-01-15

    Cobaltabisdicarbollide (COSAN) [3,3'-Co(1,2-C2B9H11)2](-), is a complex boron-based anion that has the unusual property of self-assembly into membranes and vesicles. These membranes have similar dimensions to biological membranes found in cells, and previously COSAN has been shown to pass through synthetic lipid membranes and those of living cells without causing breakdown of membrane barrier properties. Here, we investigate the interaction of this inorganic membrane system with living cells. We show that COSAN has no immediate effect on cell viability, and cells fully recover when COSAN is removed following exposure for hours to days. COSAN elicits a range of cell biological effects, including altered cell morphology, inhibition of cell growth and, in some cases, apoptosis. These observations reveal a new biology at the interface between inorganic, synthetic COSAN membranes and naturally occurring biological membranes.

  13. Programming biological models in Python using PySB.

    Science.gov (United States)

    Lopez, Carlos F; Muhlich, Jeremy L; Bachman, John A; Sorger, Peter K

    2013-01-01

    Mathematical equations are fundamental to modeling biological networks, but as networks get large and revisions frequent, it becomes difficult to manage equations directly or to combine previously developed models. Multiple simultaneous efforts to create graphical standards, rule-based languages, and integrated software workbenches aim to simplify biological modeling but none fully meets the need for transparent, extensible, and reusable models. In this paper we describe PySB, an approach in which models are not only created using programs, they are programs. PySB draws on programmatic modeling concepts from little b and ProMot, the rule-based languages BioNetGen and Kappa and the growing library of Python numerical tools. Central to PySB is a library of macros encoding familiar biochemical actions such as binding, catalysis, and polymerization, making it possible to use a high-level, action-oriented vocabulary to construct detailed models. As Python programs, PySB models leverage tools and practices from the open-source software community, substantially advancing our ability to distribute and manage the work of testing biochemical hypotheses. We illustrate these ideas using new and previously published models of apoptosis.

  14. The binding, transport and fate of aluminium in biological cells.

    Science.gov (United States)

    Exley, Christopher; Mold, Matthew J

    2015-04-01

    Aluminium is the most abundant metal in the Earth's crust and yet, paradoxically, it has no known biological function. Aluminium is biochemically reactive, it is simply that it is not required for any essential process in extant biota. There is evidence neither of element-specific nor evolutionarily conserved aluminium biochemistry. This means that there are no ligands or chaperones which are specific to its transport, there are no transporters or channels to selectively facilitate its passage across membranes, there are no intracellular storage proteins to aid its cellular homeostasis and there are no pathways which evolved to enable the metabolism and excretion of aluminium. Of course, aluminium is found in every compartment of every cell of every organism, from virus through to Man. Herein we have investigated each of the 'silent' pathways and metabolic events which together constitute a form of aluminium homeostasis in biota, identifying and evaluating as far as is possible what is known and, equally importantly, what is unknown about its uptake, transport, storage and excretion. Copyright © 2014 Elsevier GmbH. All rights reserved.

  15. Development and Implementation of Biological Circuits Using Excitable and Non-Excitable Cells

    Energy Technology Data Exchange (ETDEWEB)

    Casasnovas-Orus, V.; Gomez-Cid, L.; Hernandez-Romero, I.; Fuentes, L.; Guillem, M.S.; Atienza, F.; Fernandez-Aviles, F.; Climent, A.M.

    2016-07-01

    Compared to conventional computation systems, living beings require reduced power and raw materials consumption, inviting to explore the concept of biological circuits. In this project, a proof-of-concept of logical biocircuits using cell patterns has been developed. These were based upon differential ionic communication between cells, being the cells types used excitable and non-excitable, modeled by cardiomyocytes and fibroblasts correspondingly. To begin, patterns for the basic logic computation blocks were designed, including the OR gate, AND gate and logic memory. The designs were evaluated with mathematical models and in vitro experiments. Results of mathematical modeling indicated that theoretical approval of the biocircuit function. Regarding in vitro biocircuit implementation, three different selective cell localization techniques proved useful for the pattern creation. Evaluation with optical mapping confirmed the operation of the OR gate and logic memory. More resolution in the cell placement strategy will be needed to observe the proper AND gate operation. Thus, fine-tuning of the implementation process will enable the construction of more complex biocircuits that will take on clinical applications relating to electric stimulation of tissues and programmed drug delivery. (Author)

  16. Transcriptomic signatures shaped by cell proportions shed light on comparative developmental biology

    Czech Academy of Sciences Publication Activity Database

    Pantalacci, S.; Gueguen, L.; Petit, C.; Lambert, A.; Peterková, Renata; Sémon, E.

    2017-01-01

    Roč. 18, feb (2017), s. 29 ISSN 1474-760X R&D Projects: GA ČR(CZ) GB14-37368G Institutional support: RVO:68378041 Keywords : comparative transcriptomics * developmental biology * transcriptomic signature Subject RIV: EA - Cell Biology OBOR OECD: Developmental biology Impact factor: 11.908, year: 2016

  17. WWW.Cell Biology Education: Using the World Wide Web to Develop a New Teaching Topic

    Science.gov (United States)

    Blystone, Robert V.; MacAlpine, Barbara

    2005-01-01

    "Cell Biology Education" calls attention each quarter to several Web sites of educational interest to the biology community. The Internet provides access to an enormous array of potential teaching materials. In this article, the authors describe one approach for using the World Wide Web to develop a new college biology laboratory exercise. As a…

  18. Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Xihang Chen

    2018-01-01

    Full Text Available Autophagy is a highly conserved cellular process that degrades modified, surplus, or harmful cytoplasmic components by sequestering them in autophagosomes which then fuses with the lysosome for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis, as well as for remodeling during normal development. Impairment of this process has been implicated in various diseases, in the pathogenic response to bacterial and viral infections, and in aging. Pluripotent stem cells, with their ability to self-replicate and to give rise to any specialized cell type, are very valuable resources for cell-based medical therapies and open a number of promising avenues for studying human development and disease. It has been suggested that autophagy is vital for the maintenance of cellular homeostasis in stem cells, and subsequently more in-depth knowledge about the regulation of autophagy in stem cell biology has been acquired recently. In this review, we describe the most significant advances in the understanding of autophagy regulation in hematopoietic and mesenchymal stem cells, as well as in induced pluripotent stem cells. In particular, we highlight the roles of various autophagy activities in the regulation of self-renewal and differentiation of these stem cells.

  19. Action of radiations on some biological model systems. Technical progress report, 1 October 1975--1 June 1976

    International Nuclear Information System (INIS)

    Stein, G.

    1976-01-01

    Work during the period 1st October 1975 to 1st June 1976 is reviewed. The topics investigated include: investigation of the action of ionizing radiation on enzyme proteins, using the technique of pulse rdiolysis; the use of fast nanosecond laser pulse techniques in the study of biochemical and biological model systems; and the action of ionizing radiation on mammalian cells, particularly at low doses. Using chromatin as the model substance, radiation biological processes at the nucleoprotein level were investigated

  20. UML as a cell and biochemistry modeling language.

    Science.gov (United States)

    Webb, Ken; White, Tony

    2005-06-01

    The systems biology community is building increasingly complex models and simulations of cells and other biological entities, and are beginning to look at alternatives to traditional representations such as those provided by ordinary differential equations (ODE). The lessons learned over the years by the software development community in designing and building increasingly complex telecommunication and other commercial real-time reactive systems, can be advantageously applied to the problems of modeling in the biology domain. Making use of the object-oriented (OO) paradigm, the unified modeling language (UML) and Real-Time Object-Oriented Modeling (ROOM) visual formalisms, and the Rational Rose RealTime (RRT) visual modeling tool, we describe a multi-step process we have used to construct top-down models of cells and cell aggregates. The simple example model described in this paper includes membranes with lipid bilayers, multiple compartments including a variable number of mitochondria, substrate molecules, enzymes with reaction rules, and metabolic pathways. We demonstrate the relevance of abstraction, reuse, objects, classes, component and inheritance hierarchies, multiplicity, visual modeling, and other current software development best practices. We show how it is possible to start with a direct diagrammatic representation of a biological structure such as a cell, using terminology familiar to biologists, and by following a process of gradually adding more and more detail, arrive at a system with structure and behavior of arbitrary complexity that can run and be observed on a computer. We discuss our CellAK (Cell Assembly Kit) approach in terms of features found in SBML, CellML, E-CELL, Gepasi, Jarnac, StochSim, Virtual Cell, and membrane computing systems.