WorldWideScience

Sample records for modeling cell biology

  1. Spatial Modeling Tools for Cell Biology

    Science.gov (United States)

    2006-10-01

    of the cells total volume. The cytosol contains thousands of enzymes that are responsible for the catalyzation of glycolysis and gluconeogenesis ... dog , swine and pig models [Pantely, 1990, 1991; Stanley 1992]. In these studies, blood flow through the left anterior descending (LAD) coronary...perfusion. In conclusion, even thought our model falls within the (rather large) error bounds of experimental dog , pig and swine models, the

  2. Systems modelling and the development of coherent cell biological knowledge

    NARCIS (Netherlands)

    Verhoeff, R.; Waarlo, A.J.; Boersma, K.T.

    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 freeliving

  3. 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.

  4. 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...

  5. 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.

  6. Theories and models on the Biology of Cells in Space

    Science.gov (United States)

    Todd, P.; Klaus, D. M.

    A wide variety of observations on cells in space, admittedly made under constraining and unnatural conditions in many 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 the symposium on ``Theories and Models on the Biology of Cells in Space'' are dedicated to the subject of theplausibility of cellular responses to gravity -- inertial accelerations between 0 and 9.8 m/s^2 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.

  7. 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.

  8. 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…

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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…

  15. 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.

  16. 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

  17. 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

  18. [Biological characteristics of an established model of ovarian cancer in mice and its homologous cell lines].

    Science.gov (United States)

    Zhang, Zheng-Mao; Zhang, Chao; Zhang, Feng-Hua; Shan, Bao-En; Nakagawa, Shinsaku

    2006-06-01

    There are no specific methods for early diagnosis of ovarian cancer, recurrence prevention and drug-resistance. The experimental mouse model of ovarian cancer could help to reveal the biological and genetic features of ovarian cancer, and provide rational basis for further intervention strategy. This study was to establish a model of ovarian cancer in mice and homologous cell line, and analyze its biological characteristics. Ovarian cancer was developed in 8-week-old female F1 (C57BL/6N x C3H/He) mice by a single whole-body neutron irradiation of 2.7 Gy from a (252)Cf source. A metastatic cell line was established through serial subcutaneous transplantation of the primary tumor for 11 generations, and then tumor cells were transferred to in vitro cultivation. These cells were cloned for more than 6 months. The biological characteristics of the tumors and the homologous cell line were determined by cellular and molecular biological techniques. The grafted tumors in mice were successively passaged for 11 generations with a successful inoculation rate of 96% during 23 months. A tumor cell line OV99 isolated from the grafted tumors was established after 6 months and grew steadily. Morphologic characters and ultrastructures of OV99 cells were accorded with those of ovarian cancer epithelia. The chromosomal analysis of OV99 cells revealed aneuploid pattern of 76 chromosomes. Flow cytometry (FCM) and reverse transcription-polymerase chain reaction (RT-PCR) showed same features between OV99 cells and positive control ovarian cancer cell line OVHM, including distribution of cell cycle, rapid growth rate and the expression of P21, P185, P53, proliferating nuclear cell antigen (PCNA) and Cyclin D proteins, and MAGE-1 and MAGE-3 mRNA. Establishment of the ovarian carcinoma animal model in mice and OV99, a cell line owns biologic characteristics of ovarian cancer cells, provides experimental materials for further investigation of ovarian carcinoma.

  19. Proteomics-based systems biology modeling of bovine germinal vesicle stage oocyte and cumulus cell interaction.

    Directory of Open Access Journals (Sweden)

    Divyaswetha Peddinti

    Full Text Available BACKGROUND: Oocytes are the female gametes which establish the program of life after fertilization. Interactions between oocyte and the surrounding cumulus cells at germinal vesicle (GV stage are considered essential for proper maturation or 'programming' of oocytes, which is crucial for normal fertilization and embryonic development. However, despite its importance, little is known about the molecular events and pathways involved in this bidirectional communication. METHODOLOGY/PRINCIPAL FINDINGS: We used differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT on bovine GV oocyte and cumulus cells and identified 811 and 1247 proteins in GV oocyte and cumulus cells, respectively; 371 proteins were significantly differentially expressed between each cell type. Systems biology modeling, which included Gene Ontology (GO and canonical genetic pathway analysis, showed that cumulus cells have higher expression of proteins involved in cell communication, generation of precursor metabolites and energy, as well as transport than GV oocytes. Our data also suggests a hypothesis that oocytes may depend on the presence of cumulus cells to generate specific cellular signals to coordinate their growth and maturation. CONCLUSIONS/SIGNIFICANCE: Systems biology modeling of bovine oocytes and cumulus cells in the context of GO and protein interaction networks identified the signaling pathways associated with the proteins involved in cell-to-cell signaling biological process that may have implications in oocyte competence and maturation. This first comprehensive systems biology modeling of bovine oocytes and cumulus cell proteomes not only provides a foundation for signaling and cell physiology at the GV stage of oocyte development, but are also valuable for comparative studies of other stages of oocyte development at the molecular level.

  20. 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...

  1. 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.

  2. [Cell biology and cosmetology].

    Science.gov (United States)

    Traniello, S; Cavalletti, T

    1991-01-01

    Cellular biology can become the natural support of research in the field of cosmetics because it is able to provide alternative experimental models which can partially replace the massive use of laboratory animals. Cultures of human skin cells could be used in tests investigating irritation of the skin. We have developed an "in vitro" experimental model that allows to evaluate the damage caused by the free radicals to the fibroblasts in culture and to test the protective action of the lipoaminoacids. Experimenting on human cell cultures presents the advantage of eliminating the extrapolation between the different species, of allowing a determination of the biological action of a substance and of evaluating its dose/response effect. This does not mean that "in vitro" experimenting could completely replace experimenting on living animals, but the "in vitro" model can be introduced in the realisation of preliminary screenings.

  3. 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.

  4. Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Karig, David K [ORNL; Siuti, Piro [ORNL; Dar, Roy D. [University of Tennessee, Knoxville (UTK); Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL; Simpson, Michael L [ORNL

    2011-01-01

    Cells offer natural examples of highly efficient networks of nanomachines. Accordingly, both intracellular and intercellular communication mechanisms in nature are looked to as a source of inspiration and instruction for engineered nanocommunication. Harnessing biological functionality in this manner requires an interdisciplinary approach that integrates systems biology, synthetic biology, and nanofabrication. Recent years have seen the amassing of a tremendous wealth of data from the sequencing of new organisms and from high throughput expression experiments. At the same time, a deeper fundamental understanding of individual cell function has been developed, as exemplified by the growth of fields such as noise biology, which seeks to characterize the role of noise in gene expression. The availability of well characterized biological components coupled with a deeper understanding of cell function has led to efforts to engineer both living cells and to create bio-like functionality in non-living substrates in the field of synthetic biology. Here, we present a model system that exemplifies the synergism between these realms of research. We propose a synthetic gene network for operation in a nanofabricated cell mimic array that propagates a biomolecular signal over long distances using the phenomenon of stochastic resonance. Our system consists of a bacterial quorum sensing signal molecule, a bistable genetic switch triggered by this signal, and an array of nanofabricated cell mimic wells that contain the genetic system. An optimal level of noise in the system helps to propagate a time-varying AHL signal over long distances through the array of mimics. This noise level is determined both by the system volume and by the parameters of the genetic network. Our proposed genetically driven stochastic resonance system serves as a testbed for exploring the potential harnessing of gene expression noise to aid in the transmission of a time-varying molecular signal.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Untangling the Biology of Genetic Cardiomyopathies with Pluripotent Stem Cell Disease Models

    NARCIS (Netherlands)

    Buikema, Jan W; Wu, Sean M

    PURPOSE OF REVIEW: Recently, the discovery of strategies to reprogram somatic cells into induced pluripotent stem (iPS) cells has led to a major paradigm change in developmental and stem cell biology. The application of iPS cells and their cardiac progeny has opened novel directions to study

  11. 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

  12. 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.

  13. 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…

  14. 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

  15. 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.

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

    Science.gov (United States)

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

    2016-03-01

    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 H2O2. This artificial model system can provide a systemic means to elucidate the complex interactions between biological materials and non-thermal plasma.

  17. 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.

  18. 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.

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

    Science.gov (United States)

    Guerrier, C.; Holcman, D.

    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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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

  6. 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...... 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...... 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...

  7. 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.

  8. Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy.

    Science.gov (United States)

    Vicente-Dueñas, Carolina; Hauer, Julia; Ruiz-Roca, Lucía; Ingenhag, Deborah; Rodríguez-Meira, Alba; Auer, Franziska; Borkhardt, Arndt; Sánchez-García, Isidro

    2015-06-01

    Cancer is a clonal malignant disease originated in a single cell and characterized by the accumulation of partially differentiated cells that are phenotypically reminiscent of normal stages of differentiation. According to current models, therapeutic strategies that block oncogene activity are likely to selectively target tumor cells. However, recent evidences have revealed that cancer stem cells could arise through a tumor stem cell reprogramming mechanism, suggesting that genetic lesions that initiate the cancer process might be dispensable for tumor progression and maintenance. This review addresses the impact of these results toward a better understanding of cancer development and proposes new approaches to treat cancer in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Evaluation of cell tolerability of a series of lipoamino acids using biological membranes and a biomembrane model.

    Science.gov (United States)

    Pignatello, R; Noce, C; Campisi, A; Acquaviva, R; Bucolo, C; Puglisi, G; Toth, I

    2007-04-01

    The interaction of a series of amphiphilic 2-alkyl aminoacids (lipoamino acids, LAAs) with different cell cultures and biomembrane models was investigated. LAAs can be useful promoieties to modify the physico-chemical properties of many drugs, and in particular their lipophilicity. Tests were performed in vitro on mammalian cells (murine astrocytes) and human red blood cells (haemolysis), and in vivo on rabbit eye as alternative models to assess the tolerability or the potential damaging effects of these compounds on different biological systems. The mode of interaction of LAAs with pure phospholipid multilamellar liposomes, taken as a biomembrane model, was also analysed by differential scanning calorimetry experiments. Different tolerability/toxicity patterns were obtained in the various models; in particular, the most lipophilic terms of the series, methyl 2-aminohexadecanoate (LAA16), displayed haemolytic activity and toxicity for mouse astrocyte cultures. A specific assay confirmed that LAA16 acted at level of cell membranes, while neither any damaging effects on nucleus or apoptotic induction were observed. The shorter-chain LAAs and the tetradecyl homologue (LAA14) showed the best compatibility with the various cell models.

  10. Biological and microbial fuel cells

    OpenAIRE

    Scott, Keith; Yu, Eileen Hao; Ghangrekar, Makarand Madhao; Erable, Benjamin; Duţeanu, Narcis Mihai

    2012-01-01

    Biological fuel cells have attracted increasing interest in recent years because of their applications in environmental treatment, energy recovery, and small-scale power sources. Biological fuel cells are capable of producing electricity in the same way as a chemical fuel cell: there is a constant supply of fuel into the anode and a constant supply of oxidant into the cathode; however, typically the fuel is a hydrocarbon compound present in the wastewater, for example. Microbial fuel cells (M...

  11. Evaluation of the oscillatory interference model of grid cell firing through analysis and measured period variance of some biological oscillators.

    Directory of Open Access Journals (Sweden)

    Eric A Zilli

    2009-11-01

    Full Text Available Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models. Burak and Fiete (2009, PLoS Comput Biol recently examined noise in two continuous attractor models, but did not consider oscillatory interference models in detail. Here we analyze an oscillatory interference model to examine the effects of noise on its stability and spatial firing properties. We show analytically that the square of the drift in encoded position due to noise is proportional to time and inversely proportional to the number of oscillators. We also show there is a relatively fixed breakdown point, independent of many parameters of the model, past which noise overwhelms the spatial signal. Based on this result, we show that a pair of oscillators are expected to maintain a stable grid for approximately t = 5mu(3/(4pisigma(2 seconds where mu is the mean period of an oscillator in seconds and sigma(2 its variance in seconds(2. We apply this criterion to recordings of individual persistent spiking neurons in postsubiculum (dorsal presubiculum and layers III and V of entorhinal cortex, to subthreshold membrane potential oscillation recordings in layer II stellate cells of medial entorhinal cortex and to values from the literature regarding medial septum theta bursting cells. All oscillators examined have expected stability times far below those seen in experimental recordings of grid cells, suggesting the examined biological oscillators are unfit as a substrate for current implementations of oscillatory interference models. However, oscillatory interference models can tolerate small amounts of noise, suggesting the utility of circuit level effects which might reduce oscillator variability. Further implications for grid cell models are discussed.

  12. 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

  13. 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).

  14. 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.

  15. 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...

  16. 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…

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  5. 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.

  6. 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.

  7. 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 well as the cellular organization of the process of homologous recombination. Herein we review the cell biological aspects of mitotic homologous recombination with a focus on Saccharomyces cerevisiae and mammalian cells, but will also draw on findings from other experimental systems. Key topics...

  8. 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...

  9. 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.

  10. Instance-Based Generative Biological Shape Modeling.

    Science.gov (United States)

    Peng, Tao; Wang, Wei; Rohde, Gustavo K; Murphy, Robert F

    2009-01-01

    Biological shape modeling is an essential task that is required for systems biology efforts to simulate complex cell behaviors. Statistical learning methods have been used to build generative shape models based on reconstructive shape parameters extracted from microscope image collections. However, such parametric modeling approaches are usually limited to simple shapes and easily-modeled parameter distributions. Moreover, to maximize the reconstruction accuracy, significant effort is required to design models for specific datasets or patterns. We have therefore developed an instance-based approach to model biological shapes within a shape space built upon diffeomorphic measurement. We also designed a recursive interpolation algorithm to probabilistically synthesize new shape instances using the shape space model and the original instances. The method is quite generalizable and therefore can be applied to most nuclear, cell and protein object shapes, in both 2D and 3D.

  11. 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...

  12. 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.

  13. 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.

  14. Melanocyte stem cells: biology and current aspects.

    Science.gov (United States)

    Gola, Monika; Czajkowski, Rafał; Bajek, Anna; Dura, Aleksander; Drewa, Tomasz

    2012-10-01

    Epidermal stem cells have become an object of intensive research. The epidermis constitutes one of the main sources of stem cells and is a tissue of choice for use in exploring their biology. Stratified squamous epithelium (epidermis) possesses the capacity for self-renewal and repair due to the presence of epidermal stem cells (ESC). They have been identified within basal layer of the interfollicular epidermis (IFE), in the "bulge" of the hair follicles of rodents, and also in the human follicular bulge. Melanocyte stem cells (MSC) from hair follicles (precisely from the bulge region, which also contains epidermal stem cells) provide an attractive model for the study of stem cells and their regulation at the niche. This review summarizes the rapidly developing field of epidermal stem cell research and their application in regenerative medicine, paying particular attention to melanocyte stem cells, their biology and some of the processes that occur during hair graying and regeneration of the pigmentary system, as well as discussing how aged-associated changes in the melanocyte stem cells compartment impact hair graying. This review also includes differentiation of human skin stem cells into functional epidermal melanocytes.

  15. Basic statistics in cell biology.

    Science.gov (United States)

    Vaux, David L

    2014-01-01

    The physicist Ernest Rutherford said, "If your experiment needs statistics, you ought to have done a better experiment." Although this aphorism remains true for much of today's research in cell biology, a basic understanding of statistics can be useful to cell biologists to help in monitoring the conduct of their experiments, in interpreting the results, in presenting them in publications, and when critically evaluating research by others. However, training in statistics is often focused on the sophisticated needs of clinical researchers, psychologists, and epidemiologists, whose conclusions depend wholly on statistics, rather than the practical needs of cell biologists, whose experiments often provide evidence that is not statistical in nature. This review describes some of the basic statistical principles that may be of use to experimental biologists, but it does not cover the sophisticated statistics needed for papers that contain evidence of no other kind.

  16. 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

  17. 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...

  18. 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.

  19. 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.

  20. The consideration of biological effectiveness of low energy protons using biophysical modeling of the effects induced by exposure of V79 cells.

    Science.gov (United States)

    Khvostunov, I K; Nikjoo, H; Uehara, S; Hoshi, M

    2010-01-01

    We have applied Monte Carlo track structure simulations to estimate relative biological effectiveness (RBE) of low-energy protons using biophysical modelling of radiation effects induced by exposure of V79 cells growing in mono-layer. The microscopic energy deposition in cell nucleus and sub-nucleus volumes was investigated in order to understand the reasons of enhanced biological effectiveness near Bragg peak. Theoretical estimations of RBE based on frequency/dose average lineal energy and calculated yields of initial DNA breaks were collated with experimental RBE(M) data. It was found: 1) dose average lineal energy for whole cell nucleus as a function of proton energy shows a distinct peak at 550 keV; 2) the peak values for sub-nucleus volumes are large compared with the whole cell nucleus; 3) the yield of complex DNA breaks correlates with experimental RBE(M) data.

  1. 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.

  2. 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...

  3. 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-yr 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 to which students' data interpretations were valid and/or generative. By analyzing small-group audio recordings during in-class activities, we demonstrated how students used instructor-provided models to build and refine data interpretations. Often, students used models to broaden the scope of data interpretations, tying conclusions to a biological significance. Coding analysis revealed several strategies and challenges that were common among students in this collaborative setting. Spontaneous argumentation was present in 82% of transcripts, suggesting that data interpretation using models may be a way to elicit this important disciplinary practice. Argumentation dialogue included frequent co-construction of claims backed by evidence from data. Other common strategies included collaborative decoding of data representations and noticing data patterns before making interpretive claims. Focusing on irrelevant data patterns was the most common challenge. Our findings provide evidence to support the feasibility of supporting students' data-interpretation skills within a large lecture course. © 2016 P. Zagallo et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). 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).

  4. Modelling biological pathway dynamics with Timed Automata

    NARCIS (Netherlands)

    Schivo, Stefano; Scholma, Jetse; Urquidi Camacho, R.A.; Wanders, B.; van der Vet, P.E.; Karperien, Hermanus Bernardus Johannes; Langerak, Romanus; van de Pol, Jan Cornelis; Post, Janine Nicole

    2012-01-01

    When analysing complex interaction networks occurring in biological cells, a biologist needs computational support in order to understand the effects of signalling molecules (e.g. growth factors, drugs). ANIMO (Analysis of Networks with Interactive MOdelling) is a tool that allows the user to create

  5. Compositional Modeling of Biological Systems

    OpenAIRE

    Zámborszky, Judit

    2010-01-01

    Molecular interactions are wired in a fascinating way resulting in complex behavior of bio-logical systems. Theoretical modeling provides us a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological systems calls for conceptual tools that manage the combinatorial explosion of the set of possible interac-tions. A suitable conceptual tool to attack complexity is compositionality, already success-fully used in the process algebra field ...

  6. A Three-Dimensional Cell Culture Model to Study the Mechano-Biological Behavior in Periodontal Ligament Regeneration

    Science.gov (United States)

    Oortgiesen, Daniel A.W.; Yu, Na; Bronckers, Antonius L.J.J.; Yang, Fang; Walboomers, X. Frank

    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 examine the effect of mechanical load in vitro. In the current in vitro study, green fluorescent protein labeled periodontal ligament (PDL) cells form rat incisors were embedded in a 3D matrix and exposed to mechanical loading alone, to a chemical stimulus (Emdogain; enamel matrix derivative [EMD]) alone, or a combination of both. Loading consisted of unilateral stretching (8%, 1 Hz) and was applied for 1, 3, or 5 days. Results showed that PDL cells were distributed and randomly oriented within the artificial PDL space in static culture. On mechanical loading, the cells showed higher cell numbers. Moreover, cells realigned perpendicular to the stretching force depending on time and position, with great analogy to natural PDL tissue. EMD application gave a significant effect on growth and upregulated bone sialoprotein (BSP) and collagen type-I (Col-I), whereas Runx-2 was downregulated. This implies that PDL cells under loading might tend to act similar to bone-like cells (BSP and Col-I) but at the same time, react tendon like (Runx-2). The combination of chemical and mechanical stimulation seems possible, but does not show synergistic effects. In this study, a new model was successfully introduced in the field of PDL-related regenerative research. Besides validating the 3D model to mimic an authentic PDL space, it also provided a useful and well-controlled approach to study cell response to mechanical loading and other stimuli. PMID:21913838

  7. 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

  8. Cell Biology of the Caenorhabditis elegans Nucleus

    Science.gov (United States)

    Cohen-Fix, Orna; Askjaer, Peter

    2017-01-01

    Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology. PMID:28049702

  9. 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......, as model systems to understand the fundamental properties of biomembranes. The properties of lipid bilayers can be studied at different time and length scales. For some properties it is sufficient to envision a membrane as an elastic sheet, while for others it is important to take into account the details...... 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...

  10. 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.

  11. 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.

  12. From biological membranes to biomimetic model membranes

    Directory of Open Access Journals (Sweden)

    Eeman, M.

    2010-01-01

    Full Text Available Biological membranes play an essential role in the cellular protection as well as in the control and the transport of nutrients. Many mechanisms such as molecular recognition, enzymatic catalysis, cellular adhesion and membrane fusion take place into the biological membranes. In 1972, Singer et al. provided a membrane model, called fluid mosaic model, in which each leaflet of the bilayer is formed by a homogeneous environment of lipids in a fluid state including globular assembling of proteins and glycoproteins. Since its conception in 1972, many developments were brought to this model in terms of composition and molecular organization. The main development of the fluid mosaic model was made by Simons et al. (1997 and Brown et al. (1997 who suggested that membrane lipids are organized into lateral microdomains (or lipid rafts with a specific composition and a molecular dynamic that are different to the composition and the dynamic of the surrounding liquid crystalline phase. The discovery of a phase separation in the plane of the membrane has induced an explosion in the research efforts related to the biology of cell membranes but also in the development of new technologies for the study of these biological systems. Due to the high complexity of biological membranes and in order to investigate the biological processes that occur on the membrane surface or within the membrane lipid bilayer, a large number of studies are performed using biomimicking model membranes. This paper aims at revisiting the fundamental properties of biological membranes in terms of membrane composition, membrane dynamic and molecular organization, as well as at describing the most common biomimicking models that are frequently used for investigating biological processes such as membrane fusion, membrane trafficking, pore formation as well as membrane interactions at a molecular level.

  13. 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...

  14. 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).

  15. Label-Free Biosensors for Cell Biology

    Directory of Open Access Journals (Sweden)

    Ye Fang

    2011-01-01

    Full Text Available Label-free biosensors for studying cell biology have finally come of age. Recent developments have advanced the biosensors from low throughput and high maintenance research tools to high throughput and low maintenance screening platforms. In parallel, the biosensors have evolved from an analytical tool solely for molecular interaction analysis to powerful platforms for studying cell biology at the whole cell level. This paper presents historical development, detection principles, and applications in cell biology of label-free biosensors. Future perspectives are also discussed.

  16. Lung cancer stem cell: fancy conceptual model of tumor biology or cornerstone of a forthcoming therapeutic breakthrough?

    Science.gov (United States)

    Sourisseau, Tony; Hassan, Khaled A; Wistuba, Ignacio; Penault-Llorca, Frédérique; Adam, Julien; Deutsch, Eric; Soria, Jean-Charles

    2014-01-01

    Cancer research has received a fresh impetus from the concept of cancer stem cell (CSC) which postulates the existence of a tumor cell population uniquely endowed with self-renewal capacity and therapy resistance. Despite recent progresses including targeted therapy, lung cancer treatment remains a challenge owing largely to disease recurrence. Providing a conceptual model of tumor resistance and disease relapse, the lung CSC has received extensive attention, leading to a flourishing literature and several ongoing clinical trials. In this study, we will discuss the data suggesting the existence of CSC in lung tumors and the potential clinical utility of CSCs as prognostic markers or cellular targets of new therapeutic strategies. We will also touch on the new fundamental developments of the CSC concept that ought to be considered if the integration of the CSC concept into clinical practice is to be successful and impact on lung cancer treatment.

  17. 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...

  18. 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.

  19. 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.

  20. 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...

  1. 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...

  2. Cell Biology of Prokaryotic Organelles

    OpenAIRE

    Murat, Dorothee; Byrne, Meghan; Komeili, Arash

    2010-01-01

    Mounting evidence in recent years has challenged the dogma that prokaryotes are simple and undefined cells devoid of an organized subcellular architecture. In fact, proteins once thought to be the purely eukaryotic inventions, including relatives of actin and tubulin control prokaryotic cell shape, DNA segregation, and cytokinesis. Similarly, compartmentalization, commonly noted as a distinguishing feature of eukaryotic cells, is also prevalent in the prokaryotic world in the form of protein-...

  3. Analysis of single biological cells

    International Nuclear Information System (INIS)

    Watt, Frank

    2002-01-01

    The extraction of elemental information from single cultured cells using nuclear microscopy is an area of great potential because it can provide both quantitative information on the uptake of elements by the cell, and also its elemental response to a wide variety of external stimuli. A recent technique based on nuclear physics technology enables the analysis of single cells down to the parts per million level to be achieved

  4. Editorial, Seminars in Cell & Developmental Biology

    OpenAIRE

    Davis, Frank; Higson, Seamus P. J.

    2009-01-01

    It is a pleasure to introduce this special edition of Cell and Development Biology dedicated to the field and application of Biosensors. This edition comprises seven reviews covering the most active research areas where we believe some of the most prominent advances in the field are likely to emerge in the near to medium term. In line with scope of this journal, some emphasis is given towards techniques applicable to Cell Biology.

  5. Use of Animation in Teaching Cell Biology

    OpenAIRE

    Stith, Bradley J.

    2004-01-01

    To address the different learning styles of students, and because students can access animation from off-campus computers, the use of digital animation in teaching cell biology has become increasingly popular. Sample processes from cell biology that are more clearly presented in animation than in static illustrations are identified. The value of animation is evaluated on whether the process being taught involves motion, cellular location, or sequential order of numerous events. Computer progr...

  6. 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.

  7. Spherical cancer models in tumor biology.

    Science.gov (United States)

    Weiswald, Louis-Bastien; Bellet, Dominique; Dangles-Marie, Virginie

    2015-01-01

    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. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  8. 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.)

  9. Ependymal cells: biology and pathology.

    Science.gov (United States)

    Del Bigio, Marc R

    2010-01-01

    The literature was reviewed to summarize the current understanding of the role of ciliated ependymal cells in the mammalian brain. Previous reviews were summarized. Publications from the past 10 years highlight interactions between ependymal cells and the subventricular zone and the possible role of restricted ependymal populations in neurogenesis. Ependymal cells provide trophic support and possibly metabolic support for progenitor cells. Channel proteins such as aquaporins may be important for determining water fluxes at the ventricle wall. The junctional and anchoring proteins are now fairly well understood, as are proteins related to cilia function. Defects in ependymal adhesion and cilia function can cause hydrocephalus through several different mechanisms, one possibility being loss of patency of the cerebral aqueduct. Ependymal cells are susceptible to infection by a wide range of common viruses; while they may act as a line of first defense, they eventually succumb to repeated attacks in long-lived organisms. Ciliated ependymal cells are almost certainly important during brain development. However, the widespread absence of ependymal cells from the adult human lateral ventricles suggests that they may have only regionally restricted value in the mature brain of large size.

  10. 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.

  11. The Kynurenine Pathway in Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Simon P. Jones

    2013-01-01

    Full Text Available The kynurenine pathway (KP is the main catabolic pathway of the essential amino acid tryptophan. The KP has been identified to play a critical role in regulating immune responses in a variety of experimental settings. It is also known to be involved in several neuroinflammatory diseases including Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. This review considers the current understanding of the role of the KP in stem cell biology. Both of these fundamental areas of cell biology have independently been the focus of a burgeoning research interest in recent years. A systematic review of how the two interact has not yet been conducted. Several inflammatory and infectious diseases in which the KP has been implicated include those for which stem cell therapies are being actively explored at a clinical level. Therefore, it is highly relevant to consider the evidence showing that the KP influences stem cell biology and impacts the functional behavior of progenitor cells.

  12. The kynurenine pathway in stem cell biology.

    Science.gov (United States)

    Jones, Simon P; Guillemin, Gilles J; Brew, Bruce J

    2013-09-15

    The kynurenine pathway (KP) is the main catabolic pathway of the essential amino acid tryptophan. The KP has been identified to play a critical role in regulating immune responses in a variety of experimental settings. It is also known to be involved in several neuroinflammatory diseases including Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. This review considers the current understanding of the role of the KP in stem cell biology. Both of these fundamental areas of cell biology have independently been the focus of a burgeoning research interest in recent years. A systematic review of how the two interact has not yet been conducted. Several inflammatory and infectious diseases in which the KP has been implicated include those for which stem cell therapies are being actively explored at a clinical level. Therefore, it is highly relevant to consider the evidence showing that the KP influences stem cell biology and impacts the functional behavior of progenitor cells.

  13. Measuring cell identity in noisy biological systems

    Science.gov (United States)

    Birnbaum, Kenneth D.; Kussell, Edo

    2011-01-01

    Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty measure dSpec, which measures the effect of noise on specificity. Using global gene expression data from the mouse brain, plant root and human white blood cells, we show that Spec identifies genes with variable expression levels that are nonetheless highly specific of particular cell types. When samples from different individuals are used, dSpec measures genes’ transcriptional plasticity in each cell type. Our approach is broadly applicable to mapped gene expression measurements in stem cell biology, developmental biology, cancer biology and biomarker identification. As an example of such applications, we show that Spec identifies a new class of biomarkers, which exhibit variable expression without compromising specificity. The approach provides a unifying theoretical framework for quantifying specificity in the presence of noise, which is widely applicable across diverse biological systems. PMID:21803789

  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. 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.

  16. 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 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...... made recently in the field of stem cell biology, researchers now have improved tools to define novel populations of stem cells, examine them ex vivo using conditions that promote self-renewal, track them into recipients, and determine whether they can contribute to the repair of damaged tissues...

  17. 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.

  18. 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.

  19. 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

  20. Cell biology solves mysteries of reproduction.

    Science.gov (United States)

    Sutovsky, Peter

    2012-09-01

    Reproduction and fertility have been objects of keen inquiry since the dawn of humanity. Medieval anatomists provided the first accurate depictions of the female reproductive system, and early microscopists were fascinated by the magnified sight of sperm cells. Initial successes were achieved in the in vitro fertilization of frogs and the artificial insemination of dogs. Gamete and embryo research was in the cradle of modern cell biology, providing the first evidence of the multi-cellular composition of living beings and pointing out the importance of chromosomes for heredity. In the 20th century, reproductive research paved the way for the study of the cytoskeleton, cell signaling, and the cell cycle. In the last three decades, the advent of reproductive cell biology has brought us human in vitro fertilization, animal cloning, and human and animal embryonic stem cells. It has contributed to the development of transgenesis, proteomics, genomics, and epigenetics. This Special Issue represents a sample of the various areas of reproductive biology, with emphasis on molecular and cell biological aspects. Advances in spermatology, ovarian function, fertilization, and maternal-fetal interactions are discussed within the framework of fertility and diseases such as endometriosis and diabetes.

  1. 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

  2. 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

  3. TinkerCell: modular CAD tool for synthetic biology.

    Science.gov (United States)

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

    2009-10-29

    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. 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. 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 accept

  4. 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

  5. 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.

  6. 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.

  7. 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).

  8. 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.

  9. 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...

  10. 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.

  11. Nonlinear Rheology in a Model Biological Tissue.

    Science.gov (United States)

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

    2017-04-14

    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.

  12. Optofluidic cell manipulation for a biological microbeam

    Science.gov (United States)

    Grad, Michael; Bigelow, Alan W.; Garty, Guy; Attinger, Daniel; Brenner, David J.

    2013-01-01

    This paper describes the fabrication and integration of light-induced dielectrophoresis for cellular manipulation in biological microbeams. An optoelectronic tweezers (OET) cellular manipulation platform was designed, fabricated, and tested at Columbia University's Radiological Research Accelerator Facility (RARAF). The platform involves a light induced dielectrophoretic surface and a microfluidic chamber with channels for easy input and output of cells. The electrical conductivity of the particle-laden medium was optimized to maximize the dielectrophoretic force. To experimentally validate the operation of the OET device, we demonstrate UV-microspot irradiation of cells containing green fluorescent protein (GFP) tagged DNA single-strand break repair protein, targeted in suspension. We demonstrate the optofluidic control of single cells and groups of cells before, during, and after irradiation. The integration of optofluidic cellular manipulation into a biological microbeam enhances the facility's ability to handle non-adherent cells such as lymphocytes. To the best of our knowledge, this is the first time that OET cell handling is successfully implemented in a biological microbeam.

  13. 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.

  14. 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.

  15. 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.; 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

  16. 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

  17. 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...

  18. 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.

  19. 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

  20. 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...

  1. 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.

  2. Stem Cells: A Renaissance in Human Biology Research.

    Science.gov (United States)

    Wu, Jun; Izpisua Belmonte, Juan Carlos

    2016-06-16

    The understanding of human biology and how it relates to that of other species represents an ancient quest. Limited access to human material, particularly during early development, has restricted researchers to only scratching the surface of this inherently challenging subject. Recent technological innovations, such as single cell "omics" and human stem cell derivation, have now greatly accelerated our ability to gain insights into uniquely human biology. The opportunities afforded to delve molecularly into scarce material and to model human embryogenesis and pathophysiological processes are leading to new insights of human development and are changing our understanding of disease and choice of therapy options. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Redefining plant systems biology: from cell to ecosystem.

    Science.gov (United States)

    Keurentjes, Joost J B; Angenent, Gerco C; Dicke, Marcel; Dos Santos, Vítor A P Martins; Molenaar, Jaap; van der Putten, Wim H; de Ruiter, Peter C; Struik, Paul C; Thomma, Bart P H J

    2011-04-01

    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 agricultural productivity while decreasing the ecological footprint. This requires a holistic systems biology approach that couples different aggregation levels while considering the variables that affect these biological systems from cell to community. The challenge is to generate accurate experimental data that can be used together with modelling concepts and techniques that allow experimentally verifying in silico predictions. The coupling of aggregation levels in plant sciences, termed Integral Quantification of Biological Organization (IQ(BiO)), might enhance our abilities to generate new desired plant phenotypes. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Aging and cancer cell biology, 2007.

    Science.gov (United States)

    Campisi, Judith

    2007-06-01

    This Hot Topics review, the second in a new Aging Cell series, discusses articles published in the last year that have stimulated new ideas about the tangled relationship of aging to cancer cell biology. The year's highlights include reports on the ability of Mdm2 mutations to diminish risks of cancer in aging mice, on proliferative competition between oncogenic cells and bone marrow stem cells, and on the role of metalloproteinases in overcoming age-associated barriers to tumor invasion. Of particular interest were three articles showing that diminished activity of the tumor-suppressor gene p16/INK4a, while increasing the risk of cancer mortality, can lead to improved function in several varieties of age-sensitive stem cells.

  5. Cells — An Open Access Journal of Cell Biology

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-01-01

    Full Text Available To expand the open access publishing project of our newly founded company MDPI [1,2] based in Basel, Switzerland, we are in the process of launching new journals. Based on our success in running journals that represent key areas in science and technology, such as Molecules [3], Sensors [4], Energies [5], Viruses [6], Pharmaceuticals [7], Cancers [8] and Toxins [9], we are launching a new journal entitled Cells. It is an open access journal combining cell biology, molecular biology and biophysics, toward an understanding of cell structure, function and interactions. [...

  6. Glycoengineering in CHO Cells: Advances in Systems Biology.

    Science.gov (United States)

    Tejwani, Vijay; Andersen, Mikael R; Nam, Jong Hyun; Sharfstein, Susan T

    2018-03-01

    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, is a non-templated process. Consequently, both native and recombinant glycoprotein production generate heterogeneous mixtures containing variable amounts of different glycoforms. Stability, potency, plasma half-life, and immunogenicity of the glycoprotein biologic are directly influenced by the glycoforms. 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 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, and glycan and glycoprotein analysis that together will provide new strategies for glycoengineering of CHO cells with desired or enhanced glycosylation capabilities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. From cell biology to biotechnology in space.

    Science.gov (United States)

    Cogoli, A

    2000-09-01

    In this article I discuss the main results of our research in space biology from the simple early investigations with human lymphocytes in the early eighties until the projects in tissue engineering of the next decade on the international space station ISS. The discovery that T lymphocyte activation is nearly totally depressed in vitro in 0 g conditions showed that mammalian single cells are sensitive to the gravitational environment. Such finding had important implications in basic research, medicine and biotechnology. Low gravity can be used as a tool to investigate complicated and still obscure biological process from a new perspective not available to earth-bound laboratories. Low gravity may also favor certain bioprocesses involving the growth of tissues and thus lead to commercial and medical applications. However, shortage of crew time and of other resources, lack of sophisticated instrumentation, safety constraints pose serious limits to biological endeavors in space laboratories.

  8. 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...

  9. A cell-centered approach to developmental biology

    Science.gov (United States)

    Merks, Roeland M. H.; Glazier, James A.

    2005-07-01

    Explaining embryonic development of multicellular organisms requires insight into complex interactions between genetic regulation and physical, generic mechanisms at multiple scales. As more physicists move into developmental biology, we need to be aware of the “cultural” differences between the two fields, whose concepts of “explanations” and “models” traditionally differ: biologists aiming to identify genetic pathways and expression patterns, physicists tending to look for generic underlying principles. Here we discuss how we can combine such biological and physical approaches into a cell-centered approach to developmental biology. Genetic information can only indirectly influence the morphology and physiology of multicellular organisms. DNA translates into proteins and regulatory RNA sequences, which steer the biophysical properties of cells, their response to signals from neighboring cells, and the production and properties of extracellular matrix (ECM). We argue that in many aspects of biological development, cells’ inner workings are irrelevant: what matter are the cell's biophysical properties, the signals it emits and its responses to extracellular signals. Thus we can separate questions about genetic regulation from questions about development. First, we ask what effects a gene network has on cell phenomenology, and how it operates. We then ask through which mechanisms such single-cell phenomenology directs multicellular morphogenesis and physiology. This approach treats the cell as the fundamental module of development. We discuss how this cell-centered approach-which requires significant input from computational biophysics-can assist and supplement experimental research in developmental biology. We review cell-centered approaches, focusing in particular on the Cellular Potts Model (CPM), and present the Tissue Simulation Toolkit which implements the CPM.

  10. Multiscale mechanical modeling of soft biological tissues

    Science.gov (United States)

    Stylianopoulos, Triantafyllos

    2008-10-01

    Soft biological tissues include both native and artificial tissues. In the human body, tissues like the articular cartilage, arterial wall, and heart valve leaflets are examples of structures composed of an underlying network of collagen fibers, cells, proteins and molecules. Artificial tissues are less complex than native tissues and mainly consist of a fiber polymer network with the intent of replacing lost or damaged tissue. Understanding of the mechanical function of these materials is essential for many clinical treatments (e.g. arterial clamping, angioplasty), diseases (e.g. arteriosclerosis) and tissue engineering applications (e.g. engineered blood vessels or heart valves). This thesis presents the derivation and application of a multiscale methodology to describe the macroscopic mechanical function of soft biological tissues incorporating directly their structural architecture. The model, which is based on volume averaging theory, accounts for structural parameters such as the network volume fraction and orientation, the realignment of the fibers in response to strain, the interactions among the fibers and the interactions between the fibers and the interstitial fluid in order to predict the overall tissue behavior. Therefore, instead of using a constitutive equation to relate strain to stress, the tissue microstructure is modeled within a representative volume element (RVE) and the macroscopic response at any point in the tissue is determined by solving a micromechanics problem in the RVE. The model was applied successfully to acellular collagen gels, native blood vessels, and electrospun polyurethane scaffolds and provided accurate predictions for permeability calculations in isotropic and oriented fiber networks. The agreement of model predictions with experimentally determined mechanical properties provided insights into the mechanics of tissues and tissue constructs, while discrepancies revealed limitations of the model framework.

  11. Autophagic regulation of smooth muscle cell biology

    Directory of Open Access Journals (Sweden)

    Joshua K. Salabei

    2015-04-01

    Full Text Available Autophagy regulates the metabolism, survival, and function of numerous cell types, including those comprising the cardiovascular system. In the vasculature, changes in autophagy have been documented in atherosclerotic and restenotic lesions and in hypertensive vessels. The biology of vascular smooth muscle cells appears particularly sensitive to changes in the autophagic program. Recent evidence indicates that stimuli or stressors evoked during the course of vascular disease can regulate autophagic activity, resulting in modulation of VSMC phenotype and viability. In particular, certain growth factors and cytokines, oxygen tension, and pharmacological drugs have been shown to trigger autophagy in smooth muscle cells. Importantly, each of these stimuli has a redox component, typically associated with changes in the abundance of reactive oxygen, nitrogen, or lipid species. Collective findings support the hypothesis that autophagy plays a critical role in vascular remodeling by regulating smooth muscle cell phenotype transitions and by influencing the cellular response to stress. In this graphical review, we summarize current knowledge on the role of autophagy in the biology of the smooth muscle cell in (pathophysiology.

  12. 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.

  13. Cell-free synthetic biology forin vitroprototype 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).

  14. 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.

  15. Interdisciplinary Team Science in Cell Biology.

    Science.gov (United States)

    Horwitz, Rick

    2016-11-01

    The cell is complex. With its multitude of components, spatial-temporal character, and gene expression diversity, it is challenging to comprehend the cell as an integrated system and to develop models that predict its behaviors. I suggest an approach to address this issue, involving system level data analysis, large scale team science, and philanthropy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  3. 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.

  4. 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.

  5. Stochastic modelling of dynamical systems in biology

    NARCIS (Netherlands)

    Pellin, Danilo

    2017-01-01

    In this thesis two relevant biological problems will be addressed from a statistical modelling perspective. The first regards the study of hematopoiesis, a still not well understood biological process rarely observable in humans due to technical and ethical reasons. Hematopoiesis is responsible for

  6. 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.

  7. Cell-Free Synthetic Biology: Engineering Beyond the Cell.

    Science.gov (United States)

    Perez, Jessica G; Stark, Jessica C; Jewett, Michael C

    2016-12-01

    Cell-free protein synthesis (CFPS) technologies have enabled inexpensive and rapid recombinant protein expression. Numerous highly active CFPS platforms are now available and have recently been used for synthetic biology applications. In this review, we focus on the ability of CFPS to expand our understanding of biological systems and its applications in the synthetic biology field. First, we outline a variety of CFPS platforms that provide alternative and complementary methods for expressing proteins from different organisms, compared with in vivo approaches. Next, we review the types of proteins, protein complexes, and protein modifications that have been achieved using CFPS systems. Finally, we introduce recent work on genetic networks in cell-free systems and the use of cell-free systems for rapid prototyping of in vivo networks. Given the flexibility of cell-free systems, CFPS holds promise to be a powerful tool for synthetic biology as well as a protein production technology in years to come. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Extending the knowledge in histochemistry and cell biology.

    Science.gov (United States)

    Heupel, Wolfgang-Moritz; Drenckhahn, Detlev

    2010-01-01

    Central to modern Histochemistry and Cell Biology stands the need for visualization of cellular and molecular processes. In the past several years, a variety of techniques has been achieved bridging traditional light microscopy, fluorescence microscopy and electron microscopy with powerful software-based post-processing and computer modeling. Researchers now have various tools available to investigate problems of interest from bird's- up to worm's-eye of view, focusing on tissues, cells, proteins or finally single molecules. Applications of new approaches in combination with well-established traditional techniques of mRNA, DNA or protein analysis have led to enlightening and prudent studies which have paved the way toward a better understanding of not only physiological but also pathological processes in the field of cell biology. This review is intended to summarize articles standing for the progress made in "histo-biochemical" techniques and their manifold applications.

  13. Modelling collagen diseases: STRUCTURAL BIOLOGY

    OpenAIRE

    Brodsky, Barbara; Baum, Jean

    2008-01-01

    Mutations in collagen lead to hereditary disorders such as brittle-bone disease. Peptide models for aberrant collagens are beginning to clarify how these amino-acid replacements lead to clinical problems.

  14. 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

  15. 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

  16. Cell wall biology: perspectives from cell wall imaging.

    Science.gov (United States)

    Lee, Kieran J D; Marcus, Susan E; Knox, J Paul

    2011-03-01

    Polysaccharide-rich plant cell walls are important biomaterials that underpin plant growth, are major repositories for photosynthetically accumulated carbon, and, in addition, impact greatly on the human use of plants. Land plant cell walls contain in the region of a dozen major polysaccharide structures that are mostly encompassed by cellulose, hemicelluloses, and pectic polysaccharides. During the evolution of land plants, polysaccharide diversification appears to have largely involved structural elaboration and diversification within these polysaccharide groups. Cell wall chemistry is well advanced and a current phase of cell wall science is aimed at placing the complex polysaccharide chemistry in cellular contexts and developing a detailed understanding of cell wall biology. Imaging cell wall glycomes is a challenging area but recent developments in the establishment of cell wall molecular probe panels and their use in high throughput procedures are leading to rapid advances in the molecular understanding of the spatial heterogeneity of individual cell walls and also cell wall differences at taxonomic levels. The challenge now is to integrate this knowledge of cell wall heterogeneity with an understanding of the molecular and physiological mechanisms that underpin cell wall properties and functions.

  17. Femtosecond diffractive imaging of biological cells

    Energy Technology Data Exchange (ETDEWEB)

    Marvin Seibert, M; Boutet, Sebastien; Svenda, Martin; Ekeberg, Tomas; Maia, Filipe R N C; TImneanu, Nicusor; Caleman, Carl; Hajdu, Janos [Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, Box 596, SE-75124 Uppsala (Sweden); Bogan, Michael J [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Barty, Anton; Hau-Riege, Stefan; Frank, Matthias; Benner, Henry [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550 (United States); Lee, Joanna Y [Department of Biology, Stanford University, Stanford, CA 94305 (United States); Marchesini, Stefano [Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Shaevitz, Joshua W [150 Carl Icahn Laboratory, Princeton University, Princeton, NJ 08544 (United States); Fletcher, Daniel A [Bioengineering and Biophysics, University of California, Berkeley, CA 94720 (United States); Bajt, Sasa [Photon Science, DESY, Notkestrasse 85, 22607 Hamburg (Germany); Andersson, Inger [Department of Molecular Biology, Swedish University of Agricultural Sciences, Husargatan 3, Box 590, SE-751 24 Uppsala (Sweden); Chapman, Henry N, E-mail: marvin@xray.bmc.uu.s, E-mail: janos@xray.bmc.uu.s [Center for Free-Electron Laser Science, University of Hamburg and DESY, Notkestrasse 85, Hamburg (Germany)

    2010-10-14

    In a flash diffraction experiment, a short and extremely intense x-ray pulse illuminates the sample to obtain a diffraction pattern before the onset of significant radiation damage. The over-sampled diffraction pattern permits phase retrieval by iterative phasing methods. Flash diffractive imaging was first demonstrated on an inorganic test object (Chapman et al 2006 Nat. Phys. 2 839-43). We report here experiments on biological systems where individual cells were imaged, using single, 10-15 fs soft x-ray pulses at 13.5 nm wavelength from the FLASH free-electron laser in Hamburg. Simulations show that the pulse heated the sample to about 160 000 K but not before an interpretable diffraction pattern could be obtained. The reconstructed projection images return the structures of the intact cells. The simulations suggest that the average displacement of ions and atoms in the hottest surface layers remained below 3 A during the pulse.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Experimental determination of folding factor of benign breast cancer cell (MCF10A) and its effect on contact models and 3D manipulation of biological particles.

    Science.gov (United States)

    Korayem, M H; Shahali, S; Rastegar, Z

    2017-12-02

    Plasma membrane of most cells is not smooth. The surfaces of both small and large micropermeable cells are folded and corrugated which makes mammalian cells to have a larger membrane surface than the supposed ideal mode, that is, the smooth sphere of the same volume. Since cancer is an anthropic disease, cancer cells tend to have a larger membrane area than normal cells. Therefore, cancer cells have higher folding factor and larger radius than normal and healthy cells. On the other hand, the prevalence of breast cancer has prompted researchers to improve the treatment options raised for the disease in the past. In this paper, the impact of folding factor of the cell surface has been investigated. Considering that AFM is one of the most effective tools in performing the tests at micro- and nanoscales, it was used to determine the topography of MCF10 cells and then the resulting images and results were used to experimentally extract the folding factor of cells. By applying this factor in the Hertz, DMT and JKR contact models in the elastic and viscoelastic states, these models have been modified and the simulation of the three models shows that the simulation results are closer to the experimental results by considering the folding in the calculations. Additionally, the simulation of 3D manipulation has been done in both elastic and viscoelastic states with and without consideration of folding. Finally, the results were compared to investigate the effects of folding of the cell surface to the critical force and critical time of sliding and rolling in contact with the substrate and AFM tip in the 3D manipulation model.

  3. 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.

  4. Stochastic models for cell division

    Science.gov (United States)

    Stukalin, Evgeny; Sun, Sean

    2013-03-01

    The probability of cell division per unit time strongly depends of age of cells, i.e., time elapsed since their birth. The theory of cell populations in the age-time representation is systematically applied for modeling cell division for different spreads in generation times. We use stochastic simulations to address the same issue at the level of individual cells. Our approach unlike deterministic theory enables to analyze the size fluctuations of cell colonies at different growth conditions (in the absence and in the presence of cell death, for initially synchronized and asynchronous cell populations, for conditions of restricted growth). We find the simple quantitative relation between the asymptotic values of relative size fluctuations around mean values for initially synchronized cell populations under growth and the coefficients of variation of generation times. Effect of initial age distribution for asynchronous growth of cell cultures is also studied by simulations. The influence of constant cell death on fluctuations of sizes of cell populations is found to be essential even for small cell death rates, i.e., for realistic growth conditions. The stochastic model is generalized for biologically relevant case that involves both cell reproduction and cell differentiation.

  5. 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)

  6. Bridging physics and biology teaching through modeling

    Science.gov (United States)

    Hoskinson, Anne-Marie; Couch, Brian A.; Zwickl, Benjamin M.; Hinko, Kathleen A.; Caballero, Marcos D.

    2014-05-01

    As the frontiers of biology become increasingly interdisciplinary, the physics education community has engaged in ongoing efforts to make physics classes more relevant to life science majors. These efforts are complicated by the many apparent differences between these fields, including the types of systems that each studies, the behavior of those systems, the kinds of measurements that each makes, and the role of mathematics in each field. Nonetheless, physics and biology are both sciences that rely on observations and measurements to construct models of the natural world. In this article, we propose that efforts to bridge the teaching of these two disciplines must emphasize shared scientific practices, particularly scientific modeling. We define modeling using language common to both disciplines and highlight how an understanding of the modeling process can help reconcile apparent differences between the teaching of physics and biology. We elaborate on how models can be used for explanatory, predictive, and functional purposes and present common models from each discipline demonstrating key modeling principles. By framing interdisciplinary teaching in the context of modeling, we aim to bridge physics and biology teaching and to equip students with modeling competencies applicable in any scientific discipline.

  7. Cytoview: Development of a cell modelling framework

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    The fundamental unit of living tissue, in fact of life itself, is the biological cell. Currently there is enormous interest in in silico modelling of the cell .... classification and cell type relationships, newer vocabulary is required to describe a single cell itself with all its sub- cellular structures. Further, this vocabulary should pave way.

  8. 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…

  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...... research papers reporting major recent progress by the PROSPECTS groups, including improvements to the resolution and sensitivity of the Orbitrap family of mass spectrometers, systematic detection of proteins using highly characterized antibody collections, and new methods for absolute as well as relative...

  10. 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...

  11. 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.

  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. Setting Parameters for Biological Models With ANIMO

    Directory of Open Access Journals (Sweden)

    Stefano Schivo

    2014-03-01

    Full Text Available 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 between biological entities in form of a graph, while the parameters determine the speed of occurrence of such interactions. When a mismatch is observed between the behavior of an ANIMO model and experimental data, we want to update the model so that it explains the new data. In general, the topology of a model can be expanded with new (known or hypothetical nodes, and enables it to match experimental data. However, the unrestrained addition of new parts to a model causes two problems: models can become too complex too fast, to the point of being intractable, and too many parts marked as "hypothetical" or "not known" make a model unrealistic. Even if changing the topology is normally the easier task, these problems push us to try a better parameter fit as a first step, and resort to modifying the model topology only as a last resource. In this paper we show the support added in ANIMO to ease the task of expanding the knowledge on biological networks, concentrating in particular on the parameter settings.

  14. Glycoengineering in CHO cells: Advances in systems biology

    DEFF Research Database (Denmark)

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

    2018-01-01

    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...

  15. Compartmentalized Signaling in Neurons: From Cell Biology to Neuroscience.

    Science.gov (United States)

    Terenzio, Marco; Schiavo, Giampietro; Fainzilber, Mike

    2017-11-01

    Neurons are the largest known cells, with complex and highly polarized morphologies. As such, neuronal signaling is highly compartmentalized, requiring sophisticated transfer mechanisms to convey and integrate information within and between sub-neuronal compartments. Here, we survey different modes of compartmentalized signaling in neurons, highlighting examples wherein the fundamental cell biological processes of protein synthesis and degradation, membrane trafficking, and organelle transport are employed to enable the encoding and integration of information, locally and globally within a neuron. Comparisons to other cell types indicate that neurons accentuate widely shared mechanisms, providing invaluable models for the compartmentalization and transfer mechanisms required and used by most eukaryotic cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  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 cell biology of renal filtration

    Science.gov (United States)

    Quaggin, Susan E.

    2015-01-01

    The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate and functionally elegant structure called the renal glomerulus. Normal glomerular function retains circulating cells and valuable macromolecular components of plasma in blood, resulting in urine with just trace amounts of proteins. Endothelial cells of glomerular capillaries, the podocytes wrapped around them, and the fused extracellular matrix these cells form altogether comprise the glomerular filtration barrier, a dynamic and highly selective filter that sieves on the basis of molecular size and electrical charge. Current understanding of the structural organization and the cellular and molecular basis of renal filtration draws from studies of human glomerular diseases and animal models of glomerular dysfunction. PMID:25918223

  18. Bridging the gap between cell biology and organic chemistry: chemical synthesis and biological application of lipidated peptides and proteins.

    Science.gov (United States)

    Peters, Carsten; Wagner, Melanie; Völkert, Martin; Waldmann, Herbert

    2002-09-01

    We have developed a basic concept for studying cell biological phenomena using an interdisciplinary approach starting from organic chemistry. Based on structural information available for a given biological phenomenon, unsolved chemical problems are identified. For their solution, new synthetic pathways and methods are developed, which reflect the state of the art in synthesising lipidated peptide conjugates. These compounds are used as molecular probes for the investigation of biological phenomena that involve both the determination of biophysical properties and cell biological studies. The interplay between organic synthesis, biophysics and cell biology in the study of protein lipidation may open up new and alternative opportunities to gain knowledge about the biological phenomenon that could not be obtained by employing biological techniques alone. This fruitful combination is highlighted using the Ras protein as an outstanding example. Included herein is: the development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of the biophysical properties, in particular the ability to bind to model membranes, and finally the use of synthetic Ras peptides and proteins in cell biological experiments.

  19. 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

  20. Stochastic resonance in biological nonlinear evolution models

    Science.gov (United States)

    Dunkel, Jörn; Hilbert, Stefan; Schimansky-Geier, Lutz; Hänggi, Peter

    2004-05-01

    We investigate stochastic resonance in the nonlinear, one-dimensional Fisher-Eigen model (FEM), which represents an archetypal model for biological evolution based on a global coupling scheme. In doing so we consider different periodically driven fitness functions which govern the evolution of a biological phenotype population. For the case of a simple harmonic fitness function we are able to derive the exact analytic solution for the asymptotic probability density. A distinct feature of this solution is a phase lag between the driving signal and the linear response of the system. Furthermore, for more complex systems a general perturbation theory (linear response approximation) is put forward. Using the latter approach, we investigate stochastic resonance in terms of the spectral amplification measure for a quadratic, a quartic single-peaked, and for a bistable fitness function. Our analytical results are also compared with those of detailed numerical simulations. Our findings vindicate that stochastic resonance does occur in these nonlinear, globally coupled biological systems.

  1. Mathematical Modeling of Complex Biological Systems

    OpenAIRE

    Fischer, Hans Peter

    2008-01-01

    To understand complex biological systems such as cells, tissues, or even the human body, it is not sufficient to identify and characterize the individual molecules in the system. It also is necessary to obtain a thorough understanding of the interaction between molecules and pathways. This is even truer for understanding complex diseases such as cancer, Alzheimer’s disease, or alcoholism. With recent technological advances enabling researchers to monitor complex cellular processes on the mole...

  2. 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

  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. Honeydew honey: biological effects on skin cells.

    Science.gov (United States)

    Martinotti, Simona; Calabrese, Giorgio; Ranzato, Elia

    2017-11-01

    Honey is a natural product well known by humankind and now reconsidered for its use as topical agent for wound and burn treatments. Floral honey is made by honeybees from the nectar of blossoms, while honeydew honey is prepared from secretions of plants or excretions of plant-sucking insects. Chemical composition is different between blossom and honeydew honeys and there is very few information about the biological properties of honeydew honey. So, this study was specifically designed to explore the potential wound healing effects of the honeydew honey. We used in vitro scratch wound healing model consisting of fibroblasts and keratinocytes. Data showed that honeydew honeys is able to increase wound closure by acting both on fibroblasts and keratinocytes. Based on our findings, honeydew honey has the potential to be useful for clinical settings.

  5. Seminars in Cell and Developmental Biology Model Systems for the Study of Heart Development and Disease Cardiac Neural Crest and Conotruncal Malformations

    Science.gov (United States)

    Hutson, Mary R.; Kirby, Margaret L.

    2007-01-01

    Neural crest cells are multipotential cells that delaminate from the dorsal neural tube and migrate widely throughout the body. A subregion of the cranial neural crest originating between the otocyst and somite 3 has been called “cardiac neural crest” because of the importance of these cells in heart development. Much of what we know about the contribution and function of the cardiac neural crest in cardiovascular development has been learned in the chick embryo using quail-chick chimeras to study neural crest migration and derivatives and using ablation of premigratory neural crest cells to study their function. These studies show that cardiac crest cells are absolutely required to form the aorticopulmonary septum dividing the cardiac arterial pole into systemic and pulmonary circulations. They support the normal development and patterning of derivatives of the caudal pharyngeal arches and pouches, including the great arteries and the thymus, thyroid and parathyroids. Recently, cardiac neural crest cells have been shown to modulate signaling in the pharynx during the lengthening of the outflow tract by the secondary heart field. Most of the genes associated with cardiac neural crest function have been identified using mouse models. These studies show that the neural crest cells may not be the direct cause of abnormal cardiovascular development but they are a major component in the complex tissue interactions in the caudal pharynx and outflow tract. Since cardiac neural crest cells span from the caudal pharynx into the outflow tract, they are especially susceptible to any perturbation in or by other cells in these regions. Thus, understanding congenital cardiac outflow malformations in human sequences of malformations as represented by the DiGeorge syndrome will necessarily require understanding development of the cardiac neural crest. PMID:17224285

  6. 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 ...

  7. 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...

  8. Modeling nonspecific interactions at biological interfaces

    Science.gov (United States)

    White, Andrew D.

    Difficulties in applied biomaterials often arise from the complexities of interactions in biological environments. These interactions can be broadly broken into two categories: those which are important to function (strong binding to a single target) and those which are detrimental to function (weak binding to many targets). These will be referred to as specific and nonspecific interactions, respectively. Nonspecific interactions have been central to failures of biomaterials, sensors, and surface coatings in harsh biological environments. There is little modeling work on studying nonspecific interactions. Modeling all possible nonspecific interactions within a biological system is difficult, yet there are ways to both indirectly model nonspecific interactions and directly model many interactions using machine-learning. This research utilizes bioinformatics, phenomenological modeling, molecular simulations, experiments, and stochastic modeling to study nonspecific interactions. These techniques are used to study the hydration molecules which resist nonspecific interactions, the formation of salt bridges, the chemistry of protein surfaces, nonspecific stabilization of proteins in molecular chaperones, and analysis of high-throughput screening experiments. The common aspect for these systems is that nonspecific interactions are more important than specific interactions. Studying these disparate systems has created a set of principles for resisting nonspecific interactions which have been experimentally demonstrated with the creation and testing of novel materials which resist nonspecific interactions.

  9. 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.

  10. 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...... timed automata and most recently hybrid systems using the tool Uppaal SMC. In this paper we enable the application of SMC to complex biological systems, by combining Uppaal SMC with ANIMO, a plugin of the tool Cytoscape used by biologists, as well as with SimBiology®, a plugin of Matlab to simulate...

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:26821940

  12. 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.

  13. 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…

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

    Directory of Open Access Journals (Sweden)

    Alvaro C Ucero

    2010-04-01

    Full Text Available Alvaro C Ucero1,*, Sara Gonçalves2,*, Alberto Benito-Martin1, Beatriz Santamaría1, Adrian M Ramos1, Sergio Berzal1, Marta Ruiz-Ortega1, Jesus Egido1, Alberto Ortiz11Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain; 2Nefrologia e Transplantação Renal, Hospital de Santa Maria EPE, Lisbon, Portugal *Both authors contributed equally to the manuscriptAbstract: 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.Keywords: urinary tract obstruction, renal injury, fluid mechanics, molecular cell biology

  15. 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.

  16. Cytoview: Development of a cell modelling framework

    Indian Academy of Sciences (India)

    2007-07-06

    Jul 6, 2007 ... Home; Journals; Journal of Biosciences; Volume 32; Issue 5. Cytoview: Development of a cell modelling framework ... The framework serves as a first step in integrating different levels of data available for a biological cell and has the potential to lead to development of computational models in our pursuit to ...

  17. 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.

  18. 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 : cell ular 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

  19. 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…

  20. Cell Biology and Microbiology: A Continuous Cross-Feeding.

    Science.gov (United States)

    Pizarro-Cerdá, Javier; Cossart, Pascale

    2016-07-01

    Microbiology and cell biology both involve the study of cells, albeit at different levels of complexity and scale. Interactions between both fields during the past 25 years have led to major conceptual and technological advances that have reshaped the whole biology landscape and its biomedical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Structural sensitivity of biological models revisited.

    Science.gov (United States)

    Cordoleani, Flora; Flora, Cordoleani; Nerini, David; David, Nerini; Gauduchon, Mathias; Mathias, Gauduchon; Morozov, Andrew; Andrew, Morozov; Poggiale, Jean-Christophe; Jean-Christophe, Poggiale

    2011-08-21

    Enhancing the predictive power of models in biology is a challenging issue. Among the major difficulties impeding model development and implementation are the sensitivity of outcomes to variations in model parameters, the problem of choosing of particular expressions for the parametrization of functional relations, and difficulties in validating models using laboratory data and/or field observations. In this paper, we revisit the phenomenon which is referred to as structural sensitivity of a model. Structural sensitivity arises as a result of the interplay between sensitivity of model outcomes to variations in parameters and sensitivity to the choice of model functions, and this can be somewhat of a bottleneck in improving the models predictive power. We provide a rigorous definition of structural sensitivity and we show how we can quantify the degree of sensitivity of a model based on the Hausdorff distance concept. We propose a simple semi-analytical test of structural sensitivity in an ODE modeling framework. Furthermore, we emphasize the importance of directly linking the variability of field/experimental data and model predictions, and we demonstrate a way of assessing the robustness of modeling predictions with respect to data sampling variability. As an insightful illustrative example, we test our sensitivity analysis methods on a chemostat predator-prey model, where we use laboratory data on the feeding of protozoa to parameterize the predator functional response. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Synthetic Biology: A Bridge between Artificial and Natural Cells

    Science.gov (United States)

    Ding, Yunfeng; Wu, Fan; Tan, Cheemeng

    2014-01-01

    Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications. PMID:25532531

  3. 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

  4. Anomalous transport in the crowded world of biological cells

    International Nuclear Information System (INIS)

    Höfling, Felix; Franosch, Thomas

    2013-01-01

    A ubiquitous observation in cell biology is that the diffusive motion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarizing their densely packed and heterogeneous structures. The most familiar phenomenon is a sublinear, power-law increase of the mean-square displacement (MSD) as a function of the lag time, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations in time, non-Gaussian distributions of spatial displacements, heterogeneous diffusion and a fraction of immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarize some widely used theoretical models: Gaussian models like fractional Brownian motion and Langevin equations for visco-elastic media, the continuous-time random walk model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Particular emphasis is put on the spatio-temporal properties of the transport in terms of two-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even if the MSDs are identical. Then, we review the theory underlying commonly applied experimental techniques in the presence of anomalous transport like single-particle tracking, fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP). We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where a variety of model systems mimic physiological crowding conditions. Finally, computer simulations are discussed which play an important

  5. Anomalous transport in the crowded world of biological cells.

    Science.gov (United States)

    Höfling, Felix; Franosch, Thomas

    2013-04-01

    A ubiquitous observation in cell biology is that the diffusive motion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarizing their densely packed and heterogeneous structures. The most familiar phenomenon is a sublinear, power-law increase of the mean-square displacement (MSD) as a function of the lag time, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations in time, non-Gaussian distributions of spatial displacements, heterogeneous diffusion and a fraction of immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarize some widely used theoretical models: Gaussian models like fractional Brownian motion and Langevin equations for visco-elastic media, the continuous-time random walk model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Particular emphasis is put on the spatio-temporal properties of the transport in terms of two-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even if the MSDs are identical. Then, we review the theory underlying commonly applied experimental techniques in the presence of anomalous transport like single-particle tracking, fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP). We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where a variety of model systems mimic physiological crowding conditions. Finally, computer simulations are discussed which play an important

  6. Cell biology of mycobacterium tuberculosis phagosome.

    Science.gov (United States)

    Vergne, Isabelle; Chua, Jennifer; Singh, Sudha B; Deretic, Vojo

    2004-01-01

    Phagocytosis and phagolysosome biogenesis represent fundamental biological processes essential for proper tissue homeostasis, development, elimination of invading microorganisms, and antigen processing and presentation. Phagosome formation triggers a preprogrammed pathway of maturation into the phagolysosome, a process controlled by Ca2+ and the regulators of organellar trafficking centered around the small GTP-binding proteins Rabs and their downstream effectors, including lipid kinases, organellar tethering molecules, and membrane fusion apparatus. Mycobacterium tuberculosis is a potent human pathogen parasitizing macrophages. It interferes with the Rab-controlled membrane trafficking and arrests the maturing phagosome at a stage where no harm can be done to the pathogen while the delivery of nutrients and membrane to the vacuole harboring the microorganism continues. This process, referred to as the M. tuberculosis phagosome maturation arrest or inhibition of phagosome-lysosome fusion, is critical for M. tuberculosis persistence in human populations. It also provides a general model system for dissecting the phagolysosome biogenesis pathways. Here we review the fundamental trafficking processes targeted by M. tuberculosis and the mycobacterial products that interfere with phagosomal maturation.

  7. 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)

  8. 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…

  9. 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.

    2015-01-01

    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. PMID:26668171

  10. 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.

  11. 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.

  12. A Role for SHIP in Stem Cell Biology and Transplantation

    OpenAIRE

    Kerr, William G.

    2008-01-01

    Inositol phospholipid signaling pathways have begun to emerge as important players in stem cell biology and bone marrow transplantation [1–4]. The SH2-containing Inositol Phosphatase (SHIP) is among the enzymes that can modify endogenous mammalian phosphoinositides. SHIP encodes an isoform specific to pluripotent stem (PS) cells [5,6] plays a role in hematopoietic stem (HS) cell biology [7,8] and allogeneic bone marrow (BM) transplantation [1,2,9,10]. Here I discuss our current understanding ...

  13. 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

  14. 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.

  15. Cell kinetics and radiation biology (review)

    International Nuclear Information System (INIS)

    Denekamp, J.

    1986-01-01

    Variation in radiosensitivity around the cell cycle, and the extent of radiation-induced delay in cell cycle progression result in variable time of expression of radiation injury in normal tissues, ranging from a few days in intestine to weeks, months or years in slowly proliferating tissues. Radiosensitivity of tumours, to single doses, is dominated by hypoxic cells arising from the imbalance between tumour cell production and the proliferation and branching of blood vessels needed to bring oxygen and other nutrients to each cell. Response to fractionated radiotherapy schedules is also influenced by the cell kinetic parameters of the cells comprising each tissue or tumour. Slowly cycling cells show much more dramatic changes with fractionation, dose rate or l.e.t. Rapidly cycling cells redistribute around the cell cycle when the cells in sensitive phases have been killed, experiencing less mitotic delay than slowly proliferating cells. Reoxygenation seems more effective in tumours with rapidly cycling cells and high natural cell loss rates. Compensatory repopulation within a treatment schedule may spare skin and mucosa but not slowly proliferating tissues. Tumour cell proliferation during fractionated radiotherapy may be an important limiting factor of treatment success. (U.K.)

  16. Quasi – biological model of radiogenic cancer morbidity

    Directory of Open Access Journals (Sweden)

    A. T. Gubin

    2015-01-01

    Full Text Available The methods: Linear differential equations were used to formalize contemporary assumptions of self –sustaining tissue cell kinetics under the impact of adverse factors, on the formation and repairing of cell “pre-cancer” defects, on inheritance and retaining such defects in daughter cells which results in malignant neoplasms, on age-dependent impairment of human body’s function to eliminate such cells.The results: The model reproduces the well-known regularities of radiogenic cancer morbidity increase depending on instantaneous radiation exposure age and on attained age: the relative reduction at increased radiation age which the model attributes to age decrease of stem cells, relative reduction at increased time after radiation induced by “sorting out” of cells with “pre-cancer” defects, absolute increase with age proportional to natural cause mortality rate.The relevance of the developed quasi-biological model is displayed via comparison to the ICRP model for radiogenic increase of solid carcinomas’ morbidity after single radiation exposure. The latter model had been developed after Japanese cohort observations. For both genders high goodness-of-fit was achieved between the models at values of Gompertz’ law factor which had been defined for men and women in this cohort via selecting the value of the only free parameter indicating age-dependent exponential retardation of stem cells’ division.The conclusion: The proposed model suggests that the estimation of radiogenic risk inter-population transfer can be done on the basis of the data on age-dependent mortality intensity increase from all natural causes. The model also creates the premises for inter-species transfer of risk following the well-known parameters of cell populations’ kinetics in animal’s organs and tissues and Gompertz’s law parameters. This model is applicable also for analyses of age-dependent changes of background cancer morbidity. 

  17. 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

  18. Integrative biological simulation praxis: Considerations from physics, philosophy, and data/model curation practices

    OpenAIRE

    Sarma, Gopal P.; Faundez, Victor

    2017-01-01

    ABSTRACT Integrative biological simulations have a varied and controversial history in the biological sciences. From computational models of organelles, cells, and simple organisms, to physiological models of tissues, organ systems, and ecosystems, a diverse array of biological systems have been the target of large-scale computational modeling efforts. Nonetheless, these research agendas have yet to prove decisively their value among the broader community of theoretical and experimental biolo...

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. Stem cells: Biology and clinical potential

    African Journals Online (AJOL)

    ajl yemi

    2011-12-30

    Dec 30, 2011 ... stem cells that may be utilized in this way, their pattern of development, their plasticity in terms of differentiation and ..... under pathological condition or injury, and the study of these stem cells appeared to be unrelated to .... structure harboring ependymal cells and astrocytes that play a role very similar to ...

  5. 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.

  6. 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

  7. 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.

  8. 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...

  9. Ising models of strongly coupled biological networks with multivariate interactions

    Science.gov (United States)

    Merchan, Lina; Nemenman, Ilya

    2013-03-01

    Biological networks consist of a large number of variables that can be coupled by complex multivariate interactions. However, several neuroscience and cell biology experiments have reported that observed statistics of network states can be approximated surprisingly well by maximum entropy models that constrain correlations only within pairs of variables. We would like to verify if this reduction in complexity results from intricacies of biological organization, or if it is a more general attribute of these networks. We generate random networks with p-spin (p > 2) interactions, with N spins and M interaction terms. The probability distribution of the network states is then calculated and approximated with a maximum entropy model based on constraining pairwise spin correlations. Depending on the M/N ratio and the strength of the interaction terms, we observe a transition where the pairwise approximation is very good to a region where it fails. This resembles the sat-unsat transition in constraint satisfaction problems. We argue that the pairwise model works when the number of highly probable states is small. We argue that many biological systems must operate in a strongly constrained regime, and hence we expect the pairwise approximation to be accurate for a wide class of problems. This research has been partially supported by the James S McDonnell Foundation grant No.220020321.

  10. 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.

  11. 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…

  12. Erythrocytes as a biological model for screening of xenobiotics toxicity.

    Science.gov (United States)

    Farag, Mayada Ragab; Alagawany, Mahmoud

    2018-01-05

    Erythrocytes are the main cells in circulation. They are devoid of internal membrane structures and easy to be isolated and handled providing a good model for different assays. Red blood cells (RBCs) plasma membrane is a multi-component structure that keeps the cell morphology, elasticity, flexibility and deformability. Alteration of membrane structure upon exposure to xenobiotics could induce various cellular abnormalities and releasing of intracellular components. Therefore the morphological changes and extracellular release of haemoglobin [hemolysis] and increased content of extracellular adenosine triphosphate (ATP) [as signs of membrane stability] could be used to evaluate the cytotoxic effects of various molecules. The nucleated RBCs from birds, fish and amphibians can be used to evaluate genotoxicity of different xenobiotics using comet, DNA fragmentation and micronucleus assays. The RBCs could undergo programmed cell death (eryptosis) in response to injury providing a useful model to analyze some mechanisms of toxicity that could be implicated in apoptosis of nucleated cells. Erythrocytes are vulnerable to peroxidation making it a good biological membrane model for analyzing the oxidative stress and lipid peroxidation of various xenobiotics. The RBCs contain a large number of enzymatic and non-enzymatic antioxidants. The changes of the RBCs antioxidant capacity could reflect the capability of xenobiotics to generate reactive oxygen species (ROS) resulting in oxidative damage of tissue. These criteria make RBCs a valuable in vitro model to evaluate the cytotoxicity of different natural or synthetic and organic or inorganic molecules by cellular damage measures. Copyright © 2017. Published by Elsevier B.V.

  13. 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

  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. 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.

  16. Biotic-Abiotic Nanoscale Interactions in Biological Fuel Cells

    Science.gov (United States)

    2014-03-28

    such as ATP. This strategy, called oxidative phosphorylation, is embraced by all respiratory microorganisms. Most eukaryotes and many prokaryotes are...AFRL-OSR-VA-TR-2014-0087 (YIP-10) BIOTIC-ABIOTIC NANOSCALE INTERACTIONS IN BIOLOGICAL FUEL CELLS Mohamed El-Naggar UNIVERSITY OF SOUTHERN CALIFORNIA...Interactions in Biological Fuel Cells Award Number: FA9550-10-1-0144 Start Date: 04/15/2010 Program Manager: Patrick O. Bradshaw, PhD Air

  17. 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.

  18. 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

  19. Radiation biology of human mammary epithelial cells

    International Nuclear Information System (INIS)

    Smith, H.S.; Yang, T.C.; Stampfer, M.R.; Hackett, A.J.

    1982-01-01

    Techniques have been developed for growing mass cultures of normal mammary epithelial cells (from reduction mammoplasties) and, most recently, for growing mammary epithelial cells in a highly efficient clonal assay. The availability of this clonal assay has enabled us to examine the dose-response curves for x rays

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. Systemic Modeling of Biological Functions in Consideration of Physiome Project

    Science.gov (United States)

    Minamitani, Haruyuki

    Emerging of the physiome project provides various influences on the medical, biological and pharmaceutical development. In this paper, as an example of physiome research, neural network model analysis providing the conduction mechanisms of pain and tactile sensations was presented, and the functional relations between neural activities of the network cells and stimulus intensity applied on the peripheral receptive fields were described. The modeling presented here is based on the various assumptions made by the results of physiological and anatomical studies reported in the literature. The functional activities of spinothalamic and thalamocortical cells show a good agreement with the physiological and psychophysical functions of somatosensory system that are very instructive for covering the gap between physiologically and psychophysically aspects of pain and tactile sensation.

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. The model of drugs distribution dynamics in biological tissue

    Science.gov (United States)

    Ginevskij, D. A.; Izhevskij, P. V.; Sheino, I. N.

    2017-09-01

    The dose distribution by Neutron Capture Therapy follows the distribution of 10B in the tissue. The modern models of pharmacokinetics of drugs describe the processes occurring in conditioned "chambers" (blood-organ-tumor), but fail to describe the spatial distribution of the drug in the tumor and in normal tissue. The mathematical model of the spatial distribution dynamics of drugs in the tissue, depending on the concentration of the drug in the blood, was developed. The modeling method is the representation of the biological structure in the form of a randomly inhomogeneous medium in which the 10B distribution occurs. The parameters of the model, which cannot be determined rigorously in the experiment, are taken as the quantities subject to the laws of the unconnected random processes. The estimates of 10B distribution preparations in the tumor and healthy tissue, inside/outside the cells, are obtained.

  10. 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....

  11. Topological Data Analysis of Biological Aggregation Models

    Science.gov (United States)

    Topaz, Chad M.; Ziegelmeier, Lori; Halverson, Tom

    2015-01-01

    We apply tools from topological data analysis to two mathematical models inspired by biological aggregations such as bird flocks, fish schools, and insect swarms. Our data consists of numerical simulation output from the models of Vicsek and D'Orsogna. These models are dynamical systems describing the movement of agents who interact via alignment, attraction, and/or repulsion. Each simulation time frame is a point cloud in position-velocity space. We analyze the topological structure of these point clouds, interpreting the persistent homology by calculating the first few Betti numbers. These Betti numbers count connected components, topological circles, and trapped volumes present in the data. To interpret our results, we introduce a visualization that displays Betti numbers over simulation time and topological persistence scale. We compare our topological results to order parameters typically used to quantify the global behavior of aggregations, such as polarization and angular momentum. The topological calculations reveal events and structure not captured by the order parameters. PMID:25970184

  12. Accelerating Bayesian inference for evolutionary biology models.

    Science.gov (United States)

    Meyer, Xavier; Chopard, Bastien; Salamin, Nicolas

    2017-03-01

    Bayesian inference is widely used nowadays and relies largely on Markov chain Monte Carlo (MCMC) methods. Evolutionary biology has greatly benefited from the developments of MCMC methods, but the design of more complex and realistic models and the ever growing availability of novel data is pushing the limits of the current use of these methods. We present a parallel Metropolis-Hastings (M-H) framework built with a novel combination of enhancements aimed towards parameter-rich and complex models. We show on a parameter-rich macroevolutionary model increases of the sampling speed up to 35 times with 32 processors when compared to a sequential M-H process. More importantly, our framework achieves up to a twentyfold faster convergence to estimate the posterior probability of phylogenetic trees using 32 processors when compared to the well-known software MrBayes for Bayesian inference of phylogenetic trees. https://bitbucket.org/XavMeyer/hogan. nicolas.salamin@unil.ch. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  13. Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry.

    Science.gov (United States)

    Harris, D Calvin; Jewett, Michael C

    2012-10-01

    Just as synthetic organic chemistry once revolutionized the ability of chemists to build molecules (including those that did not exist in nature) following a basic set of design rules, cell-free synthetic biology is beginning to provide an improved toolbox and faster process for not only harnessing but also expanding the chemistry of life. At the interface between chemistry and biology, research in cell-free synthetic systems is proceeding in two different directions: using synthetic biology for synthetic chemistry and using synthetic chemistry to reprogram or mimic biology. In the coming years, the impact of advances inspired by these approaches will make possible the synthesis of nonbiological polymers having new backbone compositions, new chemical properties, new structures, and new functions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. 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

  15. 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...

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Cell biology. An age of instability.

    Science.gov (United States)

    Sinclair, David A

    2003-09-26

    It is well established that as we age our cancer risk increases dramatically. As Sinclair explains in his Perspective, the link between cancer and aging is now solidified by new work in budding yeast (McMurray and Gottschling). As yeast cells age there is a marked increase in their genetic instability (a hallmark of cancer), which is independent of the mechanism that determines their life-span.

  2. Endothelial progenitor cell biology in ankylosing spondylitis.

    Science.gov (United States)

    Verma, Inderjeet; Syngle, Ashit; Krishan, Pawan

    2015-03-01

    Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). EPCs were depleted in AS patients as compared to healthy controls (CD34(+) /CD133(+) : 0.027 ± 0.010% vs. 0.044 ± 0.011%, P < 0.001). EPC depletions were significantly associated with disease duration (r = -0.52, P = 0.01), BASDAI (r = -0.45, P = 0.04) and C-reactive protein (r = -0.5, P = 0.01). This is the first study to demonstrate endothelial progenitor cell depletion in AS patients. EPC depletions inversely correlate with disease duration, disease activity and inflammation, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  3. Grasping the nature of the cell interior: from Physiological Chemistry to Chemical Biology.

    Science.gov (United States)

    Kyne, Ciara; Crowley, Peter B

    2016-08-01

    Current models of the cell interior emphasise its crowded, chemically complex and dynamically organised structure. Although the chemical composition of cells is known, the cooperative intermolecular interactions that govern cell ultrastructure are poorly understood. A major goal of biochemistry is to capture these myriad interactions in vivo. We consider the landmark discoveries that have shaped this objective, starting from the vitalist framework established by early natural philosophers. Through this historical revisionism, we extract important lessons for the bioinspired chemists of today. Scientific specialisation tends to insulate seminal ideas and hamper the unification of paradigms across biology. Therefore, we call for interdisciplinary collaboration in grappling with the complex cell interior. Recent successes in integrative structural biology and chemical biology demonstrate the power of hybrid approaches. The future roles of the (bio)chemist and model systems are also discussed as starting points for in vivo explorations. © 2016 Federation of European Biochemical Societies.

  4. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  5. 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.

  6. 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.

  7. The emerging role of systems biology for engineering protein production in CHO cells.

    Science.gov (United States)

    Kuo, Chih-Chung; Chiang, Austin Wt; Shamie, Isaac; Samoudi, Mojtaba; Gutierrez, Jahir M; Lewis, Nathan E

    2017-12-06

    To meet the ever-growing demand for effective, safe, and affordable protein therapeutics, decades of intense efforts have aimed to maximize the quantity and quality of recombinant proteins produced in CHO cells. Bioprocessing innovations and cell engineering efforts have improved product titer; however, uncharacterized cellular processes and gene regulatory mechanisms still hinder cell growth, specific productivity, and protein quality. Herein, we summarize recent advances in systems biology and data-driven approaches aiming to unravel how molecular pathways, cellular processes, and extrinsic factors (e.g. media supplementation) influence recombinant protein production. In particular, as the available omics data for CHO cells continue to grow, predictive models and screens will be increasingly used to unravel the biological drivers of protein production, which can be used with emerging genome editing technologies to rationally engineer cells to further control the quantity, quality and affordability of many biologic drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Cell Biology of Ischemia/Reperfusion Injury

    Science.gov (United States)

    Kalogeris, Theodore; Baines, Christopher P.; Krenz, Maike; Korthuis, Ronald J.

    2014-01-01

    Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues. PMID:22878108

  9. 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).

  10. 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

  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 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.

  12. New Materials for Biological Fuel Cells

    Science.gov (United States)

    2012-04-01

    been demonstrated to produce their own conductive nanowires (called pilli) that aid in the transfer of electrons via DET between the microbe and the... biopolymer chitosan, aids dispersion of various nanomaterials, including graphene, easing the formation of thin film electrodes. Again the model...electrodes have been shown to be advantageous when used as enzyme anodes with immobilized oxidases or dehydrogenases or with microorganisms

  13. Finding the key - cell biology and science education.

    Science.gov (United States)

    Miller, Kenneth R

    2010-12-01

    No international research community, cell biology included, can exist without an educational community to renew and replenish it. Unfortunately, cell biology researchers frequently regard their work as independent of the process of education and see little reason to reach out to science teachers. For cell biology to continue to prosper, I argue that researchers must support education in at least three ways. First, we must view education and research as part of a single scientific community. Second, we should take advantage of new technologies to connect the research laboratory to the classroom. Finally, we must take the initiative in defending the integrity of science teaching, particularly when education is under attack for political or religious reasons. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Neural stem cell biology in vertebrates and invertebrates: more alike than different?

    Science.gov (United States)

    Brand, Andrea H; Livesey, Frederick J

    2011-05-26

    Many of the regulatory mechanisms controlling neural stem cell behavior are proving to be conserved between organisms as diverse as worms and man. Common principles are emerging with respect to the regulation of neural stem cell division and the specification of distinct stem and progenitor cell types. Great progress has been made in recent years in identifying the cellular mechanisms underpinning these processes, thanks in large part to the cross-fertilization of research on different model systems. We review here recent findings that highlight hitherto unappreciated similarities in the cell and molecular biology of neural stem cell self-renewal and differentiation between invertebrates and vertebrates. As well as underscoring the possible conservation of stem cell mechanisms across phyla, these similarities are proving to be practically useful in studying neural stem cell biology in health and disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Reductionism and explanation in cell biology.

    Science.gov (United States)

    Nurse, P

    1998-01-01

    It is likely to be impossible or very difficult to provide a detailed description of the molecular interactions underlying all cellular phenomena. However, methods and ways of thinking are now available or being developed that can deal better with the complexity and greater extension in space and time found at the level of the cell. This will lead to the identification of some components or groups of components as being of particular importance for a cellular phenomenon which can then be studied in detailed molecular terms. In other cases detailed molecular characterization may be replaced by a logical description of the process which emphasizes the information flow and processing rather than the nature of the individual components and their interactions. This may provide an adequate explanation for an appropriate understanding of the cellular phenomena involved.

  16. 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.

  17. Mechanisms of bacterial morphogenesis: evolutionary cell biology approaches provide new insights.

    Science.gov (United States)

    Jiang, Chao; Caccamo, Paul D; Brun, Yves V

    2015-04-01

    How Darwin's "endless forms most beautiful" have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field of bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating "evolutionary thinking" into bacterial cell biology in the genomic era. © 2015 WILEY Periodicals, Inc.

  18. Biological darkening of ice: measurements and models

    Science.gov (United States)

    Cook, J.; Tedstone, A.; Hodson, A. J.; Williamson, C.; McCutcheon, J.; Tranter, M.

    2017-12-01

    Biological growth occurs in the ablation zones of glaciers and ice sheets, resulting in a reduction of the ice albedo. Given the critical role of albedo in determining the surface energy balance - and therefore melt rate - of a mass of ice, understanding and quantifying biological albedo reduction is fundamental to predicting future ice dynamics. This may be particularly important on ablating ice on the western Greenland Ice Sheet, where a `dark ice zone' of varying spatial extent may be partly or mostly explained by biological growth. However, our ability to quantify and predict the contribution of biological impurities to the overall energy balance of glacial systems is currently limited by a lack of understanding of the mechanisms of biological darkening, difficulties in determining the spatial extent of biological impurities and uncertainty in isolating biological from non-biological albedo reduction. Here, new spectral measurements are presented for ice containing varying amounts of biological impurities which were obtained on the ground using a field spectrometer and from the air using a purpose built UAV on the Greenland Ice Sheet in summer 2016 and 2017. Distinctive spectral signatures are identified and used to map the spatial extent of algal blooms on the ice surface. A new radiative transfer scheme (BioSNICAR) for predicting the albedo of snow or ice discolored by microbial life is also described, offering insight into the mechanisms of biological darkening. Together, these demonstrate the critical role played by pigmented algae in darkening ice surfaces and provide a framework for predicting biological albedo reduction in future climate scenarios.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. Network-Based Models in Molecular Biology

    Science.gov (United States)

    Beyer, Andreas

    Biological systems are characterized by a large number of diverse interactions. Interaction maps have been used to abstract those interactions at all biological scales ranging from food webs at the ecosystem level down to protein interaction networks at the molecular scale.

  5. 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…

  6. "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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. Xenografted tissue models for the study of human endometrial biology.

    Science.gov (United States)

    Kuokkanen, Satu; Zhu, Liyin; Pollard, Jeffrey W

    The human endometrium undergoes extensive morphological, biochemical and molecular changes under the influence of female sex steroid hormones. Besides the fact that estrogen stimulates endometrial cell proliferation and progesterone inhibits this proliferation and induces differentiation, there is limited knowledge about precise molecular mechanisms underlying human endometrial biology. The importance of paracrine signaling in endometrial physiology explains why in vitro culture of endometrial cells has been challenging. Researchers, therefore, have developed alternative experimental in vivo models for the study of endometrial biology. The objective of this review is to summarize the recent developments and work on these in vivo endometrial research models. The in vivo recombinant tissue models in which wild-type endometrial cells are combined with endometrial cells from a gene-targeted mouse strain followed by xenografting to host mice have been critical in confirming the significance of paracrine signaling between the epithelium and stroma in the growth regulation of the endometrium. Additionally, these studies have uncovered differences between the mouse and human, emphasizing the need for the development of experimental models specifically of the human endometrium. Recently, xenotransplants of human endometrial fragments into the subcutaneous space of host mice and endometrial xenografts of dissociated and recombined epithelial and stromal cells beneath the kidney capsule of immunodeficient host mice have proven to be highly promising tools for in vivo research of endometrial functions. For the first time, the latter approach provides an immense opportunity for the application of genome engineering, such as targeted ablation of endometrial genes for example by using CRISPR/CAS9 system. This research will begin to elucidate the functional role of specific genes in this complex tissue. Another advantage of xenotransplantation and xenograft models of the human

  12. Somatic cell genetics and the radiation biology of mammalian cells

    International Nuclear Information System (INIS)

    Puck, T.T.

    1984-01-01

    Early application of somatic cell genetics to mammalian cell radiobiology provided a definitive measurement of the mean lethal dose of ionizing radiation for mammalian cells and re-defined cellular radiosensitivity in a quantitative fashion with important implications in radiotherapy. These studies demonstrated that the killing of mammalian cells by ionizing radiation is due to damage to the DNA. They first established the fundamental role of cell turnover in determining some of the major pathological effects of the mammalian radiation syndrome. They made possible production and study of many kinds of mutant and hybrid cells including radiation-repair deficient mutants. Methods of genetic-biochemical analysis of mutants and hybrids have been devised which make possible identification of specific metabolic effects resulting from irradiation and similar actions. These studies have demonstrated that X-irradiated cells can be used as feeder layers for nourishing other cells dependent on specific cell-cell interactions for their growth. More recently, new applications have provided improved detection and quantitation of effects of low levels of radiation and other mutagens, and have made possible fine structure mapping of human genes

  13. 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.

  14. 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.

  15. 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

  16. Modelling biological and chemically induced precipitation of calcium phosphate in enhanced biological phosphorus removal systems.

    Science.gov (United States)

    Barat, R; Montoya, T; Seco, A; Ferrer, J

    2011-06-01

    The biologically induced precipitation processes can be important in wastewater treatment, in particular treating raw wastewater with high calcium concentration combined with Enhanced Biological Phosphorus Removal. Currently, there is little information and experience in modelling jointly biological and chemical processes. This paper presents a calcium phosphate precipitation model and its inclusion in the Activated Sludge Model No 2d (ASM2d). The proposed precipitation model considers that aqueous phase reactions quickly achieve the chemical equilibrium and that aqueous-solid change is kinetically governed. The model was calibrated using data from four experiments in a Sequencing Batch Reactor (SBR) operated for EBPR and finally validated with two experiments. The precipitation model proposed was able to reproduce the dynamics of amorphous calcium phosphate (ACP) formation and later crystallization to hydroxyapatite (HAP) under different scenarios. The model successfully characterised the EBPR performance of the SBR, including the biological, physical and chemical processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Biologically constrained optimization based cell membrane segmentation in C. elegans embryos.

    Science.gov (United States)

    Azuma, Yusuke; Onami, Shuichi

    2017-06-19

    Recent advances in bioimaging and automated analysis methods have enabled the large-scale systematic analysis of cellular dynamics during the embryonic development of Caenorhabditis elegans. Most of these analyses have focused on cell lineage tracing rather than cell shape dynamics. Cell shape analysis requires cell membrane segmentation, which is challenging because of insufficient resolution and image quality. This problem is currently solved by complicated segmentation methods requiring laborious and time consuming parameter adjustments. Our new framework BCOMS (Biologically Constrained Optimization based cell Membrane Segmentation) automates the extraction of the cell shape of C. elegans embryos. Both the segmentation and evaluation processes are automated. To automate the evaluation, we solve an optimization problem under biological constraints. The performance of BCOMS was validated against a manually created ground truth of the 24-cell stage embryo. The average deviation of 25 cell shape features was 5.6%. The deviation was mainly caused by membranes parallel to the focal planes, which either contact the surfaces of adjacent cells or make no contact with other cells. Because segmentation of these membranes was difficult even by manual inspection, the automated segmentation was sufficiently accurate for cell shape analysis. As the number of manually created ground truths is necessarily limited, we compared the segmentation results between two adjacent time points. Across all cells and all cell cycles, the average deviation of the 25 cell shape features was 4.3%, smaller than that between the automated segmentation result and ground truth. BCOMS automated the accurate extraction of cell shapes in developing C. elegans embryos. By replacing image processing parameters with easily adjustable biological constraints, BCOMS provides a user-friendly framework. The framework is also applicable to other model organisms. Creating the biological constraints is a

  18. 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.

  19. 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

  20. 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

  1. Biology Based Lung Cancer Model for Chronic Low Radon Exposures

    International Nuclear Information System (INIS)

    Truta-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

    2008-01-01

    Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival.To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates

  2. 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.

  3. Invertebrates as model organisms for research on aging biology.

    Science.gov (United States)

    Murthy, Mahadev; Ram, Jeffrey L

    2015-01-30

    Invertebrate model systems, such as nematodes and fruit flies, have provided valuable information about the genetics and cellular biology involved in aging. However, limitations of these simple, genetically tractable organisms suggest the need for other model systems, some of them invertebrate, to facilitate further advances in the understanding of mechanisms of aging and longevity in mammals, including humans. This paper introduces 10 review articles about the use of invertebrate model systems for the study of aging by authors who participated in an 'NIA-NIH symposium on aging in invertebrate model systems' at the 2013 International Congress for Invertebrate Reproduction and Development. In contrast to the highly derived characteristics of nematodes and fruit flies as members of the superphylum Ecdysozoa, cnidarians, such as Hydra, are more 'basal' organisms that have a greater number of genetic orthologs in common with humans. Moreover, some other new model systems, such as the urochordate Botryllus schlosseri , the tunicate Ciona , and the sea urchins (Echinodermata) are members of the Deuterostomia, the same superphylum that includes all vertebrates, and thus have mechanisms that are likely to be more closely related to those occurring in humans. Additional characteristics of these new model systems, such as the recent development of new molecular and genetic tools and a more similar pattern to humans of regeneration and stem cell function suggest that these new model systems may have unique advantages for the study of mechanisms of aging and longevity.

  4. 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 ...

  5. Systems biology: From the cell to the brain

    Indian Academy of Sciences (India)

    Systems biology: From the cell to the brain. SITABHRA SINHA. 1,∗. , T JESAN. 2 and NIVEDITA CHATTERJEE. 3. 1. The Institute of Mathematical Sciences, CIT Campus, Taramani, Chennai 600 113, India. 2. Health Physics Division, Bhabha Atomic Research Centre, Kalpakkam 603 201, India. 3. Vision Research ...

  6. 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…

  7. 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

  8. The cell biology of HIV-1 and other retroviruses

    Directory of Open Access Journals (Sweden)

    Mouland Andrew J

    2006-11-01

    Full Text Available Abstract In recognition of the growing influence of cell biology in retrovirus research, we recently organized a Summer conference sponsored by the American Society for Cell Biology (ASCB on the Cell Biology of HIV-1 and other Retroviruses (July 20–23, 2006, Emory University, Atlanta, Georgia. The meeting brought together a number of leading investigators interested in the interplay between cell biology and retrovirology with an emphasis on presentation of new and unpublished data. The conference was arranged from early to late events in the virus replication cycle, with sessions on viral fusion, entry, and transmission; post-entry restrictions to retroviral infection; nuclear import and integration; gene expression/regulation of retroviral Gag and genomic RNA; and assembly/release. In this review, we will attempt to touch briefly on some of the highlights of the conference, and will emphasize themes and trends that emerged at the meeting. Meeting report The conference began with a keynote address from W. Sundquist on the biochemistry of HIV-1 budding. This presentation will be described in the section on Assembly and Release of Retroviruses.

  9. Information Literacy in Biology Education: An Example from an Advanced Cell Biology Course

    Science.gov (United States)

    2005-01-01

    Information literacy skills are critically important for the undergraduate biology student. The ability to find, understand, evaluate, and use information, whether from the scientific literature or from Web resources, is essential for a good understanding of a topic and for the conduct of research. A project in which students receive information literacy instruction and then proceed to select, update, and write about a current research topic in an upper-level cell biology course is described. Students research the chosen topic using paper and electronic resources, generate a list of relevant articles, prepare abstracts based on papers read, and, finally, prepare a “state-of-the-art” paper on the topic. This approach, which extends over most of one semester, has resulted in a number of well-researched and well-written papers that incorporate some of the latest research in cell biology. The steps in this project have also led to students who are prepared to address future projects on new and complex topics. The project is part of an undergraduate course in cell biology, but parts of the assignments can be modified to fit a variety of subject areas and levels. PMID:16341261

  10. 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.

  11. Phase-field theories for mathematical modeling of biological membranes.

    Science.gov (United States)

    Lázaro, Guillermo R; Pagonabarraga, Ignacio; Hernández-Machado, Aurora

    2015-01-01

    Biological membranes are complex structures whose mechanics are usually described at a mesoscopic level, such as the Helfrich bending theory. In this article, we present the phase-field methods, a useful tool for studying complex membrane problems which can be applied to very different phenomena. We start with an overview of the general theory of elasticity, paying special attention to its derivation from a molecular scale. We then study the particular case of membrane elasticity, explicitly obtaining the Helfrich bending energy. Within the framework of this theory, we derive a phase-field model for biological membranes and explore its physical basis and interpretation in terms of membrane elasticity. We finally explain three examples of applications of these methods to membrane related problems. First, the case of vesicle pearling and tubulation, when lipidic vesicles are exposed to the presence of hydrophobic polymers that anchor to the membrane, inducing a shape instability. Finally, we study the behavior of red blood cells while flowing in narrow microchannels, focusing on the importance of membrane elasticity to the cell flow capabilities. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Insights into neural stem cell biology from flies.

    Science.gov (United States)

    Egger, Boris; Chell, James M; Brand, Andrea H

    2008-01-12

    Drosophila neuroblasts are similar to mammalian neural stem cells in their ability to self-renew and to produce many different types of neurons and glial cells. In the past two decades, great advances have been made in understanding the molecular mechanisms underlying embryonic neuroblast formation, the establishment of cell polarity and the temporal regulation of cell fate. It is now a challenge to connect, at the molecular level, the different cell biological events underlying the transition from neural stem cell maintenance to differentiation. Progress has also been made in understanding the later stages of development, when neuroblasts become mitotically inactive, or quiescent, and are then reactivated postembryonically to generate the neurons that make up the adult nervous system. The ability to manipulate the steps leading from quiescence to proliferation and from proliferation to differentiation will have a major impact on the treatment of neurological injury and neurodegenerative disease.

  13. Biology and clinical utilization of mesenchymal progenitor cells

    Directory of Open Access Journals (Sweden)

    J.J. Minguell

    2000-08-01

    Full Text Available Within the complex cellular arrangement found in the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal progenitor cells (MPC. These cells can be expanded ex vivo and induced, either in vitro or in vivo, to terminally differentiate into at least seven types of cells: osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes and hematopoietic-supporting stroma. This broad multipotentiality, the feasibility to obtain MPC from bone marrow, cord and peripheral blood and their transplantability support the impact that the use of MPC will have in clinical settings. However, a number of fundamental questions about the cellular and molecular biology of MPC still need to be resolved before these cells can be used for safe and effective cell and gene therapies intended to replace, repair or enhance the physiological function of the mesenchymal and/or hematopoietic systems.

  14. Mathematical modeling of the evolution of a simple biological system

    Digital Repository Service at National Institute of Oceanography (India)

    Gonsalves, M.J.B.D.; Neetu, S.; Krishnan, K.P.; Attri, K.; LokaBharathi, P.A.

    Paula, Goa 403 004, India. Phone: +91 0832 2450624, Fax: +91 0832 2450606, e-mail: mjudith@nio.org Introduction In India, classroom education in biology does not generally include an exercise in which the data can be used to develop models.... This has hampered exposure to quantitative tools in biology, much to the disadvantage of students. The purpose of this note is to report an exercise we carried out to expose traditional biologists educated in India to mathematical modelling of biological...

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Digital Learning Material for Model Building in Molecular Biology

    Science.gov (United States)

    Aegerter-Wilmsen, Tinri; Janssen, Fred; Hartog, Rob; Bisseling, Ton

    2005-01-01

    Building models to describe processes forms an essential part of molecular biology research. However, in molecular biology curricula little attention is generally being paid to the development of this skill. In order to provide students the opportunity to improve their model building skills, we decided to develop a number of digital cases about…

  20. 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.

  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. Extracellular Vesicles: Evolving Factors in Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Muhammad Nawaz

    2016-01-01

    Full Text Available Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

  3. Extracellular Vesicles: Evolving Factors in Stem Cell Biology

    Science.gov (United States)

    Nawaz, Muhammad; Fatima, Farah; Vallabhaneni, Krishna C.; Penfornis, Patrice; Valadi, Hadi; Ekström, Karin; Kholia, Sharad; Whitt, Jason D.; Fernandes, Joseph D.; Pochampally, Radhika; Squire, Jeremy A.; Camussi, Giovanni

    2016-01-01

    Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies. PMID:26649044

  4. 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.

  5. 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

  6. 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…

  7. 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.

  8. Cdc48: A Swiss Army Knife of Cell Biology

    Directory of Open Access Journals (Sweden)

    Guem Hee Baek

    2013-01-01

    Full Text Available Cdc48 (also called VCP and p97 is an abundant protein that plays essential regulatory functions in a broad array of cellular processes. Working with various cofactors, Cdc48 utilizes its ATPase activity to promote the assembly and disassembly of protein complexes. Here, we review key biological functions and regulation of Cdc48 in ubiquitin-related events. Given the broad employment of Cdc48 in cell biology and its intimate ties to human diseases (e.g., amyotrophic lateral sclerosis, studies of Cdc48 will bring significant insights into the mechanism and function of ubiquitin in health and diseases.

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

    Directory of Open Access Journals (Sweden)

    Matthew Emerson Randolph

    2015-10-01

    Full Text Available 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, 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 muscular dystrophies. The biology of muscle stem cells varies depending on their embryologic origins and 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.

  10. 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

  11. 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.

  12. 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.

  13. Modeling the mechanisms of biological GTP hydrolysis

    DEFF Research Database (Denmark)

    Carvalho, Alexandra T.P.; Szeler, Klaudia; Vavitsas, Konstantinos

    2015-01-01

    in which GTP hydrolysis is activated and regulated is still a controversial topic and well-designed simulations can play an important role in resolving and rationalizing the experimental data. In this review, we discuss the contributions of computational biology to our understanding of GTP hydrolysis...

  14. The cell biology of lignification in higher plants.

    Science.gov (United States)

    Barros, Jaime; Serk, Henrik; Granlund, Irene; Pesquet, Edouard

    2015-06-01

    Lignin is a polyphenolic polymer that strengthens and waterproofs the cell wall of specialized plant cell types. Lignification is part of the normal differentiation programme and functioning of specific cell types, but can also be triggered as a response to various biotic and abiotic stresses in cells that would not otherwise be lignifying. Cell wall lignification exhibits specific characteristics depending on the cell type being considered. These characteristics include the timing of lignification during cell differentiation, the palette of associated enzymes and substrates, the sub-cellular deposition sites, the monomeric composition and the cellular autonomy for lignin monomer production. This review provides an overview of the current understanding of lignin biosynthesis and polymerization at the cell biology level. The lignification process ranges from full autonomy to complete co-operation depending on the cell type. The different roles of lignin for the function of each specific plant cell type are clearly illustrated by the multiple phenotypic defects exhibited by knock-out mutants in lignin synthesis, which may explain why no general mechanism for lignification has yet been defined. The range of phenotypic effects observed include altered xylem sap transport, loss of mechanical support, reduced seed protection and dispersion, and/or increased pest and disease susceptibility. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. Cell lineage tree models of neurogenesis.

    Science.gov (United States)

    Slater, Jennifer L; Landman, Kerry A; Hughes, Barry D; Shen, Qin; Temple, Sally

    2009-01-21

    The production of neurons to form the mammalian cortex, known as embryonic cortical neurogenesis, is a complex developmental process. Insight into the process of cell division during neurogenesis is provided by murine cortical cell lineage trees, recorded through experimental observation. Recurring patterns within cell lineage trees may be indicative of predetermined cell behaviour. The application of mathematical modelling to this process requires careful consideration and identification of the key features to be incorporated into the model. A biologically plausible stochastic model of evolution of cell lineage trees is developed, based on the most important known features of neurogenesis. Tractable means of measuring lineage tree shape are discussed. Symmetry is identified as a significant feature of shape and is measured using Colless's Index of Imbalance. Distributions of tree size and imbalance for large tree sizes are computed and results compared to experimental data. Several refinements to the model are investigated, when the cell division probabilities are weighted according to cell generation. Two models involving generation-dependent cell division probabilities produce imbalance distributions which are the most consistent with the available experimental results. The results indicate that a stochastic cell division mechanism is a plausible basis of mammalian neurogenesis.

  20. 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.).

  1. 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...

  2. 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

  3. Modelling and Inference Strategies for Biological Systems

    OpenAIRE

    Palmisano, Alida

    2010-01-01

    For many years, computers have played an important role in helping scientists to store, manipulate, and analyze data coming from many different disciplines. In recent years, however, new technological capabilities and new ways of thinking about the usefulness of computer science is extending the reach of computers from simple analysis of collected data to hypothesis generation. The aim of this work is to provide a contribution in the Computational Systems Biology field. The main purpose of...

  4. A guide to numerical modelling in systems biology

    CERN Document Server

    Deuflhard, Peter

    2015-01-01

    This book is intended for students of computational systems biology with only a limited background in mathematics. Typical books on systems biology merely mention algorithmic approaches, but without offering a deeper understanding. On the other hand, mathematical books are typically unreadable for computational biologists. The authors of the present book have worked hard to fill this gap. The result is not a book on systems biology, but on computational methods in systems biology. This book originated from courses taught by the authors at Freie Universität Berlin. The guiding idea of the courses was to convey those mathematical insights that are indispensable for systems biology, teaching the necessary mathematical prerequisites by means of many illustrative examples and without any theorems. The three chapters cover the mathematical modelling of biochemical and physiological processes, numerical simulation of the dynamics of biological networks, and identification of model parameters by means of comparisons...

  5. Shedding light on the cell biology of extracellular vesicles.

    Science.gov (United States)

    van Niel, Guillaume; D'Angelo, Gisela; Raposo, Graça

    2018-04-01

    Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.

  6. 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.

  7. Crosstalk between clinical orthodontics and bone cell biology

    OpenAIRE

    小林, 泰浩

    2003-01-01

    The recent discovery of receptor activator of nuclear factor k B ligand (RANKL)-RANK interaction confirms the well-known hypothesis that osteoblasts play an essential role in osteoclast differentiation. Osteoblasts express RANKL as a membrane-associated factor in response to various factors such as 1,25 dihydroxy vitamin D_3, parathyroid hormone, prostaglandin E_2 and Interluekin-11. The recent progress of bone cell biology has been exploring the mechanism of tooth movement for clinical ortho...

  8. Influence of cytoskeleton on nanoparticle migration in biological cells

    Czech Academy of Sciences Publication Activity Database

    Tarasenko, Alexander; Jastrabík, Lubomír

    2009-01-01

    Roč. 95, č. 17 (2009), 173705/1-173705/3 ISSN 0003-6951 R&D Projects: GA MŠk(CZ) 1M06002; GA AV ČR 1QS100100563 Institutional research plan: CEZ:AV0Z10100522 Keywords : particle diffusion * cytoskeleton proteins * biological cells Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.554, year: 2009

  9. Modelling biological pathway dynamics with Timed Automata

    NARCIS (Netherlands)

    Schivo, Stefano; Scholma, Jetse; Wanders, B.; Urquidi Camacho, Ricardo A.; van der Vet, P.E.; Karperien, Hermanus Bernardus Johannes; Langerak, Romanus; van de Pol, Jan Cornelis; Post, Janine Nicole

    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 to

  10. T-cell Lymphomas: Updates in Biology and Diagnosis.

    Science.gov (United States)

    Ondrejka, Sarah L; Hsi, Eric D

    2016-03-01

    Nodal-based peripheral T-cell lymphomas are heterogeneous malignancies with overlapping morphology and clinical features. However, the current World Health Organization classification scheme separates these tumors into prognostically relevant categories. Since its publication, efforts to uncover the gene expression profiles and molecular alterations have subdivided these categories further, and distinct subgroups are emerging with specific profiles that reflect the cell of origin for these tumors and their microenvironment. Identification of the perturbed biologic pathways may prove useful in selecting patients for specific therapies and associating biomarkers with survival and relapse. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 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.

  12. Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology

    Science.gov (United States)

    Pei, Duanqing; Xu, Jianyong; Zhuang, Qiang; Tse, Hung-Fat; Esteban, Miguel A.

    The potential of human embryonic stem cells (ESCs) for regenerative medicine is unquestionable, but practical and ethical considerations have hampered clinical application and research. In an attempt to overcome these issues, the conversion of somatic cells into pluripotent stem cells similar to ESCs, commonly termed nuclear reprogramming, has been a top objective of contemporary biology. More than 40 years ago, King, Briggs, and Gurdon pioneered somatic cell nuclear reprogramming in frogs, and in 1981 Evans successfully isolated mouse ESCs. In 1997 Wilmut and collaborators produced the first cloned mammal using nuclear transfer, and then Thomson obtained human ESCs from in vitro fertilized blastocysts in 1998. Over the last 2 decades we have also seen remarkable findings regarding how ESC behavior is controlled, the importance of which should not be underestimated. This knowledge allowed the laboratory of Shinya Yamanaka to overcome brilliantly conceptual and technical barriers in 2006 and generate induced pluripotent stem cells (iPSCs) from mouse fibroblasts by overexpressing defined combinations of ESC-enriched transcription factors. Here, we discuss some important implications of human iPSCs for biology and medicine and also point to possible future directions.

  13. ARM-Cortex M3-Based Two-Wheel Robot for Assessing Grid Cell Model of Medial Entorhinal Cortex: Progress towards Building Robots with Biologically Inspired Navigation-Cognitive Maps

    Directory of Open Access Journals (Sweden)

    J. Cuneo

    2017-01-01

    Full Text Available This article presents the implementation and use of a two-wheel autonomous robot and its effectiveness as a tool for studying the recently discovered use of grid cells as part of mammalian’s brains space-mapping circuitry (specifically the medial entorhinal cortex. A proposed discrete-time algorithm that emulates the medial entorhinal cortex is programed into the robot. The robot freely explores a limited laboratory area in the manner of a rat or mouse and reports information to a PC, thus enabling research without the use of live individuals. Position coordinate neural maps are achieved as mathematically predicted although for a reduced number of implemented neurons (i.e., 200 neurons. However, this type of computational embedded system (robot’s microcontroller is found to be insufficient for simulating huge numbers of neurons in real time (as in the medial entorhinal cortex. It is considered that the results of this work provide an insight into achieving an enhanced embedded systems design for emulating and understanding mathematical neural network models to be used as biologically inspired navigation system for robots.

  14. Low Voltage Transmission Electron Microscopy in Cell Biology.

    Science.gov (United States)

    Bendayan, Moise; Paransky, Eugene

    2015-07-01

    Low voltage transmission electron microscopy (LVTEM) was employed to examine biological tissues with accelerating voltages as low as 5kV. Tissue preparation was modified to take advantage of the low-voltage techniques. Treatments with heavy metals, such as post-fixation with osmium tetroxide, on block and counterstaining were omitted. Sections (40nm) were thinner than usual and generated highly contrasted images. General appearance of the cells remains similar to that of conventional TEM. New features were however revealed. The matrix of the pancreatic granules displays heterogeneity with partitions that may correspond to the inner-segregation of their secretory proteins. Mitochondria revealed the presence of the ATP synthase granules along their cristea. The nuclear dense chromatin displayed a honeycomb organization while distinct beads, nucleosomes, aligned along thin threads were seen in the dispersed chromatin. Nuclear pore protein complexes revealed their globular nature. The intercalated disks in cardiac muscle displayed their fine structural organization. These features correlate well with data described or predicted by cell and molecular biology. These new aspects are not revealed when thicker and conventionally osmicated tissue sections were examined by LVTEM, indicating that major masking effects are associated with standard TEM techniques. Immunogold was adapted to LVTEM further enhancing its potential in cell biology. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

    African Journals Online (AJOL)

    Further, in the BSR model the end-product sulphide has a gaseous equilibrium not in the UCTADM1 model, and hence the physical gas exchange for sulphide is included. The BSR biological, chemical and physical processes are integrated with those of the UCTADM1 model, to give a complete kinetic model for competitive ...

  16. 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...

  17. A Modeling Approach to Teaching Evolutionary Biology in High Schools.

    Science.gov (United States)

    Passmore, Cynthia; Stewart, Jim

    2002-01-01

    Describes the commitments and research that went into the design of a 9-week high school course in evolutionary biology designed to bring students to an understanding of the practice of evolutionary biology by engaging them in developing, elaborating, and using one of the discipline's most important explanatory models. (Contains 39 references.)…

  18. 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.

  19. 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...

  20. Regenerative Endodontic Procedures: A Perspective from Stem Cell Niche Biology.

    Science.gov (United States)

    Marí-Beffa, Manuel; Segura-Egea, Juan José; Díaz-Cuenca, Aránzazu

    2017-01-01

    Endodontics uses cell therapy strategies to treat pulpal and periapical diseases. During these therapies, surgeons aim to reconstruct the natural microenvironments that regulate the activity of dental stem cells. We searched for more than 400 articles in PubMed using key words from regenerative endodontics and dental stem cell biology. In 268 articles, we reviewed what factors may influence histologic results after preclinical dental treatments that use regenerative endodontic procedures after pulpectomy. Several factors, such as the origin of stem cells, the biomimicry of scaffolds used, and the size of lesions, are considered to influence the histologic appearance of the regenerated pulp-dentin complex after treatments. Information is accumulating on transcription factors that generate the pulp-dentin complex and survival/trophic factors that would benefit niche recovery and histologic results. In this article, we discuss the noninterchangeability of stem cells, the influence of dentin-entrapped molecule release on pulp regeneration and survival of stem cells, and the need of positional markers to assess treatments histologically. The ex vivo amplification of appropriate dental stem cells, the search for scaffolds storing the molecular diversity entrapped in the dentin, and the use of positional transcription factors as histologic markers are necessary to improve future preclinical experiments. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  1. Computational Modeling, Formal Analysis, and Tools for Systems Biology.

    Directory of Open Access Journals (Sweden)

    Ezio Bartocci

    2016-01-01

    Full Text Available As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  2. 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.)

  3. Integrated modelling of physical, chemical and biological weather

    DEFF Research Database (Denmark)

    Kurganskiy, Alexander

    Integrated modelling of physical, chemical and biological weather has been widely considered during the recent decades. Such modelling includes interactions of atmospheric physics and chemical/biological aerosol concentrations. Emitted aerosols are subject to atmospheric transport, dispersion...... and deposition, but in turn they impact the radiation as well as cloud and precipitation formation. The present study focuses on birch pollen modelling as well as on physical and chemical weather with emphasis on black carbon (BC) aerosol modelling. The Enviro-HIRLAM model has been used for the study...

  4. 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...

  5. Cell-Free Production of Protein Biologics Within 24 H.

    Science.gov (United States)

    Sullivan, Challise J; Pendleton, Erik D; Dresios, John

    2018-01-01

    Protein biologics have emerged as a safe and effective group of drug products that can be used in a variety of medical disorders and clinical settings, including treatment of orphan diseases, personalized medicine, and point-of-care applications. However, the full potential of protein biologics for such applications will not be realized until there are methods available for rapid and cost-effective production of small scale products for individual needs. Here, we describe a modular and scalable method for rapid and adaptable production of protein-based medical products at small doses. The method includes cell-free synthesis of the protein target in a reactor module followed by a fluidic process for protein purification. As a proof of concept, we describe the application of this method for expression and purification of a bioactive pharmaceutically relevant protein biologic, recombinant human erythropoietin, at a single dose within 24 h. This method can be applied toward the development of automated platforms for rapid and adaptive production of protein biologics at the point of care in response to specific medical needs.

  6. 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.

  7. Female versus male biological identities of nanoparticles determine the interaction with immune cells in fish

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Miclaus, Teodora; Murugadoss, Sivakumar

    2017-01-01

    can acquire a differential biological identity. Here we examined whether a unique biological identity acquired from sex-specific protein repertoires could alter the degree of nanoparticle uptake by cognate immune cells. We chose zebrafish as a model species of which blood plasma is sexually contrasted...... by the unique presence/absence of the egg yolk precursor protein vitellogenin. Sex-specific protein coronas were thus formed around 70 nm SiO2 nanoparticles using female/male blood plasma from zebrafish or fetal bovine serum as a non-native reference. In contrast to protein coronas formed of male blood plasma......, a “female” biological identity of the nanoparticles was represented by prevailing contribution of vitellogenins to the corona proteome. We then exposed zebrafish blood cells to the three types of pre-formed nanoparticle–protein complexes and compared nanoparticle uptake using flow cytometry. Lymphoid...

  8. Unified Mie and fractal scattering by biological cells and subcellular structures.

    Science.gov (United States)

    Wu, Tao T; Qu, Jianan Y; Xu, Min

    2007-08-15

    Angle-resolved light scattering spectroscopy of biological cells is investigated in the visible wavelength range. A unified Mie and fractal model is shown to provide an accurate global agreement with light scattering spectra from 1.1 degrees to 165 degrees scattering angles. It is found that light scattering in forward directions (Mie scattering by the bare cell and nucleus, whereas light scattering at large angles (>20 degrees ) is determined by fractal scattering by subcellular structures. The findings are consistent with the results of experimental investigation of the contributions of different cellular components to light scattering by cells.

  9. 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 appearanc...

  10. 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

  11. 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.

  12. 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.

  13. A dynamic model for functional mapping of biological rhythms.

    Science.gov (United States)

    Fu, Guifang; Luo, Jiangtao; Berg, Arthur; Wang, Zhong; Li, Jiahan; Das, Kiranmoy; Li, Runze; Wu, Rongling

    2011-01-01

    Functional mapping is a statistical method for mapping quantitative trait loci (QTLs) that regulate the dynamic pattern of a biological trait. This method integrates mathematical aspects of biological complexity into a mixture model for genetic mapping and tests the genetic effects of QTLs by comparing genotype-specific curve parameters. As a way of quantitatively specifying the dynamic behavior of a system, differential equations have proven to be powerful for modeling and unraveling the biochemical, molecular, and cellular mechanisms of a biological process, such as biological rhythms. The equipment of functional mapping with biologically meaningful differential equations provides new insights into the genetic control of any dynamic processes. We formulate a new functional mapping framework for a dynamic biological rhythm by incorporating a group of ordinary differential equations (ODE). The Runge-Kutta fourth order algorithm was implemented to estimate the parameters that define the system of ODE. The new model will find its implications for understanding the interplay between gene interactions and developmental pathways in complex biological rhythms.

  14. 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.

  15. Viral immune evasion strategies and the underlying cell biology.

    Science.gov (United States)

    Lorenzo, M E; Ploegh, H L; Tirabassi, R S

    2001-02-01

    Evasion of the immune system by viruses is a well-studied field. It remains a challenge to understand how these viral tactics affect pathogenesis and the viral lifecycle. At the same time, the study of viral proteins involved in immune evasion has helped us to better understand a number of cellular processes at the molecular level. Here we review recent data on different viral tactics for immune evasion and highlight what these viral interventions might teach us about cell biology. Copyright 2001 Academic Press.

  16. A modified microdosimetric kinetic model for relative biological effectiveness calculation

    Science.gov (United States)

    Chen, Yizheng; Li, Junli; Li, Chunyan; Qiu, Rui; Wu, Zhen

    2018-01-01

    In the heavy ion therapy, not only the distribution of physical absorbed dose, but also the relative biological effectiveness (RBE) weighted dose needs to be taken into account. The microdosimetric kinetic model (MKM) can predict the RBE value of heavy ions with saturation-corrected dose-mean specific energy, which has been used in clinical treatment planning at the National Institute of Radiological Sciences. In the theoretical assumption of the MKM, the yield of the primary lesion is independent of the radiation quality, while the experimental data shows that DNA double strand break (DSB) yield, considered as the main primary lesion, depends on the LET of the particle. Besides, the β parameter of the MKM is constant with LET resulting from this assumption, which also differs from the experimental conclusion. In this study, a modified MKM was developed, named MMKM. Based on the experimental DSB yield of mammalian cells under the irradiation of ions with different LETs, a RBEDSB (RBE for the induction of DSB)-LET curve was fitted as the correction factor to modify the primary lesion yield in the MKM, and the variation of the primary lesion yield with LET is considered in the MMKM. Compared with the present the MKM, not only the α parameter of the MMKM for mono-energetic ions agree with the experimental data, but also the β parameter varies with LET and the variation trend of the experimental result can be reproduced on the whole. Then a spread-out Bragg peaks (SOBP) distribution of physical dose was simulated with Geant4 Monte Carlo code, and the biological and clinical dose distributions were calculated, under the irradiation of carbon ions. The results show that the distribution of clinical dose calculated with the MMKM is closed to the distribution with the MKM in the SOBP, while the discrepancy before and after the SOBP are both within 10%. Moreover, the MKM might overestimate the clinical dose at the distal end of the SOBP more than 5% because of its

  17. Bionic models for identification of biological systems

    Science.gov (United States)

    Gerget, O. M.

    2017-01-01

    This article proposes a clinical decision support system that processes biomedical data. For this purpose a bionic model has been designed based on neural networks, genetic algorithms and immune systems. The developed system has been tested on data from pregnant women. The paper focuses on the approach to enable selection of control actions that can minimize the risk of adverse outcome. The control actions (hyperparameters of a new type) are further used as an additional input signal. Its values are defined by a hyperparameter optimization method. A software developed with Python is briefly described.

  18. Modeling the Biological Diversity of Pig Carcasses

    DEFF Research Database (Denmark)

    Erbou, Søren Gylling Hemmingsen

    for extracting and modeling meaningful information from the vast amount of information available from non-invasive imaging data. The lean meat percentage (LMP) is a common standard for measuring the quality of pig carcasses. Measuring the LMP using CT and using this as a reference for calibration of online...... more spatially localized modes of variation that are easier interpretable and the latter enables the use of PDM’s without the need for full point correspondence of new data. There is great potential in applying CT as non-invasive modality in the meat industry, e.g. in population based studies...

  19. 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

  20. 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.

  1. 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

  2. Modeling and simulation of biological systems using SPICE language

    Science.gov (United States)

    Lallement, Christophe; Haiech, Jacques

    2017-01-01

    The article deals with BB-SPICE (SPICE for Biochemical and Biological Systems), an extension of the famous Simulation Program with Integrated Circuit Emphasis (SPICE). BB-SPICE environment is composed of three modules: a new textual and compact description formalism for biological systems, a converter that handles this description and generates the SPICE netlist of the equivalent electronic circuit and NGSPICE which is an open-source SPICE simulator. In addition, the environment provides back and forth interfaces with SBML (System Biology Markup Language), a very common description language used in systems biology. BB-SPICE has been developed in order to bridge the gap between the simulation of biological systems on the one hand and electronics circuits on the other hand. Thus, it is suitable for applications at the interface between both domains, such as development of design tools for synthetic biology and for the virtual prototyping of biosensors and lab-on-chip. Simulation results obtained with BB-SPICE and COPASI (an open-source software used for the simulation of biochemical systems) have been compared on a benchmark of models commonly used in systems biology. Results are in accordance from a quantitative viewpoint but BB-SPICE outclasses COPASI by 1 to 3 orders of magnitude regarding the computation time. Moreover, as our software is based on NGSPICE, it could take profit of incoming updates such as the GPU implementation, of the coupling with powerful analysis and verification tools or of the integration in design automation tools (synthetic biology). PMID:28787027

  3. A Transformative Model for Undergraduate Quantitative Biology Education

    Science.gov (United States)

    Driscoll, Tobin A.; Dhurjati, Prasad; Pelesko, John A.; Rossi, Louis F.; Schleiniger, Gilberto; Pusecker, Kathleen; White, Harold B.

    2010-01-01

    The BIO2010 report recommended that students in the life sciences receive a more rigorous education in mathematics and physical sciences. The University of Delaware approached this problem by (1) developing a bio-calculus section of a standard calculus course, (2) embedding quantitative activities into existing biology courses, and (3) creating a new interdisciplinary major, quantitative biology, designed for students interested in solving complex biological problems using advanced mathematical approaches. To develop the bio-calculus sections, the Department of Mathematical Sciences revised its three-semester calculus sequence to include differential equations in the first semester and, rather than using examples traditionally drawn from application domains that are most relevant to engineers, drew models and examples heavily from the life sciences. The curriculum of the B.S. degree in Quantitative Biology was designed to provide students with a solid foundation in biology, chemistry, and mathematics, with an emphasis on preparation for research careers in life sciences. Students in the program take core courses from biology, chemistry, and physics, though mathematics, as the cornerstone of all quantitative sciences, is given particular prominence. Seminars and a capstone course stress how the interplay of mathematics and biology can be used to explain complex biological systems. To initiate these academic changes required the identification of barriers and the implementation of solutions. PMID:20810949

  4. A transformative model for undergraduate quantitative biology education.

    Science.gov (United States)

    Usher, David C; Driscoll, Tobin A; Dhurjati, Prasad; Pelesko, John A; Rossi, Louis F; Schleiniger, Gilberto; Pusecker, Kathleen; White, Harold B

    2010-01-01

    The BIO2010 report recommended that students in the life sciences receive a more rigorous education in mathematics and physical sciences. The University of Delaware approached this problem by (1) developing a bio-calculus section of a standard calculus course, (2) embedding quantitative activities into existing biology courses, and (3) creating a new interdisciplinary major, quantitative biology, designed for students interested in solving complex biological problems using advanced mathematical approaches. To develop the bio-calculus sections, the Department of Mathematical Sciences revised its three-semester calculus sequence to include differential equations in the first semester and, rather than using examples traditionally drawn from application domains that are most relevant to engineers, drew models and examples heavily from the life sciences. The curriculum of the B.S. degree in Quantitative Biology was designed to provide students with a solid foundation in biology, chemistry, and mathematics, with an emphasis on preparation for research careers in life sciences. Students in the program take core courses from biology, chemistry, and physics, though mathematics, as the cornerstone of all quantitative sciences, is given particular prominence. Seminars and a capstone course stress how the interplay of mathematics and biology can be used to explain complex biological systems. To initiate these academic changes required the identification of barriers and the implementation of solutions.

  5. Contemporary Phage Biology: From Classic Models to New Insights.

    Science.gov (United States)

    Ofir, Gal; Sorek, Rotem

    2018-03-08

    Bacteriophages, discovered about a century ago, have been pivotal as models for understanding the fundamental principles of molecular biology. While interest in phage biology declined after the phage "golden era," key recent developments, including advances in phage genomics, microscopy, and the discovery of the CRISPR-Cas anti-phage defense system, have sparked a renaissance in phage research in the past decade. This review highlights recently discovered unexpected complexities in phage biology, describes a new arsenal of phage genes that help them overcome bacterial defenses, and discusses advances toward documentation of the phage biodiversity on a global scale. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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 ...

  8. 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...

  9. 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.

  10. 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.

  11. Integrated modelling of physical, chemical and biological weather

    DEFF Research Database (Denmark)

    Kurganskiy, Alexander

    forecasts. The BC modelling study was performed for a modelling domain covering most of the Northern Hemisphere with focus on the EU and Arctic regions. Verification of BC concentrations against observations showed a good agreement for the EU air quality measurement sites. However, the Arctic region turned......Integrated modelling of physical, chemical and biological weather has been widely considered during the recent decades. Such modelling includes interactions of atmospheric physics and chemical/biological aerosol concentrations. Emitted aerosols are subject to atmospheric transport, dispersion...... and deposition, but in turn they impact the radiation as well as cloud and precipitation formation. The present study focuses on birch pollen modelling as well as on physical and chemical weather with emphasis on black carbon (BC) aerosol modelling. The Enviro-HIRLAM model has been used for the study...

  12. 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.

  13. 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.

  14. A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

    Science.gov (United States)

    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. PMID:27187178

  15. Thyroid C-Cell Biology and Oncogenic Transformation.

    Science.gov (United States)

    Cote, Gilbert J; Grubbs, Elizabeth G; Hofmann, Marie-Claude

    2015-01-01

    The thyroid parafollicular cell, or commonly named "C-cell," functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that multiple endocrine neoplasia type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma (MTC). Thyroid C-cells are known to express RET at high levels relative to most cell types; therefore, aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET, the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations have uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation, will help in the development of novel molecular-targeted therapies.

  16. 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.

  17. Continuous time boolean modeling for biological signaling: application of Gillespie algorithm

    Directory of Open Access Journals (Sweden)

    Stoll Gautier

    2012-08-01

    Full Text Available Abstract 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. Background 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. Results 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

  18. The use of buccal cells in human biological monitoring

    Directory of Open Access Journals (Sweden)

    Ewa Błaszczyk

    2012-12-01

    Full Text Available One of the basic methods for determining the degree of environmental risk posed to humans is identification of harmful substances in various environmental elements (air, water, soil, food. In contrast to environmental monitoring human biological monitoring (HBM enables the estimation of an absorbed dose, general or localized in a specific organ. HBM enables the assessment of exposure to substances which are absorbed by the body via different exposure pathways and with different contaminant carriers. It is based on the measurement of indicators, the so-called biomarkers, in body fluids (blood, urine, saliva, etc. or in tissues and organs. Biomarkers can be divided into markers of exposure, effects and susceptibility. A particularly useful method is determination of adducts, i.e. carcinogenic compounds (or their metabolites with proteins or DNA, which are markers of exposure. Biomarkers of biological effects are different cytogenetic changes, including micronuclei. These are extranuclear structures containing fragments of chromatin (arising as a result of DNA breaks or whole chromosomes (damage to the spindle apparatus during mitosis. Up to now most studies on the DNA adduct levels and micronuclei have been conducted in peripheral lymphocytes. At present, studies using blood, especially in children to restricted to ethical aspects, and therefore tests using epithelial cells from the oral cavity have become more popular. Epithelial cells are the main building material of an epithelial tissue which makes up about 60% of all cells of the human body. The main function of the epithelial tissue is covering and lining of the outer and inner surfaces of the body. Epithelium underwent high specialisation in various parts of the human body, which is associated with its structure and function. Human oral cavity is covered by stratified squamous epithelium, which is comprised of cells called keratinocytes. Oral epithelial cells may differentiate in two

  19. Bio-logic builder: a non-technical tool for building dynamical, qualitative models.

    Science.gov (United States)

    Helikar, Tomáš; Kowal, Bryan; Madrahimov, Alex; Shrestha, Manish; Pedersen, Jay; Limbu, Kahani; Thapa, Ishwor; Rowley, Thaine; Satalkar, Rahul; Kochi, Naomi; Konvalina, John; Rogers, Jim A

    2012-01-01

    Computational modeling of biological processes is a promising tool in biomedical research. While a large part of its potential lies in the ability to integrate it with laboratory research, modeling currently generally requires a high degree of training in mathematics and/or computer science. To help address this issue, we have developed a web-based tool, Bio-Logic Builder, that enables laboratory scientists to define mathematical representations (based on a discrete formalism) of biological regulatory mechanisms in a modular and non-technical fashion. As part of the user interface, generalized "bio-logic" modules have been defined to provide users with the building blocks for many biological processes. To build/modify computational models, experimentalists provide purely qualitative information about a particular regulatory mechanisms as is generally found in the laboratory. The Bio-Logic Builder subsequently converts the provided information into a mathematical representation described with Boolean expressions/rules. We used this tool to build a number of dynamical models, including a 130-protein large-scale model of signal transduction with over 800 interactions, influenza A replication cycle with 127 species and 200+ interactions, and mammalian and budding yeast cell cycles. We also show that any and all qualitative regulatory mechanisms can be built using this tool.

  20. Pharmacology and toxicology of diphenyl diselenide in several biological models

    Directory of Open Access Journals (Sweden)

    R.M. Rosa

    2007-10-01

    Full Text Available The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of d-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.

  1. How chemistry supports cell biology: the chemical toolbox at your service.

    Science.gov (United States)

    Wijdeven, Ruud H; Neefjes, Jacques; Ovaa, Huib

    2014-12-01

    Chemical biology is a young and rapidly developing scientific field. In this field, chemistry is inspired by biology to create various tools to monitor and modulate biochemical and cell biological processes. Chemical contributions such as small-molecule inhibitors and activity-based probes (ABPs) can provide new and unique insights into previously unexplored cellular processes. This review provides an overview of recent breakthroughs in chemical biology that are likely to have a significant impact on cell biology. We also discuss the application of several chemical tools in cell biology research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Using views of Systems Biology Cloud: application for model building.

    Science.gov (United States)

    Ruebenacker, Oliver; Blinov, Michael

    2011-03-01

    A large and growing network ("cloud") of interlinked terms and records of items of Systems Biology knowledge is available from the web. These items include pathways, reactions, substances, literature references, organisms, and anatomy, all described in different data sets. Here, we discuss how the knowledge from the cloud can be molded into representations (views) useful for data visualization and modeling. We discuss methods to create and use various views relevant for visualization, modeling, and model annotations, while hiding irrelevant details without unacceptable loss or distortion. We show that views are compatible with understanding substances and processes as sets of microscopic compounds and events respectively, which allows the representation of specializations and generalizations as subsets and supersets respectively. We explain how these methods can be implemented based on the bridging ontology Systems Biological Pathway Exchange (SBPAX) in the Systems Biology Linker (SyBiL) we have developed.

  3. 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.

  4. An integrated physical and biological model for anaerobic lagoons.

    Science.gov (United States)

    Wu, Binxin; Chen, Zhenbin

    2011-04-01

    A computational fluid dynamics (CFD) model that integrates physical and biological processes for anaerobic lagoons is presented. In the model development, turbulence is represented using a transition k-ω model, heat conduction and solar radiation are included in the thermal model, biological oxygen demand (BOD) reduction is characterized by first-order kinetics, and methane yield rate is expressed as a linear function of temperature. A test of the model applicability is conducted in a covered lagoon digester operated under tropical climate conditions. The commercial CFD software, ANSYS-Fluent, is employed to solve the integrated model. The simulation procedures include solving fluid flow and heat transfer, predicting local resident time based on the converged flow fields, and calculating the BOD reduction and methane production. The simulated results show that monthly methane production varies insignificantly, but the time to achieve a 99% BOD reduction in January is much longer than that in July. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Parameter estimation and model selection in computational biology.

    Directory of Open Access Journals (Sweden)

    Gabriele Lillacci

    2010-03-01

    Full Text Available A central challenge in computational modeling of biological systems is the determination of the model parameters. Typically, only a fraction of the parameters (such as kinetic rate constants are experimentally measured, while the rest are often fitted. The fitting process is usually based on experimental time course measurements of observables, which are used to assign parameter values that minimize some measure of the error between these measurements and the corresponding model prediction. The measurements, which can come from immunoblotting assays, fluorescent markers, etc., tend to be very noisy and taken at a limited number of time points. In this work we present a new approach to the problem of parameter selection of biological models. We show how one can use a dynamic recursive estimator, known as extended Kalman filter, to arrive at estimates of the model parameters. The proposed method follows. First, we use a variation of the Kalman filter that is particularly well suited to biological applications to obtain a first guess for the unknown parameters. Secondly, we employ an a posteriori identifiability test to check the reliability of the estimates. Finally, we solve an optimization problem to refine the first guess in case it should not be accurate enough. The final estimates are guaranteed to be statistically consistent with the measurements. Furthermore, we show how the same tools can be used to discriminate among alternate models of the same biological process. We demonstrate these ideas by applying our methods to two examples, namely a model of the heat shock response in E. coli, and a model of a synthetic gene regulation system. The methods presented are quite general and may be applied to a wide class of biological systems where noisy measurements are used for parameter estimation or model selection.

  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. 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

  8. An update of human mesenchymal stem cell biology and their clinical uses

    DEFF Research Database (Denmark)

    Zaher, Walid; Harkness, Linda; Kermani, Abbas Jafari

    2014-01-01

    In the past decade, an increasing urge to develop new and novel methods for the treatment of degenerative diseases where there is currently no effective therapy has lead to the emerging of the cell therapy or cellular therapeutics approach for the management of those conditions where organ...... and in vivo. Consequently, stromal (mesenchymal) stem cells (MSCs) are being introduced into many clinical trials due to their ease of isolation and efficacy in treating a number of disease conditions in animal preclinical disease models. The aim of this review is to revise MSC biology, their potential...

  9. 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.

  10. Modeling Biology Spanning Different Scales: An Open Challenge

    Directory of Open Access Journals (Sweden)

    Filippo Castiglione

    2014-01-01

    Full Text Available It is coming nowadays more clear that in order to obtain a unified description of the different mechanisms governing the behavior and causality relations among the various parts of a living system, the development of comprehensive computational and mathematical models at different space and time scales is required. This is one of the most formidable challenges of modern biology characterized by the availability of huge amount of high throughput measurements. In this paper we draw attention to the importance of multiscale modeling in the framework of studies of biological systems in general and of the immune system in particular.

  11. 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...

  12. Cultivation and Biological Characterization of Chicken Primordial Germ Cells

    Directory of Open Access Journals (Sweden)

    Meng Ji

    2016-01-01

    Full Text Available The purpose of this work was to investigate the isolation, culture process of chicken gonadal primordial germ cells (PGCs and study their biological characterization. PGCs were harvested from 5.5-day-old chicken embryonic genital ridges and explanted onto chicken embryonic fibroblasts (CEFs. The results showed that the primary cultivation of chicken PGCs on their own gonadal stroma cells were better than CEFs at first two days for reproduction. The conditioned media supported the growth and colony formation of PGCs for a prolonged time in vitro and maintained a normal diploid karyotype, which were positively stained by alkaline phosphatase (AKP, periodic acid Schiff (PAS and reacted with anti-SSEA-1, SSEA-3, Oct4, Blimp1 and Sox2. Real-time PCR showed that they expressed the stage specific genes CVH, Blimp1 and Dazl, the stem cell specific genes Sox2, Pouv and Nanog. They also formed the embryoid bodies (EBs. These results suggested that the chicken PGCs cultured in vitro not only had strong self-renewal ability, but also had the potential capability of multi-lineage differentiation.

  13. 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...

  14. 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.

  15. Modeling and analysis of modular structure in diverse biological networks.

    Science.gov (United States)

    Al-Anzi, Bader; Gerges, Sherif; Olsman, Noah; Ormerod, Christopher; Piliouras, Georgios; Ormerod, John; Zinn, Kai

    2017-06-07

    Biological networks, like most engineered networks, are not the product of a singular design but rather are the result of a long process of refinement and optimization. Many large real-world networks are comprised of well-defined and meaningful smaller modules. While engineered networks are designed and refined by humans with particular goals in mind, biological networks are created by the selective pressures of evolution. In this paper, we seek to define aspects of network architecture that are shared among different types of evolved biological networks. First, we developed a new mathematical model, the Stochastic Block Model with Path Selection (SBM-PS) that simulates biological network formation based on the selection of edges that increase clustering. SBM-PS can produce modular networks whose properties resemble those of real networks. Second, we analyzed three real networks of very different types, and showed that all three can be fit well by the SBM-PS model. Third, we showed that modular elements within the three networks correspond to meaningful biological structures. The networks chosen for analysis were a proteomic network composed of all proteins required for mitochondrial function in budding yeast, a mesoscale anatomical network composed of axonal connections among regions of the mouse brain, and the connectome of individual neurons in the nematode C. elegans. We find that the three networks have common architectural features, and each can be divided into subnetworks with characteristic topologies that control specific phenotypic outputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Individual cell-based models of cell scatter of ARO and MLP-29 cells in response to hepatocyte growth factor.

    Science.gov (United States)

    Scianna, Marco; Merks, Roeland M H; Preziosi, Luigi; Medico, Enzo

    2009-09-07

    The different behaviors of colonies of two cell lines, ARO (thyroid carcinoma-derived cells) and MLP-29 (mouse liver progenitor cells), in response to hepatocyte growth factor (HGF) are described deducing suitable cellular Potts models (CPM). It is shown how increased motility and decreased adhesiveness are responsible for cell-cell dissociation and tissue invasion in the ARO cells. On the other hand, it is shown that, in addition to the biological mechanisms above, it is necessary to include directional persistence in cell motility and HGF diffusion to describe the scattering and the branching processes characteristic of MLP-29 cells.

  17. 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…

  18. 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.

  19. Lipids in cell biology: how can we understand them better?

    Science.gov (United States)

    Muro, Eleonora; Atilla-Gokcumen, G. Ekin; Eggert, Ulrike S.

    2014-01-01

    Lipids are a major class of biological molecules and play many key roles in different processes. The diversity of lipids is on the same order of magnitude as that of proteins: cells express tens of thousands of different lipids and hundreds of proteins to regulate their metabolism and transport. Despite their clear importance and essential functions, lipids have not been as well studied as proteins. We discuss here some of the reasons why it has been challenging to study lipids and outline technological developments that are allowing us to begin lifting lipids out of their “Cinderella” status. We focus on recent advances in lipid identification, visualization, and investigation of their biophysics and perturbations and suggest that the field has sufficiently advanced to encourage broader investigation into these intriguing molecules. PMID:24925915

  20. Classification of biological cells using a sound wave based flow cytometer

    Science.gov (United States)

    Strohm, Eric M.; Gnyawali, Vaskar; Van De Vondervoort, Mia; Daghighi, Yasaman; Tsai, Scott S. H.; Kolios, Michael C.

    2016-03-01

    A flow cytometer that uses sound waves to determine the size of biological cells is presented. In this system, a microfluidic device made of polydimethylsiloxane (PDMS) was developed to hydrodynamically flow focus cells in a single file through a target area. Integrated into the microfluidic device was an ultrasound transducer with a 375 MHz center frequency, aligned opposite the transducer was a pulsed 532 nm laser focused into the device by a 10x objective. Each passing cell was insonfied with a high frequency ultrasound pulse, and irradiated with the laser. The resulting ultrasound and photoacoustic waves from each cell were analyzed using signal processing methods, where features in the power spectra were compared to theoretical models to calculate the cell size. Two cell lines with different size distributions were used to test the system: acute myeloid leukemia cells (AML) and melanoma cells. Over 200 cells were measured using this system. The average calculated diameter of the AML cells was 10.4 +/- 2.5 μm using ultrasound, and 11.4 +/- 2.3 μm using photoacoustics. The average diameter of the melanoma cells was 16.2 +/- 2.9 μm using ultrasound, and 18.9 +/- 3.5 μm using photoacoustics. The cell sizes calculated using ultrasound and photoacoustic methods agreed with measurements using a Coulter Counter, where the AML cells were 9.8 +/- 1.8 μm and the melanoma cells were 16.0 +/- 2.5 μm. These results demonstrate a high speed method of assessing cell size using sound waves, which is an alternative method to traditional flow cytometry techniques.

  1. Understanding pollen tube growth: the hydrodynamic model versus the cell wall model

    NARCIS (Netherlands)

    Zonia, L.; Munnik, T.

    2011-01-01

    Scientific progress stimulates the evolution of models used to understand and conceptualize biological behaviors. The widely accepted cell wall model of pollen tube growth explains stochastic growth of the apical pectin wall, but fails to explain the mechanism driving oscillations in growth and cell

  2. Biological processing of dinuclear ruthenium complexes in eukaryotic cells.

    Science.gov (United States)

    Li, Xin; Heimann, Kirsten; Dinh, Xuyen Thi; Keene, F Richard; Collins, J Grant

    2016-10-20

    The biological processing - mechanism of cellular uptake, effects on the cytoplasmic and mitochondrial membranes, intracellular sites of localisation and induction of reactive oxygen species - of two dinuclear polypyridylruthenium(ii) complexes has been examined in three eukaryotic cells lines. Flow cytometry was used to determine the uptake of [{Ru(phen)2}2{μ-bb12}](4+) (Rubb12) and [Ru(phen)2(μ-bb7)Ru(tpy)Cl](3+) {Rubb7-Cl, where phen = 1,10-phenanthroline, tpy = 2,2':6',2''-terpyridine and bbn = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane} in baby hamster kidney (BHK), human embryonic kidney (HEK-293) and liver carcinoma (HepG2) cell lines. The results demonstrated that the major uptake mechanism for Rubb12 and Rubb7-Cl was active transport, although with a significant contribution from carrier-assisted diffusion for Rubb12 and passive diffusion for Rubb7-Cl. Flow cytometry coupled with Annexin V/TO-PRO-3 double-staining was used to compare cell death by membrane damage or apoptosis. Rubb12 induced significant direct membrane damage, particularly with HepG2 cells, while Rubb7-Cl caused considerably less membrane damage but induced greater levels of apoptosis. Confocal microscopy, coupled with JC-1 assays, demonstrated that Rubb12 depolarises the mitochondrial membrane, whereas Rubb7-Cl had a much smaller affect. Cellular localisation experiments indicated that Rubb12 did not accumulate in the mitochondria, whereas significant mitochondrial accumulation was observed for Rubb7-Cl. The effect of Rubb12 and Rubb7-Cl on intracellular superoxide dismutase activity showed that the ruthenium complexes could induce cell death via a reactive oxygen species-mediated pathway. The results of this study demonstrate that Rubb12 predominantly kills eukaryotic cells by damaging the cytoplasmic membrane. As this dinuclear ruthenium complex has been previously shown to exhibit greater toxicity towards bacteria than eukaryotic cells, the results of the present study suggest that

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 75 FR 9905 - Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological...

    Science.gov (United States)

    2010-03-04

    ... Viral Vaccines for Infectious Disease Indications; Availability AGENCY: Food and Drug Administration... and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease... vaccines for the characterization and qualification of cell substrates, viral seeds, and other biological...

  10. 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:

  11. Systems Biology in Immunology – A Computational Modeling Perspective

    Science.gov (United States)

    Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra; Fraser, Iain D. C.

    2011-01-01

    Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and conduct simulations of immune function, We provide descriptions of the key data gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease. PMID:21219182

  12. Modeling and simulation of biological systems using SPICE language.

    Directory of Open Access Journals (Sweden)

    Morgan Madec

    Full Text Available The article deals with BB-SPICE (SPICE for Biochemical and Biological Systems, an extension of the famous Simulation Program with Integrated Circuit Emphasis (SPICE. BB-SPICE environment is composed of three modules: a new textual and compact description formalism for biological systems, a converter that handles this description and generates the SPICE netlist of the equivalent electronic circuit and NGSPICE which is an open-source SPICE simulator. In addition, the environment provides back and forth interfaces with SBML (System Biology Markup Language, a very common description language used in systems biology. BB-SPICE has been developed in order to bridge the gap between the simulation of biological systems on the one hand and electronics circuits on the other hand. Thus, it is suitable for applications at the interface between both domains, such as development of design tools for synthetic biology and for the virtual prototyping of biosensors and lab-on-chip. Simulation results obtained with BB-SPICE and COPASI (an open-source software used for the simulation of biochemical systems have been compared on a benchmark of models commonly used in systems biology. Results are in accordance from a quantitative viewpoint but BB-SPICE outclasses COPASI by 1 to 3 orders of magnitude regarding the computation time. Moreover, as our software is based on NGSPICE, it could take profit of incoming updates such as the GPU implementation, of the coupling with powerful analysis and verification tools or of the integration in design automation tools (synthetic biology.

  13. Biology of Zika Virus Infection in Human Skin Cells.

    Science.gov (United States)

    Hamel, Rodolphe; Dejarnac, Ophélie; Wichit, Sineewanlaya; Ekchariyawat, Peeraya; Neyret, Aymeric; Luplertlop, Natthanej; Perera-Lecoin, Manuel; Surasombatpattana, Pornapat; Talignani, Loïc; Thomas, Frédéric; Cao-Lormeau, Van-Mai; Choumet, Valérie; Briant, Laurence; Desprès, Philippe; Amara, Ali; Yssel, Hans; Missé, Dorothée

    2015-09-01

    Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus. Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal

  14. 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…

  15. Integrative biological simulation praxis: Considerations from physics, philosophy, and data/model curation practices.

    Science.gov (United States)

    Sarma, Gopal P; Faundez, Victor

    2017-01-01

    Integrative biological simulations have a varied and controversial history in the biological sciences. From computational models of organelles, cells, and simple organisms, to physiological models of tissues, organ systems, and ecosystems, a diverse array of biological systems have been the target of large-scale computational modeling efforts. Nonetheless, these research agendas have yet to prove decisively their value among the broader community of theoretical and experimental biologists. In this commentary, we examine a range of philosophical and practical issues relevant to understanding the potential of integrative simulations. We discuss the role of theory and modeling in different areas of physics and suggest that certain sub-disciplines of physics provide useful cultural analogies for imagining the future role of simulations in biological research. We examine philosophical issues related to modeling which consistently arise in discussions about integrative simulations and suggest a pragmatic viewpoint that balances a belief in philosophy with the recognition of the relative infancy of our state of philosophical understanding. Finally, we discuss community workflow and publication practices to allow research to be readily discoverable and amenable to incorporation into simulations. We argue that there are aligned incentives in widespread adoption of practices which will both advance the needs of integrative simulation efforts as well as other contemporary trends in the biological sciences, ranging from open science and data sharing to improving reproducibility.

  16. 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.

  17. Epigenetic and genetic mechanisms in red cell biology.

    Science.gov (United States)

    Hewitt, Kyle J; Sanalkumar, Rajendran; Johnson, Kirby D; Keles, Sunduz; Bresnick, Emery H

    2014-05-01

    Erythropoiesis, in which hematopoietic stem cells (HSCs) generate lineage-committed progenitors that mature into erythrocytes, is regulated by numerous chromatin modifying and remodeling proteins. We will focus on how epigenetic and genetic mechanisms mesh to establish the erythroid transcriptome and how studying erythropoiesis can yield genomic principles. Trans-acting factor binding to small DNA motifs (cis-elements) underlies regulatory complex assembly at specific chromatin sites, and therefore unique transcriptomes. As cis-elements are often very small, thousands or millions of copies of a given element reside in a genome. Chromatin restricts factor access in a context-dependent manner, and cis-element-binding factors recruit chromatin regulators that mediate functional outputs. Technologies to map chromatin attributes of loci in vivo, to edit genomes and to sequence whole genomes have been transformative in discovering critical cis-elements linked to human disease. Cis-elements mediate chromatin-targeting specificity, and chromatin regulators dictate cis-element accessibility/function, illustrating an amalgamation of genetic and epigenetic mechanisms. Cis-elements often function ectopically when studied outside of their endogenous loci, and complex strategies to identify nonredundant cis-elements require further development. Facile genome-editing technologies provide a new approach to address this problem. Extending genetic analyses beyond exons and promoters will yield a rich pipeline of cis-element alterations with importance for red cell biology and disease.

  18. History of the Department of Cell Biology at Yale School of Medicine, 1813-2010

    Science.gov (United States)

    Lentz, Thomas L.

    2011-01-01

    The Department of Cell Biology at the Yale University School of Medicine was established in 1983. It was preceded by the Section of Cell Biology, which was formed in 1973 when George E. Palade and collaborators came to Yale from the Rockefeller University. Cell Biology at Yale had its origins in the Department of Anatomy that existed from the beginning of classes at the Medical Institution of Yale College in 1813. This article reviews the history of the Department of Anatomy at Yale and its evolution into Cell Biology that began with the introduction of histology into the curriculum in the 1860s. The formation and development of the Section and Department of Cell Biology in the second half of the 20th century to the present time are described. Biographies and research activities of the chairs and key faculty in anatomy and cell biology are provided. PMID:21698037

  19. 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.

  20. Probabilistic Model Checking of Biological Systems with Uncertain Kinetic Rates

    Science.gov (United States)

    Barbuti, Roberto; Levi, Francesca; Milazzo, Paolo; Scatena, Guido

    We present an abstraction of the probabilistic semantics of Multiset Rewriting to formally express systems of reactions with uncertain kinetic rates. This allows biological systems modelling when the exact rates are not known, but are supposed to lie in some intervals. On these (abstract) models we perform probabilistic model checking obtaining lower and upper bounds for the probabilities of reaching states satisfying given properties. These bounds are under- and over-approximations, respectively, of the probabilities one would obtain by verifying the models with exact kinetic rates belonging to the intervals.

  1. Modeling and Simulation Tools: From Systems Biology to Systems Medicine.

    Science.gov (United States)

    Olivier, Brett G; Swat, Maciej J; Moné, Martijn J

    2016-01-01

    Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools.

  2. CSML2SBML: a novel tool for converting quantitative biological pathway models from CSML into SBML.

    Science.gov (United States)

    Li, Chen; Nagasaki, Masao; Ikeda, Emi; Sekiya, Yayoi; Miyano, Satoru

    2014-07-01

    CSML and SBML are XML-based model definition standards which are developed with the aim of creating exchange formats for modeling, visualizing and simulating biological pathways. In this article we report a release of a format convertor for quantitative pathway models, namely CSML2SBML. It translates models encoded by CSML into SBML without loss of structural and kinetic information. The simulation and parameter estimation of the resulting SBML model can be carried out with compliant tool CellDesigner for further analysis. The convertor is based on the standards CSML version 3.0 and SBML Level 2 Version 4. In our experiments, 11 out of 15 pathway models in CSML model repository and 228 models in Macrophage Pathway Knowledgebase (MACPAK) are successfully converted to SBML models. The consistency of the resulting model is validated by libSBML Consistency Check of CellDesigner. Furthermore, the converted SBML model assigned with the kinetic parameters translated from CSML model can reproduce the same dynamics with CellDesigner as CSML one running on Cell Illustrator. CSML2SBML, along with its instructions and examples for use are available at http://csml2sbml.csml.org. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Quantitative computational models of molecular self-assembly in systems biology

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-06-01

    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.

  4. 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.

  5. The cell biology of cross-presentation and the role of dendritic cell subsets.

    Science.gov (United States)

    Lin, Ming-Lee; Zhan, Yifan; Villadangos, Jose A; Lew, Andrew M

    2008-01-01

    The cell biology of cross-presentation is reviewed regarding exogenous antigen uptake, antigen degradation and entry into the major histocompatibility complex class I pathway. Whereas cross-presentation is not associated with enhanced phagocytic ability, certain receptors may favour uptake for cross-presentation for example mannose receptor for soluble glycoproteins. Perhaps, the defining property of the cross-presenting cell is some specialization in host machinery for handling and transport of antigen across organelles. Both cytosolic and vacuolar pathways are discussed. Which dendritic cell (DC) subset is the cross-presenting cell is explored. Cross-presentation is found within the CD8(+) subset resident in lymphoid organs. The role of other DC subsets (especially the migratory CD8(-) DC) and the route of antigen delivery are also discussed. Further consideration is given to antigen transfer between DC subsets and differential presentation to naive vs memory T cells.

  6. Forces due to surface water measured by force microscopy. Consequences for anchoring biological cells to surfaces

    International Nuclear Information System (INIS)

    Schilcher, K.

    1997-05-01

    Interaction forces in 'Scanning Force Microscopy' (SFM). Force curves revealed exponentially decaying, attractive forces between silicon tip and silicon sample in aqueous media. Replacing the silicon sample by a sheet of mica, the interaction forces had both, an attractive and a repulsive component. Addition of salts generally reduced the forces. At 500 mM salt concentration, the attractive force became quantized with a residual force value of 23 pN. The attractive force is attributed to the gain in energy of water molecules which are released from surface water into free water during tip-sample approach. This conclusion is supported by a statistical model. The repulsive force contribution in the case of mica, is caused by hydration forces due to the spatial organization of crystalline water on the mica surface. Anchoring of biological cells. Molecular resolution of cell surfaces by SFM requires cell anchoring without interference with cell physiology. For this a novel strategy, 'hydrophobic anchoring' was designed. It avoids strong attractive forces between cell and by using a flexible spacer molecule. It establishes anchoring by a lipid (bound to the spacer), which weakly interacts with the hydrophobic core of the cell membrane. The method was subjected to tests using RBL-2H3, CH0 αβ and HEK-293 cells. The strength of cell anchoring was assayed by shear forces. In all cases 'hydrophobic anchoring' via a spacer caused elective anchoring much beyond controls. Such cell anchoring was employed for the imaging of RBL-2H3 cells by SFM. Images showed considerable finer details than images of loosely adsorbed cells. With about 50 rim resolution, SFM succeeded in imaging microvilli, filopodia, single cytoskeletal fibers (microtubules, microfilaments) and vesicles. In addition, as a consequence of cell stimulation upon ionomycin treatment, lamellae formation and the appearance of secretory granules on top of them were observed which indicates the viability of anchored

  7. An Improved Swarm Optimization for Parameter Estimation and Biological Model Selection

    Science.gov (United States)

    Abdullah, Afnizanfaizal; Deris, Safaai; Mohamad, Mohd Saberi; Anwar, Sohail

    2013-01-01

    One of the key aspects of computational systems biology is the investigation on the dynamic biological processes within cells. Computational models are often required to elucidate the mechanisms and principles driving the processes because of the nonlinearity and complexity. The models usually incorporate a set of parameters that signify the physical properties of the actual biological systems. In most cases, these parameters are estimated by fitting the model outputs with the corresponding experimental data. However, this is a challenging task because the available experimental data are frequently noisy and incomplete. In this paper, a new hybrid optimization method is proposed to estimate these parameters from the noisy and incomplete experimental data. The proposed method, called Swarm-based Chemical Reaction Optimization, integrates the evolutionary searching strategy employed by the Chemical Reaction Optimization, into the neighbouring searching strategy of the Firefly Algorithm method. The effectiveness of the method was evaluated using a simulated nonlinear model and two biological models: synthetic transcriptional oscillators, and extracellular protease production models. The results showed that the accuracy and computational speed of the proposed method were better than the existing Differential Evolution, Firefly Algorithm and Chemical Reaction Optimization methods. The reliability of the estimated parameters was statistically validated, which suggests that the model outputs produced by these parameters were valid even when noisy and incomplete experimental data were used. Additionally, Akaike Information Criterion was employed to evaluate the model selection, which highlighted the capability of the proposed method in choosing a plausible model based on the experimental data. In conclusion, this paper presents the effectiveness of the proposed method for parameter estimation and model selection problems using noisy and incomplete experimental data. This

  8. An improved swarm optimization for parameter estimation and biological model selection.

    Directory of Open Access Journals (Sweden)

    Afnizanfaizal Abdullah

    Full Text Available One of the key aspects of computational systems biology is the investigation on the dynamic biological processes within cells. Computational models are often required to elucidate the mechanisms and principles driving the processes because of the nonlinearity and complexity. The models usually incorporate a set of parameters that signify the physical properties of the actual biological systems. In most cases, these parameters are estimated by fitting the model outputs with the corresponding experimental data. However, this is a challenging task because the available experimental data are frequently noisy and incomplete. In this paper, a new hybrid optimization method is proposed to estimate these parameters from the noisy and incomplete experimental data. The proposed method, called Swarm-based Chemical Reaction Optimization, integrates the evolutionary searching strategy employed by the Chemical Reaction Optimization, into the neighbouring searching strategy of the Firefly Algorithm method. The effectiveness of the method was evaluated using a simulated nonlinear model and two biological models: synthetic transcriptional oscillators, and extracellular protease production models. The results showed that the accuracy and computational speed of the proposed method were better than the existing Differential Evolution, Firefly Algorithm and Chemical Reaction Optimization methods. The reliability of the estimated parameters was statistically validated, which suggests that the model outputs produced by these parameters were valid even when noisy and incomplete experimental data were used. Additionally, Akaike Information Criterion was employed to evaluate the model selection, which highlighted the capability of the proposed method in choosing a plausible model based on the experimental data. In conclusion, this paper presents the effectiveness of the proposed method for parameter estimation and model selection problems using noisy and incomplete

  9. 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.

  10. Analyzing Students' Understanding of Models and Modeling Referring to the Disciplines Biology, Chemistry, and Physics

    Science.gov (United States)

    Krell, Moritz; Reinisch, Bianca; Krüger, Dirk

    2015-01-01

    In this study, secondary school students' (N?=?617; grades 7 to 10) understanding of models and modeling was assessed using tasks which explicitly refer to the scientific disciplines of biology, chemistry, and physics and, as a control, to no scientific discipline. The students' responses are interpreted as their biology-, chemistry-, and…

  11. A model of how different biology experts explain molecular and cellular mechanisms.

    Science.gov (United States)

    Trujillo, Caleb M; Anderson, Trevor R; Pelaez, Nancy J

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. © 2015 C. M. Trujillo et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). 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. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Integrated Raman and angular scattering of single biological cells

    Science.gov (United States)

    Smith, Zachary J.

    2009-12-01

    epi- and trans-illumination modalities are also discussed. In addition, transilluminated Raman and elastic-scattering spectra were obtained from several biological test-cases, including Streptococcus pneumoniae, baker's yeast, and single human immune cells. Both the Raman and elastic-scattering channels extract information from these samples that are well in line with their known characteristics from the literature. Finally, we report on an experiment in which CD8+ T lymphocytes were stimulated by exposure to the antigens staphylococcal enterotoxin B and phorbol myristate acetate. Clear chemical and morphological differences were observed between the activated and unactivated cells, with the results correlating well to analysis performed on parallel samples using fluorescent stains and a flow cytometer.

  18. Complex Behavior in Simple Models of Biological Coevolution

    Science.gov (United States)

    Rikvold, Per Arne

    We explore the complex dynamical behavior of simple predator-prey models of biological coevolution that account for interspecific and intraspecific competition for resources, as well as adaptive foraging behavior. In long kinetic Monte Carlo simulations of these models we find quite robust 1/f-like noise in species diversity and population sizes, as well as power-law distributions for the lifetimes of individual species and the durations of quiet periods of relative evolutionary stasis. In one model, based on the Holling Type II functional response, adaptive foraging produces a metastable low-diversity phase and a stable high-diversity phase.

  19. Models to study gravitational biology of Mammalian reproduction

    Science.gov (United States)

    Tou, Janet; Ronca, April; Grindeland, Richard; Wade, Charles

    2002-01-01

    Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.

  20. 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)

  1. An Abstraction Theory for Qualitative Models of Biological Systems

    Directory of Open Access Journals (Sweden)

    Richard Banks

    2010-10-01

    Full Text Available Multi-valued network models are an important qualitative modelling approach used widely by the biological community. In this paper we consider developing an abstraction theory for multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. This is important as it aids the analysis and comparison of multi-valued networks and in particular, helps address the well-known problem of state space explosion associated with such analysis. We also consider developing techniques for efficiently identifying abstractions and so provide a basis for the automation of this task. We illustrate the theory and techniques developed by investigating the identification of abstractions for two published MVN models of the lysis-lysogeny switch in the bacteriophage lambda.

  2. Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy.

    Science.gov (United States)

    Fernandez-Moure, Joseph; Moore, Caitlyn A; Kim, Keemberly; Karim, Azim; Smith, Kevin; Barbosa, Zonia; Van Eps, Jeffrey; Rameshwar, Pranela; Weiner, Bradley

    2018-01-01

    Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.

  3. Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis.

    Science.gov (United States)

    Ludvigsen, Eva

    2007-01-01

    Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of

  4. A model of heavy ion detection in physical and biological systems

    International Nuclear Information System (INIS)

    Waligorski, M.P.R.

    1988-01-01

    Track structure theory (the Katz model) and its application to the detection of heavy ions in physical and biological systems are reviewed. Following the use of a new corrected formula describing the radial distribution of average dose around the path of a heavy ion, based on results of Monte Carlo calculations and on results of experimental measurements, better agreement is achieved between model calculations and experimentally measured relative effectiveness, for enzymatic and viral systems, for the Fricke dosemeter and for alanine and thermoluminescent (TDL-700) dosemeters irradiated with beams of heavy charged particles. From experimentally measured RBE dependences for survival and frequency of neoplastic transformations in a mammalian cell culture irradiated with beams of energetic heavy ions, values of model parameters for these biological endpoints have been extracted, and a model extrapolation to the low-dose region performed. Results of model calculations are then compared with evaluations of the lung cancer hazard in populations exposed to radon and its progeny. The model can be applied to practical phenomenological analysis of radiation damage in solid-state systems and to dosimetry of charged particle and fast neutron beams using a variety of detectors. The model can also serve as a guide in building more basic models of the action of ionizing radiation with physical and biological systems and guide of development of models of radiation risk more relevant than that used presently. 185 refs., 31 figs., 3 tabs. (author)

  5. 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)

  6. Translational research in ovarian carcinoma : cell biological aspects of drug resistance and tumor aggressiveness

    NARCIS (Netherlands)

    Zee, Ate Gerard Jan van der

    1994-01-01

    In this thesis diverse cell biological features that in cultured (ovarian) tumor cells have been linked to drug resistance and/or tumor aggressiveness are studied in tumor specimens of epithelial ovarian carcinomas.

  7. Modelling biological depth perception in binocular vision: the local disparity estimation.

    Science.gov (United States)

    Lungeanu, D; Popa, C; Hotca, S; Macovievici, G

    1998-01-01

    This paper presents an approach to solving the correspondence problem in binocular vision and to computing the local horizontal disparity map using a biologically inspired algorithm. A computer application was developed as a tool for implementing, developing, and testing computational models for stereopsis, and also as a framework for integrating the disparity map with other perspective clues. Two models for stereopsis have been implemented. One of them is biologically inspired (it models the behaviour of simple and complex cells from the striate cortex) and the other is the 'classical' model of David Marr and Tomaso Poggio, implemented in order to have a comparison term for the simulation results. The paper details the results obtained on random-dot stereograms and on pairs of real images.

  8. 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.

  9. Bifurcations of a class of singular biological economic models

    International Nuclear Information System (INIS)

    Zhang Xue; Zhang Qingling; Zhang Yue

    2009-01-01

    This paper studies systematically a prey-predator singular biological economic model with time delay. It shows that this model exhibits two bifurcation phenomena when the economic profit is zero. One is transcritical bifurcation which changes the stability of the system, and the other is singular induced bifurcation which indicates that zero economic profit brings impulse, i.e., rapid expansion of the population in biological explanation. On the other hand, if the economic profit is positive, at a critical value of bifurcation parameter, the system undergoes a Hopf bifurcation, i.e., the increase of delay destabilizes the system and bifurcates into small amplitude periodic solution. Finally, by using Matlab software, numerical simulations illustrate the effectiveness of the results obtained here. In addition, we study numerically that the system undergoes a saddle-node bifurcation when the bifurcation parameter goes through critical value of positive economic profit.

  10. Enterococcus infection biology: lessons from invertebrate host models.

    Science.gov (United States)

    Yuen, Grace J; Ausubel, Frederick M

    2014-03-01

    The enterococci are commensals of the gastrointestinal tract of many metazoans, from insects to humans. While they normally do not cause disease in the intestine, they can become pathogenic when they infect sites outside of the gut. Recently, the enterococci have become important nosocomial pathogens, with the majority of human enterococcal infections caused by two species, Enterococcus faecalis and Enterococcus faecium. Studies using invertebrate infection models have revealed insights into the biology of enterococcal infections, as well as general principles underlying host innate immune defense. This review highlights recent findings on Enterococcus infection biology from two invertebrate infection models, the greater wax moth Galleria mellonella and the free-living bacteriovorous nematode Caenorhabditis elegans.

  11. [The investigation of blood cells of middle and old age in patients with bronchial asthma and chronic obstructive pulmonary disease by atomic force microscopy. Similarities and differences with the biological animal model].

    Science.gov (United States)

    Zabiniakov, N A; Prashchayeu, K I; Ryzhak, G A; Poltorackij, A N; Anosova, E I; Azarow, K S

    2016-01-01

    The investigation of reactive changes of blood cells in such diseases as COPD or asthma in people of different age groups is the very difficult problem. Simulating the same conditions in animals that occur in humans with these diseases can serve as a reliable practical model. It is possible because the changes which take places at the cellular level in animals might reflect a similar trend in the human body.

  12. A computational systems biology software platform for multiscale modeling and simulation: Integrating whole-body physiology, disease biology, and molecular reaction networks

    Directory of Open Access Journals (Sweden)

    Thomas eEissing

    2011-02-01

    Full Text Available Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multi-scale by nature, project work and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.

  13. 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…

  14. 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

  15. 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.

  16. Integrated, multi-scale, spatial-temporal cell biology--A next step in the post genomic era.

    Science.gov (United States)

    Horwitz, Rick

    2016-03-01

    New microscopic approaches, high-throughput imaging, and gene editing promise major new insights into cellular behaviors. When coupled with genomic and other 'omic information and "mined" for correlations and associations, a new breed of powerful and useful cellular models should emerge. These top down, coarse-grained, and statistical models, in turn, can be used to form hypotheses merging with fine-grained, bottom up mechanistic studies and models that are the back bone of cell biology. The goal of the Allen Institute for Cell Science is to develop the top down approach by developing a high throughput microscopy pipeline that is integrated with modeling, using gene edited hiPS cell lines in various physiological and pathological contexts. The output of these experiments and models will be an "animated" cell, capable of integrating and analyzing image data generated from experiments and models. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. WE-DE-202-03: Modeling of Biological Processes - What Happens After Early Molecular Damage?

    International Nuclear Information System (INIS)

    McMahon, S.

    2016-01-01

    Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological

  18. Boolean Networks in Inference and Dynamic Modeling of Biological Systems at the Molecular and Physiological Level

    Science.gov (United States)

    Thakar, Juilee; Albert, Réka

    The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References

  19. Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision.

    Science.gov (United States)

    Zhong, Bineng; Pan, Shengnan; Zhang, Hongbo; Wang, Tian; Du, Jixiang; Chen, Duansheng; Cao, Liujuan

    2016-01-01

    In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of training data. Finally, to alleviate the tracker drifting problem caused by model updating, we jointly consider three different types of positive samples. Extensive experiments validate the robustness and effectiveness of the proposed method.

  20. Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform

    International Nuclear Information System (INIS)

    Eschrich, Steven; Zhang Hongling; Zhao Haiyan; Boulware, David; Lee, Ji-Hyun; Bloom, Gregory; Torres-Roca, Javier F.

    2009-01-01

    Purpose: The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers. Methods and Materials: Radiosensitivity, as represented by the survival fraction at 2 Gy was modeled in 48 human cancer cell lines. We applied a linear regression algorithm that integrates gene expression with biological variables, including ras status (mut/wt), tissue of origin and p53 status (mut/wt). Results: The biomarker discovery platform is a network representation of the top 500 genes identified by linear regression analysis. This network was reduced to a 10-hub network that includes c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1, and IRF1. Nine targets associated with radiosensitization drugs are linked to the network, demonstrating clinical relevance. Furthermore, the model identified four significant radiosensitivity clusters of terms and genes. Ras was a dominant variable in the analysis, as was the tissue of origin, and their interaction with gene expression but not p53. Overrepresented biological pathways differed between clusters but included DNA repair, cell cycle, apoptosis, and metabolism. The c-Jun network hub was validated using a knockdown approach in 8 human cell lines representing lung, colon, and breast cancers. Conclusion: We have developed a novel radiation-biomarker discovery platform using a systems biology modeling approach. We believe this platform will play a central role in the integration of biology into clinical radiation oncology practice.