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Sample records for affect biological systems

  1. Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits.

    PubMed

    Watson, Emma; MacNeil, Lesley T; Ritter, Ashlyn D; Yilmaz, L Safak; Rosebrock, Adam P; Caudy, Amy A; Walhout, Albertha J M

    2014-02-13

    Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology.

  2. Fertilization regimes affect the soil biological characteristics of a sudangrass and ryegrass rotation system.

    PubMed

    Li, WenXi; Lu, JianWei; Li, FangBai; Wang, Yan; Lu, JunMing; Li, XiaoKun

    2011-06-01

    The sudangrass (Sorghum sudanense) and ryegrass (Lolium multiflorum L.) rotation is an intensive and new cropping system in Central China. Nutrient management practices in this rotation system may influence soil fertility, the important aspects of which are soil biological properties and quality. As sensitive soil biological properties and quality indicators, soil microbial community activity, microbial biomass, enzyme activities, soil organic matter (SOM) and total N resulting from different fertilization regimes in this rotation system were studied through a four-year field experiment from April 2005 to May 2009. Treatments included control (CK), fertilizer phosphorus and potassium (PK), fertilizer nitrogen and potassium (NK), fertilizer nitrogen and phosphorus (NP) and a fertilizer nitrogen, phosphorus and potassium combination (NPK). Soil microbial community activities in the NK, NP and NPK treatments were significantly lower than those in the CK and PK treatments after the sudangrass and ryegrass trial. The highest microbial biomass C, microbial biomass N, SOM, total N, sucrase and urease activities were found in the NPK treatment, and these soil quality indicators were significantly higher in the NK, NP and NPK treatments than in the PK and CK treatments. Soil microbial biomass and enzyme activities were positively associated with SOM in the sudangrass and ryegrass rotation system, indicating that fertilization regimes, especially N application, reduced microbial community activity in the soil. Proper fertilization regimes will increase microbial biomass, enzyme activity and SOM and improve soil fertility.

  3. How does the entering of copper nanoparticles into biological wastewater treatment system affect sludge treatment for VFA production.

    PubMed

    Chen, Hong; Chen, Yinguang; Zheng, Xiong; Li, Xiang; Luo, Jingyang

    2014-10-15

    Usually the studies regarding the effect of engineered nanoparticles (NPs), which are released to wastewater treatment plant, on sludge anaerobic treatment in the literature have been conducted by directly adding NPs to sludge treatment system. Actually, NPs must enter into the wastewater treatment facility from influent before sludge being treated. Thus, the documented results can not reflect the real situations. During sludge anaerobic treatment for producing volatile fatty acids (VFA, the preferred carbon source for wastewater biological nutrient removal), it was found in this study that the entering of CuNPs to biological wastewater treatment system had no significant effect on sludge-derived VFA generation, while direct addition of CuNPs to sludge fermentation reactor caused a much lower VFA production, when compared to the control test. Further investigation revealed that the entering of CuNPs into wastewater biological treatment system improved sludge solubilization due to the decline of sludge particle size and the increase of sludge microorganism cells breakage. In addition, there was no obvious influence on hydrolysis, while significant inhibition was observed on acidification, resulting in the final VFA production similar to the control. When CuNPs were directly added to the fermentation system, the solubilization was little influenced, however the hydrolysis and acidification were seriously inhibited, causing the ultimate VFA generation decreased. Therefore, selecting proper method close to the real situation is vital to accurately assess the toxicity of nanoparticles on sludge anaerobic fermentation.

  4. Systems interface biology

    PubMed Central

    Doyle, Francis J; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines. PMID:16971329

  5. Systems interface biology.

    PubMed

    Doyle, Francis J; Stelling, Jörg

    2006-10-22

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines.

  6. Systems Biology of Embryogenesis

    PubMed Central

    Edelman, Lucas B.; Chandrasekaran, Sriram; Price, Nathan D.

    2010-01-01

    The development of a complete organism from a single cell involves extraordinarily complex orchestration of biological processes that vary intricately across space and time. Systems biology seeks to describe how all elements of a biological system interact in order to understand, model, and ultimately predict aspects of emergent biological processes. Embryogenesis represents an extraordinary opportunity – and challenge – for the application of systems biology. Systems approaches have already been used successfully to study various aspects of development, from complex intracellular networks to 4D models of organogenesis. Going forward, great advancements and discoveries can be expected from systems approaches applied to embryogenesis and developmental biology. PMID:20003850

  7. Word selection affects perceptions of synthetic biology.

    PubMed

    Pearson, Brianna; Snell, Sam; Bye-Nagel, Kyri; Tonidandel, Scott; Heyer, Laurie J; Campbell, A Malcolm

    2011-07-21

    Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008). Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

  8. Word selection affects perceptions of synthetic biology

    PubMed Central

    2011-01-01

    Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008). Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create". PMID:21777466

  9. Biological conversion system

    DOEpatents

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  10. Computational Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2013-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  11. Computational systems chemical biology.

    PubMed

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  12. Teaching systems biology.

    PubMed

    Alves, R; Vilaprinyo, E; Sorribas, A

    2011-03-01

    Advances in systems biology are increasingly dependent upon the integration of various types of data and different methodologies to reconstruct how cells work at the systemic level. Thus, teams with a varied array of expertise and people with interdisciplinary training are needed. So far this training was thought to be more productive if aimed at the Masters or PhD level. At this level, multiple specialised and in-depth courses on the different subject matters of systems biology are taught to already well-prepared students. This approach is mostly based on the recognition that systems biology requires a wide background that is hard to find in undergraduate students. Nevertheless, and given the importance of the field, the authors argue that exposition of undergraduate students to the methods and paradigms of systems biology would be advantageous. Here they present and discuss a successful experiment in teaching systems biology to third year undergraduate biotechnology students at the University of Lleida in Spain. The authors' experience, together with that from others, argues for the adequateness of teaching systems biology at the undergraduate level. [Includes supplementary material].

  13. Systems Biology of Metabolism.

    PubMed

    Nielsen, Jens

    2017-03-08

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed. Expected final online publication date for the Annual Review of Biochemistry Volume 86 is June 20, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  14. Computational Systems Biology

    SciTech Connect

    McDermott, Jason E.; Samudrala, Ram; Bumgarner, Roger E.; Montogomery, Kristina; Ireton, Renee

    2009-05-01

    Computational systems biology is the term that we use to describe computational methods to identify, infer, model, and store relationships between the molecules, pathways, and cells (“systems”) involved in a living organism. Based on this definition, the field of computational systems biology has been in existence for some time. However, the recent confluence of high throughput methodology for biological data gathering, genome-scale sequencing and computational processing power has driven a reinvention and expansion of this field. The expansions include not only modeling of small metabolic{Ishii, 2004 #1129; Ekins, 2006 #1601; Lafaye, 2005 #1744} and signaling systems{Stevenson-Paulik, 2006 #1742; Lafaye, 2005 #1744} but also modeling of the relationships between biological components in very large systems, incluyding whole cells and organisms {Ideker, 2001 #1124; Pe'er, 2001 #1172; Pilpel, 2001 #393; Ideker, 2002 #327; Kelley, 2003 #1117; Shannon, 2003 #1116; Ideker, 2004 #1111}{Schadt, 2003 #475; Schadt, 2006 #1661}{McDermott, 2002 #878; McDermott, 2005 #1271}. Generally these models provide a general overview of one or more aspects of these systems and leave the determination of details to experimentalists focused on smaller subsystems. The promise of such approaches is that they will elucidate patterns, relationships and general features that are not evident from examining specific components or subsystems. These predictions are either interesting in and of themselves (for example, the identification of an evolutionary pattern), or are interesting and valuable to researchers working on a particular problem (for example highlight a previously unknown functional pathway). Two events have occurred to bring about the field computational systems biology to the forefront. One is the advent of high throughput methods that have generated large amounts of information about particular systems in the form of genetic studies, gene expression analyses (both protein and

  15. Plant Systems Biology (editorial)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In June 2003, Plant Physiology published an Arabidopsis special issue devoted to plant systems biology. The intention of Natasha Raikhel and Gloria Coruzzi, the two editors of this first-of-its-kind issue, was ‘‘to help nucleate this new effort within the plant community’’ as they considered that ‘‘...

  16. Biological system interactions.

    PubMed Central

    Adomian, G; Adomian, G E; Bellman, R E

    1984-01-01

    Mathematical modeling of cellular population growth, interconnected subsystems of the body, blood flow, and numerous other complex biological systems problems involves nonlinearities and generally randomness as well. Such problems have been dealt with by mathematical methods often changing the actual model to make it tractable. The method presented in this paper (and referenced works) allows much more physically realistic solutions. PMID:6585837

  17. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    SciTech Connect

    Galitski, Timothy P.

    2008-04-01

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  18. Can Polyphosphate Biochemistry Affect Biological Apatite Saturation?

    NASA Astrophysics Data System (ADS)

    Omelon, S. J.; Matsuura, N.; Gorelikov, I.; Wynnyckyj, C.; Grynpas, M. D.

    2010-12-01

    (estimated to be 1 g apatite/mL). Carbonates (as NaHCO3 or CaCO3) were used to buffer the protons produced upon polyP hydrolytic degradation to Pi, releasing Ca+2, increasing apatite saturation for precipitation. Initial Ca:P ratios (by EDS) was <1, indicative of Ca-polyP. After incubation, Ca:P ratios were >1, suggesting the formation of Ca-PO4 minerals. XRD results identified Na-Ca- carbonate phases, & hydroxyapatite & carbonated apatite, & residual carbonate reagent. Further optimization of this biological apatite precipitation system will be presented. 1 Kornberg, A., Ann Rev Biochem 1999 (68) 89 2 Kulaev IS, Vagabov VM, Kulakovskaya TV (2004) The Biochemistry of Inorganic Polyphosphates. Chichester, England, John Wiley & Sons, Ltd. 3 Blake, R. E., O’Neil, J.R., and Surov, A. Am J Sci 2005 (305) 596 4 Heersche, J. N. M. et al. (1990) Bone Regulatory Factors; Plenum Press: New York 5 Omelon et al., PLoS ONE 2009 4(5), e5634

  19. Biological sex affects the neurobiology of autism.

    PubMed

    Lai, Meng-Chuan; Lombardo, Michael V; Suckling, John; Ruigrok, Amber N V; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C L; Craig, Michael C; Murphy, Declan G M; Bullmore, Edward T; Baron-Cohen, Simon

    2013-09-01

    In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the 'extreme male brain' theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P < 0.001) overlapped with areas that were sexually dimorphic in neurotypical controls, in both grey and white matter, suggesting neural 'masculinization'. This was not seen in males with autism. How differences in neuroanatomy

  20. Systems biology of aging.

    PubMed

    Bolt, Kendra; Bergman, Aviv

    2015-01-01

    Human aging occurs at rates that vary widely between organisms and cell types. We hypothesize that in both cases, variation is due to differences in heat production, heat management and molecular susceptibility to heat-induced change. Metabolic rates have long been implored for their contributions to the aging process, with a negative correlation observed between basal metabolic rate and lifespan (Savage et al., Proc Natl Acad Sci U S A 104:4718–4723, 2007, Economos, Exp Gerontol 17:145–152, 1982, Keys et al., Metabolism 22:579–587, 1973, O’Connor et al., Comp Biochem Physiol Part A, Molr & Integr Physiol 133:835–842, 2002, Speakman, J Exp Biol 208:1717–1730, 2005, Poehlman, J Am Geriatrics Soc 41:552–559, 1993). Small amounts of heat are the well-known byproduct of metabolism and other biological processes, and despite their magnitude, are sufficient to elicit alterations in biomolecular characteristics (Somero, Ann Rev Physiol 57:43–68, 1995). Existing theories of aging suggest that damage occurs to the conformations or sequences of molecules, which only shifts focus onto the implied failure of repair mechanisms. Contrarily, heat-induced changes affect the behavioral characteristics of molecules and are thus able to persist “under the radar” of heat shock proteins and other canalizing mechanisms, which recognize only physical aberrancies (Rutherford and Lindquist, Nature 396:336–342, 1998, Siegal and Bergman, Proc Natl Acad Sci U S A 99:10528–10532, 2002, Waddington, Nature 150:563–565, 1942). According to our hypothesis, behavioral changes to the binding affinities, kinetics, motilities, and functionalities are dependent on minute energetic fields within and between molecules. Exposure to the thermal byproducts of metabolism cause heritable shifts in molecular interaction schemes and diminish the integrity of genetic and epigenetic networks. Restructured topologies alter the emergent properties of networks and are observed as the

  1. Industrial systems biology.

    PubMed

    Otero, José Manuel; Nielsen, Jens

    2010-02-15

    The chemical industry is currently undergoing a dramatic change driven by demand for developing more sustainable processes for the production of fuels, chemicals, and materials. In biotechnological processes different microorganisms can be exploited, and the large diversity of metabolic reactions represents a rich repository for the design of chemical conversion processes that lead to efficient production of desirable products. However, often microorganisms that produce a desirable product, either naturally or because they have been engineered through insertion of heterologous pathways, have low yields and productivities, and in order to establish an economically viable process it is necessary to improve the performance of the microorganism. Here metabolic engineering is the enabling technology. Through metabolic engineering the metabolic landscape of the microorganism is engineered such that there is an efficient conversion of the raw material, typically glucose, to the product of interest. This process may involve both insertion of new enzymes activities, deletion of existing enzyme activities, but often also deregulation of existing regulatory structures operating in the cell. In order to rapidly identify the optimal metabolic engineering strategy the industry is to an increasing extent looking into the use of tools from systems biology. This involves both x-ome technologies such as transcriptome, proteome, metabolome, and fluxome analysis, and advanced mathematical modeling tools such as genome-scale metabolic modeling. Here we look into the history of these different techniques and review how they find application in industrial biotechnology, which will lead to what we here define as industrial systems biology.

  2. Systems biology: a biologist's viewpoint.

    PubMed

    Bose, Biplab

    2013-12-01

    The debate over reductionism and antireductionism in biology is very old. Even the systems approach in biology is more than five decades old. However, mainstream biology, particularly experimental biology, has broadly sidestepped those debates and ideas. Post-genome data explosion and development of high-throughput techniques led to resurfacing of those ideas and debates as a new incarnation called Systems Biology. Though experimental biologists have co-opted systems biology and hailed it as a paradigm shift, it is practiced in different shades and understood with divergent meanings. Biology has certain questions linked with organization of multiple components and processes. Often such questions involve multilevel systems. Here in this essay we argue that systems theory provides required framework and abstractions to explore those questions. We argue that systems biology should follow the logical and mathematical approach of systems theory and transmogrification of systems biology to mere collection of higher dimensional data must be avoided. Therefore, the questions that we ask and the priority of those questions should also change. Systems biology should focus on system-level properties and investigate complexity without shying away from it.

  3. Systems Biology of Coagulation

    PubMed Central

    Diamond, Scott L.

    2013-01-01

    Accurate computer simulation of blood function can inform drug target selection, patient-specific dosing, clinical trial design, biomedical device design, as well as the scoring of patient-specific disease risk and severity. These large-scale simulations rely on hundreds of independently measured physical parameters and kinetic rate constants. However, the models can be validated against large scale, patient-specific laboratory measurements. By validation with high dimensional data, modelling becomes a powerful tool to predict clinically complex scenarios. Currently, it is possible to accurately predict the clotting rate of plasma or blood in a tube as it is activated with a dose of tissue factor, even as numerous coagulation factors are altered by exogenous attenuation or potentiation. Similarly, the dynamics of platelet activation, as indicated by calcium mobilisation or inside-out signalling, can now be numerically simulated with accuracy in cases where platelets are exposed to combinations of agonists. Multiscale models have emerged to combine platelet function and coagulation kinetics into complete physics-based descriptions of thrombosis under flow. Blood flow controls platelet fluxes, delivery and removal of coagulation factors, adhesive bonding, and von Willebrand factor conformation. The field of Blood Systems Biology has now reached a stage that anticipates the inclusion of contact, complement, and fibrinolytic pathways along with models of neutrophil and endothelial activation. Along with “-omics” data sets, such advanced models seek to predict the multifactorial range of healthy responses and diverse bleeding and clotting scenarios, ultimately to understand and improve patient outcomes. PMID:23809126

  4. Biological Resource Centers and Systems Biology.

    PubMed

    Wang, Yufeng; Lilburn, Timothy G

    2009-02-11

    There are hundreds of Biological Resource Centers (BRCs) around the world, holding many little-studied microorganism. The proportion of bacterial strains that is well represented in the sequence and literature databases may be as low as 1%. This body of unexplored diversity represents an untapped source of useful strains and derived products. However, a modicum of phenotypic data is available for almost all the bacterial strains held by BRCs around the world. It is at the phenotypic level that our knowledge of the well-studied strains of bacteria and the many yet-to-be studied strains intersects. This suggests we might leverage the phenotypic data from the data-poor bacteria with the omics data from the data-rich bacteria, using our knowledge of their evolutionary relationships, to map the metabolic networks of the little-known bacteria. This systems biology-based approach is a new way to explore the diversity harbored in BRCs.

  5. Hierarchical structure of biological systems

    PubMed Central

    Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M

    2014-01-01

    A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and functioning of the biological system. Our thermodynamical approach of hierarchical character can be applied to biological systems of varying sizes through some general principles, based on the exchange of energy information and/or mass from and within the systems. PMID:24145961

  6. From systems biology to systems biomedicine.

    PubMed

    Antony, Paul M A; Balling, Rudi; Vlassis, Nikos

    2012-08-01

    Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine.

  7. The nature of systems biology.

    PubMed

    Bruggeman, Frank J; Westerhoff, Hans V

    2007-01-01

    The advent of functional genomics has enabled the molecular biosciences to come a long way towards characterizing the molecular constituents of life. Yet, the challenge for biology overall is to understand how organisms function. By discovering how function arises in dynamic interactions, systems biology addresses the missing links between molecules and physiology. Top-down systems biology identifies molecular interaction networks on the basis of correlated molecular behavior observed in genome-wide "omics" studies. Bottom-up systems biology examines the mechanisms through which functional properties arise in the interactions of known components. Here, we outline the challenges faced by systems biology and discuss limitations of the top-down and bottom-up approaches, which, despite these limitations, have already led to the discovery of mechanisms and principles that underlie cell function.

  8. [Social institutions and tempering of affects as "contraints" of social change. Norbert Elias' theory on the civilization theory in light of the biologic system theory of evolution].

    PubMed

    Weinich, Detlef

    2005-01-01

    This study is to be regarded as a contribution to interdisciplinary research and represents an attempt to clarify the question of whether and to what extent concepts that have been developed in the field of theoretical biology and which have a high degree of importance here can also be applied to sociological phenomena. In particular it is intended to examine the question of whether the civilizing process can be adequately treated using the evolutionary concept of "Constraints". This term, which has only recently been introduced into the discussion by PERE ALBERCH as an evolutionary factor, comprises all of the internal factors which influence the further course of the evolution of a system by ruling out certain possibilities, thus showing a limiting effect. Although "Constraints" go beyond the scope of Darwinian teachings about selection by the environment, they are increasingly accepted today as evolution factors by well-known exponents of Darwinian theory (cf. MAYNARD-SMITH 1985). The increase in popularity of "constraints" is also an expression of the rediscovery of a phenomenon which was originally expressed by RUPERT RIEDL and was introduced by him into German literature in the seventies. In the clarification of this question, special reference is made to the "theory of the civilizing process" by NORBERT ELIAS, since here a highly respected scholar has presented an important sociological theory. Moreover, there is such good scientific access to ELIAS because this author exemplifies his theses in historical terms and thus to a certain extent makes his explanations verifiable in scientific terms. In the treatment of this topic, the central terms and theses of ELIAS will be presented from the considerable scope of his work, and then illustrated with the help of several selected historical case studies. Furthermore, reference will be made at the relevant points to parallels and analogies which the works of ELIAS have to other, predominantly system

  9. Support system considerations for STS biological investigations

    NASA Technical Reports Server (NTRS)

    Bowman, G. H.; Sebesta, P. D.

    1978-01-01

    Equipment required for Space Transportation System biological experiments is considered, and environmental factors and operational constraints affecting the performance of experiments are examined. Specimen housing is discussed, problems associated with telemetry procedures are characterized, and attention is directed to the problems of handling hazardous fixatives, radioisotopes, and chemicals.

  10. Systems biology of human atherosclerosis.

    PubMed

    Shalhoub, Joseph; Sikkel, Markus B; Davies, Kerry J; Vorkas, Panagiotis A; Want, Elizabeth J; Davies, Alun H

    2014-01-01

    Systems biology describes a holistic and integrative approach to understand physiology and pathology. The "omic" disciplines include genomics, transcriptomics, proteomics, and metabolic profiling (metabonomics and metabolomics). By adopting a stance, which is opposing (yet complimentary) to conventional research techniques, systems biology offers an overview by assessing the "net" biological effect imposed by a disease or nondisease state. There are a number of different organizational levels to be understood, from DNA to protein, metabolites, cells, organs and organisms, even beyond this to an organism's context. Systems biology relies on the existence of "nodes" and "edges." Nodes are the constituent part of the system being studied (eg, proteins in the proteome), while the edges are the way these constituents interact. In future, it will be increasingly important to collaborate, collating data from multiple studies to improve data sets, making them freely available and undertaking integrative analyses.

  11. Imaging methodologies for systems biology.

    PubMed

    Smith, Sarah E; Slaughter, Brian D; Unruh, Jay R

    2014-01-01

    Systems biology has recently achieved significant success in the understanding of complex interconnected phenomena such as cell polarity and migration. In this context, the definition of systems biology has come to encompass the integration of quantitative measurements with sophisticated modeling approaches. This article will review recent progress in live cell imaging technologies that have expanded the possibilities of quantitative in vivo measurements, particularly in regards to molecule counting and quantitative measurements of protein concentration and dynamics. These methods have gained and continue to gain popularity with the biological community. In general, we will discuss three broad categories: protein interactions, protein quantitation, and protein dynamics.

  12. Biological Life Support Systems

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session MP2 includes short reports on: (1) Crew Regenerative Life Support in Long Duration Space Missions; (2) Bioconversion Systems for Food and Water on Long Term Space Missions; (3) Novel Laboratory Approaches to Multi-purpose Aquatic Biogenerative Closed-Loop Food Production Systems; and (4) Artificial Neural Network Derived Plant Growth Models.

  13. Teaching Biological Systems.

    ERIC Educational Resources Information Center

    Walters, Julia

    1988-01-01

    Described is an activity which allows the investigation of human body systems using textbooks to enhance research skills and providing an opportunity for collaboration between pupils. Discussed are the purpose, materials, method, and results of this teaching method. Reported are some of the advantages of using this activity in teaching systems.…

  14. Kinetic Modeling of Biological Systems

    PubMed Central

    Petzold, Linda; Pettigrew, Michel F.

    2010-01-01

    The dynamics of how the constituent components of a natural system interact defines the spatio-temporal response of the system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided. PMID:19381542

  15. Modelling codependence in biological systems.

    PubMed

    Mandel, J J; Palfreyman, N M; Dubitzky, W

    2007-01-01

    A central aim of systems biology is to elucidate the complex dynamic structure of biological systems within which functioning and control occur. The success of this endeavour requires a dialogue between the two quite distinct disciplines of life science and systems theory, and so drives the need for graphical notations which facilitate this dialogue. Several methods have been developed for modelling and simulating biochemical networks, some of which provide notations for graphicall4y constructing a model. Such notations must support the full panoply of mechanisms of systems biology, including metabolic, regulatory, signalling and transport processes. Notations in systems biology tend to fall into two groups. The first group derives its orientation from conventional biochemical pathway diagrams, and so tends to ignore the role of information processing. The second group focuses on the processing of information, incorporating information-processing ideas from other systems-oriented disciplines, such as engineering and business. This, however, can lead to the two crucial and related difficulties of impedance mismatch and conceptual baggage. Impedance mismatch concerns the rift between non-biological notations and biological reality, which forces the researcher to employ awkward workarounds when modelling uniquely biological mechanisms. Conceptual baggage can arise when, for instance, an engineering notation is adapted to cater for these distinctively biological needs, since these adaptations will, typically, never completely free the notation of the conceptual structure of its original engineering motivation. A novel formalism, codependence modelling, which seeks to combine the needs of the biologist with the mathematical rigour required to support computer simulation of dynamics is proposed here. The notion of codependence encompasses the transformation of both chemical substance and information, thus integrating both metabolic and gene regulatory processes within a

  16. Anion selectivity in biological systems.

    PubMed

    Wright, E M; Diamond, J M

    1977-01-01

    . These models succeed in predicting all five observed selectivity sequences of the halides. The models predict in addition the possible existence of two further halide sequences that arise from very strong sites and that have not yet been observed in nature. For polyatomic anions the predictions agree approximately but not completely with observations. Thyroidlike systems, which greatly prefer iodide over other halides,re interpreted as having the weakest sites. Site hydration is predicted to affect the magnitude but not the sequence of potency ratios. For the thyroidlike systems, observed potency ratios are smaller than would be expected if anions were completely dehydrated at biological sites.

  17. Circadian systems biology in Metazoa.

    PubMed

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals.

  18. GPU computing for systems biology.

    PubMed

    Dematté, Lorenzo; Prandi, Davide

    2010-05-01

    The development of detailed, coherent, models of complex biological systems is recognized as a key requirement for integrating the increasing amount of experimental data. In addition, in-silico simulation of bio-chemical models provides an easy way to test different experimental conditions, helping in the discovery of the dynamics that regulate biological systems. However, the computational power required by these simulations often exceeds that available on common desktop computers and thus expensive high performance computing solutions are required. An emerging alternative is represented by general-purpose scientific computing on graphics processing units (GPGPU), which offers the power of a small computer cluster at a cost of approximately $400. Computing with a GPU requires the development of specific algorithms, since the programming paradigm substantially differs from traditional CPU-based computing. In this paper, we review some recent efforts in exploiting the processing power of GPUs for the simulation of biological systems.

  19. Systems biology approach to bioremediation

    SciTech Connect

    Chakraborty, Romy; Wu, Cindy H.; Hazen, Terry C.

    2012-06-01

    Bioremediation has historically been approached as a ‘black box’ in terms of our fundamental understanding. Thus it succeeds and fails, seldom without a complete understanding of why. Systems biology is an integrated research approach to study complex biological systems, by investigating interactions and networks at the molecular, cellular, community, and ecosystem level. The knowledge of these interactions within individual components is fundamental to understanding the dynamics of the ecosystem under investigation. Finally, understanding and modeling functional microbial community structure and stress responses in environments at all levels have tremendous implications for our fundamental understanding of hydrobiogeochemical processes and the potential for making bioremediation breakthroughs and illuminating the ‘black box’.

  20. Workshop Introduction: Systems Biology and Biological Models

    EPA Science Inventory

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

  1. Theoretical aspects of Systems Biology.

    PubMed

    Bizzarri, Mariano; Palombo, Alessandro; Cucina, Alessandra

    2013-05-01

    The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place. In the past, biological research has focused on questions that could be answered by a reductionist program of genetics. The organism (and its development) was considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism. This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no means Systems Biology could be considered a 'simple' 'gradual' extension of Molecular Biology.

  2. Update on the biology of seasonal affective disorder.

    PubMed

    Sohn, Chang-Ho; Lam, Raymond W

    2005-08-01

    The etiology and pathophysiology of seasonal affective disorder (SAD) has been linked to the seasons and to light since its first conceptualization. Aspects of SAD that make it particularly amenable to biological investigation include the predictable recurrent episodes, the rapid response to a nonpharmacologic treatment, the specific neurovegetative features, and the availability of rich animal models of seasonality. This paper reviews new findings for the major biological hypotheses for SAD, focusing on circadian rhythms, neurotransmitters, and molecular genetics. Integrative issues and future directions for the study of SAD, including the heuristic value of a dual-vulnerability hypothesis that conceptualizes seasonality as a dimensional construct and the importance of studying endophenotypes, will be discussed.

  3. Systems biology: the reincarnation of systems theory applied in biology?

    PubMed

    Wolkenhauer, O

    2001-09-01

    With the availability of quantitative data on the transcriptome and proteome level, there is an increasing interest in formal mathematical models of gene expression and regulation. International conferences, research institutes and research groups concerned with systems biology have appeared in recent years and systems theory, the study of organisation and behaviour per se, is indeed a natural conceptual framework for such a task. This is, however, not the first time that systems theory has been applied in modelling cellular processes. Notably in the 1960s systems theory and biology enjoyed considerable interest among eminent scientists, mathematicians and engineers. Why did these early attempts vanish from research agendas? Here we shall review the domain of systems theory, its application to biology and the lessons that can be learned from the work of Robert Rosen. Rosen emerged from the early developments in the 1960s as a main critic but also developed a new alternative perspective to living systems, a concept that deserves a fresh look in the post-genome era of bioinformatics.

  4. Systems biology of industrial microorganisms.

    PubMed

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    2010-01-01

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  5. Systems Biology of Industrial Microorganisms

    NASA Astrophysics Data System (ADS)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  6. Stochastic simulation in systems biology

    PubMed Central

    Székely, Tamás; Burrage, Kevin

    2014-01-01

    Natural systems are, almost by definition, heterogeneous: this can be either a boon or an obstacle to be overcome, depending on the situation. Traditionally, when constructing mathematical models of these systems, heterogeneity has typically been ignored, despite its critical role. However, in recent years, stochastic computational methods have become commonplace in science. They are able to appropriately account for heterogeneity; indeed, they are based around the premise that systems inherently contain at least one source of heterogeneity (namely, intrinsic heterogeneity). In this mini-review, we give a brief introduction to theoretical modelling and simulation in systems biology and discuss the three different sources of heterogeneity in natural systems. Our main topic is an overview of stochastic simulation methods in systems biology. There are many different types of stochastic methods. We focus on one group that has become especially popular in systems biology, biochemistry, chemistry and physics. These discrete-state stochastic methods do not follow individuals over time; rather they track only total populations. They also assume that the volume of interest is spatially homogeneous. We give an overview of these methods, with a discussion of the advantages and disadvantages of each, and suggest when each is more appropriate to use. We also include references to software implementations of them, so that beginners can quickly start using stochastic methods for practical problems of interest. PMID:25505503

  7. Stochastic simulation in systems biology.

    PubMed

    Székely, Tamás; Burrage, Kevin

    2014-11-01

    Natural systems are, almost by definition, heterogeneous: this can be either a boon or an obstacle to be overcome, depending on the situation. Traditionally, when constructing mathematical models of these systems, heterogeneity has typically been ignored, despite its critical role. However, in recent years, stochastic computational methods have become commonplace in science. They are able to appropriately account for heterogeneity; indeed, they are based around the premise that systems inherently contain at least one source of heterogeneity (namely, intrinsic heterogeneity). In this mini-review, we give a brief introduction to theoretical modelling and simulation in systems biology and discuss the three different sources of heterogeneity in natural systems. Our main topic is an overview of stochastic simulation methods in systems biology. There are many different types of stochastic methods. We focus on one group that has become especially popular in systems biology, biochemistry, chemistry and physics. These discrete-state stochastic methods do not follow individuals over time; rather they track only total populations. They also assume that the volume of interest is spatially homogeneous. We give an overview of these methods, with a discussion of the advantages and disadvantages of each, and suggest when each is more appropriate to use. We also include references to software implementations of them, so that beginners can quickly start using stochastic methods for practical problems of interest.

  8. Mathematical methods in systems biology.

    PubMed

    Kashdan, Eugene; Duncan, Dominique; Parnell, Andrew; Schattler, Heinz

    2016-12-01

    The editors of this Special Issue of Mathematical Biosciences and Engineering were the organizers for the Third International Workshop "Mathematical Methods in System Biology" that took place on June 15-18, 2015 at the University College Dublin in Ireland. As stated in the workshop goals, we managed to attract a good mix of mathematicians and statisticians working on biological and medical applications with biologists and clinicians interested in presenting their challenging problems and looking to find mathematical and statistical tools for their solutions.

  9. Systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

    PubMed

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  10. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    PubMed Central

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

  11. Bridging the gap between systems biology and synthetic biology

    PubMed Central

    Liu, Di; Hoynes-O’Connor, Allison; Zhang, Fuzhong

    2013-01-01

    Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics, and metabolomics, aiming to fill the gap between systems and synthetic biology. PMID:23898328

  12. System biology of gene regulation.

    PubMed

    Baitaluk, Michael

    2009-01-01

    ) questions of biological relevance. Thus systems biology could be treated as such a socioscientific phenomenon and a new approach to both experiments and theory that is defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel.

  13. Rhythmic biological systems under microgravity conditions.

    PubMed

    Johnsson, A; Eidesmo, T

    1989-01-01

    Rhythmic phenomena in biology cover a wide frequency spectrum. In Space, the rhythms will encounter microgravity conditions which can, therefore, be a valuable tool for their understanding. A review and discussion of important effects of gravity/absence of gravity on biological systems will be given. Convection will be emphasized as a mechanism which is drastically reduced in Space. Microgravity might also affect the coupling between individual oscillators in a multi-oscillatory system. The environmental interference with rhythms will be discussed with a simple feedback as a starting point. Model simulations will be presented and clinostat and microgravity-conditions will be discussed in a specific case, viz. the gravitropical system of plants which can show sustained oscillations.

  14. Systems biology of diuretic resistance

    PubMed Central

    Knepper, Mark A.

    2015-01-01

    Diuretics are commonly used to treat hypertension and extracellular fluid volume expansion. However, the development of compensatory responses in the kidney limits the benefit of this class of drugs. In this issue of the JCI, Grimm and colleagues use a systems biology approach in mice lacking the kinase SPAK and unravel a complex mechanism that explains thiazide diuretic resistance. The overall process involves interactions among six different cell types in the kidney. PMID:25893597

  15. Network dynamics and systems biology

    NASA Astrophysics Data System (ADS)

    Norrell, Johannes A.

    The physics of complex systems has grown considerably as a field in recent decades, largely due to improved computational technology and increased availability of systems level data. One area in which physics is of growing relevance is molecular biology. A new field, systems biology, investigates features of biological systems as a whole, a strategy of particular importance for understanding emergent properties that result from a complex network of interactions. Due to the complicated nature of the systems under study, the physics of complex systems has a significant role to play in elucidating the collective behavior. In this dissertation, we explore three problems in the physics of complex systems, motivated in part by systems biology. The first of these concerns the applicability of Boolean models as an approximation of continuous systems. Studies of gene regulatory networks have employed both continuous and Boolean models to analyze the system dynamics, and the two have been found produce similar results in the cases analyzed. We ask whether or not Boolean models can generically reproduce the qualitative attractor dynamics of networks of continuously valued elements. Using a combination of analytical techniques and numerical simulations, we find that continuous networks exhibit two effects---an asymmetry between on and off states, and a decaying memory of events in each element's inputs---that are absent from synchronously updated Boolean models. We show that in simple loops these effects produce exactly the attractors that one would predict with an analysis of the stability of Boolean attractors, but in slightly more complicated topologies, they can destabilize solutions that are stable in the Boolean approximation, and can stabilize new attractors. Second, we investigate ensembles of large, random networks. Of particular interest is the transition between ordered and disordered dynamics, which is well characterized in Boolean systems. Networks at the

  16. Systems biology of kidney diseases.

    PubMed

    He, John Cijiang; Chuang, Peter Y; Ma'ayan, Avi; Iyengar, Ravi

    2012-01-01

    Kidney diseases manifest in progressive loss of renal function, which ultimately leads to complete kidney failure. The mechanisms underlying the origins and progression of kidney diseases are not fully understood. Multiple factors involved in the pathogenesis of kidney diseases have made the traditional candidate gene approach of limited value toward full understanding of the molecular mechanisms of these diseases. A systems biology approach that integrates computational modeling with large-scale data gathering of the molecular changes could be useful in identifying the multiple interacting genes and their products that drive kidney diseases. Advances in biotechnology now make it possible to gather large data sets to characterize the role of the genome, epigenome, transcriptome, proteome, and metabolome in kidney diseases. When combined with computational analyses, these experimental approaches will provide a comprehensive understanding of the underlying biological processes. Multiscale analysis that connects the molecular interactions and cell biology of different kidney cells to renal physiology and pathology can be utilized to identify modules of biological and clinical importance that are perturbed in disease processes. This integration of experimental approaches and computational modeling is expected to generate new knowledge that can help to identify marker sets to guide the diagnosis, monitor disease progression, and identify new therapeutic targets.

  17. Anion binding in biological systems

    NASA Astrophysics Data System (ADS)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  18. Decavanadate effects in biological systems.

    PubMed

    Aureliano, Manuel; Gândara, Ricardo M C

    2005-05-01

    Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions ("metavanadate" and "decavanadate"). It was observed that "decavanadate" promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when "decavanadate" is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems.

  19. Autonomous Biological System (ABS) experiments.

    PubMed

    MacCallum, T K; Anderson, G A; Poynter, J E; Stodieck, L S; Klaus, D M

    1998-12-01

    Three space flight experiments have been conducted to test and demonstrate the use of a passively controlled, materially closed, bioregenerative life support system in space. The Autonomous Biological System (ABS) provides an experimental environment for long term growth and breeding of aquatic plants and animals. The ABS is completely materially closed, isolated from human life support systems and cabin atmosphere contaminants, and requires little need for astronaut intervention. Testing of the ABS marked several firsts: the first aquatic angiosperms to be grown in space; the first higher organisms (aquatic invertebrate animals) to complete their life cycles in space; the first completely bioregenerative life support system in space; and, among the first gravitational ecology experiments. As an introduction this paper describes the ABS, its flight performance, advantages and disadvantages.

  20. An Automated Biological Dosimetry System

    NASA Astrophysics Data System (ADS)

    Lorch, T.; Bille, J.; Frieben, M.; Stephan, G.

    1986-04-01

    The scoring of structural chromosome aberrations in peripheral human blood lymphocytes can be used in biological dosimetry to estimate the radiation dose which an individual has received. Especially the dicentric chromosome is a rather specific indicator for an exposure to ionizing radiation. For statistical reasons, in the low dose range a great number of cells must be analysed, which is a very tedious task. The resulting high cost of a biological dose estimation limits the application of this method to cases of suspected irradiation for which physical dosimetry is not possible or not sufficient. Therefore an automated system has been designed to do the major part of the routine work. It uses a standard light microscope with motorized scanning stage, a Plumbicon TV-camera, a real-time hardware preprocessor, a binary and a grey level image buffer system. All computations are performed by a very powerful multi-microprocessor-system (POLYP) based on a MIMD-architecture. The task of the automated system can be split in finding the metaphases (see Figure 1) at low microscope magnification and scoring dicentrics at high magnification. The metaphase finding part has been completed and is now in routine use giving good results. The dicentric scoring part is still under development.

  1. Systems Biology of the Microvasculature

    PubMed Central

    Clegg, Lindsay E.; Mac Gabhann, Feilim

    2015-01-01

    The vascular network carries blood throughout the body, delivering oxygen to tissues and providing a pathway for communication between distant organs. The network is hierarchical and structured, but also dynamic, especially at the smaller scales. Remodeling of the microvasculature occurs in response to local changes in oxygen, gene expression, cell-cell communication, and chemical and mechanical stimuli from the microenvironment. These local changes occur as a result of physiological processes such as growth and exercise, as well as acute and chronic diseases including stroke, cancer, and diabetes, and pharmacological intervention. While the vasculature is an important therapeutic target in many diseases, drugs designed to inhibit vascular growth have achieved only limited success, and no drug has yet been approved to promote therapeutic vascular remodeling. This highlights the challenges involved in identifying appropriate therapeutic targets in a system as complex as the vasculature. Systems biology approaches provide a means to bridge current understanding of the vascular system, from detailed signaling dynamics measured in vitro and pre-clinical animal models of vascular disease, to a more complete picture of vascular regulation in vivo. This will translate to an improved ability to identify multi-component biomarkers for diagnosis, prognosis, and monitoring of therapy that are easy to measure in vivo, as well as better drug targets for specific disease states. In this review, we summarize systems biology approaches that have advanced our understanding of vascular function and dysfunction in vivo, with a focus on computational modeling. PMID:25839068

  2. Mood Swings: An Affective Interactive Art System

    NASA Astrophysics Data System (ADS)

    Bialoskorski, Leticia S. S.; Westerink, Joyce H. D. M.; van den Broek, Egon L.

    The progress in the field of affective computing enables the realization of affective consumer products, affective games, and affective art. This paper describes the affective interactive art system Mood Swings, which interprets and visualizes affect expressed by a person. Mood Swings is founded on the integration of a framework for affective movements and a color model. This enables Mood Swings to recognize affective movement characteristics as expressed by a person and display a color that matches the expressed emotion. With that, a unique interactive system is introduced, which can be considered as art, a game, or a combination of both.

  3. [Network structures in biological systems].

    PubMed

    Oleskin, A V

    2013-01-01

    Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

  4. Systems biology of Microbial Communities

    SciTech Connect

    Navid, A; Ghim, C; Fenley, A; Yoon, S; Lee, S; Almaas, E

    2008-04-11

    Microbes exist naturally in a wide range of environments, spanning the extremes of high acidity and high temperature to soil and the ocean, in communities where their interactions are significant. We present a practical discussion of three different approaches for modeling microbial communities: rate equations, individual-based modeling, and population dynamics. We illustrate the approaches with detailed examples. Each approach is best fit to different levels of system representation, and they have different needs for detailed biological input. Thus, this set of approaches is able to address the operation and function of microbial communities on a wide range of organizational levels.

  5. Systems biology and biomarker discovery

    SciTech Connect

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  6. Systems Biology of Fungal Infection

    PubMed Central

    Horn, Fabian; Heinekamp, Thorsten; Kniemeyer, Olaf; Pollmächer, Johannes; Valiante, Vito; Brakhage, Axel A.

    2012-01-01

    Elucidation of pathogenicity mechanisms of the most important human-pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections. A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviors in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions. We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modeling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy. PMID:22485108

  7. Leaf microbiota of strawberries as affected by biological control agents.

    PubMed

    Sylla, Justine; Alsanius, Beatrix W; Krüger, Erika; Reineke, Annette; Strohmeier, Stephan; Wohanka, Walter

    2013-10-01

    The increasing use of biological control agents (BCAs) against Botrytis cinerea in strawberry raises the question of whether there are any undesirable impacts of foliar applications of BCAs on nontarget microorganisms in the phyllosphere. Therefore, our objective was to investigate this issue within a field study. Strawberry plants were repeatedly sprayed with three BCAs-namely, RhizoVital 42 fl. (Bacillus amyloliquefaciens FZB42), Trianum-P (Trichoderma harzianum T22), and Naturalis (Beauveria bassiana ATCC 74040)-to suppress Botrytis cinerea infections. Microbial communities of differentially treated leaves were analyzed using plate counts and pyrosequencing and compared with the microbial community of nontreated leaves. Plate count results indicate that the applied Bacillus and Trichoderma spp. survived in the strawberry phyllosphere throughout the strawberry season. However, no significant impacts on the leaf microbiota could be detected by this culture-dependent technique. Pyrosequencing of internal transcribed spacer ribosomal RNA and 16S RNA sequences revealed a change in fungal composition and diversity at class level after the introduction of T. harzianum T22 to the phyllosphere, whereas the bacterial composition and diversity was not affected by either this Trichoderma preparation or the other two BCAs. Our results suggest that pyrosequencing represents a useful method for studying microbial interactions in the phyllosphere.

  8. Controlled annotations for systems biology.

    PubMed

    Juty, Nick; Laibe, Camille; Le Novère, Nicolas

    2013-01-01

    The aim of this chapter is to provide sufficient information to enable a reader, new to the subject of Systems Biology, to create and use effectively controlled annotations, using resolvable Identifiers.org Uniform Resource Identifiers (URIs). The text details the underlying requirements that have led to the development of such an identification scheme and infrastructure, the principles that underpin its syntax and the benefits derived through its use. It also places into context the relationship with other standardization efforts, how it differs from other pre-existing identification schemes, recent improvements to the system, as well as those that are planned in the future. Throughout, the reader is provided with explicit examples of use and directed to supplementary information where necessary.

  9. Engineering simulations for cancer systems biology.

    PubMed

    Bown, James; Andrews, Paul S; Deeni, Yusuf; Goltsov, Alexey; Idowu, Michael; Polack, Fiona A C; Sampson, Adam T; Shovman, Mark; Stepney, Susan

    2012-11-01

    Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions.

  10. Quantum Effects in Biological Systems

    NASA Astrophysics Data System (ADS)

    Roy, Sisir

    2014-07-01

    The debates about the trivial and non-trivial effects in biological systems have drawn much attention during the last decade or so. What might these non-trivial sorts of quantum effects be? There is no consensus so far among the physicists and biologists regarding the meaning of "non-trivial quantum effects". However, there is no doubt about the implications of the challenging research into quantum effects relevant to biology such as coherent excitations of biomolecules and photosynthesis, quantum tunneling of protons, van der Waals forces, ultrafast dynamics through conical intersections, and phonon-assisted electron tunneling as the basis for our sense of smell, environment assisted transport of ions and entanglement in ion channels, role of quantum vacuum in consciousness. Several authors have discussed the non-trivial quantum effects and classified them into four broad categories: (a) Quantum life principle; (b) Quantum computing in the brain; (c) Quantum computing in genetics; and (d) Quantum consciousness. First, I will review the above developments. I will then discuss in detail the ion transport in the ion channel and the relevance of quantum theory in brain function. The ion transport in the ion channel plays a key role in information processing by the brain.

  11. Fostering synergy between cell biology and systems biology.

    PubMed

    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.

  12. Fostering synergy between cell biology and systems biology

    PubMed Central

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

    2015-01-01

    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 critical 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. PMID:26013981

  13. Soil biological activity as affected by tillage intensity

    NASA Astrophysics Data System (ADS)

    Gajda, A.; Przewłoka, B.

    2012-02-01

    The effect of tillage intensity on changes of microbiological activity and content of particulate organic matter in soil under winter wheat duirng 3 years was studied. Microbial response related to the tillage-induced changes in soil determined on the content of biomass C and N, the rate of CO2 evolution, B/F ratio, the activity of dehydrogenases, acid and alkaline phosphatases, soil C/N ratio and microbial biomass C/N ratio confirmed the high sensitivity of soil microbial populations to the tillage system applied. After three year studies, the direct sowing system enhanced the increase of labile fraction of organic matter content in soil. There were no significant changes in the labile fraction quantity observed in soil under conventional tillage. Similar response related to the tillage intensity was observed in particulate organic matter quantities expressed as a percentage of total organic matter in soil. A high correlation coefficients calculated between contents of soil microbial biomass C and N, particulate organic matter and potentially mineralizable N, and the obtained yields of winter wheat grown on experimental fields indicated on a high importance of biological quality of status of soil for agricultural crop production.

  14. Proving Stabilization of Biological Systems

    NASA Astrophysics Data System (ADS)

    Cook, Byron; Fisher, Jasmin; Krepska, Elzbieta; Piterman, Nir

    We describe an efficient procedure for proving stabilization of biological systems modeled as qualitative networks or genetic regulatory networks. For scalability, our procedure uses modular proof techniques, where state-space exploration is applied only locally to small pieces of the system rather than the entire system as a whole. Our procedure exploits the observation that, in practice, the form of modular proofs can be restricted to a very limited set. For completeness, our technique falls back on a non-compositional counterexample search. Using our new procedure, we have solved a number of challenging published examples, including: a 3-D model of the mammalian epidermis; a model of metabolic networks operating in type-2 diabetes; a model of fate determination of vulval precursor cells in the C. elegans worm; and a model of pair-rule regulation during segmentation in the Drosophila embryo. Our results show many orders of magnitude speedup in cases where previous stabilization proving techniques were known to succeed, and new results in cases where tools had previously failed.

  15. A SYSTEMS BIOLOGY APPROACH TO DEVELOPMENTAL TOXICOLOGY

    EPA Science Inventory

    Abstract
    Recent advances in developmental biology have yielded detailed models of gene regulatory networks (GRNs) involved in cell specification and other processes in embryonic differentiation. Such networks form the bedrock on which a systems biology approach to developme...

  16. Robust design of biological circuits: evolutionary systems biology approach.

    PubMed

    Chen, Bor-Sen; Hsu, Chih-Yuan; Liou, Jing-Jia

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.

  17. Systemic affects of methamphetamine use.

    PubMed

    Hauer, Patrick

    2010-08-01

    Methamphetamine (meth) is the most widely used illegal stimulant in the United States and is especially prevalent in Midwestern states. The sense of euphoria caused by the drug, the ease of manufacturing and the relatively low cost make it a drug of choice for many. The broad range of systemic effects potentially caused by the use of this drug is wide reaching and can vary in degree and presentation from patient to patient. Abnormalities include cardiac and pulmonary disorders as well as observable integumentary problems, psychoses, CNS disturbances, problems associated with immunity and constitutional signs and symptoms. Health care providers need to be vigilant in their efforts to identify patients who may be users of meth and to identify any subtle abnormal findings that may be indicative of significant underlying systemic pathology. Questionnaires like the RAFFT (Relax, Alone, Forget, Friends, Trouble) and the MINI (Mini-International Neuropsychiatric Interview) can be helpful in identifying substance abuse disorders in patients.

  18. Spatial Aspects in Biological System Simulations

    PubMed Central

    Resat, Haluk; Costa, Michelle N.; Shankaran, Harish

    2012-01-01

    Mathematical models of the dynamical properties of biological systems aim to improve our understanding of the studied system with the ultimate goal of being able to predict system responses in the absence of experimentation. Despite the enormous advances that have been made in biological modeling and simulation, the inherently multiscale character of biological systems and the stochasticity of biological processes continue to present significant computational and conceptual challenges. Biological systems often consist of well-organized structural hierarchies, which inevitably lead to multiscale problems. This chapter introduces and discusses the advantages and shortcomings of several simulation methods that are being used by the scientific community to investigate the spatiotemporal properties of model biological systems. We first describe the foundations of the methods and then describe their relevance and possible application areas with illustrative examples from our own research. Possible ways to address the encountered computational difficulties are also discussed. PMID:21187236

  19. Introducing systems biology for nursing science.

    PubMed

    Founds, Sandra A

    2009-07-01

    Systems biology expands on general systems theory as the "omics'' era rapidly progresses. Although systems biology has been institutionalized as an interdisciplinary framework in the biosciences, it is not yet apparent in nursing. This article introduces systems biology for nursing science by presenting an overview of the theory. This framework for the study of organisms from molecular to environmental levels includes iterations of computational modeling, experimentation, and theory building. Synthesis of complex biological processes as whole systems rather than isolated parts is emphasized. Pros and cons of systems biology are discussed, and relevance of systems biology to nursing is described. Nursing research involving molecular, physiological, or biobehavioral questions may be guided by and contribute to the developing science of systems biology. Nurse scientists can proactively incorporate systems biology into their investigations as a framework for advancing the interdisciplinary science of human health care. Systems biology has the potential to advance the research and practice goals of the National Institute for Nursing Research in the National Institutes of Health Roadmap initiative.

  20. Surface coating affects behavior of metallic nanoparticles in a biological environment

    PubMed Central

    Jurašin, Darija Domazet; Ćurlin, Marija; Capjak, Ivona; Crnković, Tea; Lovrić, Marija; Babič, Michal; Horák, Daniel; Gajović, Srećko

    2016-01-01

    Summary Silver (AgNPs) and maghemite, i.e., superparamagnetic iron oxide nanoparticles (SPIONs) are promising candidates for new medical applications, which implies the need for strict information regarding their physicochemical characteristics and behavior in a biological environment. The currently developed AgNPs and SPIONs encompass a myriad of sizes and surface coatings, which affect NPs properties and may improve their biocompatibility. This study is aimed to evaluate the effects of surface coating on colloidal stability and behavior of AgNPs and SPIONs in modelled biological environments using dynamic and electrophoretic light scattering techniques, as well as transmission electron microscopy to visualize the behavior of the NP. Three dispersion media were investigated: ultrapure water (UW), biological cell culture medium without addition of protein (BM), and BM supplemented with common serum protein (BMP). The obtained results showed that different coating agents on AgNPs and SPIONs produced different stabilities in the same biological media. The combination of negative charge and high adsorption strength of coating agents proved to be important for achieving good stability of metallic NPs in electrolyte-rich fluids. Most importantly, the presence of proteins provided colloidal stabilization to metallic NPs in biological fluids regardless of their chemical composition, surface structure and surface charge. In addition, an assessment of AgNP and SPION behavior in real biological fluids, rat whole blood (WhBl) and blood plasma (BlPl), revealed that the composition of a biological medium is crucial for the colloidal stability and type of metallic NP transformation. Our results highlight the importance of physicochemical characterization and stability evaluation of metallic NPs in a variety of biological systems including as many NP properties as possible. PMID:26977382

  1. Systemic Imidacloprid Affects Intraguild Parasitoids Differently.

    PubMed

    Taylor, Sally V; Burrack, Hannah J; Roe, R Michael; Bacheler, Jack S; Sorenson, Clyde E

    2015-01-01

    Toxoneuron nigriceps (Viereck) (Hymenoptera, Braconidae) and Campoletis sonorensis (Cameron) (Hymenoptera, Ichneumonidae) are solitary endoparasitoids of the tobacco budworm, Heliothis virescens (Fabricius) (Lepidoptera, Noctuidae). They provide biological control of H. virescens populations in Southeastern US agricultural production systems. Field and greenhouse experiments conducted from 2011-2014 compared parasitism rates of parasitoids that developed inside H. virescens larvae fed on tobacco plants treated with and without imidacloprid. The parasitoids in our study did not have a similar response. Toxoneuron nigriceps had reduced parasitism rates, but parasitism rates of C. sonorensis were unaffected. Preliminary data indicate that adult female lifespans of T. nigriceps are also reduced. ELISA was used to measure concentrations of neonicotinoids, imidacloprid and imidacloprid metabolites in H. virescens larvae that fed on imidacloprid-treated plants and in the parasitoids that fed on these larvae. Concentrations were detectable in the whole bodies of parasitized H. virescens larvae, T. nigriceps larvae and T. nigriceps adults, but not in C. sonorensis larvae and adults. These findings suggest that there are effects of imidacloprid on multiple trophic levels, and that insecticide use may differentially affect natural enemies with similar feeding niches.

  2. Systemic Imidacloprid Affects Intraguild Parasitoids Differently

    PubMed Central

    Roe, R. Michael; Bacheler, Jack S.

    2015-01-01

    Toxoneuron nigriceps (Viereck) (Hymenoptera, Braconidae) and Campoletis sonorensis (Cameron) (Hymenoptera, Ichneumonidae) are solitary endoparasitoids of the tobacco budworm, Heliothis virescens (Fabricius) (Lepidoptera, Noctuidae). They provide biological control of H. virescens populations in Southeastern US agricultural production systems. Field and greenhouse experiments conducted from 2011–2014 compared parasitism rates of parasitoids that developed inside H. virescens larvae fed on tobacco plants treated with and without imidacloprid. The parasitoids in our study did not have a similar response. Toxoneuron nigriceps had reduced parasitism rates, but parasitism rates of C. sonorensis were unaffected. Preliminary data indicate that adult female lifespans of T. nigriceps are also reduced. ELISA was used to measure concentrations of neonicotinoids, imidacloprid and imidacloprid metabolites in H. virescens larvae that fed on imidacloprid-treated plants and in the parasitoids that fed on these larvae. Concentrations were detectable in the whole bodies of parasitized H. virescens larvae, T. nigriceps larvae and T. nigriceps adults, but not in C. sonorensis larvae and adults. These findings suggest that there are effects of imidacloprid on multiple trophic levels, and that insecticide use may differentially affect natural enemies with similar feeding niches. PMID:26658677

  3. S-Nitrosothiol measurements in biological systems.

    PubMed

    Gow, Andrew; Doctor, Allan; Mannick, Joan; Gaston, Benjamin

    2007-05-15

    S-Nitrosothiol (SNO) cysteine modifications are regulated signaling reactions that dramatically affect, and are affected by, protein conformation. The lability of the SNO bond can make SNO-modified proteins cumbersome to measure accurately. Here, we review methodologies for detecting SNO modifications in biology. There are three caveats. (1) Many assays for biological SNOs are used near the limit of detection: standard curves must be in the biologically relevant concentration range. (2) The assays that are most reliable are those that modify SNO protein or peptide chemistry the least. (3) Each result should be quantitatively validated using more than one assay. Improved assays are needed and are in development.

  4. Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent

    USGS Publications Warehouse

    Williams, Wyatt I.; Friedman, Jonathan M.; Gaskin, John F.; Norton, Andrew P.

    2014-01-01

    Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others.

  5. Interacting Physical and Biological Processes Affecting Nutrient Transport Through Human Dominated Landscapes

    NASA Astrophysics Data System (ADS)

    Finlay, J. C.

    2015-12-01

    Human activities increasingly dominate biogeochemical cycles of limiting nutrients on Earth. Urban and agricultural landscapes represent the largest sources of excess nutrients that drive water quality degradation. The physical structure of both urban and agricultural watersheds has been extensively modified, and these changes have large impacts on water and nutrient transport. Despite strong physical controls over nutrient transport in human dominated landscapes, biological processes play important roles in determining the fates of both nitrogen and phosphorus. This talk uses examples from research in urban and agricultural watersheds in the Midwestern USA to illustrate interactions of physical and biological controls over nutrient cycles that have shifted nitrogen (N) and phosphorus (P) sources and cycling in unexpected ways in response to management changes. In urban watersheds, efforts to improve water quality have been hindered by legacy sources of phosphorus added to storm water through transport to drainage systems by vegetation. Similarly, reductions in field erosion in agricultural watersheds have not led to major reductions in phosphorus transport, because of continued release of biological sources of P. Where management of phosphorus has been most effective in reducing eutrophication of lakes, decreases in N removal processes have led to long term increases in N concentration and transport. Together, these examples show important roles for biological processes affecting nutrient movement in highly modified landscapes. Consideration of the downstream physical and biological responses of management changes are thus critical toward identification of actions that will most effectively reduce excess nutrients watersheds and coastal zones.

  6. Systems biology and cardiac arrhythmias.

    PubMed

    Grace, Andrew A; Roden, Dan M

    2012-10-27

    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence.

  7. Financial Exigency: Need It Affect the Quality of Biology Curricula?

    ERIC Educational Resources Information Center

    Thomson, Robert G.; Abramoff, Peter

    1984-01-01

    Outlines Marquette University's response to declining enrollments and financial restraints for its undergraduate biology curriculum, beginning with a description of the old program and its problems. Discusses redefinition of laboratory role, uncoupling and reducing number of laboratories required, teacher responsibility changes, centralized…

  8. Systems biology and mechanics of growth.

    PubMed

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

    In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention.

  9. Method of measurement in biological systems

    DOEpatents

    Turteltaub, K.W.; Vogel, J.S.; Felton, J.S.; Gledhill, B.L.: Davis, J.C.; Stanker, L.H.

    1993-05-11

    A method is disclosed of quantifying molecules in biological substances, comprising: selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere; preparing a long-lived radioisotope labeled reactive chemical specie; administering the chemical specie to the biological host in doses sufficiently low to avoid significant overt damage to the biological system; allowing a period of time to elapse sufficient for dissemination and interaction of the chemical specie with the host throughout the biological system of the host; isolating a reacted fraction of the biological substance from the host in a manner sufficient to avoid contamination of the substance from extraneous sources; converting the fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation; and measuring the radioisotope concentration in the material by means of direct isotopic counting.

  10. Systems biology and mechanics of growth

    PubMed Central

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

    In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident in embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the sytems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. PMID:26352286

  11. Genomes, Phylogeny, and Evolutionary Systems Biology

    SciTech Connect

    Medina, Monica

    2005-03-25

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

  12. Graphics processing units in bioinformatics, computational biology and systems biology.

    PubMed

    Nobile, Marco S; Cazzaniga, Paolo; Tangherloni, Andrea; Besozzi, Daniela

    2016-07-08

    Several studies in Bioinformatics, Computational Biology and Systems Biology rely on the definition of physico-chemical or mathematical models of biological systems at different scales and levels of complexity, ranging from the interaction of atoms in single molecules up to genome-wide interaction networks. Traditional computational methods and software tools developed in these research fields share a common trait: they can be computationally demanding on Central Processing Units (CPUs), therefore limiting their applicability in many circumstances. To overcome this issue, general-purpose Graphics Processing Units (GPUs) are gaining an increasing attention by the scientific community, as they can considerably reduce the running time required by standard CPU-based software, and allow more intensive investigations of biological systems. In this review, we present a collection of GPU tools recently developed to perform computational analyses in life science disciplines, emphasizing the advantages and the drawbacks in the use of these parallel architectures. The complete list of GPU-powered tools here reviewed is available at http://bit.ly/gputools.

  13. The emergence of modularity in biological systems

    NASA Astrophysics Data System (ADS)

    Lorenz, Dirk M.; Jeng, Alice; Deem, Michael W.

    2011-06-01

    In this review, we discuss modularity and hierarchy in biological systems. We review examples from protein structure, genetics, and biological networks of modular partitioning of the geometry of biological space. We review theories to explain modular organization of biology, with a focus on explaining how biology may spontaneously organize to a structured form. That is, we seek to explain how biology nucleated from among the many possibilities in chemistry. The emergence of modular organization of biological structure will be described as a symmetry-breaking phase transition, with modularity as the order parameter. Experimental support for this description will be reviewed. Examples will be presented from pathogen structure, metabolic networks, gene networks, and protein-protein interaction networks. Additional examples will be presented from ecological food networks, developmental pathways, physiology, and social networks.

  14. Coupled model of physical and biological processes affecting maize pollination

    NASA Astrophysics Data System (ADS)

    Arritt, R.; Westgate, M.; Riese, J.; Falk, M.; Takle, E.

    2003-04-01

    Controversy over the use of genetically modified (GM) crops has led to increased interest in evaluating and controlling the potential for inadvertent outcrossing in open-pollinated crops such as maize. In response to this problem we have developed a Lagrangian model of pollen dispersion as a component of a coupled end-to-end (anther to ear) physical-biological model of maize pollination. The Lagrangian method is adopted because of its generality and flexibility: first, the method readily accommodates flow fields of arbitrary complexity; second, each element of the material being transported can be identified by its source, time of release, or other properties of interest. The latter allows pollen viability to be estimated as a function of such factors as travel time, temperature, and relative humidity, so that the physical effects of airflow and turbulence on pollen dispersion can be considered together with the biological aspects of pollen release and viability. Predicted dispersion of pollen compares well both to observations and to results from a simpler Gaussian plume model. Ability of the Lagrangian model to handle complex air flows is demonstrated by application to pollen dispersion in the vicinity of an agricultural shelter belt. We also show results indicating that pollen viability can be quantified by an "aging function" that accounts for temperature, humidity, and time of exposure.

  15. Biological identification systems: genetic markers.

    PubMed

    Cunningham, E P; Meghen, C M

    2001-08-01

    Individual animals differ from each other on a number of biological levels. At the most basic level, the deoxyribonucleic acid (DNA) of each animal is different, and transcription of the DNA code yields variations at the protein level, which in turn give rise to individual diversity at the physical level. In recent years, accessing the primary genetic code of individual animals has become straightforward. The authors briefly review the development of biological identification technologies and then consider in more detail the application of current DNA testing technologies to issues of traceability of live animals and derived products. Although largely focused on cattle and beef traceability, the principles described are relevant to ovine, porcine and equine traceability. The accelerating pace of innovation and development within the field of molecular genetics suggests that the technologies described may soon be superseded. However, the principles of genetic identification will remain unchanged.

  16. Controlled ecological life support system - biological problems

    NASA Technical Reports Server (NTRS)

    Moore, B., III (Editor); Macelroy, R. D. (Editor)

    1982-01-01

    The general processes and controls associated with two distinct experimental paradigms are examined. Specific areas for research related to biotic production (food production) and biotic decomposition (waste management) are explored. The workshop discussions were directed toward Elemental cycles and the biological factors that affect the transformations of nutrients into food, of food material into waste, and of waste into nutrients were discussed. To focus on biological issues, the discussion assumed that (1) food production would be by biological means (thus excluding chemical synthesis), (2) energy would not be a limiting factor, and (3) engineering capacity for composition and leak rate would be adequate.

  17. Developmental systems biology flourishing on new technologies.

    PubMed

    Han, Jing-Dong J; Liu, Yi; Xue, Huiling; Xia, Kai; Yu, Hong; Zhu, Shanshan; Chen, Zhang; Zhang, Wei; Huang, Zheng; Jin, Chunyu; Xian, Bo; Li, Jing; Hou, Lei; Han, Yixing; Niu, Chaoqun; Alcon, Timothy C

    2008-10-01

    Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies, and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches.

  18. Tillage system affects microbiological properties of soil

    NASA Astrophysics Data System (ADS)

    Delgado, A.; de Santiago, A.; Avilés, M.; Perea, F.

    2012-04-01

    Soil tillage significantly affects organic carbon accumulation, microbial biomass, and subsequently enzymatic activity in surface soil. Microbial activity in soil is a crucial parameter contributing to soil functioning, and thus a basic quality factor for soil. Since enzymes remain soil after excretion by living or disintegrating cells, shifts in their activities reflect long-term fluctuations in microbial biomass. In order to study the effects of no-till on biochemical and microbiological properties in comparison to conventional tillage in a representative soil from South Spain, an experiment was conducted since 1982 on the experimental farm of the Institute of Agriculture and Fisheries Research of Andalusia (IFAPA) in Carmona, SW Spain (37o24'07''N, 5o35'10''W). The soil at the experimental site was a very fine, montomorillonitic, thermic Chromic Haploxerert (Soil Survey Staff, 2010). A randomized complete block design involving three replications and the following two tillage treatments was performed: (i) Conventional tillage, which involved mouldboard plowing to a depth of 50 cm in the summer (once every three years), followed by field cultivation to a depth of 15 cm before sowing; crop residues being burnt, (ii) No tillage, which involved controlling weeds before sowing by spraying glyphosate and sowing directly into the crop residue from the previous year by using a planter with double-disk openers. For all tillage treatments, the crop rotation (annual crops) consisted of winter wheat, sunflower, and legumes (pea, chickpea, or faba bean, depending on the year), which were grown under rainfed conditions. Enzymatic activities (ß-glucosidase, dehydrogenase, aryl-sulphatase, acid phosphatase, and urease), soil microbial biomass by total viable cells number by acridine orange direct count, the density of cultivable groups of bacteria and fungi by dilution plating on semi-selective media, the physiological profiles of the microbial communities by BiologR, and the

  19. Applicability of computational systems biology in toxicology.

    PubMed

    Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

    2014-07-01

    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research.

  20. Cow biological type affects ground beef colour stability.

    PubMed

    Raines, Christopher R; Hunt, Melvin C; Unruh, John A

    2009-12-01

    To determine the effects of cow biological type on colour stability of ground beef, M. semimembranosus from beef-type (BSM) and dairy-type (DSM) cows was obtained 5d postmortem. Three blends (100% BSM, 50% BSM+50% DSM, 100% DSM) were adjusted to 90% and 80% lean points using either young beef trim (YBT) or beef cow trim (BCT), then packaged in high oxygen (High-O(2); 80% O(2)) modified atmosphere (MAP). The BSM+YBT patties had the brightest colour initially, but discoloured rapidly. Although DSM+BCT patties had the darkest colour initially, they discoloured least during display. Metmyoglobin reducing ability of ground DSM was up to fivefold greater than ground BSM, and TBARS values of BSM was twofold greater than DSM by the end of display (4d). Though initially darker than beef cow lean, dairy cow lean has a longer display colour life and may be advantageous to retailers using High-O(2) MAP.

  1. Recent developments in affective recommender systems

    NASA Astrophysics Data System (ADS)

    Katarya, Rahul; Verma, Om Prakash

    2016-11-01

    Recommender systems (RSs) are playing a significant role since 1990s as they provide relevant, personalized information to the users over the internet. Lots of work have been done in information filtering, utilization, and application related to RS. However, an important area recently draws our attention which is affective recommender system. Affective recommender system (ARS) is latest trending area of research, as publication in this domain are few and recently published. ARS is associated with human behaviour, human factors, mood, senses, emotions, facial expressions, body gesture and physiological with human-computer interaction (HCI). Due to this assortment and various interests, more explanation is required, as it is in premature phase and growing as compared to other fields. So we have done literature review (LR) in the affective recommender systems by doing classification, incorporate reputed articles published from the year 2003 to February 2016. We include articles which highlight, analyse, and perform a study on affective recommender systems. This article categorizes, synthesizes, and discusses the research and development in ARS. We have classified and managed ARS papers according to different perspectives: research gaps, nature, algorithm or method adopted, datasets, the platform on executed, types of information and evaluation techniques applied. The researchers and professionals will positively support this survey article for understanding the current position, research in affective recommender systems and will guide future trends, opportunity and research focus in ARS.

  2. Document Retrieval Systems; Factors Affecting Search Time.

    ERIC Educational Resources Information Center

    Montgomery, K. Leon, Ed.

    An experiment was conducted to identify some of the important parameters affecting search time, a critical cost factor in retrieval systems. Using actual computer searches of Chemical Abstracts Condensate, a comparison was made between the effectiveness of linear and inverted filing systems. Since the results indicated that it was the type and…

  3. Standards and ontologies in computational systems biology.

    PubMed

    Sauro, Herbert M; Bergmann, Frank T

    2008-01-01

    With the growing importance of computational models in systems biology there has been much interest in recent years to develop standard model interchange languages that permit biologists to easily exchange models between different software tools. In the present chapter two chief model exchange standards, SBML (Systems Biology Markup Language) and CellML are described. In addition, other related features including visual layout initiatives, ontologies and best practices for model annotation are discussed. Software tools such as developer libraries and basic editing tools are also introduced, together with a discussion on the future of modelling languages and visualization tools in systems biology.

  4. Bridging the gaps in systems biology.

    PubMed

    Cvijovic, Marija; Almquist, Joachim; Hagmar, Jonas; Hohmann, Stefan; Kaltenbach, Hans-Michael; Klipp, Edda; Krantz, Marcus; Mendes, Pedro; Nelander, Sven; Nielsen, Jens; Pagnani, Andrea; Przulj, Natasa; Raue, Andreas; Stelling, Jörg; Stoma, Szymon; Tobin, Frank; Wodke, Judith A H; Zecchina, Riccardo; Jirstrand, Mats

    2014-10-01

    Systems biology aims at creating mathematical models, i.e., computational reconstructions of biological systems and processes that will result in a new level of understanding-the elucidation of the basic and presumably conserved "design" and "engineering" principles of biomolecular systems. Thus, systems biology will move biology from a phenomenological to a predictive science. Mathematical modeling of biological networks and processes has already greatly improved our understanding of many cellular processes. However, given the massive amount of qualitative and quantitative data currently produced and number of burning questions in health care and biotechnology needed to be solved is still in its early phases. The field requires novel approaches for abstraction, for modeling bioprocesses that follow different biochemical and biophysical rules, and for combining different modules into larger models that still allow realistic simulation with the computational power available today. We have identified and discussed currently most prominent problems in systems biology: (1) how to bridge different scales of modeling abstraction, (2) how to bridge the gap between topological and mechanistic modeling, and (3) how to bridge the wet and dry laboratory gap. The future success of systems biology largely depends on bridging the recognized gaps.

  5. Biological Systems, Energy Sources, and Biology Teaching. Biology and Human Welfare.

    ERIC Educational Resources Information Center

    Tribe, Michael; Pritchard, Alan J.

    This five-chapter document (part of a series on biology and human welfare) focuses on biological systems as energy sources and on the teaching of this subject area. Chapter 1 discusses various topics related to energy and ecology, including biomass, photosynthesis and world energy balances, energy flow through ecosystems, and others. Chapter 2…

  6. The need for a biological registration system.

    PubMed

    Pihl, Todd D; Ribaudo, Randall K

    2010-06-01

    A biological registration system is capable of determining whether two complex biological molecules are the same or different, and can assign identifiers based on this determination. Although such systems are frequently employed by chemists, they are rarely used by biological scientists in the pharmaceutical industry. However, a biological registration system would have several enterprise-wide benefits, from R&D to IP to laboratory safety. Beyond these evident benefits, a biological registration system that integrates appropriately with other systems such as electronic laboratory notebooks and inventory databases could provide critical links to allow the integration of otherwise-siloed data and knowledge generated across global pharmaceutical companies and other large research institutions. Data and knowledge integration are widely recognized as critical yet elusive components of effective translational science and systems biology programs that would create greater efficiencies for drug discovery. However, determining the optimal construction of such systems remains a challenge. This feature review describes how a special interest group comprising several pharmaceutical companies and a software company was used to create a commercially viable and supportable system.

  7. Students' application of a biological concept: Factors affecting consistency

    NASA Astrophysics Data System (ADS)

    Palmer, David

    1996-12-01

    This study investigated factors affecting students' ability to apply consistently the concept of adaptations (i.e., characteristics which suit an organism to its environment). Individual interviews were carried out with 74 Year 10 students, of whom only 47% showed an understanding of the concept. These students were asked to indicate on a list of living and non-living items which ones whould have adaptations. It was found that they were more likely to apply the concept to vertebrates than to other types of living things. In addition, many students appeared to be unable to separate consistently the idea of “adaptations as characteristics” from the other everyday and scientific meanings of the terms “adapt” and “adaptation”.

  8. Biologics formulation factors affecting metal leachables from stainless steel.

    PubMed

    Zhou, Shuxia; Schöneich, Christian; Singh, Satish K

    2011-03-01

    An area of increasing concern and scientific scrutiny is the potential contamination of drug products by leachables entering the product during manufacturing and storage. These contaminants may either have a direct safety impact on the patients or act indirectly through the alteration of the physicochemical properties of the product. In the case of biotherapeutics, trace amounts of metal contaminants can arise from various sources, but mainly from contact with stainless steel (ss). The effect of the various factors, buffer species, solution fill volume per unit contact surface area, metal chelators, and pH, on metal leachables from contact with ss over time were investigated individually. Three major metal leachables, iron, chromium, and nickel, were monitored by inductively coupled plasma-mass spectrometry because they are the major components of 316L ss. Iron was primarily used to evaluate the effect of each factor since it is the most abundant. It was observed that each studied factor exhibited its own effect on metal leachables from contact with ss. The effect of buffer species and pH exhibited temperature dependence over the studied temperature range. The metal leachables decreased with the increased fill volume (mL) per unit contact ss surface area (cm(2)) but a plateau was achieved at approximately 3 mL/cm(2). Metal chelators produced the strongest effect in facilitating metal leaching. In order to minimize the metal leachables and optimize biological product stability, each formulation factor must be evaluated for its impact, to balance its risk and benefit in achieving the target drug product shelf life.

  9. Simulated microgravity affects some biological characteristics of Lactobacillus acidophilus.

    PubMed

    Shao, Dongyan; Yao, Linbo; Riaz, Muhammad Shahid; Zhu, Jing; Shi, Junling; Jin, Mingliang; Huang, Qingsheng; Yang, Hui

    2017-04-01

    The effects of weightlessness on enteric microorganisms have been extensively studied, but have mainly been focused on pathogens. As a major component of the microbiome of the human intestinal tract, probiotics are important to keep the host healthy. Accordingly, understanding their changes under weightlessness conditions has substantial value. This study was carried out to investigate the characteristics of Lactobacillus acidophilus, a typical probiotic for humans, under simulated microgravity (SMG) conditions. The results revealed that SMG had no significant impact on the morphology of L. acidophilus, but markedly shortened its lag phase, enhanced its growth rate, acid tolerance ability up to pH < 2.5, and the bile resistance at the bile concentration of <0.05%. SMG also decreased the sensitivity of L. acidophilus to cefalexin, sulfur gentamicin, and sodium penicillin. No obvious effect of SMG was observed on the adhesion ability of L. acidophilus to Caco-2 cells. Moreover, after SMG treatment, both the culture of L. acidophilus and its liquid phase exhibited higher antibacterial activity against S. typhimurium and S. aureus in a time-dependent manner. The SMG treatment also increased the in vitro cholesterol-lowering ability of L. acidophilus by regulating the expression of the key cholesterol metabolism genes CYP7A1, ABCB11, LDLR, and HMGCR in the HepG2 cell line. Thus, the SMG treatment did have considerable influence on some biological activities and characteristics of L. acidophilus related to human health. These findings provided valuable information for understanding the influence of probiotics on human health under simulated microgravity conditions, at least.

  10. Functional Translational Readthrough: A Systems Biology Perspective

    PubMed Central

    Schueren, Fabian

    2016-01-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries. PMID:27490485

  11. A framework for evolutionary systems biology

    PubMed Central

    Loewe, Laurence

    2009-01-01

    Background Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects. Results Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions in silico. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism. Conclusion EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications. PMID:19239699

  12. Controlled vocabularies and semantics in systems biology.

    PubMed

    Courtot, Mélanie; Juty, Nick; Knüpfer, Christian; Waltemath, Dagmar; Zhukova, Anna; Dräger, Andreas; Dumontier, Michel; Finney, Andrew; Golebiewski, Martin; Hastings, Janna; Hoops, Stefan; Keating, Sarah; Kell, Douglas B; Kerrien, Samuel; Lawson, James; Lister, Allyson; Lu, James; Machne, Rainer; Mendes, Pedro; Pocock, Matthew; Rodriguez, Nicolas; Villeger, Alice; Wilkinson, Darren J; Wimalaratne, Sarala; Laibe, Camille; Hucka, Michael; Le Novère, Nicolas

    2011-10-25

    The use of computational modeling to describe and analyze biological systems is at the heart of systems biology. Model structures, simulation descriptions and numerical results can be encoded in structured formats, but there is an increasing need to provide an additional semantic layer. Semantic information adds meaning to components of structured descriptions to help identify and interpret them unambiguously. Ontologies are one of the tools frequently used for this purpose. We describe here three ontologies created specifically to address the needs of the systems biology community. The Systems Biology Ontology (SBO) provides semantic information about the model components. The Kinetic Simulation Algorithm Ontology (KiSAO) supplies information about existing algorithms available for the simulation of systems biology models, their characterization and interrelationships. The Terminology for the Description of Dynamics (TEDDY) categorizes dynamical features of the simulation results and general systems behavior. The provision of semantic information extends a model's longevity and facilitates its reuse. It provides useful insight into the biology of modeled processes, and may be used to make informed decisions on subsequent simulation experiments.

  13. [System biology and synthetic biology modify drug discovery and development].

    PubMed

    Haiech, Jacques; Ranjeva, Raoul; Kilhoffer, Marie-Claude

    2012-02-01

    Life Sciences are built on observations. Right now, a more systemic approach allowing to integrate the different organizational levels in Biology is emerging. Such an approach uses a set of technologies and strategies allowing to build models that appear to be more and more predictive (omics, bioinformatics, integrative biology, computational biology…). Those models accelerate the rational development of new therapies avoiding an engineering based only on trials and errors. This approach both holistic and predictive radically modifies the discovery and development modalities used today in health industries. Moreover, because of the apparition of new jobs at the interface of disciplines, of private and public sectors and of life sciences and engineering sciences, this implies to rethink the training programs in both their contents and their pedagogical tools.

  14. A system biology approach to understand functional activity of cell communication systems.

    PubMed

    Vera, Julio; Wolkenhauer, Olaf

    2008-01-01

    Systems Biology is the quantitative analysis of dynamic interactions among several components of a biochemical system, aiming at an understanding of the behavior of the system as a whole. From an experimental perspective, systems biology is a suitable tool to support the biologist in the process of hypotheses generation and the efficient design of experiments. In this chapter, we discuss the elements of a systems biology methodology based on the interaction between experimental biologists and theoreticians. We, furthermore, show the use of such a methodology in a case study, analyzing receptor and transcription factor modulation affecting the responsiveness of the JAK2/STAT5 pathway.

  15. Parameters affecting HS emissions removal and re-circulating water quality in a pilot-scale sequential biological treatment system at a wastewater lift station in Brownsville, Texas, USA.

    PubMed

    Karre, Anand K; Bairu, Pavan; Jones, Kim D; Paca, Jan

    2012-01-01

    In this study, a pilot-scale sequential biological treatment system combining a biotrickling filter and biofilter was used to optimize the removal of variable emission H(2)S loadings ranging from 30 to 120 g m(-3) h(-1)at a wastewater lift station in Brownsville, Texas USA. The biotrickling filter recycle water pH remained between 2.0 to 3.0 during the four months of unit operation and the overall removal efficiency for H(2)S was >99%. The biotrickling filter removal efficiency was 70 ± 8%, with an elimination capacity of 10 to 80 g m(-3) h(-1) while the biofilter elimination capacity ranged from 10 to 40 g m(-3) h(-1). The sequential treatment system was operated initially at an Empty Bed Residence Time (EBRT) of 120 s (50 s for the biotrickling filter and 70 s for biofilter) for two months and then at an EBRT of 60 s (25 s for biotrickling filter and 35s for biofilter) for the remainder of the operating period; remarkably, there was only a slight decrease in removal efficiency at 60 s EBRT. In order to qualitatively evaluate the changes in recycle water quality in the system on the performance of the unit in precipitating sulfur species, the equilibrium chemical model, Visual MINTEQ was employed. The model predicted speciation results based on the feed water quality and sulfur loadings, and also forecast some iron-sulfur complexes which have potential to form some complex precipitates. This research demonstrated that low pH re-circulating water quality in the biological treatment of H(2)S was possible without compromising the high removal efficiency, and that an improved understanding of the recycle water chemistry of the trickling unit of a sequential treatment system could be useful in the overall optimization of the process.

  16. A Philosophical Perspective on Evolutionary Systems Biology.

    PubMed

    O'Malley, Maureen A; Soyer, Orkun S; Siegal, Mark L

    2015-03-01

    Evolutionary systems biology (ESB) is an emerging hybrid approach that integrates methods, models, and data from evolutionary and systems biology. Drawing on themes that arose at a cross-disciplinary meeting on ESB in 2013, we discuss in detail some of the explanatory friction that arises in the interaction between evolutionary and systems biology. These tensions appear because of different modeling approaches, diverse explanatory aims and strategies, and divergent views about the scope of the evolutionary synthesis. We locate these discussions in the context of long-running philosophical deliberations on explanation, modeling, and theoretical synthesis. We show how many of the issues central to ESB's progress can be understood as general philosophical problems. The benefits of addressing these philosophical issues feed back into philosophy too, because ESB provides excellent examples of scientific practice for the development of philosophy of science and philosophy of biology.

  17. Multiscale Computational Models of Complex Biological Systems

    PubMed Central

    Walpole, Joseph; Papin, Jason A.; Peirce, Shayn M.

    2014-01-01

    Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental platforms, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems while using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to best leverage these multiscale models to gain insight into biological systems using quantitative, biomedical engineering methods to analyze data in non-intuitive ways. These topics are discussed with a focus on the future of the field, the current challenges encountered, and opportunities yet to be realized. PMID:23642247

  18. Nonequilibrium Thermodynamics in Biological Systems

    NASA Astrophysics Data System (ADS)

    Aoki, I.

    2005-12-01

    1. Respiration Oxygen-uptake by respiration in organisms decomposes macromolecules such as carbohydrate, protein and lipid and liberates chemical energy of high quality, which is then used to chemical reactions and motions of matter in organisms to support lively order in structure and function in organisms. Finally, this chemical energy becomes heat energy of low quality and is discarded to the outside (dissipation function). Accompanying this heat energy, entropy production which inevitably occurs by irreversibility also is discarded to the outside. Dissipation function and entropy production are estimated from data of respiration. 2. Human body From the observed data of respiration (oxygen absorption), the entropy production in human body can be estimated. Entropy production from 0 to 75 years old human has been obtained, and extrapolated to fertilized egg (beginning of human life) and to 120 years old (maximum period of human life). Entropy production show characteristic behavior in human life span : early rapid increase in short growing phase and later slow decrease in long aging phase. It is proposed that this tendency is ubiquitous and constitutes a Principle of Organization in complex biotic systems. 3. Ecological communities From the data of respiration of eighteen aquatic communities, specific (i.e. per biomass) entropy productions are obtained. They show two phase character with respect to trophic diversity : early increase and later decrease with the increase of trophic diversity. The trophic diversity in these aquatic ecosystems is shown to be positively correlated with the degree of eutrophication, and the degree of eutrophication is an "arrow of time" in the hierarchy of aquatic ecosystems. Hence specific entropy production has the two phase: early increase and later decrease with time. 4. Entropy principle for living systems The Second Law of Thermodynamics has been expressed as follows. 1) In isolated systems, entropy increases with time and

  19. Vibrational resonances in biological systems at microwave frequencies.

    PubMed Central

    Adair, Robert K

    2002-01-01

    Many biological systems can be expected to exhibit resonance behavior involving the mechanical vibration of system elements. The natural frequencies of such resonances will, generally, be in the microwave frequency range. Some of these systems will be coupled to the electromagnetic field by the charge distributions they carry, thus admitting the possibility that microwave exposures may generate physiological effects in man and other species. However, such microwave excitable resonances are expected to be strongly damped by interaction with their aqueous biological environment. Although those dissipation mechanisms have been studied, the limitations on energy transfers that follow from the limited coupling of these resonances to the electromagnetic field have not generally been considered. We show that this coupling must generally be very small and thus the absorbed energy is so strongly limited that such resonances cannot affect biology significantly even if the systems are much less strongly damped than expected from basic dissipation models. PMID:11867434

  20. Method of measurement in biological systems

    DOEpatents

    Turteltaub, Kenneth W.; Vogel, John S.; Felton, James S.; Gledhill, Barton L.; Davis, Jay C.; Stanker, Larry H.

    1993-05-11

    Disclosed is a method of quantifying molecules in biological substances, comprising: a. selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere, b. preparing a long-lived radioisotope labeled reactive chemical specie, c. administering said chemical specie to said biological host in doses sufficiently low to avoid significant overt damage to the biological system thereof, d. allowing a period of time to elapse sufficient for dissemination and interaction of said chemical specie with said host throughout said biological system of said host, e. isolating a reacted fraction of the biological substance from said host in a manner sufficient to avoid contamination of said substance from extraneous sources, f. converting said fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation, and, g. measuring the radioisotope concentration in said material by means of direct isotopic counting.

  1. Method of measurement in biological systems

    DOEpatents

    Turteltaub, Kenneth W.; Vogel, John S.; Felton, James S.; Gledhill, Barton L.; Davis, Jay C.

    1994-01-01

    Disclosed is a method of quantifying molecules in biological substances comprising: a. selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere, b. preparing a long-lived radioisotope labeled reactive chemical specie, c. administering said chemical specie to said biological host in doses sufficiently low to avoid significant overt damage to the biological system thereof, d. allowing a period of time to elapse sufficient for dissemination and interaction of said chemical specie with said host throughout said biological system of said host, e. isolating a reacted fraction of the biological substance from said host in a manner sufficient to avoid contamination of said substance from extraneous sources, f. converting said fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation, and, g. measuring the radioisotope concentration in said material by means of direct isotopic counting.

  2. Method of measurement in biological systems

    DOEpatents

    Turteltaub, K.W.; Vogel, J.S.; Felton, J.S.; Gledhill, B.L.; Davis, J.C.

    1994-12-27

    Disclosed is a method of quantifying molecules in biological substances comprising: a. selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere, b. preparing a long-lived radioisotope labeled reactive chemical specie, c. administering the chemical specie to the biological host in doses sufficiently low to avoid significant overt damage to the biological system, d. allowing a period of time to elapse sufficient for dissemination and interaction of the chemical specie with the host throughout the biological system of the host, e. isolating a reacted fraction of the biological substance from the host in a manner sufficient to avoid contamination of the substance from extraneous sources, f. converting the fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation, and, g. measuring the radioisotope concentration in the material by means of direct isotopic counting. 5 figures.

  3. Computational systems biology in cancer brain metastasis.

    PubMed

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  4. A Systems Biology Approach to Iron Metabolism

    PubMed Central

    Chifman, J.; Laubenbacher, R.; Torti, S.V.

    2015-01-01

    Iron is critical to the survival of almost all living organisms. However, inappropriately low or high levels of iron are detrimental and contribute to a wide range of diseases. Recent advances in the study of iron metabolism have revealed multiple intricate pathways that are essential to the maintenance of iron homeostasis. Further, iron regulation involves processes at several scales, ranging from the subcellular to the organismal. This complexity makes a systems biology approach crucial, with its enabling technology of computational models based on a mathematical description of regulatory systems. Systems biology may represent a new strategy for understanding imbalances in iron metabolism and their underlying causes. PMID:25480643

  5. Anion transporters and biological systems.

    PubMed

    Gale, Philip A; Pérez-Tomás, Ricardo; Quesada, Roberto

    2013-12-17

    In this Account, we discuss the development of new lipid bilayer anion transporters based on the structure of anionophoric natural products (the prodigiosins) and purely synthetic supramolecular systems. We have studied the interaction of these compounds with human cancer cell lines, and, in general, the most active anion transporter compounds possess the greatest anti-cancer properties. Initially, we describe the anion transport properties of synthetic molecules that are based on the structure of the family of natural products known as the prodiginines. Obatoclax, for example, is a prodiginine derivative with an indole ring that is currently in clinical trials for use as an anti-cancer drug. The anion transport properties of the compounds were correlated with their toxicity toward small cell human lung cancer GLC4 cells. We studied related compounds with enamine moieties, tambjamines, that serve as active transporters. These molecules and others in this series could depolarize acidic compartments within GLC4 cells and trigger apoptosis. In a study of the variation of lipophilicity of a series of these compounds, we observed that, as log P increases, the anion transport efficiency reaches a peak and then decreases. In addition, we discuss the anion transport properties of series of synthetic supramolecular anion receptor species. We synthesized trisureas and thioureas based on the tren backbone, and found that the thiourea compounds effectively transport anions. Fluorination of the pendant phenyl groups in this series of compounds greatly enhances the transport properties. Similar to our earlier results, the most active anion transporters reduced the viability of human cancer cell lines by depolarizing acidic compartments in GLC4 cells and triggering apoptosis. In an attempt to produce simpler transporters that obey Lipinski's Rule of Five, we synthesized simpler systems containing a single urea or thiourea group. Once again the thiourea systems, and in particular

  6. Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

    PubMed

    De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

    2010-03-01

    The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

  7. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

    Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing. Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved. For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research. PMID:21119880

  8. Current advances in systems and integrative biology

    PubMed Central

    Robinson, Scott W.; Fernandes, Marco; Husi, Holger

    2014-01-01

    Systems biology has gained a tremendous amount of interest in the last few years. This is partly due to the realization that traditional approaches focusing only on a few molecules at a time cannot describe the impact of aberrant or modulated molecular environments across a whole system. Furthermore, a hypothesis-driven study aims to prove or disprove its postulations, whereas a hypothesis-free systems approach can yield an unbiased and novel testable hypothesis as an end-result. This latter approach foregoes assumptions which predict how a biological system should react to an altered microenvironment within a cellular context, across a tissue or impacting on distant organs. Additionally, re-use of existing data by systematic data mining and re-stratification, one of the cornerstones of integrative systems biology, is also gaining attention. While tremendous efforts using a systems methodology have already yielded excellent results, it is apparent that a lack of suitable analytic tools and purpose-built databases poses a major bottleneck in applying a systematic workflow. This review addresses the current approaches used in systems analysis and obstacles often encountered in large-scale data analysis and integration which tend to go unnoticed, but have a direct impact on the final outcome of a systems approach. Its wide applicability, ranging from basic research, disease descriptors, pharmacological studies, to personalized medicine, makes this emerging approach well suited to address biological and medical questions where conventional methods are not ideal. PMID:25379142

  9. Systems Biology: The Next Frontier for Bioinformatics

    PubMed Central

    Likić, Vladimir A.; McConville, Malcolm J.; Lithgow, Trevor; Bacic, Antony

    2010-01-01

    Biochemical systems biology augments more traditional disciplines, such as genomics, biochemistry and molecular biology, by championing (i) mathematical and computational modeling; (ii) the application of traditional engineering practices in the analysis of biochemical systems; and in the past decade increasingly (iii) the use of near-comprehensive data sets derived from ‘omics platform technologies, in particular “downstream” technologies relative to genome sequencing, including transcriptomics, proteomics and metabolomics. The future progress in understanding biological principles will increasingly depend on the development of temporal and spatial analytical techniques that will provide high-resolution data for systems analyses. To date, particularly successful were strategies involving (a) quantitative measurements of cellular components at the mRNA, protein and metabolite levels, as well as in vivo metabolic reaction rates, (b) development of mathematical models that integrate biochemical knowledge with the information generated by high-throughput experiments, and (c) applications to microbial organisms. The inevitable role bioinformatics plays in modern systems biology puts mathematical and computational sciences as an equal partner to analytical and experimental biology. Furthermore, mathematical and computational models are expected to become increasingly prevalent representations of our knowledge about specific biochemical systems. PMID:21331364

  10. Biological and Physical Thresholds in Biogeomorphologically Self-organizing Systems.

    NASA Astrophysics Data System (ADS)

    Herman, P.; Bouma, T. J.; Van de Koppel, J.; Borsje, B.; van Belzen, J.; Balke, T.

    2012-12-01

    Many coastal and estuarine landscapes are formed as a consequence of biological-physical interactions. We review examples that we recently studied: coastal vegetations, microphytobenthos-stabilized mudflats, macrofauna-dominated sediments, sand wave formation influenced by animals. In these diverse ecosystems, self-organisation of the coupled landscape results from the existence of positive feedback loops between the physical and biological components. We focus on the question where, in space and/or in time, such feedback systems develop and what determines their persistence and their ability to shape the landscape. We hypothesize that an equilibrium of forces between physical and biological factors is necessary for a feedback loop to develop. This implies a scale match and a commensurate strength of the different factors. There are many examples of systems that are physically too dynamic for the development of biological populations that affect the landscape. We also show an example where biological influence, in the form of strong grazing pressure on microphytobenthos, disrupts a self-organized system on a mudflat. Thus, we define thresholds in parameter space which constrain the development of strongly interacting biogeomorphological systems. The hypothesis of commensurate physical and biological forces as a condition for the development of biogeomorphological systems has important consequences for the establishment and recruitment of such systems. Biological interactions and biological effects on the physical system develop in time with the recruitment and maturation of the biological system. Fully developed systems can therefore be in balance with stronger physical forces than immature, early recruiting phases. This represents a successional threshold that is difficult to overcome. We stress the importance of stochastic variability in physical conditions at a diversity of scales as a prerequisite for phase transitions from physically dominated to

  11. From Artificial Chemistries to Systems Biology

    NASA Astrophysics Data System (ADS)

    Kaleta, Christoph

    Artificial Chemistries abstract from real-world chemistries by reducing them to systems of interacting and reacting molecules. They have been used to study phenomena in a wide array of fields like social and ecological modelling, evolution or chemical computing. Artificial Chemistries are inherently difficult to study and, thus, methods have been proposed to analyze their complexity. This chapter outlines how the concept of chemical organization and software dedicated at their analysis can help to ease this task. The chemical organizations of a reaction network correspond to sets of molecules that can coexist over long periods of (simulation-) time. Thus, they can be used to study the full dynamic behavior a system can exhibit without the need to simulate it in every detail. Due to this appealing property, Chemical Organization Theory has been used in the study of a wide array of systems ranging from Artificial Chemistries to real-world chemistries and biological systems. Especially the analysis of biological systems motivated an integration of the tools dedicated to the study of chemical organizations into an application framework from Systems Biology. The benefit of this integration is that tools from Systems Biology can be used without much effort along with the tools for the computation of chemical organizations and vice versa. Thus, software for the analysis of chemical organizations seamlessly integrates into a framework covering almost any aspect of network design and analysis.

  12. Systems biology solutions for biochemical production challenges.

    PubMed

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

    2017-03-16

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals.

  13. Systems medicine: evolution of systems biology from bench to bedside.

    PubMed

    Wang, Rui-Sheng; Maron, Bradley A; Loscalzo, Joseph

    2015-01-01

    High-throughput experimental techniques for generating genomes, transcriptomes, proteomes, metabolomes, and interactomes have provided unprecedented opportunities to interrogate biological systems and human diseases on a global level. Systems biology integrates the mass of heterogeneous high-throughput data and predictive computational modeling to understand biological functions as system-level properties. Most human diseases are biological states caused by multiple components of perturbed pathways and regulatory networks rather than individual failing components. Systems biology not only facilitates basic biological research but also provides new avenues through which to understand human diseases, identify diagnostic biomarkers, and develop disease treatments. At the same time, systems biology seeks to assist in drug discovery, drug optimization, drug combinations, and drug repositioning by investigating the molecular mechanisms of action of drugs at a system's level. Indeed, systems biology is evolving to systems medicine as a new discipline that aims to offer new approaches for addressing the diagnosis and treatment of major human diseases uniquely, effectively, and with personalized precision.

  14. Systems Biology Approach to Developing “Systems Therapeutics”

    PubMed Central

    2014-01-01

    The standard drug development model uses reductionist approaches to discover small molecules targeting one pathway. Although systems biology analyzes multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. Similar to that in physics where a departure from the old reductionist “Copenhagen View” of quantum physics to a new and predictive systems based, collective model has emerged yielding new breakthroughs such as the LASER, a new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called “systems therapeutics.” PMID:24900858

  15. Standards and Ontologies in Computational Systems Biology

    PubMed Central

    Sauro, Herbert M.; Bergmann, Frank

    2009-01-01

    With the growing importance of computational models in systems biology there has been much interest in recent years to develop standard model interchange languages that permit biologists to easily exchange models between different software tools. In this chapter two chief model exchange standards, SBML and CellML are described. In addition, other related features including visual layout initiatives, ontologies and best practices for model annotation are discussed. Software tools such as developer libraries and basic editing tools are also introduced together with a discussion on the future of modeling languages and visualization tools in systems biology. PMID:18793134

  16. Systems Medicine: Evolution of Systems Biology From Bench To Bedside

    PubMed Central

    Wang, Rui-Sheng; Maron, Bradley A.; Loscalzo, Joseph

    2015-01-01

    High-throughput experimental techniques for generating genomes, transcriptomes, proteomes, metabolomes, and interactomes have provided unprecedented opportunities to interrogate biological systems and human diseases on a global level. Systems biology integrates the mass of heterogeneous high-throughput data and predictive computational modeling to understand biological functions as system-level properties. Most human diseases are biological states caused by multiple components of perturbed pathways and regulatory networks rather than individual failing components. Systems biology not only facilitates basic biological research, but also provides new avenues through which to understand human diseases, identify diagnostic biomarkers, and develop disease treatments. At the same time, systems biology seeks to assist in drug discovery, drug optimization, drug combinations, and drug repositioning by investigating the molecular mechanisms of action of drugs at a system’s level. Indeed, systems biology is evolving to systems medicine as a new discipline that aims to offer new approaches for addressing the diagnosis and treatment of major human diseases uniquely, effectively, and with personalized precision. PMID:25891169

  17. Self Organizing Systems and the Research Implications for Biological Systems

    NASA Astrophysics Data System (ADS)

    Denkins-Taffe, Lauren R.; Alfred, Marcus; Lindesay, James

    2008-03-01

    The knowledge gained from the human genome project, has provided an added opportunity to study the dynamical relationships within biological systems and can lead to an increased knowledge of diseases and subsequent drug discovery. Through computation, methods in which to rebuild these systems are being studied. These methods, which have first been applied to simpler systems: predator-prey, and self sustaining ecosystems can be applied to the study of microscopic biological systems.

  18. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    SciTech Connect

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia

    2010-09-30

    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  19. Meeting report: Signal transduction meets systems biology

    PubMed Central

    2012-01-01

    In the 21st century, systems-wide analyses of biological processes are getting more and more realistic. Especially for the in depth analysis of signal transduction pathways and networks, various approaches of systems biology are now successfully used. The EU FP7 large integrated project SYBILLA (Systems Biology of T-cell Activation in Health and Disease) coordinates such an endeavor. By using a combination of experimental data sets and computational modelling, the consortium strives for gaining a detailed and mechanistic understanding of signal transduction processes that govern T-cell activation. In order to foster the interaction between systems biologists and experimentally working groups, SYBILLA co-organized the 15th meeting “Signal Transduction: Receptors, Mediators and Genes” together with the Signal Transduction Society (STS). Thus, the annual STS conference, held from November 7 to 9, 2011 in Weimar, Germany, provided an interdisciplinary forum for research on signal transduction with a major focus on systems biology addressing signalling events in T-cells. Here we report on a selection of ongoing projects of SYBILLA and how they were discussed at this interdisciplinary conference. PMID:22546078

  20. Systems biology data analysis methodology in pharmacogenomics

    PubMed Central

    Rodin, Andrei S; Gogoshin, Grigoriy; Boerwinkle, Eric

    2012-01-01

    Pharmacogenetics aims to elucidate the genetic factors underlying the individual’s response to pharmacotherapy. Coupled with the recent (and ongoing) progress in high-throughput genotyping, sequencing and other genomic technologies, pharmacogenetics is rapidly transforming into pharmacogenomics, while pursuing the primary goals of identifying and studying the genetic contribution to drug therapy response and adverse effects, and existing drug characterization and new drug discovery. Accomplishment of both of these goals hinges on gaining a better understanding of the underlying biological systems; however, reverse-engineering biological system models from the massive datasets generated by the large-scale genetic epidemiology studies presents a formidable data analysis challenge. In this article, we review the recent progress made in developing such data analysis methodology within the paradigm of systems biology research that broadly aims to gain a ‘holistic’, or ‘mechanistic’ understanding of biological systems by attempting to capture the entirety of interactions between the components (genetic and otherwise) of the system. PMID:21919609

  1. Cholesterol photosensitized oxidation in food and biological systems.

    PubMed

    Cardenia, Vladimiro; Rodriguez-Estrada, Maria Teresa; Boselli, Emanuele; Lercker, Giovanni

    2013-03-01

    Lipid oxidation is one of the main chemical degradations occurring in biological systems and leads to the formation of compounds that are related to aging and various chronic and degenerative diseases. The extent of oxidation will depend on the presence of antioxidants/pro-oxidants, the unsaturation degree of fatty acids, and environmental conditions. Lipid oxidation can also affect other molecules that have double bonds in their chemical structures, such as cholesterol. Cholesterol oxidation products (COPs) have been studied in depth, because of their negative and controversial biological effects. The formation of COPs can be particularly favored in the presence of light and photosensitizers, since they generate excited singlet oxygen that rapidly reacts with the double bond by a non radical mechanism and without any induction period. The present review intends to provide an overall and critical picture of cholesterol photosensitized oxidation in food and biological systems, and its possible impact on human health and well-being.

  2. Agent-based models in translational systems biology

    PubMed Central

    An, Gary; Mi, Qi; Dutta-Moscato, Joyeeta; Vodovotz, Yoram

    2013-01-01

    Effective translational methodologies for knowledge representation are needed in order to make strides against the constellation of diseases that affect the world today. These diseases are defined by their mechanistic complexity, redundancy, and nonlinearity. Translational systems biology aims to harness the power of computational simulation to streamline drug/device design, simulate clinical trials, and eventually to predict the effects of drugs on individuals. The ability of agent-based modeling to encompass multiple scales of biological process as well as spatial considerations, coupled with an intuitive modeling paradigm, suggests that this modeling framework is well suited for translational systems biology. This review describes agent-based modeling and gives examples of its translational applications in the context of acute inflammation and wound healing. PMID:20835989

  3. Systems biology for organotypic cell cultures.

    PubMed

    Grego, Sonia; Dougherty, Edward R; Alexander, Francis J; Auerbach, Scott S; Berridge, Brian R; Bittner, Michael L; Casey, Warren; Cooley, Philip C; Dash, Ajit; Ferguson, Stephen S; Fennell, Timothy R; Hawkins, Brian T; Hickey, Anthony J; Kleensang, Andre; Liebman, Michael N J; Martin, Florian; Maull, Elizabeth A; Paragas, Jason; Qiao, Guilin Gary; Ramaiahgari, Sreenivasa; Sumner, Susan J; Yoon, Miyoung

    2016-11-14

    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.

  4. Systems Biology for Organotypic Cell Cultures

    SciTech Connect

    Grego, Sonia; Dougherty, Edward R.; Alexander, Francis J.; Auerbach, Scott S.; Berridge, Brian R.; Bittner, Michael L.; Casey, Warren; Cooley, Philip C.; Dash, Ajit; Ferguson, Stephen S.; Fennell, Timothy R.; Hawkins, Brian T.; Hickey, Anthony J.; Kleensang, Andre; Liebman, Michael N.; Martin, Florian; Maull, Elizabeth A.; Paragas, Jason; Qiao, Guilin; Ramaiahgari, Sreenivasa; Sumner, Susan J.; Yoon, Miyoung

    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.

  5. Promoting Systems Thinking through Biology Lessons

    ERIC Educational Resources Information Center

    Riess, Werner; Mischo, Christoph

    2010-01-01

    This study's goal was to analyze various teaching approaches within the context of natural science lessons, especially in biology. The main focus of the paper lies on the effectiveness of different teaching methods in promoting systems thinking in the field of Education for Sustainable Development. The following methods were incorporated into the…

  6. Glucose Disappearance in Biological Treatment Systems

    PubMed Central

    Jeris, John S.; Cardenas, Raul R.

    1966-01-01

    Laboratory scale anaerobic and aerobic treatment units were conditioned with a daily slug-feed of glucose. After a period of acclimation and stabilization, glucose disappearance was monitored continuously after the slug feed. A continuous sampling apparatus is described. Mathematical analysis of the data indicate zero-order reactions for both biological treatment systems. PMID:16349685

  7. Modular microfluidic system for biological sample preparation

    DOEpatents

    Rose, Klint A.; Mariella, Jr., Raymond P.; Bailey, Christopher G.; Ness, Kevin Dean

    2015-09-29

    A reconfigurable modular microfluidic system for preparation of a biological sample including a series of reconfigurable modules for automated sample preparation adapted to selectively include a) a microfluidic acoustic focusing filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter.

  8. Studies on Semantic Systems Chemical Biology

    ERIC Educational Resources Information Center

    Chen, Bin

    2012-01-01

    Current "one disease, one target and one drug" drug development paradigm is under question as relatively few drugs have reached the market in the last two decades. Increasingly research focus is being placed on the study of drug action against biological systems as a whole rather than against a single component (called "Systems…

  9. Systems Biology of Glucocorticoids in Muscle Disease

    DTIC Science & Technology

    2010-10-01

    SUBJECT TERMS Duchenne Muscular dystrophy , Glucocorticoids, Systems biology, Drug mechanism 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION...Introduction Duchenne muscular dystrophy (DMD) is the most common and incurable muscular dystrophy of childhood. Muscle regeneration fails with...better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant proposal is led by Dr. Eric Hoffman, and it

  10. Degeneracy and complexity in biological systems

    PubMed Central

    Edelman, Gerald M.; Gally, Joseph A.

    2001-01-01

    Degeneracy, the ability of elements that are structurally different to perform the same function or yield the same output, is a well known characteristic of the genetic code and immune systems. Here, we point out that degeneracy is a ubiquitous biological property and argue that it is a feature of complexity at genetic, cellular, system, and population levels. Furthermore, it is both necessary for, and an inevitable outcome of, natural selection. PMID:11698650

  11. Biological Indicator Systems in Floodplains - a Review

    NASA Astrophysics Data System (ADS)

    Dziock, Frank; Henle, Klaus; Foeckler, Francis; Follner, Klaus; Scholz, Mathias

    2006-08-01

    Based on a literature review, the different approaches to biological indicator systems in floodplains are summarised. Four general categories of bioindication are defined and proposed here: 1. Classification indicators, 2.1 Environmental indicators, 2.2 Biodiversity indicators, 3. Valuation indicators. Furthermore, existing approaches in floodplains are classified according to the four categories. Relevant and widely used approaches in floodplains are explained in more detail. The results of the RIVA project are put into the context of these indication approaches. It is concluded that especially functional assessment approaches using biological traits of the species can be seen as very promising and deserve more attention by conservation biologists and floodplain ecologists.

  12. Student perceptions of their biology teacher's interpersonal teaching behaviors and student achievement and affective learning outcomes

    NASA Astrophysics Data System (ADS)

    Smith, Wade Clay, Jr.

    The primary goals of this dissertation were to determine the relationships between interpersonal teaching behaviors and student achievement and affective learning outcomes. The instrument used to collect student perceptions of teacher interpersonal teaching behaviors was the Questionnaire on Teacher Interactions (QTI). The instrument used to assess student affective learning outcomes was the Biology Student Affective Instrument (BSAI). The interpersonal teaching behavior data were collected using students as the observers. 111 students in an urban influenced, rural high school answered the QTI and BSAI in September 1997 and again in April 1998. At the same time students were pre and post tested using the Biology End of Course Examination (BECE). The QTI has been used primarily in European and Oceanic areas. The instrument was also primarily used in educational stratified environment. This was the first time the BSAI was used to assess student affective learning outcomes. The BECE is a Texas normed cognitive assessment test and it is used by Texas schools districts as the end of course examination in biology. The interpersonal teaching behaviors model was tested to ascertain if predictive power in the USA and in a non-stratified educational environment. Findings indicate that the QTI is an adequate predictor of student achievement in biology. The results were not congruent with the non-USA data and results, this indicates that the QTI is a society/culturally sensitive instrument and the instrument needs to be normed to a particular society/culture before it is used to affect teachers' and students' educational environments.

  13. B chromosomes: from cytogenetics to systems biology.

    PubMed

    Valente, Guilherme T; Nakajima, Rafael T; Fantinatti, Bruno E A; Marques, Diego F; Almeida, Rodrigo O; Simões, Rafael P; Martins, Cesar

    2017-02-01

    Though hundreds to thousands of reports have described the distribution of B chromosomes among diverse eukaryote groups, a comprehensive theory of their biological role has not yet clearly emerged. B chromosomes are classically understood as a sea of repetitive DNA sequences that are poor in genes and are maintained by a parasitic-drive mechanism during cell division. Recent developments in high-throughput DNA/RNA analyses have increased the resolution of B chromosome biology beyond those of classical and molecular cytogenetic methods; B chromosomes contain many transcriptionally active sequences, including genes, and can modulate the activity of autosomal genes. Furthermore, the most recent knowledge obtained from omics analyses, which is associated with a systemic view, has demonstrated that B chromosomes can influence cell biology in a complex way, possibly favoring their own maintenance and perpetuation.

  14. Light manipulation principles in biological photonic systems

    NASA Astrophysics Data System (ADS)

    Starkey, Tim; Vukusic, Pete

    2013-10-01

    The science of light and colour manipulation continues to generate interest across a range of disciplines, from mainstream biology, across multiple physics-based fields, to optical engineering. Furthermore, the study of light production and manipulation is of significant value to a variety of industrial processes and commercial products. Among the several key methods by which colour is produced in the biological world, this review sets out to describe, in some detail, the specifics of the method involving photonics in animal and plant systems; namely, the mechanism commonly referred to as structural colour generation. Not only has this theme been a very rapidly growing area of physics-based interest, but also it is increasingly clear that the biological world is filled with highly evolved structural designs by which light and colour strongly influence behaviours and ecological functions.

  15. KPFM and PFM of Biological Systems

    SciTech Connect

    Rodriguez, Brian; Kalinin, Sergei V

    2011-01-01

    Surface potentials and electrostatic interactions in biological systems are a key element of cellular regulation and interaction. Examples include cardiac and muscular activity, voltage-gated ion channels, protein folding and assembly, and electroactive cells and electrotransduction. The coupling between electrical, mechanical, and chemical signals and responses in cellular systems necessitates the development of tools capable of measuring the distribution of charged species, surface potentials, and mechanical responses to applied electrical stimuli and vice versa, ultimately under physiological conditions. In this chapter, applications of voltage-modulated atomic force microscopy (AFM) methods including Kelvin probe force microscopy (KPFM) and piezoresponse force microscopy (PFM) to biological systems are discussed. KPFM is a force-sensitive non-contact or intermittent-contact mode AFM technique that allows electrostatic interactions and surface potentials to be addressed. Beyond long-range electrostatic interactions, the application of bias can lead to a mechanical response, e.g., due to linear piezoelectric coupling in polar biopolymers or via more complex electrotransduction and redox pathways in other biosystems. The use and development of PFM, based on direct electromechanical detection, to biological systems will also be addressed. The similarities and limitations of measuring surface potentials and electromechanical coupling in solution will be outlined.

  16. Dynamical Systems++ for a Theory of Biological System

    NASA Astrophysics Data System (ADS)

    Kaneko, Kunihiko

    2014-12-01

    Biological dynamical systems can autonomously change their rule governing the dynamics. To deal with the change in their rule, possible approaches to extend dynamical-systems theory are discussed: They include chaotic itinerancy in high-dimensional dynamical systems, discreteness-induced switches of states, and interference between slow and fast modes. Applications of these concepts to cell differentiation, adaptation, and memory are briefly reviewed, while biological evolution is discussed as selection of dynamical systems by dynamical systems. Finally, necessity of mathematical framework to deal with self-referential dynamics for the rule formation is stressed.

  17. A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

    PubMed

    Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

    2016-06-17

    Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

  18. TOPICAL REVIEW: Carbon nanomaterials in biological systems

    NASA Astrophysics Data System (ADS)

    Ke, Pu Chun; Qiao, Rui

    2007-09-01

    This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment.

  19. A systems biology starter kit for arenaviruses.

    PubMed

    Droniou-Bonzom, Magali E; Cannon, Paula M

    2012-12-01

    Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

  20. Image informatics in systems biology applications

    NASA Astrophysics Data System (ADS)

    Wong, Stephen T. C.

    2005-02-01

    Digital optical microscopy, coupled with parallel processing and a large arsenal of labeling techniques, offers tremendous values to localize, identify, and characterize cells and molecules. This generates many image informatics challenges in requiring new algorithms and tools to extract, classify, correlate, and model image features and content from massive amounts of cellular and molecular images acquired. Image informatics aims to fill this gap. Coupling automated microscopy and image analysis with biostatistical and data mining techniques to provide a system biologic approach in studying the cells, the basic unit of life, potentially leads to many exciting applications in life and health sciences. In this presentation, we describe certain new system biology applications enabled by image informatics technology.

  1. The plasminogen activator system: biology and regulation.

    PubMed

    Irigoyen, J P; Muñoz-Cánoves, P; Montero, L; Koziczak, M; Nagamine, Y

    1999-10-01

    The regulation of plasminogen activation involves genes for two plasminogen activators (tissue type and urokinase type), two specific inhibitors (type 1 and type 2), and a membrane-anchored urokinase-type plasminogen-activator-specific receptor. This system plays an important role in various biological processes involving extracellular proteolysis. Recent studies have revealed that the system, through interplay with integrins and the extracellular matrix protein vitronectin, is also involved in the regulation of cell migration and proliferation in a manner independent of proteolytic activity. The genes are expressed in many different cell types and their expression is under the control of diverse extracellular signals. Gene expression reflects the levels of the corresponding mRNA, which should be the net result of synthesis and degradation. Thus, modulation of mRNA stability is an important factor in overall regulation. This review summarizes current understanding of the biology and regulation of genes involved in plasminogen activation at different levels.

  2. Endogenous Biologically Inspired Art of Complex Systems.

    PubMed

    Ji, Haru; Wakefield, Graham

    2016-01-01

    Since 2007, Graham Wakefield and Haru Ji have looked to nature for inspiration as they have created a series of "artificial natures," or interactive visualizations of biologically inspired complex systems that can evoke nature-like aesthetic experiences within mixed-reality art installations. This article describes how they have applied visualization, sonification, and interaction design in their work with artificial ecosystems and organisms using specific examples from their exhibited installations.

  3. Leveraging systems biology approaches in clinical pharmacology

    PubMed Central

    Melas, Ioannis N; Kretsos, Kosmas; Alexopoulos, Leonidas G

    2013-01-01

    Computational modeling has been adopted in all aspects of drug research and development, from the early phases of target identification and drug discovery to the late-stage clinical trials. The different questions addressed during each stage of drug R&D has led to the emergence of different modeling methodologies. In the research phase, systems biology couples experimental data with elaborate computational modeling techniques to capture lifecycle and effector cellular functions (e.g. metabolism, signaling, transcription regulation, protein synthesis and interaction) and integrates them in quantitative models. These models are subsequently used in various ways, i.e. to identify new targets, generate testable hypotheses, gain insights on the drug's mode of action (MOA), translate preclinical findings, and assess the potential of clinical drug efficacy and toxicity. In the development phase, pharmacokinetic/pharmacodynamic (PK/PD) modeling is the established way to determine safe and efficacious doses for testing at increasingly larger, and more pertinent to the target indication, cohorts of subjects. First, the relationship between drug input and its concentration in plasma is established. Second, the relationship between this concentration and desired or undesired PD responses is ascertained. Recognizing that the interface of systems biology with PK/PD will facilitate drug development, systems pharmacology came into existence, combining methods from PK/PD modeling and systems engineering explicitly to account for the implicated mechanisms of the target system in the study of drug–target interactions. Herein, a number of popular system biology methodologies are discussed, which could be leveraged within a systems pharmacology framework to address major issues in drug development. PMID:23983165

  4. Systems biology of cancer biomarker detection.

    PubMed

    Mitra, Sanga; Das, Smarajit; Chakrabarti, Jayprokas

    2013-01-01

    Cancer systems-biology is an ever-growing area of research due to explosion of data; how to mine these data and extract useful information is the problem. To have an insight on carcinogenesis one need to systematically mine several resources, such as databases, microarray and next-generation sequences. This review encompasses management and analysis of cancer data, databases construction and data deposition, whole transcriptome and genome comparison, analysing results from high throughput experiments to uncover cellular pathways and molecular interactions, and the design of effective algorithms to identify potential biomarkers. Recent technical advances such as ChIP-on-chip, ChIP-seq and RNA-seq can be applied to get epigenetic information transformed into a high-throughput endeavour to which systems biology and bioinformatics are making significant inroads. The data from ENCODE and GENCODE projects available through UCSC genome browser can be considered as benchmark for comparison and meta-analysis. A pipeline for integrating next generation sequencing data, microarray data, and putting them together with the existing database is discussed. The understanding of cancer genomics is changing the way we approach cancer diagnosis and treatment. To give a better understanding of utilizing available resources' we have chosen oral cancer to show how and what kind of analysis can be done. This review is a computational genomic primer that provides a bird's eye view of computational and bioinformatics' tools currently available to perform integrated genomic and system biology analyses of several carcinoma.

  5. The Emergence of Modularity in Biological Systems

    PubMed Central

    Lorenz, Dirk M.; Jeng, Alice; Deem, Michael W.

    2015-01-01

    In this review, we discuss modularity and hierarchy in biological systems. We review examples from protein structure, genetics, and biological networks of modular partitioning of the geometry of biological space. We review theories to explain modular organization of biology, with a focus on explaining how biology may spontaneously organize to a structured form. That is, we seek to explain how biology nucleated from among the many possibilities in chemistry. The emergence of modular organization of biological structure will be described as a symmetry-breaking phase transition, with modularity as the order parameter. Experimental support for this description will be reviewed. Examples will be presented from pathogen structure, metabolic networks, gene networks, and protein-protein interaction networks. Additional examples will be presented from ecological food networks, developmental pathways, physiology, and social networks. There once were two watchmakers, named Hora and Tempus, who manufactured very fine watches. Both of them were highly regarded, and the phones in their workshops rang frequently — new customers were constantly calling them. However, Hora prospered, while Tempus became poorer and poorer and finally lost his shop. What was the reason? The watches the men made consisted of about 1,000 parts each. Tempus had so constructed his that if he had one partly assembled and had to put it down — to answer the phone say— it immediately fell to pieces and had to be reassembled from the elements. The better the customers liked his watches, the more they phoned him, the more difficult it became for him to find enough uninterrupted time to finish a watch. The watches that Hora made were no less complex than those of Tempus. But he had designed them so that he could put together subassemblies of about ten elements each. Ten of these subassemblies, again, could be put together into a larger subassembly; and a system of ten of the latter sub

  6. Method for photo-altering a biological system to improve biological effect

    DOEpatents

    Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

    2000-08-01

    Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

  7. Complex biological and bio-inspired systems

    SciTech Connect

    Ecke, Robert E

    2009-01-01

    The understanding and characterization ofthe fundamental processes of the function of biological systems underpins many of the important challenges facing American society, from the pathology of infectious disease and the efficacy ofvaccines, to the development of materials that mimic biological functionality and deliver exceptional and novel structural and dynamic properties. These problems are fundamentally complex, involving many interacting components and poorly understood bio-chemical kinetics. We use the basic science of statistical physics, kinetic theory, cellular bio-chemistry, soft-matter physics, and information science to develop cell level models and explore the use ofbiomimetic materials. This project seeks to determine how cell level processes, such as response to mechanical stresses, chemical constituents and related gradients, and other cell signaling mechanisms, integrate and combine to create a functioning organism. The research focuses on the basic physical processes that take place at different levels ofthe biological organism: the basic role of molecular and chemical interactions are investigated, the dynamics of the DNA-molecule and its phylogenetic role are examined and the regulatory networks of complex biochemical processes are modeled. These efforts may lead to early warning algorithms ofpathogen outbreaks, new bio-sensors to detect hazards from pathomic viruses to chemical contaminants. Other potential applications include the development of efficient bio-fuel alternative-energy processes and the exploration ofnovel materials for energy usages. Finally, we use the notion of 'coarse-graining,' which is a method for averaging over less important degrees of freedom to develop computational models to predict cell function and systems-level response to disease, chemical stress, or biological pathomic agents. This project supports Energy Security, Threat Reduction, and the missions of the DOE Office of Science through its efforts to accurately

  8. [Systems theory in medicine and biology].

    PubMed

    Feigl, W; Bonet, E M

    1989-03-15

    We try to determinate, that systems theory has to be introduced into modern medicine. The biological roots as well as the cybernetic ones are outlined. Among various concepts about systems theory the evaluation by Riedl seems to be the most efficient to explain medical procedures. His basic informations refer to von Bertalanffy, the additional introduction of a 4-cause-principle, Aristoteles, permits the explanation of complex relations. The examples of tumor and inflammation are used to demonstrate the basic idea of the formal cause as well as the final cause. The latter should also become an important fact in the solution of other medical problems.

  9. Systems biology for enhanced plant nitrogen nutrition.

    PubMed

    Gutiérrez, Rodrigo A

    2012-06-29

    Nitrogen (N)-based fertilizers increase agricultural productivity but have detrimental effects on the environment and human health. Research is generating improved understanding of the signaling components plants use to sense N and regulate metabolism, physiology, and growth and development. However, we still need to integrate these regulatory factors into signal transduction pathways and connect them to downstream response pathways. Systems biology approaches facilitate identification of new components and N-regulatory networks linked to other plant processes. A holistic view of plant N nutrition should open avenues to translate this knowledge into effective strategies to improve N-use efficiency and enhance crop production systems for more sustainable agricultural practices.

  10. Systems Biology of the Vervet Monkey

    PubMed Central

    Jasinska, Anna J.; Schmitt, Christopher A.; Service, Susan K.; Cantor, Rita M.; Dewar, Ken; Jentsch, James D.; Kaplan, Jay R.; Turner, Trudy R.; Warren, Wesley C.; Weinstock, George M.; Woods, Roger P.; Freimer, Nelson B.

    2013-01-01

    Nonhuman primates (NHP) provide crucial biomedical model systems intermediate between rodents and humans. The vervet monkey (also called the African green monkey) is a widely used NHP model that has unique value for genetic and genomic investigations of traits relevant to human diseases. This article describes the phylogeny and population history of the vervet monkey and summarizes the use of both captive and wild vervet monkeys in biomedical research. It also discusses the effort of an international collaboration to develop the vervet monkey as the most comprehensively phenotypically and genomically characterized NHP, a process that will enable the scientific community to employ this model for systems biology investigations. PMID:24174437

  11. Environmental Control of Root System Biology.

    PubMed

    Rellán-Álvarez, Rubén; Lobet, Guillaume; Dinneny, José R

    2016-04-29

    The plant root system traverses one of the most complex environments on earth. Understanding how roots support plant life on land requires knowing how soil properties affect the availability of nutrients and water and how roots manipulate the soil environment to optimize acquisition of these resources. Imaging of roots in soil allows the integrated analysis and modeling of environmental interactions occurring at micro- to macroscales. Advances in phenotyping of root systems is driving innovation in cross-platform-compatible methods for data analysis. Root systems acclimate to the environment through architectural changes that act at the root-type level as well as through tissue-specific changes that affect the metabolic needs of the root and the efficiency of nutrient uptake. A molecular understanding of the signaling mechanisms that guide local and systemic signaling is providing insight into the regulatory logic of environmental responses and has identified points where crosstalk between pathways occurs.

  12. Plant MetGenMAP: an integrative analysis system for plant systems biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have developed a web-based system, Plant MetGenMAP, which can identify significantly altered biochemical pathways and highly affected biological processes, predict functional roles of pathway genes, and potential pathway-related regulatory motifs from transcript and metabolite profile datasets. P...

  13. Systems biology in neuroscience: bridging genes to cognition.

    PubMed

    Grant, Seth G N

    2003-10-01

    Systems biology is a new branch of biology aimed at understanding biological complexity. Genomic and proteomic methods integrated with cellular and organismal analyses allow modelling of physiological processes. Progress in understanding synapse composition and new experimental and bioinformatics methods indicate the synapse is an excellent starting point for global systems biology of the brain. A neuroscience systems biology programme, organized as a consortium, is proposed.

  14. Infrared Microtransmission And Microreflectance Of Biological Systems

    NASA Astrophysics Data System (ADS)

    Hill, Steve L.; Krishnan, K.; Powell, Jay R.

    1989-12-01

    The infrared microsampling technique has been successfully applied to a variety of biological systems. A microtomed tissue section may be prepared to permit both visual and infrared discrimination. Infrared structural information may be obtained for a single cell, and computer-enhanced images of tissue specimens may be calculated from spectral map data sets. An analysis of a tissue section anomaly may gg suest eitherprotein compositional differences or a localized concentration of foreign matterp. Opaque biological materials such as teeth, gallstones, and kidney stones may be analyzed by microreflectance spectroscop. Absorption anomalies due to specular dispersion are corrected with the Kraymers-Kronig transformation. Corrected microreflectance spectra may contribute to compositional analysis and correlate diseased-related spectral differences to visual specimen anomalies.

  15. Engineering biological systems toward a sustainable bioeconomy.

    PubMed

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

  16. Fractal Scaling of Particle Size Distribution and Relationships with Topsoil Properties Affected by Biological Soil Crusts

    PubMed Central

    Gao, Guang-Lei; Ding, Guo-Dong; Wu, Bin; Zhang, Yu-Qing; Qin, Shu-Gao; Zhao, Yuan-Yuan; Bao, Yan-Feng; Liu, Yun-Dong; Wan, Li; Deng, Ji-Feng

    2014-01-01

    Background Biological soil crusts are common components of desert ecosystem; they cover ground surface and interact with topsoil that contribute to desertification control and degraded land restoration in arid and semiarid regions. Methodology/Principal Findings To distinguish the changes in topsoil affected by biological soil crusts, we compared topsoil properties across three types of successional biological soil crusts (algae, lichens, and mosses crust), as well as the referenced sandland in the Mu Us Desert, Northern China. Relationships between fractal dimensions of soil particle size distribution and selected soil properties were discussed as well. The results indicated that biological soil crusts had significant positive effects on soil physical structure (P<0.05); and soil organic carbon and nutrients showed an upward trend across the successional stages of biological soil crusts. Fractal dimensions ranged from 2.1477 to 2.3032, and significantly linear correlated with selected soil properties (R2 = 0.494∼0.955, P<0.01). Conclusions/Significance Biological soil crusts cause an important increase in soil fertility, and are beneficial to sand fixation, although the process is rather slow. Fractal dimension proves to be a sensitive and useful index for quantifying changes in soil properties that additionally implies desertification. This study will be essential to provide a firm basis for future policy-making on optimal solutions regarding desertification control and assessment, as well as degraded ecosystem restoration in arid and semiarid regions. PMID:24516668

  17. Adaptable data management for systems biology investigations

    PubMed Central

    Boyle, John; Rovira, Hector; Cavnor, Chris; Burdick, David; Killcoyne, Sarah; Shmulevich, Ilya

    2009-01-01

    Background Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage. Results The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry). We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents. Conclusion Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community. PMID:19265554

  18. The systems biology simulation core algorithm

    PubMed Central

    2013-01-01

    Background With the increasing availability of high dimensional time course data for metabolites, genes, and fluxes, the mathematical description of dynamical systems has become an essential aspect of research in systems biology. Models are often encoded in formats such as SBML, whose structure is very complex and difficult to evaluate due to many special cases. Results This article describes an efficient algorithm to solve SBML models that are interpreted in terms of ordinary differential equations. We begin our consideration with a formal representation of the mathematical form of the models and explain all parts of the algorithm in detail, including several preprocessing steps. We provide a flexible reference implementation as part of the Systems Biology Simulation Core Library, a community-driven project providing a large collection of numerical solvers and a sophisticated interface hierarchy for the definition of custom differential equation systems. To demonstrate the capabilities of the new algorithm, it has been tested with the entire SBML Test Suite and all models of BioModels Database. Conclusions The formal description of the mathematics behind the SBML format facilitates the implementation of the algorithm within specifically tailored programs. The reference implementation can be used as a simulation backend for Java™-based programs. Source code, binaries, and documentation can be freely obtained under the terms of the LGPL version 3 from http://simulation-core.sourceforge.net. Feature requests, bug reports, contributions, or any further discussion can be directed to the mailing list simulation-core-development@lists.sourceforge.net. PMID:23826941

  19. A Free Energy Principle for Biological Systems

    PubMed Central

    Karl, Friston

    2012-01-01

    This paper describes a free energy principle that tries to explain the ability of biological systems to resist a natural tendency to disorder. It appeals to circular causality of the sort found in synergetic formulations of self-organization (e.g., the slaving principle) and models of coupled dynamical systems, using nonlinear Fokker Planck equations. Here, circular causality is induced by separating the states of a random dynamical system into external and internal states, where external states are subject to random fluctuations and internal states are not. This reduces the problem to finding some (deterministic) dynamics of the internal states that ensure the system visits a limited number of external states; in other words, the measure of its (random) attracting set, or the Shannon entropy of the external states is small. We motivate a solution using a principle of least action based on variational free energy (from statistical physics) and establish the conditions under which it is formally equivalent to the information bottleneck method. This approach has proved useful in understanding the functional architecture of the brain. The generality of variational free energy minimisation and corresponding information theoretic formulations may speak to interesting applications beyond the neurosciences; e.g., in molecular or evolutionary biology. PMID:23204829

  20. Systems Biology: Impressions from a Newcomer Graduate Student in 2016

    ERIC Educational Resources Information Center

    Simpson, Melanie Rae

    2016-01-01

    As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in…

  1. The Feasibility of Systems Thinking in Biology Education

    ERIC Educational Resources Information Center

    Boersma, Kerst; Waarlo, Arend Jan; Klaassen, Kees

    2011-01-01

    Systems thinking in biology education is an up and coming research topic, as yet with contrasting feasibility claims. In biology education systems thinking can be understood as thinking backward and forward between concrete biological objects and processes and systems models representing systems theoretical characteristics. Some studies claim that…

  2. Systems Biology Toolbox for MATLAB: a computational platform for research in systems biology.

    PubMed

    Schmidt, Henning; Jirstrand, Mats

    2006-02-15

    We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis.

  3. 6th Institute for Systems Biology International Symposium: Systems Biology and the Environment

    SciTech Connect

    Galitski, Timothy P.

    2007-04-23

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology is an annual two-day event gathering the most influential researchers transforming biology into an integrative discipline investigating complex systems. In recognition of the fundamental similarity between the scientific problems addressed in environmental science and systems biology studies at the molecular, cellular, and organismal levels, the 2007 Symposium featured global leaders in “Systems Biology and the Environment.” The objective of the 2007 “Systems Biology and the Environment” International Symposium was to stimulate interdisciplinary thinking and research that spans systems biology and environmental science. This Symposium was well aligned with the DOE’s Genomics: GTL program efforts to achieve scientific objectives for each of the three DOE missions: Develop biofuels as a major secure energy source for this century; Develop biological solutions for intractable environmental problems; Understand biosystems’ climate impacts and assess sequestration strategies. Our scientific program highlighted world-class research exemplifying these priorities. The Symposium featured 45 minute lectures from 12 researchers including: Penny/Sallie Chisholm of MIT gave the keynote address “Tiny Cells, Global Impact: What Prochlorococcus Can Teach Us About Systems Biology”, plus Jim Fredrickson of PNNL, Nitin Baliga of ISB, Steve Briggs of UCSD, David Cox of Perlegen Sciences, Antoine Danchin of Institut Pasteur, John Delaney of the U of Washington, John Groopman of Johns Hopkins, Ben Kerr of the U of Washington, Steve Koonin of BP, Elliott Meyerowitz of Caltech, and Ed Rubin of LBNL. The 2007 Symposium promoted DOE’s three mission areas among scientists from multiple disciplines representing academia, non-profit research institutions, and the private sector. As in all previous Symposia, we had

  4. External magnetic fields affect the biological impacts of superparamagnetic iron nanoparticles.

    PubMed

    Shanehsazzadeh, Saeed; Lahooti, Afsaneh; Hajipour, Mohammad Javad; Ghavami, Mahdi; Azhdarzadeh, Morteza

    2015-12-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as one of the promising nanomaterials for applications in various field of nanomedicine such as targeted imaging/drug delivery, tissue engineering, hyperthermia, and gene therapy. Besides their suitable biocompatibility, SPIONs' unique magnetic properties make them an outstanding candidate for theranostic nanomedicine. Very recent progress in the field revealed that the presence of external magnetic fields may cause considerable amount of SPIONs' agglomeration in their colloidal suspension. As variation of physicochemical properties of colloidal nanoparticles has strong effect on their biological outcomes, one can expect that the SPIONs' agglomeration in the presence of external magnetic fields could change their well-recognized biological impacts. In this case, here, we probed the cellular uptake and toxicity of the SPIONs before and after exposure to external magnetic fields. We found that the external magnetic fields can affect the biological outcome of magnetic nanoparticles.

  5. Biological Diversity in the Patent System

    PubMed Central

    Oldham, Paul; Hall, Stephen; Forero, Oscar

    2013-01-01

    Biological diversity in the patent system is an enduring focus of controversy but empirical analysis of the presence of biodiversity in the patent system has been limited. To address this problem we text mined 11 million patent documents for 6 million Latin species names from the Global Names Index (GNI) established by the Global Biodiversity Information Facility (GBIF) and Encyclopedia of Life (EOL). We identified 76,274 full Latin species names from 23,882 genera in 767,955 patent documents. 25,595 species appeared in the claims section of 136,880 patent documents. This reveals that human innovative activity involving biodiversity in the patent system focuses on approximately 4% of taxonomically described species and between 0.8–1% of predicted global species. In this article we identify the major features of the patent landscape for biological diversity by focusing on key areas including pharmaceuticals, neglected diseases, traditional medicines, genetic engineering, foods, biocides, marine genetic resources and Antarctica. We conclude that the narrow focus of human innovative activity and ownership of genetic resources is unlikely to be in the long term interest of humanity. We argue that a broader spectrum of biodiversity needs to be opened up to research and development based on the principles of equitable benefit-sharing, respect for the objectives of the Convention on Biological Diversity, human rights and ethics. Finally, we argue that alternative models of innovation, such as open source and commons models, are required to open up biodiversity for research that addresses actual and neglected areas of human need. The research aims to inform the implementation of the 2010 Nagoya Protocol on Access to Genetic Resources and the Equitable Sharing of Benefits Arising from their Utilization and international debates directed to the governance of genetic resources. Our research also aims to inform debates under the Intergovernmental Committee on Intellectual

  6. Biological systems in high magnetic field

    NASA Astrophysics Data System (ADS)

    Yamagishi, A.

    1990-12-01

    Diamagnetic orientation of biological systems have been investigated theoretically and experimentally. Fibrinogen, one of blood proteins, were polymerized in static high magnetic fields up to 8 T. Clotted gels composed of oriented fibrin fibers were obtained even in a field as low as 1 T. Red blood cells (RBC) show full orientation with their plane parallel to the applied field of 4 T. It is confirmed experimentally that the magnetic orientation of RBC is caused by diamagnetic anisotropy. Full orientation is also obtained with blood platelet in a field of 3 T.

  7. Systems Biology Approaches for Identifying Adverse Drug Reactions and Elucidating Their Underlying Biological Mechanisms

    PubMed Central

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph; Moskovitch, Robert; Tatonetti, Nicholas P.

    2015-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and post-market surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, while post-market surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID:26559926

  8. Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

    PubMed

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

    2016-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work.

  9. AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

    SciTech Connect

    JOHNSON AR; CAUDILL JG; GIDDINGS RF; RODRIGUEZ JM; ROOS RC; WILDE JW

    2010-02-11

    In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimated spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

  10. Biological soil crusts emit large amounts of NO and HONO affecting the nitrogen cycle in drylands

    NASA Astrophysics Data System (ADS)

    Tamm, Alexandra; Wu, Dianming; Ruckteschler, Nina; Rodríguez-Caballero, Emilio; Steinkamp, Jörg; Meusel, Hannah; Elbert, Wolfgang; Behrendt, Thomas; Sörgel, Matthias; Cheng, Yafang; Crutzen, Paul J.; Su, Hang; Pöschl, Ulrich; Weber, Bettina

    2016-04-01

    Dryland systems currently cover ˜40% of the world's land surface and are still expanding as a consequence of human impact and global change. In contrast to that, information on their role in global biochemical processes is limited, probably induced by the presumption that their sparse vegetation cover plays a negligible role in global balances. However, spaces between the sparse shrubs are not bare, but soils are mostly covered by biological soil crusts (biocrusts). These biocrust communities belong to the oldest life forms, resulting from an assembly between soil particles and cyanobacteria, lichens, bryophytes, and algae plus heterotrophic organisms in varying proportions. Depending on the dominating organism group, cyanobacteria-, lichen-, and bryophyte-dominated biocrusts are distinguished. Besides their ability to restrict soil erosion they fix atmospheric carbon and nitrogen, and by doing this they serve as a nutrient source in strongly depleted dryland ecosystems. In this study we show that a fraction of the nitrogen fixed by biocrusts is metabolized and subsequently returned to the atmosphere in the form of nitric oxide (NO) and nitrous acid (HONO). These gases affect the radical formation and oxidizing capacity within the troposphere, thus being of particular interest to atmospheric chemistry. Laboratory measurements using dynamic chamber systems showed that dark cyanobacteria-dominated crusts emitted the largest amounts of NO and HONO, being ˜20 times higher than trace gas fluxes of nearby bare soil. We showed that these nitrogen emissions have a biogenic origin, as emissions of formerly strongly emitting samples almost completely ceased after sterilization. By combining laboratory, field, and satellite measurement data we made a best estimate of global annual emissions amounting to ˜1.1 Tg of NO-N and ˜0.6 Tg of HONO-N from biocrusts. This sum of 1.7 Tg of reactive nitrogen emissions equals ˜20% of the soil release under natural vegetation according

  11. Parallel stochastic systems biology in the cloud.

    PubMed

    Aldinucci, Marco; Torquati, Massimo; Spampinato, Concetto; Drocco, Maurizio; Misale, Claudia; Calcagno, Cristina; Coppo, Mario

    2014-09-01

    The stochastic modelling of biological systems, coupled with Monte Carlo simulation of models, is an increasingly popular technique in bioinformatics. The simulation-analysis workflow may result computationally expensive reducing the interactivity required in the model tuning. In this work, we advocate the high-level software design as a vehicle for building efficient and portable parallel simulators for the cloud. In particular, the Calculus of Wrapped Components (CWC) simulator for systems biology, which is designed according to the FastFlow pattern-based approach, is presented and discussed. Thanks to the FastFlow framework, the CWC simulator is designed as a high-level workflow that can simulate CWC models, merge simulation results and statistically analyse them in a single parallel workflow in the cloud. To improve interactivity, successive phases are pipelined in such a way that the workflow begins to output a stream of analysis results immediately after simulation is started. Performance and effectiveness of the CWC simulator are validated on the Amazon Elastic Compute Cloud.

  12. Structural Identifiability of Dynamic Systems Biology Models

    PubMed Central

    Villaverde, Alejandro F.

    2016-01-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas. PMID:27792726

  13. Avian biological clock - Immune system relationship.

    PubMed

    Markowska, Magdalena; Majewski, Paweł M; Skwarło-Sońta, Krystyna

    2017-01-01

    Biological rhythms in birds are driven by the master clock, which includes the suprachiasmatic nucleus, the pineal gland and the retina. Light/dark cycles are the cues that synchronize the rhythmic changes in physiological processes, including immunity. This review summarizes our investigations on the bidirectional relationships between the chicken pineal gland and the immune system. We demonstrated that, in the chicken, the main pineal hormone, melatonin, regulates innate immunity, maintains the rhythmicity of immune reactions and is involved in the seasonal changes in immunity. Using thioglycollate-induced peritonitis as a model, we showed that the activated immune system regulates the pineal gland by inhibition of melatonin production at the level of the key enzyme in its biosynthetic pathway, arylalkylamine-N-acetyltransferase (AANAT). Interleukin 6 and interleukin 18 seem to be the immune mediators influencing the pineal gland, directly inhibiting Aanat gene transcription and modulating expression of the clock genes Bmal1 and Per3, which in turn regulate Aanat.

  14. Systems Biology and the Future of Medicine

    PubMed Central

    Barabasi, Albert-Laszlo

    2011-01-01

    Contemporary views of human disease are based on simple correlation between clinical syndromes and pathological analysis dating from the late 19th century. While this approach to disease diagnosis, prognosis, and treatment has served the medical establishment and society well for many years, it has serious shortcomings for the modern era of the genomic medicine that stem from its reliance on reductionist principles of experimentation and analysis. Quantitative, holistic systems biology applied to human disease offers a unique approach for diagnosing established disease, defining disease predilection, and developing individualized (personalized) treatment strategies that can take full advantage of modern molecular pathobiology and the comprehensive data sets that are rapidly becoming available for populations and individuals. In this way, systems pathobiology offers the promise of redefining our approach to disease and the field of medicine. PMID:21928407

  15. Immunogenomics and systems biology of vaccines

    PubMed Central

    Buonaguro, Luigi; Pulendran, Bali

    2011-01-01

    Summary Vaccines represent a potent tool to prevent or contain infectious diseases with high morbidity or mortality. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the effective elicitation of protective immune responses by vaccines. Recent research suggests that this represents the cooperative action of the innate and adaptive immune systems. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules, whose list is constantly updated to fill the several empty spaces of this puzzle. The recent development of new technologies and computational tools permits the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review the role of the innate immunity in the host response to vaccine antigens and the potential of systems biology in providing relevant and novel insights in the mechanisms of action of vaccines to improve their design and effectiveness. PMID:21198673

  16. Biological Systems for Hydrogen Photoproduction (Presentation)

    SciTech Connect

    Ghirardi, M. L.

    2012-05-01

    This presentation summarizes NREL biological systems for hydrogen photoproduction work for the DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting, May 14-18, 2012. General goal is develop photobiological systems for large-scale, low cost and efficient H{sub 2} production from water (barriers AH, AI and AJ). Specific tasks are: (1) Address the O{sub 2} sensitivity of hydrogenases that prevent continuity of H{sub 2} photoproduction under aerobic, high solar-to-hydrogen (STH) light conversion efficiency conditions; and (2) Utilize a limited STH H{sub 2}-producing method (sulfur deprivation) as a platform to address or test other factors limiting commercial algal H{sub 2} photoproduction, including low rates due to biochemical and engineering mechanisms.

  17. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

    PubMed

    Louridas, George E; Lourida, Katerina G

    2017-02-21

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  18. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    PubMed Central

    Louridas, George E.; Lourida, Katerina G.

    2017-01-01

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy. PMID:28230815

  19. Molecular profiles to biology and pathways: a systems biology approach.

    PubMed

    Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

    2016-06-16

    Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

  20. Electromagnetic field interactions with biological systems

    SciTech Connect

    Frey, A.H. )

    1993-02-01

    This is a report on Symposia organized by the International Society for Bioelectricity and presented at the 1992 FASEB Meeting. The presentations summarized here were intended to provide a sampling of new and fruitful lines of research. The theme topics for the Symposia were cancer, neural function, cell signaling, pineal gland function, and immune system interactions. Living organisms are complex electrochemical systems that evolved over billions of years in a world with a relatively simple weak magnetic field and with few electromagnetic energy emitters. As is characteristic of living organisms, they interacted with and adapted to this environment of electric and magnetic fields. In recent years there has been a massive introduction of equipment that emits electromagnetic fields in an enormous range of new frequencies, modulations, and intensities. As living organisms have only recently found themselves immersed in this new and virtually ubiquitous environment, they have not had the opportunity to adapt to it. This gives biologists the opportunity to use these electromagnetic fields as probes to study the functioning of living systems. This is a significant opportunity, as new approaches to studying living systems so often provide the means to make great leaps in science. In recent years, a diversity of biologists have carried out experiments using electromagnetic fields to study the function of living cells and systems. This approach is now becoming quite fruitful and is yielding data that are advancing our knowledge in diverse areas of biology. 25 refs., 6 figs., 3 tabs.

  1. Kinetic approach for describing biological systems

    NASA Astrophysics Data System (ADS)

    Aristov, V. V.; Ilyin, O. V.

    2016-11-01

    We attempt to consider a biological structure as an open nonequilibrium system the properties of which can be described on the basis of kinetic approach with the help of appropriate kinetic equations. This approach allows us to evaluate in principle scales of sizes and to connect these values to the inner characteristics of the processes of kinetic interaction and advection. One can compare the results with some empirical data concerning these characteristics for bio-systems, in particular mammals, and also for some parts of the systems, say sizes of green leaves. A sense of the nonequilibrium entropy as a measure of complexity of bio-organisms is discussed. Besides the estimations of bio-systems on a global scale, possible methods to describe restricted regions (associated e.g. with living cells) as nonequilibrium open structure with specific boundaries are also discussed. A new boundary 1D problem is formulated and solved for kinetic equations with the membrane-like boundaries conditions. Non-classical transport properties in the system are found.

  2. Promoting Systems Thinking through Biology Lessons

    NASA Astrophysics Data System (ADS)

    Riess, Werner; Mischo, Christoph

    2010-04-01

    This study's goal was to analyze various teaching approaches within the context of natural science lessons, especially in biology. The main focus of the paper lies on the effectiveness of different teaching methods in promoting systems thinking in the field of Education for Sustainable Development. The following methods were incorporated into the study: special lessons designed to promote systems thinking, a computer-simulated scenario on the topic "ecosystem forest," and a combination of both special lessons and the computer simulation. These groups were then compared to a control group. A questionnaire was used to assess systems thinking skills of 424 sixth-grade students of secondary schools in Germany. The assessment differentiated between a conceptual understanding (measured as achievement score) and a reflexive justification (measured as justification score) of systems thinking. The following control variables were used: logical thinking, grades in school, memory span, and motivational goal orientation. Based on the pretest-posttest control group design, only those students who received both special instruction and worked with the computer simulation showed a significant increase in their achievement scores. The justification score increased in the computer simulation condition as well as in the combination of computer simulation and lesson condition. The possibilities and limits of promoting various forms of systems thinking by using realistic computer simulations are discussed.

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

    PubMed

    Gomez-Ramirez, Jaime; Sanz, Ricardo

    2013-09-01

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

  4. Systems biology: impressions from a newcomer graduate student in 2016.

    PubMed

    Simpson, Melanie Rae

    2016-12-01

    As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in 2016?" are somewhat more elusive. This seems to be due largely to the diversity of disciplines involved and the varying emphasis placed on the computational modeling and experimental aspects of systems biology. As such, the education of systems biology would benefit from multidisciplinary collaboration with both instructors and students from a range of disciplines within the same course. This essay is the personal reflection of a graduate student trying to get an introductory overview of the field of systems biology and some thoughts about effective education of systems biology.

  5. Dynamical Systems and Control Theory Inspired by Molecular Biology

    DTIC Science & Technology

    2014-10-02

    AFRL-OSR-VA-TR-2014-0282 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY Eduardo Sontag RUTGERS THE STATE UNIVERSITY OF NEW JERSEY...Standard Form 298 (Re . 8-98) v Prescribed by ANSI Std. Z39.18 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY AFOSR FA9550-11-1-0247...is to develop new concepts, theory, and algorithms for control and signal processing using ideas inspired by molecular systems biology. Cell biology

  6. Noise effects in two different biological systems

    NASA Astrophysics Data System (ADS)

    Spagnolo, B.; Spezia, S.; Curcio, L.; Pizzolato, N.; Fiasconaro, A.; Valenti, D.; Lo Bue, P.; Peri, E.; Colazza, S.

    2009-05-01

    We investigate the role of the colored noise in two biological systems: (i) adults of Nezara viridula (L.) (Heteroptera: Pentatomidae), and (ii) polymer translocation. In the first system we analyze, by directionality tests, the response of N. viridula individuals to subthreshold signals plus noise in their mating behaviour. The percentage of insects that react to the subthreshold signal shows a nonmonotonic behaviour, characterized by the presence of a maximum, as a function of the noise intensity. This is the signature of the non-dynamical stochastic resonance phenomenon. By using a “soft” threshold model we find that the maximum of the input-output cross correlation occurs in the same range of noise intensity values for which the behavioural activation of the insects has a maximum. Moreover this maximum value is lowered and shifted towards higher noise intensities, compared to the case of white noise. In the second biological system the noise driven translocation of short polymers in crowded solutions is analyzed. An improved version of the Rouse model for a flexible polymer is adopted to mimic the molecular dynamics by taking into account both the interactions between adjacent monomers and the effects of a Lennard-Jones potential between all beads. The polymer dynamics is simulated in a two-dimensional domain by numerically solving the Langevin equations of motion in the presence of thermal fluctuations and a colored noise source. At low temperatures or for strong colored noise intensities the translocation process of the polymer chain is delayed. At low noise intensity, as the polymer length increases, we find a nonmonotonic behaviour for the mean first translocation time of the polymer centre of inertia. We show how colored noise influences the motion of short polymers, by inducing two different regimes of translocation in the dynamics of molecule transport.

  7. Notions of similarity for systems biology models.

    PubMed

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

    2016-10-14

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

  8. A systems biology approach to learning autophagy.

    PubMed

    Klionsky, Daniel J; Kumar, Anuj

    2006-01-01

    With its relevance to our understanding of eukaryotic cell function in the normal and disease state, autophagy is an important topic in modern cell biology; yet, few textbooks discuss autophagy beyond a two- or three-sentence summary. Here, we report an undergraduate/graduate class lesson for the in-depth presentation of autophagy using an active learning approach. By our method, students will work in small groups to solve problems and interpret an actual data set describing genes involved in autophagy. The problem-solving exercises and data set analysis will instill within the students a much greater understanding of the autophagy pathway than can be achieved by simple rote memorization of lecture materials; furthermore, the students will gain a general appreciation of the process by which data are interpreted and eventually formed into an understanding of a given pathway. As the data sets used in these class lessons are largely genomic and complementary in content, students will also understand first-hand the advantage of an integrative or systems biology study: No single data set can be used to define the pathway in full-the information from multiple complementary studies must be integrated in order to recapitulate our present understanding of the pathways mediating autophagy. In total, our teaching methodology offers an effective presentation of autophagy as well as a general template for the discussion of nearly any signaling pathway within the eukaryotic kingdom.

  9. Liquid crystal assemblies in biologically inspired systems

    PubMed Central

    Safinya, Cyrus R.; Deek, Joanna; Beck, Roy; Jones, Jayna B.; Leal, Cecilia; Ewert, Kai K.; Li, Youli

    2013-01-01

    In this paper, which is part of a collection in honor of Noel Clark's remarkable career on liquid crystal and soft matter research, we present examples of biologically inspired systems, which form liquid crystal (LC) phases with their LC nature impacting biological function in cells or being important in biomedical applications. One area focuses on understanding network and bundle formation of cytoskeletal polyampholytes (filamentous-actin, microtubules, and neurofilaments). Here, we describe studies on neurofilaments (NFs), the intermediate filaments of neurons, which form open network nematic liquid crystal hydrogels in axons. Synchrotron small-angle-x-ray scattering studies of NF-protein dilution experiments and NF hydrogels subjected to osmotic stress show that neurofilament networks are stabilized by competing long-range repulsion and attractions mediated by the neurofilament's polyampholytic sidearms. The attractions are present both at very large interfilament spacings, in the weak sidearm-interpenetrating regime, and at smaller interfilament spacings, in the strong sidearm-interpenetrating regime. A second series of experiments will describe the structure and properties of cationic liposomes (CLs) complexed with nucleic acids (NAs). CL-NA complexes form liquid crystalline phases, which interact in a structure-dependent manner with cellular membranes enabling the design of complexes for efficient delivery of nucleic acid (DNA, RNA) in therapeutic applications. PMID:24558293

  10. Cell phone radiation exposure on brain and associated biological systems.

    PubMed

    Kesari, Kavindra Kumar; Siddiqui, Mohd Haris; Meena, Ramovatar; Verma, H N; Kumar, Shivendra

    2013-03-01

    Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases.

  11. Biological engineering and systems biology--new opportunities for engineers in the pharmaceutical industry.

    PubMed

    Lauffenburger, Douglas A

    2004-01-01

    The consecutive life science revolutions of molecular biology and genomic biology have led to the promise for improving human health by molecular-level interventions--but the accompanying challenge of doing so in a rational, predictive manner. Addressing this challenge, and meeting this promise, requires understanding of complex biological processes with molecular detail but in integrative fashion; the emerging field aimed at this endeavor is now commonly termed 'systems biology'. In many ways, this field is an ideal application area for the biological engineering discipline, and offers tremendous opportunities for biology-based engineers. This talk will present a view of key aspects of this vision.

  12. EUCLIS--an information system for circadian systems biology.

    PubMed

    Batista, R T B; Ramirez, D B; Santos, R D; del Rosario, M C I; Mendoza, E R

    2007-09-01

    A major barrier to progress in systems biology is the absence of suitable infrastructure for data and software integration, which would enable working biologists to use and manipulate the techniques directly. We describe the incremental development of key components of such an infrastructure for a research community focused on a specific (but important) biological system. EUCLOCK combines the expertise of 34 chronobiology laboratories from 29 institutions in 11 European countries in a 5-year effort to understand how circadian clocks are synchronised to their specific cyclic environment (entrainment). We envision that the EUCLOCK Information System (EUCLIS) will subsequently evolve to support the worldwide chronobiology community. The architecture of EUCLIS integrates a database for circadian systems biology, containing modules for experimental data (Clock Experiments) and models (Clock Models) with a digital library (Clock KnowledgeBase) for the research community. The digital library paradigm is superior to the simple 'access' or 'mining' as well as the 'data warehouse' approaches currently used in other systems as it provides a flexible framework for community information needs and the potential to use emerging reference models and standards, which will enable easier integration with other systems in the future. The main Clock KnowledgeBase components for EUCLIS V1.0, Clock Genes and Clock Library, are described in detail. An important aspect this work will need to address in the future is the integration of the database and digital library management functions.

  13. Mouse behavioural analysis in systems biology

    PubMed Central

    van Meer, Peter; Raber, Jacob

    2005-01-01

    Molecular techniques allowing in vivo modulation of gene expression have provided unique opportunities and challenges for behavioural studies aimed at understanding the function of particular genes or biological systems under physiological or pathological conditions. Although various animal models are available, the laboratory mouse (Mus musculus) has unique features and is therefore a preferred animal model. The mouse shares a remarkable genetic resemblance and aspects of behaviour with humans. In this review, first we describe common mouse models for behavioural analyses. As both genetic and environmental factors influence behavioural performance and need to be carefully evaluated in behavioural experiments, considerations for designing and interpretations of these experiments are subsequently discussed. Finally, common behavioural tests used to assess brain function are reviewed, and it is illustrated how behavioural tests are used to increase our understanding of the role of histaminergic neurotransmission in brain function. PMID:16035954

  14. Systems biology of human benzene exposure

    PubMed Central

    Zhang, Luoping; McHale, Cliona M.; Rothman, Nathaniel; Li, Guilan; Ji, Zhiying; Vermeulen, Roel; Hubbard, Alan E.; Ren, Xuefeng; Shen, Min; Rappaport, Stephen M.; North, Matthew; Skibola, Christine F.; Yin, Songnian; Vulpe, Christopher; Chanock, Stephen J.; Smith, Martyn T.; Lan, Qing

    2010-01-01

    Toxicogenomic studies, including genome-wide analyses of susceptibility genes (genomics), gene expression (transcriptomics), protein expression (proteomics), and epigenetic modifications (epigenomics), of human populations exposed to benzene are crucial to understanding gene-environment interactions, providing the ability to develop biomarkers of exposure, early effect and susceptibility. Comprehensive analysis of these toxicogenomic and epigenomic profiles by bioinformatics in the context of phenotypic endpoints, comprises systems biology, which has the potential to comprehensively define the mechanisms by which benzene causes leukemia. We have applied this approach to a molecular epidemiology study of workers exposed to benzene. Hematotoxicity, a significant decrease in almost all blood cell counts, was identified as a phenotypic effect of benzene that occurred even below 1ppm benzene exposure. We found a significant decrease in the formation of progenitor colonies arising from bone marrow stem cells with increasing benzene exposure, showing that progenitor cells are more sensitive to the effects of benzene than mature blood cells, likely leading to the observed hematotoxicity. Analysis of transcriptomics by microarray in the peripheral blood mononuclear cells of exposed workers, identified genes and pathways (apoptosis, immune response, and inflammatory response) altered at high (>10ppm) and low (<1ppm) benzene levels. Serum proteomics by SELDI-TOF-MS revealed proteins consistently down-regulated in exposed workers. Preliminary epigenomics data showed effects of benzene on the DNA methylation of specific genes. Genomic screens for candidate genes involved in susceptibility to benzene toxicity are being undertaken in yeast, with subsequent confirmation by RNAi in human cells, to expand upon the findings from candidate gene analyses. Data on these and future biomarkers will be used to populate a large toxicogenomics database, to which we will apply bioinformatic

  15. Systems Biology and Ecology of Streamlined Bacterioplankton

    NASA Astrophysics Data System (ADS)

    Giovannoni, S. J.

    2014-12-01

    complex questions hinge on translating gene frequencies into trait based ecological models that reflect the systems biology of cells.

  16. Construction of Multi-Mode Affective Learning System: Taking Affective Design as an Example

    ERIC Educational Resources Information Center

    Lin, Hao-Chiang Koong; Su, Sheng-Hsiung; Chao, Ching-Ju; Hsieh, Cheng-Yen; Tsai, Shang-Chin

    2016-01-01

    This study aims to design a non-simultaneous distance instruction system with affective computing, which integrates interactive agent technology with the curricular instruction of affective design. The research subjects were 78 students, and prototype assessment and final assessment were adopted to assess the interface and usability of the system.…

  17. Expert systems guide biological phosphorus removal

    SciTech Connect

    Krichten, D.J.; Wilson, K.D.; Tracy, K.D. )

    1991-10-01

    There is a large body of knowledge regarding optimum control strategies for new secondary wastewater treatment technology using an anaerobic selector to provide biological phosphorus removal. However, because the selector technology is new and the concepts differ somewhat from those used in conventional activated sludge wastewater treatment, a method of communicating this knowledge to plant operators is needed. Traditional methods such as classroom training and operating manuals are of limited effectiveness. The commonplace availability and low cost of the personal computer (PC) makes it practical to use a computer program to communicate the type of information required to control a wastewater treatment plant. Knowledge-based systems technology, commonly referred to as expert systems (ES) technology, is easy to use, provides useful information regarding a consistent control strategy, relieves the anxiety associated with learning a new process,' and provides instruction for inexperienced personnel. ES technology does not require special formatted input and is therefore easily accessible. All information required by the program is readily available through routine laboratory analysis, common plant instrumentation, or direct user observation. The program was designed for all levels of computer users and will run on all IBM-compatible or Apple MacIntosh systems.

  18. Systems biology and complex neurobehavioral traits.

    PubMed

    Giegling, I; Hartmann, A M; Genius, J; Benninghoff, J; Möller, H-J; Rujescu, D

    2008-09-01

    There is evidence for a strong genetic component in the etiology of schizophrenia, as demonstrated by family, twin and adoption studies suggesting a heritability of about 80%. There are several approaches in the search for genetic risk factors such as linkage or association studies. Additionally, much effort was done in refining the phenotype including neuropsychology, neurophysiology, imaging or the generation of animal models. Genes becoming associated with schizophrenia have to be tested for functionality including e.g. metabolomics, transcriptomics, proteomics, generation of transgenic mice, analysis of protein-protein interactions, allele-specific RNA expression analysis, analysis of neuronal and stem cell cultures, as well as post mortem studies and behavioral studies in rodents. This amount of data requires complex data analysis. A system's perspective can help in the analysis of the structural and functional complexity of the brain. New tools will be needed for a more complex and systemic view. The systems biology approach could be a pivotal tool in understanding of complex behavior and diseases in future.

  19. A systems biology perspective of wine fermentations.

    PubMed

    Pizarro, Francisco; Vargas, Felipe A; Agosin, Eduardo

    2007-11-01

    The yeast Saccharomyces cerevisiae is an important industrial microorganism. Nowadays, it is being used as a cell factory for the production of pharmaceuticals such as insulin, although this yeast has long been utilized in the bakery to raise dough, and in the production of alcoholic beverages, fermenting the sugars derived from rice, wheat, barley, corn and grape juice. S. cerevisiae has also been extensively used as a model eukaryotic system. In the last decade, genomic techniques have revealed important features of its molecular biology. For example, DNA array technologies are routinely used for determining gene expression levels in cells under different physiological conditions or environmental stimuli. Laboratory strains of S. cerevisiae are different from wine strains. For instance, laboratory yeasts are unable to completely transform all the sugar in the grape must into ethanol under winemaking conditions. In fact, standard culture conditions are usually very different from winemaking conditions, where multiple stresses occur simultaneously and sequentially throughout the fermentation. The response of wine yeasts to these stimuli differs in some aspects from laboratory strains, as suggested by the increasing number of studies in functional genomics being conducted on wine strains. In this paper we review the most recent applications of post-genomic techniques to understand yeast physiology in the wine industry. We also report recent advances in wine yeast strain improvement and propose a reference framework for integration of genomic information, bioinformatic tools and molecular biology techniques for cellular and metabolic engineering. Finally, we discuss the current state and future perspectives for using 'modern' biotechnology in the wine industry.

  20. Political and institutional factors affecting systems engineering

    NASA Technical Reports Server (NTRS)

    Yardley, John F.

    1993-01-01

    External groups have a significant impact on NASA's programs. Ten groups affecting NASA are identified, and examples are given for some of the them. Methods of dealing with these external inputs are discussed, the most important being good and open two way communications and an objective attitude on the part of the NASA participants. The importance of planning ahead, of developing rapport with these groups, and of effective use of NASA contractors is covered. The need for an overall strategic plan for the U.S. space program is stressed.

  1. Compatibility Issues Affecting Information Systems and Services.

    ERIC Educational Resources Information Center

    Lancaster, F. Wilfrid; Smith, Linda C.

    This UNISIST publication discusses issues related to the compatibility and standardization of bibliograpic records, index languages, software, hardware, and other information systems and services. Following an executive summary, definitions of terms, and other introductory material, existing information systems with common standards are briefly…

  2. Stem cell genome-to-systems biology.

    PubMed

    Chia, Na-Yu; Ng, Huck-Hui

    2012-01-01

    Stem cells are capable of extended proliferation and concomitantly differentiating into a plethora of specialized cell types that render them apropos for their usage as a form of regenerative medicine for cell replacement therapies. The molecular processes that underlie the ability for stem cells to self-renew and differentiate have been intriguing, and elucidating the intricacies within the genome is pertinent to enhance our understanding of stem cells. Systems biology is emerging as a crucial field in the study of the sophisticated nature of stem cells, through the adoption of multidisciplinary approaches which couple high-throughput experimental techniques with computational and mathematical analysis. This allows for the determination of the molecular constituents that govern stem cell characteristics and conjointly with functional validations via genetic perturbation and protein location binding analysis necessitate the construction of the complex transcriptional regulatory network. With the elucidation of protein-protein interaction, protein-DNA regulation, microRNA involvement as well as the epigenetic modifications, it is possible to comprehend the defining features of stem cells at the system level.

  3. Exoproteomics: exploring the world around biological systems.

    PubMed

    Armengaud, Jean; Christie-Oleza, Joseph A; Clair, Gérémy; Malard, Véronique; Duport, Catherine

    2012-10-01

    The term 'exoproteome' describes the protein content that can be found in the extracellular proximity of a given biological system. These proteins arise from cellular secretion, other protein export mechanisms or cell lysis, but only the most stable proteins in this environment will remain in abundance. It has been shown that these proteins reflect the physiological state of the cells in a given condition and are indicators of how living systems interact with their environments. High-throughput proteomic approaches based on a shotgun strategy, and high-resolution mass spectrometers, have modified the authors' view of exoproteomes. In the present review, the authors describe how these new approaches should be exploited to obtain the maximum useful information from a sample, whatever its origin. The methodologies used for studying secretion from model cell lines derived from eukaryotic, multicellular organisms, virulence determinants of pathogens and environmental bacteria and their relationships with their habitats are illustrated with several examples. The implication of such data, in terms of proteogenomics and the discovery of novel protein functions, is discussed.

  4. Systems Biology in the Context of Big Data and Networks

    PubMed Central

    Altaf-Ul-Amin, Md.; Afendi, Farit Mochamad; Kiboi, Samuel Kuria; Kanaya, Shigehiko

    2014-01-01

    Science is going through two rapidly changing phenomena: one is the increasing capabilities of the computers and software tools from terabytes to petabytes and beyond, and the other is the advancement in high-throughput molecular biology producing piles of data related to genomes, transcriptomes, proteomes, metabolomes, interactomes, and so on. Biology has become a data intensive science and as a consequence biology and computer science have become complementary to each other bridged by other branches of science such as statistics, mathematics, physics, and chemistry. The combination of versatile knowledge has caused the advent of big-data biology, network biology, and other new branches of biology. Network biology for instance facilitates the system-level understanding of the cell or cellular components and subprocesses. It is often also referred to as systems biology. The purpose of this field is to understand organisms or cells as a whole at various levels of functions and mechanisms. Systems biology is now facing the challenges of analyzing big molecular biological data and huge biological networks. This review gives an overview of the progress in big-data biology, and data handling and also introduces some applications of networks and multivariate analysis in systems biology. PMID:24982882

  5. Systems biology in the context of big data and networks.

    PubMed

    Altaf-Ul-Amin, Md; Afendi, Farit Mochamad; Kiboi, Samuel Kuria; Kanaya, Shigehiko

    2014-01-01

    Science is going through two rapidly changing phenomena: one is the increasing capabilities of the computers and software tools from terabytes to petabytes and beyond, and the other is the advancement in high-throughput molecular biology producing piles of data related to genomes, transcriptomes, proteomes, metabolomes, interactomes, and so on. Biology has become a data intensive science and as a consequence biology and computer science have become complementary to each other bridged by other branches of science such as statistics, mathematics, physics, and chemistry. The combination of versatile knowledge has caused the advent of big-data biology, network biology, and other new branches of biology. Network biology for instance facilitates the system-level understanding of the cell or cellular components and subprocesses. It is often also referred to as systems biology. The purpose of this field is to understand organisms or cells as a whole at various levels of functions and mechanisms. Systems biology is now facing the challenges of analyzing big molecular biological data and huge biological networks. This review gives an overview of the progress in big-data biology, and data handling and also introduces some applications of networks and multivariate analysis in systems biology.

  6. Apparatus and Methods for Manipulation and Optimization of Biological Systems

    NASA Technical Reports Server (NTRS)

    Ho, Chih-Ming (Inventor); Wong, Pak Kin (Inventor); Sun, Ren (Inventor); Yu, Fuqu (Inventor)

    2014-01-01

    The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

  7. How phototherapy affects the immune system

    NASA Astrophysics Data System (ADS)

    Dyson, Mary

    2008-03-01

    The immune system is a complex group of cells, tissues and organs that recognize and attack foreign substances, pathogenic organisms and cancer cells. It also responds to injury by producing inflammation. The immune system has peripheral components that include skin-associated lymphoid tissues (SALT) and mucosa-associated lymphoid tissues (MALT), located where pathogens and other harmful substances gain access to the body. Phototherapy, delivered at appropriate treatment parameters, exerts direct actions on the cellular elements of the peripheral part of the immune system since it is readily accessible to photons.

  8. [Application of systems biology and synthetic biology in strain improvement for biofuel production].

    PubMed

    Zhao, Xinqing; Bai, Fengwu; Li, Yin

    2010-07-01

    Biofuels are renewable and environmentally friendly, but high production cost makes them economically not competitive, and the development of robust strains is thus one of the prerequisites. In this article, strain improvement studies based on the information from systems biology studies are reviewed, with a focus on their applications on stress tolerance improvement. Furthermore, the contribution of systems biology, synthetic biology and metabolic engineering in strain development for biofuel production is discussed, with an expectation for developing more robust strains for biofuel production.

  9. Consistent design schematics for biological systems: standardization of representation in biological engineering

    PubMed Central

    Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

    2009-01-01

    The discovery by design paradigm driving research in synthetic biology entails the engineering of de novo biological constructs with well-characterized input–output behaviours and interfaces. The construction of biological circuits requires iterative phases of design, simulation and assembly, leading to the fabrication of a biological device. In order to represent engineered models in a consistent visual format and further simulating them in silico, standardization of representation and model formalism is imperative. In this article, we review different efforts for standardization, particularly standards for graphical visualization and simulation/annotation schemata adopted in systems biology. We identify the importance of integrating the different standardization efforts and provide insights into potential avenues for developing a common framework for model visualization, simulation and sharing across various tools. We envision that such a synergistic approach would lead to the development of global, standardized schemata in biology, empowering deeper understanding of molecular mechanisms as well as engineering of novel biological systems. PMID:19493898

  10. Consistent design schematics for biological systems: standardization of representation in biological engineering.

    PubMed

    Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

    2009-08-06

    The discovery by design paradigm driving research in synthetic biology entails the engineering of de novo biological constructs with well-characterized input-output behaviours and interfaces. The construction of biological circuits requires iterative phases of design, simulation and assembly, leading to the fabrication of a biological device. In order to represent engineered models in a consistent visual format and further simulating them in silico, standardization of representation and model formalism is imperative. In this article, we review different efforts for standardization, particularly standards for graphical visualization and simulation/annotation schemata adopted in systems biology. We identify the importance of integrating the different standardization efforts and provide insights into potential avenues for developing a common framework for model visualization, simulation and sharing across various tools. We envision that such a synergistic approach would lead to the development of global, standardized schemata in biology, empowering deeper understanding of molecular mechanisms as well as engineering of novel biological systems.

  11. Systems Biology of Microbial Exopolysaccharides Production

    PubMed Central

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran. PMID:26734603

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

    PubMed

    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.

  13. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    PubMed

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  14. Teaching Systems Biology: An Active-Learning Approach

    ERIC Educational Resources Information Center

    Kumar, Anuj

    2005-01-01

    With genomics well established in modern molecular biology, recent studies have sought to further the discipline by integrating complementary methodologies into a holistic depiction of the molecular mechanisms underpinning cell function. This genomic subdiscipline, loosely termed "systems biology," presents the biology educator with both…

  15. Integrating systems biology sources illuminates drug action

    PubMed Central

    Gottlieb, Assaf; Altman, Russ B.

    2014-01-01

    There are significant gaps in our understanding of the pathways by which drugs act. This incomplete knowledge limits our ability to use mechanistic molecular information rationally to repurpose drugs, understand their side effects, and predict their interactions with other drugs. Here we present DrugRouter: a novel method for generating drug-specific pathways of action by linking target genes, disease genes and pharmacogenes using gene interaction networks. We construct pathways for over a hundred drugs, and show that the genes included in our pathways (1) co-occur with the query drug in the literature, (2) significantly overlap or are adjacent to known drug-response pathways, and (3) are adjacent to genes that are hits in genome wide association studies assessing drug response. Finally, these computed pathways suggest novel drug repositioning opportunities (e.g., statins for follicular thyroid cancer), gene-side effect associations, and gene-drug interactions. Thus, DrugRouter generates hypotheses about drug actions using systems biology data. PMID:24577151

  16. Isotopic fractionation of tritium in biological systems.

    PubMed

    Le Goff, Pierre; Fromm, Michel; Vichot, Laurent; Badot, Pierre-Marie; Guétat, Philippe

    2014-04-01

    Isotopic fractionation of tritium is a highly relevant issue in radiation protection and requires certain radioecological considerations. Sound evaluation of this factor is indeed necessary to determine whether environmental compartments are enriched/depleted in tritium or if tritium is, on the contrary, isotopically well-distributed in a given system. The ubiquity of tritium and the standard analytical methods used to assay it may induce biases in both the measurement and the signification that is accorded to the so-called fractionation: based on an exhaustive review of the literature, we show how, sometimes large deviations may appear. It is shown that when comparing the non-exchangeable fraction of organically bound tritium (neOBT) to another fraction of tritium (e.g. tritiated water) the preparation of samples and the measurement of neOBT reported frequently led to underestimation of the ratio of tritium to hydrogen (T/H) in the non-exchangeable compartment by a factor of 5% to 50%. In the present study, corrections are proposed for most of the biological matrices studied so far. Nevertheless, the values of isotopic fractionation reported in the literature remain difficult to compare with each other, especially since the physical quantities and units often vary between authors. Some improvements are proposed to better define what should encompass the concepts of exchangeable and non-exchangeable fractions.

  17. Precision medicine driven by cancer systems biology.

    PubMed

    Filipp, Fabian V

    2017-03-07

    Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance.

  18. Radionuclide Imaging Technologies for Biological Systems

    SciTech Connect

    Howell, Calvin R.; Reid, Chantal D.; Weisenberger, Andrew G.

    2014-05-14

    The main objective of this project is to develop technologies and experimental techniques for studying the dynamics of physiological responses of plants to changes in their interface with the local environment and to educate a new generation of scientists in an interdisciplinary environment of biology, physics and engineering. Also an important goal is to perform measurements to demonstrate the new data that can be produced and made available to the plant-biology community using the imaging technologies and experimental techniques developed in this project. The study of the plant-environment interface includes a wide range of topics in plant physiology, e.g., the root-soil interface, resource availability, impact of herbivores, influence of microbes on root surface, and responses to toxins in the air and soil. The initial scientific motivation for our work is to improve understanding of the mechanisms for physiological responses to abrupt changes in the local environment, in particular, the responses that result in short-term adjustments in resource (e.g., sugars, nutrients and water) allocations. Data of time-dependent responses of plants to environmental changes are essential in developing mechanistic models for substance intake and resource allocation. Our approach is to use radioisotope tracing techniques to study whole-plant and plant organ (e.g., leaves, stems, roots) dynamical responses to abrupt changes in environmental conditions such as concentration of CO2 in the atmosphere, nutrient availability and lighting. To this aim we are collaborating with the Radiation Detector and Imaging Group at the Thomas Jefferson National Laboratory Facility (JLab) to develop gamma-ray and beta particle imaging systems optimized for plant studies. The radioisotope tracing measurements are conducted at the Phytotron facility at Duke University. The Phytotron is a controlled environment plant research facility with a variety of plant growth chambers. One chamber

  19. Probing Gravitational Sensitivity in Biological Systems Using Magnetic Body Forces

    NASA Technical Reports Server (NTRS)

    Guevorkian, Karine; Wurzel, Sam; Mihalusova, Mariana; Valles, Jim

    2003-01-01

    At Brown University, we are developing the use of magnetic body forces as a means to simulate variable gravity body forces on biological systems. This tool promises new means to probe gravi-sensing and the gravi-response of biological systems. It also has the potential as a technique for screening future systems for space flight experiments.

  20. Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

    PubMed

    Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

    2015-02-01

    Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

  1. Peroxisystem: harnessing systems cell biology to study peroxisomes.

    PubMed

    Schuldiner, Maya; Zalckvar, Einat

    2015-04-01

    In recent years, high-throughput experimentation with quantitative analysis and modelling of cells, recently dubbed systems cell biology, has been harnessed to study the organisation and dynamics of simple biological systems. Here, we suggest that the peroxisome, a fascinating dynamic organelle, can be used as a good candidate for studying a complete biological system. We discuss several aspects of peroxisomes that can be studied using high-throughput systematic approaches and be integrated into a predictive model. Such approaches can be used in the future to study and understand how a more complex biological system, like a cell and maybe even ultimately a whole organism, works.

  2. Systems Biology Applied to Heart Failure With Normal Ejection Fraction

    PubMed Central

    Mesquita, Evandro Tinoco; Jorge, Antonio Jose Lagoeiro; de Souza, Celso Vale; Cassino, João Paulo Pedroza

    2014-01-01

    Heart failure with normal ejection fraction (HFNEF) is currently the most prevalent clinical phenotype of heart failure. However, the treatments available have shown no reduction in mortality so far. Advances in the omics sciences and techniques of high data processing used in molecular biology have enabled the development of an integrating approach to HFNEF based on systems biology. This study aimed at presenting a systems-biology-based HFNEF model using the bottom-up and top-down approaches. A literature search was conducted for studies published between 1991 and 2013 regarding HFNEF pathophysiology, its biomarkers and systems biology. A conceptual model was developed using bottom-up and top-down approaches of systems biology. The use of systems-biology approaches for HFNEF, a complex clinical syndrome, can be useful to better understand its pathophysiology and to discover new therapeutic targets. PMID:24918915

  3. New frontiers in myocardial protection: a systems biology approach.

    PubMed

    Lotz, Christopher; Liem, David; Ping, Peipei

    2011-01-01

    Myocardial ischemic injury and cardioprotection are characterized by a cascade of molecular changes, which includes gene expression, protein expression, protein localization, interactions, and posttranslational modifications (PTMs). A systems biology approach allows the study of these genes and proteins on a large scale; the omics technologies have led to new discoveries that further enhance our understanding of these molecular events. The complexity of the prosurvival signaling networks in cardiac cells is increasingly recognized; they afford beneficial effects on the integrity and functionality of a common effector, the mitochondrion. Mitochondrial proteome undergoes dynamic modifications in the course of ischemic injury; depending on the degree of injury, a variety of functional clusters are being affected including the changes in their protein properties (eg, PTMs), which consequently impact their function. The mitochondrial proteome appears to have inherent molecular machinery that initiates a versatile prosurvival mode, resisting environmental challenges. The molecular features in these mitochondrial pathways enabling adaptations involve distinct phosphorylation sites, S-nitrosylation cysteine residues, and other important amino acid domains subjected to PTMs. They become critical players in the determination of cell death and survival. Cardioprotective protein kinases, such as protein kinase C∈, can activate these PTMs, and provide a unique therapeutic platform for the use of small peptide regulators. Combining genomics and metabolomics discovery with that of proteomics information allows biological insights into cardioprotection at an integrated systems level. The current review discusses the systems biology concepts of myocardial ischemic injury and cardioprotection, as well as outlines the interrelationships of proteomics, genomics, and metabolomics in the quest to comprehend the prosurvival cell-signaling networks.

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

    PubMed

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

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

  5. Systems vaccinology: Enabling rational vaccine design with systems biological approaches.

    PubMed

    Hagan, Thomas; Nakaya, Helder I; Subramaniam, Shankar; Pulendran, Bali

    2015-09-29

    Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines.

  6. A unified biological modeling and simulation system for analyzing biological reaction networks

    NASA Astrophysics Data System (ADS)

    Yu, Seok Jong; Tung, Thai Quang; Park, Junho; Lim, Jongtae; Yoo, Jaesoo

    2013-12-01

    In order to understand the biological response in a cell, a researcher has to create a biological network and design an experiment to prove it. Although biological knowledge has been accumulated, we still don't have enough biological models to explain complex biological phenomena. If a new biological network is to be created, integrated modeling software supporting various biological models is required. In this research, we design and implement a unified biological modeling and simulation system, called ezBioNet, for analyzing biological reaction networks. ezBioNet designs kinetic and Boolean network models and simulates the biological networks using a server-side simulation system with Object Oriented Parallel Accelerator Library framework. The main advantage of ezBioNet is that a user can create a biological network by using unified modeling canvas of kinetic and Boolean models and perform massive simulations, including Ordinary Differential Equation analyses, sensitivity analyses, parameter estimates and Boolean network analysis. ezBioNet integrates useful biological databases, including the BioModels database, by connecting European Bioinformatics Institute servers through Web services Application Programming Interfaces. In addition, we employ Eclipse Rich Client Platform, which is a powerful modularity framework to allow various functional expansions. ezBioNet is intended to be an easy-to-use modeling tool and a simulation system for understanding the control mechanism by monitoring the change of each component in a biological network. The simulation result can be managed and visualized on ezBioNet, which is available free of charge at http://ezbionet.sourceforge.net or http://ezbionet.cbnu.ac.kr.

  7. The Simbios National Center: Systems Biology in Motion

    PubMed Central

    Schmidt, Jeanette P.; Delp, Scott L.; Sherman, Michael A.; Taylor, Charles A.; Pande, Vijay S.; Altman, Russ B.

    2010-01-01

    Physics-based simulation is needed to understand the function of biological structures and can be applied across a wide range of scales, from molecules to organisms. Simbios (the National Center for Physics-Based Simulation of Biological Structures, http://www.simbios.stanford.edu/) is one of seven NIH-supported National Centers for Biomedical Computation. This article provides an overview of the mission and achievements of Simbios, and describes its place within systems biology. Understanding the interactions between various parts of a biological system and integrating this information to understand how biological systems function is the goal of systems biology. Many important biological systems comprise complex structural systems whose components interact through the exchange of physical forces, and whose movement and function is dictated by those forces. In particular, systems that are made of multiple identifiable components that move relative to one another in a constrained manner are multibody systems. Simbios’ focus is creating methods for their simulation. Simbios is also investigating the biomechanical forces that govern fluid flow through deformable vessels, a central problem in cardiovascular dynamics. In this application, the system is governed by the interplay of classical forces, but the motion is distributed smoothly through the materials and fluids, requiring the use of continuum methods. In addition to the research aims, Simbios is working to disseminate information, software and other resources relevant to biological systems in motion. PMID:20107615

  8. A systems biology representation of developmental anatomy

    PubMed Central

    Bard, Jonathan

    2011-01-01

    The formation of any tissue involves differentiation, cell dynamics and interactions with adjacent tissues. This paper suggests that the complexity of the system as a whole can be represented as a mathematical graph, that is, a set of connected triples of the general form [term] [term]. Computationally, such graphs are widely used for modeling data; visually, they form hierarchies and networks. For morphogenesis, the triples are of the general structure , where nouns cover tissues, molecules and networks and verbs describe processes such as moves, differentiates, grows and apoptoses. The paper considers the general formalism of graphs, where graphs are already used in biology, and how developmental anatomy may be described using this format. Representing morphogenesis as a visual graph is complicated as the formalism has to incorporate tissue types, molecular signals, networks, dynamic processes and some aspects, at least, of tissue geometry. The formation of a capillary sprout is chosen as an example of how this complexity can be represented graphically, with colour used to distinguish tissues and molecules. There are three key benefits, beyond its compactness, in using the graph formalism of morphogenesis to complement experimentation. First, it emphasizes the distributed nature of causality in morphogenesis. Secondly, producing all the triples for the visual graph requires explicit formalization of each aspect of the process, and this, in turn, often exposes gaps in knowledge and so suggests new experiments. Thirdly, once the graph has been formalized, triples can be annotated with associated information or IDs (e.g. cell types, publications, gene-expression data) that link to external online resources that may be regularly updated. Such annotations allow the graph to be viewed as a self-maintaining review. The graph approach sees dynamic processes as the drivers of developmental momentum and, because the same processes are

  9. A systems biology representation of developmental anatomy.

    PubMed

    Bard, Jonathan

    2011-06-01

    The formation of any tissue involves differentiation, cell dynamics and interactions with adjacent tissues. This paper suggests that the complexity of the system as a whole can be represented as a mathematical graph, that is, a set of connected triples of the general form [term] [term]. Computationally, such graphs are widely used for modeling data; visually, they form hierarchies and networks. For morphogenesis, the triples are of the general structure , where nouns cover tissues, molecules and networks and verbs describe processes such as moves, differentiates, grows and apoptoses. The paper considers the general formalism of graphs, where graphs are already used in biology, and how developmental anatomy may be described using this format. Representing morphogenesis as a visual graph is complicated as the formalism has to incorporate tissue types, molecular signals, networks, dynamic processes and some aspects, at least, of tissue geometry. The formation of a capillary sprout is chosen as an example of how this complexity can be represented graphically, with colour used to distinguish tissues and molecules. There are three key benefits, beyond its compactness, in using the graph formalism of morphogenesis to complement experimentation. First, it emphasizes the distributed nature of causality in morphogenesis. Secondly, producing all the triples for the visual graph requires explicit formalization of each aspect of the process, and this, in turn, often exposes gaps in knowledge and so suggests new experiments. Thirdly, once the graph has been formalized, triples can be annotated with associated information or IDs (e.g. cell types, publications, gene-expression data) that link to external online resources that may be regularly updated. Such annotations allow the graph to be viewed as a self-maintaining review. The graph approach sees dynamic processes as the drivers of developmental momentum and, because the same processes are

  10. Histopathology of Growth Anomaly Affecting the Coral, Montipora capitata: Implications on Biological Functions and Population Viability

    PubMed Central

    Burns, John H. R.; Takabayashi, Misaki

    2011-01-01

    Growth anomalies (GAs) affect the coral, Montipora capitata, at Wai'ōpae, southeast Hawai'i Island. Our histopathological analysis of this disease revealed that the GA tissue undergoes changes which compromise anatomical machinery for biological functions such as defense, feeding, digestion, and reproduction. GA tissue exhibited significant reductions in density of ova (66.1–93.7%), symbiotic dinoflagellates (38.8–67.5%), mesenterial filaments (11.2–29.0%), and nematocytes (28.8–46.0%). Hyperplasia of the basal body wall but no abnormal levels of necrosis and algal or fungal invasion was found in GA tissue. Skeletal density along the basal body wall was significantly reduced in GAs compared to healthy or unaffected sections. The reductions in density of the above histological features in GA tissue were collated with disease severity data to quantify the impact of this disease at the colony and population level. Resulting calculations showed this disease reduces the fecundity of M. capitata colonies at Wai'ōpae by 0.7–49.6%, depending on GA severity, and the overall population fecundity by 2.41±0.29%. In sum, GA in this M. capitata population reduces the coral's critical biological functions and increases susceptibility to erosion, clearly defining itself as a disease and an ecological threat. PMID:22205976

  11. Hierarchical structure of biological systems: a bioengineering approach.

    PubMed

    Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M

    2014-01-01

    A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and functioning of the biological system. Our thermodynamical approach of hierarchical character can be applied to biological systems of varying sizes through some general principles, based on the exchange of energy information and/or mass from and within the systems.

  12. New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

    PubMed Central

    Hamon, Morgan; Hong, Jong Wook

    2013-01-01

    Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843

  13. Meat science: From proteomics to integrated omics towards system biology.

    PubMed

    D'Alessandro, Angelo; Zolla, Lello

    2013-01-14

    Since the main ultimate goal of farm animal raising is the production of proteins for human consumption, research tools to investigate proteins play a major role in farm animal and meat science. Indeed, proteomics has been applied to the field of farm animal science to monitor in vivo performances of livestock animals (growth performances, fertility, milk quality etc.), but also to further our understanding of the molecular processes at the basis of meat quality, which are largely dependent on the post mortem biochemistry of the muscle, often in a species-specific way. Post mortem alterations to the muscle proteome reflect the biological complexity of the process of "muscle to meat conversion," a process that, despite decades of advancements, is all but fully understood. This is mainly due to the enormous amounts of variables affecting meat tenderness per se, including biological factors, such as animal species, breed specific-characteristic, muscle under investigation. However, it is rapidly emerging that the tender meat phenotype is not only tied to genetics (livestock breeding selection), but also to extrinsic factors, such as the rearing environment, feeding conditions, physical activity, administration of hormonal growth promotants, pre-slaughter handling and stress, post mortem handling. From this intricate scenario, biochemical approaches and systems-wide integrated investigations (metabolomics, transcriptomics, interactomics, phosphoproteomics, mathematical modeling), which have emerged as complementary tools to proteomics, have helped establishing a few milestones in our understanding of the events leading from muscle to meat conversion. The growing integration of omics disciplines in the field of systems biology will soon contribute to take further steps forward.

  14. On the interplay between mathematics and biology: hallmarks toward a new systems biology.

    PubMed

    Bellomo, Nicola; Elaiw, Ahmed; Althiabi, Abdullah M; Alghamdi, Mohammed Ali

    2015-03-01

    This paper proposes a critical analysis of the existing literature on mathematical tools developed toward systems biology approaches and, out of this overview, develops a new approach whose main features can be briefly summarized as follows: derivation of mathematical structures suitable to capture the complexity of biological, hence living, systems, modeling, by appropriate mathematical tools, Darwinian type dynamics, namely mutations followed by selection and evolution. Moreover, multiscale methods to move from genes to cells, and from cells to tissue are analyzed in view of a new systems biology approach.

  15. Graphic Representation of Carbon Dioxide Equilibria in Biological Systems.

    ERIC Educational Resources Information Center

    Kindig, Neal B.; Filley, Giles F.

    1983-01-01

    The log C-pH diagram is a useful means of displaying quantitatively the many variables (including temperature) that determine acid-base equilibria in biological systems. Presents the diagram as extended to open/closed biological systems and derives a new water-ion balance method for determining equilibrium pH. (JN)

  16. Biologic treatments for systemic rheumatic diseases

    PubMed Central

    Shirota, Y; Illei, GG; Nikolov, NP

    2009-01-01

    Many rheumatologic disorders, most notably Sjögren's syndrome, are associated with dental complications and in some cases oral diseases may trigger or drive connective tissue disease. During the past three decades the treatment in rheumatology was revolutionized by the introduction of disease-modifying anti-rheumatic drugs. Advances in our understanding of the pathogenesis of rheumatic diseases have led to the discovery of critical mechanisms of inflammation and autoimmunity and the invention of new target-specific biologic agents. In this review, we will summarize the current state of biologic therapies in rheumatology and discuss the implications of these on oral health and disease. PMID:18282173

  17. [Relationship between system biology and traditional Chinese constitutional medicine].

    PubMed

    Zhang, Wei-Rong; Li, Jing

    2006-11-01

    Life system and medicine are both complex systems. Recently, traditional biologists have acquired tremendous data from high-speed development of all kinds of species group. However, how to use these data to interpret the mechanisms of diseases and health has become the research target of current investigators. The booms of system biology provide new thought and research methods to tackle this problem. This paper emphasizes the relationship between system biology and traditional Chinese constitutional medicine.

  18. A Systems Approach to Biology (SAB).

    ERIC Educational Resources Information Center

    Bush, Kenneth H.; And Others

    This pupil's study guide is intended to be used with audio-taped biology modules. Each of the units (on laboratory techniques, plant and animal diversity, chemistry, cells, energy, microbiology, genetics, and development) contains an abstract providing an overview of the unit, the rationale and performance objectives for each module, questions to…

  19. Physics and Size in Biological Systems.

    ERIC Educational Resources Information Center

    Barnes, George

    1989-01-01

    Described is the subject of biological scaling for physics teachers including examples and in-depth reading. Topics are elements of scaling, terminal velocities, Lilliputian and Brobdingnagian, brain evolution, dolphin echolocation, surface tension, gravity change, food and oxygen, and seeing. Ten references on physics and size, and ten questions…

  20. Phase Transitions in Biological Systems with Many Components.

    PubMed

    Jacobs, William M; Frenkel, Daan

    2017-02-28

    Biological mixtures such as the cytosol may consist of thousands of distinct components. There is now a substantial body of evidence showing that, under physiological conditions, intracellular mixtures can phase separate into spatially distinct regions with differing compositions. In this article we present numerical evidence indicating that such spontaneous compartmentalization exploits general features of the phase diagram of a multicomponent biomolecular mixture. In particular, we show that demixed domains are likely to segregate when the variance in the intermolecular interaction strengths exceeds a well-defined threshold. Multiple distinct phases are likely to become stable under very similar conditions, which can then be tuned to achieve multiphase coexistence. As a result, only minor adjustments to the composition of the cytosol or the strengths of the intermolecular interactions are needed to regulate the formation of different domains with specific compositions, implying that phase separation is a robust mechanism for creating spatial organization. We further predict that this functionality is only weakly affected by increasing the number of components in the system. Our model therefore suggests that, for purely physico-chemical reasons, biological mixtures are naturally poised to undergo a small number of demixing phase transitions.

  1. Functional Synchronization of Biological Rhythms in a Tritrophic System

    PubMed Central

    Zhang, Sufang; Wei, Jianing; Guo, Xiaojiao; Liu, Tong-Xian; Kang, Le

    2010-01-01

    In a tritrophic system formed by a plant, an herbivore and a natural enemy, each component has its own biological rhythm. However, the rhythm correlations among the three levels and the underlying mechanisms in any tritrophic system are largely unknown. Here, we report that the rhythms exhibited bidirectional correlations in a model tritrophic system involving a lima bean, a pea leafminer and a parasitoid. From the bottom-up perspective, the rhythm was initiated from herbivore feeding, which triggered the rhythms of volatile emissions; then the rhythmic pattern of parasitoid activities was affected, and these rhythms were synchronized by a light switch signal. Increased volatile concentration can enhance the intensity of parasitoid locomotion and oviposition only under light. From the top-down perspective, naive and oviposition-experienced parasitoids were able to utilize the different volatile rhythm information from the damaged plant to locate host leafminers respectively. Our results indicated that the three interacting organisms in this system can achieve rhythmic functional synchronization under a natural light-dark photoperiod, but not under constant light or darkness. These findings provide new insight into the rhythm synchronization of three key players that contribute to the utilization of light and chemical signals, and our results may be used as potential approaches for manipulating natural enemies. PMID:20552008

  2. Advancing Systems Biology in the International Conference on Intelligent Biology and Medicine (ICIBM) 2015.

    PubMed

    Zhao, Zhongming; Liu, Yunlong; Huang, Yufei; Huang, Kun; Ruan, Jianhua

    2016-08-26

    The 2015 International Conference on Intelligent Biology and Medicine (ICIBM 2015) was held on November 13-15, 2015 in Indianapolis, Indiana, USA. ICIBM 2015 included eight scientific sessions, three tutorial sessions, one poster session, and four keynote presentations that covered the frontier research in broad areas related to bioinformatics, systems biology, big data science, biomedical informatics, pharmacogenomics, and intelligent computing. Here, we present a summary of the 10 research articles that were selected from ICIBM 2015 and included in the supplement to BMC Systems Biology.

  3. Integrative Systems Biology for Data Driven Knowledge Discovery

    PubMed Central

    Greene, Casey S.; Troyanskaya, Olga G.

    2015-01-01

    Integrative systems biology is an approach that brings together diverse high throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost effective manner. Using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of yet unknown components of a system of interest and how its malfunction leads to disease. PMID:21044756

  4. Robert Rosen in the age of systems biology.

    PubMed

    Thomas, S Randall

    2007-10-01

    The widespread use of the term Systems Biology (SB) signals a welcome recognition that organisms must be understood as integrated systems. Although just what this is taken to mean varies from one group to another, it generally implies a focus on biological functions and processes rather than on biological parts and a reliance on mathematical modeling to arrive at an understanding of these biological processes based on biological observations or measurements. SB, thus, falls directly in the line of reflection carried out by Robert Rosen throughout his work. In the present article, we briefly introduce the various currents of SB and then point out several ways Rosen's work can be used to avoid certain pitfalls associated with the use of dynamical systems models for the study of complex systems, as well as to inspire a productive path forward based on loosely organized cooperation among dispersed laboratories.

  5. Electromagnetic fields as structure-function zeitgebers in biological systems: environmental orchestrations of morphogenesis and consciousness

    PubMed Central

    Rouleau, Nicolas; Dotta, Blake T.

    2014-01-01

    Within a cell system structure dictates function. Any interaction between cells, or a cell and its environment, has the potential to have long term implications on the function of a given cell and emerging cell aggregates. The structure and function of cells are continuously subjected to modification by electrical and chemical stimuli. However, biological systems are also subjected to an ever-present influence: the electromagnetic (EM) environment. Biological systems have the potential to be influenced by subtle energies which are exchanged at atomic and subatomic scales as EM phenomena. These energy exchanges have the potential to manifest at higher orders of discourse and affect the output (behavior) of a biological system. Here we describe theoretical and experimental evidence of EM influence on cells and the integration of whole systems. Even weak interactions between EM energies and biological systems display the potential to affect a developing system. We suggest the growing literature of EM effects on biological systems has significant implications to the cell and its functional aggregates. PMID:25426035

  6. Identifying biologically meaningful hot-weather events using threshold temperatures that affect life-history.

    PubMed

    Cunningham, Susan J; Kruger, Andries C; Nxumalo, Mthobisi P; Hockey, Philip A R

    2013-01-01

    Increases in the frequency, duration and intensity of heat waves are frequently evoked in climate change predictions. However, there is no universal definition of a heat wave. Recent, intense hot weather events have caused mass mortalities of birds, bats and even humans, making the definition and prediction of heat wave events that have the potential to impact populations of different species an urgent priority. One possible technique for defining biologically meaningful heat waves is to use threshold temperatures (T(thresh)) above which known fitness costs are incurred by species of interest. We set out to test the utility of this technique using T(thresh) values that, when exceeded, affect aspects of the fitness of two focal southern African bird species: the southern pied babbler Turdiodes bicolor (T(thresh) = 35.5 °C) and the common fiscal Lanius collaris (T(thresh) = 33 °C). We used these T(thresh) values to analyse trends in the frequency, duration and intensity of heat waves of magnitude relevant to the focal species, as well as the annual number of hot days (maximum air temperature > T(thresh)), in north-western South Africa between 1961 and 2010. Using this technique, we were able to show that, while all heat wave indices increased during the study period, most rapid increases for both species were in the annual number of hot days and in the maximum intensity (and therefore intensity variance) of biologically meaningful heat waves. Importantly, we also showed that warming trends were not uniform across the study area and that geographical patterns in warming allowed both areas of high risk and potential climate refugia to be identified. We discuss the implications of the trends we found for our focal species, and the utility of the T(thresh) technique as a conservation tool.

  7. Methods of information geometry in computational system biology (consistency between chemical and biological evolution).

    PubMed

    Astakhov, Vadim

    2009-01-01

    Interest in simulation of large-scale metabolic networks, species development, and genesis of various diseases requires new simulation techniques to accommodate the high complexity of realistic biological networks. Information geometry and topological formalisms are proposed to analyze information processes. We analyze the complexity of large-scale biological networks as well as transition of the system functionality due to modification in the system architecture, system environment, and system components. The dynamic core model is developed. The term dynamic core is used to define a set of causally related network functions. Delocalization of dynamic core model provides a mathematical formalism to analyze migration of specific functions in biosystems which undergo structure transition induced by the environment. The term delocalization is used to describe these processes of migration. We constructed a holographic model with self-poetic dynamic cores which preserves functional properties under those transitions. Topological constraints such as Ricci flow and Pfaff dimension were found for statistical manifolds which represent biological networks. These constraints can provide insight on processes of degeneration and recovery which take place in large-scale networks. We would like to suggest that therapies which are able to effectively implement estimated constraints, will successfully adjust biological systems and recover altered functionality. Also, we mathematically formulate the hypothesis that there is a direct consistency between biological and chemical evolution. Any set of causal relations within a biological network has its dual reimplementation in the chemistry of the system environment.

  8. An evaluation of a foundational course in high school biology as measured by cognitive and affective factors

    NASA Astrophysics Data System (ADS)

    Rudolph, Cynthia Thompson

    There is little written about the use of foundational courses in high school science. This study seeks to identify if a foundational course in high school biology improves student outcomes as measured by Biology I EOC exam proficiency scale scores and student growth. Efforts were made to determine differences in cognitive skill areas and affective/conative skill areas as students progress from the foundational course of Greenhouse Biology (GH Bio) to Biology I. Three years of test score data from over 15,000 student participants are evaluated, as well as extant survey data from biology teachers and district student scheduling personnel. Findings from the study indicate GH Bio does make a difference in academic outcomes in students taking the foundational course before taking the Biology I course, and subsequently, the Biology I EOC exam. Findings also show there are cognitive, affective, and conative differences between the GH Bio students and their non-GH Bio peers while in Biology I. The study also seeks to determine why some students are scheduled for GH Bio and others are not. Findings indicate there are variances as to the reasons and intent for scheduling students into GH Bio. Some students who could benefit from the course are not being scheduled into the course.

  9. Functional connectivity in the resting brain as biological correlate of the Affective Neuroscience Personality Scales.

    PubMed

    Deris, Nadja; Montag, Christian; Reuter, Martin; Weber, Bernd; Markett, Sebastian

    2017-02-15

    According to Jaak Panksepp's Affective Neuroscience Theory and the derived self-report measure, the Affective Neuroscience Personality Scales (ANPS), differences in the responsiveness of primary emotional systems form the basis of human personality. In order to investigate neuronal correlates of personality, the underlying neuronal circuits of the primary emotional systems were analyzed in the present fMRI-study by associating the ANPS to functional connectivity in the resting brain. N=120 healthy participants were invited for the present study. The results were reinvestigated in an independent, smaller sample of N=52 participants. A seed-based whole brain approach was conducted with seed-regions bilaterally in the basolateral and superficial amygdalae. The selection of seed-regions was based on meta-analytic data on affective processing and the Juelich histological atlas. Multiple regression analyses on the functional connectivity maps revealed associations with the SADNESS-scale in both samples. Functional resting-state connectivity between the left basolateral amygdala and a cluster in the postcentral gyrus, and between the right basolateral amygdala and clusters in the superior parietal lobe and subgyral in the parietal lobe was associated with SADNESS. No other ANPS-scale revealed replicable results. The present findings give first insights into the neuronal basis of the SADNESS-scale of the ANPS and support the idea of underlying neuronal circuits. In combination with previous research on genetic associations of the ANPS functional resting-state connectivity is discussed as a possible endophenotype of personality.

  10. Evolutionary systems biology of amino acid biosynthetic cost in yeast.

    PubMed

    Barton, Michael D; Delneri, Daniela; Oliver, Stephen G; Rattray, Magnus; Bergman, Casey M

    2010-08-17

    Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental conditions, we conclude that

  11. Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

    PubMed

    Degrazio, Dominick

    Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level.

  12. Synthetic biology: advancing the design of diverse genetic systems

    PubMed Central

    Wang, Yen-Hsiang; Wei, Kathy Y.; Smolke, Christina D.

    2013-01-01

    A main objective of synthetic biology is to make the process of designing genetically-encoded biological systems more systematic, predictable, robust, scalable, and efficient. The examples of genetic systems in the field vary widely in terms of operating hosts, compositional approaches, and network complexity, ranging from a simple genetic switch to search-and-destroy systems. While significant advances in synthesis capabilities support the potential for the implementation of pathway- and genome-scale programs, several design challenges currently restrict the scale of systems that can be reasonably designed and implemented. Synthetic biology offers much promise in developing systems to address challenges faced in manufacturing, the environment and sustainability, and health and medicine, but the realization of this potential is currently limited by the diversity of available parts and effective design frameworks. As researchers make progress in bridging this design gap, advances in the field hint at ever more diverse applications for biological systems. PMID:23413816

  13. Tracing organizing principles: learning from the history of systems biology.

    PubMed

    Green, Sara; Wolkenhauer, Olaf

    2013-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to "reverse engineer" the functional organization of biological systems using methodologies from mathematics, engineering and computer science while taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational and system-level properties, ii) the inherent critique of reductionism and fragmentation of knowledge resulting from overspecialization, and iii) the insight that the ideal of formulating abstract organizing principles is complementary to, rather than conflicting with, the aim of formulating detailed explanations of biological mechanisms. We argue that looking back not only helps us understand the current practice but also points to possible future directions for systems biology.

  14. The reallocation of carbon in P deficient lupins affects biological nitrogen fixation.

    PubMed

    Kleinert, Aleysia; Venter, Mauritz; Kossmann, Jens; Valentine, Alexander

    2014-11-01

    It is not known how phosphate (P) deficiency affects the allocation of carbon (C) to biological nitrogen fixation (BNF) in legumes. The alteration of the respiratory and photosynthetic C costs of BNF was investigated under P deficiency. Although BNF can impose considerable sink stimulation on host respiratory and photosynthetic C, it is not known how the change in the C and energy allocation during P deficiency may affect BNF. Nodulated Lupinus luteus plants were grown in sand culture, using a modified Long Ashton nutrient solution containing no nitrogen (N) for ca. four weeks, after which one set was exposed to a P-deficient nutrient medium, while the other set continued growing on a P-sufficient nutrient medium. Phosphorus stress was measured at 20 days after onset of P-starvation. During P stress the decline in nodular P levels was associated with lower BNF and nodule growth. There was also a shift in the balance of photosynthetic and respiratory C toward a loss of C during P stress. Below-ground respiration declined under limiting P conditions. However, during this decline there was also a shift in the proportion of respiratory energy from maintenance toward growth respiration. Under P stress, there was an increased allocation of C toward root growth, thereby decreasing the amount of C available for maintenance respiration. It is therefore possible that the decline in BNF under P deficiency may be due to this change in resource allocation away from respiration associated with direct nutrient uptake, but rather toward a long term nutrient acquisition strategy of increased root growth.

  15. Systems approaches for synthetic biology: a pathway toward mammalian design.

    PubMed

    Rekhi, Rahul; Qutub, Amina A

    2013-01-01

    We review methods of understanding cellular interactions through computation in order to guide the synthetic design of mammalian cells for translational applications, such as regenerative medicine and cancer therapies. In doing so, we argue that the challenges of engineering mammalian cells provide a prime opportunity to leverage advances in computational systems biology. We support this claim systematically, by addressing each of the principal challenges to existing synthetic bioengineering approaches-stochasticity, complexity, and scale-with specific methods and paradigms in systems biology. Moreover, we characterize a key set of diverse computational techniques, including agent-based modeling, Bayesian network analysis, graph theory, and Gillespie simulations, with specific utility toward synthetic biology. Lastly, we examine the mammalian applications of synthetic biology for medicine and health, and how computational systems biology can aid in the continued development of these applications.

  16. Functional groups affect physical and biological properties of dextran-based hydrogels.

    PubMed

    Sun, Guoming; Shen, Yu-I; Ho, Chia Chi; Kusuma, Sravanti; Gerecht, Sharon

    2010-06-01

    Modification of dextran backbone allows the development of a hydrogel with specific characteristics. To enhance their functionality for tissue-engineered scaffolds, a series of dextran-based macromers was synthesized by incorporating various functional groups, including allyl isocyanate (Dex-AI), ethylamine (Dex-AE), chloroacetic acid (Dex-AC), or maleic-anhydride (Dex-AM) into dextrans. The dextran-based biodegradable hybrid hydrogels are developed by integrating polyethylene glycol diacrylate (PEGDA). To explore the effect of different derivatives on hydrogel properties, three different ratios of Dex/PEGDA are examined: low (20/80), medium (40/60), and high (60/40). Differences in physical and biological properties of the hydrogels are found, including swelling, degradation rate, mechanics, crosslinking density, biocompatibility (in vitro and in vivo), and vascular endothelial growth factor release. The results also indicate that the incorporation of amine groups into dextran gives rise to hydrogels with better biocompatible and release properties. We, therefore, conclude that the incorporation of different functional groups affects the fundamental properties of a dextran-based hydrogel network, and that amine groups are preferred to generate hydrogels for biomedical use.

  17. Cognitive structure and the affective domain: on knowing and feeling in biology

    NASA Astrophysics Data System (ADS)

    Thompson, Tressa L.; Mintzes, Joel J.

    2002-06-01

    This cross-age study explored the structural complexity and propositional validity of knowledge about and attitudes toward sharks, and the relationships among knowledge and attitudes. Responses were elicited from a convenience sample of students (5th, 8th and 11th grade, and college level) and senior citizens (n = 238). All subjects constructed a concept map on sharks and responded to a Likert-type attitude inventory. Based on the work of Novak and Gowin (Leaning How to Learn, Cambridge University Press, 1984), concept maps were scored for frequencies of non-redundant concepts and scientifically valid relationships, levels of hierarchy, incidence of branching and number of crosslinks. The attitude inventory, emerging from Kellert's (The Value of Life: Biological Diversity and Human Society, Island Press, 1996) work, generated subscale scores on four affective dimensions: scientific, naturalistic, moralistic and utilitarian/negative. Significant differences were found among subject groups on all knowledge structure variables and attitudinal dimensions. Gender differences were documented on three of four attitude subscales. A series of simple, mulitiple and canonical correlations revealed moderately strong relationships between knowledge structure variables and attitudinal dimensions. The pattern of these relationships supports conservation education efforts and instructional practices that encourage meaningful learning, knowledge restructuring and conceptual change (Mintzes et al., Assessing Science Understanding: A Human Constructivist View, Academic Press, 2000).

  18. Food source affects the expression of vitellogenin and fecundity of a biological control agent, Neoseiulus cucumeris.

    PubMed

    Zhao, Yunlong; Li, Dunsong; Zhang, Min; Chen, Wei; Zhang, Guren

    2014-07-01

    Neoseiulus cucumeris (Oudemans) (Acari: Phytoseiidae) is one of the most widely used and important biological control agents for thrips and other small pests worldwide. In the present study, we cloned two cDNAs of vitellogenins (Vgs, NcVg1 and NcVg2) and analyzed the effect of food source on the expression of both Vgs and fecundity in female adults. NcVgs showed higher sequence similarity to Vgs from Parasitiformes. Both neighbor-joining and maximum likelihood methods for phylogenetic analysis of NcVgs yielded similar topologies and showed that the Parasitiformes except Haemaphysalis longicornis segregated into a single clade that was separated into two subclades including one of both Vgs from N. cucumeris. Both transcripts, NcVg1 and NcVg2 revealed similar trends during developmental periods and reached the maximum level at the pre-oviposition period. When fed with different food sources, both NcVg1 and NcVg2 of female adults demonstrated a significant difference (P < 0.05) during the pre-oviposition period. Meanwhile, a positive correlation between the expression of Vgs and fecundity was observed. Therefore, the nutrients provided by the food sources affected fecundity resulting in differential expression of Vgs. Vitellogenin expression can be used as a molecular marker of fecundity of N. cucumeris.

  19. Noninvasive biological sensor system for detection of drunk driving.

    PubMed

    Murata, Kohji; Fujita, Etsunori; Kojima, Shigeyuki; Maeda, Shinitirou; Ogura, Yumi; Kamei, Tsutomu; Tsuji, Toshio; Kaneko, Shigehiko; Yoshizumi, Masao; Suzuki, Nobutaka

    2011-01-01

    Systems capable of monitoring the biological condition of a driver and issuing warnings during instances of drowsiness have recently been studied. Moreover, many researchers have reported that biological signals, such as brain waves, pulsation waves, and heart rate, are different between people who have and have not consumed alcohol. Currently, we are developing a noninvasive system to detect individuals driving under the influence of alcohol by measuring biological signals. We used the frequency time series analysis to attempt to distinguish between normal and intoxicated states of a person as the basis of the sensing system.

  20. Virtual Tissues and Developmental Systems Biology (book chapter)

    EPA Science Inventory

    Virtual tissue (VT) models provide an in silico environment to simulate cross-scale properties in specific tissues or organs based on knowledge of the underlying biological networks. These integrative models capture the fundamental interactions in a biological system and enable ...

  1. Systems Biology-Derived Discoveries of Intrinsic Clocks

    PubMed Central

    Millius, Arthur; Ueda, Hiroki R.

    2017-01-01

    A systems approach to studying biology uses a variety of mathematical, computational, and engineering tools to holistically understand and model properties of cells, tissues, and organisms. Building from early biochemical, genetic, and physiological studies, systems biology became established through the development of genome-wide methods, high-throughput procedures, modern computational processing power, and bioinformatics. Here, we highlight a variety of systems approaches to the study of biological rhythms that occur with a 24-h period—circadian rhythms. We review how systems methods have helped to elucidate complex behaviors of the circadian clock including temperature compensation, rhythmicity, and robustness. Finally, we explain the contribution of systems biology to the transcription–translation feedback loop and posttranslational oscillator models of circadian rhythms and describe new technologies and “–omics” approaches to understand circadian timekeeping and neurophysiology. PMID:28220104

  2. Systems Biology-Derived Discoveries of Intrinsic Clocks.

    PubMed

    Millius, Arthur; Ueda, Hiroki R

    2017-01-01

    A systems approach to studying biology uses a variety of mathematical, computational, and engineering tools to holistically understand and model properties of cells, tissues, and organisms. Building from early biochemical, genetic, and physiological studies, systems biology became established through the development of genome-wide methods, high-throughput procedures, modern computational processing power, and bioinformatics. Here, we highlight a variety of systems approaches to the study of biological rhythms that occur with a 24-h period-circadian rhythms. We review how systems methods have helped to elucidate complex behaviors of the circadian clock including temperature compensation, rhythmicity, and robustness. Finally, we explain the contribution of systems biology to the transcription-translation feedback loop and posttranslational oscillator models of circadian rhythms and describe new technologies and "-omics" approaches to understand circadian timekeeping and neurophysiology.

  3. In Vitro Electrochemistry of Biological Systems

    PubMed Central

    Adams, Kelly L.; Puchades, Maja; Ewing, Andrew G.

    2009-01-01

    This article reviews recent work involving electrochemical methods for in vitro analysis of biomolecules, with an emphasis on detection and manipulation at and of single cells and cultures of cells. The techniques discussed include constant potential amperometry, chronoamperometry, cellular electroporation, scanning electrochemical microscopy, and microfluidic platforms integrated with electrochemical detection. The principles of these methods are briefly described, followed in most cases with a short description of an analytical or biological application and its significance. The use of electrochemical methods to examine specific mechanistic issues in exocytosis is highlighted, as a great deal of recent work has been devoted to this application. PMID:20151038

  4. Affective Neuronal Selection: The Nature of the Primordial Emotion Systems

    PubMed Central

    Toronchuk, Judith A.; Ellis, George F. R.

    2013-01-01

    Based on studies in affective neuroscience and evolutionary psychiatry, a tentative new proposal is made here as to the nature and identification of primordial emotional systems. Our model stresses phylogenetic origins of emotional systems, which we believe is necessary for a full understanding of the functions of emotions and additionally suggests that emotional organizing systems play a role in sculpting the brain during ontogeny. Nascent emotional systems thus affect cognitive development. A second proposal concerns two additions to the affective systems identified by Panksepp. We suggest there is substantial evidence for a primary emotional organizing program dealing with power, rank, dominance, and subordination which instantiates competitive and territorial behavior and is an evolutionary contributor to self-esteem in humans. A program underlying disgust reactions which originally functioned in ancient vertebrates to protect against infection and toxins is also suggested. PMID:23316177

  5. Systems Biology and Genomics of Breast Cancer

    PubMed Central

    Perou, Charles M.; Børresen-Dale, Anne-Lise

    2011-01-01

    It is now accepted that breast cancer is not a single disease, but instead it is composed of a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Gene expression profiling using DNA microarrays has contributed significantly to our understanding of the molecular heterogeneity of breast tumor formation, progression, and recurrence. For example, at least two clinical diagnostic assays exist (i.e., OncotypeDX RS and Mammaprint®) that are able to predict outcome in patients using patterns of gene expression and predetermined mathematical algorithms. In addition, a new molecular taxonomy based upon the inherent, or “intrinsic,” biology of breast tumors has been developed; this taxonomy is called the “intrinsic subtypes of breast cancer,” which now identifies five distinct tumor types and a normal breast-like group. Importantly, the intrinsic subtypes of breast cancer predict patient relapse, overall survival, and response to endocrine and chemotherapy regimens. Thus, most of the clinical behavior of a breast tumor is already written in its subtype profile. Here, we describe the discovery and basic biology of the intrinsic subtypes of breast cancer, and detail how this interacts with underlying genetic alternations, response to therapy, and the metastatic process. PMID:21047916

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

    PubMed

    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).

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

    PubMed Central

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

    2014-01-01

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

  8. Impact of yeast systems biology on industrial biotechnology.

    PubMed

    Petranovic, Dina; Vemuri, Goutham N

    2009-11-01

    Systems biology is yet an emerging discipline that aims to quantitatively describe and predict the functioning of a biological system. This nascent discipline relies on the recent advances in the analytical technology (such as DNA microarrays, mass spectromety, etc.) to quantify cellular characteristics (such as gene expression, protein and metabolite abundance, etc.) and computational methods to integrate information from these measurements. The model eukaryote, Saccharomyces cerevisiae, has played a pivotal role in the development of many of these analytical and computational methods and consequently is the biological system of choice for testing new hypotheses. The knowledge gained from such studies in S. cerevisiae is proving to be extremely useful in designing metabolism that is targeted to specific industrial applications. As a result, the portfolio of products that are being produced using this yeast is expanding rapidly. We review the recent developments in yeast systems biology and how they relate to industrial biotechnology.

  9. Advancing metabolic engineering through systems biology of industrial microorganisms.

    PubMed

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

    Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further.

  10. Multistability and its robustness of a class of biological systems.

    PubMed

    Li, Yuanlong; Lin, Zongli

    2013-12-01

    Multistability of biological systems with complex nonlinear regulatory schemes is an important research topic in system biology. In many models of biological systems, the regulatory functions are of saturation type. The linear sectors, in which the saturation type functions reside, have been extensively adopted to deal with these saturation type functions. The stability analysis resulting from linear sectors is however often conservative as a wide linear section is required to include a large portion of a saturation type function. In this paper, we utilize piecewise linear sectors, recently adopted in nonlinear control theory, to investigate multistability of a class of biological systems with sum regulatory schemes. We will estimate the domain of attraction of each stable equilibrium and examine the robust stability of each equilibrium in the face of disturbances that are bounded in magnitude or energy. A genetic toggle switch in Escherichia coli is employed as an example to illustrate the applicability and effectiveness of our analysis method.

  11. Software for systems biology: from tools to integrated platforms.

    PubMed

    Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

    2011-11-03

    Understanding complex biological systems requires extensive support from software tools. Such tools are needed at each step of a systems biology computational workflow, which typically consists of data handling, network inference, deep curation, dynamical simulation and model analysis. In addition, there are now efforts to develop integrated software platforms, so that tools that are used at different stages of the workflow and by different researchers can easily be used together. This Review describes the types of software tools that are required at different stages of systems biology research and the current options that are available for systems biology researchers. We also discuss the challenges and prospects for modelling the effects of genetic changes on physiology and the concept of an integrated platform.

  12. Light microscopy applications in systems biology: opportunities and challenges

    PubMed Central

    2013-01-01

    Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. PMID:23578051

  13. Learning Delayed Influences of Biological Systems

    PubMed Central

    Ribeiro, Tony; Magnin, Morgan; Inoue, Katsumi; Sakama, Chiaki

    2015-01-01

    Boolean networks are widely used model to represent gene interactions and global dynamical behavior of gene regulatory networks. To understand the memory effect involved in some interactions between biological components, it is necessary to include delayed influences in the model. In this paper, we present a logical method to learn such models from sequences of gene expression data. This method analyzes each sequence one by one to iteratively construct a Boolean network that captures the dynamics of these observations. To illustrate the merits of this approach, we apply it to learning real data from bioinformatic literature. Using data from the yeast cell cycle, we give experimental results and show the scalability of the method. We show empirically that using this method we can handle millions of observations and successfully capture delayed influences of Boolean networks. PMID:25642421

  14. Microfluidic systems for electrochemical and biological studies

    SciTech Connect

    Ackler, H., LLNL

    1998-05-01

    Microfluidic devices with microelectrodes have the potential to enable studies of phenomena at size scales where behavior may be dominated by different mechanisms than at macroscales. Through our work developing microfluidic devices for dielectrophoretic separation and sensing of cells and particles, we have fabricated devices from which general or more specialized research devices may be derived. Fluid channels from 80 {micro}m wide X 20 {micro}m deep to 1 mm wide to 200 {micro}m deep have been fabricated in glass, with lithographically patterned electrodes from 10 to 80 {micro}m wide on one or both sides on the channels and over topographies tens of microns in heights. the devices are designed to easily interface to electronic and fluidic interconnect packages that permit reuse of devices, rather than one-time use, crude glue-based methods. Such devices may be useful for many applications of interest to the electrochemical and biological community.

  15. Systems biology: a new tool for farm animal science.

    PubMed

    Hollung, Kristin; Timperio, Anna M; Olivan, Mamen; Kemp, Caroline; Coto-Montes, Ana; Sierra, Veronica; Zolla, Lello

    2014-03-01

    It is rapidly emerging that the tender meat phenotype is affected by an enormous amount of variables, not only tied to genetics (livestock breeding selection), but also to extrinsic factors, such as feeding conditions, physical activity, rearing environment, administration of hormonal growth promotants, pre-slaughter handling and stress. Proteomics has been widely accepted by meat scientists over the last years and is now commonly used to shed light on the postmortem processes involved in meat tenderization. This review discusses the latest findings with the use of proteomics and systems biology to study the different biochemical pathways postmortem aiming at understanding the concerted action of different molecular mechanisms responsible for meat quality. The conversion of muscle to meat postmortem can be described as a sequence of events involving molecular pathways controlled by a complex interplay of many factors. Among the different pathways emerging are the influence of apoptosis and lately also the role of autophagy in muscle postmortem development. This review thus, focus on how systems-wide integrated investigations (metabolomics, transcriptomics, interactomics, phosphoproteomics, mathematical modeling), which have emerged as complementary tools to proteomics, have helped establishing a few milestones in our understanding of the events leading from muscle to meat conversion.

  16. Toward Computer-Aided Affective Learning Systems: A Literature Review

    ERIC Educational Resources Information Center

    Moridis, C. N.; Economides, A. A.

    2008-01-01

    The aim of this survey is to provide an overview of the various components of "computer aided affective learning systems." The research is classified into 3 main scientific areas that are integral parts of the development of these kinds of systems. The three main scientific areas are: i) emotions and their connection to learning; ii) affect…

  17. Systems chemical biology and the Semantic Web: what they mean for the future of drug discovery research.

    PubMed

    Wild, David J; Ding, Ying; Sheth, Amit P; Harland, Lee; Gifford, Eric M; Lajiness, Michael S

    2012-05-01

    Systems chemical biology, the integration of chemistry, biology and computation to generate understanding about the way small molecules affect biological systems as a whole, as well as related fields such as chemogenomics, are central to emerging new paradigms of drug discovery such as drug repurposing and personalized medicine. Recent Semantic Web technologies such as RDF and SPARQL are technical enablers of systems chemical biology, facilitating the deployment of advanced algorithms for searching and mining large integrated datasets. In this paper, we aim to demonstrate how these technologies together can change the way that drug discovery is accomplished.

  18. Systems biology of asthma and allergic diseases: a multiscale approach.

    PubMed

    Bunyavanich, Supinda; Schadt, Eric E

    2015-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High-throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article we review the technologies and approaches for system-wide profiling, as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually captured health profiles will contribute to more accurate systems biology views of asthma and allergy.

  19. Non-equilibrium thermodynamics of thiol/disulfide redox systems: A perspective on redox systems biology

    PubMed Central

    Kemp, Melissa; Go, Young-Mi; Jones, Dean P.

    2008-01-01

    Understanding the dynamics of redox elements in biologic systems remains a major challenge for redox signaling and oxidative stress research. Central redox elements include evolutionarily conserved subsets of cysteines and methionines of proteins which function as sulfur switches and labile reactive oxygen species (ROS) and reactive nitrogen species (RNS) which function in redox signaling. The sulfur switches depend upon redox environments in which rates of oxidation are balanced with rates of reduction through the thioredoxins, glutathione/glutathione disulfide and cysteine/cystine redox couples. These central couples, which we term redox control nodes, are maintained at stable but non-equilibrium steady states, are largely independently regulated in different subcellular compartments and are quasi-independent from each other within compartments. Disruption of the redox control nodes can differentially affect sulfur switches, thereby creating a diversity of oxidative stress responses. Systems biology provides approaches to address the complexity of these responses. In the present review, we summarize thiol/disulfide pathway, redox potential and rate information as a basis for kinetic modeling of sulfur switches. The summary identifies gaps in knowledge especially related to redox communication between compartments, definition of redox pathways and discrimination between types of sulfur switches. A formulation for kinetic modeling of GSH/GSSG redox control indicates that systems biology could encourage novel therapeutic approaches to protect against oxidative stress by identifying specific redox-sensitive sites which could be targeted for intervention. PMID:18155672

  20. Exploring lipids with nonlinear optical microscopy in multiple biological systems

    NASA Astrophysics Data System (ADS)

    Alfonso-Garcia, Alba

    Lipids are crucial biomolecules for the well being of humans. Altered lipid metabolism may give rise to a variety of diseases that affect organs from the cardiovascular to the central nervous system. A deeper understanding of lipid metabolic processes would spur medical research towards developing precise diagnostic tools, treatment methods, and preventive strategies for reducing the impact of lipid diseases. Lipid visualization remains a complex task because of the perturbative effect exerted by traditional biochemical assays and most fluorescence markers. Coherent Raman scattering (CRS) microscopy enables interrogation of biological samples with minimum disturbance, and is particularly well suited for label-free visualization of lipids, providing chemical specificity without compromising on spatial resolution. Hyperspectral imaging yields large datasets that benefit from tailored multivariate analysis. In this thesis, CRS microscopy was combined with Raman spectroscopy and other label-free nonlinear optical techniques to analyze lipid metabolism in multiple biological systems. We used nonlinear Raman techniques to characterize Meibum secretions in the progression of dry eye disease, where the lipid and protein contributions change in ratio and phase segregation. We employed similar tools to examine lipid droplets in mice livers aboard a spaceflight mission, which lose their retinol content contributing to the onset of nonalcoholic fatty-liver disease. We also focused on atherosclerosis, a disease that revolves around lipid-rich plaques in arterial walls. We examined the lipid content of macrophages, whose variable phenotype gives rise to contrasting healing and inflammatory activities. We also proposed new label-free markers, based on lifetime imaging, for macrophage phenotype, and to detect products of lipid oxidation. Cholesterol was also detected in hepatitis C virus infected cells, and in specific strains of age-related macular degeneration diseased cells by

  1. New approaches in data integration for systems chemical biology.

    PubMed

    Seoane, Jose A; López-Campos, Guillermo; Dorado, Julian; Martin-Sanchez, Fernando

    2013-01-01

    Advances done in "-Omics" technologies in the last 20 years have made available to the researches huge amounts of data spanning a wide variety of biological processes from gene sequences to the metabolites present in a cell at a particular time. The management, analysis and representation of these data have been facilitated by mean of the advances made by biomedical informatics in areas such as data architecture and integration systems. However, despite the efforts done by biologists in this area, research in drug design adds a new level of information by incorporating data related with small molecules, which increases the complexity of these integration systems. Current knowledge in molecular biology has shown that it is possible to use comprehensive and integrative approaches to understand the biological processes from a systems perspective and that pathological processes can be mapped into biological networks. Therefore, current strategies for drug design are focusing on how to interact with or modify those networks to achieve the desired effects on what is called systems chemical biology. In this review several approaches for data integration in systems chemical biology will be analysed and described. Furthermore, because of the increasing relevance of the development and use of nanomaterials and their expected impact in the near future, the requirements of integration systems that incorporate these new data types associated with nanomaterials will also be analysed.

  2. Mathematical and Computational Modeling in Complex Biological Systems

    PubMed Central

    Li, Wenyang; Zhu, Xiaoliang

    2017-01-01

    The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology. PMID:28386558

  3. Apparatus and methods for manipulation and optimization of biological systems

    NASA Technical Reports Server (NTRS)

    Ho, Chih-Ming (Inventor); Wong, Pak Kin (Inventor); Sun, Ren (Inventor); Yu, Fuqu (Inventor)

    2012-01-01

    The invention provides systems and methods for manipulating, e.g., optimizing and controlling, biological systems, e.g., for eliciting a more desired biological response of biological sample, such as a tissue, organ, and/or a cell. In one aspect, systems and methods of the invention operate by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system, e.g., a bioreactor. In alternative aspects, systems include a device for sustaining cells or tissue samples, one or more actuators for stimulating the samples via biochemical, electromagnetic, thermal, mechanical, and/or optical stimulation, one or more sensors for measuring a biological response signal of the samples resulting from the stimulation of the sample. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The compositions and methods of the invention can be used, e.g., to for systems optimization of any biological manufacturing or experimental system, e.g., bioreactors for proteins, e.g., therapeutic proteins, polypeptides or peptides for vaccines, and the like, small molecules (e.g., antibiotics), polysaccharides, lipids, and the like. Another use of the apparatus and methods includes combination drug therapy, e.g. optimal drug cocktail, directed cell proliferations and differentiations, e.g. in tissue engineering, e.g. neural progenitor cells differentiation, and discovery of key parameters in complex biological systems.

  4. Systems Biology and Bioinformatics in Medical Applications

    DTIC Science & Technology

    2009-10-01

    number of genes affecting virulence toward Caenorhabditis elegans and Dictyostelium discoideum (40) that await further characteriza- tion. A well...complex by sequence analysis of the 16S-23S rRNA gene spacer region. J. Clin. Microbiol. 43:1632–1639. 9. Choi, C . H., E. Y. Lee, Y. C . Lee, T. I. Park, H...carried beta- lactamase gene Resistance gene (s) Class A Class C Class D Tetra-cycline Chloram- phenicol Trimetho- prim-sulfa gyrA/parC QRDRa AB0057

  5. Heparin affin regulatory peptide/pleiotrophin negatively affects diverse biological activities in C6 glioma cells.

    PubMed

    Parthymou, Anastasia; Lampropoulou, Evgenia; Mikelis, Constantinos; Drosou, Georgia; Papadimitriou, Evangelia

    2008-01-01

    Heparin affin regulatory peptide (HARP) or pleiotrophin seems to be involved in the progression of several tumors of diverse origin. In this study, we tried to determine the role of HARP in rat C6 glioma cells by using an antisense strategy for inhibition of HARP expression. Decrease of the expression of endogenous HARP in C6 cells (AS-C6 cells) significantly increased proliferation, migration, and anchorage-independent growth of cells. Implantation of AS-C6 cells onto chicken embryo chorioallantoic membranes resulted in a significant increase of tumor-induced angiogenesis compared with that induced by non-transfected or C6 cells transfected with the plasmid alone (PC-C6 cells). In the same line, conditioned medium from AS-C6 cells significantly increased endothelial cell proliferation, migration, and tube formation in vitro compared with the effect of conditioned medium from C6 or PC-C6 cells. Interestingly, vascular endothelial growth factor (VEGF) induced C6 cell proliferation and migration, and SU1496, a selective inhibitor of VEGF receptor 2 (VEGFR2), blocked increased glioma cell growth, migration, and angiogenicity observed in AS-C6 cell cultures. The above results seem to be due to a direct interaction between HARP and VEGF in the culture medium of C6 and PC-C6 cells, while AS-C6 cells secreted comparable amounts of VEGF that do not interact with HARP. Collectively, these data suggest that HARP negatively affects diverse biological activities in C6 glioma cells, mainly due to binding of HARP to VEGF, which may sequester secreted VEGF from signalling through VEGFR2.

  6. Bionic models for identification of biological systems

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2014-01-01

    Motivation: 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. Results: 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. Availability and implementation: 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. Contact: seunghwa.kang@pnnl.gov PMID:25064572

  8. Integrative system biology strategies for disease biomarker discovery.

    PubMed

    Zhang, Haiyuan; Hu, Hao; Deng, Cao; Chun, Yeona; Zhou, Shengtao; Huang, Fuqiang; Zhou, Qin

    2012-05-01

    Biomarkers are currently widely used to diagnose diseases, monitor treatments, and evaluate potential drug candidates. Research of differential Omics accelerate the advancements of biomarkers' discovery. By extracting biological knowledge from the 'omics' through integration, integrative system biology creates predictive models of cells, organs, biochemical processes and complete organisms, in addition to identifying human disease biomarkers. Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. Several integrative system biology approaches have been developed and applied to the discovery of disease biomarkers from databases. In this review, we highlight several of these approaches and identify future steps in the context of the field of integrative system biology.

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

    PubMed Central

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    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. PMID:26795950

  10. Integrated Design of Antibodies for Systems Biology Using Ab Designer.

    PubMed

    Pisitkun, Trairak; Dummer, Patrick; Somparn, Poorichaya; Hirankarn, Nattiya; Kopp, Jeffrey B; Knepper, Mark A

    2014-03-24

    In the current era of large-scale biology, systems biology has evolved as a powerful approach to identify complex interactions within biological systems. In addition to high throughput identification and quantification techniques, methods based on high-quality mono-specific antibodies remain an essential element of the approach. To assist the large-scale design and production of peptide-directed antibodies for systems biology studies, we developed a fully integrated online application, AbDesigner (http://helixweb.nih.gov/AbDesigner/), to help researchers select optimal peptide immunogens for antibody generation against relatively disordered regions of target proteins. Here we describe AbDesigner in terms of its features, comparing it to other software tools, and use it to design three antibodies against kidney disease-related proteins in human, viz. nephrin, podocin, and apolipoprotein L1.

  11. Virtual Tissues and Developmental Systems Biology

    EPA Science Inventory

    Computational modeling of embryonic systems to analyze how 'core development processes' are wired together. Has the potential to address environmental and human health factors with broad scientific and economic impacts.

  12. Construction of a Linux based chemical and biological information system.

    PubMed

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

    A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.

  13. Computational Proteomics: High-throughput Analysis for Systems Biology

    SciTech Connect

    Cannon, William R.; Webb-Robertson, Bobbie-Jo M.

    2007-01-03

    High-throughput (HTP) proteomics is a rapidly developing field that offers the global profiling of proteins from a biological system. The HTP technological advances are fueling a revolution in biology, enabling analyses at the scales of entire systems (e.g., whole cells, tumors, or environmental communities). However, simply identifying the proteins in a cell is insufficient for understanding the underlying complexity and operating mechanisms of the overall system. Systems level investigations are relying more and more on computational analyses, especially in the field of proteomics generating large-scale global data.

  14. TGF-β stimulation in human and murine cells reveals commonly affected biological processes and pathways at transcription level

    PubMed Central

    2014-01-01

    Background The TGF-β signaling pathway is a fundamental pathway in the living cell, which plays a key role in many central cellular processes. The complex and sometimes contradicting mechanisms by which TGF-β yields phenotypic effects are not yet completely understood. In this study we investigated and compared the transcriptional response profile of TGF-β1 stimulation in different cell types. For this purpose, extensive experiments are performed and time-course microarray data are generated in human and mouse parenchymal liver cells, human mesenchymal stromal cells and mouse hematopoietic progenitor cells at different time points. We applied a panel of bioinformatics methods on our data to uncover common patterns in the dynamic gene expression response in respective cells. Results Our analysis revealed a quite variable and multifaceted transcriptional response profile of TGF-β1 stimulation, which goes far beyond the well-characterized classical TGF-β1 signaling pathway. Nonetheless, we could identify several commonly affected processes and signaling pathways across cell types and species. In addition our analysis suggested an important role of the transcription factor EGR1, which appeared to have a conserved influence across cell-types and species. Validation via an independent dataset on A549 lung adenocarcinoma cells largely confirmed our findings. Network analysis suggested explanations, how TGF-β1 stimulation could lead to the observed effects. Conclusions The analysis of dynamical transcriptional response to TGF-β treatment experiments in different human and murine cell systems revealed commonly affected biological processes and pathways, which could be linked to TGF-β1 via network analysis. This helps to gain insights about TGF-β pathway activities in these cell systems and its conserved interactions between the species and tissue types. PMID:24886091

  15. Systems biology: the role of engineering in the reverse engineering of biological signaling.

    PubMed

    Iglesias, Pablo A

    2013-05-31

    One of the principle tasks of systems biology has been the reverse engineering of signaling networks. Because of the striking similarities to engineering systems, a number of analysis and design tools from engineering disciplines have been used in this process. This review looks at several examples including the analysis of homeostasis using control theory, the attenuation of noise using signal processing, statistical inference and the use of information theory to understand both binary decision systems and the response of eukaryotic chemotactic cells.

  16. Ideas and perspectives: climate-relevant marine biologically driven mechanisms in Earth system models

    NASA Astrophysics Data System (ADS)

    Hense, Inga; Stemmler, Irene; Sonntag, Sebastian

    2017-01-01

    The current generation of marine biogeochemical modules in Earth system models (ESMs) considers mainly the effect of marine biota on the carbon cycle. We propose to also implement other biologically driven mechanisms in ESMs so that more climate-relevant feedbacks are captured. We classify these mechanisms in three categories according to their functional role in the Earth system: (1) biogeochemical pumps, which affect the carbon cycling; (2) biological gas and particle shuttles, which affect the atmospheric composition; and (3) biogeophysical mechanisms, which affect the thermal, optical, and mechanical properties of the ocean. To resolve mechanisms from all three classes, we find it sufficient to include five functional groups: bulk phyto- and zooplankton, calcifiers, and coastal gas and surface mat producers. We strongly suggest to account for a larger mechanism diversity in ESMs in the future to improve the quality of climate projections.

  17. Circadian systems biology: When time matters

    PubMed Central

    Fuhr, Luise; Abreu, Mónica; Pett, Patrick; Relógio, Angela

    2015-01-01

    The circadian clock is a powerful endogenous timing system, which allows organisms to fine-tune their physiology and behaviour to the geophysical time. The interplay of a distinct set of core-clock genes and proteins generates oscillations in expression of output target genes which temporally regulate numerous molecular and cellular processes. The study of the circadian timing at the organismal as well as at the cellular level outlines the field of chronobiology, which has been highly interdisciplinary ever since its origins. The development of high-throughput approaches enables the study of the clock at a systems level. In addition to experimental approaches, computational clock models exist which allow the analysis of rhythmic properties of the clock network. Such mathematical models aid mechanistic understanding and can be used to predict outcomes of distinct perturbations in clock components, thereby generating new hypotheses regarding the putative function of particular clock genes. Perturbations in the circadian timing system are linked to numerous molecular dysfunctions and may result in severe pathologies including cancer. A comprehensive knowledge regarding the mechanistic of the circadian system is crucial to develop new procedures to investigate pathologies associated with a deregulated clock. In this manuscript we review the combination of experimental methodologies, bioinformatics and theoretical models that have been essential to explore this remarkable timing-system. Such an integrative and interdisciplinary approach may provide new strategies with regard to chronotherapeutic treatment and new insights concerning the restoration of the circadian timing in clock-associated diseases. PMID:26288701

  18. Learned Inequality: Racial Labels in the Biology Curriculum Can Affect the Development of Racial Prejudice

    ERIC Educational Resources Information Center

    Donovan, Brian M.

    2017-01-01

    For over a century, genetic arguments for the existence of racial inequality have been used to oppose policies that promote social equality. And, over that same time period, American biology textbooks have repeatedly discussed genetic differences between races. This experiment tests whether racial terminology in the biology curriculum causes…

  19. Biological treatment of clogged emitters in a drip irrigation system.

    PubMed

    Sahin, Ustün; Anapali, Omer; Dönmez, Mesude Figen; Sahin, Fikrettin

    2005-09-01

    This study was conducted to investigate microbial organisms that can be used for preventing clogging in drip irrigation systems caused by biological factors. A total of 25 fungi isolate and 121 bacterial strains were isolated from water samples collected from drip irrigation systems in tomato greenhouses in the eastern Anatolia region of Turkey in the spring season of 2001. Biological clogging of emitters in a model drip irrigation system was experimentally caused by application of the microorganisms (fungi and bacteria) isolated in the study. Three antagonistic bacterial strains in the genus Bacillus spp (ERZ, OSU-142) and Burkholdria spp (OSU-7) were used for treatment of biological clogging of the emitters. The results showed that the antagonistic bacterial strains tested have the potential to be used as anti-clogging agents for treatment of emitters in drip irrigation system. This is the first study that demonstrated that antagonistic microorganisms can be utilized for treatment of clogging in drip irrigation systems.

  20. Using the Unified Modelling Language (UML) to guide the systemic description of biological processes and systems.

    PubMed

    Roux-Rouquié, Magali; Caritey, Nicolas; Gaubert, Laurent; Rosenthal-Sabroux, Camille

    2004-07-01

    One of the main issues in Systems Biology is to deal with semantic data integration. Previously, we examined the requirements for a reference conceptual model to guide semantic integration based on the systemic principles. In the present paper, we examine the usefulness of the Unified Modelling Language (UML) to describe and specify biological systems and processes. This makes unambiguous representations of biological systems, which would be suitable for translation into mathematical and computational formalisms, enabling analysis, simulation and prediction of these systems behaviours.

  1. Applications of targeted proteomics in systems biology and translational medicine

    PubMed Central

    Root, Alex; Sander, Chris; Aebersold, Ruedi

    2015-01-01

    Biological systems are composed of numerous components of which proteins are of particularly high functional significance. Network models are useful abstractions for studying these components in context. Network representations display molecules as nodes and their interactions as edges. Because they are difficult to directly measure, functional edges are frequently inferred from suitably structured datasets consisting of the accurate and consistent quantification of network nodes under a multitude of perturbed conditions. For the precise quantification of a finite list of proteins across a wide range of samples, targeted proteomics exemplified by selected/multiple reaction monitoring (SRM, MRM) mass spectrometry has proven useful and has been applied to a variety of questions in systems biology and clinical studies. Here, we survey the literature of studies using SRM‐MS in systems biology and clinical proteomics. Systems biology studies frequently examine fundamental questions in network biology, whereas clinical studies frequently focus on biomarker discovery and validation in a variety of diseases including cardiovascular disease and cancer. Targeted proteomics promises to advance our understanding of biological networks and the phenotypic significance of specific network states and to advance biomarkers into clinical use. PMID:26097198

  2. Engineering plant metabolism into microbes: from systems biology to synthetic biology.

    PubMed

    Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

    2013-04-01

    Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms.

  3. COULD ETHINYL ESTRADIOL AFFECT THE POPULATION BIOLOGY OF CUNNER, TAUTOGOLABRUS ADSPERSUS

    EPA Science Inventory

    Endocrine disrupting chemicals in the environment may disturb the population dynamics of wildlife by affecting reproductive output and embryonic development of organisms. This study used a population model to evaluate whether ethinyl estradiol (EE2 could affect cunner Tautogolabr...

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

    PubMed Central

    2010-01-01

    Background 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. Results 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. Conclusions 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. PMID:21114840

  5. Neural systems supporting the control of affective and cognitive conflicts.

    PubMed

    Ochsner, Kevin N; Hughes, Brent; Robertson, Elaine R; Cooper, Jeffrey C; Gabrieli, John D E

    2009-09-01

    Although many studies have examined the neural bases of controlling cognitive responses, the neural systems for controlling conflicts between competing affective responses remain unclear. To address the neural correlates of affective conflict and their relationship to cognitive conflict, the present study collected whole-brain fMRI data during two versions of the Eriksen flanker task. For these tasks, participants indicated either the valence (affective task) or the semantic category (cognitive task) of a central target word while ignoring flanking words that mapped onto either the same (congruent) or a different (incongruent) response as the target. Overall, contrasts of incongruent > congruent trials showed that bilateral dorsal ACC, posterior medial frontal cortex, and dorsolateral pFC were active during both kinds of conflict, whereas rostral medial pFC and left ventrolateral pFC were differentially active during affective or cognitive conflict, respectively. Individual difference analyses showed that separate regions of rostral cingulate/ventromedial pFC and left ventrolateral pFC were positively correlated with the magnitude of response time interference. Taken together, the findings that controlling affective and cognitive conflicts depends upon both common and distinct systems have important implications for understanding the organization of control systems in general and their potential dysfunction in clinical disorders.

  6. EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY

    PubMed Central

    Davidson, Eric H.

    2011-01-01

    At present several entirely different explanatory approaches compete to illuminate the mechanisms by which animal body plans have evolved. Their respective relevance is briefly considered here in the light of modern knowledge of genomes and the regulatory processes by which development is controlled. Just as development is a system property of the regulatory genome, so causal explanation of evolutionary change in developmental process must be considered at a system level. Here I enumerate some mechanistic consequences that follow from the conclusion that evolution of the body plan has occurred by alteration of the structure of developmental gene regulatory networks. The hierarchy and multiple additional design features of these networks act to produce Boolean regulatory state specification functions at upstream phases of development of the body plan. These are created by the logic outputs of network subcircuits, and in modern animals these outputs are impervious to continuous adaptive variation unlike genes operating more peripherally in the network. PMID:21320483

  7. Evolutionary bioscience as regulatory systems biology.

    PubMed

    Davidson, Eric H

    2011-09-01

    At present several entirely different explanatory approaches compete to illuminate the mechanisms by which animal body plans have evolved. Their respective relevance is briefly considered here in the light of modern knowledge of genomes and the regulatory processes by which development is controlled. Just as development is a system property of the regulatory genome, causal explanation of evolutionary change in developmental process must be considered at a system level. Here I enumerate some mechanistic consequences that follow from the conclusion that evolution of the body plan has occurred by alteration of the structure of developmental gene regulatory networks. The hierarchy and multiple additional design features of these networks act to produce Boolean regulatory state specification functions at upstream phases of development of the body plan. These are created by the logic outputs of network subcircuits, and in modern animals these outputs are impervious to continuous adaptive variation unlike genes operating more peripherally in the network.

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

    PubMed

    Thompson, R C A; Jenkins, D J

    2014-10-15

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

  9. Single cell sequencing approaches for complex biological systems.

    PubMed

    Baslan, Timour; Hicks, James

    2014-06-01

    Biological phenotype is the output of complex interactions between heterogeneous cells within a specified niche. These interactions are tightly governed and regulated by the genetic, epigenetic, and transcriptional states of single cells, with deregulation of these states resulting in disease. As such, genome wide single cell investigations are bound to enhance our knowledge of the underlying principles that govern biological systems. Recent technological advances have enabled such investigations in the form of single-cell sequencing. Here, we review the most recent developments in genome wide profiling of single cells, discuss some of the novel biological observations gleaned by such investigations, and touch upon the promise of single cell sequencing in unraveling biological systems.

  10. Thermostability of Biological Systems: Fundamentals, Challenges, and Quantification

    PubMed Central

    He, Xiaoming

    2011-01-01

    This review examines the fundamentals and challenges in engineering/understanding the thermostability of biological systems over a wide temperature range (from the cryogenic to hyperthermic regimen). Applications of the bio-thermostability engineering to either destroy unwanted or stabilize useful biologicals for the treatment of diseases in modern medicine are first introduced. Studies on the biological responses to cryogenic and hyperthermic temperatures for the various applications are reviewed to understand the mechanism of thermal (both cryo and hyperthermic) injury and its quantification at the molecular, cellular and tissue/organ levels. Methods for quantifying the thermophysical processes of the various applications are then summarized accounting for the effect of blood perfusion, metabolism, water transport across cell plasma membrane, and phase transition (both equilibrium and non-equilibrium such as ice formation and glass transition) of water. The review concludes with a summary of the status quo and future perspectives in engineering the thermostability of biological systems. PMID:21769301

  11. Biological indicators for monitoring water quality of MTF canals system

    NASA Technical Reports Server (NTRS)

    Sethi, S. L.

    1975-01-01

    Biological models, diversity indexes, were developed to predict environmental effects of NASA's Mississippi test facility (MTF) chemical operations on canal systems in the area. To predict the effects on local streams, a physical model of unpolluted streams was established. The model is fed by artesian well water free of background levels of pollutants. The species diversity and biota composition of unpolluted MTF stream was determined; resulting information will be used to form baseline data for future comparisons. Biological modeling was accomplished by adding controlled quantities or kinds of chemical pollutants and evaluating the effects of these chemicals on the biological life of the stream.

  12. Human likeness: cognitive and affective factors affecting adoption of robot-assisted learning systems

    NASA Astrophysics Data System (ADS)

    Yoo, Hosun; Kwon, Ohbyung; Lee, Namyeon

    2016-07-01

    With advances in robot technology, interest in robotic e-learning systems has increased. In some laboratories, experiments are being conducted with humanoid robots as artificial tutors because of their likeness to humans, the rich possibilities of using this type of media, and the multimodal interaction capabilities of these robots. The robot-assisted learning system, a special type of e-learning system, aims to increase the learner's concentration, pleasure, and learning performance dramatically. However, very few empirical studies have examined the effect on learning performance of incorporating humanoid robot technology into e-learning systems or people's willingness to accept or adopt robot-assisted learning systems. In particular, human likeness, the essential characteristic of humanoid robots as compared with conventional e-learning systems, has not been discussed in a theoretical context. Hence, the purpose of this study is to propose a theoretical model to explain the process of adoption of robot-assisted learning systems. In the proposed model, human likeness is conceptualized as a combination of media richness, multimodal interaction capabilities, and para-social relationships; these factors are considered as possible determinants of the degree to which human cognition and affection are related to the adoption of robot-assisted learning systems.

  13. Enterobacter aerogenes Needle Stick Leads to Improved Biological Management System

    SciTech Connect

    Johanson, Richard E.

    2004-08-01

    A laboratory worker who received a needle stick from a contaminated needle while working with a culture containing Enterobactor aerogenes developed a laboratory acquired infection. Although this organism has been shown to cause community and nosocomial infections, there have been no documented cases of a laboratory acquired infections. Lessons learned from the event led to corrective actions which included modification of lab procedures, development of a biological inventory tracking and risk identification system and the establishment of an effective biological safety program.

  14. An E-learning System based on Affective Computing

    NASA Astrophysics Data System (ADS)

    Duo, Sun; Song, Lu Xue

    In recent years, e-learning as a learning system is very popular. But the current e-learning systems cannot instruct students effectively since they do not consider the emotional state in the context of instruction. The emergence of the theory about "Affective computing" can solve this question. It can make the computer's intelligence no longer be a pure cognitive one. In this paper, we construct an emotional intelligent e-learning system based on "Affective computing". A dimensional model is put forward to recognize and analyze the student's emotion state and a virtual teacher's avatar is offered to regulate student's learning psychology with consideration of teaching style based on his personality trait. A "man-to-man" learning environment is built to simulate the traditional classroom's pedagogy in the system.

  15. Modeling of biological intelligence for SCM system optimization.

    PubMed

    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.

  16. Modeling of Biological Intelligence for SCM System Optimization

    PubMed Central

    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

  17. Conference Scene: Systems biology and personalized health science and translation.

    PubMed

    Siest, Gérard; Ndiaye, Ndeye Coumba; El Shamieh, Said; Shahabi, Payman; Stathopoulou, Maria; Saleh, Abdel Salam; Godjo, Thibaut; Albertini, Laetitia; Visvikis-Siest, Sophie

    2013-12-01

    After a 1-day advanced course on systems biology, the main themes of this 3-day colloquium were developed: from systems biology to systems medicine with special applications to cancer; pharmacogenomics in drug discovery and clinical application; and epigenomics and genome-wide association studies in cardiovascular diseases. In two roundtable discussions on pharmacogenomics and genome-wide association studies, the progress and the difficulties in the implementation of omics technologies in clinical practice were discussed. Three workshops were also organized on technical tools linked to the meeting themes.

  18. Phase transitions in fluids and biological systems

    NASA Astrophysics Data System (ADS)

    Sipos, Maksim

    In this thesis, I consider systems from two seemingly different fields: fluid dynamics and microbial ecology. In these systems, the unifying features are the existences of global non-equilibrium steady states. I consider generic and statistical models for transitions between these global states, and I relate the model results with experimental data. A theme of this thesis is that these rather simple, minimal models are able to capture a lot of functional detail about complex dynamical systems. In Part I, I consider the transition between laminar and turbulent flow. I find that quantitative and qualitative features of pipe flow experiments, the superexponential lifetime and the splitting of turbulent puffs, and the growth rate of turbulent slugs, can all be explained by a coarse-grained, phenomenological model in the directed percolation universality class. To relate this critical phenomena approach closer to the fluid dynamics, I consider the transition to turbulence in the Burgers equation, a simplified model for Navier-Stokes equations. Via a transformation to a model of directed polymers in a random medium, I find that the transition to Burgers turbulence may also be in the directed percolation universality class. This evidence implies that the turbulent-to-laminar transition is statistical in nature and does not depend on details of the Navier-Stokes equations describing the fluid flow. In Part II, I consider the disparate subject of microbial ecology where the complex interactions within microbial ecosystems produce observable patterns in microbe abundance, diversity and genotype. In order to be able to study these patterns, I develop a bioinformatics pipeline to multiply align and quickly cluster large microbial metagenomics datasets. I also develop a novel metric that quantifies the degree of interactions underlying the assembly of a microbial ecosystem, particularly the transition between neutral (random) and niche (deterministic) assembly. I apply this

  19. Towards Environmental Systems Biology of Shewanella

    SciTech Connect

    Fredrickson, Jim K.; Romine, Margaret F.; Beliaev, Alex S.; Auchutung, Jennifer M.; Driscoll, Michael E.; Gardner, Timothy S.; Nealson, Kenneth H.; Osterman, Andrei L.; Pinchuk, Grigoriy E.; Reed, Jennifer L.; Rodionov, Dmitry; Rodrigues, Jorge L.M.; Saffarini, Daad; Serres, Margrethe H.; Spormann, Alfred M.; Zhulin, Igor B.; Tiedje, James M.

    2008-07-07

    Abstract: Shewanella are known for versatility in their electron accepting capacities, which allow them to couple decomposition of organic matter to reduction of the variety of terminal electron acceptors encountered in the stratified environments they inhabit. Due to their diverse metabolic capabilities, shewanellae play important roles in carbon cycling and have considerable potential for remediation of contaminated environments and use in microbial fuel cells. Systems-level analysis of the model species, S. oneidensis MR-1, and other members of this genus have provided significant insights into the signal transduction proteins, regulators, and metabolic and respiratory subsystems governing the remarkable versatility of the shewanellae.

  20. Decoherence and spin echo in biological systems.

    PubMed

    Nesterov, Alexander I; Berman, Gennady P

    2015-05-01

    The spin-echo approach is extended to include biocomplexes for which the interaction with dynamical noise, produced by the protein environment, is strong. Significant restoration of the free induction decay signal due to homogeneous (decoherence) and inhomogeneous (dephasing) broadening is demonstrated analytically and numerically for both an individual dimer of interacting chlorophylls and for an ensemble of dimers. Our approach does not require the use of small interaction constants between the electron states and the protein fluctuations. It is based on an exact and closed system of ordinary differential equations that can be easily solved for a wide range of parameters that are relevant for bioapplications.

  1. Advances in Systems Biology, Advances in Experimental Medicine and Biology Volume 547

    SciTech Connect

    Opresko, Lee; Gephart, Julie M.; Mann, Michaela B.

    2002-12-02

    This is the inaugural year for a new series of symposia on systems biology. Particular focus will be on identifying current breakthrough technologies and their application to important model systems. By integrating computational sciences, high-throughput technologies and quantitative biology, we hope to facilitate advancements in this important new area of research.In this first year we are focusing on the four different research areas contained within the new U.S. Department of Energy (DOE) Genomes to Life program. This program is the successor to the Human Genome Project and exceeds it in scope and ambition. Its goal is to understand the basis of life and ?to venture beyond characterizing such individual life components as genes and other DNA sequences toward a more comprehensive, integrated view of biology at a whole-systems level.? These goals will be met by1. identifying the protein machines that carry out critical life functions2. characterizing the gene regulatory networks that control these machines3. exploring the functional repertoire of complex microbial communities in their natural environments to provide a foundation for understanding and using their remarkably diverse capabilities to address DOE missions4. developing the computational capabilities to integrate and understand these data and begin to model complex biological systems.

  2. Probing the biology of dry biological systems to address the basis of seed longevity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drying cells reduces molecular mobility and slows chemical and physical reactions. As a result, dry biological systems deteriorate slowly. The time course of deterioration in a population of living cells often follows a sigmoidal pattern in which aging is occurring but no changes to viability are ...

  3. Transport processes in biological systems: Tumoral cells and human brain

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2014-01-01

    The entropy generation approach has been developed for the analysis of complex systems, with particular regards to biological systems, in order to evaluate their stationary states. The entropy generation is related to the transport processes related to exergy flows. Moreover, cancer can be described as an open complex dynamic and self-organizing system. Consequently, it is used as an example useful to evaluate the different thermo-chemical quantities of the transport processes in normal and in tumoral cells systems.

  4. Carelessness and Affect in an Intelligent Tutoring System for Mathematics

    ERIC Educational Resources Information Center

    San Pedro, Maria Ofelia Z.; de Baker, Ryan S. J.; Rodrigo, Ma. Mercedes T.

    2014-01-01

    We investigate the relationship between students' affect and their frequency of careless errors while using an Intelligent Tutoring System for middle school mathematics. A student is said to have committed a careless error when the student's answer is wrong despite knowing the skill required to provide the correct answer. We operationalize the…

  5. Agent Based Affective Tutoring Systems: A Pilot Study

    ERIC Educational Resources Information Center

    Mao, Xia; Li, Zheng

    2010-01-01

    An important trend in the development of Intelligent tutoring systems (ITSs) has been that providing the student with a more personalized and friendly environment for learning. Many researchers now feel strongly that the ITSs would significantly improve performance if they could adapt to the affective state of the learner. This idea has spawned…

  6. Using Student Support Systems to Increase Cognitive and Affective Outcomes.

    ERIC Educational Resources Information Center

    Soled, Suzanne Wegener; Bosma, Jennifer F.

    1992-01-01

    Student support systems (small groups of students who meet to learn), help combat the problem of large student-to-teacher ratios and increase cognitive and affective outcomes. Small groups allow large amounts of participation and interaction, rapid error correction, individualized practice, and self-paced work that actively involves students in…

  7. Reproducible quantitative proteotype data matrices for systems biology

    PubMed Central

    Röst, Hannes L.; Malmström, Lars; Aebersold, Ruedi

    2015-01-01

    Historically, many mass spectrometry–based proteomic studies have aimed at compiling an inventory of protein compounds present in a biological sample, with the long-term objective of creating a proteome map of a species. However, to answer fundamental questions about the behavior of biological systems at the protein level, accurate and unbiased quantitative data are required in addition to a list of all protein components. Fueled by advances in mass spectrometry, the proteomics field has thus recently shifted focus toward the reproducible quantification of proteins across a large number of biological samples. This provides the foundation to move away from pure enumeration of identified proteins toward quantitative matrices of many proteins measured across multiple samples. It is argued here that data matrices consisting of highly reproducible, quantitative, and unbiased proteomic measurements across a high number of conditions, referred to here as quantitative proteotype maps, will become the fundamental currency in the field and provide the starting point for downstream biological analysis. Such proteotype data matrices, for example, are generated by the measurement of large patient cohorts, time series, or multiple experimental perturbations. They are expected to have a large effect on systems biology and personalized medicine approaches that investigate the dynamic behavior of biological systems across multiple perturbations, time points, and individuals. PMID:26543201

  8. Free radical biology of the cardiovascular system.

    PubMed

    Chen, Alex F; Chen, Dan-Dan; Daiber, Andreas; Faraci, Frank M; Li, Huige; Rembold, Christopher M; Laher, Ismail

    2012-07-01

    Most cardiovascular diseases (CVDs), as well as age-related cardiovascular alterations, are accompanied by increases in oxidative stress, usually due to increased generation and/or decreased metabolism of ROS (reactive oxygen species; for example superoxide radicals) and RNS (reactive nitrogen species; for example peroxynitrite). The superoxide anion is generated by several enzymatic reactions, including a variety of NADPH oxidases and uncoupled eNOS (endothelial NO synthase). To relieve the burden caused by this generation of free radicals, which also occurs as part of normal physiological processes, such as mitochondrial respiratory chain activity, mammalian systems have developed endogenous antioxidant enzymes. There is an increased usage of exogenous antioxidants such as vitamins C and E by many patients and the general public, ostensibly in an attempt to supplement intrinsic antioxidant activity. Unfortunately, the results of large-scale trails do not generate much enthusiasm for the continued use of antioxidants to mitigate free-radical-induced changes in the cardiovascular system. In the present paper, we review the clinical use of antioxidants by providing the rationale for their use and describe the outcomes of several large-scale trails that largely display negative outcomes. We also describe the emerging understanding of the detailed regulation of superoxide generation by an uncoupled eNOS and efforts to reverse eNOS uncoupling. SIRT1 (sirtuin 1), which regulates the expression and activity of multiple pro- and anti-oxidant enzymes, could be considered a candidate molecule for a 'molecular switch'.

  9. The Use of an Electronic Response System in Teaching Biology

    ERIC Educational Resources Information Center

    Bessler, William C.; Nisbet, Jerry J.

    1971-01-01

    An electronic student response system was used in teaching college biology to non-science students. Achievement of this treatment group was compared with that of the control group (not utilizing the response system). The only statistical significant difference found in an analysis of covariance was an interaction between treatment group and time…

  10. Systems Biology and Mode of Action Based Risk Assessment.

    EPA Science Inventory

    The application of systems biology approaches has greatly increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnost...

  11. Systems Biology and Mode of Action Based Risk Assessment

    EPA Science Inventory

    The application of systems biology has increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnostic purposes and targ...

  12. Understanding quantitative genetics in the systems biology era.

    PubMed

    Zhu, Mengjin; Yu, Mei; Zhao, Shuhong

    2009-01-01

    Biology is now entering the new era of systems biology and exerting a growing influence on the future development of various disciplines within life sciences. In early classical and molecular periods of Biology, the theoretical frames of classical and molecular quantitative genetics have been systematically established, respectively. With the new advent of systems biology, there is occurring a paradigm shift in the field of quantitative genetics. Where and how the quantitative genetics would develop after having undergone its classical and molecular periods? This is a difficult question to answer exactly. In this perspective article, the major effort was made to discuss the possible development of quantitative genetics in the systems biology era, and for which there is a high potentiality to develop towards "systems quantitative genetics". In our opinion, the systems quantitative genetics can be defined as a new discipline to address the generalized genetic laws of bioalleles controlling the heritable phenotypes of complex traits following a new dynamic network model. Other issues from quantitative genetic perspective relating to the genetical genomics, the updates of network model, and the future research prospects were also discussed.

  13. Model-Based Analysis of the Role of Biological, Hydrological and Geochemical Factors Affecting Uranium Bioremediation

    SciTech Connect

    Zhao, Jiao; Scheibe, Timothy D.; Mahadevan, Radhakrishnan

    2011-01-24

    Uranium contamination is a serious concern at several sites motivating the development of novel treatment strategies such as the Geobacter-mediated reductive immobilization of uranium. However, this bioremediation strategy has not yet been optimized for the sustained uranium removal. While several reactive-transport models have been developed to represent Geobacter-mediated bioremediation of uranium, these models often lack the detailed quantitative description of the microbial process (e.g., biomass build-up in both groundwater and sediments, electron transport system, etc.) and the interaction between biogeochemical and hydrological process. In this study, a novel multi-scale model was developed by integrating our recent model on electron capacitance of Geobacter (Zhao et al., 2010) with a comprehensive simulator of coupled fluid flow, hydrologic transport, heat transfer, and biogeochemical reactions. This mechanistic reactive-transport model accurately reproduces the experimental data for the bioremediation of uranium with acetate amendment. We subsequently performed global sensitivity analysis with the reactive-transport model in order to identify the main sources of prediction uncertainty caused by synergistic effects of biological, geochemical, and hydrological processes. The proposed approach successfully captured significant contributing factors across time and space, thereby improving the structure and parameterization of the comprehensive reactive-transport model. The global sensitivity analysis also provides a potentially useful tool to evaluate uranium bioremediation strategy. The simulations suggest that under difficult environments (e.g., highly contaminated with U(VI) at a high migration rate of solutes), the efficiency of uranium removal can be improved by adding Geobacter species to the contaminated site (bioaugmentation) in conjunction with the addition of electron donor (biostimulation). The simulations also highlight the interactive effect of

  14. Nuclear magnetic resonance studies of biological systems

    SciTech Connect

    Antypas, W.G. Jr.

    1988-01-01

    The difference between intracellular and extracellular proton relaxation rates provides the basis for the determination of the mean hemoglobin concentration (MHC) in red blood cells. The observed water T{sub 1} relaxation data from red blood cell samples under various conditions were fit to the complete equation for the time-dependent decay of magnetization for a two-compartment system including chemical exchange. The MHC for each sample was calculated from the hematocrit and the intracellular water fraction as determined by NMR. The binding of the phosphorylcholine (PC) analogue, 2-(trimethylphosphonio)-ethylphosphate (phosphoryl-phosphocholine, PPC) to the PC binding myeloma proteins TEPC-15, McPC 603, and MOPC 167 was studied by {sup 31}P NMR.

  15. The genotype-phenotype maps of systems biology and quantitative genetics: distinct and complementary.

    PubMed

    Landry, Christian R; Rifkin, Scott A

    2012-01-01

    The processes by which genetic variation in complex traits is generated and maintained in populations has for a long time been treated in abstract and statistical terms. As a consequence, quantitative genetics has provided limited insights into our understanding of the molecular bases of quantitative trait variation. With the developing technological and conceptual tools of systems biology, cellular and molecular processes are being described in greater detail. While we have a good description of how signaling and other molecular networks are organized in the cell, we still do not know how genetic variation affects these pathways, because systems and molecular biology usually ignore the type and extent of genetic variation found in natural populations. Here we discuss the quantitative genetics and systems biology approaches for the study of complex trait architecture and discuss why these two disciplines would synergize with each other to answer questions that neither of the two could answer alone.

  16. Behavior and toxicity of graphene and its functionalized derivatives in biological systems.

    PubMed

    Yang, Kai; Li, Yingjie; Tan, Xiaofang; Peng, Rui; Liu, Zhuang

    2013-05-27

    Graphene, as a class of 2D carbon nanomaterial, has attracted tremendous interest in different areas in recent years including biomedicine. The toxicity and behavior of graphene in biological systems are thus important fundamental issues that require significant attention. In this article, the toxicity of graphene is reviewed by describing the behavior of graphene and its derivatives in microorganisms, cells, and animals. Despite certain inconsistencies in several detailed experimental results and hypotheses of toxicity mechanisms, results from numerous reports all agree that the physicochemical properties such as surface functional groups, charges, coatings, sizes, and structural defects of graphene may affect its in vitro/in vivo behavior as well as its toxicity in biological systems. It is hoped that this review article will provide an overview understanding of the impacts, behavior, and toxicology of graphene and its derivatives in various biological systems.

  17. Sequencing biological and physical events affects specific frequency bands within the human premotor cortex: an intracerebral EEG study.

    PubMed

    Caruana, Fausto; Sartori, Ivana; Lo Russo, Giorgio; Avanzini, Pietro

    2014-01-01

    Evidence that the human premotor cortex (PMC) is activated by cognitive functions involving the motor domain is classically explained as the reactivation of a motor program decoupled from its executive functions, and exploited for different purposes by means of a motor simulation. In contrast, the evidence that PMC contributes to the sequencing of non-biological events cannot be explained by the simulationist theory. Here we investigated how motor simulation and event sequencing coexist within the PMC and how these mechanisms interact when both functions are executed. We asked patients with depth electrodes implanted in the PMC to passively observe a randomized arrangement of images depicting biological actions and physical events and, in a second block, to sequence them in the correct order. This task allowed us to disambiguate between the simple observation of actions, their sequencing (recruiting different motor simulation processes), as well as the sequencing of non-biological events (recruiting a sequencer mechanism non dependant on motor simulation). We analysed the response of the gamma, alpha and beta frequency bands to evaluate the contribution of each brain rhythm to the observation and sequencing of both biological and non-biological stimuli. We found that motor simulation (biological>physical) and event sequencing (sequencing>observation) differently affect the three investigated frequency bands: motor simulation was reflected on the gamma and, partially, in the beta, but not in the alpha band. In contrast, event sequencing was also reflected on the alpha band.

  18. A dynamic interface for capsaicinoid systems biology.

    PubMed

    Mazourek, Michael; Pujar, Anuradha; Borovsky, Yelena; Paran, Ilan; Mueller, Lukas; Jahn, Molly M

    2009-08-01

    Capsaicinoids are the pungent alkaloids that give hot peppers (Capsicum spp.) their spiciness. While capsaicinoids are relatively simple molecules, much is unknown about their biosynthesis, which spans diverse metabolisms of essential amino acids, phenylpropanoids, benzenoids, and fatty acids. Pepper is not a model organism, but it has access to the resources developed in model plants through comparative approaches. To aid research in this system, we have implemented a comprehensive model of capsaicinoid biosynthesis and made it publicly available within the SolCyc database at the SOL Genomics Network (http://www.sgn.cornell.edu). As a preliminary test of this model, and to build its value as a resource, targeted transcripts were cloned as candidates for nearly all of the structural genes for capsaicinoid biosynthesis. In support of the role of these transcripts in capsaicinoid biosynthesis beyond correct spatial and temporal expression, their predicted subcellular localizations were compared against the biosynthetic model and experimentally determined compartmentalization in Arabidopsis (Arabidopsis thaliana). To enable their use in a positional candidate gene approach in the Solanaceae, these genes were genetically mapped in pepper. These data were integrated into the SOL Genomics Network, a clade-oriented database that incorporates community annotation of genes, enzymes, phenotypes, mutants, and genomic loci. Here, we describe the creation and integration of these resources as a holistic and dynamic model of the characteristic specialized metabolism of pepper.

  19. [Pleasure, pain and affectivity in the nervous system].

    PubMed

    Houdart, R

    1999-01-01

    Affectivity plays an essential role in human life. It gives life its quality, and is responsible for what human beings have always considered to be main endeavor happiness. Still, looking for its description or organisation, in physiology or neurology, treatises is fruitless; there only one of its components is described pain, with no mention of pleasure. We wish to show, here, first, that pain and pleasure, depend of a same function, of which they are, of sorts, both extremities, and which in nothing but the most primitive function of the nervous system, and secondly, that this function in one of the components of an "affectivity center", which has its organisation in the limbic system. This center, integrating all the informations that arrives to the nervous system, triggers to each of them neuro-vegetative and neuro-hormonal informations that are "felt" by the organism, and thus transforms the information in a subjective feeling.

  20. Using a systems biological approach to develop novel therapeutics.

    SciTech Connect

    Forst, C.

    2001-01-01

    With the human genome sequence available and with an exponentially growing number of completely sequenced genomes from various model organisms, the research paradigm is shifted towards the analysis of the function of interacting genes and gene-product. The reduced estimate of 30,000-40,000 genes in the human genome strongly indicates that the functional complexity expected for an organism such as human may originate in locations and processes beyond the identified genes. Functional genomics emerges as valuable research area for the identification of key-players in the complex processes within a living organism. It is complemented by Systems Biology [7,103,104], a new research area that combines data obtained from Functional Genomics analysis with biocomputation and simulation of cellular networks. Both Functional Genomics and Systems Biology outline the analysis, prediction and control of complex biological systems.

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

    NASA Astrophysics Data System (ADS)

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-01

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

  2. Analysing hierarchy in the organization of biological and physical systems.

    PubMed

    Jagers op Akkerhuis, Gerard A J M

    2008-02-01

    A structured approach is discussed for analysing hierarchy in the organization of biological and physical systems. The need for a structured approach follows from the observation that many hierarchies in the literature apply conflicting hierarchy rules and include ill-defined systems. As an alternative, we suggest a framework that is based on the following analytical steps: determination of the succession stage of the universe, identification of a specific system as part of the universe, specification of external influences on a system's creation and analysis of a system's internal organization. At the end, the paper discusses practical implications of the proposed method for the analysis of system organization and hierarchy in biology, ecology and physics.

  3. NETWORKS, BIOLOGY AND SYSTEMS ENGINEERING: A CASE STUDY IN INFLAMMATION

    PubMed Central

    Foteinou, P.T.; Yang, E.; Androulakis, I. P.

    2009-01-01

    Biological systems can be modeled as networks of interacting components across multiple scales. A central problem in computational systems biology is to identify those critical components and the rules that define their interactions and give rise to the emergent behavior of a host response. In this paper we will discuss two fundamental problems related to the construction of transcription factor networks and the identification of networks of functional modules describing disease progression. We focus on inflammation as a key physiological response of clinical and translational importance. PMID:20161495

  4. The Development and Application of Affective Assessment in an Upper-Level Cell Biology Course

    ERIC Educational Resources Information Center

    Kitchen, Elizabeth; Reeve, Suzanne; Bell, John D.; Sudweeks, Richard R.; Bradshaw, William S.

    2007-01-01

    This study exemplifies how faculty members can develop instruments to assess affective responses of students to the specific features of the courses they teach. Means for assessing three types of affective responses are demonstrated: (a) student attitudes towards courses with differing instructional objectives and methodologies, (b) student…

  5. Systems Biology of Meridians, Acupoints, and Chinese Herbs in Disease

    PubMed Central

    Lin, Li-Ling; Wang, Ya-Hui; Lai, Chi-Yu; Chau, Chan-Lao; Su, Guan-Chin; Yang, Chun-Yi; Lou, Shu-Ying; Chen, Szu-Kai; Hsu, Kuan-Hao; Lai, Yen-Ling; Wu, Wei-Ming; Huang, Jian-Long; Liao, Chih-Hsin; Juan, Hsueh-Fen

    2012-01-01

    Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM). They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies. PMID:23118787

  6. Does Eating Breakfast Affect the Performance of College Students on Biology Exams?

    ERIC Educational Resources Information Center

    Phillips, Gregory W.

    2005-01-01

    This study examined the breakfast eating habits of 1,259 college students over an eleven year period to determine if eating breakfast had an impact upon their grade on a General Biology exam. The study determined that there was a significant difference in the performance on the exam with a higher percent of the participants, who had eaten…

  7. From biological models to the evolution of robot control systems.

    PubMed

    Bullinaria, John A

    2003-10-15

    Attempts to formulate realistic models of the development of the human oculomotor control system have led to the conclusion that evolutionary factors play a crucial role. Moreover, even rather coarse simulations of the biological evolutionary processes result in adaptable control systems that are considerably more efficient than those designed by human researchers. In this paper I shall describe some of the aspects of these biological models that are likely to be useful for building robot control systems. In particular, I shall consider the evolution of appropriate innate starting points for learning/adaptation, patterns of learning rates that vary across different system components, learning rates that vary during the system's lifetime, and the relevance of individual differences across the evolved populations.

  8. Implementation of integral feedback control in biological systems.

    PubMed

    Somvanshi, Pramod R; Patel, Anilkumar K; Bhartiya, Sharad; Venkatesh, K V

    2015-01-01

    Integral control design ensures that a key variable in a system is tightly maintained within acceptable levels. This approach has been widely used in engineering systems to ensure offset free operation in the presence of perturbations. Several biological systems employ such an integral control design to regulate cellular processes. An integral control design motif requires a negative feedback and an integrating process in the network loop. This review describes several biological systems, ranging from bacteria to higher organisms in which the presence of integral control principle has been hypothesized. The review highlights that in addition to the negative feedback, occurrence of zero-order kinetics in the process is a key element to realize the integral control strategy. Although the integral control motif is common to these systems, the mechanisms involved in achieving it are highly specific and can be incorporated at the level of signaling, metabolism, or at the phenotypic levels.

  9. Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness.

    PubMed

    Petruzzello, S J; Hall, E E; Ekkekakis, P

    2001-01-01

    Previous research has shown that regional brain activation, assessed via frontal electroencephalographic (EEG) asymmetry, predicts affective responsivity to aerobic exercise. To replicate and extend this work, in the present study we examined whether resting brain activation was associated with affective responses to an acute bout of aerobic exercise and the extent to which aerobic fitness mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n = 45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre- and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted positive affect (as measured by the energetic arousal subscale of the Activation Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG asymmetry predicted affect only in the high-fit group, suggesting the effect might be mediated by some factor related to fitness. It was also shown that subjects with relatively greater left frontal activation had significantly more energy (i.e., activated pleasant affect) following exercise than subjects with relatively greater right frontal activation. In conclusion, aerobic fitness influenced the relationship between resting frontal asymmetry and exercise-related affective responsivity.

  10. Global research priorities for infections that affect the nervous system.

    PubMed

    John, Chandy C; Carabin, Hélène; Montano, Silvia M; Bangirana, Paul; Zunt, Joseph R; Peterson, Phillip K

    2015-11-19

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

  11. Global research priorities for infections that affect the nervous system

    PubMed Central

    John, Chandy C.; Carabin, Hélène; Montano, Silvia M.; Bangirana, Paul; Zunt, Joseph R.; Peterson, Phillip K.

    2015-01-01

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries. PMID:26580325

  12. Moss systems biology en route: phytohormones in Physcomitrella development.

    PubMed

    Decker, E L; Frank, W; Sarnighausen, E; Reski, R

    2006-05-01

    The moss Physcomitrella patens has become a powerful model system in modern plant biology. Highly standardized cell culture techniques, as well as the necessary tools for computational biology, functional genomics and proteomics have been established. Large EST collections are available and the complete moss genome will be released soon. A simple body plan and the small number of different cell types in Physcomitrella facilitate the study of developmental processes. In the filamentous juvenile moss tissue, developmental decisions rely on the differentiation of single cells. Developmental steps are controlled by distinct phytohormones and integration of environmental signals. Especially the phytohormones auxin, cytokinin, and abscisic acid have distinct effects on early moss development. In this article, we review current knowledge about phytohormone influences on early moss development in an attempt to fully unravel the complex regulatory signal transduction networks underlying the developmental decisions of single plant cells in a holistic systems biology approach.

  13. The challenges for molecular nutrition research 4: the "nutritional systems biology level".

    PubMed

    van Ommen, Ben; Cavallieri, Duccio; Roche, Helen M; Klein, Ulla I; Daniel, Hannelore

    2008-12-01

    Nutritional systems biology may be defined as the ultimate goal of molecular nutrition research, where all relevant aspects of regulation of metabolism in health and disease states at all levels of its complexity are taken into account to describe the molecular physiology of nutritional processes. The complexity spans from intracellular to inter-organ dynamics, and involves iterations between mathematical modelling and analysis employing all profiling methods and other biological read-outs. On the basis of such dynamic models we should be enabled to better understand how the nutritional status and nutritional challenges affect human metabolism and health. Although the achievement of this proposition may currently sound unrealistic, many initiatives in theoretical biology and biomedical sciences work on parts of the solution. This review provides examples and some recommendations for the molecular nutrition research arena to move onto the systems level.

  14. Evolutionary Tradeoffs between Economy and Effectiveness in Biological Homeostasis Systems

    PubMed Central

    Szekely, Pablo; Sheftel, Hila; Mayo, Avi; Alon, Uri

    2013-01-01

    Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals. PMID:23950698

  15. Cambridge Healthtech Institute's Fourth Annual In silico Biology Conference "Modeling Systems Biology for Research and Target Prioritization"

    SciTech Connect

    Forst, C.

    2002-01-01

    In silico biology, the computer aided analysis of biological systems, is a relatively young research area. It first has been coined in the late 1990's and emerged from Theoretical and Computational Biology. As in other fields before, biology experiences an increased use of systems mathematics and computer simulation. With the human genome sequence available, with an exponentially growing number of completely sequenced genomes from various model organisms and with expression and proteomic data at hand, the research paradigm is shifted towards systems analysis and simulation. Computer aided modeling of complex biomolecules and assemblies are already routinely performed. Nowadays, theoretical description and computer simulation of cellular components in larger intra- and inter-cellular networks is of growing importance. Together with classic biological and clinical experiments as well as data from functional genomics, in silico biology will take the leading role in the analysis of biological systems.

  16. The ERATO Systems Biology Workbench: enabling interaction and exchange between software tools for computational biology.

    PubMed

    Hucka, M; Finney, A; Sauro, H M; Bolouri, H; Doyle, J; Kitano, H

    2002-01-01

    Researchers in computational biology today make use of a large number of different software packages for modeling, analysis, and data manipulation and visualization. In this paper, we describe the ERATO Systems Biology Workbench (SBW), a software framework that allows these heterogeneous application components--written in diverse programming languages and running on different platforms--to communicate and use each others' data and algorithmic capabilities. Our goal is to create a simple, open-source software infrastructure which is effective, easy to implement and easy to understand. SBW uses a broker-based architecture and enables applications (potentially running on separate, distributed computers) to communicate via a simple network protocol. The interfaces to the system are encapsulated in client-side libraries that we provide for different programming languages. We describe the SBW architecture and the current set of modules, as well as alternative implementation technologies.

  17. Can Computer Animations Affect College Biology Students' Conceptions about Diffusion and Osmosis?

    ERIC Educational Resources Information Center

    Sanger, Michael J.; Brecheisen, Dorothy M.; Hynek, Brian M.

    2001-01-01

    Investigates whether viewing computer animations representing the process of diffusion and osmosis affects students' conceptions. Discusses the difficulties of implementing computer animations in the classroom. (Contains 27 references.) (YDS)

  18. Systems biology of cisplatin resistance: past, present and future

    PubMed Central

    Galluzzi, L; Vitale, I; Michels, J; Brenner, C; Szabadkai, G; Harel-Bellan, A; Castedo, M; Kroemer, G

    2014-01-01

    The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant

  19. Workshop Report: Systems Biology for Organotypic Cell Cultures

    SciTech Connect

    Grego, Sonia; Dougherty, Edward R.; Alexander, Francis Joseph; Auerbach, Scott S.; Berridge, Brian R.; Bittner, Michael L.; Casey, Warren; Cooley, Philip C.; Dash, Ajit; Ferguson, Stephen F.; Fennell, Timothy R.; Hawkins, Brian T.; Hickey, Anthony J.; Kleensang, Andre; Liebman, Michael; Martin, Florian; Maull, Elizabeth A.; Paragas, Jason; Qiao, Guilin; Ramaiahgari, Sreenivasa; Sumner, Susan J.; Yoon, Miyoung

    2016-11-14

    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.

  20. Workshop Report: Systems Biology for Organotypic Cell Cultures

    DOE PAGES

    Grego, Sonia; Dougherty, Edward R.; Alexander, Francis Joseph; ...

    2016-11-14

    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/genomicmore » 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.« less

  1. International Conference on Intelligent Systems for Molecular Biology (ISMB)

    SciTech Connect

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas; Komandurglayavilli, Ravikumar; Mahony, Shaun; Marinescu, Voichita; Mayrose, Itay; Minin, Vladimir; Neeman, Yossef; Nimrod, Guy; Novotny, Marian; Opiyo, Stephen; Portugaly, Elon; Sadka, Tali; Sakabe, Noboru; Sarkar, Indra; Schaub, Marc; Shafer, Paul; Shmygelska, Olena; Singer, Gregory; Song, Yun; Soumyaroop, Bhattacharya; Stadler, Michael; Strope, Pooja; Su, Rong; Tabach, Yuval; Tae, Hongseok; Taylor, Todd; Terribilini, Michael; Thomas, Asha; Tran, Nam; Tseng, Tsai-Tien; Vashist, Akshay; Vijaya, Parthiban; Wang, Kai; Wang, Ting; Wei, Lai; Woo, Yong; Wu, Chunlei; Yamanishi, Yoshihiro; Yan, Changhui; Yang, Jack; Yang, Mary; Ye, Ping; Zhang, Miao

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  2. Request for Travel Funds for Systems Radiation Biology Workshop

    SciTech Connect

    Barcellos-Hoff, Mary Helen

    2014-03-22

    The 3rd International Systems Radiation Biology Workshop brought together the major European, US and Japanese research programs on radiation risk as well as selected experts representing systems biological approaches to discuss how the new methodologies could be best exploited for low dose research. A significant part of the workshop was devoted to discussions organised as breakout group sessions. To facilitate discussions number of participants was limited to 60 persons. To achieve the goals of this symposium in this international conference, support from DOE is vital. Hence, this proposal requested support in the amount of $15,000 to cover the travel expenses of international experts and radiation biology scientists from the United States. This supporting mechanism was clearly identified to the selected US participants as a conference support award from the DOE (See attached PDF). The workshop was an outstanding opportunity to strengthen interactions between leading experts in the emerging areas of radiation sciences, and will also provide opportunities for younger scientists to meet with experts and discuss their results. This workshop was designed to endorse active engagement in international collaboration. A major objective of this conference was to effectively communicate research results, in order to ensure that current thinking reflects sound science of radiation biology. Further, this international event addressed the use and success of scientific initiatives in radiation biology for policymakers, standard-setters, and the general public.

  3. Does nitrate co-pollution affect biological responses of an aquatic plant to two common herbicides?

    PubMed

    Nuttens, A; Chatellier, S; Devin, S; Guignard, C; Lenouvel, A; Gross, E M

    2016-08-01

    Aquatic systems in agricultural landscapes are subjected to multiple stressors, among them pesticide and nitrate run-off, but effects of both together have rarely been studied. We investigated possible stress-specific and interaction effects using the new OECD test organism, Myriophyllum spicatum, a widespread aquatic plant. In a fully factorial design, we used two widely applied herbicides, isoproturon and mesosulfuron-methyl, in concentration-response curves at two nitrate levels (219.63 and 878.52mg N-NO3). We applied different endpoints reflecting plant performance such as growth, pigment content, content in phenolic compounds, and plant stoichiometry. Relative growth rates based on length (RGR-L) were affected strongly by both herbicides, while effects on relative growth rate based on dry weight (RGR-DW) were apparent for isoproturon but hardly visible for mesosulfuron-methyl due to an increase in dry matter content. The higher nitrate level further reduced growth rates, specifically with mesosulfuron-methyl. Effects were visible between 50 and 500μgL(-1) for isoproturon and 0.5-5μgL(-1) for mesosulfuron-methyl, with some differences between endpoints. The two herbicides had opposite effects on chlorophyll, carotenoid and nitrogen contents in plants, with values increasing with increasing concentrations of isoproturon and decreasing for mesosulfuron-methyl. Herbicides and nitrate level exhibited distinct effects on the content in phenolic compounds, with higher nitrate levels reducing total phenolic compounds in controls and with isoproturon, but not with mesosulfuron-methyl. Increasing concentrations of mesosulfuron-methyl lead to a decline of total phenolic compounds, while isoproturon had little effect. Contents of carbon, nitrogen and phosphorus changed depending on the stressor combination. We observed higher phosphorus levels in plants exposed to certain concentrations of herbicides, potentially indicating a metabolic response. The C:N molar ratio

  4. CINRG: Systems Biology of Glucocorticoids in Muscle Disease

    DTIC Science & Technology

    2012-10-01

    wasting effects chronic glucocorticoids have on normal muscle. The goal of this proposal is to use computational systems biology approach to model the... approaches to test the hypothesis that the effect of glucocorticoids on reducing inappropriate cross-talk in TGFβ networks improves muscle regeneration... approach can use hidden variables to represent possible factors contributing to regulatory interactions that are not measured, introducing Time

  5. Proceedings: Second international conference on intelligent systems for molecular biology

    SciTech Connect

    Altman, R.; Brutlag, D.; Karp, P.; Lathrop, R.; Searls, D.

    1994-12-31

    This volume provided full papers for presentations at the Second International Conference on Intelligent Systems for Molecular Biology held August 14-17, 1994 at Stanford University, Stanford, California. Each individual paper has been separately abstracted and indexed for the database.

  6. Systems Biology Approach to Understanding Post-traumatic Stress Disorder

    DTIC Science & Technology

    2015-01-14

    interests are in systems biology, network science, modeling and analysis of circadian rhythms, drug delivery for diabetes , and model-based control. Review...symptoms have been proposed, including predator- exposure,145–147 exposure to single prolonged stress,148 and exposure to foot shock149,150 with

  7. Systems biology and the discovery of diagnostic biomarkers.

    PubMed

    Wang, Kai; Lee, Inyoul; Carlson, George; Hood, Leroy; Galas, David

    2010-01-01

    Systems biology is an approach to the science that views biology as an information science, studies biological systems as a whole and their interactions with the environment. This approach, for the reasons described here, has particular power in the search for informative diagnostic biomarkers of diseases because it focuses on the fundamental causes and keys on the identification and understanding of disease- perturbed molecular networks. In this review, we describe some recent developments that have used systems biology to address complex diseases - prion disease and drug induced liver injury- and use these as examples to illustrate the importance of understanding network structure and dynamics. The knowledge of network dynamics through in vitro experimental perturbation and modeling allows us to determine the state of the networks, to identify molecular correlates, and to derive new disease treatment approaches to reverse the pathology or prevent its progress into a more severe state through the manipulation of network states. This general approach, including diagnostics and therapeutics, is becoming known as systems medicine.

  8. Cancer systems biology: signal processing for cancer research.

    PubMed

    Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei

    2011-04-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.

  9. Systems Biology & Mode of Action Based Risk Assessment

    EPA Science Inventory

    The application of systems biology for risk assessment of environmental chemicals is a national extension of its use in pharmaceutical research. The basis for this is the concept of a key event network that builds on existing mode of action frameworks for risk assessment. The a...

  10. Systems biology markup language: Level 2 and beyond.

    PubMed

    Finney, A; Hucka, M

    2003-12-01

    The SBML (systems biology markup language) is a standard exchange format for computational models of biochemical networks. We continue developing SBML collaboratively with the modelling community to meet their evolving needs. The recently introduced SBML Level 2 includes several enhancements to the original Level 1, and features under development for SBML Level 3 include model composition, multistate chemical species and diagrams.

  11. Recent advances in intravital imaging of dynamic biological systems.

    PubMed

    Kikuta, Junichi; Ishii, Masaru

    2012-01-01

    Intravital multiphoton microscopy has opened a new era in the field of biological imaging. Focal excitation of fluorophores by simultaneous attack of multiple (normally "two") photons generates images with high spatial resolution, and use of near-infrared lasers for multiphoton excitation allows penetration of thicker specimens, enabling biologists to visualize living cellular dynamics deep inside tissues and organs without thin sectioning. Moreover, the minimized photo-bleaching and toxicity associated with multiphoton techniques is beneficial for imaging of live specimens for extended observation periods. Here we focus on recent findings using intravital multiphoton imaging of dynamic biological systems such as the immune system and bone homeostasis. The immune system comprises highly dynamic networks, in which many cell types actively travel throughout the body and interact with each other in specific areas. Therefore, real-time intravital imaging represents a powerful tool for understanding the mechanisms underlying this dynamic system.

  12. Direction of Biological Motion Affects Early Brain Activation: A Link with Social Cognition

    PubMed Central

    Pegna, Alan John; Gehring, Elise; Meyer, Georg; Del Zotto, Marzia

    2015-01-01

    A number of EEG studies have investigated the time course of brain activation for biological movement over this last decade, however the temporal dynamics of processing are still debated. Moreover, the role of direction of movement has not received much attention even though it is an essential component allowing us to determine the intentions of the moving agent, and thus permitting the anticipation of potential social interactions. In this study, we examined event-related responses (ERPs) in 15 healthy human participants to light point walkers and their scrambled counterparts, whose movements occurred either in the radial or in the lateral plane. Compared to scrambled motion (SM), biological motion (BM) showed an enhanced negativity between 210 and 360ms. A source localization algorithm (sLORETA) revealed that this was due to an increase in superior and middle temporal lobe activity. Regarding direction, we found that radial BM produced an enhanced P1 compared to lateral BM, lateral SM and radial SM. This heightened P1 was due to an increase in activity in extrastriate regions, as well as in superior temporal, medial parietal and medial prefrontal areas. This network is known to be involved in decoding the underlying intentionality of the movement and in the attribution of mental states. The social meaning signaled by the direction of biological motion therefore appears to trigger an early response in brain activity. PMID:26121591

  13. Systems Biology and Cancer Prevention: All Options on the Table

    PubMed Central

    Rosenfeld, Simon; Kapetanovic, Izet

    2008-01-01

    In this paper, we outline the status quo and approaches to further development of the systems biology concepts with focus on applications in cancer prevention science. We discuss the biological aspects of cancer research that are of primary importance in cancer prevention, motivations for their mathematical modeling and some recent advances in computational oncology. We also make an attempt to outline in big conceptual terms the contours of future work aimed at creation of large-scale computational and informational infrastructure for using as a routine tool in cancer prevention science and decision making. PMID:19787092

  14. Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders

    PubMed Central

    Parikshak, Neelroop N.; Gandal, Michael J.; Geschwind, Daniel H.

    2015-01-01

    Genetic and genomic approaches have implicated hundreds of genetic loci in neurodevelopmental disorders and neurodegeneration, but mechanistic understanding continues to lag behind the pace of gene discovery. Understanding the role of specific genetic variants in the brain involves dissecting a functional hierarchy that encompasses molecular pathways, diverse cell types, neural circuits and, ultimately, cognition and behaviour. With a focus on transcriptomics, this Review discusses how high-throughput molecular, integrative and network approaches inform disease biology by placing human genetics in a molecular systems and neurobiological context. We provide a framework for interpreting network biology studies and leveraging big genomics data sets in neurobiology. PMID:26149713

  15. The solar system: Importance of research to the biological sciences

    NASA Technical Reports Server (NTRS)

    Klein, Harold P.

    1992-01-01

    An attempt is made to describe the scope of scientific areas that comprise the current field of exobiology in the United States. From investigations of astrophysical phenomena that deal with the birth of stars and planetary systems to questions of molecular biology involving phylogenetic relationships among organisms, from attempts to simulate the synthesis of biological precursor molecules in the chemistry laboratory to making measurements of the organic constituents of Titan's atmosphere, these researches all converge toward a common objective--answering the question of how life came about in the universe.

  16. Enhanced Sampling Techniques in Molecular Dynamics Simulations of Biological Systems

    PubMed Central

    Bernardi, Rafael C.; Melo, Marcelo C. R.; Schulten, Klaus

    2014-01-01

    Background Molecular Dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. Scope of review In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Major Conclusions Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. General Significance Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. PMID:25450171

  17. Link between truncated fractals and coupled oscillators in biological systems.

    PubMed

    Paar, V; Pavin, N; Rosandić, M

    2001-09-07

    This article aims at providing a new theoretical insight into the fundamental question of the origin of truncated fractals in biological systems. It is well known that fractal geometry is one of the characteristics of living organisms. However, contrary to mathematical fractals which are self-similar at all scales, the biological fractals are truncated, i.e. their self-similarity extends at most over a few orders of magnitude of separation. We show that nonlinear coupled oscillators, modeling one of the basic features of biological systems, may generate truncated fractals: a truncated fractal pattern for basin boundaries appears in a simple mathematical model of two coupled nonlinear oscillators with weak dissipation. This fractal pattern can be considered as a particular hidden fractal property. At the level of sufficiently fine precision technique the truncated fractality acts as a simple structure, leading to predictability, but at a lower level of precision it is effectively fractal, limiting the predictability of the long-term behavior of biological systems. We point out to the generic nature of our result.

  18. Predictive modelling of complex agronomic and biological systems.

    PubMed

    Keurentjes, Joost J B; Molenaar, Jaap; Zwaan, Bas J

    2013-09-01

    Biological systems are tremendously complex in their functioning and regulation. Studying the multifaceted behaviour and describing the performance of such complexity has challenged the scientific community for years. The reduction of real-world intricacy into simple descriptive models has therefore convinced many researchers of the usefulness of introducing mathematics into biological sciences. Predictive modelling takes such an approach another step further in that it takes advantage of existing knowledge to project the performance of a system in alternating scenarios. The ever growing amounts of available data generated by assessing biological systems at increasingly higher detail provide unique opportunities for future modelling and experiment design. Here we aim to provide an overview of the progress made in modelling over time and the currently prevalent approaches for iterative modelling cycles in modern biology. We will further argue for the importance of versatility in modelling approaches, including parameter estimation, model reduction and network reconstruction. Finally, we will discuss the difficulties in overcoming the mathematical interpretation of in vivo complexity and address some of the future challenges lying ahead.

  19. Sensitivity analysis of dynamic biological systems with time-delays

    PubMed Central

    2010-01-01

    Background Mathematical modeling has been applied to the study and analysis of complex biological systems for a long time. Some processes in biological systems, such as the gene expression and feedback control in signal transduction networks, involve a time delay. These systems are represented as delay differential equation (DDE) models. Numerical sensitivity analysis of a DDE model by the direct method requires the solutions of model and sensitivity equations with time-delays. The major effort is the computation of Jacobian matrix when computing the solution of sensitivity equations. The computation of partial derivatives of complex equations either by the analytic method or by symbolic manipulation is time consuming, inconvenient, and prone to introduce human errors. To address this problem, an automatic approach to obtain the derivatives of complex functions efficiently and accurately is necessary. Results We have proposed an efficient algorithm with an adaptive step size control to compute the solution and dynamic sensitivities of biological systems described by ordinal differential equations (ODEs). The adaptive direct-decoupled algorithm is extended to solve the solution and dynamic sensitivities of time-delay systems describing by DDEs. To save the human effort and avoid the human errors in the computation of partial derivatives, an automatic differentiation technique is embedded in the extended algorithm to evaluate the Jacobian matrix. The extended algorithm is implemented and applied to two realistic models with time-delays: the cardiovascular control system and the TNF-α signal transduction network. The results show that the extended algorithm is a good tool for dynamic sensitivity analysis on DDE models with less user intervention. Conclusions By comparing with direct-coupled methods in theory, the extended algorithm is efficient, accurate, and easy to use for end users without programming background to do dynamic sensitivity analysis on complex

  20. [Fluorosis of coal burning affects the male reproductive system].

    PubMed

    Li, Jun-Feng; Feng, Jin; Xiao, Yue-Hai; Sun, Fa

    2014-01-01

    Fluorosis of coal burning is a new type of endemic fluorosis in China, which affects the male reproductive system. Furthermore, the content of fluoride in the semen, sperm mortality, sperm concentration and the incidence of infertility are higher in severe fluorosis areas than in mild- and non-fluorosis areas, so are the levels of serum follicle-stimulating hormone and luteinizing hormone. However, the levels of inhibin B, serum testosterone and estradiol show different degrees of reduction in severe fluorosis areas. Accordingly, fluorosis of coal burning, just like other endemic fluorosis, may affect the structure of male reproductive organs, the generation of sperm and reproductive endocrinology, resulting in the decline of men's reproductive ability.

  1. Two classes of bipartite networks: nested biological and social systems.

    PubMed

    Burgos, Enrique; Ceva, Horacio; Hernández, Laura; Perazzo, R P J; Devoto, Mariano; Medan, Diego

    2008-10-01

    Bipartite graphs have received some attention in the study of social networks and of biological mutualistic systems. A generalization of a previous model is presented, that evolves the topology of the graph in order to optimally account for a given contact preference rule between the two guilds of the network. As a result, social and biological graphs are classified as belonging to two clearly different classes. Projected graphs, linking the agents of only one guild, are obtained from the original bipartite graph. The corresponding evolution of its statistical properties is also studied. An example of a biological mutualistic network is analyzed in detail, and it is found that the model provides a very good fitting of all the main statistical features. The model also provides a proper qualitative description of the same features observed in social webs, suggesting the possible reasons underlying the difference in the organization of these two kinds of bipartite networks.

  2. Specifications of Standards in Systems and Synthetic Biology.

    PubMed

    Schreiber, Falk; Bader, Gary D; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan

    2015-09-04

    Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation). Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/. So far the different standards were published and made accessible through the standards’ web- pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

  3. How does obesity affect the endocrine system? A narrative review.

    PubMed

    Poddar, M; Chetty, Y; Chetty, V T

    2017-03-15

    Obesity is a chronic, relapsing medical condition that results from an imbalance of energy expenditure and consumption. It is a leading cause of preventable illness, disability and premature death. The causes of obesity are multifactorial and include behavioural, socioeconomic, genetic, environmental and psychosocial factors. Rarely are endocrine diseases, e.g., hypothyroidism or Cushing's syndrome, the cause of obesity. What is less understood is how obesity affects the endocrine system. In this review, we will discuss the impact of obesity on multiple endocrine systems, including the hypothalamic-pituitary axis, changes in vitamin D homeostasis, gender steroids and thyroid hormones. We will also examine the renin angiotensin aldosterone system and insulin pathophysiology associated with obesity. We will provide a general overview of the biochemical changes that can be seen in patients with obesity, review possible aetiologies of these changes and briefly consider current guidelines on their management. This review will not discuss endocrine causes of obesity.

  4. Correlation between BMI and PASI in patients affected by moderate to severe psoriasis undergoing biological therapy.

    PubMed

    Bardazzi, F; Balestri, R; Baldi, E; Antonucci, A; De Tommaso, S; Patrizi, A

    2010-01-01

    Obesity is common in psoriatic patients, and it has been shown to be important for many aspects of the condition. In particular, low-calorie diets can improve the symptoms and response to treatment in pustular psoriasis. The present study investigates the influence of body-weight alteration on the disease's clinical manifestations in moderate to severe psoriasis patients treated with biological drugs. Finally, the influence of a caloric restriction was assessed. This observational transversal study enrolled 33 patients attending our Severe Psoriasis Outpatient Clinic, who were treated with biological drugs. Body Mass Index (BMI) was used as a diagnostic indicator of being overweight and of obesity. Waist circumference was also measured. Body weight and Psoriasis Area Severity Index (PASI) index were measured at follow-up visits at 4 and 8 months. Nonparametric test of Mann-Whitney was used to detect the differences between patient groups. Fisher's exact test was performed to evaluate the different results depending on the therapeutic changes of BMI. There was a strong prevalence of overweight-obese individuals in the group with a mean BMI of 30.59 +/- 6.94. Waist circumference was also above normal in the majority of the patients. Obese patients had a PASI index higher than the average of the whole group (25.03 +/- 12.43), with grade III obese patients having an average PASI of 44 +/- 3.37. At the first and second follow-ups, patients who put on weight did not achieve PASI 50; patients who had a stable weight presented variable response to treatment, while patients who decreased their weight achieved PASI 90 or PASI 75 even when not responding at the first. Further studies are needed to understand if the poor response observed in heavier patients is due to biological drugs pharmacokinetics or because therapy should be BMI based rather than administered in fixed doses, posing then an ethical consideration.

  5. Using Quantum Mechanical Approaches to Study Biological Systems

    PubMed Central

    2015-01-01

    Conspectus Quantum mechanics (QM) has revolutionized our understanding of the structure and reactivity of small molecular systems. Given the tremendous impact of QM in this research area, it is attractive to believe that this could also be brought into the biological realm where systems of a few thousand atoms and beyond are routine. Applying QM methods to biological problems brings an improved representation to these systems by the direct inclusion of inherently QM effects such as polarization and charge transfer. Because of the improved representation, novel insights can be gleaned from the application of QM tools to biomacromolecules in aqueous solution. To achieve this goal, the computational bottlenecks of QM methods had to be addressed. In semiempirical theory, matrix diagonalization is rate limiting, while in density functional theory or Hartree–Fock theory electron repulsion integral computation is rate-limiting. In this Account, we primarily focus on semiempirical models where the divide and conquer (D&C) approach linearizes the matrix diagonalization step with respect to the system size. Through the D&C approach, a number of applications to biological problems became tractable. Herein, we provide examples of QM studies on biological systems that focus on protein solvation as viewed by QM, QM enabled structure-based drug design, and NMR and X-ray biological structure refinement using QM derived restraints. Through the examples chosen, we show the power of QM to provide novel insights into biological systems, while also impacting practical applications such as structure refinement. While these methods can be more expensive than classical approaches, they make up for this deficiency by the more realistic modeling of the electronic nature of biological systems and in their ability to be broadly applied. Of the tools and applications discussed in this Account, X-ray structure refinement using QM models is now generally available to the community in the

  6. Systems Biology of Clostridium Acetobutylicum: Sugar Metabolism and TNT Reduction

    NASA Astrophysics Data System (ADS)

    Hurley, Margaret; Sund, Christian; Servinsky, Matthew

    2010-03-01

    Rapid advancements in biotechnology are expected to impact multiple areas of interest to the Army, including decontamination, degradation of toxic chemicals and biofuels. This project is a joint experimental/computational effort to map out the metabolic pathways in Clostridium acetobutylicum, and use this information to develop a systems biology model of this system. This organism has been chosen specifically due to the fact that it has potential application to both biofuel production and nitroaromatic degradation. It is hoped that a systems biology model may provide key information to enhance both of these processes. Details will be presented of a first-generation model of central carbon metabolism in C. Acet., developed upon gene expression data accumulated from bacteria grown on different carbohydrate sources. Additional work will discuss the effect of TNT exposure and potential relevant enhancements of the model.

  7. Modeling Functional Motions of Biological Systems by Customized Natural Moves.

    PubMed

    Demharter, Samuel; Knapp, Bernhard; Deane, Charlotte M; Minary, Peter

    2016-08-23

    Simulating the functional motions of biomolecular systems requires large computational resources. We introduce a computationally inexpensive protocol for the systematic testing of hypotheses regarding the dynamic behavior of proteins and nucleic acids. The protocol is based on natural move Monte Carlo, a highly efficient conformational sampling method with built-in customization capabilities that allows researchers to design and perform a large number of simulations to investigate functional motions in biological systems. We demonstrate the use of this protocol on both a protein and a DNA case study. Firstly, we investigate the plasticity of a class II major histocompatibility complex in the absence of a bound peptide. Secondly, we study the effects of the epigenetic mark 5-hydroxymethyl on cytosine on the structure of the Dickerson-Drew dodecamer. We show how our customized natural moves protocol can be used to investigate causal relationships of functional motions in biological systems.

  8. Systems biology for understanding and engineering of heterotrophic oleaginous microorganisms.

    PubMed

    Park, Beom Gi; Kim, Minsuk; Kim, Joonwon; Yoo, Heewang; Kim, Byung-Gee

    2017-01-01

    Heterotrophic oleaginous microorganisms continue to draw interest as they can accumulate a large amount of lipids which is a promising feedstock for the production of biofuels and oleochemicals. Nutrient limitation, especially nitrogen limitation, is known to effectively trigger the lipid production in these microorganisms. For the aim of developing improved strains, the mechanisms behind the lipid production have been studied for a long time. Nowadays, system-level understanding of their metabolism and associated metabolic switches is attainable with modern systems biology tools. This work reviews the systems biology studies, based on (i) top-down, large-scale 'omics' tools, and (ii) bottom-up, mathematical modeling methods, on the heterotrophic oleaginous microorganisms with an emphasis on further application to metabolic engineering.

  9. Biological, mechanical, and technological considerations affecting the longevity of intracortical electrode recordings.

    PubMed

    Harris, James P; Tyler, Dustin J

    2013-01-01

    Intracortical electrodes are important tools, with applications ranging from fundamental laboratory studies to potential solutions to intractable clinical applications. However, the longevity and reliability of the interfaces remain their major limitation to the wider implementation and adoption of this technology, especially in broader translational work. Accordingly, this review summarizes the most significant biological and technical factors influencing the long-term performance of intracortical electrodes. In a laboratory setting, intracortical electrodes have been used to study the normal and abnormal function of the brain. This improved understanding has led to valuable insights regarding many neurological conditions. Likewise, clinical applications of intracortical brain-machine interfaces offer the ability to improve the quality of life of many patients afflicted with high-level paralysis from spinal cord injury, brain stem stroke, amyotrophic lateral sclerosis, or other conditions. It is widely hypothesized that the tissue response to the electrodes, including inflammation, limits their longevity. Many studies have examined and modified the tissue response to intracortical electrodes to improve future intracortical electrode technologies. Overall, the relationship between biological, mechanical, and technological considerations are crucial for the fidelity of chronic electrode recordings and represent a presently active area of investigation in the field of neural engineering.

  10. He throws like a girl (but only when he's sad): emotion affects sex-decoding of biological motion displays.

    PubMed

    Johnson, Kerri L; McKay, Lawrie S; Pollick, Frank E

    2011-05-01

    Gender stereotypes have been implicated in sex-typed perceptions of facial emotion. Such interpretations were recently called into question because facial cues of emotion are confounded with sexually dimorphic facial cues. Here we examine the role of visual cues and gender stereotypes in perceptions of biological motion displays, thus overcoming the morphological confounding inherent in facial displays. In four studies, participants' judgments revealed gender stereotyping. Observers accurately perceived emotion from biological motion displays (Study 1), and this affected sex categorizations. Angry displays were overwhelmingly judged to be men; sad displays were judged to be women (Studies 2-4). Moreover, this pattern remained strong when stimuli were equated for velocity (Study 3). We argue that these results were obtained because perceivers applied gender stereotypes of emotion to infer sex category (Study 4). Implications for both vision sciences and social psychology are discussed.

  11. Improving Collaboration by Standardization Efforts in Systems Biology

    PubMed Central

    Dräger, Andreas; Palsson, Bernhard Ø.

    2014-01-01

    Collaborative genome-scale reconstruction endeavors of metabolic networks would not be possible without a common, standardized formal representation of these systems. The ability to precisely define biological building blocks together with their dynamic behavior has even been considered a prerequisite for upcoming synthetic biology approaches. Driven by the requirements of such ambitious research goals, standardization itself has become an active field of research on nearly all levels of granularity in biology. In addition to the originally envisaged exchange of computational models and tool interoperability, new standards have been suggested for an unambiguous graphical display of biological phenomena, to annotate, archive, as well as to rank models, and to describe execution and the outcomes of simulation experiments. The spectrum now even covers the interaction of entire neurons in the brain, three-dimensional motions, and the description of pharmacometric studies. Thereby, the mathematical description of systems and approaches for their (repeated) simulation are clearly separated from each other and also from their graphical representation. Minimum information definitions constitute guidelines and common operation protocols in order to ensure reproducibility of findings and a unified knowledge representation. Central database infrastructures have been established that provide the scientific community with persistent links from model annotations to online resources. A rich variety of open-source software tools thrives for all data formats, often supporting a multitude of programing languages. Regular meetings and workshops of developers and users lead to continuous improvement and ongoing development of these standardization efforts. This article gives a brief overview about the current state of the growing number of operation protocols, mark-up languages, graphical descriptions, and fundamental software support with relevance to systems biology. PMID:25538939

  12. Systems Biology Knowledgebase for a New Era in Biology A Genomics:GTL Report from the May 2008 Workshop

    SciTech Connect

    Gregurick, S.; Fredrickson, J. K.; Stevens, R.

    2009-03-01

    Biology has entered a systems-science era with the goal to establish a predictive understanding of the mechanisms of cellular function and the interactions of biological systems with their environment and with each other. Vast amounts of data on the composition, physiology, and function of complex biological systems and their natural environments are emerging from new analytical technologies. Effectively exploiting these data requires developing a new generation of capabilities for analyzing and managing the information. By revealing the core principles and processes conserved in collective genomes across all biology and by enabling insights into the interplay between an organism's genotype and its environment, systems biology will allow scientific breakthroughs in our ability to project behaviors of natural systems and to manipulate and engineer managed systems. These breakthroughs will benefit Department of Energy (DOE) missions in energy security, climate protection, and environmental remediation.

  13. Neuroscience in the era of functional genomics and systems biology.

    PubMed

    Geschwind, Daniel H; Konopka, Genevieve

    2009-10-15

    Advances in genetics and genomics have fuelled a revolution in discovery-based, or hypothesis-generating, research that provides a powerful complement to the more directly hypothesis-driven molecular, cellular and systems neuroscience. Genetic and functional genomic studies have already yielded important insights into neuronal diversity and function, as well as disease. One of the most exciting and challenging frontiers in neuroscience involves harnessing the power of large-scale genetic, genomic and phenotypic data sets, and the development of tools for data integration and mining. Methods for network analysis and systems biology offer the promise of integrating these multiple levels of data, connecting molecular pathways to nervous system function.

  14. From globally coupled maps to complex-systems biology

    SciTech Connect

    Kaneko, Kunihiko

    2015-09-15

    Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.

  15. Understanding genetic variation – the value of systems biology

    PubMed Central

    Hütt, Marc-Thorsten

    2014-01-01

    Pharmacology is currently transformed by the vast amounts of genome-associated information available for system-level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks. PMID:24725073

  16. Newton, Laplace, and The Epistemology of Systems Biology

    PubMed Central

    Bittner, Michael L.; Dougherty, Edward R.

    2012-01-01

    For science, theoretical or applied, to significantly advance, researchers must use the most appropriate mathematical methods. A century and a half elapsed between Newton’s development of the calculus and Laplace’s development of celestial mechanics. One cannot imagine the latter without the former. Today, more than three-quarters of a century has elapsed since the birth of stochastic systems theory. This article provides a perspective on the utilization of systems theory as the proper vehicle for the development of systems biology and its application to complex regulatory diseases such as cancer. PMID:23170064

  17. From globally coupled maps to complex-systems biology

    NASA Astrophysics Data System (ADS)

    Kaneko, Kunihiko

    2015-09-01

    Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.

  18. From globally coupled maps to complex-systems biology.

    PubMed

    Kaneko, Kunihiko

    2015-09-01

    Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.

  19. Newton, laplace, and the epistemology of systems biology.

    PubMed

    Bittner, Michael L; Dougherty, Edward R

    2012-01-01

    For science, theoretical or applied, to significantly advance, researchers must use the most appropriate mathematical methods. A century and a half elapsed between Newton's development of the calculus and Laplace's development of celestial mechanics. One cannot imagine the latter without the former. Today, more than three-quarters of a century has elapsed since the birth of stochastic systems theory. This article provides a perspective on the utilization of systems theory as the proper vehicle for the development of systems biology and its application to complex regulatory diseases such as cancer.

  20. Climate warming affects biological invasions by shifting interactions of plants and herbivores.

    PubMed

    Lu, Xinmin; Siemann, Evan; Shao, Xu; Wei, Hui; Ding, Jianqing

    2013-08-01

    Plants and herbivorous insects can each be dramatically affected by temperature. Climate warming may impact plant invasion success directly but also indirectly through changes in their natural enemies. To date, however, there are no tests of how climate warming shifts the interactions among invasive plants and their natural enemies to affect invasion success. Field surveys covering the full latitudinal range of invasive Alternanthera philoxeroides in China showed that a beetle introduced for biocontrol was rare or absent at higher latitudes. In contrast, plant cover and mass increased with latitude. In a 2-year field experiment near the northern limit of beetle distribution, we found the beetle sustained populations across years under elevated temperature, dramatically decreasing A. philoxeroides growth, but it failed to overwinter in ambient temperature. Together, these results suggest that warming will allow the natural enemy to expand its range, potentially benefiting biocontrol in regions that are currently too cold for the natural enemy. However, the invader may also expand its range further north in response to warming. In such cases where plants tolerate cold better than their natural enemies, the geographical gap between plant and herbivorous insect ranges may not disappear but will shift to higher latitudes, leading to a new zone of enemy release. Therefore, warming will not only affect plant invasions directly but also drive either enemy release or increase that will result in contrasting effects on invasive plants. The findings are also critical for future management of invasive species under climate change.

  1. Does the different mowing regime affect soil biological activity and floristic composition of thermophilous Pieniny meadow?

    NASA Astrophysics Data System (ADS)

    Józefowska, Agnieszka; Zaleski, Tomasz; Zarzycki, Jan

    2016-04-01

    The study area was located in the Pieniny National Park in the Carpathian Mountain (Southern Poland). About 30% of Park's area is covered by meadows. The climax stage of this area is forest. Therefore extensive use is indispensable action to keep semi-natural grassland such as termophilous Pieniny meadows, which are characterized by a very high biodiversity. The purpose of this research was to answer the question, how the different way of mowing: traditional scything (H), and mechanical mowing (M) or abandonment of mowing (N) effect on the biological activity of soil. Soil biological activity has been expressed by microbial and soil fauna activity. Microbial activity was described directly by count of microorganisms and indirectly by enzymatic activity (dehydrogenase - DHA) and the microbial biomass carbon content (MBC). Enchytraeidae and Lumbricidae were chosen as representatives of soil fauna. Density and species diversity of this Oligochaeta was determined. Samples were collected twice in June (before mowing) and in September (after mowing). Basic soil properties, such as pH value, organic carbon and nitrogen content, moisture and temperature, were determined. Mean count of vegetative bacteria forms, fungi and Actinobacteria was higher in H than M and N. Amount of bacteria connected with nitrification and denitrification process and Clostridium pasteurianum was the highest in soil where mowing was discontinued 11 years ago. The microbial activity measured indirectly by MBC and DHA indicated that the M had the highest activity. The soil biological activity in second term of sampling had generally higher activity than soil collected in June. That was probably connected with highest organic carbon content in soil resulting from mowing and the end of growing season. Higher earthworm density was in mowing soil (220 and 208 individuals m-2 in H and M respectively) compare to non-mowing one (77 ind. m-2). The density of Enchytraeidae was inversely, the higher density

  2. How do wettability, zeta potential and hydroxylation degree affect the biological response of biomaterials?

    PubMed

    Spriano, S; Sarath Chandra, V; Cochis, A; Uberti, F; Rimondini, L; Bertone, E; Vitale, A; Scolaro, C; Ferrari, M; Cirisano, F; Gautier di Confiengo, G; Ferraris, S

    2017-05-01

    It is well known that composition, electric charge, wettability and roughness of implant surfaces have great influence on their interaction with the biological fluids and tissues, but systematic studies of different materials in the same experimental conditions are still lacking in the scientific literature. The aim of this research is to investigate the correlations between some surface characteristics (wettability, zeta potential and hydroxylation degree) and the biological response (protein adsorption, blood wettability, cell and bacterial adhesion) to some model biomaterials. The resulting knowledge can be applied for the development of future innovative surfaces for implantable biomaterials. Roughness was not considered as a variable because it is a widely explored feature: smooth surfaces prepared by a controlled protocol were compared in order to have no roughness effects. Three oxides (ZrO2, Al2O3, SiO2), three metals (316LSS steel, Ti, Nb) and two polymers (corona treated polystyrene for cell culture and untreated polystyrene for bacteria culture), widely used for biomedical applications, were considered. The surfaces were characterized by contact profilometry, SEM-EDS, XPS, FTIR, zeta potential and wettability with different fluids. Protein adsorption, blood wettability, bacterial and cell adhesion were evaluated in order to investigate the correlations between the surface physiochemical properties and biological responses. From a methodological standpoint, XPS and electrokinetic measurements emerged as the more suitable techniques respectively for the evaluation of hydroxylation degree and surface charge/isoelectric point. Moreover, determination of wettability by blood appeared a specific and crucial test, the results of which are not easily predictable by using other type of tests. Hydroxylation degree resulted correlated to the wettability by water, but not directly to surface charge. Wetting tests with different media showed the possibility to

  3. Two faces of entropy and information in biological systems.

    PubMed

    Mitrokhin, Yuriy

    2014-10-21

    The article attempts to overcome the well-known paradox of contradictions between the emerging biological organization and entropy production in biological systems. It is assumed that quality, speculative correlation between entropy and antientropy processes taking place both in the past and today in the metabolic and genetic cellular systems may be perfectly authorized for adequate description of the evolution of biological organization. So far as thermodynamic entropy itself cannot compensate for the high degree of organization which exists in the cell, we discuss the mode of conjunction of positive entropy events (mutations) in the genetic systems of the past generations and the formation of organized structures of current cells. We argue that only the information which is generated in the conditions of the information entropy production (mutations and other genome reorganization) in genetic systems of the past generations provides the physical conjunction of entropy and antientropy processes separated from each other in time generations. It is readily apparent from the requirements of the Second law of thermodynamics.

  4. Sex differences in parking are affected by biological and social factors.

    PubMed

    Wolf, Claudia C; Ocklenburg, Sebastian; Oren, Beyza; Becker, Cordula; Hofstätter, Andrea; Bös, Christa; Popken, Markus; Thorstensen, Truls; Güntürkün, Onur

    2010-07-01

    The stereotype of women's limited parking skills is deeply anchored in modern culture. Although laboratory tests prove men's average superiority in visuospatial tasks and parking requires complex, spatial skills, underlying mechanisms remain unexplored. Here, we investigated performance of beginners (nine women, eight men) and more experienced drivers (21 women, 27 men) at different parking manoeuvres. Furthermore, subjects conducted the mental rotation test and self-assessed their parking skills. We show that men park more accurately and especially faster than women. Performance is related to mental rotation skills and self-assessment in beginners, but only to self-assessment in more experienced drivers. We assume that, due to differential feedback, self-assessment incrementally replaces the controlling influence of mental rotation, as parking is trained with increasing experience. Results suggest that sex differences in spatial cognition persist in real-life situations, but that socio-psychological factors modulate the biological causes of sex differences.

  5. Hundreds of variants clustered in genomic loci and biological pathways affect human height

    PubMed Central

    Lango Allen, Hana; Estrada, Karol; Lettre, Guillaume; Berndt, Sonja I.; Weedon, Michael N.; Rivadeneira, Fernando; Willer, Cristen J.; Jackson, Anne U.; Vedantam, Sailaja; Raychaudhuri, Soumya; Ferreira, Teresa; Wood, Andrew R.; Weyant, Robert J.; Segrè, Ayellet V.; Speliotes, Elizabeth K.; Wheeler, Eleanor; Soranzo, Nicole; Park, Ju-Hyun; Yang, Jian; Gudbjartsson, Daniel; Heard-Costa, Nancy L.; Randall, Joshua C.; Qi, Lu; Smith, Albert Vernon; Mägi, Reedik; Pastinen, Tomi; Liang, Liming; Heid, Iris M.; Luan, Jian'an; Thorleifsson, Gudmar; Winkler, Thomas W.; Goddard, Michael E.; Lo, Ken Sin; Palmer, Cameron; Workalemahu, Tsegaselassie; Aulchenko, Yurii S.; Johansson, Åsa; Zillikens, M.Carola; Feitosa, Mary F.; Esko, Tõnu; Johnson, Toby; Ketkar, Shamika; Kraft, Peter; Mangino, Massimo; Prokopenko, Inga; Absher, Devin; Albrecht, Eva; Ernst, Florian; Glazer, Nicole L.; Hayward, Caroline; Hottenga, Jouke-Jan; Jacobs, Kevin B.; Knowles, Joshua W.; Kutalik, Zoltán; Monda, Keri L.; Polasek, Ozren; Preuss, Michael; Rayner, Nigel W.; Robertson, Neil R.; Steinthorsdottir, Valgerdur; Tyrer, Jonathan P.; Voight, Benjamin F.; Wiklund, Fredrik; Xu, Jianfeng; Zhao, Jing Hua; Nyholt, Dale R.; Pellikka, Niina; Perola, Markus; Perry, John R.B.; Surakka, Ida; Tammesoo, Mari-Liis; Altmaier, Elizabeth L.; Amin, Najaf; Aspelund, Thor; Bhangale, Tushar; Boucher, Gabrielle; Chasman, Daniel I.; Chen, Constance; Coin, Lachlan; Cooper, Matthew N.; Dixon, Anna L.; Gibson, Quince; Grundberg, Elin; Hao, Ke; Junttila, M. Juhani; Kaplan, Lee M.; Kettunen, Johannes; König, Inke R.; Kwan, Tony; Lawrence, Robert W.; Levinson, Douglas F.; Lorentzon, Mattias; McKnight, Barbara; Morris, Andrew P.; Müller, Martina; Ngwa, Julius Suh; Purcell, Shaun; Rafelt, Suzanne; Salem, Rany M.; Salvi, Erika; Sanna, Serena; Shi, Jianxin; Sovio, Ulla; Thompson, John R.; Turchin, Michael C.; Vandenput, Liesbeth; Verlaan, Dominique J.; Vitart, Veronique; White, Charles C.; Ziegler, Andreas; Almgren, Peter; Balmforth, Anthony J.; Campbell, Harry; Citterio, Lorena; De Grandi, Alessandro; Dominiczak, Anna; Duan, Jubao; Elliott, Paul; Elosua, Roberto; Eriksson, Johan G.; Freimer, Nelson B.; Geus, Eco J.C.; Glorioso, Nicola; Haiqing, Shen; Hartikainen, Anna-Liisa; Havulinna, Aki S.; Hicks, Andrew A.; Hui, Jennie; Igl, Wilmar; Illig, Thomas; Jula, Antti; Kajantie, Eero; Kilpeläinen, Tuomas O.; Koiranen, Markku; Kolcic, Ivana; Koskinen, Seppo; Kovacs, Peter; Laitinen, Jaana; Liu, Jianjun; Lokki, Marja-Liisa; Marusic, Ana; Maschio, Andrea; Meitinger, Thomas; Mulas, Antonella; Paré, Guillaume; Parker, Alex N.; Peden, John F.; Petersmann, Astrid; Pichler, Irene; Pietiläinen, Kirsi H.; Pouta, Anneli; Ridderstråle, Martin; Rotter, Jerome I.; Sambrook, Jennifer G.; Sanders, Alan R.; Schmidt, Carsten Oliver; Sinisalo, Juha; Smit, Jan H.; Stringham, Heather M.; Walters, G.Bragi; Widen, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Zagato, Laura; Zgaga, Lina; Zitting, Paavo; Alavere, Helene; Farrall, Martin; McArdle, Wendy L.; Nelis, Mari; Peters, Marjolein J.; Ripatti, Samuli; van Meurs, Joyce B.J.; Aben, Katja K.; Ardlie, Kristin G; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Collins, Francis S.; Cusi, Daniele; den Heijer, Martin; Eiriksdottir, Gudny; Gejman, Pablo V.; Hall, Alistair S.; Hamsten, Anders; Huikuri, Heikki V.; Iribarren, Carlos; Kähönen, Mika; Kaprio, Jaakko; Kathiresan, Sekar; Kiemeney, Lambertus; Kocher, Thomas; Launer, Lenore J.; Lehtimäki, Terho; Melander, Olle; Mosley, Tom H.; Musk, Arthur W.; Nieminen, Markku S.; O'Donnell, Christopher J.; Ohlsson, Claes; Oostra, Ben; Palmer, Lyle J.; Raitakari, Olli; Ridker, Paul M.; Rioux, John D.; Rissanen, Aila; Rivolta, Carlo; Schunkert, Heribert; Shuldiner, Alan R.; Siscovick, David S.; Stumvoll, Michael; Tönjes, Anke; Tuomilehto, Jaakko; van Ommen, Gert-Jan; Viikari, Jorma; Heath, Andrew C.; Martin, Nicholas G.; Montgomery, Grant W.; Province, Michael A.; Kayser, Manfred; Arnold, Alice M.; Atwood, Larry D.; Boerwinkle, Eric; Chanock, Stephen J.; Deloukas, Panos; Gieger, Christian; Grönberg, Henrik; Hall, Per; Hattersley, Andrew T.; Hengstenberg, Christian; Hoffman, Wolfgang; Lathrop, G.Mark; Salomaa, Veikko; Schreiber, Stefan; Uda, Manuela; Waterworth, Dawn; Wright, Alan F.; Assimes, Themistocles L.; Barroso, Inês; Hofman, Albert; Mohlke, Karen L.; Boomsma, Dorret I.; Caulfield, Mark J.; Cupples, L.Adrienne; Erdmann, Jeanette; Fox, Caroline S.; Gudnason, Vilmundur; Gyllensten, Ulf; Harris, Tamara B.

    2010-01-01

    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence phenotype. Genome-wide association (GWA) studies have identified >600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the utility of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P=0.016), and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants, and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented amongst variants that alter amino acid structure of proteins and expression levels of nearby genes. Our data explain ∼10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to ∼16% of phenotypic variation (∼20% of heritable variation). Although additional approaches are needed to fully dissect the genetic architecture of polygenic human traits, our findings indicate that GWA studies can identify large numbers of loci that

  6. Interactions between Artificial Gravity, the Affected Physiological Systems, and Nutrition

    NASA Technical Reports Server (NTRS)

    Heer, Martina; Baecker, Nathalie; Zwart, Sara; Smith, Scott

    2006-01-01

    Malnutrition, either by insufficient supply of some nutrients or by overfeeding, has a profound effect on the health of an organism. Therefore, optimal nutrition is a necessity in normal gravity on Earth, in microgravity, and when applying artificial gravity to the human system. Reduced physical activity, such as observed in microgravity or bed rest, has an effect on many physiological systems, such as the cardiovascular, musculoskeletal, immune, and body fluids regulation systems. There is currently no countermeasure that is effective to counteract both the cardiovascular and musculoskeletal deconditioning when applied for a short duration (see Chapter 1). Artificial gravity therefore seems the simplest physiological approach to keep these systems intact. The application of intermittent daily dose of artificial gravity by means of centrifugation has often been proposed as a potential countermeasure against the physiological deconditioning induced by spaceflight. However, neither the optimal gravity level, nor its optimal duration of exposure have been enough studied to recommend a validated, effective, and efficient artificial gravity application. As discussed in previous chapters, artificial gravity has a very high potential to counteract any changes caused by reduced physical activity. The nutrient supply, which ideally should match the actual needs, will interact with these changes and therefore has also to be taken into account. This chapter reviews the potential interactions between these nutrients (energy intake, vitamins, minerals) and the other physiological systems affected by artificial gravity generated by an on-board short-radius centrifuge.

  7. Systems biology, adverse outcome pathways, and ecotoxicology in the 21st century

    EPA Science Inventory

    While many definitions of systems biology exist, the majority of these contain most (if not all) of the following elements: global measurements of biological molecules to the extent technically feasible, dynamic measurements of key biological molecules to establish quantitative r...

  8. Systems biology approaches to identify developmental bases for lung diseases.

    PubMed

    Bhattacharya, Soumyaroop; Mariani, Thomas J

    2013-04-01

    A greater understanding of the regulatory processes contributing to lung development could be helpful to identify strategies to ameliorate morbidity and mortality in premature infants and to identify individuals at risk for congenital and/or chronic lung diseases. Over the past decade, genomics technologies have enabled the production of rich gene expression databases providing information for all genes across developmental time or in diseased tissue. These data sets facilitate systems biology approaches for identifying underlying biological modules and programs contributing to the complex processes of normal development and those that may be associated with disease states. The next decade will undoubtedly see rapid and significant advances in redefining both lung development and disease at the systems level.

  9. Fluorescence dynamics of biological systems using synchrotron radiation

    SciTech Connect

    Gratton, E.; Mantulin, W.W.; Weber, G.; Royer, C.A.; Jameson, D.M.; Reininger, R.; Hansen, R.

    1996-09-01

    A beamline for time-resolved fluorescence spectroscopy of biological systems is under construction at the Synchrotron Radiation Center. The fluorometer, operating in the frequency domain, will take advantage of the time structure of the synchrotron radiation light pulses to determine fluorescence lifetimes. Using frequency-domain techniques, the instrument can achieve an ultimate time resolution on the order of picoseconds. Preliminary experiments have shown that reducing the intensity of one of the fifteen electron bunches in the storage ring allows measurement of harmonic frequencies equivalent to the single-bunch mode. This mode of operation of the synchrotron significantly extends the range of lifetimes that can be measured. The wavelength range (encompassing the visible and ultraviolet), the range of measurable lifetimes, and the stability and reproducibility of the storage ring pulses should make this beamline a versatile tool for the investigation of the complex fluorescence decay of biological systems. {copyright} {ital 1996 American Institute of Physics.}

  10. Hemodynamically Driven Vein Graft Remodeling: A Systems Biology Approach

    PubMed Central

    Berceli, Scott A.; Tran-Son-Tay, Roger; Garbey, Marc; Jiang, Zhihua

    2011-01-01

    Despite intense investigation over several decades to understand the mechanisms of vein graft failure, few therapeutic modalities have emerged. Emphasis using standard reductionist approaches has been focused on cataloging the components involved in the early events following vein graft implantation, but limited insight has been gained in understanding the dynamic interaction of these components. We propose that the application of systems theory offers the opportunity for significant advances in this area. Focused on modeling the dynamic relationships that define living organisms, systems biology provides the necessary tools to further our understanding of the complex series of overlapping biologic events on surgical implantation of the vein graft. Through the use of ordinary differential equation and agent-based modeling techniques, we present our ongoing efforts to define the nonlinear interactions between hemodynamics and vascular adaptation. PMID:19426605

  11. Systems Biology in Immunology – A Computational Modeling Perspective

    PubMed Central

    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. Extended physics as a theoretical framework for systems biology?

    PubMed

    Miquel, Paul-Antoine

    2011-08-01

    In this essay we examine whether a theoretical and conceptual framework for systems biology could be built from the Bailly and Longo (2008, 2009) proposal. These authors aim to understand life as a coherent critical structure, and propose to develop an extended physical approach of evolution, as a diffusion of biomass in a space of complexity. Their attempt leads to a simple mathematical reconstruction of Gould's assumption (1989) concerning the bacterial world as a "left wall of least complexity" that we will examine. Extended physical systems are characterized by their constructive properties. Time is acting and new properties emerge by their history that can open the list of their initial properties. This conceptual and theoretical framework is nothing more than a philosophical assumption, but as such it provides a new and exciting approach concerning the evolution of life, and the transition between physics and biology.

  13. Systems biology of IL-6, IL-12 family cytokines.

    PubMed

    Dittrich, Anna; Hessenkemper, Wiebke; Schaper, Fred

    2015-10-01

    Interleukin-6-type cytokines play important roles in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation and differentiation and act as key player during inflammation and immune response. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches are used to tackle this challenge in an iterative process of quantitative experimental and mathematical analyses. Here we review quantitative experimental studies and systems biology approaches dealing with the function of Interleukin-6-type cytokines in physiological and pathophysiological conditions. These approaches cover the analyses of signal transduction on a cellular level up to pharmacokinetic and pharmacodynamic studies on a whole organism level.

  14. Autoimmune disorders affecting both the central and peripheral nervous system.

    PubMed

    Kamm, Christoph; Zettl, Uwe K

    2012-01-01

    Various case series of patients with autoimmune demyelinating disease affecting both the central and peripheral nervous system (CNS and PNS), either sequentially or simultaneously, have been reported for decades, but their frequency is considerably lower than that of the "classical" neurological autoimmune diseases affecting only either CNS or PNS, such as multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP) or Guillain-Barré-Syndrome (GBS), and attempts to define or even recognize the former as a clinical entity have remained elusive. Frequently, demyelination started with CNS involvement with subsequent PNS pathology, in some cases with a relapsing-remitting course. Three potential mechanisms for the autoimmune etiology of these conditions can be discussed: (I) They could be caused by a common autoimmunological reactivity against myelin antigens or epitopes present in both the central and peripheral nervous system; (II) They could be due to a higher general susceptibility to autoimmune disease, which in some cases may have been caused or exacerbated by immunomodulatory treatment, e.g. b-interferon; (III) Their co-occurrence might be coincidental. Another example of an autoimmune disease variably involving the central or peripheral nervous system or both is the overlapping and continuous clinical spectrum of Fisher syndrome (FS), as a variant of GBS, and Bickerstaff brainstem encephalitis (BBE). Recent data from larger patient cohorts with demonstration of common autoantibodies, antecedent infections, and results of detailed clinical, neuroimaging and neurophysiological investigations suggest that these three conditions are not separate disorders, but rather form a continuous spectrum with variable central and peripheral nervous system involvement. We herein review clinical and paraclinical data and therapeutic options of these disorders and discuss potential underlying common vs. divergent immunopathogenic mechanisms.

  15. Smart interactive electronic system for monitoring the electromagnetic activities of biological systems

    NASA Astrophysics Data System (ADS)

    Popa, Sorin G.; Shahinpoor, Mohsen

    2001-08-01

    A novel electronic device capable of sensing and monitoring the myoelectric, polarization wave and electromagnetic activities of the biological systems and in particular the human body is presented. It is known that all the physical and chemical processes within biological systems are associated with polarization, depolarization waves from the brain, neural signals and myoelectric processes that manifest themselves in ionic and dipole motion. The technology developed in our laboratory is based on certain charge motion sensitive electronics. The electronic system developed is capable of sensing the electromagnetic activities of biological systems. The information obtained is then processed by specialized software in order to interpret it from physical and chemical point of view.

  16. So, you want to be a systems biologist? Determinants for creating graduate curricula in systems biology.

    PubMed

    Voit, E O; Kemp, M L

    2011-01-01

    Systems biology is uniquely situated at the interface of computing, mathematics, engineering and the biological sciences. This positioning creates unique challenges and opportunities over other interdisciplinary studies when developing academic curricula. Integrative systems biology attempts to span the field from observation to innovation, and thus requires successful students to gain skills from mining to manipulation. The authors outline examples of graduate program structures, as well as curricular aspects and assessment metrics that can be customised around the environmental niche of the academic institution towards the formalisation of effective educational opportunities in systems biology. Some of this material was presented at the 2009 Foundations of Systems Biology in Engineering (FOSBE 2009) Conference in Denver, August 2009.

  17. Evaluation of the Biolog automated microbial identification system

    NASA Technical Reports Server (NTRS)

    Klingler, J. M.; Stowe, R. P.; Obenhuber, D. C.; Groves, T. O.; Mishra, S. K.; Pierson, D. L.

    1992-01-01

    Biolog's identification system was used to identify 39 American Type Culture Collection reference taxa and 45 gram-negative isolates from water samples. Of the reference strains, 98% were identified to genus level and 76% to species level within 4 to 24 h. Identification of some authentic strains of Enterobacter, Klebsiella, and Serratia was unreliable. A total of 93% of the water isolates were identified.

  18. Ultrashort Laser Pulse Induced Electromagnetic Stress on Biological Macromolecular Systems.

    DTIC Science & Technology

    1979-11-01

    ULTRASHORT LASER PULSE INDUCED ~~~~~ ELECTROMAGNET IC STRESS ON BIOLOGICAL MACROMOLECULAR SYSTEMS Adam P. Bruckner , Ph.D. ( i~iiCJ. Michael ...AFSC, Brooks Air Force Base, Texas. Dr. John Taboada (RZL) was the Laboratory Project Scientjst..in...Charge When U.S. Goverrijie~t drawings...available to the general public , including foreignnations. Thi s technical report has been reviewed and is approved for publ i-cation. OHN TABOADA , Ph.D

  19. Systems Biology of Polycystic Kidney Disease: a Critical Review

    PubMed Central

    Menezes, Luis Fernando; Germino, Gregory G

    2015-01-01

    The proliferation and diminishing costs of ‘omics’ approaches have finally opened the doors for small and medium laboratories to enter the ‘systems biology era’. This is a welcome evolution that requires a new framework to design, interpret and validate studies. Here we highlight some of the challenges, contributions, and prospects of the“cyst-ems biology” of polycystic kidney disease. PMID:25641951

  20. Microbiological evaluation of the mobile biological isolator system

    NASA Technical Reports Server (NTRS)

    Taylor, D. M.; Morelli, F.; Neiderheiser, W.; Tratz, W. M.

    1979-01-01

    Evaluations on critical components of the mobile biological isolation system were performed. High efficiency particulate air filter efficiency and suit integrity were found to withstand repeated ethylene oxide (ETO) sterilizations. The minimum ETO sterilization time required to inactivate all contaminant organisms was established at four hours. Two days of aerating at 120 F was found to dissipate all harmful ETO residuals from the suit. Donning and doffing procedures were clarified and written specifically for isolation rooms.

  1. Antiestrogen Resistance and the Application of Systems Biology

    PubMed Central

    Bouker, Kerrie B.; Wang, Yue; Xuan, Jianhua; Clarke, Robert

    2012-01-01

    Understanding the molecular changes that drive an acquired antiestrogen resistance phenotype is of major clinical relevance. Previous methodologies for addressing this question have taken a single gene/pathway approach and the resulting gains have been limited in terms of their clinical impact. Recent systems biology approaches allow for the integration of data from high throughput “-omics” technologies. We highlight recent advances in the field of antiestrogen resistance with a focus on transcriptomics, proteomics and methylomics. PMID:23539064

  2. Dynamical Systems and Control Theory Inspired by Molecular Biology

    DTIC Science & Technology

    2011-02-20

    is odd) steady states, there never are more than 2n − 1 steady states, that for parameters near the standard Michaelis - Menten quasi-steady state...conditions, there are at most n + 1 steady states and that for parameters far from the standard Michaelis - Menten quasi-steady state conditions, there is at...moments for certain stochastic kinetics : We have recently started research into stochastic aspects in systems biology. Deterministic mod- els

  3. Electromechanical imaging of biological systems with sub-10 nm resolution

    NASA Astrophysics Data System (ADS)

    Kalinin, Sergei V.; Rodriguez, B. J.; Jesse, S.; Thundat, T.; Gruverman, A.

    2005-08-01

    Electromechanical imaging of tooth dentin and enamel has been performed with sub-10nm resolution using piezoresponse force microscopy. Characteristic piezoelectric domain size and local protein fiber ordering in dentin have been determined. The shape of a single protein fibril in enamel is visualized in real space and local hysteresis loops are measured. Because of the ubiquitous presence of piezoelectricity in biological systems, this approach is expected to find broad application in high-resolution studies of a wide range of biomaterials.

  4. Interactions of nanomaterials and biological systems: implications to personalized nanomedicine☆

    PubMed Central

    Zhang, Xue-Qing; Xu, Xiaoyang; Bertrand, Nicolas; Pridgen, Eric; Swami, Archana; Farokhzad, Omid C.

    2012-01-01

    The application of nanotechnology to personalized medicine provides an unprecedented opportunity to improve the treatment of many diseases. Nanomaterials offer several advantages as therapeutic and diagnostic tools due to design flexibility, small sizes, large surface-to-volume ratio, and ease of surface modification with multivalent ligands to increase avidity for target molecules. Nanomaterials can be engineered to interact with specific biological components, allowing them to benefit from the insights provided by personalized medicine techniques. To tailor these interactions, a comprehensive knowledge of how nanomaterials interact with biological systems is critical. Herein, we discuss how the interactions of nanomaterials with biological systems can guide their design for diagnostic, imaging and drug delivery purposes. A general overview of nanomaterials under investigation is provided with an emphasis on systems that have reached clinical trials. Finally, considerations for the development of personalized nanomedicines are summarized such as the potential toxicity, scientific and technical challenges in fabricating them, and regulatory and ethical issues raised by the utilization of nanomaterials. PMID:22917779

  5. Designing the Cloud-based DOE Systems Biology Knowledgebase

    SciTech Connect

    Lansing, Carina S.; Liu, Yan; Yin, Jian; Corrigan, Abigail L.; Guillen, Zoe C.; Kleese van Dam, Kerstin; Gorton, Ian

    2011-09-01

    Systems Biology research, even more than many other scientific domains, is becoming increasingly data-intensive. Not only have advances in experimental and computational technologies lead to an exponential increase in scientific data volumes and their complexity, but increasingly such databases themselves are providing the basis for new scientific discoveries. To engage effectively with these community resources, integrated analyses, synthesis and simulation software is needed, regularly supported by scientific workflows. In order to provide a more collaborative, community driven research environment for this heterogeneous setting, the Department of Energy (DOE) has decided to develop a federated, cloud based cyber infrastructure - the Systems Biology Knowledgebase (Kbase). Pacific Northwest National Laboratory (PNNL) with its long tradition in data intensive science lead two of the five initial pilot projects, these two focusing on defining and testing the basic federated cloud-based system architecture and develop a prototype implementation. Hereby the community wide accessibility of biological data and the capability to integrate and analyze this data within its changing research context were seen as key technical functionalities the Kbase needed to enable. In this paper we describe the results of our investigations into the design of a cloud based federated infrastructure for: (1) Semantics driven data discovery, access and integration; (2) Data annotation, publication and sharing; (3) Workflow enabled data analysis; and (4) Project based collaborative working. We describe our approach, exemplary use cases and our prototype implementation that demonstrates the feasibility of this approach.

  6. Development of a biological treatment system for Hanford groundwater remediation

    SciTech Connect

    Brouns, T.M.; Koegler, S.S.; Heath, W.O.; Fredrickson, J.K. ); Stensel, H.D. ); Johnstone, D.L. ); Donaldson, T.L. )

    1990-04-01

    The primary objective of the biological treatment program is to develop and demonstrate a biological process for Hanford groundwater remediation that is capable of nitrate (NO {sub 3}{sup {minus}}) and organic contaminant destruction. Biodenitrification using facultative anaerobic microorganisms is a promising technology for the simultaneous removal of NO{sub 3}{sup {minus}} and organics from contaminated aqueous streams. During FY 1989, microbial consortium from the Hanford groundwater was shown to degrade both NO{sub 3}{sup {minus}} and carbon tetrachloride (CC1{sub 4}). A pilot-scale treatment system was subsequently designed and constructed based on the results of laboratory- and bench-scale testing. The pilot-scale system demonstrated continuous degradation of NO{sub 3}{sup {minus}} and CC1{sub 4} in a simulated groundwater. This report summarizes the results of biological groundwater treatment studies performed during FY 1989 at the pilot-, laboratory-, and bench-scales. Pilot-scale test were conducted using a simulate Hanford groundwater with a continuous stirred-tank bioreactor (CSTR) and a fluidized-bed bioreactor that was added to the pilot-scale treatment system in FY 1989. Laboratory test focused on the degradation of CC1{sub 4} and on the microbial toxicity from CC1{sub 4}, hexavalent chromium (Cr{plus} {sup 6}), and cyanide (CN){sup {minus}} 15 refs., 18 figs., 1 tab.

  7. The potential role of aerobic biological waste treatment in regenerative life support systems

    NASA Technical Reports Server (NTRS)

    Shuler, M. L.; Nafis, D.; Sze, E.

    1981-01-01

    The purpose of the paper is to make a preliminary assessment of the feasibility of using aerobic biological waste treatment in closed systems. Issues that are addressed in this paper are: (1) how high a degree of material balance is possible, (2) how much might such a system weigh, and (3) how would system closure and weight be affected if animals were included in the system. A computer model has been developed to calculate for different scenarios the compositions and amounts of the streams entering or leaving the waste treatment system and to estimate the launch weight of such a system. A bench scale apparatus has been built to mimic the proposed waste treatment system; the experiments are used to verify model predictions and to improve model parameter estimations.

  8. Demonstration Bulletin: Aqueous Biological Treatment System (Fixed-Film Biodegradation), Biotrol, Inc

    EPA Science Inventory

    This patented biological treatment system, called the BioTrol Aqueous Treatment System (BATS)., uses an amended microbial population to achieve biological degradation. The system is considered amended when a specific microorganism is added to the indigenous microbial population ...

  9. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    PubMed Central

    Nottale, Laurent

    2014-01-01

    We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space—or of the underlying medium—can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations—geodesic, quantum-like, fluid mechanical, stochastic—of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided. PMID:24709901

  10. Macroscopic quantum-type potentials in theoretical systems biology.

    PubMed

    Nottale, Laurent

    2013-12-30

    We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space-or of the underlying medium-can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations-geodesic, quantum-like, fluid mechanical, stochastic-of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided.

  11. Biological surface engineering: a simple system for cell pattern formation.

    PubMed

    Zhang, S; Yan, L; Altman, M; Lässle, M; Nugent, H; Frankel, F; Lauffenburger, D A; Whitesides, G M; Rich, A

    1999-07-01

    Biological surface engineering using synthetic biological materials has a great potential for advances in our understanding of complex biological phenomena. We developed a simple system to engineer biologically relevant surfaces using a combination of self-assembling oligopeptide monolayers and microcontact printing (muCP). We designed and synthesized two oligopeptides containing a cell adhesion motif (RADS)n (n = 2 and 3) at the N-terminus, followed by an oligo(alanine) linker and a cysteine residue at the C-terminus. The thiol group of cysteine allows the oligopeptides to attach covalently onto a gold-coated surface to form monolayers. We then microfabricated a variety of surface patterns using the cell adhesion peptides in combination with hexa-ethylene glycol thiolate which resist non-specific adsorption of proteins and cells. The resulting patterns consist of areas either supporting or inhibiting cell adhesion, thus they are capable of aligning cells in a well-defined manner, leading to specific cell array and pattern formations.

  12. On Mechanical Transitions in Biologically Motivated Soft Matter Systems

    NASA Astrophysics Data System (ADS)

    Fogle, Craig

    The notion of phase transitions as a characterization of a change in physical properties pervades modern physics. Such abrupt and fundamental changes in the behavior of physical systems are evident in condensed matter system and also occur in nuclear and subatomic settings. While this concept is less prevalent in the field of biology, recent advances have pointed to its relevance in a number of settings. Recent studies have modeled both the cell cycle and cancer as phase transition in physical systems. In this dissertation we construct simplified models for two biological systems. As described by those models, both systems exhibit phase transitions. The first model is inspired by the shape transition in the nuclei of neutrophils during differentiation. During differentiation the nucleus transitions from spherical to a shape often described as "beads on a string." As a simplified model of this system, we investigate the spherical-to-wrinkled transition in an elastic core bounded to a fluid shell system. We find that this model exhibits a first-order phase transition, and the shape that minimizes the energy of the system scales as (micror3/kappa). . The second system studied is motivated by the dynamics of globular proteins. These proteins may undergoes conformational changes with large displacements relative to their size. Transitions between conformational states are not possible if the dynamics are governed strictly by linear elasticity. We construct a model consisting of an predominantly elastic region near the energetic minimum of the system and a non-linear softening of the system at a critical displacement. We find that this simple model displays very rich dynamics include a sharp dynamical phase transition and driving-force-dependent symmetry breaking.

  13. Web API for biology with a workflow navigation system.

    PubMed

    Kwon, Yeondae; Shigemoto, Yasumasa; Kuwana, Yoshikazu; Sugawara, Hideaki

    2009-07-01

    DNA Data Bank of Japan (DDBJ) provides Web-based systems for biological analysis, called Web APIs for biology (WABI). So far, we have developed over 20 SOAP services and several workflows that consist of a series of method invocations. In this article, we present newly developed services of WABI, that is, REST-based Web services, additional workflows and a workflow navigation system. Each Web service and workflow can be used as a complete service or a building block for programmers to construct more complex information processing systems. The workflow navigation system aims to help non-programming biologists perform analysis tasks by providing next applicable services on Web browsers according to the output of a previously selected service. With this function, users can apply multiple services consecutively only by following links without any programming or manual copy-and-paste operations on Web browsers. The listed services are determined automatically by the system referring to the dictionaries of service categories, the input/output types of services and HTML tags. WABI and the workflow navigation system are freely accessible at http://www.xml.nig.ac.jp/index.html and http://cyclamen.ddbj.nig.ac.jp/, respectively.

  14. Area-wide biological control of disease vectors and agents affecting wildlife.

    PubMed

    Reichard, R E

    2002-04-01

    Two examples of area-wide programmes, employing the sterile insect technique (SIT), which have eradicated a parasite and a disease vector common to domestic and wild animals are described. New World screwworm (NWS), Cochliomyia hominivorax, caused significant morbidity and mortality of livestock and wild mammals in tropical and subtropical areas of America before eradication was achieved in North America using the SIT and other components of an integrated pest management (IPM) programme. Movement of wild as well as domestic animals from an area which is infested with screwworm to a free area requires prophylactic treatment. Tsetse fly-borne trypanosomosis has an immense influence on the distribution of people and livestock in Africa. The immunotolerance of wildlife to the parasites is an important factor in maintaining some areas livestock free as wildlife refuges. Slaughter has ceased of wild hoofstock species considered to be disease reservoirs for control purposes. The SIT, combined with other IPM measures, has resulted in the eradication of the tsetse fly and trypanosomosis from Zanzibar. Other programmes in Africa are underway. Microbial 'biopesticides' have also been employed successfully against plant insect pests and some vectors of human disease. It seems likely that for the immediate future, wildlife may benefit from area-wide biological control programmes, intended mainly to protect humans and/or domestic animals.

  15. Acute ethanol administration affects zebrafish preference for a biologically inspired robot.

    PubMed

    Spinello, Chiara; Macrì, Simone; Porfiri, Maurizio

    2013-08-01

    Preclinical animal models constitute a cornerstone against which the reward processes involved in drug addiction are often studied and dissected. While rodents have traditionally represented the species of choice, a growing body of literature indicates that zebrafish are emerging as a valuable model organism. Specifically, several studies demonstrate that the effects of ethanol at the level of emotional- and cognitive-related domains can be reliably investigated using zebrafish. The rapidly evolving nature of these efforts allows substantial room for the development of novel experimental paradigms suited to this freshwater species. The field of ethorobotics may prove particularly beneficial, due to its ability to convey fully controllable and easily reproducible experimental tools. In this study, we addressed the possibility of using a biologically inspired robot to investigate the emotionally related properties of ethanol in a preference task in zebrafish. To this aim, we evaluated wild-type zebrafish preference toward a robotic stimulus and addressed whether ethanol administration (0.25% and 1.00% ethanol/water concentration) may alter such preferences. In accordance with our previous studies, we observed that zebrafish exhibit a natural attraction toward the robot. Additionally, in agreement with our predictions, we showed that ethanol administration abolishes such preferences. This work is the first to demonstrate that robotic stimuli can be used in zebrafish to investigate the reward-related properties of alcohol.

  16. Rearing environment affects development of the immune system in neonates.

    PubMed

    Inman, C F; Haverson, K; Konstantinov, S R; Jones, P H; Harris, C; Smidt, H; Miller, B; Bailey, M; Stokes, C

    2010-06-01

    Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect the direction of immune responses in later life. There is a need for a manipulable animal model of environmental influences on the development of microbiota and the immune system during early life. We assessed the effects of rearing under low- (farm, sow) and high-hygiene (isolator, milk formula) conditions on intestinal microbiota and immune development in neonatal piglets, because they can be removed from the mother in the first 24 h for rearing under controlled conditions and, due to placental structure, neither antibody nor antigen is transferred in utero. Microbiota in both groups was similar between 2 and 5 days. However, by 12-28 days, piglets reared on the mother had more diverse flora than siblings reared in isolators. Dendritic cells accumulated in the intestinal mucosa in both groups, but more rapidly in isolator piglets. Importantly, the minority of 2-5-day-old farm piglets whose microbiota resembled that of an older (12-28-day-old) pig also accumulated dendritic cells earlier than the other farm-reared piglets. Consistent with dendritic cell control of T cell function, the effects on T cells occurred at later time-points, and mucosal T cells from high-hygiene, isolator pigs made less interleukin (IL)-4 while systemic T cells made more IL-2. Neonatal piglets may be a valuable model for studies of the effects of interaction between microbiota and immune development on allergy.

  17. Lean Big Data integration in systems biology and systems pharmacology.

    PubMed

    Ma'ayan, Avi; Rouillard, Andrew D; Clark, Neil R; Wang, Zichen; Duan, Qiaonan; Kou, Yan

    2014-09-01

    Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in gene and protein expression in human cell lines can be combined with knowledge about human disease, side effects induced by drugs, and mouse phenotypes. Such data integration efforts can be achieved through the conversion of data from the various resources into single-node-type networks, gene-set libraries, or multipartite graphs. This approach can lead us to the identification of more relationships between genes, drugs, and phenotypes as well as benchmark computational and experimental methods. Overall, this lean 'Big Data' integration strategy will bring us closer toward the goal of realizing personalized medicine.

  18. Concluding remarks of Autonomous Biological Systems (ABS) experiments.

    PubMed

    Ishikawa, Y; Kobayashi, K; Mizutani, H; Kawasaki, Y; Koike, J; Ijiri, K; Yamashita, M; Sugiura, K; Poynter, J; MacCallum, T; Anderson, G

    1998-12-01

    Team efforts for analysis on the Autonomous Biological Systems (ABS) space experiments are summarized here to conclude scientific findings, and to scope the extended studies in future. From the three experiments on Space Shuttle and Space Station Mir, a closed ecological system modeled by the ABS was verified to be capable of sustaining its members of animals and plants under space environment for a period of several months. The animals successfully completed their life cycle in space during the course of these experiments, this was the first time that the life cycle of higher organisms had been completed in space and ecological system. Importance of gravity for ecology was proven at the same time. Gravity is a dominant factor for ecology by formulating spatial patterns and distribution of members of ecological system. Under microgravity, the fate of ecological system was found highly sensitive against the variation of environmental factor, such as light illumination cycle.

  19. Factors affecting the flight capacity of Tetrastichus planipennisi (Hymenoptera: Eulophidae), a classical biological control agent of Agrilus planipennis (Coleoptera: Buprestidae).

    PubMed

    Fahrner, Samuel J; Lelito, Jonathan P; Blaedow, Karen; Heimpel, George E; Aukema, Brian H

    2014-12-01

    The dispersal characteristics of a biological control agent can have direct implications on the ability of that agent to control populations of a target host. Tetrastichus planipennisi Yang (Hymenoptera: Eulophidae) is a parasitic wasp native to eastern Asia that has been introduced into the United States as part of a classical biological control program against the emerald ash borer Agrilus planipennis Fairmaire (Coleoptera: Buprestidae). We used computer-monitored flight mills to investigate the role of age, feeding status, mating status, and size on the flight capacity of female T. planipennisi over a 24-h period. We also compared flight capacity between sexes. Flight distance of female T. planipennisi representative of populations released in the biological control program averaged 1.26 km in 24 h with a maximum flight of just over 7 km. Median flight distance, however, was 422 m. The flight capacity of females fed a honey-water solution was 41× that of females provided only water, who flew very little. Larger females were capable of flying farther distances, but age did not affect the flight capacity of females up to 70 d posteclosion. Females dispersed 6× farther than did their smaller, male counterparts. The implications of our findings to host-parasitoid interactions and release protocols for distributing T. planipennisi are discussed.

  20. Wearable System for Acquisition and Monitoring of Biological Signals

    NASA Astrophysics Data System (ADS)

    Piccinini, D. J.; Andino, N. B.; Ponce, S. D.; Roberti, MA; López, y. N.

    2016-04-01

    This paper presents a modular, wearable system for acquisition and wireless transmission of biological signals. Configurable slaves for different signals (such as ECG, EMG, inertial sensors, and temperature) based in the ADS1294 Medical Analog Front End are connected to a Master, based in the CC3200 microcontroller, both from Texas Instruments. The slaves are configurable according to the specific application, providing versatility to the wearable system. The battery consumption is reduced, through a couple of Li-ion batteries and the circuit has also a battery charger. A custom made box was designed and fabricated in a 3D printer, preserving the requirements of low cost, low weight and safety recommendations.

  1. Recent Applications of Kirkwood-Buff Theory to Biological Systems

    PubMed Central

    Pierce, Veronica; Kang, Myungshim; Aburi, Mahalaxmi; Weerasinghe, Samantha; Smith, Paul E.

    2008-01-01

    The effect of cosolvents on biomolecular equilibria has traditionally been rationalized using simple binding models. More recently, a renewed interest in the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided new information on the effects of osmolytes and denaturants and their interactions with biomolcules. Here we review the status of KB theory as applied to biological systems. In particular, the existing models of denaturation are analyzed in terms of KB theory, and the use of KB theory to interpret computer simulation data for these systems is discussed. PMID:18043873

  2. Mass balances for a biological life support system simulation model

    NASA Technical Reports Server (NTRS)

    Volk, Tyler; Rumel, John D.

    1987-01-01

    Design decisions to aid the development of future space-based biological life support systems (BLSS) can be made with simulation models. Here the biochemical stoichiometry is developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady-state system with wheat as the sole food source.

  3. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    PubMed

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.

  4. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    PubMed Central

    He, Fei; Murabito, Ettore; Westerhoff, Hans V.

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. PMID:27075000

  5. Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

    PubMed

    Hucka, M; Finney, A; Bornstein, B J; Keating, S M; Shapiro, B E; Matthews, J; Kovitz, B L; Schilstra, M J; Funahashi, A; Doyle, J C; Kitano, H

    2004-06-01

    Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

  6. Nutrient availability affects pigment production but not growth in lichens of biological soil crusts

    USGS Publications Warehouse

    Bowker, M.A.; Koch, G.W.; Belnap, J.; Johnson, N.C.

    2008-01-01

    Recent research suggests that micronutrients such as Mn may limit growth of slow-growing biological soil crusts (BSCs) in some of the drylands of the world. These soil surface communities contribute strongly to arid ecosystem function and are easily degraded, creating a need for new restoration tools. The possibility that Mn fertilization could be used as a restoration tool for BSCs has not been tested previously. We used microcosms in a controlled greenhouse setting to investigate the hypothesis that Mn may limit photosynthesis and consequently growth in Collema tenax, a dominant N-fixing lichen found in BSCs worldwide. We found no evidence to support our hypothesis; furthermore, addition of other nutrients (primarily P, K, and Zn) had a suppressive effect on gross photosynthesis (P = 0.05). We also monitored the growth and physiological status of our microcosms and found that other nutrients increased the production of scytonemin, an important sunscreen pigment, but only when not added with Mn (P = 0.01). A structural equation model indicated that this effect was independent of any photosynthesis-related variable. We propose two alternative hypotheses to account for this pattern: (1) Mn suppresses processes needed to produce scytonemin; and (2) Mn is required to suppress scytonemin production at low light, when it is an unnecessary photosynthate sink. Although Mn fertilization does not appear likely to increase photosynthesis or growth of Collema, it could have a role in survivorship during environmentally stressful periods due to modification of scytonemin production. Thus, Mn enrichment should be studied further for its potential to facilitate BSC rehabilitation. ?? 2008 Elsevier Ltd.

  7. Normal and impaired charge transport in biological systems

    NASA Astrophysics Data System (ADS)

    Miller, John H.; Villagrán, Martha Y. Suárez; Maric, Sladjana; Briggs, James M.

    2015-03-01

    We examine the physics behind some of the causes (e.g., hole migration and localization that cause incorrect base pairing in DNA) and effects (due to amino acid replacements affecting mitochondrial charge transport) of disease-implicated point mutations, with emphasis on mutations affecting mitochondrial DNA (mtDNA). First we discuss hole transport and localization in DNA, including some of our quantum mechanical modeling results, as they relate to certain mutations in cancer. Next, we give an overview of electron and proton transport in the mitochondrial electron transport chain, and how such transport can become impaired by mutations implicated in neurodegenerative diseases, cancer, and other major illnesses. In particular, we report on our molecular dynamics (MD) studies of a leucine→arginine amino acid replacement in ATP synthase, encoded by the T→G point mutation at locus 8993 of mtDNA. This mutation causes Leigh syndrome, a devastating maternally inherited neuromuscular disorder, and has been found to trigger rapid tumor growth in prostate cancer cell lines. Our MD results suggest, for the first time, that this mutation adversely affects water channels that transport protons to and from the c-ring of the rotary motor ATP synthase, thus impairing the ability of the motor to produce ATP. Finally, we discuss possible future research topics for biological physics, such as mitochondrial complex I, a large proton-pumping machine whose physics remains poorly understood.

  8. Enabling Systems Biology: A Scientific Problem-Solving Environment

    SciTech Connect

    Singhal, Mudita; Stephan, Eric G.; Klicker, Kyle R.; Trease, Lynn L.; Chin, George; Gracio, Deborah K.; Payne, Deborah A.

    2004-06-06

    Biologists today are striving to solve multidisciplinary, complex systems biology questions. To successfully address these questions, software tools must be created to allow scientists to capture data and information, to share this information, and to analyze the data as elements of a complete system. At Pacific Northwest National Laboratory (PNNL) we are creating the Computational Cell Environment (CCE), a biology-centered collaborative problem-solving environment (PSE) with the goal of providing data retrieval, management, and analysis through all aspects of biological study including sequencing, gene/protein expression, networks, and communities. A horizontal prototype called BioPSE, demonstrates this vision. Our initial work is centered on developing the Distributed Data Management and Analysis subsystem which is an innovative scientific user environment as well as a specific tool for retrieving data from multiple heterogonous data stores; providing storage facilities that support pedigree tracking and data and information analysis under a common user interface. With time, many such individual subsystems will be developed and integrated to fulfill the CCE vision.

  9. Scaling Reversible Adhesion in Synthetic and Biological Systems

    NASA Astrophysics Data System (ADS)

    Bartlett, Michael; Irschick, Duncan; Crosby, Alfred

    2013-03-01

    High capacity, easy release polymer adhesives, as demonstrated by a gecko's toe, present unique opportunities for synthetic design. However, without a framework that connects biological and synthetic adhesives from basic nanoscopic features to macroscopic systems, synthetic mimics have failed to perform favorably at large length scales. Starting from an energy balance, we develop a scaling approach to understand unstable interfacial fracture over multiple length scales. The simple theory reveals that reversibly adhesive polymers do not rely upon fibrillar features but require contradicting attributes: maximum compliance normal to the substrate and minimum compliance in the loading direction. We use this counterintuitive criterion to create reversible, easy release adhesives at macroscopic sizes (100 cm2) with unprecedented force capacities on the order of 3000 N. Importantly, we achieve this without fibrillar features, supporting our predictions and emphasizing the importance of subsurface anatomy in biological adhesive systems. Our theory describes adhesive force capacity as a function of material properties and geometry and is supported by over 1000 experiments, spanning both synthetic and biological adhesives, with agreement over 14 orders of magnitude in adhesive force.

  10. Soil organic matter dynamics under Beech and Hornbeam as affected by soil biological activity

    NASA Astrophysics Data System (ADS)

    Kooijman, A. M.; Cammeraat, L. H.

    2009-04-01

    Organic matter dynamics are highly affected both the soil fauna as well as the source of organic matter, having important consequences for the spatial heterogeneity of organic matter storage and conversion. We studied oldgrowth mixed deciduous forests in Central-Luxemburg on decalcified dolomitic marl, dominated by high-degradable hornbeam (Carpinus betulus L.) or low-degradable beech (Fagus sylvatica L.). Decomposition was measured both in the laboratory and in the field. Litter decomposition was higher for hornbeam than for beech under laboratory conditions, but especially in the field, which is mainly to be attributed to macro-fauna activity, specifically to earthworms (Lumbricus terrestris and Allolobophora species). We also investigated differences between beech and hornbeam with regard to litter input and habitat conditions. Total litter input was the same, but contribution of beech and hornbeam litter clearly differed between the two species. Also, mass of the ectorganic horizon and soil C:N ratio were significantly higher for beech, which was reflected in clear differences in the development of ectorganic profiles on top of the soil. Under beech a mull-moder was clearly present with a well developed fermentation and litter horizon, whereas under hornbeam all litter is incorporated into the soil, leaving the mineral soil surface bear in late summer (mull-type of horizon). In addition to litter quality, litter decomposition was affected by pH and soil moisture. Both pH and soil moisture were higher under hornbeam than under beech, which may reflect differences in soil development and litter quality effects over longer time scales. Under beech, dense layers of low-degradable litter may prevent erosion, and increase clay eluviation and leaching of base cations, leading to acid and dry conditions, which further decrease litter decay. Under hornbeam, the soil is not protected by a litter layer, and clay eluviation and acidification may be counteracted by erosion

  11. Comprehensive Evaluation of Biological Growth Control by Chlorine-Based Biocides in Power Plant Cooling Systems Using Tertiary Effluent

    PubMed Central

    Chien, Shih-Hsiang; Dzombak, David A.; Vidic, Radisav D.

    2013-01-01

    Abstract Recent studies have shown that treated municipal wastewater can be a reliable cooling water alternative to fresh water. However, elevated nutrient concentration and microbial population in wastewater lead to aggressive biological proliferation in the cooling system. Three chlorine-based biocides were evaluated for the control of biological growth in cooling systems using tertiary treated wastewater as makeup, based on their biocidal efficiency and cost-effectiveness. Optimal chemical regimens for achieving successful biological growth control were elucidated based on batch-, bench-, and pilot-scale experiments. Biocide usage and biological activity in planktonic and sessile phases were carefully monitored to understand biological growth potential and biocidal efficiency of the three disinfectants in this particular environment. Water parameters, such as temperature, cycles of concentration, and ammonia concentration in recirculating water, critically affected the biocide performance in recirculating cooling systems. Bench-scale recirculating tests were shown to adequately predict the biocide residual required for a pilot-scale cooling system. Optimal residuals needed for proper biological growth control were 1, 2–3, and 0.5–1 mg/L as Cl2 for NaOCl, preformed NH2Cl, and ClO2, respectively. Pilot-scale tests also revealed that Legionella pneumophila was absent from these cooling systems when using the disinfectants evaluated in this study. Cost analysis showed that NaOCl is the most cost-effective for controlling biological growth in power plant recirculating cooling systems using tertiary-treated wastewater as makeup. PMID:23781129

  12. Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

    NASA Technical Reports Server (NTRS)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

    The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

  13. [Alternative tactile system: C-fibers coding the affective aspect].

    PubMed

    Hua, Qing-Ping; Luo, Fei

    2007-10-01

    It has been accepted that human tactile sensation is mediated exclusively by large myelinated (Abeta) fibres. Nevertheless, recent studies indicated a dual mechanoceptive innervation of the skin in various mammals. Besides the known A fibers, the skin is also innervated by slow-conducting, low-threshold, small unmyelinated (C) afferents. These unmyelinated fibers respond vigorously to innocuous skin deformation, but poorly to rapid skin movement. They project to outer lamina II of spinal cord, and form synapse with the secondary sensory neurons. The latter then project to insular cortex via spinothalamic tracts. Functional magnetic resonance imaging (fMRI) studies showed that a slowly moving tactile stimulus along hairy skin produced a strong activation of the insular cortex. Pleasant touch has also been demonstrated to activate orbitofrontal cortex adjacent to areas responding to pleasant taste and smell. Overall, the response characteristics and activated brain regions suggest that they are related with the limbic system and affective aspect rather than tactile discriminative function.

  14. Ghosts, UFOs, and magic: positive affect and the experiential system.

    PubMed

    King, Laura A; Burton, Chad M; Hicks, Joshua A; Drigotas, Stephen M

    2007-05-01

    Three studies examined the potential interactions of the experiential system and positive affect (PA) in predicting superstitious beliefs and sympathetic magic. In Study 1, experientiality and induced positive mood interacted to predict the emergence of belief in videos purporting to show unidentified flying objects or ghosts. In Study 2, naturally occurring PA interacted with experientiality to predict susceptibility to sympathetic magic, specifically difficulty in throwing darts at a picture of a baby (demonstrating the law of similarity). In Study 3, induced mood interacted with experientiality to predict sitting farther away from, and expressing less liking for, a partner who had stepped in excrement (demonstrating the law of contagion). Results are interpreted as indicating that PA promotes experiential processing. Implications for the psychology of nonrational beliefs and behaviors are discussed.

  15. Artificial cells: building bioinspired systems using small-scale biology.

    PubMed

    Zhang, Ying; Ruder, Warren C; LeDuc, Philip R

    2008-01-01

    Artificial cells have generated much interest since the concept was introduced by Aleksandr Oparin in the 1920s, and they have had an impact on the pharmaceutical and biotechnology industry in various areas, including potential therapeutic applications. Here, we discuss the development of small-scale, bio-inspired artificial cell components that recreate the function of key cellular and physiological systems. We describe artificial cells, selected current applications and how small-scale biology could be used to provide what might be a next-generation approach in this area. We believe that this type of work is in its infancy and that exploiting small-scale biological inspiration in the field of artificial cells has great potential for successes in the future.

  16. Intranasal delivery of biologics to the central nervous system.

    PubMed

    Lochhead, Jeffrey J; Thorne, Robert G

    2012-05-15

    Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS.

  17. Computational intelligence approaches for pattern discovery in biological systems.

    PubMed

    Fogel, Gary B

    2008-07-01

    Biology, chemistry and medicine are faced by tremendous challenges caused by an overwhelming amount of data and the need for rapid interpretation. Computational intelligence (CI) approaches such as artificial neural networks, fuzzy systems and evolutionary computation are being used with increasing frequency to contend with this problem, in light of noise, non-linearity and temporal dynamics in the data. Such methods can be used to develop robust models of processes either on their own or in combination with standard statistical approaches. This is especially true for database mining, where modeling is a key component of scientific understanding. This review provides an introduction to current CI methods, their application to biological problems, and concludes with a commentary about the anticipated impact of these approaches in bioinformatics.

  18. ``Recycling'' Geophysics: Monitoring and Isotopic Analysis of Engineered Biological Systems

    NASA Astrophysics Data System (ADS)

    Doherty, R.; Singh, K. P.; Ogle, N.; Ntarlagiannis, D.

    2010-12-01

    The emerging sub discipline of biogeophysics has provoked debate on the mechanisms of microbial processes that may contribute to geophysical signatures. At field scales geophysical signatures are often non unique due to the many parameters (physical, chemical, and biological) that are involved. It may be easier to apply geophysical techniques such as electrodic potential (EP), self potential (SP) and induced polarization (IP) to engineered biological systems where there is a degree of control over the design of the physical and chemical domain. Here we present results of a column experiment that was designed to anaerobically biodegrade dissolved organic matter in landfill leachate. The column utilises a recycled porous media (concrete) to help sequester organic carbon. Electrodic potential, self potential and induced polarisation are used in conjunction with chemical and isotopic techniques to monitor the effectiveness of this approach. Preliminary carbon and oxygen isotopic analysis on concrete from the column in contact with leachate show isotopic enrichment suggesting abiotic precipitation of carbonates.

  19. Process-based design of dynamical biological systems

    PubMed Central

    Tanevski, Jovan; Todorovski, Ljupčo; Džeroski, Sašo

    2016-01-01

    The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered. PMID:27686219

  20. Epigenomics and the concept of degeneracy in biological systems

    PubMed Central

    Mason, Paul H.; Barron, Andrew B.

    2014-01-01

    Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

  1. Epigenomics and the concept of degeneracy in biological systems.

    PubMed

    Maleszka, Ryszard; Mason, Paul H; Barron, Andrew B

    2014-05-01

    Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy-referring to the multiple pathways that a system recruits to achieve functional plasticity-is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability.

  2. Microbial diversity of biological filters in recirculating aquaculture systems.

    PubMed

    Schreier, Harold J; Mirzoyan, Natella; Saito, Keiko

    2010-06-01

    Development of environmentally sustainable farming of marine and freshwater species using recirculating aquaculture systems (RASs) requires a complete understanding of the biological component involved in wastewater treatment. This component integrates biofilters composed of microbial communities whose structure, dynamics, and activities are responsible for system success. Engineering highly efficient, environmentally sound, disease-free, and economically viable systems necessitates a thorough knowledge of microbial processes involved in all facets of RAS biofilters and has only recently been the focus of comprehensive studies. These studies have included the application of molecular tools to characterize community diversity and have identified key processes useful for improving system performance. In this paper we summarize the current understanding of the microbial diversity and physiology of RAS biofilters and discuss directions for future studies.

  3. Process-based design of dynamical biological systems

    NASA Astrophysics Data System (ADS)

    Tanevski, Jovan; Todorovski, Ljupčo; Džeroski, Sašo

    2016-09-01

    The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered.

  4. Mass balances for a biological life support system simulation model

    NASA Technical Reports Server (NTRS)

    Volk, Tyler; Rummel, John D.

    1987-01-01

    Design decisions to aid the development of future space based biological life support systems (BLSS) can be made with simulation models. The biochemistry stoichiometry was developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady state system with wheat as the sole food source. The large scale dynamics of a materially closed (BLSS) computer model is described in a companion paper. An extension of this methodology can explore multifood systems and more complex biochemical dynamics while maintaining whole system closure as a focus.

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

    PubMed

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

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

  6. Systems biology of the autophagy-lysosomal pathway.

    PubMed

    Jegga, Anil G; Schneider, Lonnie; Ouyang, Xiaosen; Zhang, Jianhua

    2011-05-01

    The mechanisms of the control and activity of the autophagy-lysosomal protein degradation machinery are emerging as an important theme for neurodevelopment and neurodegeneration. However, the underlying regulatory and functional networks of known genes controlling autophagy and lysosomal function and their role in disease are relatively unexplored. We performed a systems biology-based integrative computational analysis to study the interactions between molecular components and to develop models for regulation and function of genes involved in autophagy and lysosomal function. Specifically, we analyzed transcriptional and microRNA-based post-transcriptional regulation of these genes and performed functional enrichment analyses to understand their involvement in nervous system-related diseases and phenotypes. Transcriptional regulatory network analysis showed that binding sites for transcription factors, SREBP1, USF, AP-1 and NFE2, are common among autophagy and lysosomal genes. MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. Pathway enrichment analyses revealed that the mTOR and insulin signaling pathways are important in the regulation of genes involved in autophagy. In addition, we found that glycosaminoglycan and glycosphingolipid pathways also make a major contribution to lysosomal gene regulation. The analysis confirmed the known contribution of the autophagy-lysosomal genes to Alzheimer and Parkinson diseases and also revealed potential involvement in tuberous sclerosis, neuronal ceroidlipofuscinoses, sepsis and lung, liver and prostatic neoplasms. To further probe the impact of autophagy-lysosomal gene deficits on neurologically-linked phenotypes, we also mined the mouse knockout phenotype data for the autophagylysosomal genes and found them to be highly predictive of nervous system dysfunction. Overall this study demonstrates the utility of systems

  7. High intensity exercise affects diurnal variation of some biological markers in trained subjects.

    PubMed

    Hammouda, O; Chtourou, H; Chahed, H; Ferchichi, S; Chaouachi, A; Kallel, C; Miled, A; Chamari, K; Souissi, N

    2012-11-01

    The study investigated if markers of muscle injury and antioxidant status were affected by a Wingate test performed at 2 different times of day. 15 young male footballers performed 2 tests (randomized) at 07:00-h and 17:00-h. Fasting blood samples were collected before and 3 min after each test for assessment of markers of muscle injury and antioxidant status. Resting oral temperature was recorded during each session. Peak power (10.76 ± 1.05 vs. 11.15 ± 0.83 W.kg( - 1)) and fatigue index (0.41 ± 0.04 vs. 0.49 ± 0.13%) during the Wingate test, and core temperature, were significantly higher (all p<0.05) in the evening. Markers of muscle injury were significantly higher in the evening before and after exercise (e. g., 148.7 ± 67.05 vs. 195 ± 74.6 and 191.6 ± 79.52 vs. 263.6 ± 96.06 IU.L (- 1), respectively, for creatine kinase; both p<0.001). Antioxidant parameters increased after the Wingate test but only resting values were significantly higher in the morning (e. g., 1.33 ± 0.19 vs. 1.19 ± 0.14 µmol.L (- 1) for total antioxidant status; p<0.05). The results indicate that muscle injury and antioxidant activity after the Wingate test were higher in the evening, suggesting a possible link between the biochemical measures and the diurnal fluctuation of anaerobic performance. However, repetition of this study after prescribed rather than self-selected exercise intensity is recommended.

  8. Computational Systems Biology in Cancer: Modeling Methods and Applications

    PubMed Central

    Materi, Wayne; Wishart, David S.

    2007-01-01

    In recent years it has become clear that carcinogenesis is a complex process, both at the molecular and cellular levels. Understanding the origins, growth and spread of cancer, therefore requires an integrated or system-wide approach. Computational systems biology is an emerging sub-discipline in systems biology that utilizes the wealth of data from genomic, proteomic and metabolomic studies to build computer simulations of intra and intercellular processes. Several useful descriptive and predictive models of the origin, growth and spread of cancers have been developed in an effort to better understand the disease and potential therapeutic approaches. In this review we describe and assess the practical and theoretical underpinnings of commonly-used modeling approaches, including ordinary and partial differential equations, petri nets, cellular automata, agent based models and hybrid systems. A number of computer-based formalisms have been implemented to improve the accessibility of the various approaches to researchers whose primary interest lies outside of model development. We discuss several of these and describe how they have led to novel insights into tumor genesis, growth, apoptosis, vascularization and therapy. PMID:19936081

  9. The emerging genomics and systems biology research lead to systems genomics studies.

    PubMed

    Yang, Mary Qu; Yoshigoe, Kenji; Yang, William; Tong, Weida; Qin, Xiang; Dunker, A; Chen, Zhongxue; Arbania, Hamid R; Liu, Jun S; Niemierko, Andrzej; Yang, Jack Y

    2014-01-01

    Synergistically integrating multi-layer genomic data at systems level not only can lead to deeper insights into the molecular mechanisms related to disease initiation and progression, but also can guide pathway-based biomarker and drug target identification. With the advent of high-throughput next-generation sequencing technologies, sequencing both DNA and RNA has generated multi-layer genomic data that can provide DNA polymorphism, non-coding RNA, messenger RNA, gene expression, isoform and alternative splicing information. Systems biology on the other hand studies complex biological systems, particularly systematic study of complex molecular interactions within specific cells or organisms. Genomics and molecular systems biology can be merged into the study of genomic profiles and implicated biological functions at cellular or organism level. The prospectively emerging field can be referred to as systems genomics or genomic systems biology. The Mid-South Bioinformatics Centre (MBC) and Joint Bioinformatics Ph.D. Program of University of Arkansas at Little Rock and University of Arkansas for Medical Sciences are particularly interested in promoting education and research advancement in this prospectively emerging field. Based on past investigations and research outcomes, MBC is further utilizing differential gene and isoform/exon expression from RNA-seq and co-regulation from the ChiP-seq specific for different phenotypes in combination with protein-protein interactions, and protein-DNA interactions to construct high-level gene networks for an integrative genome-phoneme investigation at systems biology level.

  10. Identification of key water quality characteristics affecting the filterability of biologically treated effluent in low-pressure membrane filtration.

    PubMed

    Nguyen, T; Fan, L; Roddick, F A; Harris, J L

    2010-01-01

    There are many water quality characteristics which could influence the filterability of biologically treated effluent from Melbourne's Western Treatment Plant (WTP). Statistical correlation was used to identify the key water characteristics affecting the microfiltration (MF) and ultrafiltration (UF) filterability in terms of permeate volume of the treated effluent. The models developed showed that turbidity, dissolved organic carbon (DOC) and total suspended solids (TSS) were the key factors which influenced the MF and UF filterability. Turbidity was the dominant factor affecting the accuracy of the model for MF filterability while DOC was the major factor affecting the accuracy of the model for UF filterability. A prediction accuracy of 85% was obtained for MF and 86% for UF filterability of the WTP effluent. The characteristics of the organic components of the wastewater were demonstrated by EEM spectra to have seasonal variation which would have reduced the prediction accuracy. As turbidity, DOC and TSS can be determined on-line, the models would be useful for rapid prediction of the filterability of WTP effluent and this may assist the control of low-pressure membrane filtration processes.

  11. Disciplinary baptisms: a comparison of the naming stories of genetics, molecular biology, genomics, and systems biology.

    PubMed

    Powell, Alexander; O'Malley, Maureen A; Müller-Wille, Staffan; Calvert, Jane; Dupré, John

    2007-01-01

    Understanding how scientific activities use naming stories to achieve disciplinary status is important not only for insight into the past, but for evaluating current claims that new disciplines are emerging. In order to gain a historical understanding of how new disciplines develop in relation to these baptismal narratives, we compare two recently formed disciplines, systems biology and genomics, with two earlier related life sciences, genetics and molecular biology. These four disciplines span the twentieth century, a period in which the processes of disciplinary demarcation fundamentally changed from those characteristic of the nineteenth century. We outline how the establishment of each discipline relies upon an interplay of factors that include paradigmatic achievements, technological innovation, and social formations. Our focus, however, is the baptism stories that give the new discipline a founding narrative and articulate core problems, general approaches and constitutive methods. The highly plastic process of achieving disciplinary identity is further marked by the openness of disciplinary definition, tension between technological possibilities and the ways in which scientific issues are conceived and approached, synthesis of reductive and integrative strategies, and complex social interactions. The importance--albeit highly variable--of naming stories in these four cases indicates the scope for future studies that focus on failed disciplines or competing names. Further attention to disciplinary histories could, we suggest, give us richer insight into scientific development.

  12. Systems Biology and P4 Medicine: Past, Present, and Future

    PubMed Central

    Hood, Leroy

    2013-01-01

    Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB) has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes) for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.). The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to detect and treat

  13. Unmanned Aircraft Systems complement biologging in spatial ecology studies.

    PubMed

    Mulero-Pázmány, Margarita; Barasona, Jose Ángel; Acevedo, Pelayo; Vicente, Joaquín; Negro, Juan José

    2015-11-01

    The knowledge about the spatial ecology and distribution of organisms is important for both basic and applied science. Biologging is one of the most popular methods for obtaining information about spatial distribution of animals, but requires capturing the animals and is often limited by costs and data retrieval. Unmanned Aircraft Systems (UAS) have proven their efficacy for wildlife surveillance and habitat monitoring, but their potential contribution to the prediction of animal distribution patterns and abundance has not been thoroughly evaluated. In this study, we assess the usefulness of UAS overflights to (1) get data to model the distribution of free-ranging cattle for a comparison with results obtained from biologged (GPS-GSM collared) cattle and (2) predict species densities for a comparison with actual density in a protected area. UAS and biologging derived data models provided similar distribution patterns. Predictions from the UAS model overestimated cattle densities, which may be associated with higher aggregated distributions of this species. Overall, while the particular researcher interests and species characteristics will influence the method of choice for each study, we demonstrate here that UAS constitute a noninvasive methodology able to provide accurate spatial data useful for ecological research, wildlife management and rangeland planning.

  14. Cellular respiration: replicating in vivo systems biology for in ...

    EPA Pesticide Factsheets

    This editorial develops a philosophy for expanding the scope of Journal of Breath Research (JBR) into the realm of cellular level study, and links certain topics back to more traditional systemic research for understanding human health based on exhaled breath constituents. The express purpose is to provide a publication outlet for novel breath related research that includes in vitro studies, especially those that explore the biological origin and expression of compounds that may ultimately influence the constituents of exhaled breath. The new topics include all manner of methods and instrumentations for making in vivo and in vitro measurements, the use of different biological media (blood, urine saliva, swabs) including human and microbial cell-lines, in vitro kinetic studies of metabolism, and advances in ex vivo methods for maintaining metabolic competency and viability of biological samples. Traditionally, JBR has published articles on human breath analysis for diagnosing disease, tracking health state, assessing the dose and effect of exogenous chemicals, and contributions of malodorous compounds from the oral/nasal cavity. These have also included research describing novel sampling and analytical technologies, most notably those implementing mass spectrometry, chemical sensors and optical measurement instrumentation (Amann and Smith 2013). The journal’s original scope has also embraced animal models as surrogates for human sampling, new mathematical and

  15. Analytical approaches to metabolomics and applications to systems biology.

    PubMed

    Wang, Jeffrey H; Byun, Jaeman; Pennathur, Subramaniam

    2010-09-01

    Phenotypic expression of renal diseases encompasses a complex interaction between genetic, environmental, and local tissue factors. The level of complexity requires integrated understanding of perturbations in the network of genes, proteins, and metabolites. Metabolomics attempts to systematically identify and quantitate metabolites from biological samples. The small molecules represent the end result of complexity of biological processes in a given cell, tissue, or organ, and thus form attractive candidates to understand disease phenotypes. Metabolites represent a diverse group of low-molecular-weight structures including lipids, amino acids, peptides, nucleic acids, and organic acids, which makes comprehensive analysis a difficult analytical challenge. The recent rapid development of a variety of analytical platforms based on mass spectrometry and nuclear magnetic resonance have enabled separation, characterization, detection, and quantification of such chemically diverse structures. Continued development of bioinformatics and analytical strategies will accelerate widespread use and integration of metabolomics into systems biology. Here, we will discuss analytical and bioinformatic techniques and highlight recent studies that use metabolomics in understanding pathophysiology of disease processes.

  16. Multimode lasers as analogs of complex biological systems (a survey)

    NASA Astrophysics Data System (ADS)

    Danilov, O. B.; Rosanov, N. N.; Solov'ev, N. A.; Soms, L. N.

    2016-04-01

    Simulating the activity of complex biological systems, in particular, the human brain, is a topical problem the solution of which is necessary both for understanding their functioning and for developing new classes of computational system based on operating principles of the brain. Some features and analogies that can be found in the operation of laser systems and brain and used for developing new generation computational systems are discussed. The appropriateness of such analogies is justified by the fact that both laser systems and the brain are open (interacting with the environment) dissipative spatially distributed nonlinear systems. Therefore, laser optical systems and, in particular, systems with dissipative optical solitons offer an opportunity to experimentally and theoretically model some important cognitive brain functions. One of particularities of the brain operation is the ability to manipulate images. Proceeding from this, in this work, problems related to generation and amplification with laser of spatial structures (images), as well as to amplification of signals coming to it from outside are discussed.

  17. Novel metaheuristic for parameter estimation in nonlinear dynamic biological systems

    PubMed Central

    Rodriguez-Fernandez, Maria; Egea, Jose A; Banga, Julio R

    2006-01-01

    Background We consider the problem of parameter estimation (model calibration) in nonlinear dynamic models of biological systems. Due to the frequent ill-conditioning and multi-modality of many of these problems, traditional local methods usually fail (unless initialized with very good guesses of the parameter vector). In order to surmount these difficulties, global optimization (GO) methods have been suggested as robust alternatives. Currently, deterministic GO methods can not solve problems of realistic size within this class in reasonable computation times. In contrast, certain types of stochastic GO methods have shown promising results, although the computational cost remains large. Rodriguez-Fernandez and coworkers have presented hybrid stochastic-deterministic GO methods which could reduce computation time by one order of magnitude while guaranteeing robustness. Our goal here was to further reduce the computational effort without loosing robustness. Results We have developed a new procedure based on the scatter search methodology for nonlinear optimization of dynamic models of arbitrary (or even unknown) structure (i.e. black-box models). In this contribution, we describe and apply this novel metaheuristic, inspired by recent developments in the field of operations research, to a set of complex identification problems and we make a critical comparison with respect to the previous (above mentioned) successful methods. Conclusion Robust and efficient methods for parameter estimation are of key importance in systems biology and related areas. The new metaheuristic presented in this paper aims to ensure the proper solution of these problems by adopting a global optimization approach, while keeping the computational effort under reasonable values. This new metaheuristic was applied to a set of three challenging parameter estimation problems of nonlinear dynamic biological systems, outperforming very significantly all the methods previously used for these benchmark

  18. Listeriomics: an Interactive Web Platform for Systems Biology of Listeria.

    PubMed

    Bécavin, Christophe; Koutero, Mikael; Tchitchek, Nicolas; Cerutti, Franck; Lechat, Pierre; Maillet, Nicolas; Hoede, Claire; Chiapello, Hélène; Gaspin, Christine; Cossart, Pascale

    2017-01-01

    As for many model organisms, the amount of Listeria omics data produced has recently increased exponentially. There are now >80 published complete Listeria genomes, around 350 different transcriptomic data sets, and 25 proteomic data sets available. The analysis of these data sets through a systems biology approach and the generation of tools for biologists to browse these various data are a challenge for bioinformaticians. We have developed a web-based platform, named Listeriomics, that integrates different tools for omics data analyses, i.e., (i) an interactive genome viewer to display gene expression arrays, tiling arrays, and sequencing data sets along with proteomics and genomics data sets; (ii) an expression and protein atlas that connects every gene, small RNA, antisense RNA, or protein with the most relevant omics data; (iii) a specific tool for exploring protein conservation through the Listeria phylogenomic tree; and (iv) a coexpression network tool for the discovery of potential new regulations. Our platform integrates all the complete Listeria species genomes, transcriptomes, and proteomes published to date. This website allows navigation among all these data sets with enriched metadata in a user-friendly format and can be used as a central database for systems biology analysis. IMPORTANCE In the last decades, Listeria has become a key model organism for the study of host-pathogen interactions, noncoding RNA regulation, and bacterial adaptation to stress. To study these mechanisms, several genomics, transcriptomics, and proteomics data sets have been produced. We have developed Listeriomics, an interactive web platform to browse and correlate these heterogeneous sources of information. Our website will allow listeriologists and microbiologists to decipher key regulation mechanism by using a systems biology approach.

  19. Listeriomics: an Interactive Web Platform for Systems Biology of Listeria

    PubMed Central

    Koutero, Mikael; Tchitchek, Nicolas; Cerutti, Franck; Lechat, Pierre; Maillet, Nicolas; Hoede, Claire; Chiapello, Hélène; Gaspin, Christine

    2017-01-01

    ABSTRACT As for many model organisms, the amount of Listeria omics data produced has recently increased exponentially. There are now >80 published complete Listeria genomes, around 350 different transcriptomic data sets, and 25 proteomic data sets available. The analysis of these data sets through a systems biology approach and the generation of tools for biologists to browse these various data are a challenge for bioinformaticians. We have developed a web-based platform, named Listeriomics, that integrates different tools for omics data analyses, i.e., (i) an interactive genome viewer to display gene expression arrays, tiling arrays, and sequencing data sets along with proteomics and genomics data sets; (ii) an expression and protein atlas that connects every gene, small RNA, antisense RNA, or protein with the most relevant omics data; (iii) a specific tool for exploring protein conservation through the Listeria phylogenomic tree; and (iv) a coexpression network tool for the discovery of potential new regulations. Our platform integrates all the complete Listeria species genomes, transcriptomes, and proteomes published to date. This website allows navigation among all these data sets with enriched metadata in a user-friendly format and can be used as a central database for systems biology analysis. IMPORTANCE In the last decades, Listeria has become a key model organism for the study of host-pathogen interactions, noncoding RNA regulation, and bacterial adaptation to stress. To study these mechanisms, several genomics, transcriptomics, and proteomics data sets have been produced. We have developed Listeriomics, an interactive web platform to browse and correlate these heterogeneous sources of information. Our website will allow listeriologists and microbiologists to decipher key regulation mechanism by using a systems biology approach. PMID:28317029

  20. Systems biology in 3D space--enter the morphome.

    PubMed

    Lucocq, John M; Mayhew, Terry M; Schwab, Yannick; Steyer, Anna M; Hacker, Christian

    2015-02-01

    Systems-based understanding of living organisms depends on acquiring huge datasets from arrays of genes, transcripts, proteins, and lipids. These data, referred to as 'omes', are assembled using 'omics' methodologies. Currently a comprehensive, quantitative view of cellular and organellar systems in 3D space at nanoscale/molecular resolution is missing. We introduce here the term 'morphome' for the distribution of living matter within a 3D biological system, and 'morphomics' for methods of collecting 3D data systematically and quantitatively. A sampling-based approach termed stereology currently provides rapid, precise, and minimally biased morphomics. We propose that stereology solves the 'big data' problem posed by emerging wide-scale electron microscopy (EM) and can establish quantitative links between the newer nanoimaging platforms such as electron tomography, cryo-EM, and correlative microscopy.