WorldWideScience

Sample records for metabolism cell biology

  1. SYSTEMS BIOLOGY AND METABOLIC ENGINEERING OF ARTHROSPIRA CELL FACTORIES

    Directory of Open Access Journals (Sweden)

    Amornpan Klanchui

    2012-10-01

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

  2. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

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

    Directory of Open Access Journals (Sweden)

    Paula Jouhten

    2012-10-01

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

  4. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  5. Expanding the chemical palate of cells by combining systems biology and metabolic engineering.

    Science.gov (United States)

    Curran, Kathleen A; Alper, Hal S

    2012-07-01

    The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and specialty chemicals. Much of this rapid expansion in the field has been, in part, due to synergies and advances in the area of systems biology. Specifically, the availability of functional genomics, metabolomics and transcriptomics data has resulted in the potential to produce a wealth of new products, both natural and non-natural, in cellular factories. The sheer amount and diversity of this data however, means that uncovering and unlocking novel chemistries and insights is a non-obvious exercise. To address this issue, a number of computational tools and experimental approaches have been developed to help expedite the design process to create new cellular factories. This review will highlight many of the systems biology enabling technologies that have reduced the design cycle for engineered hosts, highlight major advances in the expanded diversity of products that can be synthesized, and conclude with future prospects in the field of metabolic engineering. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism

    Science.gov (United States)

    Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.

    2017-01-01

    Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

  7. Visualizing Single Cell Biology: Nanosims Studies of Carbon and Nitrogen Metabolism in Diazotrophic Cyanobacteria

    Science.gov (United States)

    Pett-Ridge, J.; Finzi, J. A.; Capone, D. G.; Popa, R.; Nealson, K. H.; Ng, W.; Spormann, A. M.; Hutcheon, I. D.; Weber, P. K.

    2007-12-01

    , inter-species transfers (with Rhizobium epibionts), and within-cell depth profiles. Spatial enrichment patterns were correlated with morphological features evidenced in TEM images of microtomed filaments. These features indicate how 15N and 13C "hotspots" are dispersed throughout individual cells in different species, and may indicate isolated locations of increased N2 fixation, sites of amino acid/protein synthesis, or cyanophycin storage granules. This combination of Nano-Secondary Ion Mass Spectrometry (NanoSIMS) analysis and high resolution microscopy allows isotopic analysis to be linked to morphological features and holds great promise for fine-scale studies of bacteria metabolism.

  8. Approaches to systems biology. Four methods to study single-cell gene expression, cell motility, antibody reactivity, and respiratory metabolism

    DEFF Research Database (Denmark)

    Hagedorn, Peter

    To understand how complex systems, such as cells, function, comprehensive Measurements of their constituent parts must be made. This can be achieved by combining methods that are each optimized to measure specific parts of the system. Four such methods,each covering a different area, are presented...... from such measurements allows models of the system to be developed and tested. For each of the methods, such analysis and modelling approaches have beenapplied and are presented: Differentially regulated genes are identified and classified according to function; cell-specfic motility models...... are developed that can distinguish between different surfaces; a method for selecting repertoires of antigens thatseparate mice based on their response to treatment is developed; and the observed concentrations of free and bound NADH is used to build and test a basic model of respiratory metabolism...

  9. Mesangial cell biology

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-15

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

  10. Mesangial cell biology

    International Nuclear Information System (INIS)

    Abboud, Hanna E.

    2012-01-01

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

  11. Networks in Cell Biology

    Science.gov (United States)

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

    2010-05-01

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

  12. Biological fuel cells and their applications

    OpenAIRE

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

    2004-01-01

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

  13. Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

    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......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...... 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....

  16. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

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

  17. Applications of NMR in biological metabolic research

    International Nuclear Information System (INIS)

    Nie Jiarui; Li Xiuqin; He Chunjian

    1989-01-01

    The nuclear magnetic resonance has become a powerful means of studying biological metabolism in non-invasive and non-destructive way. Being used to study the metabolic processes of living system in normal physiological conditions as well as in molecular level, the method is better than other conventional approaches. Using important parameters such as NMR-chemical shifts, longitudinal relaxation time and transverse relaxation time, it is possible to probe the metabolic processes as well as conformation, concentration, transportation and distribution of reacting and resulting substances. The NMR spectroscopy of 1 H, 31 P and 13 C nuclei has already been widely used in metabolic researches

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

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

  1. Translational environmental biology: cell biology informing conservation.

    Science.gov (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

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

  2. Biology of Schwann cells.

    Science.gov (United States)

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

    2013-01-01

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

  3. 2009 Archaea: Ecology, Metabolism & Molecular Biology GRC

    Energy Technology Data Exchange (ETDEWEB)

    Furlow, Julie Maupin- [Univ. of Florida, Gainesville, FL (United States)

    2009-07-26

    Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses; and industrial applications. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  4. 2011 Archaea: Ecology, Metabolism, & Molecular Biology

    Energy Technology Data Exchange (ETDEWEB)

    Keneth Stedman

    2011-08-05

    Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  5. Illuminating Cell Biology

    Science.gov (United States)

    2002-01-01

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

  6. Mammalian cell biology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  8. Lycopene metabolism and its biological significance12345

    Science.gov (United States)

    2012-01-01

    The beneficial effects of a high intake of tomatoes and tomato products on the risk of certain chronic diseases have been presented in many epidemiologic studies, with the suggestion that lycopene (a major carotenoid in tomatoes) is a micronutrient with important health benefits. Within the past few years, we have gained greater knowledge of the metabolism of lycopene and the biological effects of lycopene derivatives. In particular, the characterization and study of β-carotene 9′,10′-oxygenase has shown that this enzyme can catalyze the excentric cleavage of both provitamin and non–provitamin A carotenoids to form apo-10′-carotenoids, including apo-10′-lycopenoids from lycopene. This raised an important question of whether the effect of lycopene on various cellular functions and signaling pathways is a result of the direct actions of intact lycopene or its derivatives. Several reports, including our own, support the notion that the biological activities of lycopene can be mediated by apo-10′-lycopenoids. More research is clearly needed to identify and characterize additional lycopene metabolites and their biological activities, which will potentially provide invaluable insights into the mechanisms underlying the effects of lycopene in humans. PMID:23053559

  9. [THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].

    Science.gov (United States)

    Titov, V N

    2015-11-01

    The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.

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

    Science.gov (United States)

    Loew, L M; Schaff, J C

    2001-10-01

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

  11. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

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

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

    Science.gov (United States)

    Karig, David K

    2017-06-01

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

  13. Systems Biology of Metabolism: Annual Review of Biochemistry

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    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 descr...

  14. Mechanics rules cell biology

    Directory of Open Access Journals (Sweden)

    Wang James HC

    2010-07-01

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

  15. Molecular biology of the cell

    National Research Council Canada - National Science Library

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

    2007-01-01

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

  16. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

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

  17. Bacterial microcompartments as metabolic modules for plant synthetic biology.

    Science.gov (United States)

    Gonzalez-Esquer, C Raul; Newnham, Sarah E; Kerfeld, Cheryl A

    2016-07-01

    Bacterial microcompartments (BMCs) are megadalton-sized protein assemblies that enclose segments of metabolic pathways within cells. They increase the catalytic efficiency of the encapsulated enzymes while sequestering volatile or toxic intermediates from the bulk cytosol. The first BMCs discovered were the carboxysomes of cyanobacteria. Carboxysomes compartmentalize the enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) with carbonic anhydrase. They enhance the carboxylase activity of RuBisCO by increasing the local concentration of CO2 in the vicinity of the enzyme's active site. As a metabolic module for carbon fixation, carboxysomes could be transferred to eukaryotic organisms (e.g. plants) to increase photosynthetic efficiency. Within the scope of synthetic biology, carboxysomes and other BMCs hold even greater potential when considered a source of building blocks for the development of nanoreactors or three-dimensional scaffolds to increase the efficiency of either native or heterologously expressed enzymes. The carboxysome serves as an ideal model system for testing approaches to engineering BMCs because their expression in cyanobacteria provides a sensitive screen for form (appearance of polyhedral bodies) and function (ability to grow on air). We recount recent progress in the re-engineering of the carboxysome shell and core to offer a conceptual framework for the development of BMC-based architectures for applications in plant synthetic biology. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  20. Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions.

    Science.gov (United States)

    Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Liu, Long

    By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Hematopoietic stem cell fate through metabolic control.

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2018-05-25

    Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

  2. Molecular biology of the cell

    CERN Document Server

    Alberts, Bruce; Lewis, Julian

    2000-01-01

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

  3. Snail modulates cell metabolism in MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Haraguchi, Misako, E-mail: haraguci@m3.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Indo, Hiroko P. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Iwasaki, Yasumasa [Health Care Center, Kochi University, Kochi 780-8520 (Japan); Iwashita, Yoichiro [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Fukushige, Tomoko [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Majima, Hideyuki J. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Izumo, Kimiko; Horiuchi, Masahisa [Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Kanekura, Takuro [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Furukawa, Tatsuhiko [Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Ozawa, Masayuki [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan)

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  4. Developmental biology, the stem cell of biological disciplines

    OpenAIRE

    Gilbert, Scott F.

    2017-01-01

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

  5. Cancer Cell Metabolism: One Hallmark, Many Faces

    OpenAIRE

    Cantor, Jason R.; Sabatini, David M.

    2012-01-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such chang...

  6. Metabolic features of the cell danger response.

    Science.gov (United States)

    Naviaux, Robert K

    2014-05-01

    The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

  7. Melphalan metabolism in cultured cells

    International Nuclear Information System (INIS)

    Seagrave, J.C.; Valdez, J.G.; Tobey, R.A.; Gurley, L.R.

    1985-06-01

    Procedures are presented for the adaptation of reversed-phase-HPLC methods to accomplish separation and isolation of the cancer therapeutic drug melphalan (L-phenylalanine mustard) and its metabolic products from whole cells. Five major degradation products of melphalan were observed following its hydrolysis in phosphate buffer in vitro. The two most polar of these products (or modifications of them) were also found in the cytosol of Chinese hamster CHO cells. The amounts of these two polar products (shown not to be mono- or dihydroxymelphalan) were significantly changed by the pretreatment of cells with ZnC1 2 , one being increased in amount while the other was reduced to an insignificant level. In ZnC1 2 -treated cells, there was also an increased binding of melphalan (or its derivatives) to one protein fraction resolved by gel filtration-HPLC. These observations suggest that changes in polar melphalan products, and perhaps their interaction with a protein, may by involved in the reduction of melphalan cytotoxicity observed in ZnC1 2 -treated cells. While ZnC1 2 is also known to increase the level of glutathione in cells, no significant amounts of glutathione-melphalan derivatives of the type formed non-enzymatically in vitro could be detected in ZnC1 2 -treated or untreated cells. Formation of derivatives of melphalan with glutathione catabolic products in ZnC1 2 -treated cells has not yet been eliminated, however. 17 refs., 5 figs., 1 tab

  8. Cell-selective metabolic labeling of biomolecules with bioorthogonal functionalities.

    Science.gov (United States)

    Xie, Ran; Hong, Senlian; Chen, Xing

    2013-10-01

    Metabolic labeling of biomolecules with bioorthogonal functionalities enables visualization, enrichment, and analysis of the biomolecules of interest in their physiological environments. This versatile strategy has found utility in probing various classes of biomolecules in a broad range of biological processes. On the other hand, metabolic labeling is nonselective with respect to cell type, which imposes limitations for studies performed in complex biological systems. Herein, we review the recent methodological developments aiming to endow metabolic labeling strategies with cell-type selectivity. The cell-selective metabolic labeling strategies have emerged from protein and glycan labeling. We envision that these strategies can be readily extended to labeling of other classes of biomolecules. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Alternative Cell Death Pathways and Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2013-01-01

    Full Text Available While necroptosis has for long been viewed as an accidental mode of cell death triggered by physical or chemical damage, it has become clear over the last years that necroptosis can also represent a programmed form of cell death in mammalian cells. Key discoveries in the field of cell death research, including the identification of critical components of the necroptotic machinery, led to a revised concept of cell death signaling programs. Several regulatory check and balances are in place in order to ensure that necroptosis is tightly controlled according to environmental cues and cellular needs. This network of regulatory mechanisms includes metabolic pathways, especially those linked to mitochondrial signaling events. A better understanding of these signal transduction mechanisms will likely contribute to open new avenues to exploit our knowledge on the regulation of necroptosis signaling for therapeutic application in the treatment of human diseases.

  10. Recent applications of synthetic biology tools for yeast metabolic engineering

    DEFF Research Database (Denmark)

    Jensen, Michael Krogh; Keasling, Jay

    2015-01-01

    to engineer microbial chemical factories has steadily decreased, improvement is still needed. Through the development of synthetic biology tools for key microbial hosts, it should be possible to further decrease the development times and improve the reliability of the resulting microorganism. Together...... with continuous decreases in price and improvements in DNA synthesis, assembly and sequencing, synthetic biology tools will rationalize time-consuming strain engineering, improve control of metabolic fluxes, and diversify screening assays for cellular metabolism. This review outlines some recently developed...... synthetic biology tools and their application to improve production of chemicals and fuels in yeast. Finally, we provide a perspective for the challenges that lie ahead....

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

    Science.gov (United States)

    Gilbert, Scott F

    2017-12-01

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

  12. Cancer cell metabolism: one hallmark, many faces.

    Science.gov (United States)

    Cantor, Jason R; Sabatini, David M

    2012-10-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

  13. Measuring Biological Age via Metabonomics: The Metabolic Age Score.

    Science.gov (United States)

    Hertel, Johannes; Friedrich, Nele; Wittfeld, Katharina; Pietzner, Maik; Budde, Kathrin; Van der Auwera, Sandra; Lohmann, Tobias; Teumer, Alexander; Völzke, Henry; Nauck, Matthias; Grabe, Hans Jörgen

    2016-02-05

    Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity. Applying a nonlinear regression technique, we constructed a metabonomic measurement for biological age, the metabolic age score, based on urine data measured via (1)H NMR spectroscopy. We validated the score in two large independent population-based samples by revealing its significant associations with chronological age and age-related clinical phenotypes as well as its independent predictive value for survival over approximately 13 years of follow-up. Furthermore, the metabolic age score was prognostic for weight loss in a sample of individuals who underwent bariatric surgery. We conclude that the metabolic age score is an informative measurement of biological age with possible applications in personalized medicine.

  14. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    NARCIS (Netherlands)

    He, F.; Murabito, E.; Westerhoff, H.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 throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental

  15. Investigating cholesterol metabolism and ageing using a systems biology approach.

    Science.gov (United States)

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2017-08-01

    CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

  16. Stem cell biology meets systems biology

    OpenAIRE

    Roeder, I.; Radtke, F.

    2009-01-01

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

  17. Category of Metabolic-Replication Systems in Biology and Medicine

    OpenAIRE

    I. C. Baianu

    2012-01-01

    Metabolic-repair models, or (M,R)-systems were introduced in Relational Biology by Robert Rosen. Subsequently, Rosen represented such (M,R)-systems (or simply MRs)in terms of categories of sets, deliberately selected without any structure other than the discrete topology of sets. Theoreticians of life's origins postulated that Life on Earth has begun with the simplest possible organism, called the primordial. Mathematicians interested in biology attempted to answer this important questio...

  18. Stochastic processes in cell biology

    CERN Document Server

    Bressloff, Paul C

    2014-01-01

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

  19. New paradigms for metabolic modeling of human cells

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    review recent work on reconstruction of GEMs for human cell/tissue types and cancer, and the use of GEMs for identification of metabolic changes occurring in response to disease development. We further discuss how GEMs can be used for the development of efficient therapeutic strategies. Finally......, challenges in integration of cell/tissue models for simulation of whole body functions as well as integration of GEMs with other biological networks for generating complete cell/tissue models are presented.......Abnormalities in cellular functions are associated with the progression of human diseases, often resulting in metabolic reprogramming. GEnome-scale metabolic Models (GEMs) have enabled studying global metabolic reprogramming in connection with disease development in a systematic manner. Here we...

  20. Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

    Directory of Open Access Journals (Sweden)

    Sriram Chandrasekaran

    2017-12-01

    Full Text Available Summary: Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates. The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells. Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive and primed cells. Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate. : Chandrasekaran et al. use computational modeling, metabolomics, and metabolic inhibitors to discover metabolic differences between various pluripotent stem cell states and infer their impact on stem cell fate decisions. Keywords: systems biology, stem cell biology, metabolism, genome-scale modeling, pluripotency, histone methylation, naive (ground state, primed state, cell fate, metabolic network

  1. Metabolic and biological prospecting of Coreopsis tinctoria

    Directory of Open Access Journals (Sweden)

    Luís Gaspar

    2011-12-01

    Full Text Available Coreopsis tinctoria Nutt., Asteraceae, flowering tops infusion has been traditionally used in many countries to control hyperglycaemia. In this work we report for the first time fatty acids and volatile compounds in this species. Fifteen fatty acids and sixteen volatile compounds were determined by GC-ITMS, being saturated fatty acids and monoterpenes the main compounds. The antioxidant and antibacterial potential of this matrix was checked for the first time by several in vitro assays. A concentration-dependent activity was noticed against DPPH, nitric oxide and superoxide radicals. Antibacterial capacity was assessed against Gram-positive and Gram-negative bacteria, being more effective against the first. Additionally, acetylcholinesterase and butyrylcholinesterase inhibitory activity was also evaluated, but no effect was found. Our results provide evidence of a wide diversity of compounds with several biological properties, improving the knowledge on this poorly studied matrix, which can lead to an increment of the use of C. tinctoria flowering tops, namely in food and pharmaceutical applications.

  2. Metabolic and biological prospecting of Coreopsis tinctoria

    Directory of Open Access Journals (Sweden)

    Luís Gaspar

    2012-04-01

    Full Text Available Coreopsis tinctoria Nutt., Asteraceae, flowering tops infusion has been traditionally used in many countries to control hyperglycaemia. In this work we report for the first time fatty acids and volatile compounds in this species. Fifteen fatty acids and sixteen volatile compounds were determined by GC-ITMS, being saturated fatty acids and monoterpenes the main compounds. The antioxidant and antibacterial potential of this matrix was checked for the first time by several in vitro assays. A concentration-dependent activity was noticed against DPPH, nitric oxide and superoxide radicals. Antibacterial capacity was assessed against Gram-positive and Gram-negative bacteria, being more effective against the first. Additionally, acetylcholinesterase and butyrylcholinesterase inhibitory activity was also evaluated, but no effect was found. Our results provide evidence of a wide diversity of compounds with several biological properties, improving the knowledge on this poorly studied matrix, which can lead to an increment of the use of C. tinctoria flowering tops, namely in food and pharmaceutical applications.

  3. Review of Microfluidic Photobioreactor Technology for Metabolic Engineering and Synthetic Biology of Cyanobacteria and Microalgae

    Directory of Open Access Journals (Sweden)

    Ya-Tang Yang

    2016-10-01

    Full Text Available One goal of metabolic engineering and synthetic biology for cyanobacteria and microalgae is to engineer strains that can optimally produce biofuels and commodity chemicals. However, the current workflow is slow and labor intensive with respect to assembly of genetic parts and characterization of production yields because of the slow growth rates of these organisms. Here, we review recent progress in the microfluidic photobioreactors and identify opportunities and unmet needs in metabolic engineering and synthetic biology. Because of the unprecedented experimental resolution down to the single cell level, long-term real-time monitoring capability, and high throughput with low cost, microfluidic photobioreactor technology will be an indispensible tool to speed up the development process, advance fundamental knowledge, and realize the full potential of metabolic engineering and synthetic biology for cyanobacteria and microalgae.

  4. A new radiation biology: epigenetics, exosomes and metabolism

    International Nuclear Information System (INIS)

    Atkinson, M.J.

    2016-01-01

    Exposure to ionizing radiation leads to chronic disease, including cancer, cardiovascular disease, neurocognitive deficits and possibly metabolic diseases. The prevailing paradigm of radiation biology considers DNA damage to be the initiating event. Misrepair of initial DNA damage leads to gene mutations that promote clonal expansion and eventually malignancy. However, the paradigm is inconsistent with some recent radiobiological observations

  5. Structural Systems Biology Evaluation of Metabolic Thermotolerance in Escherichia coli

    DEFF Research Database (Denmark)

    Chang, Roger L.; Andrews, Kathleen; Kim, Donghyuk

    2013-01-01

    Improve the System A "systems biology" approach may clarify, for example, how particular proteins determine sensitivity of bacteria to extremes of temperature. Chang et al. (p. 1220) integrated information on protein structure with a model of metabolism, thus associating the protein structure of ...

  6. Connecting Mitochondria, Metabolism, and Stem Cell Fate

    Science.gov (United States)

    Wanet, Anaïs; Arnould, Thierry; Najimi, Mustapha

    2015-01-01

    As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. PMID:26134242

  7. Laboratory of Cell and Molecular Biology

    Data.gov (United States)

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

  8. Automatic detection of biological cells

    International Nuclear Information System (INIS)

    Alves Da Costa, Caiuby

    1983-01-01

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

  9. Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

    Directory of Open Access Journals (Sweden)

    Matthew J Robertson

    Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

  10. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    Science.gov (United States)

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

  11. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

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

    2015-08-01

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

  12. B-Cell Metabolic Remodeling and Cancer

    DEFF Research Database (Denmark)

    Franchina, Davide G.; Grusdat, Melanie; Brenner, Dirk

    2018-01-01

    Cells of the immune system display varying metabolic profiles to fulfill their functions. B lymphocytes overcome fluctuating energy challenges as they transition from the resting state and recirculation to activation, rapid proliferation, and massive antibody production. Only through a controlled...

  13. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Spitz, Douglas R.

    2014-01-01

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O 2 and H 2 O 2 ) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  14. Spatial Modeling Tools for Cell Biology

    National Research Council Canada - National Science Library

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-12-02

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

  16. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Controlling cell-free metabolism through physiochemical perturbations.

    Science.gov (United States)

    Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

    2018-01-01

    Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

  18. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2016-01-01

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

  19. A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Reifman Jaques

    2009-09-01

    Full Text Available Abstract Background Because metabolism is fundamental in sustaining microbial life, drugs that target pathogen-specific metabolic enzymes and pathways can be very effective. In particular, the metabolic challenges faced by intracellular pathogens, such as Mycobacterium tuberculosis, residing in the infected host provide novel opportunities for therapeutic intervention. Results We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in its metabolic pathways are inhibited. Combining detailed models of enzyme kinetics, a complete metabolic network description as modeled by flux balance analysis, and a dynamic cell population growth model, we quantitatively modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the growth of M. tuberculosis in a medium whose carbon source was restricted to fatty acids, and that of the 5'-O-(N-salicylsulfamoyl adenosine inhibitor in a medium with low-iron concentration. Conclusion The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions/constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on in vitro growth of M. tuberculosis cells.

  20. Glutathione Primes T Cell Metabolism for Inflammation

    DEFF Research Database (Denmark)

    Mak, Tak W.; Grusdat, Melanie; Duncan, Gordon S.

    2017-01-01

    the activation of mammalian target of rapamycin-1 (mTOR) and expression of NFAT and Myc transcription factors, abrogating the energy utilization and Myc-dependent metabolic reprogramming that allows activated T cells to switch to glycolysis and glutaminolysis. In vivo, T-cell-specific ablation of murine Gclc...

  1. Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammad Abdel-Mawgoud

    2018-03-01

    Full Text Available Glycosylated lipids (GLs are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

  2. Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Anja Karlstaedt

    2018-06-01

    Full Text Available Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

  3. Understanding specificity in metabolic pathways-Structural biology of human nucleotide metabolism

    International Nuclear Information System (INIS)

    Welin, Martin; Nordlund, Paer

    2010-01-01

    Interactions are the foundation of life at the molecular level. In the plethora of activities in the cell, the evolution of enzyme specificity requires the balancing of appropriate substrate affinity with a negative selection, in order to minimize interactions with other potential substrates in the cell. To understand the structural basis for enzyme specificity, the comparison of structural and biochemical data between enzymes within pathways using similar substrates and effectors is valuable. Nucleotide metabolism is one of the largest metabolic pathways in the human cell and is of outstanding therapeutic importance since it activates and catabolises nucleoside based anti-proliferative drugs and serves as a direct target for anti-proliferative drugs. In recent years the structural coverage of the enzymes involved in human nucleotide metabolism has been dramatically improved and is approaching completion. An important factor has been the contribution from the Structural Genomics Consortium (SGC) at Karolinska Institutet, which recently has solved 33 novel structures of enzymes and enzyme domains in human nucleotide metabolism pathways and homologs thereof. In this review we will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.

  4. Synthetic biology for engineering acetyl coenzyme a metabolism in yeast

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2014-01-01

    The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels, chemicals, and pharmaceuticals. The use of this cell factory for cost-efficient production of novel fuels and chemicals requires high yields and low by-product production. Many industrially interesting...... chemicals are biosynthesized from acetyl coenzyme A (acetyl-CoA), which serves as a central precursor metabolite in yeast. To ensure high yields in production of these chemicals, it is necessary to engineer the central carbon metabolism so that ethanol production is minimized (or eliminated) and acetyl...

  5. Cell signalling and phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-01-01

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  6. Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

    Directory of Open Access Journals (Sweden)

    Teresa G. Valencak

    2017-08-01

    Full Text Available Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders. Keywords: Body fatness, Adipose tissue, Sex-specific differences, Adipokines, Adipocytes, Obesity, Energy metabolism

  7. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna

    2015-01-01

    Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...... based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted...... for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies....

  8. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

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

    2017-01-02

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

  9. Studying cell biology in the skin.

    Science.gov (United States)

    Morrow, Angel; Lechler, Terry

    2015-11-15

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

  10. Molecular Imaging Of Metabolic Reprogramming In Mutant IDH Cells

    Directory of Open Access Journals (Sweden)

    Pavithra eViswanath

    2016-03-01

    Full Text Available Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG. Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG. In turn, 2-HG, which has been termed an oncometabolite, inhibits key α-KG- dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprogramming that extends beyond 2-HG production, and this reprogramming often differs from what has been previously reported in other cancer types. In this review we will discuss in detail what is known to date about the metabolic reprogramming of mutant IDH cells and how this reprogramming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo.

  11. Cell Biology of Cnidarian-Dinoflagellate Symbiosis

    Science.gov (United States)

    Allemand, Denis; Weis, Virginia M.

    2012-01-01

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

  12. BIOLOGICALLY INSPIRED HARDWARE CELL ARCHITECTURE

    DEFF Research Database (Denmark)

    2010-01-01

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

  13. Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals.

    Science.gov (United States)

    Jullesson, David; David, Florian; Pfleger, Brian; Nielsen, Jens

    2015-11-15

    Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals

    DEFF Research Database (Denmark)

    Jullesson, David; David, Florian; Pfleger, Brian

    2015-01-01

    Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played...... chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes....... an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine...

  15. Synthetic biology approaches to engineer T cells.

    Science.gov (United States)

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

    2015-08-01

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

  16. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    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. © 2016 The Author(s).

  17. Biological effect of hydrolyzed collagen on bone metabolism.

    Science.gov (United States)

    Daneault, Audrey; Prawitt, Janne; Fabien Soulé, Véronique; Coxam, Véronique; Wittrant, Yohann

    2017-06-13

    Osteoporosis is a chronic and asymptomatic disease characterized by low bone mass and skeletal microarchitectural deterioration, increased risk of fracture, and associated comorbidities most prevalent in the elderly. Due to an increasingly aging population, osteoporosis has become a major health issue requiring innovative disease management. Proteins are important for bone by providing building blocks and by exerting specific regulatory function. This is why adequate protein intake plays a considerable role in both bone development and bone maintenance. More specifically, since an increase in the overall metabolism of collagen can lead to severe dysfunctions and a more fragile bone matrix and because orally administered collagen can be digested in the gut, cross the intestinal barrier, enter the circulation, and become available for metabolic processes in the target tissues, one may speculate that a collagen-enriched diet provides benefits for the skeleton. Collagen-derived products such as gelatin or hydrolyzed collagen (HC) are well acknowledged for their safety from a nutritional point of view; however, what is their impact on bone biology? In this manuscript, we critically review the evidence from literature for an effect of HC on bone tissues in order to determine whether HC may represent a relevant alternative in the design of future nutritional approaches to manage osteoporosis prevention.

  18. The cell biology of bone growth.

    Science.gov (United States)

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

    1994-02-01

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

  19. The biology of lysine acetylation integrates transcriptional programming and metabolism

    Directory of Open Access Journals (Sweden)

    Mujtaba Shiraz

    2011-03-01

    Full Text Available Abstract The biochemical landscape of lysine acetylation has expanded from a small number of proteins in the nucleus to a multitude of proteins in the cytoplasm. Since the first report confirming acetylation of the tumor suppressor protein p53 by a lysine acetyltransferase (KAT, there has been a surge in the identification of new, non-histone targets of KATs. Added to the known substrates of KATs are metabolic enzymes, cytoskeletal proteins, molecular chaperones, ribosomal proteins and nuclear import factors. Emerging studies demonstrate that no fewer than 2000 proteins in any particular cell type may undergo lysine acetylation. As described in this review, our analyses of cellular acetylated proteins using DAVID 6.7 bioinformatics resources have facilitated organization of acetylated proteins into functional clusters integral to cell signaling, the stress response, proteolysis, apoptosis, metabolism, and neuronal development. In addition, these clusters also depict association of acetylated proteins with human diseases. These findings not only support lysine acetylation as a widespread cellular phenomenon, but also impel questions to clarify the underlying molecular and cellular mechanisms governing target selectivity by KATs. Present challenges are to understand the molecular basis for the overlapping roles of KAT-containing co-activators, to differentiate between global versus dynamic acetylation marks, and to elucidate the physiological roles of acetylated proteins in biochemical pathways. In addition to discussing the cellular 'acetylome', a focus of this work is to present the widespread and dynamic nature of lysine acetylation and highlight the nexus that exists between epigenetic-directed transcriptional regulation and metabolism.

  20. Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

    Science.gov (United States)

    Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

    2010-10-01

    Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

  1. Teaching Cell Biology in Primary Schools

    Directory of Open Access Journals (Sweden)

    Francele de Abreu Carlan

    2014-01-01

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

  2. Computational Tools for Stem Cell Biology.

    Science.gov (United States)

    Bian, Qin; Cahan, Patrick

    2016-12-01

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

  3. Bioengineering thermodynamics of biological cells.

    Science.gov (United States)

    Lucia, Umberto

    2015-12-01

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

  4. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    Science.gov (United States)

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  5. Interfacing nanostructures to biological cells

    Science.gov (United States)

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

    2012-09-04

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

  6. The cell biology of aging.

    Science.gov (United States)

    Hayflick, L

    1985-02-01

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

  7. DESHARKY: automatic design of metabolic pathways for optimal cell growth.

    Science.gov (United States)

    Rodrigo, Guillermo; Carrera, Javier; Prather, Kristala Jones; Jaramillo, Alfonso

    2008-11-01

    The biological solution for synthesis or remediation of organic compounds using living organisms, particularly bacteria and yeast, has been promoted because of the cost reduction with respect to the non-living chemical approach. In that way, computational frameworks can profit from the previous knowledge stored in large databases of compounds, enzymes and reactions. In addition, the cell behavior can be studied by modeling the cellular context. We have implemented a Monte Carlo algorithm (DESHARKY) that finds a metabolic pathway from a target compound by exploring a database of enzymatic reactions. DESHARKY outputs a biochemical route to the host metabolism together with its impact in the cellular context by using mathematical models of the cell resources and metabolism. Furthermore, we provide the sequence of amino acids for the enzymes involved in the route closest phylogenetically to the considered organism. We provide examples of designed metabolic pathways with their genetic load characterizations. Here, we have used Escherichia coli as host organism. In addition, our bioinformatic tool can be applied for biodegradation or biosynthesis and its performance scales with the database size. Software, a tutorial and examples are freely available and open source at http://soft.synth-bio.org/desharky.html

  8. Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels

    Energy Technology Data Exchange (ETDEWEB)

    Kuk Lee, Sung; Chou, Howard; Ham, Timothy S.; Soon Lee, Taek; Keasling, Jay D.

    2009-12-02

    The ability to generate microorganisms that can produce biofuels similar to petroleum-based transportation fuels would allow the use of existing engines and infrastructure and would save an enormous amount of capital required for replacing the current infrastructure to accommodate biofuels that have properties significantly different from petroleum-based fuels. Several groups have demonstrated the feasibility of manipulating microbes to produce molecules similar to petroleum-derived products, albeit at relatively low productivity (e.g. maximum butanol production is around 20 g/L). For cost-effective production of biofuels, the fuel-producing hosts and pathways must be engineered and optimized. Advances in metabolic engineering and synthetic biology will provide new tools for metabolic engineers to better understand how to rewire the cell in order to create the desired phenotypes for the production of economically viable biofuels.

  9. Cell biology of mitotic recombination

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2015-01-01

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

  10. Cell biology experiments conducted in space

    Science.gov (United States)

    Taylor, G. R.

    1977-01-01

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

  11. Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

    NARCIS (Netherlands)

    Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

    2011-01-01

    In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

  12. Fluid models and simulations of biological cell phenomena

    Science.gov (United States)

    Greenspan, H. P.

    1982-01-01

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

  13. METABOLIC MAPPING BY ENZYME HISTOCHEMISTRY IN LIVING ANIMALS, TISSUES AND CELLS

    NARCIS (Netherlands)

    van Noorden, C. J. F.

    2009-01-01

    Imaging of reporter molecules such as fluorescent proteins in intact animals, tissue and cells has become an indispensable tool in cell biology Imaging activity of enzymes, which is called metabolic mapping, provides information on subcellular localisation in combination with function of the enzymes

  14. GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes

    Directory of Open Access Journals (Sweden)

    Nakayama Yoichi

    2006-03-01

    Full Text Available Abstract Background Successful realization of a "systems biology" approach to analyzing cells is a grand challenge for our understanding of life. However, current modeling approaches to cell simulation are labor-intensive, manual affairs, and therefore constitute a major bottleneck in the evolution of computational cell biology. Results We developed the Genome-based Modeling (GEM System for the purpose of automatically prototyping simulation models of cell-wide metabolic pathways from genome sequences and other public biological information. Models generated by the GEM System include an entire Escherichia coli metabolism model comprising 968 reactions of 1195 metabolites, achieving 100% coverage when compared with the KEGG database, 92.38% with the EcoCyc database, and 95.06% with iJR904 genome-scale model. Conclusion The GEM System prototypes qualitative models to reduce the labor-intensive tasks required for systems biology research. Models of over 90 bacterial genomes are available at our web site.

  15. Electromagnetic effects - From cell biology to medicine.

    Science.gov (United States)

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

    2009-01-01

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

  16. Prion potency in stem cells biology.

    Science.gov (United States)

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

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

  17. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  18. Metabolism of labeled parathyroid hormone. V. Collected biological studies

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, W F; Neuman, M W; Lane, K; Miller, L; Sammon, P J

    1975-01-01

    Biologically active /sup 125/I-labeled parathyroid hormone (/sup 125/I-PTH) was used in a series of studies in dogs and chickens designed to confirm and augment earlier studies in rats. As in rats, a three exponential equation was required to describe disappearance of /sup 125/I-PTH from the blood in the dog. The first two ''half-lives'' (1.8 and 7 min) accounted for the bulk of the dose. Also as in rats, deposition of apparently intact hormone took place rapidly in kidney, liver and bone in both the dog and the chicken. Degradation occurred very rapidly in all three target organs. Three labeled hormones of different biological activities were compared in the rat. Inactive, oxidized hormone was rejected by the liver but showed markedly increased deposition in kidney and the higher the purity of the hormone the higher was its uptake by liver. Exploration of a wide range of dosages revealed few effects on distribution (smaller depositon in liver and kidney at highest dosages, 65 ..mu..g/rat). Fresh sera did not degrade hormone rapidly or extensively. There was no deposition of hormone in intestinal mucosa, marrow, and red cells. Nephrectomy increased deposition in liver and bone. Finally, the perfused liver was capable of extensive degradation of the hormone.

  19. Countercurrent distribution of biological cells

    Science.gov (United States)

    Brooks, D. E.

    1979-01-01

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

  20. The central dogma of cell biology.

    Science.gov (United States)

    Cooper, S

    1981-06-01

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

  1. CellNet: Network Biology Applied to Stem Cell Engineering

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Artis, David

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Owens, T; Zeine, R

    1989-01-01

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

  4. Enhanced Biological Phosphorus Removal : Metabolic Insights and Salinity Effects

    NARCIS (Netherlands)

    Welles, L.

    2015-01-01

    Enhanced biological phosphorus removal (EBPR) is a biological process for efficient phosphate removal from wastewaters through intracellular storage of polyphosphate by polyphosphate-accumulating organisms (PAO) and subsequent removal of PAO from the system through wastage of sludge. In comparison

  5. Cellular metabolic rates from primary dermal fibroblast cells isolated from birds of different body masses.

    Science.gov (United States)

    Jimenez, Ana Gabriela; Williams, Joseph B

    2014-10-01

    The rate of metabolism is the speed at which organisms use energy, an integration of energy transformations within the body; it governs biological processes that influence rates of growth and reproduction. Progress at understanding functional linkages between whole organism metabolic rate and underlying mechanisms that influence its magnitude has been slow despite the central role this issue plays in evolutionary and physiological ecology. Previous studies that have attempted to relate how cellular processes translate into whole-organism physiology have done so over a range of body masses of subjects. However, the data still remains controversial when observing metabolic rates at the cellular level. To bridge the gap between these ideas, we examined cellular metabolic rate of primary dermal fibroblasts isolated from 49 species of birds representing a 32,000-fold range in body masses to test the hypothesis that metabolic rate of cultured cells scales with body size. We used a Seahorse XF-96 Extracellular flux analyzer to measure cellular respiration in fibroblasts. Additionally, we measured fibroblast size and mitochondrial content. We found no significant correlation between cellular metabolic rate, cell size, or mitochondrial content and body mass. Additionally, there was a significant relationship between cellular basal metabolic rate and proton leak in these cells. We conclude that metabolic rate of cells isolated in culture does not scale with body mass, but cellular metabolic rate is correlated to growth rate in birds. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Metabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells

    Science.gov (United States)

    Kamel, Peter I.; Qu, Xin; Geiszler, Andrew M.; Nagrath, Deepak; Harmancey, Romain; Taegtmeyer, Heinrich; Grande-Allen, K. Jane

    2014-01-01

    Despite a high incidence of calcific aortic valve disease in metabolic syndrome, there is little information about the fundamental metabolism of heart valves. Cell metabolism is a first responder to chemical and mechanical stimuli, but it is unknown how such signals employed in valve tissue engineering impact valvular interstitial cell (VIC) biology and valvular disease pathogenesis. In this study porcine aortic VICs were seeded into three-dimensional collagen gels and analysed for gel contraction, lactate production and glucose consumption in response to manipulation of metabolic substrates, including glucose, galactose, pyruvate and glutamine. Cell viability was also assessed in two-dimensional culture. We found that gel contraction was sensitive to metabolic manipulation, particularly in nutrient-depleted medium. Contraction was optimal at an intermediate glucose concentration (2 g l−1) with less contraction with excess (4.5 g l−1) or reduced glucose (1 g l−1). Substitution with galactose delayed contraction and decreased lactate production. In low sugar concentrations, pyruvate depletion reduced contraction. Glutamine depletion reduced cell metabolism and viability. Our results suggest that nutrient depletion and manipulation of metabolic substrates impacts the viability, metabolism and contractile behaviour of VICs. Particularly, hyperglycaemic conditions can reduce VIC interaction with and remodelling of the extracellular matrix. These results begin to link VIC metabolism and macroscopic behaviour such as cell–matrix interaction. PMID:25320066

  7. Physical, chemical, and metabolic state sensors expand the synthetic biology toolbox for Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Immethun, Cheryl M; DeLorenzo, Drew M; Focht, Caroline M; Gupta, Dinesh; Johnson, Charles B; Moon, Tae Seok

    2017-07-01

    Many under-developed organisms possess important traits that can boost the effectiveness and sustainability of microbial biotechnology. Photoautotrophic cyanobacteria can utilize the energy captured from light to fix carbon dioxide for their metabolic needs while living in environments not suited for growing crops. Various value-added compounds have been produced by cyanobacteria in the laboratory; yet, the products' titers and yields are often not industrially relevant and lag behind what have been accomplished in heterotrophic microbes. Genetic tools for biological process control are needed to take advantage of cyanobacteria's beneficial qualities, as tool development also lags behind what has been created in common heterotrophic hosts. To address this problem, we developed a suite of sensors that regulate transcription in the model cyanobacterium Synechocystis sp. PCC 6803 in response to metabolically relevant signals, including light and the cell's nitrogen status, and a family of sensors that respond to the inexpensive chemical, l-arabinose. Increasing the number of available tools enables more complex and precise control of gene expression. Expanding the synthetic biology toolbox for this cyanobacterium also improves our ability to utilize this important under-developed organism in biotechnology. Biotechnol. Bioeng. 2017;114: 1561-1569. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Mermelstein, Claudia; Costa, Manoel Luis

    2017-04-01

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

  9. AFM Nanotools for Surgery of Biological Cells

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-01

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

  10. Implications of Big Data for cell biology

    OpenAIRE

    Dolinski, Kara; Troyanskaya, Olga G.

    2015-01-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

  12. Technological Development of High-Performance MALDI Mass Spectrometry Imaging for the Study of Metabolic Biology

    Energy Technology Data Exchange (ETDEWEB)

    Feenstra, Adam D. [Iowa State Univ., Ames, IA (United States)

    2016-12-17

    This thesis represents efforts made in technological developments for the study of metabolic biology in plants, specifically maize, using matrix-assisted laser desorption/ ionization-mass spectrometry imaging.

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

    Science.gov (United States)

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

    2018-06-20

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

  14. From genomes to in silico cells via metabolic networks

    DEFF Research Database (Denmark)

    Borodina, Irina; Nielsen, Jens

    2005-01-01

    Genome-scale metabolic models are the focal point of systems biology as they allow the collection of various data types in a form suitable for mathematical analysis. High-quality metabolic networks and metabolic networks with incorporated regulation have been successfully used for the analysis...... of phenotypes from phenotypic arrays and in gene-deletion studies. They have also been used for gene expression analysis guided by metabolic network structure, leading to the identification of commonly regulated genes. Thus, genome-scale metabolic modeling currently stands out as one of the most promising...

  15. Biological Aging and Life Span Based on Entropy Stress via Organ and Mitochondrial Metabolic Loading

    Directory of Open Access Journals (Sweden)

    Kalyan Annamalai

    2017-10-01

    Full Text Available The energy for sustaining life is released through the oxidation of glucose, fats, and proteins. A part of the energy released within each cell is stored as chemical energy of Adenosine Tri-Phosphate molecules, which is essential for performing life-sustaining functions, while the remainder is released as heat in order to maintain isothermal state of the body. Earlier literature introduced the availability concepts from thermodynamics, related the specific irreversibility and entropy generation rates to metabolic efficiency and energy release rate of organ k, computed whole body specific entropy generation rate of whole body at any given age as a sum of entropy generation within four vital organs Brain, Heart, Kidney, Liver (BHKL with 5th organ being the rest of organs (R5 and estimated the life span using an upper limit on lifetime entropy generated per unit mass of body, σM,life. The organ entropy stress expressed in terms of lifetime specific entropy generated per unit mass of body organs (kJ/(K kg of organ k was used to rank organs and heart ranked highest while liver ranked lowest. The present work includes the effects of (1 two additional organs: adipose tissue (AT and skeletal muscles (SM which are of importance to athletes; (2 proportions of nutrients oxidized which affects blood temperature and metabolic efficiencies; (3 conversion of the entropy stress from organ/cellular level to mitochondrial level; and (4 use these parameters as metabolism-based biomarkers for quantifying the biological aging process in reaching the limit of σM,life. Based on the 7-organ model and Elia constants for organ metabolic rates for a male of 84 kg steady mass and using basic and derived allometric constants of organs, the lifetime energy expenditure is estimated to be 2725 MJ/kg body mass while lifetime entropy generated is 6050 kJ/(K kg body mass with contributions of 190; 1835.0; 610; 290; 700; 1470 and 95 kJ/K contributed by AT-BHKL-SM-R7 to 1 kg body

  16. Enhanced Biological Phosphorus Removal: Metabolic Insights and Salinity Effects

    OpenAIRE

    Welles, L.

    2015-01-01

    Enhanced biological phosphorus removal (EBPR) is a biological process for efficient phosphate removal from wastewaters through intracellular storage of polyphosphate by polyphosphate-accumulating organisms (PAO) and subsequent removal of PAO from the system through wastage of sludge. In comparison to physical and chemical phosphorus removal processes, the biological process has several advantages such as high removal efficiency, low cost, and no chemical sludge production, but disturbances an...

  17. Covariation of metabolic rates and cell size in coccolithophores

    Science.gov (United States)

    Aloisi, G.

    2015-08-01

    Coccolithophores are sensitive recorders of environmental change. The size of their coccosphere varies in the ocean along gradients of environmental conditions and provides a key for understanding the fate of this important phytoplankton group in the future ocean. But interpreting field changes in coccosphere size in terms of laboratory observations is hard, mainly because the marine signal reflects the response of multiple morphotypes to changes in a combination of environmental variables. In this paper I examine the large corpus of published laboratory experiments with coccolithophores looking for relations between environmental conditions, metabolic rates and cell size (a proxy for coccosphere size). I show that growth, photosynthesis and, to a lesser extent, calcification covary with cell size when pCO2, irradiance, temperature, nitrate, phosphate and iron conditions change. With the exception of phosphate and temperature, a change from limiting to non-limiting conditions always results in an increase in cell size. An increase in phosphate or temperature (below the optimum temperature for growth) produces the opposite effect. The magnitude of the coccosphere-size changes observed in the laboratory is comparable to that observed in the ocean. If the biological reasons behind the environment-metabolism-size link are understood, it will be possible to use coccosphere-size changes in the modern ocean and in marine sediments to investigate the fate of coccolithophores in the future ocean. This reasoning can be extended to the size of coccoliths if, as recent experiments are starting to show, coccolith size reacts to environmental change proportionally to coccosphere size. The coccolithophore database is strongly biased in favour of experiments with the coccolithophore Emiliania huxleyi (E. huxleyi; 82 % of database entries), and more experiments with other species are needed to understand whether these observations can be extended to coccolithophores in general. I

  18. From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes.

    Science.gov (United States)

    Corcoran, Callan C; Grady, Cameron R; Pisitkun, Trairak; Parulekar, Jaya; Knepper, Mark A

    2017-03-01

    The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database ( https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1,647 genes to these pathways, representing ~7 percent of the protein-coding genome. To illustrate the use of the database, we apply it to the area of kidney physiology. In so doing, we have created an additional database ( Database of Metabolic Enzymes in Kidney Tubule Segments: https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/), mapping mRNA abundance measurements (mined from RNA-Seq studies) for all metabolic enzymes to each of 14 renal tubule segments. We carry out bioinformatics analysis of the enzyme expression pattern among renal tubule segments and mine various data sources to identify vasopressin-regulated metabolic enzymes in the renal collecting duct. Copyright © 2017 the American Physiological Society.

  19. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

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

  20. From gametogenesis and stem cells to cancer: common metabolic themes.

    Science.gov (United States)

    Pereira, Sandro L; Rodrigues, Ana Sofia; Sousa, Maria Inês; Correia, Marcelo; Perestrelo, Tânia; Ramalho-Santos, João

    2014-01-01

    Both pluripotent stem cells (PSCs) and cancer cells have been described as having similar metabolic pathways, most notably a penchant for favoring glycolysis even under aerobiosis, suggesting common themes that might be explored for both stem cell differentiation and anti-oncogenic purposes. A search of the scientific literature available in the PubMed/Medline was conducted for studies on metabolism and mitochondrial function related to gametogenesis, early development, stem cells and cancers in the reproductive system, notably breast, prostate, ovarian and testicular cancers. Both PSCs and some types of cancer cells, particularly reproductive cancers, were found to obtain energy mostly by glycolysis, often reducing mitochondrial activity and oxidative phosphorylation. This strategy links proliferating cells, allowing for the biosynthesis reactions necessary for cell division. Interventions that affect metabolic pathways, and force cells to change their preferences, can lead to shifts in cell status, increasing either pluripotency or differentiation of stem cells, and causing cancer cells to become more or less aggressive. Interestingly metabolic changes in many cases seemed to lead to cell transformation, not necessarily follow it, suggesting a direct role of metabolic choices in influencing the (epi)genetic program of different cell types. There are uncanny similarities between PSCs and cancer cells at the metabolic level. Furthermore, metabolism may also play a direct role in cell status and targeting metabolic pathways could therefore be a promising strategy for both the control of cancer cell proliferation and the regulation of stem cell physiology, in terms of manipulating stem cells toward relevant phenotypes that may be important for tissue engineering, or making cancer cells become less tumorigenic. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For

  1. The changing world of modern cell biology.

    Science.gov (United States)

    Misteli, Tom

    2009-01-12

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

  2. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    Science.gov (United States)

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator

    OpenAIRE

    Fabian V Filipp

    2013-01-01

    Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor acti...

  4. Dihydroceramide biology - Structure-specific metabolism and intracellular localization

    NARCIS (Netherlands)

    Kok, JW; NikolovaKarakashian, M; Klappe, K; Alexander, C; Merrill, AH

    1997-01-01

    This study utilized fluorescent analogs to characterize the intracellular transport and metabolism of dihydroceramide (DN-Cer), an intermediate in de novo sphingolipid biosynthesis, When 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoyl-DH-Cer (C-6-NBD-DH-Cer) was incubated with HT29, NRK, BHK,

  5. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

    2016-01-01

    Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

  6. Proteomics in studying cancer stem cell biology.

    Science.gov (United States)

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

    2012-06-01

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

  7. III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect.

    Science.gov (United States)

    Witkiewicz, Halina; Oh, Phil; Schnitzer, Jan E

    2013-01-01

    cell cycle through mitosis, indicated that Warburg effect had a fundamental biological significance extending to non-malignant tissues. The approach used here could facilitate integration of accumulated cyber knowledge on cancer metabolism into predictive science.

  8. Random distribution of nucleoli in metabolic cells

    Energy Technology Data Exchange (ETDEWEB)

    Beckman, R.J.; Waterman, M.S.

    1977-01-01

    Hasofer (1974) has studied a probabilistic model for the fusion of nucleoli in metabolic cells. The nucleoli are uniformly distributed at points in the nucleus, assumed to be a sphere. The nucleoli grow from a point to a maximum size during interphase, and fusion is said to occur if the nucleoli touch. For this model, Hasofer calculated the probability of fusion and found it much smaller than experimental data would indicate. Experimental data of this type is taken by use of a microscope where a two-dimensional view or projection of the three-dimensional cell is obtained. Hasofer implicitly assumes that actual fusion can be distinguished from the case where the two nucleoli do not touch but their two-dimensional projections overlap. It is assumed, in this letter, that these two cases cannot be distinguished. The probability obtained by Beckman and Waterman is larger than Hasofer's and a much better fit to the experimental data is obtained. Even if true fusion can be unfailingly distinguished from overlap of the two-dimensional projections, it is hoped that these calculations will allow someone to propose the correct (non-uniform) model. It is concluded, for the assumptions used, that there is not sufficient evidence to reject the hypothesis of uniform distribution of the nucleoli.

  9. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  10. Stem cell metabolism in tissue development and aging

    Science.gov (United States)

    Shyh-Chang, Ng; Daley, George Q.; Cantley, Lewis C.

    2013-01-01

    Recent advances in metabolomics and computational analysis have deepened our appreciation for the role of specific metabolic pathways in dictating cell fate. Once thought to be a mere consequence of the state of a cell, metabolism is now known to play a pivotal role in dictating whether a cell proliferates, differentiates or remains quiescent. Here, we review recent studies of metabolism in stem cells that have revealed a shift in the balance between glycolysis, mitochondrial oxidative phosphorylation and oxidative stress during the maturation of adult stem cells, and during the reprogramming of somatic cells to pluripotency. These insights promise to inform strategies for the directed differentiation of stem cells and to offer the potential for novel metabolic or pharmacological therapies to enhance regeneration and the treatment of degenerative disease. PMID:23715547

  11. Metabolic Plasticity of Stem Cells and Macrophages in Cancer

    Directory of Open Access Journals (Sweden)

    Jelena Krstic

    2017-08-01

    Full Text Available In addition to providing essential molecules for the overall function of cells, metabolism plays an important role in cell fate and can be affected by microenvironmental stimuli as well as cellular interactions. As a specific niche, tumor microenvironment (TME, consisting of different cell types including stromal/stem cells and immune cells, is characterized by distinct metabolic properties. This review will be focused on the metabolic plasticity of mesenchymal stromal/stem cells (MSC and macrophages in TME, as well as on how the metabolic state of cancer stem cells (CSC, as key drivers of oncogenesis, affects their generation and persistence. Namely, heterogenic metabolic phenotypes of these cell populations, which include various levels of dependence on glycolysis or oxidative phosphorylation are closely linked to their complex roles in cancer progression. Besides well-known extrinsic factors, such as cytokines and growth factors, the differentiation and activation states of CSC, MSC, and macrophages are coordinated by metabolic reprogramming in TME. The significance of mutual metabolic interaction between tumor stroma and cancer cells in the immune evasion and persistence of CSC is currently under investigation.

  12. Biological functions of histidine-dipeptides and metabolic syndrome

    OpenAIRE

    Song, Byeng Chun; Joo, Nam-Seok; Aldini, Giancarlo; Yeum, Kyung-Jin

    2014-01-01

    The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced gly...

  13. Biochemistry and biology: heart-to-heart to investigate cardiac progenitor cells.

    Science.gov (United States)

    Chimenti, Isotta; Forte, Elvira; Angelini, Francesco; Messina, Elisa; Giacomello, Alessandro

    2013-02-01

    Cardiac regenerative medicine is a rapidly evolving field, with promising future developments for effective personalized treatments. Several stem/progenitor cells are candidates for cardiac cell therapy, and emerging evidence suggests how multiple metabolic and biochemical pathways strictly regulate their fate and renewal. In this review, we will explore a selection of areas of common interest for biology and biochemistry concerning stem/progenitor cells, and in particular cardiac progenitor cells. Numerous regulatory mechanisms have been identified that link stem cell signaling and functions to the modulation of metabolic pathways, and vice versa. Pharmacological treatments and culture requirements may be exploited to modulate stem cell pluripotency and self-renewal, possibly boosting their regenerative potential for cell therapy. Mitochondria and their many related metabolites and messengers, such as oxygen, ROS, calcium and glucose, have a crucial role in regulating stem cell fate and the balance of their functions, together with many metabolic enzymes. Furthermore, protein biochemistry and proteomics can provide precious clues on the definition of different progenitor cell populations, their physiology and their autocrine/paracrine regulatory/signaling networks. Interdisciplinary approaches between biology and biochemistry can provide productive insights on stem/progenitor cells, allowing the development of novel strategies and protocols for effective cardiac cell therapy clinical translation. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-04

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

  15. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  16. Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment.

    Science.gov (United States)

    Hawk, Mark A; Schafer, Zachary T

    2018-01-16

    Non-transformed cells that become detached from the extracellular matrix (ECM) undergo dysregulation of redox homeostasis and cell death. In contrast, cancer cells often acquire the ability to mitigate programmed cell death pathways and recalibrate the redox balance to survive after ECM detachment, facilitating metastatic dissemination. Accordingly, recent studies of the mechanisms by which cancer cells overcome ECM detachment-induced metabolic alterations have focused on mechanisms in redox homeostasis. The insights into these mechanisms may inform the development of therapeutics that manipulate redox homeostasis to eliminate ECM-detached cancer cells. Here, we review how ECM-detached cancer cells balance redox metabolism for survival. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2014-08-14

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

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

    Science.gov (United States)

    Hodgman, C Eric; Jewett, Michael C

    2012-05-01

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

  19. Biophysical mechanisms complementing "classical" cell biology.

    Science.gov (United States)

    Funk, Richard H W

    2018-01-01

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

  20. Nanobodies and recombinant binders in cell biology

    Science.gov (United States)

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

    2015-01-01

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

  1. Nanobodies and recombinant binders in cell biology.

    Science.gov (United States)

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

    2015-06-08

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

  2. INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division

    Directory of Open Access Journals (Sweden)

    Graeme J. Gowans

    2018-01-01

    Full Text Available Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC. Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC1-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin to restrict proliferation to metabolically optimal states.

  3. The Emerging Cell Biology of Thyroid Stem Cells

    Science.gov (United States)

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

    2011-01-01

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

  4. Can molecular cell biology explain chromosome motions?

    Directory of Open Access Journals (Sweden)

    Gagliardi L

    2011-05-01

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

  5. Cell Biology of Astrocyte-Synapse Interactions.

    Science.gov (United States)

    Allen, Nicola J; Eroglu, Cagla

    2017-11-01

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

  6. The Halogenated Metabolism of Brown Algae (Phaeophyta, Its Biological Importance and Its Environmental Significance

    Directory of Open Access Journals (Sweden)

    Stéphane La Barre

    2010-03-01

    Full Text Available Brown algae represent a major component of littoral and sublittoral zones in temperate and subtropical ecosystems. An essential adaptive feature of this independent eukaryotic lineage is the ability to couple oxidative reactions resulting from exposure to sunlight and air with the halogenations of various substrates, thereby addressing various biotic and abiotic stresses i.e., defense against predators, tissue repair, holdfast adhesion, and protection against reactive species generated by oxidative processes. Whereas marine organisms mainly make use of bromine to increase the biological activity of secondary metabolites, some orders of brown algae such as Laminariales have also developed a striking capability to accumulate and to use iodine in physiological adaptations to stress. We review selected aspects of the halogenated metabolism of macrophytic brown algae in the light of the most recent results, which point toward novel functions for iodide accumulation in kelps and the importance of bromination in cell wall modifications and adhesion properties of brown algal propagules. The importance of halogen speciation processes ranges from microbiology to biogeochemistry, through enzymology, cellular biology and ecotoxicology.

  7. Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles.

    Science.gov (United States)

    Gerasimaitė, Rūta; Mayer, Andreas

    2016-02-01

    Inorganic polyphosphate (polyP) is found in all living organisms. The known polyP functions in eukaryotes range from osmoregulation and virulence in parasitic protozoa to modulating blood coagulation, inflammation, bone mineralization and cellular signalling in mammals. However mechanisms of regulation and even the identity of involved proteins in many cases remain obscure. Most of the insights obtained so far stem from studies in the yeast Saccharomyces cerevisiae. Here, we provide a short overview of the properties and functions of known yeast polyP metabolism enzymes and discuss future directions for polyP research. © 2016 Authors; published by Portland Press Limited.

  8. Kinetic modeling of cell metabolism for microbial production.

    Science.gov (United States)

    Costa, Rafael S; Hartmann, Andras; Vinga, Susana

    2016-02-10

    Kinetic models of cellular metabolism are important tools for the rational design of metabolic engineering strategies and to explain properties of complex biological systems. The recent developments in high-throughput experimental data are leading to new computational approaches for building kinetic models of metabolism. Herein, we briefly survey the available databases, standards and software tools that can be applied for kinetic models of metabolism. In addition, we give an overview about recently developed ordinary differential equations (ODE)-based kinetic models of metabolism and some of the main applications of such models are illustrated in guiding metabolic engineering design. Finally, we review the kinetic modeling approaches of large-scale networks that are emerging, discussing their main advantages, challenges and limitations. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  10. Metabolism and biological effects of alpha-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Bair, W. J.

    1979-05-01

    The emphasis of much of the current and planned research on the toxicity of alpha-emitting radionuclides is directed toward the complexities of actual and potential conditions of occupational environmental exposures of human beings. These, as well as the more limited studies on mechanisms of biological transport and effects, should increase our ability to predict health risks more accurately and to deal more confidently with human exposures, if and when they occur.

  11. Genome-scale metabolic models as platforms for strain design and biological discovery.

    Science.gov (United States)

    Mienda, Bashir Sajo

    2017-07-01

    Genome-scale metabolic models (GEMs) have been developed and used in guiding systems' metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models.

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  13. Systems biology of human metabolism - Defining the epithelial to mesenchymal transition and the activity of human gluconokinase

    OpenAIRE

    Rohatgi, Neha

    2016-01-01

    Studying human metabolism is crucial for the understanding of diseases and improvement of therapy as metabolic alterations are central to a number of human diseases. A variety of experimental disciplines, such as biochemistry, biophysics and systems biology are involved in the elucidation of metabolic pathways. The work presented in this thesis is divided into three main studies, which expand the knowledge of human metabolism using systems biology and biochemical techniques....

  14. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

    Science.gov (United States)

    Zhang, Jing; Lu, Shaohua; Zhou, Ye; Meng, Kun; Chen, Zhipeng; Cui, Yizhi; Shi, Yunfeng; Wang, Tong; He, Qing-Yu

    2017-07-01

    Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Wolkenhauer, Olaf; Mesarovic, Mihajlo

    2005-05-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  17. Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte

    modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....... and metabolic pathways that are necessary or related to establishment of chronic infections. Archetypal analysis showed to be successful in extracting relevant phenotypes from global gene expression da-­‐ ta. Furthermore, genome-­‐scale metabolic modeling showed to be useful in connecting the genotype...

  18. The Future of Metabolic Engineering and Synthetic Biology: Towards a Systematic Practice

    Science.gov (United States)

    Yadav, Vikramaditya G.; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

    2012-01-01

    Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. PMID:22629571

  19. The future of metabolic engineering and synthetic biology: towards a systematic practice.

    Science.gov (United States)

    Yadav, Vikramaditya G; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

    2012-05-01

    Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as 'multivariate modular metabolic engineering' (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Metabolic, Replication and Genomic Category of Systems in Biology, Bioinformatics and Medicine

    OpenAIRE

    I. C. Baianu

    2012-01-01

    Metabolic-repair models, or (M,R)-systems were introduced in Relational Biology by Robert Rosen. Subsequently, Rosen represented such (M,R)-systems (or simply MRs)in terms of categories of sets, deliberately selected without any structure other than the discrete topology of sets. Theoreticians of life’s origins postulated that Life on Earth has begun with the simplest possible organism, called the primordial. Mathematicians interested in biology attempted to answer this important quest...

  1. Black pepper (Piper nigrum) essential oil demonstrates tissue remodeling and metabolism modulating potential in human cells.

    Science.gov (United States)

    Han, Xuesheng; Beaumont, Cody; Rodriguez, Damian; Bahr, Tyler

    2018-05-17

    Very few studies have investigated the biological activities of black pepper essential oil (BPEO) in human cells. Therefore, in the current study, we examined the biological activities of BPEO in cytokine-stimulated human dermal fibroblasts by analyzing the levels of 17 important protein biomarkers pertinent to inflammation and tissue remodeling. BPEO exhibited significant antiproliferative activity in these skin cells and significantly inhibited the production of Collagen I, Collagen III, and plasminogen activator inhibitor 1. In addition, we studied the effect of BPEO on the regulation of genome-wide expression and found that BPEO diversely modulated global gene expression. Further analysis showed that BPEO affected many important genes and signaling pathways closely related to metabolism, inflammation, tissue remodeling, and cancer signaling. This study is the first to provide evidence of the biological activities of BPEO in human dermal fibroblasts. The data suggest that BPEO possesses promising potential to modulate the biological processes of tissue remodeling, wound healing, and metabolism. Although further research is required, BPEO appears to be a good therapeutic candidate for a variety of health conditions including wound care and metabolic diseases. Research into the biological and pharmacological mechanisms of action of BPEO and its major active constituents is recommended. Copyright © 2018 John Wiley & Sons, Ltd.

  2. Cell biology apps for Apple devices.

    Science.gov (United States)

    Stark, Louisa A

    2012-01-01

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

  3. Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells

    DEFF Research Database (Denmark)

    Raggi, Chiara; Gammella, Elena; Correnti, Margherita

    2017-01-01

    Cholangiocarcinoma (CCA) is a devastating liver tumour arising from malignant transformation of bile duct epithelial cells. Cancer stem cells (CSC) are a subset of tumour cells endowed with stem-like properties, which play a role in tumour initiation, recurrence and metastasis. In appropriate con...... compartment as a novel metabolic factor involved in CCA growth, may have implications for a better therapeutic approach....

  4. Vitamin K metabolism in Chinese Hamster Ovary cells

    International Nuclear Information System (INIS)

    Hoffman, H.S.

    1986-01-01

    Recent investigations suggest that vitamin K may have functions other than in blood coagulation and calcification. The present study was undertaken to investigate this hypothesis using cells in culture. Chinese Hamster Ovary (CHO) cells were chosen due to their active metabolism and growth and lack of similarity to liver and bone cells, in which vitamin K metabolism is well known. Cells were adapted to serum-free media, incubated in media containing the appropriate concentrations of vitamin K for specified times, scraped from plates, pelleted, extensively washed to remove adhering vitamin K, extracted with chloroform:methanol (2:1, v/v) and analyzed on C18 HPLC columns. Uptake of vitamin K by CHO cells follows saturation kinetics at vitamin K concentrations up to 25 μ M and is transported into cells at the rate of 10 pmol/min. 10 6 cells. After 24 hours, 3 H vitamin K is metabolized by CHO cells to several compounds, the major of which was isolated and identified as vitamin K epoxide. In 3 experiments, after 24 hours, the average cellular uptake of vitamin K was 8% with approximately half being metabolized to vitamin K epoxide. These results demonstrate that vitamin K is metabolized in cells with widely different functions and suggest a generalized function for vitamin K which has yet to be elucidated

  5. The binding, transport and fate of aluminium in biological cells.

    Science.gov (United States)

    Exley, Christopher; Mold, Matthew J

    2015-04-01

    Aluminium is the most abundant metal in the Earth's crust and yet, paradoxically, it has no known biological function. Aluminium is biochemically reactive, it is simply that it is not required for any essential process in extant biota. There is evidence neither of element-specific nor evolutionarily conserved aluminium biochemistry. This means that there are no ligands or chaperones which are specific to its transport, there are no transporters or channels to selectively facilitate its passage across membranes, there are no intracellular storage proteins to aid its cellular homeostasis and there are no pathways which evolved to enable the metabolism and excretion of aluminium. Of course, aluminium is found in every compartment of every cell of every organism, from virus through to Man. Herein we have investigated each of the 'silent' pathways and metabolic events which together constitute a form of aluminium homeostasis in biota, identifying and evaluating as far as is possible what is known and, equally importantly, what is unknown about its uptake, transport, storage and excretion. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

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

    2014-08-25

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

  7. Metabolic rate determines haematopoietic stem cell self-renewal.

    Science.gov (United States)

    Sastry, P S R K

    2004-01-01

    The number of haematopoietic stem cells (HSCs) per animal is conserved across species. This means the HSCs need to maintain hematopoiesis over a longer period in larger animals. This would result in the requirement of stem cell self-renewal. At present the three existing models are the stochastic model, instructive model and the third more recently proposed is the chiaro-scuro model. It is a well known allometric law that metabolic rate scales to the three quarter power. Larger animals have a lower metabolic rate, compared to smaller animals. Here it is being hypothesized that metabolic rate determines haematopoietic stem cell self-renewal. At lower metabolic rate the stem cells commit for self-renewal, where as at higher metabolic rate they become committed to different lineages. The present hypothesis can explain the salient features of the different models. Recent findings regarding stem cell self-renewal suggest an important role for Wnt proteins and their receptors known as frizzleds, which are an important component of cell signaling pathway. The role of cGMP in the Wnts action provides further justification for the present hypothesis as cGMP is intricately linked to metabolic rate. One can also explain the telomere homeostasis by the present hypothesis. One prediction of the present hypothesis is with reference to the limit of cell divisions known as Hayflick limit, here it is being suggested that this is the result of metabolic rate in laboratory conditions and there can be higher number of cell divisions in vivo if the metabolic rate is lower. Copyright 2004 Elsevier Ltd.

  8. Metabolism during ECM Detachment: Achilles Heel of Cancer Cells?

    Science.gov (United States)

    Mason, Joshua A; Hagel, Kimberly R; Hawk, Mark A; Schafer, Zachary T

    2017-07-01

    Integrin-mediated attachment to the extracellular matrix (ECM) is required to combat the induction of programmed cell death in a variety of distinct cell types. If cells fail to maintain proper ECM attachment, they become subject to elimination via an apoptotic cell death program known as anoikis. However, anoikis inhibition is not sufficient to promote the long-term survival of ECM-detached cells. Several recent studies have unveiled the profound (anoikis-independent) impact of cell metabolism on the viability of ECM-detached cells. Thus, we posit that, during metastatic dissemination (when cancer cells are exposed to periods of ECM detachment), cancer cells must alter their metabolism in a fashion that promotes survival and ultimately contributes to metastatic outgrowth. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Computational biology approaches to plant metabolism and photosynthesis: applications for corals in times of climate change and environmental stress.

    Science.gov (United States)

    Crabbe, M James C

    2010-08-01

    Knowledge of factors that are important in reef resilience helps us to understand how reef ecosystems react following major anthropogenic and environmental disturbances. The symbiotic relationship between the photosynthetic zooxanthellae algal cells and corals is that the zooxanthellae provide the coral with carbon, while the coral provides protection and access to enough light for the zooxanthellae to photosynthesise. This article reviews some recent advances in computational biology relevant to photosynthetic organisms, including Beyesian approaches to kinetics, computational methods for flux balances in metabolic processes, and determination of clades of zooxanthallae. Application of these systems will be important in the conservation of coral reefs in times of climate change and environmental stress.

  10. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Madhavan, Aravind [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Rajiv Gandhi Centre for Biotechnology, Trivandrum (India); Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran, E-mail: sindhurgcb@gmail.com; Sukumaran, Rajeev K. [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Pandey, Ashok [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Center for Innovative and Applied Bioprocessing, Mohali, Punjab (India); Castro, Galliano Eulogio [Dpt. Ingeniería Química, Ambiental y de los Materiales Edificio, Universidad de Jaén, Jaén (Spain)

    2017-04-25

    The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  11. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    Directory of Open Access Journals (Sweden)

    Raveendran Sindhu

    2017-04-01

    Full Text Available The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  12. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    International Nuclear Information System (INIS)

    Madhavan, Aravind; Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran; Sukumaran, Rajeev K.; Pandey, Ashok; Castro, Galliano Eulogio

    2017-01-01

    The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  13. Metabolism in time and space – exploring the frontier of developmental biology

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Alena; Tennessen, J. M.

    2017-01-01

    Roč. 144, č. 18 (2017), s. 3193-3198 ISSN 0950-1991 Institutional support: RVO:60077344 Keywords : metabolism * mitochondria * aerobic glycolysis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.843, year: 2016 http://dev.biologists.org/content/144/18/3193

  14. Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3

    Science.gov (United States)

    Rimmelé, Pauline; Liang, Raymond; Bigarella, Carolina L; Kocabas, Fatih; Xie, Jingjing; Serasinghe, Madhavika N; Chipuk, Jerry; Sadek, Hesham; Zhang, Cheng Cheng; Ghaffari, Saghi

    2015-01-01

    Hematopoietic stem cells (HSC) are primarily dormant but have the potential to become highly active on demand to reconstitute blood. This requires a swift metabolic switch from glycolysis to mitochondrial oxidative phosphorylation. Maintenance of low levels of reactive oxygen species (ROS), a by-product of mitochondrial metabolism, is also necessary for sustaining HSC dormancy. Little is known about mechanisms that integrate energy metabolism with hematopoietic stem cell homeostasis. Here, we identify the transcription factor FOXO3 as a new regulator of metabolic adaptation of HSC. ROS are elevated in Foxo3−/− HSC that are defective in their activity. We show that Foxo3−/− HSC are impaired in mitochondrial metabolism independent of ROS levels. These defects are associated with altered expression of mitochondrial/metabolic genes in Foxo3−/− hematopoietic stem and progenitor cells (HSPC). We further show that defects of Foxo3−/− HSC long-term repopulation activity are independent of ROS or mTOR signaling. Our results point to FOXO3 as a potential node that couples mitochondrial metabolism with HSC homeostasis. These findings have critical implications for mechanisms that promote malignant transformation and aging of blood stem and progenitor cells. PMID:26209246

  15. Integrating cell biology and proteomic approaches in plants.

    Science.gov (United States)

    Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef

    2017-10-03

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

  16. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity

    Directory of Open Access Journals (Sweden)

    Anna Rzepecka-Stojko

    2015-12-01

    Full Text Available Bee pollen constitutes a natural source of antioxidants such as phenolic acids and flavonoids, which are responsible for its biological activity. Research has indicated the correlation between dietary polyphenols and cardioprotective, hepatoprotective, anti-inflammatory, antibacterial, anticancerogenic, immunostimulating, antianaemic effects, as well as their beneficial influence on osseous tissue. The beneficial effects of bee pollen on health result from the presence of phenolic acids and flavonoids which possess anti-inflammatory properties, phytosterol and linolenic acid which play an anticancerogenic role, and polysaccharides which stimulate immunological activity. Polyphenols are absorbed in the alimentary tract, metabolised by CYP450 enzymes, and excreted with urine and faeces. Flavonoids and phenolic acids are characterised by high antioxidative potential, which is closely related to their chemical structure. The high antioxidant potential of phenolic acids is due to the presence and location of hydroxyl groups, a carboxyl group in the immediate vicinity of ortho-diphenolic substituents, and the ethylene group between the phenyl ring and the carboxyl group. As regards flavonoids, essential structural elements are hydroxyl groups at the C5 and C7 positions in the A ring, and at the C3′ and C4′ positions in the B ring, and a hydroxyl group at the C3 position in the C ring. Furthermore, both, the double bond between C2 and C3, and a ketone group at the C4 position in the C ring enhance the antioxidative potential of these compounds. Polyphenols have an ideal chemical structure for scavenging free radicals and for creating chelates with metal ions, which makes them effective antioxidants in vivo.

  17. Cell-surface display of enzymes by the yeast Saccharomyces cerevisiae for synthetic biology.

    Science.gov (United States)

    Tanaka, Tsutomu; Kondo, Akihiko

    2015-02-01

    In yeast cell-surface displays, functional proteins, such as cellulases, are genetically fused to an anchor protein and expressed on the cell surface. Saccharomyces cerevisiae, which is often utilized as a cell factory for the production of fuels, chemicals, and proteins, is the most commonly used yeast for cell-surface display. To construct yeast cells with a desired function, such as the ability to utilize cellulose as a substrate for bioethanol production, cell-surface display techniques for the efficient expression of enzymes on the cell membrane need to be combined with metabolic engineering approaches for manipulating target pathways within cells. In this Minireview, we summarize the recent progress of biorefinery fields in the development and application of yeast cell-surface displays from a synthetic biology perspective and discuss approaches for further enhancing cell-surface display efficiency. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  18. The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

    Science.gov (United States)

    Ganguli, Suman; Hunt, C Anthony

    2004-01-01

    Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

  19. Reproductive hormones and metabolic syndrome in 24 testicular cancer survivors and their biological brothers

    DEFF Research Database (Denmark)

    Bandak, M.; Jorgensen, N.; Juul, A.

    2017-01-01

    ) criteria comprised the main outcome measures of the study. Median age was similar in testicular cancer survivors and their biological brothers [44 years (IQR 39–50) vs. 46 (40–53) years respectively (p = 0.1)]. In testicular cancer survivors, follow-up since treatment was 12 years (7–19). Serum levels...... was to clarify if testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to their biological brothers. A cross-sectional study of testicular cancer survivors (ClinicalTrials.gov number, NCT02240966) was conducted between 2014 and 2016. Of 158 testicular...... cancer survivors included, 24 had a biological brother who accepted to participate in the study. Serum levels of reproductive hormones and prevalence of metabolic syndrome according to International Diabetes Federation Criteria and National Cholesterol Education Program (Adult Treatment Panel III...

  20. Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries.

    Science.gov (United States)

    Hong, Kuk-Ki; Nielsen, Jens

    2012-08-01

    Metabolic engineering is the enabling science of development of efficient cell factories for the production of fuels, chemicals, pharmaceuticals, and food ingredients through microbial fermentations. The yeast Saccharomyces cerevisiae is a key cell factory already used for the production of a wide range of industrial products, and here we review ongoing work, particularly in industry, on using this organism for the production of butanol, which can be used as biofuel, and isoprenoids, which can find a wide range of applications including as pharmaceuticals and as biodiesel. We also look into how engineering of yeast can lead to improved uptake of sugars that are present in biomass hydrolyzates, and hereby allow for utilization of biomass as feedstock in the production of fuels and chemicals employing S. cerevisiae. Finally, we discuss the perspectives of how technologies from systems biology and synthetic biology can be used to advance metabolic engineering of yeast.

  1. Metabolic Regulation of a Bacterial Cell System with Emphasis on Escherichia coli Metabolism

    Science.gov (United States)

    Shimizu, Kazuyuki

    2013-01-01

    It is quite important to understand the overall metabolic regulation mechanism of bacterial cells such as Escherichia coli from both science (such as biochemistry) and engineering (such as metabolic engineering) points of view. Here, an attempt was made to clarify the overall metabolic regulation mechanism by focusing on the roles of global regulators which detect the culture or growth condition and manipulate a set of metabolic pathways by modulating the related gene expressions. For this, it was considered how the cell responds to a variety of culture environments such as carbon (catabolite regulation), nitrogen, and phosphate limitations, as well as the effects of oxygen level, pH (acid shock), temperature (heat shock), and nutrient starvation. PMID:25937963

  2. Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

    Czech Academy of Sciences Publication Activity Database

    Rychtarčíková, Zuzana; Lettlová, Sandra; Tomkova, Veronika; Korenková, Vlasta; Langerová, Lucie; Simonova, Ekaterina; Zjablovskaja, Polina; Alberich-Jorda, Meritxell; Neužil, Jiří; Truksa, Jaroslav

    2017-01-01

    Roč. 8, č. 4 (2017), s. 6376-6398 ISSN 1949-2553 R&D Projects: GA ČR GA13-28830S; GA ČR GA15-03796S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : tumor-initiating cells * breast cancer * iron metabolism Subject RIV: FD - Oncology ; Hematology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cell biology; Cell biology (UMG-J) Impact factor: 5.168, year: 2016

  3. Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP

    Directory of Open Access Journals (Sweden)

    Jarmon G. Lees

    2017-01-01

    Full Text Available Metabolism is central to embryonic stem cell (ESC pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway activity has been highlighted by extensive studies of their impact on preimplantation embryo development, physiology, and viability. ESC similarly modulate their metabolism in response to altered metabolite levels, with changes in nutrient availability shown to have a lasting impact on derived cell identity through the regulation of the epigenetic landscape. Further, the preferential use of glucose and anaplerotic glutamine metabolism serves to not only support cell growth and proliferation but also minimise reactive oxygen species production. However, the perinuclear localisation of spherical, electron-poor mitochondria in ESC is proposed to sustain ESC nuclear-mitochondrial crosstalk and a mitochondrial-H2O2 presence, to facilitate signalling to support self-renewal through the stabilisation of HIFα, a process that may be favoured under physiological oxygen. The environment in which a cell is grown is therefore a critical regulator and determinant of cell fate, with metabolism, and particularly mitochondria, acting as an interface between the environment and the epigenome.

  4. Glucose metabolism regulates T cell activation, differentiation and functions

    Directory of Open Access Journals (Sweden)

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  5. Ovarian tumor-initiating cells display a flexible metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  6. Ovarian tumor-initiating cells display a flexible metabolism

    International Nuclear Information System (INIS)

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-01-01

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

  7. Genome Annotation in a Community College Cell Biology Lab

    Science.gov (United States)

    Beagley, C. Timothy

    2013-01-01

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

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

    Science.gov (United States)

    2003-01-01

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

  9. Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data

    DEFF Research Database (Denmark)

    Yang, Laurence; Tan, Justin; O'Brien, Edward J.

    2015-01-01

    based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma......Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood...... at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass...

  10. Biological effects of radiation

    International Nuclear Information System (INIS)

    2013-01-01

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  11. Polyamine metabolism in synchronously growing mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Heby, O.; Marton, L.J.; Gray, J.W.; Lindl, P.A.; Wilson, C.B.

    1976-03-02

    The times of synthesis of the polyamines putrescine, spermidine and spermine in relation to the cell cycle have been examined in Chinese hamster ovary (CHO) cells synchronized by selective detachment of mitotic cells. This technique produced cell populations with narrow age distributions. Following plating, the cells grew with high synchrony for more than one cell cycle in monolayer culture. At various times after plating, the distribution of cells among the G1, S and G2M phases of the cell cycle was calculated from DNA histograms obtained by flow microfluorometric analysis. At these same times L-ornithine decarboxylase assays and polyamine determinations showed that the synthesis of the polyamines was initiated in mid-G1 and that the polyamines started to accumulate towards the end of the G1 phase. Maximal rate of synthesis was obtained as the cells started to synthesize DNA and the highest polyamine content was obtained in the beginning of the S phase. Synthesis and accumulation of the polyamines decreased significantly during mid-S but towards the end of the S phase they increased again. The polyamine biosynthetic activity and the concentration of the polyamines reached a second maximum prior to cell division. The role of the polyamines in the traverse of the cell cycle and especially in the initiation or continuation of DNA synthesis is indicated also by the fact that fewer cells were found in the S phase when spermidine and spermine synthesis was inhibited by methylglyoxal-bis(guanylhydrazone).

  12. Expanding beyond canonical metabolism: Interfacing alternative elements, synthetic biology, and metabolic engineering

    Directory of Open Access Journals (Sweden)

    Kevin B. Reed

    2018-03-01

    Full Text Available Metabolic engineering offers an exquisite capacity to produce new molecules in a renewable manner. However, most industrial applications have focused on only a small subset of elements from the periodic table, centered around carbon biochemistry. This review aims to illustrate the expanse of chemical elements that can currently (and potentially be integrated into useful products using cellular systems. Specifically, we describe recent advances in expanding the cellular scope to include the halogens, selenium and the metalloids, and a variety of metal incorporations. These examples range from small molecules, heteroatom-linked uncommon elements, and natural products to biomining and nanotechnology applications. Collectively, this review covers the promise of an expanded range of elemental incorporations and the future impacts it may have on biotechnology.

  13. Synthetic biology: programming cells for biomedical applications.

    Science.gov (United States)

    Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  15. A Diagnostic Assessment for Introductory Molecular and Cell Biology

    Science.gov (United States)

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

    2010-01-01

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

  16. Alternative Educational Approach to Introducing Cell Biology

    Directory of Open Access Journals (Sweden)

    Rosilane T. Silva

    2005-07-01

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

  17. Yeast cell metabolism investigated by CO{_2} production and soft X-ray irradiation

    Science.gov (United States)

    Masini, A.; Batani, D.; Previdi, F.; Milani, M.; Pozzi, A.; Turcu, E.; Huntington, S.; Takeyasu, H.

    1999-01-01

    Results obtained using a new technique for studying cell metabolism are presented. The technique, consisting in CO2 production monitoring, has been applied to Saccharomyces cerevisiae yeast cells. Also the cells were irradiated using the soft X-ray laser-plasma source at Rutherford Appleton Laboratory with the aim of producing a damage of metabolic processes at the wall level, responsible for fermentation, without great interference with respiration, taking place in mitochondria, and DNA activity. The source was calibrated with PIN diodes and X-ray spectrometers and used Teflon stripes as target, emitting X-rays at about 0.9 keV, with a very low penetration in biological material. X-ray doses delivered to the different cell compartments were calculated following a Lambert-Bouguet-Beer law. Immediately after irradiation, the damage to metabolic activity was measured again by monitoring CO2 production. Results showed a general reduction in gas production by irradiated samples, together with non-linear and non-monotone response to dose. There was also evidence of oscillations in cell metabolic activity and of X-ray induced changes in oscillation frequency.

  18. Influence of the Tumor Microenvironment on Cancer Cells Metabolic Reprogramming

    Directory of Open Access Journals (Sweden)

    Victoire Gouirand

    2018-04-01

    Full Text Available As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells. However, the microenvironments of primary tumor and metastatic niches differ tremendously in their cellular/acellular components and available nutrients. Therefore, cancer cells must develop a metabolic flexibility conferring on them the ability to satisfy their biomass and energetic demands at both primary and metastasis sites. In this review, we propose a brief overview of how proliferating cancer cells take advantage of their surrounding microenvironment to satisfy their high metabolic demand at both primary and metastasis sites.

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

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  1. Cell signalling and phospholipid metabolism. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-12-31

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  2. Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

    Directory of Open Access Journals (Sweden)

    Chonglong Wang

    2014-09-01

    Full Text Available Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

  3. Synthetic biology and metabolic engineering for marine carotenoids: new opportunities and future prospects.

    Science.gov (United States)

    Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

    2014-09-17

    Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

  4. Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

    Science.gov (United States)

    Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

    2014-01-01

    Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations. PMID:25233369

  5. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook; Kang, Keon Wook; Oh, Soo Jin; Lee, Ki Ho; Kim, Hwan Mook; Ma, Jin Yeul; Kim, Sang Kyum

    2011-01-01

    Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to ∼ 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research highlights: → MCF-7/Adr cells showed decreases in cellular GSH

  6. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    Science.gov (United States)

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Metabolism of murine TH 17 cells: Impact on cell fate and function.

    Science.gov (United States)

    Wang, Ran; Solt, Laura A

    2016-04-01

    An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T-cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T-cell fate decisions, including the development of TH 17 versus T regulatory (Treg) cells. TH 17 cells have garnered significant attention due to their roles in the pathology of immune-mediated inflammatory diseases. Attempts to characterize TH 17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the TH 17/Treg balance and present factors that mediate TH 17-cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T-helper-cell differentiation, hypoxia inducible factor 1 alpha (HIF1α) promotion of glycolysis to favor TH 17-cell development, and ACC1-dependent de novo fatty acid synthesis favoring TH 17-cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating TH 17-cell metabolism for the treatment of TH 17-mediated diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Methods for modeling chinese hamster ovary (cho) cell metabolism

    DEFF Research Database (Denmark)

    2015-01-01

    Embodiments of the present invention generally relate to the computational analysis and characterization biological networks at the cellular level in Chinese Hamster Ovary (CHO) cells. Based on computational methods utilizing a hamster reference genome, the invention provides methods for identify...

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

    Science.gov (United States)

    Wright, Robin; Boggs, James

    2002-01-01

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

  10. Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Laura R. Jarboe

    2010-01-01

    Full Text Available Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors.

  11. Reproductive hormones and metabolic syndrome in 24 testicular cancer survivors and their biological brothers.

    Science.gov (United States)

    Bandak, M; Jørgensen, N; Juul, A; Lauritsen, J; Kier, M G G; Mortensen, M S; Oturai, P S; Mortensen, J; Hojman, P; Helge, J W; Daugaard, G

    2017-07-01

    Testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to healthy controls. However, because of the fetal etiology of testicular cancer, familial unrelated healthy men might not be an optimal control group. The objective of this study was to clarify if testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to their biological brothers. A cross-sectional study of testicular cancer survivors (ClinicalTrials.gov number, NCT02240966) was conducted between 2014 and 2016. Of 158 testicular cancer survivors included, 24 had a biological brother who accepted to participate in the study. Serum levels of reproductive hormones and prevalence of metabolic syndrome according to International Diabetes Federation Criteria and National Cholesterol Education Program (Adult Treatment Panel III) criteria comprised the main outcome measures of the study. Median age was similar in testicular cancer survivors and their biological brothers [44 years (IQR 39-50) vs. 46 (40-53) years respectively (p = 0.1)]. In testicular cancer survivors, follow-up since treatment was 12 years (7-19). Serum levels of luteinizing hormone and follicle-stimulating hormone were elevated (p ≤ 0.001), while total testosterone, free testosterone, inhibin B and anti-Müllerian hormone were lower (p ≤ 0.001) in testicular cancer survivors than in their biological brothers. The prevalence of metabolic syndrome was similar and apart from HDL-cholesterol, which was lower in testicular cancer survivors (p = 0.01); there were no differences in the individual components of the metabolic syndrome between testicular cancer survivors and their brothers. In conclusion, gonadal function was impaired in testicular cancer survivors, while we did not detect any difference in the prevalence of metabolic syndrome between testicular cancer survivors and their biological brothers. © 2017 American

  12. Natural Compounds as Regulators of the Cancer Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Claudia Cerella

    2013-01-01

    Full Text Available Even though altered metabolism is an “old” physiological mechanism, only recently its targeting became a therapeutically interesting strategy and by now it is considered an emerging hallmark of cancer. Nevertheless, a very poor number of compounds are under investigation as potential modulators of cell metabolism. Candidate agents should display selectivity of action towards cancer cells without side effects. This ideal favorable profile would perfectly overlap the requisites of new anticancer therapies and chemopreventive strategies as well. Nature represents a still largely unexplored source of bioactive molecules with a therapeutic potential. Many of these compounds have already been characterized for their multiple anticancer activities. Many of them are absorbed with the diet and therefore possess a known profile in terms of tolerability and bioavailability compared to newly synthetized chemical compounds. The discovery of important cross-talks between mediators of the most therapeutically targeted aberrancies in cancer (i.e., cell proliferation, survival, and migration and the metabolic machinery allows to predict the possibility that many anticancer activities ascribed to a number of natural compounds may be due, in part, to their ability of modulating metabolic pathways. In this review, we attempt an overview of what is currently known about the potential of natural compounds as modulators of cancer cell metabolism.

  13. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

    Science.gov (United States)

    Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

    2016-07-01

    A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

  14. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    DEFF Research Database (Denmark)

    Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways...

  15. Metabolic disposition and biological significance of simple phenols of dietary origin: hydroxytyrosol and tyrosol.

    Science.gov (United States)

    Rodríguez-Morató, Jose; Boronat, Anna; Kotronoulas, Aristotelis; Pujadas, Mitona; Pastor, Antoni; Olesti, Eulalia; Pérez-Mañá, Clara; Khymenets, Olha; Fitó, Montserrat; Farré, Magí; de la Torre, Rafael

    2016-05-01

    Hydroxytyrosol and tyrosol are dietary phenolic compounds present in virgin olive oil and wine. Both compounds are also endogenously synthesized in our body as byproducts of dopamine and tyramine metabolisms, respectively. Over the last decades, research into hydroxytyrosol and tyrosol has experienced an increasing interest due to the role that these compounds may play in the prevention of certain pathologies (e.g. cardiovascular, metabolic, neurodegenerative diseases and cancer). The translation of promising in vitro and in vivo biological effects from preclinical studies to the context of human disease prevention initially depends on whether the dose ingested becomes available at the site of action. In this regard, information regarding the bioavailability and metabolic disposition of hydroxytyrosol and tyrosol is of most importance to evaluate the impact they may have on human health. In this review, we discuss and summarize the state of the art of the scientific evidence regarding the processes of absorption, distribution, metabolism and excretion of both hydroxytyrosol and tyrosol. We also examine the impact of these compounds and their metabolites on biological activity in terms of beneficial health effects. Finally, we evaluate the different analytical approaches that have been developed to measure the plasma and urinary levels of hydroxytyrosol, tyrosol and their metabolites.

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

    Science.gov (United States)

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

    2012-03-01

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

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

    OpenAIRE

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

    2013-01-01

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

  18. Beyond reductionism: metabolic circularity as a guiding vision for a real biology of systems.

    Science.gov (United States)

    Cornish-Bowden, Athel; Cárdenas, María Luz; Letelier, Juan-Carlos; Soto-Andrade, Jorge

    2007-03-01

    The definition of life has excited little interest among molecular biologists during the past half-century, and the enormous development in biology during that time has been largely based on an analytical approach in which all biological entities are studied in terms of their components, the process being extended to greater and greater detail without limit. The benefits of this reductionism are so obvious that they need no discussion, but there have been costs as well, and future advances, for example, for creating artificial life or for taking biotechnology beyond the level of tinkering, will need more serious attention to be given to the question of what makes a living organism living. According to Robert Rosen's theory of metabolism-replacement systems, the central idea missing from molecular biology is that of metabolic circularity, most evident from the obvious but commonly ignored fact that proteins are not given from outside but are products of metabolism, and thus metabolites. Among other consequences, this implies that the usual distinction between proteome and metabolome is conceptually artificial -- however useful it may be in practice -- as the proteome is part of the metabolome.

  19. The biology of innate lymphoid cells

    NARCIS (Netherlands)

    Artis, David; Spits, Hergen

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

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

  1. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.

    Directory of Open Access Journals (Sweden)

    Robert W Tilghman

    Full Text Available Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa, cells on soft substrates (150-300 Pa exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins and glycolysis (e.g., phosphofructokinase-1, whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical

  2. Biological cell controllable patch-clamp microchip

    Science.gov (United States)

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

    2010-12-01

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

  3. Stem cells: a plant biology perspective

    NARCIS (Netherlands)

    Scheres, B.J.G.

    2005-01-01

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

  4. Biology at a single cell level

    CSIR Research Space (South Africa)

    Mthunzi, P

    2012-10-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    Science.gov (United States)

    Melton, Douglas A

    2016-01-01

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

  7. Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

    Science.gov (United States)

    Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Lee, Jong Ho

    2017-01-01

    The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72) or metabolically unhealthy overweight (MUO, n = 45). The immune response was measured by circulating levels of natural killer (NK) cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant) and 41% lower interleukin (IL)-12 levels (significant). The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05) than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities. PMID:29238351

  8. Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

    Directory of Open Access Journals (Sweden)

    Minjoo Kim

    2017-11-01

    Full Text Available The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72 or metabolically unhealthy overweight (MUO, n = 45. The immune response was measured by circulating levels of natural killer (NK cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant and 41% lower interleukin (IL-12 levels (significant. The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05 than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities.

  9. Metabolic behavior of cell surface biotinylated proteins

    International Nuclear Information System (INIS)

    Hare, J.F.; Lee, E.

    1989-01-01

    The turnover of proteins on the surface of cultured mammalian cells was measured by a new approach. Reactive free amino or sulfhydryl groups on surface-accessible proteins were derivatized with biotinyl reagents and the proteins solubilized from culture dishes with detergent. Solubilized, biotinylated proteins were then adsorbed onto streptavidin-agarose, released with sodium dodecyl sulfate and mercaptoethanol, and separated on polyacrylamide gels. Biotin-epsilon-aminocaproic acid N-hydroxysuccinimide ester (BNHS) or N-biotinoyl-N'-(maleimidohexanoyl)hydrazine (BM) were the derivatizing agents. Only 10-12 bands were adsorbed onto streptavidin-agarose from undervatized cells or from derivatized cells treated with free avidin at 4 degrees C. Two-dimensional isoelectric focusing-sodium dodecyl sulfate gel electrophoresis resolved greater than 100 BNHS-derivatized proteins and greater than 40 BM-derivatized proteins. There appeared to be little overlap between the two groups of derivatized proteins. Short-term pulse-chase studies showed an accumulation of label into both groups of biotinylated proteins up until 1-2 h of chase and a rapid decrease over the next 1-5 h. Delayed appearance of labeled protein at the cell surface was attributed to transit time from site of synthesis. The unexpected and unexplained rapid disappearance of pulse-labeled proteins from the cell surface was invariant for all two-dimensionally resolved proteins and was sensitive to temperature reduction to 18 degrees C. Long-term pulse-chase experiments beginning 4-8 h after the initiation of chase showed the disappearance of derivatized proteins to be a simple first-order process having a half-life of 115 h in the case of BNHS-derivatized proteins and 30 h in the case of BM-derivatized proteins

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

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

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

  11. Advances in Retinal Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    Science.gov (United States)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  14. Melatonin redirects carbohydrates metabolism during sugar starvation in plant cells.

    Science.gov (United States)

    Kobylińska, Agnieszka; Borek, Sławomir; Posmyk, Małgorzata M

    2018-05-01

    Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin efficacy eliminates oxidative stress (direct and indirect antioxidant) and moreover induce plant stress reaction and switch on different defence strategies (preventively and interventively actions). In this report, the impact of exogenous melatonin on carbohydrate metabolism in Nicotiana tabacum L. line Bright Yellow 2 (BY-2) suspension cells during sugar starvation was examined. We analysed starch concentration, α-amylase and PEPCK activity as well as proteolytic activity in culture media. It has been shown that BY-2 cell treatment with 200 nM of melatonin improved viability of sugar-starved cells. It was correlated with higher starch content and phosphoenolpyruvate carboxykinase (PEPCK) activity. The obtained results revealed that exogenous melatonin under specific conditions (stress) can play regulatory role in sugar metabolism, and it may modulate carbohydrate concentration in etiolated BY-2 cells. Moreover, our results confirmed the hypothesis that if the starch is synthesised even in sugar-starved cells, it is highly probable that melatonin shifts the BY-2 cell metabolism on gluconeogenesis pathway and allows for synthesis of carbohydrates from nonsugar precursors, that is amino acids. These points to another defence strategy that was induced by exogenous melatonin applied in plants to overcome adverse environmental conditions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Metabolic Compartmentation – A System Level Property of Muscle Cells

    Directory of Open Access Journals (Sweden)

    Theo Wallimann

    2008-05-01

    Full Text Available Problems of quantitative investigation of intracellular diffusion and compartmentation of metabolites are analyzed. Principal controversies in recently published analyses of these problems for the living cells are discussed. It is shown that the formal theoretical analysis of diffusion of metabolites based on Fick’s equation and using fixed diffusion coefficients for diluted homogenous aqueous solutions, but applied for biological systems in vivo without any comparison with experimental results, may lead to misleading conclusions, which are contradictory to most biological observations. However, if the same theoretical methods are used for analysis of actual experimental data, the apparent diffusion constants obtained are orders of magnitude lower than those in diluted aqueous solutions. Thus, it can be concluded that local restrictions of diffusion of metabolites in a cell are a system-level properties caused by complex structural organization of the cells, macromolecular crowding, cytoskeletal networks and organization of metabolic pathways into multienzyme complexes and metabolons. This results in microcompartmentation of metabolites, their channeling between enzymes and in modular organization of cellular metabolic networks. The perspectives of further studies of these complex intracellular interactions in the framework of Systems Biology are discussed.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

    Stick, R.; Dráber, Pavel

    2017-01-01

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

  18. Glycoengineering in CHO cells: Advances in systems biology

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  19. Cell Division and Evolution of Biological Tissues

    Science.gov (United States)

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

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

  20. Glial cell biology in the Great Lakes region.

    Science.gov (United States)

    Feinstein, Douglas L; Skoff, Robert P

    2016-03-31

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

  1. Oral Gingival Cell Cigarette Smoke Exposure Induces Muscle Cell Metabolic Disruption

    Directory of Open Access Journals (Sweden)

    Andrea C. Baeder

    2016-01-01

    Full Text Available Cigarette smoke exposure compromises health through damaging multiple physiological systems, including disrupting metabolic function. The purpose of this study was to determine the role of oral gingiva in mediating the deleterious metabolic effects of cigarette smoke exposure on skeletal muscle metabolic function. Using an in vitro conditioned medium cell model, skeletal muscle cells were incubated with medium from gingival cells treated with normal medium or medium containing suspended cigarette smoke extract (CSE. Following incubation of muscle cells with gingival cell conditioned medium, muscle cell mitochondrial respiration and insulin signaling and action were determined as an indication of overall muscle metabolic health. Skeletal muscle cells incubated with conditioned medium of CSE-treated gingival cells had a profound reduction in mitochondrial respiration and respiratory control. Furthermore, skeletal muscle cells had a greatly reduced response in insulin-stimulated Akt phosphorylation and glycogen synthesis. Altogether, these results provide a novel perspective on the mechanism whereby cigarette smoke affects systemic metabolic function. In conclusion, we found that oral gingival cells treated with CSE create an altered milieu that is sufficient to both disrupted skeletal muscle cell mitochondrial function and insulin sensitivity.

  2. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

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

  3. Dendritic cells: biology of the skin

    NARCIS (Netherlands)

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

    2009-01-01

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

  4. Role of innate lymphoid cells in obesity and metabolic disease

    Science.gov (United States)

    Saetang, Jirakrit; Sangkhathat, Surasak

    2018-01-01

    The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

  5. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism.

    Science.gov (United States)

    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-02-27

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.

  6. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Science.gov (United States)

    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-01-01

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions. DOI: http://dx.doi.org/10.7554/eLife.10250.001 PMID:26920219

  7. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Tim A D Smith

    Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

  8. Study on substrate metabolism process of saline waste sludge and its biological hydrogen production potential.

    Science.gov (United States)

    Zhang, Zengshuai; Guo, Liang; Li, Qianqian; Zhao, Yangguo; Gao, Mengchun; She, Zonglian

    2017-07-01

    With the increasing of high saline waste sludge production, the treatment and utilization of saline waste sludge attracted more and more attention. In this study, the biological hydrogen production from saline waste sludge after heating pretreatment was studied. The substrate metabolism process at different salinity condition was analyzed by the changes of soluble chemical oxygen demand (SCOD), carbohydrate and protein in extracellular polymeric substances (EPS), and dissolved organic matters (DOM). The excitation-emission matrix (EEM) with fluorescence regional integration (FRI) was also used to investigate the effect of salinity on EPS and DOM composition during hydrogen fermentation. The highest hydrogen yield of 23.6 mL H 2 /g VSS and hydrogen content of 77.6% were obtained at 0.0% salinity condition. The salinity could influence the hydrogen production and substrate metabolism of waste sludge.

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

    Science.gov (United States)

    Qian, Tongcheng; Wang, Yingxiao

    2010-10-01

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

  10. Combined metabonomic and quantitative real-time PCR analyses reveal systems metabolic changes in Jurkat T-cells treated with HIV-1 Tat protein.

    Science.gov (United States)

    Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

    2012-11-02

    HIV-1 Tat protein is released by infected cells and can affect bystander uninfected T cells and induce numerous biological responses which contribute to its pathogenesis. To elucidate the complex pathogenic mechanism, we conducted a comprehensive investigation on Tat protein-related extracellular and intracellular metabolic changes in Jurkat T-cells using combined gas chromatography-mass spectrometry (GC-MS), reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and a hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS)-based metabonomics approach. Quantitative real-time PCR (qRT-PCR) analyses were further employed to measure expressions of several relevant enzymes together with perturbed metabolic pathways. Combined metabonomic and qRT-PCR analyses revealed that HIV-1 Tat caused significant and comprehensive metabolic changes, as represented by significant changes of 37 metabolites and 10 relevant enzymes in HIV-1 Tat-treated cells. Using MetaboAnalyst 2.0, it was found that 11 pathways (Impact-value >0.10) among the regulated pathways were acutely perturbed, including sphingolipid metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, inositol phosphate metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism, pentose phosphate pathway, glycerophospholipid metabolism, glycolysis or gluconeogenesis. These results provide metabolic evidence of the complex pathogenic mechanism of HIV-1 Tat protein as a "viral toxin", and would help obligate Tat protein as "an important target" for therapeutic intervention and vaccine development.

  11. Cells, targets, and molecules in radiation biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

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

  12. Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco Method.

    Science.gov (United States)

    Jiang, X Y; Wang, J F; Zhu, G H; Ma, M Y; Lai, Y; Zhou, H

    2016-06-01

    To detect the changes of microbial community functional diversity of corpses with different postmortem interval (PMI) and to evaluate forensic application value for estimating PMI. The cultivation of microbial community from the anal swabs of a Sus scrofa and a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Microplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial community on the decomposed corpse under natural environment were also observed. The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples became relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components (accumulative contribution ratio >90%).The carbon source tsquare-analysis showed that N -acetyl- D -glucosamine and L -serine were the dominant carbon sources for estimating the PMI (0=240 h) of the Sus scrofa and human corpse. The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI. Copyright© by the Editorial Department of Journal of Forensic Medicine

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

    Science.gov (United States)

    Noisa, Parinya; Raivio, Taneli

    2014-09-01

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

  14. Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3

    NARCIS (Netherlands)

    Doddaballapur, Anuradha; Michalik, Katharina M.; Manavski, Yosif; Lucas, Tina; Houtkooper, Riekelt H.; You, Xintian; Chen, Wei; Zeiher, Andreas M.; Potente, Michael; Dimmeler, Stefanie; Boon, Reinier A.

    2015-01-01

    Cellular metabolism was recently shown to regulate endothelial cell phenotype profoundly. Whether the atheroprotective biomechanical stimulus elicited by laminar shear stress modulates endothelial cell metabolism is not known. Here, we show that laminar flow exposure reduced glucose uptake and

  15. N-Glycosylation optimization of recombinant antibodies in CHO cell through process and metabolic engineering

    DEFF Research Database (Denmark)

    Fan, Yuzhou

    , analysis, control and optimization of N-glycosylation were thoroughly reviewed. In particular, how to control and optimize N-glycosylation in CHO cells was exclusively studied. The main focus of this PhD project is to find effective approaches of modulating N-glycosylation of CHO-derived recombinant...... galactose as feed additives, changing process parameters such as seeding density and cultivation duration are all demonstrated to be effective. The causal explanation of their impact on glycosylation can be various, including product, metabolism, proteome and physiology-associated mechanism. In the middle...... part of the thesis, both literature reviews and experimental applications were provided to demonstrate how to use omics data and implement systems biology to understand biological activities, especially N-glycosylation in CHO cells. In the last part of the thesis, the second strategy that apply genetic...

  16. Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

    Science.gov (United States)

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2013-11-15

    Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.

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

    Science.gov (United States)

    Pollard, Steven M

    2016-11-15

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

  18. Measuring cell cycle progression kinetics with metabolic labeling and flow cytometry.

    Science.gov (United States)

    Fleisig, Helen; Wong, Judy

    2012-05-22

    Precise control of the initiation and subsequent progression through the various phases of the cell cycle are of paramount importance in proliferating cells. Cell cycle division is an integral part of growth and reproduction and deregulation of key cell cycle components have been implicated in the precipitating events of carcinogenesis. Molecular agents in anti-cancer therapies frequently target biological pathways responsible for the regulation and coordination of cell cycle division. Although cell cycle kinetics tend to vary according to cell type, the distribution of cells amongst the four stages of the cell cycle is rather consistent within a particular cell line due to the consistent pattern of mitogen and growth factor expression. Genotoxic events and other cellular stressors can result in a temporary block of cell cycle progression, resulting in arrest or a temporary pause in a particular cell cycle phase to allow for instigation of the appropriate response mechanism. The ability to experimentally observe the behavior of a cell population with reference to their cell cycle progression stage is an important advance in cell biology. Common procedures such as mitotic shake off, differential centrifugation or flow cytometry-based sorting are used to isolate cells at specific stages of the cell cycle. These fractionated, cell cycle phase-enriched populations are then subjected to experimental treatments. Yield, purity and viability of the separated fractions can often be compromised using these physical separation methods. As well, the time lapse between separation of the cell populations and the start of experimental treatment, whereby the fractionated cells can progress from the selected cell cycle stage, can pose significant challenges in the successful implementation and interpretation of these experiments. Other approaches to study cell cycle stages include the use of chemicals to synchronize cells. Treatment of cells with chemical inhibitors of key

  19. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging

    OpenAIRE

    Palmer, Clovis S.; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M.

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impa...

  20. Enzyme and metabolic engineering for the production of novel biopolymers: crossover of biological and chemical processes.

    Science.gov (United States)

    Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2013-12-01

    The development of synthetic biology has transformed microbes into useful factories for producing valuable polymers and/or their precursors from renewable biomass. Recent progress at the interface of chemistry and biology has enabled the production of a variety of new biopolymers with properties that substantially differ from their petroleum-derived counterparts. This review touches on recent trials and achievements in the field of biopolymer synthesis, including chemo-enzymatically synthesized aliphatic polyesters, wholly biosynthesized lactate-based polyesters, polyhydroxyalkanoates and other unusual bacterially synthesized polyesters. The expanding diversities in structure and the material properties of biopolymers are key for exploring practical applications. The enzyme and metabolic engineering approaches toward this goal are discussed by shedding light on the successful case studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

    Science.gov (United States)

    Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

    2011-03-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

  4. Single-cell sequencing in stem cell biology.

    Science.gov (United States)

    Wen, Lu; Tang, Fuchou

    2016-04-15

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

  5. [Metabolic changes in cells under electromagnetic radiation of mobile communication systems].

    Science.gov (United States)

    Iakimenko, I L; Sidorik, E P; Tsybulin, A S

    2011-01-01

    Review is devoted to the analysis of biological effects of microwaves. The results of last years' researches indicated the potential risks of long-term low-level microwaves exposure for human health. The analysis of metabolic changes in living cells under the exposure of microwaves from mobile communication systems indicates that this factor is stressful for cells. Among the reproducible effects of low-level microwave radiation are overexpression of heat shock proteins, an increase of reactive oxygen species level, an increase of intracellular Ca2+, damage of DNA, inhibition of DNA reparation, and induction of apoptosis. Extracellular-signal-regulated kinases ERK and stress-related kinases p38MAPK are involved in metabolic changes. Analysis of current data suggests that the concept of exceptionally thermal mechanism of biological effects of microwaves is not correct. In turn, this raises the question of the need to revaluation of modern electromagnetic standards based on thermal effects of non-ionizing radiation on biological systems.

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

    Science.gov (United States)

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

    2015-12-15

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

  7. Micro and nano-platforms for biological cell analysis

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  8. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    International Nuclear Information System (INIS)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

    2011-01-01

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  9. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  10. Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakagami

    2015-01-01

    Full Text Available 4H-1-benzopyran-4-ones (chromones are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E-3-(4-hydroxystyryl-6-methoxy-4H-chromen-4-one (compound 11, (E-6-methoxy-3-(4-methoxystyryl-4H-chromen-4-one (compound 4, (E-6-methoxy-3-(3,4,5-trimethoxystyryl-4H-chromen-4-one (compound 6 showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  13. Recent developments in systems biology and metabolic engineering of plant microbe interactions

    Directory of Open Access Journals (Sweden)

    Vishal Kumar

    2016-09-01

    Full Text Available Microorganisms play a crucial role in the sustainability of the various ecosystems. The characterization of various interactions between microorganisms and other biotic factors is a necessary footstep to understand the association and functions of microbial communities. Among the different microbial interactions in an ecosystem, plant-microbe interaction plays an important role to balance the ecosystem. The present review explores plant microbe interactions using gene editing and system biology tools towards the comprehension in improvement of plant traits. Further, system biology tools like FBA, OptKnock and constrain based modeling helps in understanding such interactions as a whole. In addition, various gene editing tools have been summarized and a strategy has been hypothesized for the development of disease free plants. Furthermore, we have tried to summarize the predictions through data retrieved from various types of sources such as high throughput sequencing data (e.g. single nucleotide polymorphism (SNP detection, RNA-seq, proteomics and metabolic models have been reconstructed from such sequences for species communities. It is well known fact that systems biology approaches and modeling of biological networks will enable us to learn the insight of such network and will also help further in understanding these interactions.

  14. Synthetic biology of cyanobacterial cell factories

    NARCIS (Netherlands)

    Angermayr, S.A.

    2014-01-01

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

  15. Cell biology of homologous recombination in yeast

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  16. Wnt Signaling in Cancer Stem Cell Biology

    NARCIS (Netherlands)

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-01-01

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

  17. Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

    Science.gov (United States)

    Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

    2017-10-01

    Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

  18. High-dimensional single-cell cancer biology.

    Science.gov (United States)

    Irish, Jonathan M; Doxie, Deon B

    2014-01-01

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

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

    Science.gov (United States)

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

    2010-01-01

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

  20. The relationship of metabolic burden to productivity levels in CHO cell lines.

    Science.gov (United States)

    Zou, Wu; Edros, Raihana; Al-Rubeai, Mohamed

    2018-03-01

    The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell-specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody. In all three cell lines, the inhibitory effect of these parameters on proliferation was demonstrated. Additionally, compared to the control, specific productivity was enhanced under all conditions and exhibited a consistent cell line specific pattern, with maximum increases (50-290%) in the low producer, and minimum increases (7-20%) in the high producer. Thus, the high-producing cell line was less responsive to environmental perturbations than the low-producing cell line. We hypothesize that this difference is most likely due to the bottleneck associated with a higher metabolic burden caused by higher antibody expression. Increased recombinant mRNA levels and pyruvate carboxylase activities due to low temperature and hyperosmotic stress were found to be positively associated with the metabolic burden. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  1. TOR, the Gateway to Cellular Metabolism, Cell Growth, and Disease.

    Science.gov (United States)

    Blenis, John

    2017-09-21

    Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  3. Biological Influence of Deuterium on Procariotic and Eukaryotic Cells

    OpenAIRE

    Oleg Mosin; Ignat Ignatov

    2014-01-01

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

  4. Biofuel production in Escherichia coli. The role of metabolic engineering and synthetic biology

    Energy Technology Data Exchange (ETDEWEB)

    Clomburg, James M. [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Gonzalez, Ramon [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Rice Univ., Houston, TX (United States). Dept. of Bioengineering

    2010-03-15

    The microbial production of biofuels is a promising avenue for the development of viable processes for the generation of fuels from sustainable resources. In order to become cost and energy effective, these processes must utilize organisms that can be optimized to efficiently produce candidate fuels from a variety of feedstocks. Escherichia coli has become a promising host organism for the microbial production of biofuels in part due to the ease at which this organism can be manipulated. Advancements in metabolic engineering and synthetic biology have led to the ability to efficiently engineer E. coli as a biocatalyst for the production of a wide variety of potential biofuels from several biomass constituents. This review focuses on recent efforts devoted to engineering E. coli for the production of biofuels, with emphasis on the key aspects of both the utilization of a variety of substrates as well as the synthesis of several promising biofuels. Strategies for the efficient utilization of carbohydrates, carbohydrate mixtures, and noncarbohydrate carbon sources will be discussed along with engineering efforts for the exploitation of both fermentative and nonfermentative pathways for the production of candidate biofuels such as alcohols and higher carbon biofuels derived from fatty acid and isoprenoid pathways. Continued advancements in metabolic engineering and synthetic biology will help improve not only the titers, yields, and productivities of biofuels discussed herein, but also increase the potential range of compounds that can be produced. (orig.)

  5. Metabolism and toxicological analysis of synthetic cannabinoids in biological fluids and tissues.

    Science.gov (United States)

    Presley, B C; Gurney, S M R; Scott, K S; Kacinko, S L; Logan, B K

    2016-07-01

    Synthetic cannabinoids, which began proliferating in the United States in 2009, have gone through numerous iterations of modification to their chemical structures. More recent generations of compounds have been associated with significant adverse outcomes following use, including cognitive and psychomotor impairment, seizures, psychosis, tissue injury and death. These effects increase the urgency for forensic and public health laboratories to develop methods for the detection and identification of novel substances, and apply these to the determination of their metabolism and disposition in biological samples. This comprehensive review describes the history of the appearance of the drugs in the United States, discusses the naming conventions emerging to designate new structures, and describes the most prominent new compounds linked to the adverse effects now associated with their use. We review in depth the metabolic pathways that have been elucidated for the major members of each of the prevalent synthetic cannabinoid drug subclasses, the enzyme systems responsible for their metabolism, and the use of in silico approaches to assist in predicting and identifying the metabolites of novel compounds and drug subclasses that will continue to appear. Finally, we review and critique analytical methods applied to the detection of the drugs and their metabolites, including immunoassay screening, and liquid chromatography mass spectrometry confirmatory techniques applied to urine, serum, whole blood, oral fluid, hair, and tissues. Copyright © 2016 Central Police University.

  6. Determining the bacterial cell biology of Planctomycetes.

    Science.gov (United States)

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

    2017-04-10

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

  7. Molecular biological features of male germ cell differentiation

    Science.gov (United States)

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

    2007-01-01

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

  8. Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

    International Nuclear Information System (INIS)

    Zhang, Min; Chai, Yang D; Brumbaugh, Jeffrey; Liu, Xiaojun; Rabii, Ramin; Feng, Sizhe; Misuno, Kaori; Messadi, Diana; Hu, Shen

    2014-01-01

    Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

  9. Investigations on the role of hemoglobin in sulfide metabolism by intact human red blood cells.

    Science.gov (United States)

    Bianco, Christopher L; Savitsky, Anton; Feelisch, Martin; Cortese-Krott, Miriam M

    2018-03-01

    In addition to their role as oxygen transporters, red blood cells (RBCs) contribute to cardiovascular homeostasis by regulating nitric oxide (NO) metabolism via interaction of hemoglobin (Hb) with nitrite and NO itself. RBCs were proposed to also participate in sulfide metabolism. Although Hb is known to react with sulfide, sulfide metabolism by intact RBCs has not been characterized so far. Therefore we explored the role of Hb in sulfide metabolism in intact human RBCs. We find that upon exposure of washed RBCs to sulfide, no changes in oxy/deoxyhemoglobin (oxy/deoxyHb) are observed by UV-vis and EPR spectroscopy. However, sulfide reacts with methemoglobin (metHb), forming a methemoglobin-sulfide (metHb-SH) complex. Moreover, while metHb-SH is stable in cell-free systems even in the presence of biologically relevant thiols, it gradually decomposes to produce oxyHb, inorganic polysulfides and thiosulfate in intact cells, as detected by EPR and mass spectrometry. Taken together, our results demonstrate that under physiological conditions RBCs are able to metabolize sulfide via intermediate formation of a metHb-SH complex, which subsequently decomposes to oxyHb. We speculate that decomposition of metHb-SH is preceded by an inner-sphere electron transfer, forming reduced Hb (which binds oxygen to form oxyHb) and thiyl radical (a process we here define as "reductive sulfhydration"), which upon release, gives rise to the oxidized products, thiosulfate and polysulfides. Thus, not only is metHb an efficient scavenger and regulator of sulfide in blood, intracellular sulfide itself may play a role in keeping Hb in the reduced oxygen-binding form and, therefore, be involved in RBC physiology and function. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

    Science.gov (United States)

    Eggert, F-Michael; Levin, Liran

    2018-01-01

    In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of

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

    Science.gov (United States)

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

    2015-08-03

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

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

    Science.gov (United States)

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

    2015-01-01

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

  13. TinkerCell: modular CAD tool for synthetic biology

    Science.gov (United States)

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

    2009-01-01

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

  14. TinkerCell: modular CAD tool for synthetic biology

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T

    2009-10-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  16. Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells

    Directory of Open Access Journals (Sweden)

    Yan Yin

    2012-11-01

    Developmental exposure to diethylstilbestrol (DES causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of peroxisome proliferator-activated receptor-γ (PPARγ-mediated adipogenesis and lipid metabolism, including PPARγ itself, are targets of DES in the neonatal uterus. Transmission electron microscopy and Oil-Red O staining further demonstrate a dramatic increase in lipid deposition in uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor-induced reproductive abnormalities.

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

    Science.gov (United States)

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

    2016-04-18

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

  18. Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data.

    Science.gov (United States)

    Yang, Laurence; Tan, Justin; O'Brien, Edward J; Monk, Jonathan M; Kim, Donghyuk; Li, Howard J; Charusanti, Pep; Ebrahim, Ali; Lloyd, Colton J; Yurkovich, James T; Du, Bin; Dräger, Andreas; Thomas, Alex; Sun, Yuekai; Saunders, Michael A; Palsson, Bernhard O

    2015-08-25

    Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

  19. Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae*

    Science.gov (United States)

    Medeiros, Rychelle Clayde Affonso; Girardi, Karina do Carmo de Vasconcelos; Cardoso, Fernanda Karlla Luz; Mietto, Bruno de Siqueira; Pinto, Thiago Gomes de Toledo; Gomez, Lilian Sales; Rodrigues, Luciana Silva; Gandini, Mariana; Amaral, Julio Jablonski; Antunes, Sérgio Luiz Gomes; Corte-Real, Suzana; Rosa, Patricia Sammarco; Pessolani, Maria Cristina Vidal; Nery, José Augusto da Costa; Sarno, Euzenir Nunes; Batista-Silva, Leonardo Ribeiro; Sola-Penna, Mauro; Oliveira, Marcus Fernandes; Moraes, Milton Ozório; Lara, Flavio Alves

    2016-01-01

    Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. PMID:27555322

  20. Posttranscriptional RNA Modifications: playing metabolic games in a cell's chemical Legoland.

    Science.gov (United States)

    Helm, Mark; Alfonzo, Juan D

    2014-02-20

    Nature combines existing biochemical building blocks, at times with subtlety of purpose. RNA modifications are a prime example of this, where standard RNA nucleosides are decorated with chemical groups and building blocks that we recall from our basic biochemistry lectures. The result: a wealth of chemical diversity whose full biological relevance has remained elusive despite being public knowledge for some time. Here, we highlight several modifications that, because of their chemical intricacy, rely on seemingly unrelated pathways to provide cofactors for their synthesis. Besides their immediate role in affecting RNA function, modifications may act as sensors and transducers of information that connect a cell's metabolic state to its translational output, carefully orchestrating a delicate balance between metabolic rate and protein synthesis at a system's level. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: a study of human melanoma multicellular spheroids.

    Science.gov (United States)

    Rofstad, E K; Eide, K; Skøyum, R; Hystad, M E; Lyng, H

    1996-09-01

    The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia- induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WIX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-microM spheroids were 32 +/- 12% (BEX-c) and 2.5 +/- 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 +/- 6% (BEX-c) and 1.4 +/- 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c showed lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of

  2. The role of EMMPRIN in T cell biology and immunological diseases.

    Science.gov (United States)

    Hahn, Jennifer Nancy; Kaushik, Deepak Kumar; Yong, V Wee

    2015-07-01

    EMMPRIN (CD147), originally described as an inducer of the expression of MMPs, has gained attention in its involvement in various immunologic diseases, such that anti-EMMPRIN antibodies are considered as potential therapeutic medications. Given that MMPs are involved in the pathogenesis of various disease states, it is relevant that targeting an upstream inducer would make for an effective therapeutic strategy. Additionally, EMMPRIN is now appreciated to have multiple roles apart from MMP induction, including in cellular functions, such as migration, adhesion, invasion, energy metabolism, as well as T cell activation and proliferation. Here, we review what is known about EMMPRIN in numerous immunologic/inflammatory disease conditions with a particular focus on its complex roles in T cell biology. © Society for Leukocyte Biology.

  3. Systems-biology dissection of eukaryotic cell growth

    Directory of Open Access Journals (Sweden)

    Andrews Justen

    2010-05-01

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

  4. Heavy ion induced DNA transfer in biological cells

    International Nuclear Information System (INIS)

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

    2004-01-01

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

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

    Science.gov (United States)

    Beagley, C Timothy

    2013-01-01

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

  6. Collective Sensing of β-Cells Generates the Metabolic Code

    Directory of Open Access Journals (Sweden)

    Dean Korošak

    2018-01-01

    Full Text Available Major part of a pancreatic islet is composed of β-cells that secrete insulin, a key hormone regulating influx of nutrients into all cells in a vertebrate organism to support nutrition, housekeeping or energy storage. β-cells constantly communicate with each other using both direct, short-range interactions through gap junctions, and paracrine long-range signaling. However, how these cell interactions shape collective sensing and cell behavior in islets that leads to insulin release is unknown. When stimulated by specific ligands, primarily glucose, β-cells collectively respond with expression of a series of transient Ca2+ changes on several temporal scales. Here we reanalyze a set of Ca2+ spike trains recorded in acute rodent pancreatic tissue slice under physiological conditions. We found strongly correlated states of co-spiking cells coexisting with mostly weak pairwise correlations widespread across the islet. Furthermore, the collective Ca2+ spiking activity in islet shows on-off intermittency with scaling of spiking amplitudes, and stimulus dependent autoassociative memory features. We use a simple spin glass-like model for the functional network of a β-cell collective to describe these findings and argue that Ca2+ spike trains produced by collective sensing of β-cells constitute part of the islet metabolic code that regulates insulin release and limits the islet size.

  7. Metabolism plays the key roles in Th cells differentiation

    Directory of Open Access Journals (Sweden)

    A. Hosseinzadeh

    2016-12-01

    Full Text Available The increasing rate of autoimmunity in recent decades cannot be related to only genetic instabilities and disorders. Diet can directly influence our health. Studies have shown that there is a relationship between nutritional elements and alteration in the immune system. Among immune cells, the function of T lymphocyte is important in directing immune response. T CD4+ cells lead other immune cells to respond to pathogens by secreting cytokines. HIV+ patients, who have largely lost their T CD4+ cells, are susceptible to opportunistic infections, which do not normally affect healthy people. It seems that the metabolism of T cells is critical for their differentiation and their consequent functions. After activation, T cells need to undergo clonal expansion, which is a high energy- consuming process. Studies have shown that specific metabolites deprivation or their excess supply affects T CD4+cells subsets differentiation. Abnormal induction of subsets of T CD4+ cells causes some autoimmunity reactions and hyper-sensitivity as well, which may result from imbalance of diet uptake. In this mini-review, we describe the findings about fatty acids, glucose, amino acids, and vitamins, which are effective in determining the fates of T CD4+ cells. These findings may help us uncover the role of diet in autoimmune diseases.

  8. Site-specific distribution of claudin-based paracellular channels with roles in biological fluid flow and metabolism.

    Science.gov (United States)

    Tanaka, Hiroo; Tamura, Atsushi; Suzuki, Koya; Tsukita, Sachiko

    2017-10-01

    The claudins are a family of membrane proteins with at least 27 members in humans and mice. The extracellular regions of claudin proteins play essential roles in cell-cell adhesion and the paracellular barrier functions of tight junctions (TJs) in epithelial cell sheets. Furthermore, the extracellular regions of some claudins function as paracellular channels in the paracellular barrier that allow the selective passage of water, ions, and/or small organic solutes across the TJ in the extracellular space. Structural analyses have revealed a common framework of transmembrane, cytoplasmic, and extracellular regions among the claudin-based paracellular barriers and paracellular channels; however, differences in the claudins' extracellular regions, such as their charges and conformations, determine their properties. Among the biological systems that involve fluid flow and metabolism, it is noted that hepatic bile flow, renal Na + reabsorption, and intestinal nutrient absorption are dynamically regulated via site-specific distributions of paracellular channel-forming claudins in tissue. Here, we focus on how site-specific distributions of claudin-2- and claudin-15-based paracellular channels drive their organ-specific functions in the liver, kidney, and intestine. © 2017 New York Academy of Sciences.

  9. Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC?1

    OpenAIRE

    Fujita, Mayumi; Imadome, Kaori; Imai, Takashi

    2017-01-01

    We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC?1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC?1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC?1 cells, metabolome analysis of the invaded PANC?1 compared with the whole cultured PANC?1 was performed using CE?TOFMS, and concentrations of 110 met...

  10. Diet and cognition: interplay between cell metabolism and neuronal plasticity.

    Science.gov (United States)

    Gomez-Pinilla, Fernando; Tyagi, Ethika

    2013-11-01

    To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

  11. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

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

    2016-06-01

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

  12. Cell biological study on ataxia-telangiectasia

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  13. Biological Evaluation of Single Cell Protein

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  14. Advancing Stem Cell Biology toward Stem Cell Therapeutics

    OpenAIRE

    Scadden, David; Srivastava, Alok

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

    Science.gov (United States)

    Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

    2017-06-01

    Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

  17. Changes in ceramide metabolism are essential in Madin-Darby canine kidney cell differentiation.

    Science.gov (United States)

    Pescio, Lucila Gisele; Santacreu, Bruno Jaime; Lopez, Vanina Gisela; Paván, Carlos Humberto; Romero, Daniela Judith; Favale, Nicolás Octavio; Sterin-Speziale, Norma Beatriz

    2017-07-01

    Ceramides (Cers) and complex sphingolipids with defined acyl chain lengths play important roles in numerous cell processes. Six Cer synthase (CerS) isoenzymes (CerS1-6) are the key enzymes responsible for the production of the diversity of molecular species. In this study, we investigated the changes in sphingolipid metabolism during the differentiation of Madin-Darby canine kidney (MDCK) cells. By MALDI TOF TOF MS, we analyzed the molecular species of Cer, glucosylceramide (GlcCer), lactosylceramide (LacCer), and SM in nondifferentiated and differentiated cells (cultured under hypertonicity). The molecular species detected were the same, but cells subjected to hypertonicity presented higher levels of C24:1 Cer, C24:1 GlcCer, C24:1 SM, and C16:0 LacCer. Consistently with the molecular species, MDCK cells expressed CerS2, CerS4, and CerS6, but with no differences during cell differentiation. We next evaluated the different synthesis pathways with sphingolipid inhibitors and found that cells subjected to hypertonicity in the presence of amitriptyline, an inhibitor of acid sphingomyelinase, showed decreased radiolabeled incorporation in LacCer and cells did not develop a mature apical membrane. These results suggest that hypertonicity induces the endolysosomal degradation of SM, generating the Cer used as substrate for the synthesis of specific molecular species of glycosphingolipids that are essential for MDCK cell differentiation. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

    Zeng, Y

    2017-04-29

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

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

    Science.gov (United States)

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

    2011-09-23

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

  20. Endothelial cell energy metabolism, proliferation, and apoptosis in pulmonary hypertension.

    Science.gov (United States)

    Xu, Weiling; Erzurum, Serpil C

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease characterized by impaired regulation of pulmonary hemodynamics and excessive growth and dysfunction of the endothelial cells that line the arteries in PAH lungs. Establishment of methods for culture of pulmonary artery endothelial cells from PAH lungs has provided the groundwork for mechanistic translational studies that confirm and extend findings from model systems and spontaneous pulmonary hypertension in animals. Endothelial cell hyperproliferation, survival, and alterations of biochemical-metabolic pathways are the unifying endothelial pathobiology of the disease. The hyperproliferative and apoptosis-resistant phenotype of PAH endothelial cells is dependent upon the activation of signal transducer and activator of transcription (STAT) 3, a fundamental regulator of cell survival and angiogenesis. Animal models of PAH, patients with PAH, and human PAH endothelial cells produce low nitric oxide (NO). In association with the low level of NO, endothelial cells have reduced mitochondrial numbers and cellular respiration, which is associated with more than a threefold increase in glycolysis for energy production. The shift to glycolysis is related to low levels of NO and likely to the pathologic expression of the prosurvival and proangiogenic signal transducer, hypoxia-inducible factor (HIF)-1, and the reduced mitochondrial antioxidant manganese superoxide dismutase (MnSOD). In this article, we review the phenotypic changes of the endothelium in PAH and the biochemical mechanisms accounting for the proliferative, glycolytic, and strongly proangiogenic phenotype of these dysfunctional cells, which consequently foster the panvascular progressive pulmonary remodeling in PAH. © 2011 American Physiological Society.

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

    Science.gov (United States)

    Cornelison, Ddw

    2018-01-01

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

  2. Metabolism of 4-nitrobiphenyl (NBP) by cultured rat urothelial cells

    International Nuclear Information System (INIS)

    Swaminathan, S.; Lang, D.B.; Reznikoff, C.A.

    1986-01-01

    The potential of rat urothelial cells to metabolize NBP was evaluated by incubating 4.3 x 10 7 viable cells with 20 μM [ 3 H]NBP in a serum free medium for 48 hours. The culture medium was examined for metabolites of NBP by extraction with ethyl acetate and subsequent chromatographic analysis. High pressure liquid chromatography of the solvent extract using a Whatman ODS-3, C-18 column in 70% methanol-water at a flow rate of 1 ml/min revealed two major peaks at retention times of approximately 8 and 13 min. Thin layer chromatography showed two regions of radioactivity at Rf values of 0.35 and 0.83, the latter corresponding with NBP. Based on the chromatographic data the metabolite with the retention time of 8.0 min in HPLC and an Rf of 0.35 in TLC has been tentatively identified as 4-acetylaminobiphenyl. Analysis of binding to proteins and nucleic acids following exposure to [ 3 H]NBP revealed a significant amount (0.03% of initially applied radioactivity) in the protein fractions. Control samples of NBP incubated in medium, without the urothelial cells revealed only the parent compound. These data suggest that rat bladder cells possess the metabolic capability to reduce NBP and to generate reactive metabolites that bind to cellular macromolecules

  3. Cell Hydration as a Biomarker for Estimation of Biological Effects of Nonionizing Radiation on Cells and Organisms

    Directory of Open Access Journals (Sweden)

    Sinerik Ayrapetyan

    2014-01-01

    Full Text Available “Changes in cell hydration” have been hypothesized as an input signal for intracellular metabolic cascade responsible for biological effects of nonionizing radiation (NIR. To test this hypothesis a comparative study on the impacts of different temperature and NIR (infrasound frequency mechanical vibration (MV, static magnetic field (SMF, extremely low frequency electromagnetic field (ELF EMF, and microwave (MW pretreated water on the hydration of barley seeds in its dormant and germination periods was performed. In dormant state temperature sensitivity (Q10 of seed hydration in distilled water (DW was less than 2, and it was nonsensitive to NIR treated DW, whereas during the germination period (48–72 hours seeds hydration exhibited temperature sensitivity Q10>2 and higher sensitivity to NIR treated DW. Obtained data allow us to suggest that the metabolic driving of intracellular water dynamics accompanied by hydrogen bonding and breaking is more sensitive to NIR-induced water structure changes in seed bathing aqua medium than the simple thermodynamic processes such as osmotic gradient driven water absorption by seeds in dormant state. Therefore, cell hydration is suggested to be a universal and extrasensitive biomarker for detection of biological effects of NIR on cells and organisms.

  4. The Emerging Role of PEDF in Stem Cell Biology

    Science.gov (United States)

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

    2012-01-01

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

  5. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

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

  6. The impact of metabolism on aging and cell size in single yeast cells

    NARCIS (Netherlands)

    Huberts, Daphne

    2015-01-01

    The aim of this thesis was to determine how metabolism affects yeast aging in single yeast cells using a novel microfluidic device. We first review how cells are able to sense nutrients in their environment and then describe the use of the microfluidic dissection platform that greatly improves our

  7. Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC-1.

    Science.gov (United States)

    Fujita, Mayumi; Imadome, Kaori; Imai, Takashi

    2017-05-01

    We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC-1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC-1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC-1 cells, metabolome analysis of the invaded PANC-1 compared with the whole cultured PANC-1 was performed using CE-TOFMS, and concentrations of 110 metabolites were measured. In contrast to the whole cultured cells, the invaded PANC-1 was characterized as a population with reduced levels of amino acids and TCA cycle intermediates, and decreased and increased intermediates in glycolysis and nucleic acid metabolism. In particular, the ratio of both adenosine and guanosine energy charge was reduced in the invaded cells, revealing that the consumption of ATP and GTP was high in the invaded cells, and thus suggesting that ATP- or GTP-generating pathways are stimulated. In addition, the GSH/GSSG ratio was low in the invaded cells, but these cells had a higher surviving fraction after exposure to hydrogen peroxide. Thus, the invaded cells were the population resistant to oxidative stress. Furthermore, reduction in intracellular GSH content inhibited PANC-1 invasiveness, indicated that GSH has an important role in PANC-1 invasiveness. Overall, we propose the invaded cells have several unique metabolic profiles. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  8. Cell wall-bound silicon optimizes ammonium uptake and metabolism in rice cells.

    Science.gov (United States)

    Sheng, Huachun; Ma, Jie; Pu, Junbao; Wang, Lijun

    2018-05-16

    Turgor-driven plant cell growth depends on cell wall structure and mechanics. Strengthening of cell walls on the basis of an association and interaction with silicon (Si) could lead to improved nutrient uptake and optimized growth and metabolism in rice (Oryza sativa). However, the structural basis and physiological mechanisms of nutrient uptake and metabolism optimization under Si assistance remain obscure. Single-cell level biophysical measurements, including in situ non-invasive micro-testing (NMT) of NH4+ ion fluxes, atomic force microscopy (AFM) of cell walls, and electrolyte leakage and membrane potential, as well as whole-cell proteomics using isobaric tags for relative and absolute quantification (iTRAQ), were performed. The altered cell wall structure increases the uptake rate of the main nutrient NH4+ in Si-accumulating cells, whereas the rate is only half in Si-deprived counterparts. Rigid cell walls enhanced by a wall-bound form of Si as the structural basis stabilize cell membranes. This, in turn, optimizes nutrient uptake of the cells in the same growth phase without any requirement for up-regulation of transmembrane ammonium transporters. Optimization of cellular nutrient acquisition strategies can substantially improve performance in terms of growth, metabolism and stress resistance.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Amrendra Kumar

    2017-12-01

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

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

    Science.gov (United States)

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

    2017-06-15

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

  13. Metabolic and physiologic studies of nonimmune lymphoid cells cytotoxic for fibroblastic cells in vitro

    International Nuclear Information System (INIS)

    Mayhew, E.; Bennett, M.

    1974-01-01

    An in vitro reaction between mouse lymphoid cells and target fibroblastic cells in wells of microtest plates, which appears to simulate the in vivo rejection of hemopoietic allografts, has been analyzed for metabolic and physiologic requirements. Protein synthesis was required for only the first few hours of culture. Inhibition of RNA synthesis and alteration of cell surface charge with various agents were without obvious effects. Metabolic slowing at 4 0 C or deviation of the pH of the culture medium suppressed the reaction. Thymus cells, which are not cytotoxic in this system, significantly but not completely inhibited the cytotoxicity of lymph node cells. Antiserum directed against target cells specifically protected them from the cytotoxic lymphoid cells in the absence of complement. Precursors of cytotoxic lymphoid cells were radiosensitive, unlike the cytotoxic cells themselves. BALB/c anti-C57BL/6 spleen cell serum and 89 Sr both are able to prevent rejection of marrow allografts in vivo. Lymphoid cells incubated with this antiserum plus complement lost much of their cytotoxicity but were still effective at high ratios of aggressor to target cells. Lymphoid cells of mice treated with 89 Sr were effectively cytotoxic but lost practically all of their cytotoxicity after incubation with the antiserum plus complement. Thus, it appears that this reaction detects two different cytotoxic lymphoid cells, either of which can function in vitro. Both cell types may need to cooperate in vivo during marrow allograft rejections

  14. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

    Science.gov (United States)

    Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

    2013-01-01

    Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

  15. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

    Science.gov (United States)

    Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

    2017-09-05

    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-01

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

  17. Cell biology of the Koji mold Aspergillus oryzae.

    Science.gov (United States)

    Kitamoto, Katsuhiko

    2015-01-01

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

  18. Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells

    Science.gov (United States)

    Li, Xiaoran; Kan, Quancheng; Fan, Zhirui; Li, Yaqing; Ji, Yasai; Zhao, Jing; Zhang, Mingzhi; Grigalavicius, Mantas; Berge, Viktor; Goscinski, Mariusz Adam; M. Nesland, Jahn; Suo, Zhenhe

    2017-01-01

    One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the “Warburg Effect”, in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout. It was discovered that the MPC1 gene knockout cells revealed a metabolism reprogramming to aerobic glycolysis with reduced ATP production, and the cells became more migratory and resistant to both chemotherapy and radiotherapy. In addition, the MPC1 knockout cells expressed significantly higher levels of the stemness markers Nanog, Hif1α, Notch1, CD44 and ALDH. To further verify the correlation of MPC gene function and cell stemness/metabolic reprogramming, MPC inhibitor UK5099 was applied in two ovarian cancer cell lines and similar results were obtained. Taken together, our results reveal that functional MPC may determine the fate of metabolic program and the stemness status of cancer cells in vitro. PMID:28624784

  19. The role of cell hydration in realization of biological effects of non-ionizing radiation (NIR).

    Science.gov (United States)

    Ayrapetyan, Sinerik

    2015-09-01

    The weak knowledge on the nature of cellular and molecular mechanisms of biological effects of NIR such as static magnetic field, infrasound frequency of mechanical vibration, extremely low frequency of electromagnetic fields and microwave serves as a main barrier for adequate dosimetry from the point of Public Health. The difficulty lies in the fact that the biological effects of NIR depend not only on their thermodynamic characteristics but also on their frequency and intensity "windows", chemical and physical composition of the surrounding medium, as well as on the initial metabolic state of the organism. Therefore, only biomarker can be used for adequate estimation of biological effect of NIR on organisms. Because of the absence of such biomarker(s), organizations having the mission to monitor hazardous effects of NIR traditionally base their instruction on thermodynamic characteristics of NIR. Based on the high sensitivity to NIR of both aqua medium structure and cell hydration, it is suggested that cell bathing medium is one of the primary targets and cell hydration is a biomarker for NIR effects on cells and organisms. The purpose of this article is to present a short review of literature and our own experimental data on the effects of NIR on plants' seeds germination, microbe growth and development, snail neurons and heart muscle, rat's brain and heart tissues.

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

    Science.gov (United States)

    Sobus, Samantha L; Warren, Graham W

    2014-12-01

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

  1. Teaching Cell and Molecular Biology for Gender Equity

    Science.gov (United States)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    NARCIS (Netherlands)

    Bernardo, Maria Ester

    2010-01-01

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

  4. Metabolism and biological activity of 24,25-dihydroxyvitamin D3 in the chick

    International Nuclear Information System (INIS)

    Holick, M.F.; Baxter, L.A.; Schraufrogel, P.K.; Tavela, T.E.; DeLuca, H.F.

    1976-01-01

    The vitamin, 24R,24,25-dihydroxyvitamin D 3 , is capable of inducing a minimal intestinal calcium transport response in chicks when compared to an equal amount of 25-hydroxyvitamin D 3 . 1,24,25-Trihydroxyvitamin D 3 is also less active than 1,25-dihydroxyvitamin D 3 , and its activity is much shorter lived than that of 1,25-dihydroxyvitamin D 3 . A comparison of the metabolism of 25-hydroxy[26,27- 3 H]vitamin D 3 and 24,25-dihydroxy[26,27- 3 H]vitamin D 3 in the rat and chick shows that 24,25-dihydroxyvitamin D 3 and 1,24,25-trihydroxyvitamin D 3 disappear at least 10 times more rapidly from the blood and intestine of chicks. Furthermore, examination of the excretory products from both of these species demonstrates that chicks receiving a single dose of 24,25-dihydroxy[26,27- 3 H]vitamin D 3 excrete 66% of the total radioactivity by 48 hours, whereas rats receiving the same dose excrete less than one-half that amount. These results demonstrate that 24,25-dihydroxyvitamin D 3 is considerably less biologically active in the chick than in the rat, probably due to more rapid metabolism and excretion

  5. Brassinosteroid regulates cell elongation by modulating gibberellin metabolism in rice.

    Science.gov (United States)

    Tong, Hongning; Xiao, Yunhua; Liu, Dapu; Gao, Shaopei; Liu, Linchuan; Yin, Yanhai; Jin, Yun; Qian, Qian; Chu, Chengcai

    2014-11-01

    Brassinosteroid (BR) and gibberellin (GA) are two predominant hormones regulating plant cell elongation. A defect in either of these leads to reduced plant growth and dwarfism. However, their relationship remains unknown in rice (Oryza sativa). Here, we demonstrated that BR regulates cell elongation by modulating GA metabolism in rice. Under physiological conditions, BR promotes GA accumulation by regulating the expression of GA metabolic genes to stimulate cell elongation. BR greatly induces the expression of D18/GA3ox-2, one of the GA biosynthetic genes, leading to increased GA1 levels, the bioactive GA in rice seedlings. Consequently, both d18 and loss-of-function GA-signaling mutants have decreased BR sensitivity. When excessive active BR is applied, the hormone mostly induces GA inactivation through upregulation of the GA inactivation gene GA2ox-3 and also represses BR biosynthesis, resulting in decreased hormone levels and growth inhibition. As a feedback mechanism, GA extensively inhibits BR biosynthesis and the BR response. GA treatment decreases the enlarged leaf angles in plants with enhanced BR biosynthesis or signaling. Our results revealed a previously unknown mechanism underlying BR and GA crosstalk depending on tissues and hormone levels, which greatly advances our understanding of hormone actions in crop plants and appears much different from that in Arabidopsis thaliana. © 2014 American Society of Plant Biologists. All rights reserved.

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

    Science.gov (United States)

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

  7. Are natural killer cells protecting the metabolically healthy obese patient?

    LENUS (Irish Health Repository)

    Lynch, Lydia A

    2012-02-01

    With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight-management clinic and 11 lean healthy controls. Patients were classified into metabolically "healthy obese" (n = 26; mean age 42.6 years, mean BMI 46.8 kg\\/m(2)) or "unhealthy obese" (n = 26; mean age 45 years, mean BMI 47.5 kg\\/m(2)) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.

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

    Directory of Open Access Journals (Sweden)

    Yuhao Jiao

    2016-10-01

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

  9. Precision control of recombinant gene transcription for CHO cell synthetic biology.

    Science.gov (United States)

    Brown, Adam J; James, David C

    2016-01-01

    The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

  10. Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.

    Science.gov (United States)

    Maciak, S; Bonda-Ostaszewska, E; Czarnołęski, M; Konarzewski, M; Kozłowski, J

    2014-03-01

    Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  11. Metabolically engineered cells for the production of polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    2005-01-01

    The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves...... improvement of the PUFA content in the host organism through fermentation optimization, e.g. decreasing the temperature and/or designing an optimal medium, or through improving the flux towards fatty acids by metabolic engineering, e.g. through over-expression of fatty acid synthases, over-expression of other...

  12. Cholesterol metabolism in blood cells of irradiated rats

    International Nuclear Information System (INIS)

    Novoselova, E.G.; Kulagina, T.P.; Potekhina, N.I.

    1985-01-01

    Cholesterol metabolism in blood erythrocytes and lymphocytes of irradiated rats has been investigated. It has been found that at all terms and doses of irradiation, a suppression of the synthesis of erythrocyte cholesterol is observed. The increase of cholesterol quantiy in erythrocytes upon total gamma irradiation in the 10 Gr dose possibly is the result of growth of cholesterol transfer from plasma into erythrocyte cells. The study of the cholesterol synthesis in suspension of lymphocytes elminated from peripheral blood of control and irradiated rats has shown that at irradiation doses of 4 and 10 Gr in an hour acivation of cholesterol synthesis in vitro takes places

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

    Science.gov (United States)

    Arroyo, Marino; Trepat, Xavier

    2017-02-01

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

  14. The place of viruses in biology in light of the metabolism- versus-replication-first debate.

    Science.gov (United States)

    López-García, Purificación

    2012-01-01

    The last decade has seen a revival of old virocentric ideas. These concepts are heterogeneous, extending from proposals that consider viruses functionally as living beings and/or as descendants of viral lineages that preceded cell evolution to other claims that consider viruses and/or some viral families a fourth domain of life. While the debates about whether viruses are alive or not and whether some virus-like replicators preceded the first cells fall under the long-lasting dichotomous view on the nature and origin of life (metabolism- versus replication-first), the claim that some giant viruses form a fourth domain in an organismal tree of life is not consistent with current evidence and can be falsified.

  15. Cell Wall Metabolism in Response to Abiotic Stress

    Science.gov (United States)

    Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

    2015-01-01

    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

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

    Science.gov (United States)

    Ng, Annie; Barker, Nick

    2015-10-01

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

  17. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi

    2016-10-24

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  18. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi; Saito, Toshiyuki; Ohyanagi, Hajime; Okumura, Jun; Ishige, Kentaro; Suzuki, Harukazu; Nakamura, Takuji; Komatsu, Setsuko

    2016-01-01

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  19. Yeast genetics and molecular biology

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    This book covers subjects and the following titles: cell biology; RNA processing and translation; organelle biogenesis; cell division cycle; mating physiology; recombination and repair; retro-transposition; and metabolic regulating mechanisms

  20. Microbial regulation of GLP-1 and L-cell biology

    DEFF Research Database (Denmark)

    Greiner, Thomas U; Bäckhed, Gert Fredrik

    2016-01-01

    BACKGROUND: The gut microbiota is associated with several of metabolic diseases, including obesity and type 2 diabetes and affects host physiology through distinct mechanisms. The microbiota produces a vast array of metabolites that signal to host cells in the intestine as well as in more distal...... organs. SCOPE OF REVIEW: Enteroendocrine cells acts as 'chemo sensors' of the intestinal milieu by expressing a large number of receptors, which respond to different metabolites and nutrients, and signal to host by a wide variety of hormones. However, enteroendocrine cells differ along the length...... of the gut in terms of hormones expressed and receptor repertoire. Also, the microbial ecology and dietary substrates differ along the length of the gut, providing further evidence for unique functions of specific subpopulations among enteroendocrine cells. Here we will review how the gut microbiota...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Bertazza, Loris; Mocellin, Simone

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  4. Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic β-cells.

    Science.gov (United States)

    Lenzen, Sigurd

    2017-08-01

    Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the β-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the β-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status. This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the β-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development. The weak antioxidative defense equipment in the different subcellular organelles makes the β-cells particularly vulnerable and prone to mitochondrial, peroxisomal and ER stress. Looking upon the enzyme deficiencies which are responsible for the low antioxidative defense status of the pancreatic β-cells it is the lack of enzymatic capacity for H 2 O 2 inactivation at all major subcellular sites. Diabetes is the most prevalent metabolic disorder with a steadily increasing incidence of both type 1 and type 2 diabetes worldwide. The weak protection of the pancreatic β-cells against oxidative stress is a major reason for their particular vulnerability. Thus, careful protection of the β-cells is required for prevention of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    KAUST Repository

    Hefzi, Hooman; Ang, Kok  Siong; Hanscho, Michael; Bordbar, Aarash; Ruckerbauer, David; Lakshmanan, Meiyappan; Orellana, Camila  A.; Baycin-Hizal, Deniz; Huang, Yingxiang; Ley, Daniel; Martinez, Veronica  S.; Kyriakopoulos, Sarantos; Jimé nez, Natalia  E.; Zielinski, Daniel  C.; Quek, Lake-Ee; Wulff, Tune; Arnsdorf, Johnny; Li, Shangzhong; Lee, Jae  Seong; Paglia, Giuseppe; Loira, Nicolas; Spahn, Philipp  N.; Pedersen, Lasse  E.; Gutierrez, Jahir  M.; King, Zachary  A.; Lund, Anne  Mathilde; Nagarajan, Harish; Thomas, Alex; Abdel-Haleem, Alyaa M.; Zanghellini, Juergen; Kildegaard, Helene  F.; Voldborg, Bjø rn  G.; Gerdtzen, Ziomara  P.; Betenbaugh, Michael  J.; Palsson, Bernhard  O.; Andersen, Mikael  R.; Nielsen, Lars  K.; Borth, Nicole; Lee, Dong-Yup; Lewis, Nathan  E.

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess

  6. Tomography studies of biological cells on polymer scaffolds

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  7. Tensegrity I. Cell structure and hierarchical systems biology

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

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

  8. [Biological function of trophology and the pathogenesis of metabolic syndrome--syndrome of overeating. Phylogenetically theory of general pathology, role of leptin and adiponectin].

    Science.gov (United States)

    Titov, V N

    2014-01-01

    Metabolic syndrome (overeating) is a phylogenetically-determined succession of symptoms with the same pathogenesis. There is only one etiological factor, namely, increased consumption of physiologically optimal food. Enterocytes and omental fat cells are a phylogenetically early paracrine-regulated cell community that realizes the biological reactions of exo- and endotrophy. Visceral obesity, high levels of unesterified fatty acids (FA), formation of a pool of micellar FA in the blood, integration of these FA into endothelial cell plasma membrane and enlargement of adipocytes are the causes of hydrodynamic pressure elevation. Toll-like receptors recognize the associates between albumin and greater than physiological number of FA as "foreing" and initiate inflammatory response. "Endoplasm stress" develops in lipid-overloaded cells, protein synthesis (folding) in them is impaired and apoptosis-like cell death is activated. Visceral fat is a phylogenetically early depot of FA to fulfill the biological function of homeostasis, trophology, endoecology and adaptation; it is regulated at the level of paracrine communities and is anatomically limited. The subcutaneous fat depot fulfills the phylogenetically late function of locomotion; the depot size is not anatomically limited. Visceral fat cells have no receptors for phylogenetically late insulin (INS); specialized adipocyes bearing INS and GLUT4 receptors are cells that form the subcutaneous depot. These cells are regulated by phylogenetically late humoral factors at the entire body level. Leptin is an initiator of humoral hypothalamic regulation of in vivo number of ontogenetically programmed number of visceral INS-insensitive fat cells. It prevents "endoplasm stress" and apoptosis, being designed to regulate the amount of consumed food. Leptin initiates storage of FA from visceral pool into subcutaneous pool. Adiponectin is a phylogenetically late humoral hypothalamic regulatory factor that controls optimal number of

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

    Science.gov (United States)

    Randolph, Matthew E.; Pavlath, Grace K.

    2015-01-01

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

  10. Clonal characterization of rat muscle satellite cells: proliferation, metabolism and differentiation define an intrinsic heterogeneity.

    Directory of Open Access Journals (Sweden)

    Carlo A Rossi

    2010-01-01

    Full Text Available Satellite cells (SCs represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible. Even though the pool of SCs is accepted as the major, and possibly the only, source of myonuclei in postnatal muscle, it is likely that SCs are not all multipotent stem cells and evidences for diversities within the myogenic compartment have been described both in vitro and in vivo. Here, by isolating single fibers from rat flexor digitorum brevis (FDB muscle we were able to identify and clonally characterize two main subpopulations of SCs: the low proliferative clones (LPC present in major proportion (approximately 75% and the high proliferative clones (HPC, present instead in minor amount (approximately 25%. LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if co-cultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (DeltaPsi(m, ATP balance and Reactive Oxygen Species (ROS generation underlying diversities in metabolism that precede differentiation. Notably, SCs heterogeneity is retained in vivo. SCs may therefore be comprised of two distinct, though not irreversibly committed, populations of cells distinguishable for prominent differences in basal biological features such as proliferation, metabolism and differentiation. By these means, novel insights on SCs heterogeneity are provided and evidences for biological readouts potentially relevant for diagnostic purposes described.

  11. [Thiamine and its derivatives in the regulation of cell metabolism].

    Science.gov (United States)

    Tylicki, Adam; Siemieniuk, Magdalena

    2011-07-06

    For over 70 years thiamine (vitamin B1) has aroused the interest of biologists, biochemists and medical doctors because of its multilateral participation in key biochemical and physiological processes. The thiamine molecule is composed of pyrimidine and thiazole rings which are linked by a methylene bridge. It is synthesized by microorganisms, fungi and plants, whereas animals and humans have to obtain it from food. There are several known forms of vitamin B1 inside cells: free thiamine, three phosphate esters (mono-, di-, and triphosphate), and the recently found adenosine thiamine triphosphate. Thiamine has a dual, coenzymatic and non-coenzymatic role. First of all, it is a precursor of thiamin diphosphate, which is a coenzyme for over 20 characterized enzymes which are involved in cell bioenergetic processes leading to the synthesis of ATP. Moreover, these enzymes take part in the biosynthesis of pentose (required for the synthesis of nucleotides), amino acids and other organic compounds of cell metabolism. On the other hand, recent discoveries show the non-coenzymatic role of thiamine derivatives in the process of regulation of gene expression (riboswitches in microorganisms and plants), the stress response, and perhaps so far unknown signal transduction pathways associated with adverse environmental conditions, or transduction of nerve signals with participation of thiamine triphosphate and adenosine thiamine triphosphate. From the clinical point of view thiamine deficiency is related to beri-beri, Parkinson disease, Alzheimer disease, Wernicke-Korsakoff syndrome and other pathologies of the nervous system, and it is successfully applied in medical practice. On the other hand, identifying new synthetic analogues of thiamine which could be used as cytostatics, herbicides or agents preventing deficiency of vitamin B1 is currently the major goal of the research. In this paper we present the current state of knowledge of thiamine and its derivatives, indicating

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

    Science.gov (United States)

    Goldstein, Lawrence S B

    2012-11-12

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

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

    Science.gov (United States)

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

    2017-01-24

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

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

    Science.gov (United States)

    Thomas, Daniel; Majeti, Ravindra

    2017-03-23

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

  15. The effects of capsaicin and capsaicinoid analogs on metabolic molecular targets in highly energetic tissues and cell types.

    Science.gov (United States)

    Gannon, Nicholas P; Lambalot, Emily L; Vaughan, Roger A

    2016-05-01

    There is increasing interest in dietary chemicals that may provide benefits for pathologies such as diabetes and obesity. Capsaicinoids found in chili peppers and pepper extracts, are responsible for the "hot" or "spicy" sensation associated with these foods. Capsaicinoid consumption is also associated with enhanced metabolism, making them potentially therapeutic for metabolic disease by promoting weight loss. This review summarizes much of the current experimental evidence (ranging from basic to applied investigations) of the biochemical and molecular metabolic effects of capsaicinoids in metabolically significant cell types. Along with influencing metabolic rate, findings demonstrate capsaicinoids appear to alter molecular metabolic signaling, regulate hunger and satiety, blood metabolites, and catecholamine release. Notably, the majority of the experiments summarized herein utilized isolated supplemental or research grade capsaicinoids rather than natural food sources for experimental interventions. Additional work should be conducted using primary food sources of capsaicin to explore pharmacological, physiological, and metabolic benefits of both chronic and acute capsaicin consumption. © 2016 BioFactors, 42(3):229-246, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  16. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  17. Metabolic Ride” - One Concept Evaluation Tool For Metabolic Biochemistry Teaching For Graduate Students In Biological Sciences And Related Areas.

    Directory of Open Access Journals (Sweden)

    H. H. Gaeta et al.

    2017-07-01

    Full Text Available Biochemistry subject in general has a high degree of difficulty and complexity. Therefore, application of playful and creative games as teaching methodology has spread in various disciplines of life sciences. "METABOLIC RIDE" board game is a conceptual and perceptual evaluation tool for metabolic biochemistry teaching, aiming to review concepts transmitted in classroom, promoting a competitive challenge to students without denying tools that are at their disposal, stimulating their skills. OBJECTIVES. Correlate metabolic routes importance and their interconnections to establish that metabolic pathways are interconnected, such as a railway map. MATERIAL AND METHODS. This game was developed based on a board game Ticket to Ride. Players purchase enzyme cards, which must be used to claim metabolic routes. The goal is to complete the route previously drawn to earn points and the player who builds the longest continuous route will also earn bonus points. In each turn, players can: buy more card, claim a route or pick up additional destination tickets. The game should be played in groups of 5 to 6 students in 6 to 8 groups. Previously there will be theoretical classes. The activity was designed to last 4 hours. Use of didatic books and internet by players are encouraged. RESULTS. This game proved to be an excellent tool for student’s complementary evaluation, which stimulated teamwork and competitiveness within classroom, which allowed to analyze student’s perception regarding metabolic subjects. On the other hand, for teacher and students participating in compulsory traineeship program this game demonstrated to students new ways to approach complex subjects in biochemistry using creativity. CONCLUSION: Overall, students had a good impression of “Metabolic Ride” game since it helped to secure and administer metabolism subject in a competitive and team work way.

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

    Science.gov (United States)

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

  19. The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: A systems biology approach

    NARCIS (Netherlands)

    Calçada, D.; Vianello, D.; Giampieri, E.; Sala, C.; Castellani, G.; Graaf, A.A. de; Kremer, S.H.A.; Ommen, B. van; Feskens, E.; Santoro, A.; Franceschi, C.; Bouwman, J.

    2014-01-01

    Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic

  20. Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

    Science.gov (United States)

    Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

    2016-09-02

    To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

  1. Dissection of Biological Property of Chinese Acupuncture Point Zusanli Based on Long-Term Treatment via Modulating Multiple Metabolic Pathways

    Directory of Open Access Journals (Sweden)

    Guangli Yan

    2013-01-01

    Full Text Available Acupuncture has a history of over 3000 years and is a traditional Chinese medical therapy that uses hair-thin metal needles to puncture the skin at specific points on the body to promote wellbeing, while its molecular mechanism and ideal biological pathways are still not clear. High-throughput metabolomics is the global assessment of endogenous metabolites within a biologic system and can potentially provide a more accurate snap shot of the actual physiological state. We hypothesize that acupuncture-treated human would produce unique characterization of metabolic phenotypes. In this study, UPLC/ESI-HDMS coupled with pattern recognition methods and system analysis were carried out to investigate the mechanism and metabolite biomarkers for acupuncture treatment at “Zusanli” acupoint (ST-36 as a case study. The top 5 canonical pathways including alpha-linolenic acid metabolism, d-glutamine and d-glutamate metabolism, citrate cycle, alanine, aspartate, and glutamate metabolism, and vitamin B6 metabolism pathways were acutely perturbed, and 53 differential metabolites were identified by chemical profiling and may be useful to clarify the physiological basis and mechanism of ST-36. More importantly, network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Urine metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture.

  2. Dissection of Biological Property of Chinese Acupuncture Point Zusanli Based on Long-Term Treatment via Modulating Multiple Metabolic Pathways.

    Science.gov (United States)

    Yan, Guangli; Zhang, Aihua; Sun, Hui; Cheng, Weiping; Meng, Xiangcai; Liu, Li; Zhang, Yingzhi; Xie, Ning; Wang, Xijun

    2013-01-01

    Acupuncture has a history of over 3000 years and is a traditional Chinese medical therapy that uses hair-thin metal needles to puncture the skin at specific points on the body to promote wellbeing, while its molecular mechanism and ideal biological pathways are still not clear. High-throughput metabolomics is the global assessment of endogenous metabolites within a biologic system and can potentially provide a more accurate snap shot of the actual physiological state. We hypothesize that acupuncture-treated human would produce unique characterization of metabolic phenotypes. In this study, UPLC/ESI-HDMS coupled with pattern recognition methods and system analysis were carried out to investigate the mechanism and metabolite biomarkers for acupuncture treatment at "Zusanli" acupoint (ST-36) as a case study. The top 5 canonical pathways including alpha-linolenic acid metabolism, d-glutamine and d-glutamate metabolism, citrate cycle, alanine, aspartate, and glutamate metabolism, and vitamin B6 metabolism pathways were acutely perturbed, and 53 differential metabolites were identified by chemical profiling and may be useful to clarify the physiological basis and mechanism of ST-36. More importantly, network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Urine metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture.

  3. Multiplexed genome engineering and genotyping methods applications for synthetic biology and metabolic engineering.

    Science.gov (United States)

    Wang, Harris H; Church, George M

    2011-01-01

    Engineering at the scale of whole genomes requires fundamentally new molecular biology tools. Recent advances in recombineering using synthetic oligonucleotides enable the rapid generation of mutants at high efficiency and specificity and can be implemented at the genome scale. With these techniques, libraries of mutants can be generated, from which individuals with functionally useful phenotypes can be isolated. Furthermore, populations of cells can be evolved in situ by directed evolution using complex pools of oligonucleotides. Here, we discuss ways to utilize these multiplexed genome engineering methods, with special emphasis on experimental design and implementation. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: Role of nonoxidative metabolism

    International Nuclear Information System (INIS)

    Wu Hai; Cai Ping; Clemens, Dahn L.; Jerrells, Thomas R.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S.

    2006-01-01

    Chronic alcohol abuse, a major health problem, causes liver and pancreatic diseases and is known to impair hepatic alcohol dehydrogenase (ADH). Hepatic ADH-catalyzed oxidation of ethanol is a major pathway for the ethanol disposition in the body. Hepatic microsomal cytochrome P450 (CYP2E1), induced in chronic alcohol abuse, is also reported to oxidize ethanol. However, impaired hepatic ADH activity in a rat model is known to facilitate a nonoxidative metabolism resulting in formation of nonoxidative metabolites of ethanol such as fatty acid ethyl esters (FAEEs) via a nonoxidative pathway catalyzed by FAEE synthase. Therefore, the metabolic basis of ethanol-induced cytotoxicity was determined in HepG2 cells and recombinant HepG2 cells transfected with ADH (VA-13), CYP2E1 (E47) or ADH + CYP2E1 (VL-17A). Western blot analysis shows ADH deficiency in HepG2 and E47 cells, compared to ADH-overexpressed VA-13 and VL-17A cells. Attached HepG2 cells and the recombinant cells were incubated with ethanol, and nonoxidative metabolism of ethanol was determined by measuring the formation of FAEEs. Significantly higher levels of FAEEs were synthesized in HepG2 and E47 cells than in VA-13 and VL-17A cells at all concentrations of ethanol (100-800 mg%) incubated for 6 h (optimal time for the synthesis of FAEEs) in cell culture. These results suggest that ADH-catalyzed oxidative metabolism of ethanol is the major mechanism of its disposition, regardless of CYP2E1 overexpression. On the other hand, diminished ADH activity facilitates nonoxidative metabolism of ethanol to FAEEs as found in E47 cells, regardless of CYP2E1 overexpression. Therefore, CYP2E1-mediated oxidation of ethanol could be a minor mechanism of ethanol disposition. Further studies conducted only in HepG2 and VA-13 cells showed lower ethanol disposition and ATP concentration and higher accumulation of neutral lipids and cytotoxicity (apoptosis) in HepG2 cells than in VA-13 cells. The apoptosis observed in HepG2 vs

  5. Chimeric animal models in human stem cell biology.

    Science.gov (United States)

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

    2009-01-01

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

  6. Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

    Science.gov (United States)

    Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

    2004-02-12

    A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

  7. Metabolic cooperativity between epithelial cells and adipocytes of mice

    International Nuclear Information System (INIS)

    Bartley, J.C.; Emerman, J.T.; Bissell, M.J.

    1981-01-01

    We have demonstrated that glycogen and lipid synthesis in adipocytes is modulated by the lactational state and that this modulation in mammary adipocytes requires the presence of the adjacent epithelial cells. Glycogen and lipid synthesis from [ 14 C]glucose was measured in mammary fat pads cleared of epithelium, in abdominal fat pads, and in adipocytes from both sources and from intact mammary gland of mature virgin, pregnant, and lactating mice. Accumulation of glycogen, the activity of glycogen synthase, and the lipogenic rate in abdominal and mammary adipocytes remained high during pregnancy but decreased to insignificant levels by early lactation. The depressant effects of lactation were observed solely in those mammary adipocytes isolated from intact glands. The presence of mammary epithelial cells was also required to effect the stimulated lipogenesis in mammary adipocytes during pregnancy. We conclude that the metabolic activity of adipocytes is modulated both during pregnancy and lactation to channel nutrients to the mammary epithelial cell. The fact that the changes occur in mammary adipocytes only when epithelial cells are present indicates that local as well as systemic factors are operating in these modulations

  8. Interplay Between Diet, Gut Microbiota, Immune Cells and Energy Metabolism in Obesity Development

    DEFF Research Database (Denmark)

    Danneskiold-Samsøe, Niels Banhos

    Obesity and associated metabolic disorders such as type 2 diabetes are major causes of morbidity and mortality globally. A major contributor to development of the obesity pandemic has been the increasing intake of energy dense diets, consisting of dietary fats combined with high-glycemic carbohyd......Obesity and associated metabolic disorders such as type 2 diabetes are major causes of morbidity and mortality globally. A major contributor to development of the obesity pandemic has been the increasing intake of energy dense diets, consisting of dietary fats combined with high......-glycemic carbohydrates such as refined grains and sugars. The lack of sufficient therapeutic options for obesity, and the inability of most individuals to reduce energy intake or increase expenditure highlight the importance of understanding its underlying biological mechanisms. Obesity is associated with low...... in glucose intolerance without inflammatory changes in visceral fat or the liver, but with changes to the gut microbiota. Finally we find that fat cell specific activity of cyclooxygenase-2, an enzyme important for metabolism of fat, decreases body fat mass and increases insulin sensitivity associated...

  9. Mesenchymal stem cells from different murine tissues have differential capacity to metabolize extracellular nucleotides.

    Science.gov (United States)

    Iser, Isabele C; Bracco, Paula A; Gonçalves, Carlos E I; Zanin, Rafael F; Nardi, Nance B; Lenz, Guido; Battastini, Ana Maria O; Wink, Márcia R

    2014-10-01

    Mesenchymal stem cells (MSCs) have shown a great potential for cell-based therapy and many different therapeutic purposes. Despite the recent advances in the knowledge of MSCs biology, their biochemical and molecular properties are still poorly defined. Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-nucleotidase (eNT/CD73) are widely expressed enzymes that hydrolyze extracellular nucleotides, generating an important cellular signaling cascade. Currently, studies have evidenced the relationship between the purinergic system and the development, maintenance, and differentiation of stem cells. The objective of this study is to identify the NTPDases and eNT/CD73 and compare the levels of nucleotide hydrolysis on MSCs isolated from different murine tissues (bone marrow, lung, vena cava, kidney, pancreas, spleen, skin, and adipose tissue). MSCs from all tissues investigated expressed the ectoenzymes at different levels. In MSCs from pancreas and adipose tissue, the hydrolysis of triphosphonucleosides was significantly higher when compared to the other cells. The diphosphonucleosides were hydrolyzed at a higher rate by MSC from pancreas when compared to MSC from other tissues. The differential nucleotide hydrolysis activity and enzyme expression in these cells suggests that MSCs play different roles in regulating the purinergic system in these tissues. Overall MSCs are an attractive adult-derived cell population for therapies, however, the fact that ecto-nucleotide metabolism can affect the microenvironment, modulating important events, such as immune response, makes the assessment of this metabolism an important part of the characterization of MSCs to be applied therapeutically. © 2014 Wiley Periodicals, Inc.

  10. 100 years after Smoluchowski: stochastic processes in cell biology

    International Nuclear Information System (INIS)

    Holcman, D; Schuss, Z

    2017-01-01

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

  11. A real-time measurement system for parameters of live biology metabolism process with fiber optics

    Science.gov (United States)

    Tao, Wei; Zhao, Hui; Liu, Zemin; Cheng, Jinke; Cai, Rong

    2010-08-01

    Energy metabolism is one of the basic life activities of cellular in which lactate, O2 and CO2 will be released into the extracellular environment. By monitoring the quantity of these parameters, the mitochondrial performance will be got. A continuous measurement system for the concentration of O2, CO2 and PH value is introduced in this paper. The system is made up of several small-sized fiber optics biosensors corresponding to the container. The setup of the system and the principle of measurement of several parameters are explained. The setup of the fiber PH sensor based on principle of light absorption is also introduced in detail and some experimental results are given. From the results we can see that the system can measure the PH value precisely suitable for cell cultivation. The linear and repeatable accuracies are 3.6% and 6.7% respectively, which can fulfill the measurement task.

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Todd, P.; Klaus, D. M.

    1996-01-01

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

  16. Synthetic biology in cell-based cancer immunotherapy.

    Science.gov (United States)

    Chakravarti, Deboki; Wong, Wilson W

    2015-08-01

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

  17. Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

    Science.gov (United States)

    Nocca, G; De Palma, F; Minucci, A; De Sole, P; Martorana, G E; Callà, C; Morlacchi, C; Gozzo, M L; Gambarini, G; Chimenti, C; Giardina, B; Lupi, A

    2007-03-01

    Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

  18. Micrasterias as a model system in plant cell biology

    Directory of Open Access Journals (Sweden)

    Ursula Luetz-Meindl

    2016-07-01

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

  19. Metabolite secretion in microorganisms: the theory of metabolic overflow put to the test

    DEFF Research Database (Denmark)

    Pinu, Farhana R.; Granucci, Ninna; Daniell, James

    2018-01-01

    Introduction Microbial cells secrete many metabolites during growth, including important intermediates of the central carbon metabolism. This has not been taken into account by researchers when modeling microbial metabolism for metabolic engineering and systems biology studies. Materials and Meth...

  20. Non-invasive in-cell determination of free cytosolic [NAD+]/[NADH] ratios using hyperpolarized glucose show large variations in metabolic phenotypes

    DEFF Research Database (Denmark)

    Christensen, Caspar Elo; Karlsson, Magnus; Winther, Jakob R.

    2014-01-01

    Accumulating evidence suggest that the pyridine nucleotide NAD has far wider biological functions than its classical role in energy metabolism. NAD is used by hundreds of enzymes that catalyse substrate oxidation and as such it plays a key role in various biological processes such as aging, cell...... death and oxidative stress. It has been suggested that changes in the ratio of free cytosolic [NAD+]/[NADH] reflects metabolic alterations leading to, or correlating with, pathological states. We have designed an isotopically labelled metabolic bioprobe of free cytosolic [NAD+]/[NADH] by combining...... a magnetic enhancement technique (hyperpolarization) with cellular glycolytic activity. The bioprobe reports free cytosolic [NAD+]/[NADH] ratios based on dynamically measured in-cell [pyruvate]/ [lactate] ratios. We demonstrate its utility in breast and prostate cancer cells. The free cytosolic [NAD...

  1. Recent advances in the cell biology of aging.

    Science.gov (United States)

    Hayflick, L

    1980-01-01

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

  2. Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.

    Directory of Open Access Journals (Sweden)

    Intawat Nookaew

    Full Text Available BACKGROUND: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD. This will require methods for linking nutrient intake with specific metabolic processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density lipoprotein receptor-deficient (Ldlr -/- mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice. CONCLUSION: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity.

  3. Study of the metabolism of 13C labeled substrates by 13C NMR spectroscopy of intact cells, tissues, and organs

    International Nuclear Information System (INIS)

    Matwiyoff, N.A.; London, R.E.; Hutson, J.Y.

    1982-01-01

    Carbon-13 nuclear magnetic resonance spectroscopy, in conjunction with carbon-13 labeling, has become an important analytical technique for the study of biological systems and biologically important molecules. The growing list of its well established applications to isolated molecules in solution includes the investigation of: metabolic pathways; the microenvironments of ligands bound to proteins; the architecture and dynamics of macromolecules; the structures of coenzymes and other natural products; and the mechanisms of reactions. Recently interest has been reawakened in the use of the technique for the study of metabolic pathways and structural components in intact organelles, cells, and tissues. The promise and problems in the use of 13 C labeling in such investigations can be illustrated by the results on suspensions of the yeast, Candida utilis

  4. Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

    Directory of Open Access Journals (Sweden)

    Christian Frezza

    Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

  5. Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells.

    Directory of Open Access Journals (Sweden)

    Anders Waldenström

    Full Text Available BACKGROUND: Shedding microvesicles are membrane released vesicles derived directly from the plasma membrane. Exosomes are released membrane vesicles of late endosomal origin that share structural and biochemical characteristics with prostasomes. Microvesicles/exosomes can mediate messages between cells and affect various cell-related processes in their target cells. We describe newly detected microvesicles/exosomes from cardiomyocytes and depict some of their biological functions. METHODOLOGY/PRINCIPAL FINDINGS: Microvesicles/exosomes from media of cultured cardiomyocytes derived from adult mouse heart were isolated by differential centrifugation including preparative ultracentrifugation and identified by transmission electron microscopy and flow cytometry. They were surrounded by a bilayered membrane and flow cytometry revealed presence of both caveolin-3 and flotillin-1 while clathrin and annexin-2 were not detected. Microvesicle/exosome mRNA was identified and out of 1520 detected mRNA, 423 could be directly connected in a biological network. Furthermore, by a specific technique involving TDT polymerase, 343 different chromosomal DNA sequences were identified in the microvesicles/exosomes. Microvesicle/exosomal DNA transfer was possible into target fibroblasts, where exosomes stained for DNA were seen in the fibroblast cytosol and even in the nuclei. The gene expression was affected in fibroblasts transfected by microvesicles/exosomes and among 333 gene expression changes there were 175 upregulations and 158 downregulations compared with controls. CONCLUSIONS/SIGNIFICANCE: Our study suggests that microvesicles/exosomes released from cardiomyocytes, where we propose that exosomes derived from cardiomyocytes could be denoted "cardiosomes", can be involved in a metabolic course of events in target cells by facilitating an array of metabolism-related processes including gene expression changes.

  6. Adaptation of red cell enzymes and intermediates in metabolic disorders.

    Science.gov (United States)

    Goebel, K M; Goebel, F D; Neitzert, A; Hausmann, L; Schneider, J

    1975-01-01

    The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

  7. Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells.

    Science.gov (United States)

    VanLinden, Magali R; Dölle, Christian; Pettersen, Ina K N; Kulikova, Veronika A; Niere, Marc; Agrimi, Gennaro; Dyrstad, Sissel E; Palmieri, Ferdinando; Nikiforov, Andrey A; Tronstad, Karl Johan; Ziegler, Mathias

    2015-11-13

    The mitochondrial NAD pool is particularly important for the maintenance of vital cellular functions. Although at least in some fungi and plants, mitochondrial NAD is imported from the cytosol by carrier proteins, in mammals, the mechanism of how this organellar pool is generated has remained obscure. A transporter mediating NAD import into mammalian mitochondria has not been identified. In contrast, human recombinant NMNAT3 localizes to the mitochondrial matrix and is able to catalyze NAD(+) biosynthesis in vitro. However, whether the endogenous NMNAT3 protein is functionally effective at generating NAD(+) in mitochondria of intact human cells still remains to be demonstrated. To modulate mitochondrial NAD(+) content, we have expressed plant and yeast mitochondrial NAD(+) carriers in human cells and observed a profound increase in mitochondrial NAD(+). None of the closest human homologs of these carriers had any detectable effect on mitochondrial NAD(+) content. Surprisingly, constitutive redistribution of NAD(+) from the cytosol to the mitochondria by stable expression of the Arabidopsis thaliana mitochondrial NAD(+) transporter NDT2 in HEK293 cells resulted in dramatic growth retardation and a metabolic shift from oxidative phosphorylation to glycolysis, despite the elevated mitochondrial NAD(+) levels. These results suggest that a mitochondrial NAD(+) transporter, similar to the known one from A. thaliana, is likely absent and could even be harmful in human cells. We provide further support for the alternative possibility, namely intramitochondrial NAD(+) synthesis, by demonstrating the presence of endogenous NMNAT3 in the mitochondria of human cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.

    Science.gov (United States)

    Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

    2014-06-01

    Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.

  9. Embryological origin of the endocardium and derived valve progenitor cells: from developmental biology to stem cell-based valve repair.

    Science.gov (United States)

    Pucéat, Michel

    2013-04-01

    The cardiac valves are targets of both congenital and acquired diseases. The formation of valves during embryogenesis (i.e., valvulogenesis) originates from endocardial cells lining the myocardium. These cells undergo an endothelial-mesenchymal transition, proliferate and migrate within an extracellular matrix. This leads to the formation of bilateral cardiac cushions in both the atrioventricular canal and the outflow tract. The embryonic origin of both the endocardium and prospective valve cells is still elusive. Endocardial and myocardial lineages are segregated early during embryogenesis and such a cell fate decision can be recapitulated in vitro by embryonic stem cells (ESC). Besides genetically modified mice and ex vivo heart explants, ESCs provide a cellular model to study the early steps of valve development and might constitute a human therapeutic cell source for decellularized tissue-engineered valves. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Development of biologically modified anodes for energy harvesting using microbial fuel cells

    Science.gov (United States)

    Sumner, James J.; Ganguli, Rahul; Chmelka, Brad

    2012-06-01

    Biological fuel cells hold promise as an alternative energy source to batteries for unattended ground sensor applications due to the fact that they can be extremely long lived. This lifetime can be extended over batteries by scavenging fuel from the deployed environment. Microbial fuel cells (MFC) are one class of such sources that produce usable energy from small organic compounds (i.e. sugars, alcohols, organic acids, and biopolymers) which can be easily containerized or scavenged from the environment. The use of microorganisms as the anodic catalysts is what makes these systems unique from other biofuel cell designs. One of the main drawbacks of engineering a sensor system powered by an MFC is that power densities and current flux are extremely low in currently reported systems. The power density is limited by the mass transfer of the fuel source to the catalyst, the metabolism of the microbial catalysts and the electron transfer from the organism to the anode. This presentation will focus on the development of a new style of microbially-modified anodes which will increase power density to a level where a practical power source can be engineered. This is being achieved by developing a three dimensional matrix as an artificial, conductive biofilm. These artificial biofilms will allow the capture of a consortium of microbes designed for efficient metabolism of the available fuel source. Also it will keep the microbes close to the electrode allowing ready access by fuel and providing a low resistance passage of the liberated electrons from fuel oxidation.

  11. Biological response of HeLa cells to gold nanoparticles coated with organic molecules.

    Science.gov (United States)

    Cardoso Avila, P E; Rangel Mendoza, A; Pichardo Molina, J L; Flores Villavicencio, L L; Castruita Dominguez, J P; Chilakapati, M K; Sabanero Lopez, M

    2017-08-01

    In this work, gold nanospheres functionalized with low weight organic molecules (4-aminothiphenol and cysteamine) were synthesized in a one-step method for their in vitro cytotoxic evaluation on HeLa cells. To enhance the biocompatibility of the cysteamine-capped GNPs, BSA was used due to its broad PH stability and high binding affinity to gold nanoparticles. Besides, the widely reported silica coated gold nanorods were tested here to contrast their toxic response against our nanoparticles coated with organic molecules. Our results shown, the viability measured at 1.9×10 -5 M did not show significant differences against negative controls for all the samples; however, the metabolic activity of HeLa cells dropped when they were exposed to silica gold nanorods in the range of concentrations from 2.9×10 -7 M to 3.0×10 -4 M, while in the cases of gold nanospheres, we found that only at concentrations below 1.9×10 -5 M metabolic activity was normal. Our preliminary results did not indicate any perceivable harmful toxicity to cell membrane, cytoskeleton or nucleus due to our nanospheres at 1.9×10 -5 M. Additional test should be conducted in order to ensure a safe use of them for biological applications, and to determine the extent of possible damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Dohlman, Henrik G

    2015-03-13

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

  13. Molecular cell biology and physiology of solute transport

    Science.gov (United States)

    Caplan, Michael J.; Seo-Mayer, Patricia; Zhang, Li

    2010-01-01

    Purpose of review An enormous body of research has been focused on exploring the mechanisms through which epithelial cells establish their characteristic polarity. It is clear that under normal circumstances cell–cell contacts mediated by the calcium-dependent adhesion proteins of the intercellular adhesion junctions are required to initiate complete polarization. Furthermore, formation of the tight, or occluding, junctions that limit paracellular permeability has long been thought to help to establish polarity by preventing the diffusion of membrane proteins between the two plasmalemmal domains. This review will discuss several selected kinases and protein complexes and highlight their relevance to transporting epithelial cell polarization. Recent findings Recent work has shed new light on the roles of junctional complexes in establishing and maintaining epithelial cell polarity. In addition, work from several laboratories, suggests that the formation of these junctions is tied to processes that regulate cellular energy metabolism. Summary Junctional complexes and energy sensing kinases constitute a novel class of machinery whose capacity to generate and modulate epithelial cell polarity is likely to have wide ranging and important physiological ramifications. PMID:18695392

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

    KAUST Repository

    Islas Morales, Parsifal

    2018-01-01

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

  15. [The perfection of biology and discrepancies of humoral regulation non-surmounted in phylogenesis. The unified algorithm of pathogenesis of metabolic "pandemics" as diseases of civilization].

    Science.gov (United States)

    Titov, V N

    2014-08-01

    The striving to biological perfection became apparent under becoming of each out of seven biological functions at the consequent stages of phylogenesis: at cellular autocrine level; in paracrin regulated functional cenosis of cells, organs; at the organism level. However, regulative interaction simultaneously on all levels in vivo results in functional incoordination. There are no reasons to name them contradictions. They are targeted to development of organism; they are formed on different levels of regulation and sometimes are not comparable in full measure; incoordinations of regulation are never outdone. The striving of biology to perfection resulted in incoordinations becoming less apparent in conditions of physiological level of physical chemical parameters and concentrations of biochemical analytes staying within strict standard limits. The physiological values "are backed up" from below by realization of biological function of homeostasis. The upper level "is limited" by biological function of endoecology--leanliness of intercellular medium. The incoordinations of humoral and nervous regulation are manifested under impact of unfavorable factors of environment on organism. At that, regulatory incoordinations developed at distantly spaced degrees of phylogenesis came out as pathogenic factors of "metabolic pandemics"--civilization diseases. Ifdisease ofn oninfectious etiology is propagated in population with rate of 5 - 7% its pathogenesis is based on disorder ofb iologicalf unctions and biological reactions, meaning those impacts of environment that Homo sapiens didn't learn to match in phylogenesis. The strict normalization of biological functions and biological reactions can be the only pathogenetically and effective prevention and treatment of this pathology. The application ofp harmaceuticals is the foundation ofs ymptomatic therapy only.

  16. Towards high resolution analysis of metabolic flux in cells and tissues.

    Science.gov (United States)

    Sims, James K; Manteiga, Sara; Lee, Kyongbum

    2013-10-01

    Metabolism extracts chemical energy from nutrients, uses this energy to form building blocks for biosynthesis, and interconverts between various small molecules that coordinate the activities of cellular pathways. The metabolic state of a cell is increasingly recognized to determine the phenotype of not only metabolically active cell types such as liver, muscle, and adipose, but also other specialized cell types such as neurons and immune cells. This review focuses on methods to quantify intracellular reaction flux as a measure of cellular metabolic activity, with emphasis on studies involving cells of mammalian tissue. Two key areas are highlighted for future development, single cell metabolomics and noninvasive imaging, which could enable spatiotemporally resolved analysis and thereby overcome issues of heterogeneity, a distinctive feature of tissue metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

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

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

    Science.gov (United States)

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

    2010-04-22

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  1. β-cell function is associated with metabolic syndrome in Mexican subjects

    OpenAIRE

    Baez-Duarte, Blanca G; Sánchez-Guillén, María Del Carmen; Pérez-Fuentes, Ricardo; Zamora-Ginez, Irma; Leon-Chavez, Bertha Alicia; Revilla-Monsalve, Cristina; Islas-Andrade, Sergio

    2010-01-01

    Aims The clinical diagnosis of metabolic syndrome does not find any parameters to evaluate the insulin sensitivity (IS) or β-cell function. The evaluation of these parameters would detect early risk of developing metabolic syndrome. The aim of this study is to determine the relationship between β-cell function and presence of metabolic syndrome in Mexican subjects. Material and methods This study is part of the Mexican Survey on the Prevention of Diabetes (MexDiab Study) with headquarters in ...

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

    Science.gov (United States)

    de Oliveira, Mayara Lustosa; Galembeck, Eduardo

    2016-01-01

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

  3. Metabolic activity is necessary for activation of T suppressor cells by B cells

    International Nuclear Information System (INIS)

    Elkins, K.L.; Stashak, P.W.; Baker, P.J.

    1990-01-01

    Ag-primed B cells must express cell-surface IgM, but not IgD or Ia Ag, and must remain metabolically active, in order to activate suppressor T cells (Ts) specific for type III pneumococcal polysaccharide. Ag-primed B cells that were gamma-irradiated with 1000r, or less, retained the ability to activate Ts; however, Ag-primed B cells exposed to UV light were not able to do so. gamma-Irradiated and UV-treated Ag-primed B cells both expressed comparable levels of cell-surface IgM, and both localized to the spleen after in vivo transfer; neither could proliferate in vitro in response to mitogens. By contrast, gamma-irradiated primed B cells were still able to synthesize proteins, whereas UV-treated primed B cells could not. These findings suggest that in order for Ag-primed B cells to activate Ts, they must (a) express cell-associated IgM (sIgM) antibody bearing the idiotypic determinants of antibody specific for type III pneumococcal polysaccharide, and (b) be able to synthesize protein for either the continued expression of sIgM after cell transfer, or for the elaboration of another protein molecule that is also required for the activation of Ts; this molecule does not appear to be Ia Ag

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

    Science.gov (United States)

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

    2016-01-04

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

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

    Science.gov (United States)

    Franchi, Federico; Rodriguez-Porcel, Martin

    2017-01-01

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

  6. Leucine metabolism in regulation of insulin secretion from pancreatic beta cells

    OpenAIRE

    Yang, Jichun; Chi, Yujing; Burkhardt, Brant R.; Guan, Youfei; Wolf, Bryan A

    2010-01-01

    Leucine, a the branched-chain amino acids that must be supplied in daily diet, plays an important role in controlling protein synthesis and regulating cell metabolism in various cell types. In pancreatic β cells, leucine acutely stimulates insulin secretion by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. Leucine has also been shown to regulate gene transcription and protein synthesis in pancreatic islet β cells via both mTOR-dep...

  7. Biological response of cancer cells to radiation treatment

    Directory of Open Access Journals (Sweden)

    Rajamanickam eBaskar

    2014-11-01

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

  8. Biological behaviour of buccal cells exposed to blue light

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  9. iPS-Cinderella Story in Cell Biology

    Directory of Open Access Journals (Sweden)

    Editorial

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chengke eLiu

    2013-02-01

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

  11. Investigation of the metabolism of ergot alkaloids in cell culture by fourier transformation mass spectrometry.

    Science.gov (United States)

    Mulac, Dennis; Grote, Anna-Karina; Kleigrewe, Karin; Humpf, Hans-Ulrich

    2011-07-27

    Ergot alkaloids are known toxic secondary metabolites of the fungus Claviceps purpurea occurring in various grains, especially rye products. The liver is responsible for converting the ergot alkaloids into metabolites; however, the toxic impact of these end products of metabolism is still unknown. The aim of this study was to analyze the metabolism of ergot alkaloids in colon and liver cell lines (HT-29, HepG2), as well as in human primary renal cells (RPTEC). It was shown that cells in vitro are able to metabolize ergot alkaloids, forming a variety of metabolic compounds. Significant differences between the used cell types could be identified, and a suitable model system was established using HT-29 cells, performing an intensive metabolism to hydroxylated metabolites. The formed substances were analyzed by coupling of high-performance liquid chromatography with fluorescence detection and Fourier transformation mass spectrometry (HPLC-FLD-FTMS) as a powerful tool to identify known and unknown metabolites.

  12. Identification of cisplatin-regulated metabolic pathways in pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Louise von Stechow

    Full Text Available The chemotherapeutic compound, cisplatin causes various kinds of DNA lesions but also triggers other pertubations, such as ER and oxidative stress. We and others have shown that treatment of pluripotent stem cells with cisplatin causes a plethora of transcriptional and post-translational alterations that, to a major extent, point to DNA damage response (DDR signaling. The orchestrated DDR signaling network is important to arrest the cell cycle and repair the lesions or, in case of damage beyond repair, eliminate affected cells. Failure to properly balance the various aspects of the DDR in stem cells contributes to ageing and cancer. Here, we performed metabolic profiling by mass spectrometry of embryonic stem (ES cells treated for different time periods with cisplatin. We then integrated metabolomics with transcriptomics analyses and connected cisplatin-regulated metabolites with regulated metabolic enzymes to identify enriched metabolic pathways. These included nucleotide metabolism, urea cycle and arginine and proline metabolism. Silencing of identified proline metabolic and catabolic enzymes indicated that altered proline metabolism serves as an adaptive, rather than a toxic response. A group of enriched metabolic pathways clustered around the metabolite S-adenosylmethionine, which is a hub for methylation and transsulfuration reactions and polyamine metabolism. Enzymes and metabolites with pro- or anti-oxidant functions were also enriched but enhanced levels of reactive oxygen species were not measured in cisplatin-treated ES cells. Lastly, a number of the differentially regulated metabolic enzymes were identified as target genes of the transcription factor p53, pointing to p53-mediated alterations in metabolism in response to genotoxic stress. Altogether, our findings reveal interconnecting metabolic pathways that are responsive to cisplatin and may serve as signaling modules in the DDR in pluripotent stem cells.

  13. Epstein–Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Pier P. Piccaluga

    2018-06-01

    Full Text Available Tumor metabolism has been the object of several studies in the past, leading to the pivotal observation of a consistent shift toward aerobic glycolysis (so-called Warburg effect. More recently, several additional investigations proved that tumor metabolism is profoundly affected during tumorigenesis, including glucose, lipid and amino-acid metabolism. It is noticeable that metabolic reprogramming can represent a suitable therapeutic target in many cancer types. Epstein–Barr virus (EBV was the first virus linked with cancer in humans when Burkitt lymphoma (BL was described. Besides other well-known effects, it was recently demonstrated that EBV can induce significant modification in cell metabolism, which may lead or contribute to neoplastic transformation of human cells. Similarly, virus-induced tumorigenesis is characterized by relevant metabolic abnormalities directly induced by the oncoviruses. In this article, the authors critically review the most recent literature concerning EBV-induced metabolism alterations in lymphomas.

  14. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death

    International Nuclear Information System (INIS)

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna M; Mackinnon, A Craig Jr; Joseph, Joy; Dwinell, Michael B; Kalyanaraman, Balaraman

    2013-01-01

    Recent research has revealed that targeting mitochondrial bioenergetic metabolism is a promising chemotherapeutic strategy. Key to successful implementation of this chemotherapeutic strategy is the use of new and improved mitochondria-targeted cationic agents that selectively inhibit energy metabolism in breast cancer cells, while exerting little or no long-term cytotoxic effect in normal cells. In this study, we investigated the cytotoxicity and alterations in bioenergetic metabolism induced by mitochondria-targeted vitamin E analog (Mito-chromanol, Mito-ChM) and its acetylated ester analog (Mito-ChMAc). Assays of cell death, colony formation, mitochondrial bioenergetic function, intracellular ATP levels, intracellular and tissue concentrations of tested compounds, and in vivo tumor growth were performed. Both Mito-ChM and Mito-ChMAc selectively depleted intracellular ATP and caused prolonged inhibition of ATP-linked oxygen consumption rate in breast cancer cells, but not in non-cancerous cells. These effects were significantly augmented by inhibition of glycolysis. Mito-ChM and Mito-ChMAc exhibited anti-proliferative effects and cytotoxicity in several breast cancer cells with different genetic background. Furthermore, Mito-ChM selectively accumulated in tumor tissue and inhibited tumor growth in a xenograft model of human breast cancer. We conclude that mitochondria-targeted small molecular weight chromanols exhibit selective anti-proliferative effects and cytotoxicity in multiple breast cancer cells, and that esterification of the hydroxyl group in mito-chromanols is not a critical requirement for its anti-proliferative and cytotoxic effect

  15. Metabolomics reveals mycoplasma contamination interferes with the metabolism of PANC-1 cells.

    Science.gov (United States)

    Yu, Tao; Wang, Yongtao; Zhang, Huizhen; Johnson, Caroline H; Jiang, Yiming; Li, Xiangjun; Wu, Zeming; Liu, Tian; Krausz, Kristopher W; Yu, Aiming; Gonzalez, Frank J; Huang, Min; Bi, Huichang

    2016-06-01

    Mycoplasma contamination is a common problem in cell culture and can alter cellular functions. Since cell metabolism is either directly or indirectly involved in every aspect of cell function, it is important to detect changes to the cellular metabolome after mycoplasma infection. In this study, liquid chromatography mass spectrometry (LC/MS)-based metabolomics was used to investigate the effect of mycoplasma contamination on the cellular metabolism of human pancreatic carcinoma cells (PANC-1). Multivariate analysis demonstrated that mycoplasma contamination induced significant metabolic changes in PANC-1 cells. Twenty-three metabolites were identified and found to be involved in arginine and purine metabolism and energy supply. This study demonstrates that mycoplasma contamination significantly alters cellular metabolite levels, confirming the compelling need for routine checking of cell cultures for mycoplasma contamination, particularly when used for metabolomics studies. Graphical abstract Metabolomics reveals mycoplasma contamination changes the metabolome of PANC-1 cells.

  16. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    Science.gov (United States)

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

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

    Science.gov (United States)

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

    2014-12-15

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

  18. Glycogen metabolism in the glucose-sensing and supply-driven β-cell.

    Science.gov (United States)

    Andersson, Lotta E; Nicholas, Lisa M; Filipsson, Karin; Sun, Jiangming; Medina, Anya; Al-Majdoub, Mahmoud; Fex, Malin; Mulder, Hindrik; Spégel, Peter

    2016-12-01

    Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined. © 2016 Federation of European Biochemical Societies.

  19. Towards a sustainable bio-based economy: Redirecting primary metabolism to new products with plant synthetic biology.

    Science.gov (United States)

    Shih, Patrick M

    2018-08-01

    Humans have domesticated many plant species as indispensable sources of food, materials, and medicines. The dawning era of synthetic biology represents a means to further refine, redesign, and engineer crops to meet various societal and industrial needs. Current and future endeavors will utilize plants as the foundation of a bio-based economy through the photosynthetic production of carbohydrate feedstocks for the microbial fermentation of biofuels and bioproducts, with the end goal of decreasing our dependence on petrochemicals. As our technological capabilities improve, metabolic engineering efforts may expand the utility of plants beyond sugar feedstocks through the direct production of target compounds, including pharmaceuticals, renewable fuels, and commodity chemicals. However, relatively little work has been done to fully realize the potential in redirecting central carbon metabolism in plants for the engineering of novel bioproducts. Although our ability to rationally engineer and manipulate plant metabolism is in its infancy, I highlight some of the opportunities and challenges in applying synthetic biology towards engineering plant primary metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Ruminant Metabolic Systems Biology: Reconstruction and Integration of Transcriptome Dynamics Underlying Functional Responses of Tissues to Nutrition and Physiological Statea

    Science.gov (United States)

    Bionaz, Massimo; Loor, Juan J.

    2012-01-01

    High-throughput ‘omics’ data analysis via bioinformatics is one key component of the systems biology approach. The systems approach is particularly well-suited for the study of the interactions between nutrition and physiological state with tissue metabolism and functions during key life stages of organisms such as the transition from pregnancy to lactation in mammals, ie, the peripartal period. In modern dairy cows with an unprecedented genetic potential for milk synthesis, the nature of the physiologic and metabolic adaptations during the peripartal period is multifaceted and involves key tissues such as liver, adipose, and mammary. In order to understand such adaptation, we have reviewed several works performed in our and other labs. In addition, we have used a novel bioinformatics approach, Dynamic Impact Approach (DIA), in combination with partly previously published data to help interpret longitudinal biological adaptations of bovine liver, adipose, and mammary tissue to lactation using transcriptomics datasets. Use of DIA with transcriptomic data from those tissues during normal physiological adaptations and in animals fed different levels of energy prepartum allowed visualization and integration of most-impacted metabolic pathways around the time of parturition. The DIA is a suitable tool for applying the integrative systems biology approach. The ultimate goal is to visualize the complexity of the systems at study and uncover key molecular players involved in the tissue’s adaptations to physiological state or nutrition. PMID:22807626

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

    Science.gov (United States)

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

    2016-09-01

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

  2. Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

    Science.gov (United States)

    Bourdieu, Antonin; Avalon, Maryse; Lapostolle, Véronique; Ismail, Sadek; Mombled, Margaux; Debeissat, Christelle; Guérinet, Marianne; Duchez, Pascale; Chevaleyre, Jean; Vlaski-Lafarge, Marija; Villacreces, Arnaud; Praloran, Vincent; Ivanovic, Zoran; Brunet de la Grange, Philippe

    2018-01-01

    Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O 2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. © 2017 Wiley Periodicals, Inc.

  3. Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.

    Science.gov (United States)

    Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

    2014-02-01

    The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-09

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  6. Probing the biology of cell boundary conditions through confinement of Xenopus cell-free cytoplasmic extracts.

    Science.gov (United States)

    Bermudez, Jessica G; Chen, Hui; Einstein, Lily C; Good, Matthew C

    2017-01-01

    Cell-free cytoplasmic extracts prepared from Xenopus eggs and embryos have for decades provided a biochemical system with which to interrogate complex cell biological processes in vitro. Recently, the application of microfabrication and microfluidic strategies in biology has narrowed the gap between in vitro and in vivo studies by enabling formation of cell-size compartments containing functional cytoplasm. These approaches provide numerous advantages over traditional biochemical experiments performed in a test tube. Most notably, the cell-free cytoplasm is confined using a two- or three-dimensional boundary, which mimics the natural configuration of a cell. This strategy enables characterization of the spatial organization of a cell, and the role that boundaries play in regulating intracellular assembly and function. In this review, we describe the marriage of Xenopus cell-free cytoplasm and confinement technologies to generate synthetic cell-like systems, the recent biological insights they have enabled, and the promise they hold for future scientific discovery. © 2017 Wiley Periodicals, Inc.

  7. Metabolic enzymes: key modulators of functionality in cancer stem-like cells.

    Science.gov (United States)

    Dong, Bo-Wen; Qin, Guang-Ming; Luo, Yan; Mao, Jian-Shan

    2017-02-21

    Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs.

  8. Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

    Science.gov (United States)

    Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

    2017-01-01

    An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

  9. Biological 2-Input Decoder Circuit in Human Cells

    Science.gov (United States)

    2015-01-01

    Decoders are combinational circuits that convert information from n inputs to a maximum of 2n outputs. This operation is of major importance in computing systems yet it is vastly underexplored in synthetic biology. Here, we present a synthetic gene network architecture that operates as a biological decoder in human cells, converting 2 inputs to 4 outputs. As a proof-of-principle, we use small molecules to emulate the two inputs and fluorescent reporters as the corresponding four outputs. The experiments are performed using transient transfections in human kidney embryonic cells and the characterization by fluorescence microscopy and flow cytometry. We show a clear separation between the ON and OFF mean fluorescent intensity states. Additionally, we adopt the integrated mean fluorescence intensity for the characterization of the circuit and show that this metric is more robust to transfection conditions when compared to the mean fluorescent intensity. To conclude, we present the first implementation of a genetic decoder. This combinational system can be valuable toward engineering higher-order circuits as well as accommodate a multiplexed interface with endogenous cellular functions. PMID:24694115

  10. Lessons learned about spaceflight and cell biology experiments

    Science.gov (United States)

    Hughes-Fulford, Millie

    2004-01-01

    Conducting cell biology experiments in microgravity can be among the most technically challenging events in a biologist's life. Conflicting events of spaceflight include waiting to get manifested, delays in manifest schedules, training astronauts to not shake your cultures and to add reagents slowly, as shaking or quick injection can activate signaling cascades and give you erroneous results. It is important to select good hardware that is reliable. Possible conflicting environments in flight include g-force and vibration of launch, exposure of cells to microgravity for extended periods until hardware is turned on, changes in cabin gases and cosmic radiation. One should have an on-board 1-g control centrifuge in order to eliminate environmental differences. Other obstacles include getting your funding in a timely manner (it is not uncommon for two to three years to pass between notification of grant approval for funding and actually getting funded). That said, it is important to note that microgravity research is worthwhile since all terrestrial life evolved in a gravity field and secrets of biological function may only be answered by removing the constant of gravity. Finally, spaceflight experiments are rewarding and worth your effort and patience.

  11. Biological 2-input decoder circuit in human cells.

    Science.gov (United States)

    Guinn, Michael; Bleris, Leonidas

    2014-08-15

    Decoders are combinational circuits that convert information from n inputs to a maximum of 2(n) outputs. This operation is of major importance in computing systems yet it is vastly underexplored in synthetic biology. Here, we present a synthetic gene network architecture that operates as a biological decoder in human cells, converting 2 inputs to 4 outputs. As a proof-of-principle, we use small molecules to emulate the two inputs and fluorescent reporters as the corresponding four outputs. The experiments are performed using transient transfections in human kidney embryonic cells and the characterization by fluorescence microscopy and flow cytometry. We show a clear separation between the ON and OFF mean fluorescent intensity states. Additionally, we adopt the integrated mean fluorescence intensity for the characterization of the circuit and show that this metric is more robust to transfection conditions when compared to the mean fluorescent intensity. To conclude, we present the first implementation of a genetic decoder. This combinational system can be valuable toward engineering higher-order circuits as well as accommodate a multiplexed interface with endogenous cellular functions.

  12. Evolving cell models for systems and synthetic biology.

    Science.gov (United States)

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

    2010-03-01

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

  13. Sub-terahertz resonance spectroscopy of biological macromolecules and cells

    Science.gov (United States)

    Globus, Tatiana; Moyer, Aaron; Gelmont, Boris; Khromova, Tatyana; Sizov, Igor; Ferrance, Jerome

    2013-05-01

    Recently we introduced a Sub-THz spectroscopic system for characterizing vibrational resonance features from biological materials. This new, continuous-wave, frequency-domain spectroscopic sensor operates at room temperature between 315 and 480 GHz with spectral resolution of at least 1 GHz and utilizes the source and detector components from Virginia Diode, Inc. In this work we present experimental results and interpretation of spectroscopic signatures from bacterial cells and their biological macromolecule structural components. Transmission and absorption spectra of the bacterial protein thioredoxin, DNA and lyophilized cells of Escherichia coli (E. coli), as well as spores of Bacillus subtillis and B. atrophaeus have been characterized. Experimental results for biomolecules are compared with absorption spectra calculated using molecular dynamics simulation, and confirm the underlying physics for resonance spectroscopy based on interactions between THz radiation and vibrational modes or groups of modes of atomic motions. Such interactions result in multiple intense and narrow specific resonances in transmission/absorption spectra from nano-gram samples with spectral line widths as small as 3 GHz. The results of this study indicate diverse relaxation dynamic mechanisms relevant to sub-THz vibrational spectroscopy, including long-lasting processes. We demonstrate that high sensitivity in resolved specific absorption fingerprints provides conditions for reliable detection, identification and discrimination capability, to the level of strains of the same bacteria, and for monitoring interactions between biomaterials and reagents in near real-time. Additionally, it creates the basis for the development of new types of advanced biological sensors through integrating the developed system with a microfluidic platform for biomaterial samples.

  14. Pectin: cell biology and prospects for functional analysis.

    Science.gov (United States)

    Willats, W G; McCartney, L; Mackie, W; Knox, J P

    2001-09-01

    Pectin is a major component of primary cell walls of all land plants and encompasses a range of galacturonic acid-rich polysaccharides. Three major pectic polysaccharides (homogalacturonan, rhamnogalacturonan-I and rhamnogalacturonan-II) are thought to occur in all primary cell walls. This review surveys what is known about the structure and function of these pectin domains. The high degree of structural complexity and heterogeneity of the pectic matrix is produced both during biosynthesis in the endomembrane system and as a result of the action of an array of wall-based pectin-modifying enzymes. Recent developments in analytical techniques and in the generation of anti-pectin probes have begun to place the structural complexity of pectin in cell biological and developmental contexts. The in muro de-methyl-esterification of homogalacturonan by pectin methyl esterases is emerging as a key process for the local modulation of matrix properties. Rhamnogalacturonan-I comprises a highly diverse population of spatially and developmentally regulated polymers, whereas rhamnogalacturonan-II appears to be a highly conserved and stable pectic domain. Current knowledge of biosynthetic enzymes, plant and microbial pectinases and the interactions of pectin with other cell wall components and the impact of molecular genetic approaches are reviewed in terms of the functional analysis of pectic polysaccharides in plant growth and development.

  15. Computational Biology Methods for Characterization of Pluripotent Cells.

    Science.gov (United States)

    Araúzo-Bravo, Marcos J

    2016-01-01

    Pluripotent cells are a powerful tool for regenerative medicine and drug discovery. Several techniques have been developed to induce pluripotency, or to extract pluripotent cells from different tissues and biological fluids. However, the characterization of pluripotency requires tedious, expensive, time-consuming, and not always reliable wet-lab experiments; thus, an easy, standard quality-control protocol of pluripotency assessment remains to be established. Here to help comes the use of high-throughput techniques, and in particular, the employment of gene expression microarrays, which has become a complementary technique for cellular characterization. Research has shown that the transcriptomics comparison with an Embryonic Stem Cell (ESC) of reference is a good approach to assess the pluripotency. Under the premise that the best protocol is a computer software source code, here I propose and explain line by line a software protocol coded in R-Bioconductor for pluripotency assessment based on the comparison of transcriptomics data of pluripotent cells with an ESC of reference. I provide advice for experimental design, warning about possible pitfalls, and guides for results interpretation.

  16. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  17. Systems biology and metabolic engineering of lactic acid bacteria for improved fermented foods

    NARCIS (Netherlands)

    Flahaut, N.A.L.; Vos, de W.M.

    2014-01-01

    Lactic acid bacteria have long been used in industrial dairy and other food fermentations that make use of their metabolic activities leading to products with specific organoleptic properties. Metabolic engineering is a rational approach to steer fermentations toward the production of desired

  18. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology

    NARCIS (Netherlands)

    Herrgård, Markus J.; Swainston, Neil; Dobson, Paul; Dunn, Warwick B.; Arga, K. Yalçin; Arvas, Mikko; Blüthgen, Nils; Borger, Simon; Costenoble, Roeland; Heinemann, Matthias; Hucka, Michael; Novère, Nicolas Le; Li, Peter; Liebermeister, Wolfram; Mo, Monica L.; Oliveira, Ana Paula; Petranovic, Dina; Pettifer, Stephen; Simeonidis, Evangelos; Smallbone, Kieran; Spasić, Irena; Weichart, Dieter; Brent, Roger; Broomhead, David S.; Westerhoff, Hans V.; Kırdar, Betül; Penttilä, Merja; Klipp, Edda; Palsson, Bernhard Ø.; Sauer, Uwe; Oliver, Stephen G.; Mendes, Pedro; Nielsen, Jens; Kell, Douglas B.

    2008-01-01

    Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and

  19. Systems Biology of Metabolism: A Driver for Developing Personalized and Precision Medicine

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    for advancing the development of personalized and precision medicine to treat metabolic diseases like insulin resistance, obesity, NAFLD, NASH, and cancer. It will be illustrated how the concept of genome-scale metabolic models can be used for integrative analysis of big data with the objective of identifying...... novel biomarkers that are foundational for personalized and precision medicine....

  20. Induced Pluripotent Stem Cell-Derived Endothelial Cells in Insulin Resistance and Metabolic Syndrome.

    Science.gov (United States)

    Carcamo-Orive, Ivan; Huang, Ngan F; Quertermous, Thomas; Knowles, Joshua W

    2017-11-01

    Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations. © 2017 American Heart Association, Inc.

  1. MiR130b-Regulation of PPARγ Coactivator- 1α Suppresses Fat Metabolism in Goat Mammary Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Zhi Chen

    Full Text Available Fat metabolism is a complicated process regulated by a series of factors. microRNAs (miRNAs are a class of negative regulator of proteins and play crucial roles in many biological processes; including fat metabolism. Although there have been some researches indicating that miRNAs could influence the milk fat metabolism through targeting some factors, little is known about the effect of miRNAs on goat milk fat metabolism. Here we utilized an improved miRNA detection assay, S-Poly-(T, to profile the expression of miRNAs in the goat mammary gland in different periods, and found that miR-130b was abundantly and differentially expressed in goat mammary gland. Additionally, overexpressing miR-130b impaired adipogenesis while inhibiting miR-130b enhanced adipogenesis in goat mammary epithelial cells. Utilizing 3'-UTR assay and Western Blot analusis, the protein peroxisome proliferator-activated receptor coactivator-1α (PGC1α, a major regulator of fat metabolism, was demonstrated to be a potential target of miR-130b. Interestingly, miR-130b potently repressed PGC1α expression by targeting both the PGC1α mRNA coding and 3' untranslated regions. These findings have some insight of miR-130b in mediating adipocyte differentiation by repressing PGC1α expression and this contributes to further understanding about the functional significance of miRNAs in milk fat synthesis.

  2. Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...Heterogeneity in Metabolic Disease Using Single- Cell RNA-Seq 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen...ABSTRACT We have developed a robust protocol to generate single cell transcriptional profiles from subcutaneous adipose tissue samples of both human

  3. Cells from icons to symbols: molecularizing cell biology in the 1980s.

    Science.gov (United States)

    Serpente, Norberto

    2011-12-01

    Over centuries cells have been the target of optical and electronic microscopes as well as others technologies, with distinctive types of visual output. Whilst optical technologies produce images 'evident to the eye', the electronic and especially the molecular create images that are more elusive to conceptualization and assessment. My study applies the semiotic approach to the production of images in cell biology to capture the shift from microscopic images to non-traditional visual technologies around 1980. Here I argue that the visual shift that coincides with the growing dominance of molecular biology involves a change from iconic to symbolic forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging [version 1; referees: 4 approved

    OpenAIRE

    Clovis S. Palmer; Riya Palchaudhuri; Hassan Albargy; Mohamed Abdel-Mohsen; Suzanne M. Crowe

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impa...

  5. Systems biology perspectives on minimal and simpler cells.

    Science.gov (United States)

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

    2014-09-01

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

  6. Systems Biology Perspectives on Minimal and Simpler Cells

    Science.gov (United States)

    Xavier, Joana C.; Patil, Kiran Raosaheb

    2014-01-01

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

  7. The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Dos Santos, Guilherme Galvão; Batool, Shafqat; Hastreiter, Araceli; Sartori, Talita; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

    2017-08-01

    Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1β, IL-6 and TGF-β was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-03-17

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated.

  9. Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism

    Directory of Open Access Journals (Sweden)

    Verónica S. Martínez

    2015-12-01

    Full Text Available Metabolic flux analysis (MFA is widely used to estimate intracellular fluxes. Conventional MFA, however, is limited to continuous cultures and the mid-exponential growth phase of batch cultures. Dynamic MFA (DMFA has emerged to characterize time-resolved metabolic fluxes for the entire culture period. Here, the linear DMFA approach was extended using B-spline fitting (B-DMFA to estimate mass balanced fluxes. Smoother fits were achieved using reduced number of knots and parameters. Additionally, computation time was greatly reduced using a new heuristic algorithm for knot placement. B-DMFA revealed that Chinese hamster ovary cells shifted from 37 °C to 32 °C maintained a constant IgG volume-specific productivity, whereas the productivity for the controls peaked during mid-exponential growth phase and declined afterward. The observed 42% increase in product titer at 32 °C was explained by a prolonged cell growth with high cell viability, a larger cell volume and a more stable volume-specific productivity. Keywords: Dynamic, Metabolism, Flux analysis, CHO cells, Temperature shift, B-spline curve fitting

  10. An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells

    International Nuclear Information System (INIS)

    Mandal, Soma; Davie, James R

    2007-01-01

    The sex hormone estrogen (E2) is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+)ve breast cancer cells during E2 deprivation. Public repositories of SAGE and MA gene expression data generated from E2 deprived ER(+)ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology (GO), enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status. In all GO terms, biological process (BP), molecular function (MF), and cellular component (CC), MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein (ZR75-1) and glucose metabolism (MCF-7). A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization (electron transport, proteasome, glycolysis/gluconeogenesis) and expression (ribosome) in both cells, there was an overall similarity of ZR75-1 with ER(-)ve cell lines and ER(+)ve/ER(-)ve breast tumors. This study demonstrates integral metabolic differences may exist within the same cell subtype (luminal A) in representative ER(+)ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER(+)ve breast tumors

  11. Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space

    Science.gov (United States)

    Gmunder, F. K.; Nordau, C. G.; Tschopp, A.; Huber, B.; Cogoli, A.

    1988-01-01

    The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 microliters. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 microliter h-1). The reservoir volume of culture medium is 230 microliters. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.

  12. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment

    Directory of Open Access Journals (Sweden)

    Rui V. Simões

    2015-08-01

    Full Text Available Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells, leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1 provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2 lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism.

  13. Metabolic changes during B cell differentiation for the production of intestinal IgA antibody.

    Science.gov (United States)

    Kunisawa, Jun

    2017-04-01

    To sustain the bio-energetic demands of growth, proliferation, and effector functions, the metabolism of immune cells changes dramatically in response to immunologic stimuli. In this review, I focus on B cell metabolism, especially regarding the production of intestinal IgA antibody. Accumulating evidence has implicated not only host-derived factors (e.g., cytokines) but also gut environmental factors, including the possible involvement of commensal bacteria and diet, in the control of B cell metabolism during intestinal IgA antibody production. These findings yield new insights into the regulation of immunosurveillance and homeostasis in the gut.

  14. Molecular infection biology : interactions between microorganisms and cells

    National Research Council Canada - National Science Library

    Hacker, Jörg (Jörg Hinrich); Heesemann, Jurgen

    2002-01-01

    ... and epidemiology of infectious diseases. Investigators, specialists, clinicians, and graduate students in biology, pharmacy, and medicine will find Molecular Infection Biology an invaluable addition to their professional libraries...

  15. Resistance to Antiangiogenic Therapies by Metabolic Symbiosis in Renal Cell Carcinoma PDX Models and Patients

    Directory of Open Access Journals (Sweden)

    Gabriela Jiménez-Valerio

    2016-05-01

    Full Text Available Antiangiogenic drugs are used clinically for treatment of renal cell carcinoma (RCC as a standard first-line treatment. Nevertheless, these agents primarily serve to stabilize disease, and resistance eventually develops concomitant with progression. Here, we implicate metabolic symbiosis between tumor cells distal and proximal to remaining vessels as a mechanism of resistance to antiangiogenic therapies in patient-derived RCC orthoxenograft (PDX models and in clinical samples. This metabolic patterning is regulated by the mTOR pathway, and its inhibition effectively blocks metabolic symbiosis in PDX models. Clinically, patients treated with antiangiogenics consistently present with histologic signatures of metabolic symbiosis that are exacerbated in resistant tumors. Furthermore, the mTOR pathway is also associated in clinical samples, and its inhibition eliminates symbiotic patterning in patient samples. Overall, these data support a mechanism of resistance to antiangiogenics involving metabolic compartmentalization of tumor cells that can be inhibited by mTOR-targeted drugs.

  16. Regulation of glucose metabolism in T cells; new insight into the role of Phosphoinositide 3-kinases

    Directory of Open Access Journals (Sweden)

    David K Finlay

    2012-08-01

    Full Text Available Naïve T cells are relatively quiescent cells that only require energy to prevent atrophy and for survival and migration. However, in response to developmental or extrinsic cues T cells can engage in rapid growth and robust proliferation, produce of a range of effector molecules and migrate through peripheral tissues. To meet the significantly increased metabolic demands of these activities, T cells switch from primarily metabolizing glucose to carbon dioxide through oxidative phosphorylation to utilizing glycolysis to convert glucose to lactate (termed aerobic glycolysis. This metabolic switch allows glucose to be used as a source of carbon to generate biosynthetic precursors for the production of protein, DNA and phospholipids, and is crucial for T cells to meet metabolic demands. Phosphoinositide 3-kinases (PI3K are a family of inositol lipid kinases linked with a broad range of cellular functions in T lymphocytes that include cell growth, proliferation, metabolism, differentiation, survival and migration. Initial research described a critical role for PI3K signaling through Akt (also called Protein kinase B for the increased glucose uptake and glycolysis that accompanies T cell activation. This review article relates this original research wi