WorldWideScience

Sample records for emerging cellular molecular

  1. Signal processing for molecular and cellular biological physics: an emerging field.

    Science.gov (United States)

    Little, Max A; Jones, Nick S

    2013-02-13

    Recent advances in our ability to watch the molecular and cellular processes of life in action--such as atomic force microscopy, optical tweezers and Forster fluorescence resonance energy transfer--raise challenges for digital signal processing (DSP) of the resulting experimental data. This article explores the unique properties of such biophysical time series that set them apart from other signals, such as the prevalence of abrupt jumps and steps, multi-modal distributions and autocorrelated noise. It exposes the problems with classical linear DSP algorithms applied to this kind of data, and describes new nonlinear and non-Gaussian algorithms that are able to extract information that is of direct relevance to biological physicists. It is argued that these new methods applied in this context typify the nascent field of biophysical DSP. Practical experimental examples are supplied.

  2. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  3. Molecular, cellular, and tissue engineering

    CERN Document Server

    Bronzino, Joseph D

    2015-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

  4. Molecular and cellular heterogeneity: the hallmark of glioblastoma.

    Science.gov (United States)

    Aum, Diane J; Kim, David H; Beaumont, Thomas L; Leuthardt, Eric C; Dunn, Gavin P; Kim, Albert H

    2014-12-01

    There has been increasing awareness that glioblastoma, which may seem histopathologically similar across many tumors, actually represents a group of molecularly distinct tumors. Emerging evidence suggests that cells even within the same tumor exhibit wide-ranging molecular diversity. Parallel to the discoveries of molecular heterogeneity among tumors and their individual cells, intense investigation of the cellular biology of glioblastoma has revealed that not all cancer cells within a given tumor behave the same. The identification of a subpopulation of brain tumor cells termed "glioblastoma cancer stem cells" or "tumor-initiating cells" has implications for the management of glioblastoma. This focused review will therefore summarize emerging concepts on the molecular and cellular heterogeneity of glioblastoma and emphasize that we should begin to consider each individual glioblastoma to be an ensemble of molecularly distinct subclones that reflect a spectrum of dynamic cell states.

  5. Integrated Molecular and Cellular Biophysics

    CERN Document Server

    Raicu, Valerica

    2008-01-01

    This book integrates concepts and methods from physics, biology, biochemistry and physical chemistry into a standalone, unitary text of biophysics that aims to provide a quantitative description of structures and processes occurring in living matter. The book introduces graduate physics students and physicists interested in biophysics research to 'classical' as well as emerging areas of biophysics. The advanced undergraduate physics students and the life scientists are also invited to join in, by building on their knowledge of basic physics. Essential notions of biochemistry and biology are introduced, as necessary, throughout the book, while the reader's familiarity with basic knowledge of physics is assumed. Topics covered include interactions between biological molecules, physical chemistry of phospholipids association into bilayer membranes, DNA and protein structure and folding, passive and active electrical properties of the cell membrane, classical as well as fractal aspects of reaction kinetics and di...

  6. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  7. Molecular processes in cellular arsenic metabolism

    International Nuclear Information System (INIS)

    Thomas, David J.

    2007-01-01

    Elucidating molecular processes that underlie accumulation, metabolism and binding of iAs and its methylated metabolites provides a basis for understanding the modes of action by which iAs acts as a toxin and a carcinogen. One approach to this problem is to construct a conceptual model that incorporates available information on molecular processes involved in the influx, metabolism, binding and efflux of arsenicals in cells. This conceptual model is initially conceived as a non-quantitative representation of critical molecular processes that can be used as a framework for experimental design and prediction. However, with refinement and incorporation of additional data, the conceptual model can be expressed in mathematical terms and should be useful for quantitative estimates of the kinetic and dynamic behavior of iAs and its methylated metabolites in cells. Development of a quantitative model will be facilitated by the availability of tools and techniques to manipulate molecular processes underlying transport of arsenicals across cell membranes or expression and activity of enzymes involved in methylation of arsenicals. This model of cellular metabolism might be integrated into more complex pharmacokinetic models for systemic metabolism of iAs and its methylated metabolites. It may also be useful in development of biologically based dose-response models describing the toxic and carcinogenic actions of arsenicals

  8. Beneficial liaisons: radiobiology meets cellular and molecular biology

    International Nuclear Information System (INIS)

    Stevenson, Mary Ann; Coleman, C. Norman

    1995-01-01

    Purpose: The purpose of this course is to familiarize radiation oncologists with the concepts and terminology and molecular and cellular biology that are especially relevant to radiation oncology. The ability of radiation oncologists to remain current with the new discoveries of modern biology is essential to the development of improved therapeutic strategies and, importantly, to the proper balance between investment in technology and biology. Objective: This year, this Refresher Course is part of a three-part ''series'' including Drs. Martin Brown and Amato Giaccia. The objective is to provide continuing education for the academic and practicing radiation oncologist, physicist and biologist in the modern biologic concepts of cancer and its treatment. An effort will be made to relate these general concepts to the clinic by providing a broad view as to potential new biological treatments which might enhance the efficacy of radiation therapy. The specific focus of this Course will vary from year to year. Some of the classic radiation biology models which form the basis of clinical practice and laboratory research will be examined and 'newer' models will be presented which take into account the emerging knowledge of cellular and molecular biology. A few techniques in molecular and cellular biology will be described to the extent necessary to understand their basic concepts and their applicability. Aspects of radiation biology which will be covered include cell cycle, radiation-induced changes in the cellular phenotype, and considerations of the effect of the tumor microenvironment. It is not the expectation that the attendees will become experts in the particular subjects presented. Rather, it is the intent to increase their curiosity as to the new knowledge that is emerging and to demonstrate that these seemingly complicated areas can be understood and appreciated with a modicum of the effort

  9. Postischemic revascularization: from cellular and molecular mechanisms to clinical applications.

    Science.gov (United States)

    Silvestre, Jean-Sébastien; Smadja, David M; Lévy, Bernard I

    2013-10-01

    After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

  10. Nutritional education from Molecular and Cellular Biology

    Directory of Open Access Journals (Sweden)

    Zaida Ramona Betancourt Betancourt

    2014-12-01

    Full Text Available The nutritional education is current topic, constituting a necessity in the contemporary world, given mainly by the contribution that it makes in maintaining the human health under good conditions. Starting from this problem, it is presented this article whose objective is: to show the potential ities that the discipline Cellular and Molecular Biology offers, for the treatment of these contents, since this discipline is worked in the second semester of first year and first semester of in the formation of professors of the Biology - Geography and Bio logy - C hemistry careers which can contribute to the development of knowledge, habits and abilities that allows them to appropriate of responsible behaviours for the achievement of correct nutritional habits.

  11. Molecular and cellular endocrinology of the testis

    International Nuclear Information System (INIS)

    Stefanini, M.; Conti, M.; Geremia, R.; Ziparo, E.

    1986-01-01

    This volume contains the Proceedings of the IV European Workshop on Molecular and Cellular Endocrinology of the Testis held in Capri (Italy) between the 9th and 12th April 1986. The workshop was organized in several symposia related to some of the most relevant aspects of the regulation of testicular function. Main topics were the role of cell interactions, the mechanisms of signal transduction, gene expression and metabolic response of somatic cells as well as differentiation of germ cells. One session was devoted to prostaglandins in the male reproductive system and to brief discussions on interstitial fluid and on antispermatogenic compounds. In this book only the main lectures and some selected short papers are presented. (Auth.)

  12. Biological (molecular and cellular) markers of toxicity

    International Nuclear Information System (INIS)

    Shugart, L.R.; D'Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-01-01

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO 6 -ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O 6 -ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP

  13. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease

    Science.gov (United States)

    Anderson, Mark E.; Birren, Susan J.; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B.; Kanazawa, Hideaki; Paterson, David J.; Ripplinger, Crystal M.

    2016-01-01

    Abstract The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural–cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

  14. Cellular and Molecular Anesthesia: from Bench to Bedside

    Directory of Open Access Journals (Sweden)

    Ali Dabbagh

    2015-12-01

    Full Text Available Cellular and Molecular Anesthesia: from Bench to BedsideIn the current practice of anesthesia, each day, anesthesiologists deal with a great work: they use the cellular mechanisms of drug molecules to induce their desired effects for induction and maintenance of anesthesia to achieve appropriate tolerance of surgery and its pain, modulation of stress response, sedation needed for performing a variety of procedures, emergency anesthesia care, acute and chronic pain management or other everyday jobs of anesthesiologists during perioperative period.As a matter of fact, molecular anesthesia has been cited for more than 6 decades though in avery limited scale. In 1956, the molecular mechanisms of morphine and pethidine are described (1. Pauling in 1961 published an article in Science describing a molecular theorey for general anesthesia (2.In its report “the World in 2025”, Thomson Reuters has predicted clinical medicine would be the most active research front; while molecular biology has the 9th rank (3. But are we still practicing in clinic the same as today?In fact, the future trend of anesthesia is highly dependent on finding the novel cellular and molecular mechanisms and the possible interactions of the newly discovered molecules and inreraction mechanisms with organ systems. Today, we emphasize on the role of pharmacologists, physiologists, immunologists, anatomists, embryologists, geneticians, cellular medicine specialists, physicists and other basic science specialists; some very interesting examples are published in this volume of the Journal (4-7.However, changes that have well started now would “revolutionize” our daily practice during the next decade in such a way that it will change the basis of medicine: presumably we will have a new model medicine known as “personalized medicine” or “precision medicine”. In this approach, the content of each patient’s genes accompanied with his/her cellular and molecular analysis is

  15. Modems for emerging digital cellular-mobile radio system

    Science.gov (United States)

    Feher, Kamilo

    1991-01-01

    Digital modem techniques for emerging digital cellular telecommunications-mobile radio system applications are described and analyzed. In particular, theoretical performance, experimental results, principles of operation, and various architectures of pi/4-QPSK (pi/4-shifted coherent or differential QPSK) modems for second-generation US digital cellular radio system applications are presented. The spectral/power efficiency and performance of the pi/4-QPSK modems (American and Japanese digital cellular emerging standards) are studied and briefly compared to GMSK (Gaussian minimum-shift keying) modems (proposed for European DECT and GSM cellular standards). Improved filtering strategies and digital pilot-aided (digital channel sounding) techniques are also considered for pi/4-QPSK and other digital modems. These techniques could significantly improve the performance of digital cellular and other digital land mobile and satellite mobile radio systems. More spectrally efficient modem trends for future cellular/mobile (land mobile) and satellite communication systems applications are also highlighted.

  16. Molecular and cellular mechanisms of aortic stenosis.

    Science.gov (United States)

    Yetkin, Ertan; Waltenberger, Johannes

    2009-06-12

    Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

  17. Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

    Science.gov (United States)

    Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

    2014-01-01

    There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers. PMID:23094914

  18. Molecular biology - Part II: Beneficial liaisons: Radiobiology meets cellular and molecular biology

    International Nuclear Information System (INIS)

    Stevenson, Mary Ann; Coleman, C. Norman

    1997-01-01

    Purpose: The purpose of this course is to familiarize radiation oncologists with the concepts and terminology of molecular and cellular biology that are especially relevant to radiation oncology. The ability of radiation oncologists to remain current with the new discoveries of modern biology is essential to the development of improved therapeutic strategies and, importantly, to the proper balance between investment in technology and biology. Objective: This year, this Refresher Course is part of a three-part ''series'' including Drs. McKenna and Dritschilo. The objective is to provide continuing education for the academic and practicing radiation oncologist, physicist and biologist in the modern biologic concepts of cancer and its treatment. An effort will be made to relate these general concepts to the clinic by providing a broad view as to potential new biological treatments which might enhance the efficacy of radiation therapy. The specific focus of this Course will vary from year to year. Some of the classic radiation biology models which form the basis of clinical practice and laboratory research will be examined and 'newer' models will be presented which take into account the emerging knowledge of cellular and molecular biology. A few techniques in molecular and cellular biology will be described to the extent necessary to understand their basic concepts and their applicability. Aspects of radiation biology which will be covered include cell cycle, radiation-induced changes in the cellular phenotype, and considerations of the effect of the tumor microenvironment. It is not the expectation that the attendees will become experts in the particular subjects presented. Rather, it is the intent to increase their curiosity as to the new knowledge that is emerging and to demonstrate that these seemingly complicated areas can be understood and appreciated with a modicum of the effort

  19. Molecular biology - Part II: Beneficial liaisons: Radiobiology meets cellular and molecular biology

    International Nuclear Information System (INIS)

    Stevenson, Mary Ann; Coleman, C. Norman

    1996-01-01

    Purpose: The purpose of this course is to familiarize radiation oncologists with the concepts and terminology of molecular and cellular biology that are especially relevant to radiation oncology. The ability of radiation oncologists to remain current with the new discoveries of modern biology is essential to the development of improved therapeutic strategies and, importantly, to the proper balance between investment in technology and biology. Objective: This year, this Refresher Course is part of a three-part 'series' including Drs. Martin Brown and Amato Giaccia. The objective is to provide continuing education for the academic and practicing radiation oncologist, physicist and biologist in the modern biologic concepts of cancer and its treatment. An effort will be made to relate these general concepts to the clinic by providing a broad view as to potential new biological treatments which might enhance the efficacy of radiation therapy. The specific focus of this Course will vary from year to year. Some of the classic radiation biology models which form the basis of clinical practice and laboratory research will be examined and 'newer' models will be presented which take into account the emerging knowledge of cellular and molecular biology. A few techniques in molecular and cellular biology will be described to the extent necessary to understand their basic concepts and their applicability. Aspects of radiation biology which will be covered include cell cycle, radiation-induced changes in the cellular phenotype, and considerations of the effect of the tumor microenvironment. It is not the expectation that the attendees will become experts in the particular subjects presented. Rather, it is the intent to increase their curiosity as to the new knowledge that is emerging and to demonstrate that these seemingly complicated areas can be understood and appreciated with a modicum of the effort

  20. Symposium on molecular and cellular mechanisms of mutagenesis

    International Nuclear Information System (INIS)

    1981-01-01

    These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents

  1. Symposium on molecular and cellular mechanisms of mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    1981-01-01

    These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents. (ERB)

  2. Cellular and molecular mechanisms of metformin: an overview

    Science.gov (United States)

    Viollet, Benoit; Guigas, Bruno; Sanz Garcia, Nieves; Leclerc, Jocelyne; Foretz, Marc; Andreelli, Fabrizio

    2012-01-01

    Considerable efforts have been made since the 1950s to better understand the cellular and molecular mechanisms of action of metformin, a potent antihyperglycemic agent now recommended as the first line oral therapy for type 2 diabetes (T2D). The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory-chain complex 1. In addition, the resulting decrease in hepatic energy status activates the AMP-activated protein kinase (AMPK), a cellular metabolic sensor, providing a generally accepted mechanism for metformin action on hepatic gluconeogenic program. The demonstration that the respiratory-chain complex 1, but not AMPK, is the primary target of metformin was recently strengthened by showing that the metabolic effect of the drug is preserved in liver-specific AMPK-deficient mice. Beyond its effect on glucose metabolism, metformin was reported to restore ovarian function in polycystic ovary syndrome, reduce fatty liver and to lower microvascular and macrovascular complications associated with T2D. Its use was also recently suggested as an adjuvant treatment for cancer or gestational diabetes, and for the prevention in pre-diabetic populations. These emerging new therapeutic areas for metformin will be reviewed together with recent data from pharmacogenetic studies linking genetic variations to drug response, a promising new step towards personalized medicine in the treatment of T2D. PMID:22117616

  3. Generative mechanistic explanation building in undergraduate molecular and cellular biology

    Science.gov (United States)

    Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

    2017-09-01

    When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among scientists, we created and applied a theoretical framework to explore the strategies students use to construct explanations for 'novel' biological phenomena. Specifically, we explored how students navigated the multi-level nature of complex biological systems using generative mechanistic reasoning. Interviews were conducted with introductory and upper-division biology students at a large public university in the United States. Results of qualitative coding revealed key features of students' explanation building. Students used modular thinking to consider the functional subdivisions of the system, which they 'filled in' to varying degrees with mechanistic elements. They also hypothesised the involvement of mechanistic entities and instantiated abstract schema to adapt their explanations to unfamiliar biological contexts. Finally, we explored the flexible thinking that students used to hypothesise the impact of mutations on multi-leveled biological systems. Results revealed a number of ways that students drew mechanistic connections between molecules, functional modules (sets of molecules with an emergent function), cells, tissues, organisms and populations.

  4. Molecular and cellular mechanisms of cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

    2003-01-01

    Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

  5. Generative Mechanistic Explanation Building in Undergraduate Molecular and Cellular Biology

    Science.gov (United States)

    Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

    2017-01-01

    When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among…

  6. [Fanconi anemia: cellular and molecular features].

    Science.gov (United States)

    Macé, G; Briot, D; Guervilly, J-H; Rosselli, F

    2007-02-01

    Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure. 11 among 12 FA gene have been isolated. The biochemical functions of the FANC proteins remain poorly understood. Anyhow, to cope with DNA crosslinks a cell needs a functional FANC pathway. Moreover, the FANC proteins appear to be involved in cell protection against oxidative damage and in the control of TNF-alpha activity. In this review, we describe the current understanding of the FANC pathway and we present how it may be integrated in the complex networks of proteins involved in maintaining the cellular homeostasis.

  7. Molecular events basic to cellular radiation response

    International Nuclear Information System (INIS)

    Kolodny, G.M.

    The initiation and control of the division process in normal cells is studied to gain insight into changes in these regards caused by x-irradiation and neoplasia. The Primer Hypothesis for eukaryotic gene regulation proposes that small molecular weight RNA acts as primer for new RNA synthesis by hybridizing with DNA and there initiating the transcription of a new RNA chain. The experiments reported here indicate that small molecular weight RNA will induce the production of new proteins. These results are consistent with the Primer Hypothesis, and demonstrate that RNA can be taken up from the media by cells in culture and can induce in vitro the production of differentiated cell products

  8. Cellular and Molecular Targets of Menthol Actions

    Directory of Open Access Journals (Sweden)

    Murat Oz

    2017-07-01

    Full Text Available Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions of menthol. There has been new evidence demonstrating that menthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at least some of the biological and pharmacological effects of menthol can be mediated by alterations in cellular excitability. In this article, we examine the results of earlier studies on the actions of menthol with voltage and ligand-gated ion channels.

  9. Cellular and molecular mechanisms coordinating pancreas development.

    Science.gov (United States)

    Bastidas-Ponce, Aimée; Scheibner, Katharina; Lickert, Heiko; Bakhti, Mostafa

    2017-08-15

    The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer. © 2017. Published by The Company of Biologists Ltd.

  10. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J.; Partridge, Nicola C.

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  11. Vasculogenesis and Angiogenesis: Molecular and Cellular Controls

    Science.gov (United States)

    Kubis, N.; Levy, B.I.

    2003-01-01

    Summary Angiogenesis characterizes embryonic development, but also occurs in adulthood in physiological situations such as adaptation to muscle exercise, and in pathological conditions like cancer. Major advances have been made in understanding the molecular mechanisms responsible for vasculogenesis and angiogenesis, largely due to the use of “knock-out mice”, i.e. mice in which the gene coding for the protein under investigation has been inactivated. Interestingly, the same growth factors and their receptors are equally involved in the different aspects of vasculogenesis and angiogenesis during development and in adulthood. This review aims to describe in detail their respective roles and how interactions between them lead to a newly formed vessel. PMID:20591248

  12. Time scale of diffusion in molecular and cellular biology

    International Nuclear Information System (INIS)

    Holcman, D; Schuss, Z

    2014-01-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function. (topical review)

  13. Time scale of diffusion in molecular and cellular biology

    Science.gov (United States)

    Holcman, D.; Schuss, Z.

    2014-05-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

  14. The extracellular matrix of plants: Molecular, cellular and developmental biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.

  15. Pathogenesis of pulmonary emphysema – cellular and molecular events

    Directory of Open Access Journals (Sweden)

    Antonio Di Petta

    2010-06-01

    Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  16. Molecular and cellular insights into Zika virus-related neuropathies.

    Science.gov (United States)

    Zhou, Kai; Wang, Long; Yu, Di; Huang, Hesuyuan; Ji, Hong; Mo, Xuming

    2017-06-01

    Zika virus (ZIKV), a relatively elusive Aedes mosquito-transmitted flavivirus, had been brought into spotlight until recent widespread outbreaks accompanied by unexpectedly severe clinical neuropathies, including fetal microcephaly and Guillain-Barré syndrome (GBS) in the adult. In this review, we focus on the underlying cellular and molecular mechanisms by which vertically transmitted microorganisms reach the fetus and trigger neuropathies.

  17. Variational cellular model of the molecular and crystal electronic structure

    International Nuclear Information System (INIS)

    Ferreira, L.G.; Leite, J.R.

    1977-12-01

    A variational version of the cellular method is developed to calculate the electronic structure of molecules and crystals. Due to the simplicity of the secular equation, the method is easy to be implemented. Preliminary calculations on the hydrogen molecular ion suggest that it is also accurate and of fast convergence [pt

  18. Cellular and molecular interaction in HIV infection: A review | Timbo ...

    African Journals Online (AJOL)

    Objective: To review the cellular and molecular interactions between HIV and the host immune system that lead to full-blown AIDS. Data Sources: Published reports on HIV/host interaction during a fifteen year period beginning from 1987. Study selection: Only those studies involving humans and non-human primates were ...

  19. A comparative cellular and molecular biology of longevity database.

    Science.gov (United States)

    Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

    2013-10-01

    Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

  20. The long Tramp from Cellular Pathology to Molecular Pathology

    Directory of Open Access Journals (Sweden)

    Hans Guski

    2017-05-01

    Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules might be responsible for changes that are visible ‘in larger elements’ (at cellular level.  The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

  1. Jahn-Teller effect in molecular electronics: quantum cellular automata

    Science.gov (United States)

    Tsukerblat, B.; Palii, A.; Clemente-Juan, J. M.; Coronado, E.

    2017-05-01

    The article summarizes the main results of application of the theory of the Jahn-Teller (JT) and pseudo JT effects to the description of molecular quantum dot cellular automata (QCA), a new paradigm of quantum computing. The following issues are discussed: 1) QCA as a new paradigm of quantum computing, principles and advantages; 2) molecular implementation of QCA; 3) role of the JT effect in charge trapping, encoding of binary information in the quantum cell and non-linear cell-cell response; 4) spin-switching in molecular QCA based on mixed-valence cell; 5) intervalence optical absorption in tetrameric molecular mixed-valence cell through the symmetry assisted approach to the multimode/multilevel JT and pseudo JT problems.

  2. Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

    Science.gov (United States)

    Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

    2016-06-01

    Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

  3. Molecular imaging: current status and emerging strategies

    International Nuclear Information System (INIS)

    Pysz, M.A.; Gambhir, S.S.; Willmann, J.K.

    2010-01-01

    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  4. Cellular and Molecular Pathways Leading to External Root Resorption

    Science.gov (United States)

    Iglesias-Linares, A.; Hartsfield, J.K.

    2016-01-01

    External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation. To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption. Recent mechanisms and developments reviewed here include the role of the cellular component—specifically, the balance of CD68+, iNOS+ M1- and CD68+, CD163+ M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I. Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed. Data on recently deciphered molecular pathways are reviewed at the level of (1) clastic cell adhesion in the external apical root resorption process and the specific role of α/β integrins, osteopontin, and related extracellular matrix proteins; (2) clastic cell fusion and activation by the RANKL/RANK/OPG and ATP-P2RX7-IL1 pathways; and (3) regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels. PMID:27811065

  5. Building bridges between cellular and molecular structural biology.

    Science.gov (United States)

    Patwardhan, Ardan; Brandt, Robert; Butcher, Sarah J; Collinson, Lucy; Gault, David; Grünewald, Kay; Hecksel, Corey; Huiskonen, Juha T; Iudin, Andrii; Jones, Martin L; Korir, Paul K; Koster, Abraham J; Lagerstedt, Ingvar; Lawson, Catherine L; Mastronarde, David; McCormick, Matthew; Parkinson, Helen; Rosenthal, Peter B; Saalfeld, Stephan; Saibil, Helen R; Sarntivijai, Sirarat; Solanes Valero, Irene; Subramaniam, Sriram; Swedlow, Jason R; Tudose, Ilinca; Winn, Martyn; Kleywegt, Gerard J

    2017-07-06

    The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two main priorities: the development of tools and file formats to support segmentation (that is, the decomposition of a three-dimensional volume into regions that can be associated with defined objects), and the development of tools to support the annotation of biological structures.

  6. Molecular genetic approaches to the study of cellular senescence.

    Science.gov (United States)

    Goletz, T J; Smith, J R; Pereira-Smith, O M

    1994-01-01

    Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Natural agents: cellular and molecular mechanisms of photoprotection.

    Science.gov (United States)

    Afaq, Farrukh

    2011-04-15

    The skin is the largest organ of the body that produces a flexible and self-repairing barrier and protects the body from most common potentially harmful physical, environmental, and biological insults. Solar ultraviolet (UV) radiation is one of the major environmental insults to the skin and causes multi-tiered cellular and molecular events eventually leading to skin cancer. The past decade has seen a surge in the incidence of skin cancer due to changes in life style patterns that have led to a significant increase in the amount of UV radiation that people receive. Reducing excessive exposure to UV radiation is desirable; nevertheless this approach is not easy to implement. Therefore, there is an urgent need to develop novel strategies to reduce the adverse biological effects of UV radiation on the skin. A wide variety of natural agents have been reported to possess substantial skin photoprotective effects. Numerous preclinical and clinical studies have elucidated that natural agents act by several cellular and molecular mechanisms to delay or prevent skin cancer. In this review article, we have summarized and discussed some of the selected natural agents for skin photoprotection. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Past, Present, and Future of Molecular and Cellular Oncology

    International Nuclear Information System (INIS)

    Galluzzi, Lorenzo; Vitale, Ilio; Kroemer, Guido

    2011-01-01

    In the last 20 years, the field of cellular and molecular oncology has been born and has moved its first steps, with an increasingly rapid pace. Hundreds of oncogenic and oncosuppressive signaling cascades have been characterized, facilitating the development of an ever more refined and variegated arsenal of diagnostic and therapeutic weapons. Furthermore, several cancer-specific features and processes have been identified that constitute promising therapeutic targets. For instance, it has been demonstrated that microRNAs can play a critical role in oncogenesis and tumor suppression. Moreover, it turned out that tumor cells frequently exhibit an extensive metabolic rewiring, can behave in a stem cell-like fashion (and hence sustain tumor growth), often constitutively activate stress response pathways that allow them to survive, can react to therapy by engaging in non-apoptotic cell death programs, and sometimes die while eliciting a tumor-specific immune response. In this Perspective article, we discuss the main issues generated by these discoveries that will be in the limelight of molecular and cellular oncology research for the next, hopefully few years.

  9. Past, present and future of molecular and cellular oncology

    Directory of Open Access Journals (Sweden)

    Lorenzo eGalluzzi

    2011-03-01

    Full Text Available In the last twenty years, the field of cellular and molecular oncology has been born and has moved its first steps, with an increasingly rapid pace. Hundreds of oncogenic and oncosuppressive signaling cascades have been characterized, facilitating the development of an ever more refined and variegated arsenal of diagnostic and therapeutic weapons. Furthermore, several cancer-specific features and processes have been identified that constitute promising therapeutic targets. For instance, it has been demonstrated that microRNAs can play a critical role in oncogenesis and tumor suppression. Moreover, it turned out that tumor cells frequently exhibit an extensive metabolic rewiring, can behave in a stem cell-like fashion (and hence sustain tumor growth, often constitutively activate stress response pathways that allow them to survive, can react to therapy by engaging in non-apoptotic cell death programs, and sometimes die while eliciting a tumor-specific immune response. In this Perspective article, we discuss the main issues generated by these discoveries that will be in the limelight of molecular and cellular oncology research for the next, hopefully few years.

  10. Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

    Science.gov (United States)

    Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

    2017-01-01

    Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

  11. Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities.

    Science.gov (United States)

    Gajarsa, Jason J; Kloner, Robert A

    2011-01-01

    As more patients survive myocardial infarctions, the incidence of heart failure increases. After an infarction, the human heart undergoes a series of structural changes, which are governed by cellular and molecular mechanisms in a pathological metamorphosis termed "remodeling." This review will discuss the current developments in our understanding of these molecular and cellular events in remodeling and the various pharmacological, cellular and device therapies used to treat, and potentially retard, this condition. Specifically, this paper will examine the neurohormonal activity of the renin-angiotensin-aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets. Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed. Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future.

  12. Opioid Epidemic: Cellular & Molecular Anesthesia as a Key Solution

    Directory of Open Access Journals (Sweden)

    Ali Dabbagh

    2017-12-01

    Full Text Available Opioids are one of the most important arsenals armamentarium of physicians for fighting against pain. During the decades, opioids have been used in a wide range of indications; both for treatment of acute and chronic pain; as natural and synthetic compounds and in a variety of delivery forms from intravenous infusion to intrathecal adjuvants of local anesthetics or as transdermal patches. There is no doubt that we are in an opioid misuse epidemic status; whether in the US or other countries; but if we want to resolve this miserable multilateral complication, there is no doubt that Cellular and Molecular aspects of Anesthesia has a key role in resolving the problem; through creating an opioid free pain management era.

  13. Molecular bases of cellular senescence: Hayflick phenomenon 50 years later

    Directory of Open Access Journals (Sweden)

    Patrycja Sosińska

    2016-03-01

    Full Text Available Normal human somatic cells have strictly limited proliferative capacity and reach a state of senescence when it becomes exhausted. It is believed that senescence is a response to extensive and irreparable DNA injury, localized in telomeric and/or non-telomeric regions of the genome. Main cause of this damage is oxidative stress, increasing due to deteriorated function of mitochondria. Senescent cells accumulate in tissues during aging, which is causatively linked with the development of various pathologies in elderly individuals, including cancer. This paper, prepared exactly 50 years after Leonard Hayflick’s discovery of the relationship between cellular senescence and organismal aging is aimed at presenting the current knowledge about molecular determinants of senescence, with particular emphasis paid to the role of oxidative stress, effectors of senescence at the level of cell cycle, markers of this phenomenon, and the effect of senescent cells on the development of certain age-related diseases.

  14. Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

    Science.gov (United States)

    Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

    2016-04-01

    Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes

  15. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms.

    Science.gov (United States)

    Stenmark, Kurt R; Fagan, Karen A; Frid, Maria G

    2006-09-29

    Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.

  16. Molecular biophysics: detection and characterization of damage in molecular, cellular, and physiological systems

    International Nuclear Information System (INIS)

    Danyluk, S.S.

    1979-01-01

    This section contains summaries of research on the detection and characterization of damage in molecular, cellular, and physiological systems. Projects under investigation in this section include: chemical synthesis of nucleic acid derivatives; structural and conformational properties of biological molecules in solution; crystallographic and chemical studies of immunoglobulin structure; instrument design and development for x-ray and neutron scattering studies of biological molecules; and chromobiology and circadian regulation

  17. The Use of Cellular Automata in the Learning of Emergence

    Science.gov (United States)

    Faraco, G.; Pantano, P.; Servidio, R.

    2006-01-01

    In recent years, research efforts on complex systems have contributed to improve our ability in investigating, at different levels of complexity, the emergent behaviour shown by a system in the course of its evolution. The study of emergence, an intrinsic property of a large number of complex systems, can be tackled by making use of Cellular…

  18. Unraveling the cellular and molecular mechanisms of repetitive magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Florian eMüller-Dahlhaus

    2013-12-01

    Full Text Available Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neural plasticity is required to optimize current treatment protocols. Studies in small animals or appropriate in vitro preparations (including models of brain diseases provide highly useful experimental approaches in this context. State-of-the-art electrophysiological and live-cell imaging techniques that are well established in basic neuroscience can help answering some of the major questions in the field, such as (i which neural structures are activated during TMS, (ii how does rTMS induce Hebbian plasticity, and (iii are other forms of plasticity (e.g., metaplasticity, structural plasticity induced by rTMS? We argue that data gained from these studies will support the development of more effective and specific applications of rTMS in clinical practice.

  19. Lipoprotein(a: Cellular Effects and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Kirsten Riches

    2012-01-01

    Full Text Available Lipoprotein(a (Lp(a is an independent risk factor for the development of cardiovascular disease (CVD. Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a apart from plasma apheresis, which is costly and labour intensive. The Lp(a molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a (apo(a, both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC and endothelial cells (EC. Therefore, it is of key importance to determine the molecular pathways by which Lp(a exerts its influence on the vascular system in order to design therapeutics to target its cellular effects. This paper will summarise the role of Lp(a in modulating cell behaviour in all aspects of the vascular system including platelets, monocytes, SMC, and EC.

  20. Cellular and molecular mechanisms of alcohol-induced osteopenia.

    Science.gov (United States)

    Luo, Zhenhua; Liu, Yao; Liu, Yitong; Chen, Hui; Shi, Songtao; Liu, Yi

    2017-12-01

    Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.

  1. Doctoral conceptual thresholds in cellular and molecular biology

    Science.gov (United States)

    Feldon, David F.; Rates, Christopher; Sun, Chongning

    2017-12-01

    In the biological sciences, very little is known about the mechanisms by which doctoral students acquire the skills they need to become independent scientists. In the postsecondary biology education literature, identification of specific skills and effective methods for helping students to acquire them are limited to undergraduate education. To establish a foundation from which to investigate the developmental trajectory of biologists' research skills, it is necessary to identify those skills which are integral to doctoral study and distinct from skills acquired earlier in students' educational pathways. In this context, the current study engages the framework of threshold concepts to identify candidate skills that are both obstacles and significant opportunities for developing proficiency in conducting research. Such threshold concepts are typically characterised as transformative, integrative, irreversible, and challenging. The results from interviews and focus groups with current and former doctoral students in cellular and molecular biology suggest two such threshold concepts relevant to their subfield: the first is an ability to effectively engage primary research literature from the biological sciences in a way that is critical without dismissing the value of its contributions. The second is the ability to conceptualise appropriate control conditions necessary to design and interpret the results of experiments in an efficient and effective manner for research in the biological sciences as a discipline. Implications for prioritising and sequencing graduate training experiences are discussed on the basis of the identified thresholds.

  2. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    Science.gov (United States)

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

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

  3. Cellular and molecular aspects of plant adaptation to microgravity

    Science.gov (United States)

    Kordyum, Elizabeth; Kozeko, Liudmyla

    2016-07-01

    Elucidation of the range and mechanisms of the biological effects of microgravity is one of the urgent fundamental tasks of space and gravitational biology. The absence of forbidding on plant growth and development in orbital flight allows studying different aspects of plant adaptation to this factor that is directly connected with development of the technologies of bioregenerative life-support systems. Microgravity belongs to the environmental factors which cause adaptive reactions at the cellular and molecular levels in the range of physiological responses in the framework of genetically determined program of ontogenesis. It is known that cells of a multicellular organism not only take part in reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and molecular levels in real and simulated microgravity is considered. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in the cell organelle functional load. The maintenance of the plasmalemma fluidity at the certain level, an activation of both the antioxidant system and expression of HSP genes, especially HSP70, under increasing reactive oxygen species, lipid peroxidation intensity and alteration in protein homeostasis, are a strategic paradigm of rapid (primary) cell adaptation to microgravity. In this sense, biological membranes, especially plasmalemma, and their properties and functions may be considered as the most sensitive indicators of the influence of gravity or altered gravity on a cell. The plasmalemma lipid bilayer is a border between the cell internal content and environment, so it is a mediator

  4. Molecular and cellular mechanisms of aldosterone producing adenoma development

    Directory of Open Access Journals (Sweden)

    Sheerazed eBoulkroun

    2015-06-01

    Full Text Available Primary aldosteronism (PA is the most common form of secondary hypertension with an estimated prevalence of ~10% in referred patients. PA occurs as a result of a dysregulation of the normal mechanisms controlling adrenal aldosterone production. It is characterized by hypertension with low plasma renin and elevated aldosterone and often associated with hypokalemia. The two major causes of PA are unilateral aldosterone producing adenoma (APA and bilateral adrenal hyperplasia, accounting together for ~95% of cases. In addition to the well-characterized effect of excess mineralocorticoids on blood pressure, high levels of aldosterone also have cardiovascular, renal and metabolic consequences. Hence, long-term consequences of PA include increased risk of coronary artery disease, myocardial infarction, heart failure and atrial fibrillation. Despite recent progress in the management of patients with PA, critical issues related to diagnosis, subtype differentiation and treatment of non-surgically correctable forms still persist. A better understanding of the pathogenic mechanisms of the disease should lead to the identification of more reliable diagnostic and prognostic biomarkers for a more sensitive and specific screening and new therapeutic options. In this review we will summarize our current knowledge on the molecular and cellular mechanisms of APA development. On one hand, we will discuss how various animal models have improved our understanding of the pathophysiology of excess aldosterone production. On the other hand, we will summarize the major advances made during the last few years in the genetics of APA due to transcriptomic studies and whole exome sequencing. The identification of recurrent and somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D and ATPases (ATP1A1 and ATP2B3 allowed highlighting the central role of calcium signaling in autonomous aldosterone production by the adrenal.

  5. Molecular quantum cellular automata cell design trade-offs: latching vs. power dissipation.

    Science.gov (United States)

    Rahimi, Ehsan; Reimers, Jeffrey R

    2018-06-20

    The use of molecules to enact quantum cellular automata (QCA) cells has been proposed as a new way for performing electronic logic operations at sub-nm dimensions. A key question that arises concerns whether chemical or physical processes are to be exploited. The use of chemical reactions allows the state of a switch element to be latched in molecular form, making the output of a cell independent of its inputs, but costs energy to do the reaction. Alternatively, if purely electronic polarization is manipulated then no internal latching occurs, but no power is dissipated provided the fields from the inputs change slowly compared to the molecular response times. How these scenarios pan out is discussed by considering calculated properties of the 1,4-diallylbutane cation, a species often used as a paradigm for molecular electronic switching. Utilized are results from different calculation approaches that depict the ion either as a charge-localized mixed-valence compound functioning as a bistable switch, or else as an extremely polarizable molecule with a delocalized electronic structure. Practical schemes for using molecular cells in QCA and other devices emerge.

  6. Molecular confocal laser endomicroscopy: a novel technique for in vivo cellular characterization of gastrointestinal lesions.

    Science.gov (United States)

    Karstensen, John Gásdal; Klausen, Pia Helene; Saftoiu, Adrian; Vilmann, Peter

    2014-06-28

    While flexible endoscopy is essential for macroscopic evaluation, confocal laser endomicroscopy (CLE) has recently emerged as an endoscopic method enabling visualization at a cellular level. Two systems are currently available, one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound. The second system has a confocal microscope integrated into the distal part of an endoscope. By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure (either topically or systemically administered during on-going endoscopy), a novel world of molecular evaluation opens up. The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas, subsequently resulting in immediate individualization of treatment regimens, but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions. Furthermore, studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ, which probably can be correlated to the efficacy of the drug. However, several of the studies in this research field have been conducted in animal facilities or in vitro, while only a limited number of trials have actually been carried out in vivo. Therefore, safety issues still needs further evaluations. This review will present an overview of the implications and pitfalls, as well as future challenges of molecular CLE in gastrointestinal diseases.

  7. Bridging the gap: linking molecular simulations and systemic descriptions of cellular compartments.

    Directory of Open Access Journals (Sweden)

    Tihamér Geyer

    Full Text Available Metabolic processes in biological cells are commonly either characterized at the level of individual enzymes and metabolites or at the network level. Often these two paradigms are considered as mutually exclusive because concepts from neither side are suited to describe the complete range of scales. Additionally, when modeling metabolic or regulatory cellular systems, often a large fraction of the required kinetic parameters are unknown. This even applies to such simple and extensively studied systems like the photosynthetic apparatus of purple bacteria. Using the chromatophore vesicles of Rhodobacter sphaeroides as a model system, we show that a consistent kinetic model emerges when fitting the dynamics of a molecular stochastic simulation to a set of time dependent experiments even though about two thirds of the kinetic parameters in this system are not known from experiment. Those kinetic parameters that were previously known all came out in the expected range. The simulation model was built from independent protein units composed of elementary reactions processing single metabolites. This pools-and-proteins approach naturally compiles the wealth of available molecular biological data into a systemic model and can easily be extended to describe other systems by adding new protein or nucleic acid types. The automated parameter optimization, performed with an evolutionary algorithm, reveals the sensitivity of the model to the value of each parameter and the relative importances of the experiments used. Such an analysis identifies the crucial system parameters and guides the setup of new experiments that would add most knowledge for a systemic understanding of cellular compartments. The successful combination of the molecular model and the systemic parametrization presented here on the example of the simple machinery for bacterial photosynthesis shows that it is actually possible to combine molecular and systemic modeling. This framework can now

  8. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

    NARCIS (Netherlands)

    Denning, Denise; Roos, Wouter H

    2016-01-01

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

  9. Nonequilibrium emergent phenomena in organic molecular solids

    Energy Technology Data Exchange (ETDEWEB)

    Mitrano, Matteo

    2015-07-15

    The manipulation of matter with ultrashort laser pulses is a relevant research field from both a fundamental and an applied perspective, owing to the efficient coupling to the electronic degrees of freedom on femtosecond timescales and the ability to induce transient phases that cannot be realized in equilibrium scenarios. Strongly correlated materials are a natural environment for the observation of such novel and emergent out-of-equilibrium physics because small modifications to the electron-electron interactions can induce transitions between remarkably different macroscopic phases. One of the most effective means of modifying the effective electron-electron interactions is to perturb the crystal structure through pressure, strain or even light. However, it remains largely unexplored how perturbing the structural degrees of freedom affects the electron dynamics of the transiently driven states and how the interplay of correlations and electron-lattice interactions determine the intrinsic timescales of these nonequilibrium states. This thesis investigates how to control the light-induced nonequilibrium electronic properties in strongly correlated organics, that are highly tunable with moderate variations of external parameters, by perturbing their structural degrees of freedom, either via static pressures or vibrational excitation. We study the role of correlations in determining the relaxation rate of holes (holons) and double occupancies (doublons) in a solid state Mott insulator, the ET-F{sub 2}TCNQ, driven across a transient insulator-to-metal transition. By mapping holon-doublon lifetimes onto the ground-state electronic interactions, we found that the decay rate of the photoinjected quasiparticles depends on the degree of correlation between carriers and is affected by the presence of a competition between local recombination and delocalization of holon-doublon pairs. By optically controlling the effective correlations in organic molecular crystals through

  10. 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

  11. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    Science.gov (United States)

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

  12. Introduction to the cellular and molecular biology of cancer

    National Research Council Canada - National Science Library

    Selby, P. (Peter); Knowles, Margaret A

    2005-01-01

    ... A. Prigent 186xii CONTENTS 12 Apoptosis: molecular physiology and significance for cancer therapeutics Dean A. Fennell 210 13 Mechanisms of viral carcinogenesis Paul Farrell 229 14 Cytokines and canc...

  13. Cellular Viscosity in Prokaryotes and Thermal Stability of Low Molecular Weight Biomolecules.

    Science.gov (United States)

    Cuecas, Alba; Cruces, Jorge; Galisteo-López, Juan F; Peng, Xiaojun; Gonzalez, Juan M

    2016-08-23

    Some low molecular weight biomolecules, i.e., NAD(P)H, are unstable at high temperatures. The use of these biomolecules by thermophilic microorganisms has been scarcely analyzed. Herein, NADH stability has been studied at different temperatures and viscosities. NADH decay increased at increasing temperatures. At increasing viscosities, NADH decay rates decreased. Thus, maintaining relatively high cellular viscosity in cells could result in increased stability of low molecular weight biomolecules (i.e., NADH) at high temperatures, unlike what was previously deduced from studies in diluted water solutions. Cellular viscosity was determined using a fluorescent molecular rotor in various prokaryotes covering the range from 10 to 100°C. Some mesophiles showed the capability of changing cellular viscosity depending on growth temperature. Thermophiles and extreme thermophiles presented a relatively high cellular viscosity, suggesting this strategy as a reasonable mechanism to thrive under these high temperatures. Results substantiate the capability of thermophiles and extreme thermophiles (growth range 50-80°C) to stabilize and use generally considered unstable, universal low molecular weight biomolecules. In addition, this study represents a first report, to our knowledge, on cellular viscosity measurements in prokaryotes and it shows the dependency of prokaryotic cellular viscosity on species and growth temperature. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Lifesavers and Samaritans: emergency use of cellular (mobile) phones in Australia.

    Science.gov (United States)

    Chapman, S; Schofield, W N

    1998-11-01

    There has been highly publicised concern about possible radiation health effects from mobile phones and towers, but scant attention has been paid to the use of mobile phones in reducing notification times in emergencies. National random telephone survey of Australian mobile phone users (n = 720) and extrapolation to national user population (n = 5.1 million). Using a cellular phone, 1 in 8 users have reported a traffic accident; 1 in 4 a dangerous situation; 1 in 16 a non-road medical emergency; 1 in 20 a crime; and 1 in 45 being lost in the bush or being in difficulty at sea. Any debate about the net health impact of mobile phone proliferation must balance possible negative effects (cancer, driving incidents) with the benefits from what appears to be their widespread use in rapidly reporting emergencies and in numerous acts of often health-relevant 'cellular Samaritanism'.

  15. Cellular and molecular mechanisms of HIV-1 integration targeting.

    Science.gov (United States)

    Engelman, Alan N; Singh, Parmit K

    2018-07-01

    Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine-tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.

  16. Effects of ionizing radiation and the molecular and cellular mechanisms

    International Nuclear Information System (INIS)

    1982-01-01

    This symposium with its 60 contributions presents a survey of the current state of the art in molecular radiation biophysics and radiobiology in the FRG. Many contributions show the trend of applying findings in these fields to cancer research. The various sessions have been devoted to: 1) Radiation chemistry of biomolecules; 2) DNA damage and repair; 3) Repair of DNA damage; 4) Cell proliferation and cell inactivation; 5) Cancerogenesis, mutation and chromosomal damage; 6) Effects of heavy ions. (AJ) [de

  17. Cellular and molecular specificity of pituitary gland physiology.

    Science.gov (United States)

    Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

    2012-01-01

    The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

  18. Recent advances in the Laboratory of Molecular and Cellular Cardiology.

    Science.gov (United States)

    Breitbart, R E; London, B; Nguyen, H T; Satler, C A

    1995-12-01

    This article highlights some of the research in cardiac molecular biology in progress in the Department of Cardiology at Children's Hospital. It provides a sampling of investigative approaches to key questions in cardiovascular development and function and, as such, is intended as an overview rather than a comprehensive treatment of these problems. The featured projects, encompassing four different "model" systems, include (1) genetic analysis of the mef2 gene required for fruit fly cardial cell differentiation, (2) cardiac-specific homeobox factors in zebrafish cardiovascular development, (3) mouse transgenic and gene knockout models of cardiac potassium ion channel function, and (4) mapping and identification of human gene mutations causing long QT syndrome.

  19. 2012 Gordon Research Conference on Cellular and Molecular Fungal Biology, Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Judith [Univ. of Minnesota, Minneapolis, MN (United States)

    2012-06-22

    The Gordon Research Conference on Cellular and Molecular Fungal Biology was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genome organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.

  20. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  1. Molecular and Cellular Mechanisms of Shigella flexneri Dissemination.

    Science.gov (United States)

    Agaisse, Hervé

    2016-01-01

    The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery in humans. The disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. Here, we review the mechanisms supporting S. flexneri dissemination. The dissemination process primarily relies on actin assembly at the bacterial pole, which propels the pathogen throughout the cytosol of primary infected cells. Polar actin assembly is supported by polar expression of the bacterial autotransporter family member IcsA, which recruits the N-WASP/ARP2/3 actin assembly machinery. As motile bacteria encounter cell-cell contacts, they form plasma membrane protrusions that project into adjacent cells. In addition to the ARP2/3-dependent actin assembly machinery, protrusion formation relies on formins and myosins. The resolution of protrusions into vacuoles occurs through the collapse of the protrusion neck, leading to the formation of an intermediate membrane-bound compartment termed vacuole-like protrusions (VLPs). VLP formation requires tyrosine kinase and phosphoinositide signaling in protrusions, which relies on the integrity of the bacterial type 3 secretion system (T3SS). The T3SS is also required for escaping double membrane vacuoles through the activity of the T3SS translocases IpaB and IpaC, and the effector proteins VirA and IcsB. Numerous factors supporting envelope biogenesis contribute to IcsA exposure and maintenance at the bacterial pole, including LPS synthesis, membrane proteases, and periplasmic chaperones. Although less characterized, the assembly and function of the T3SS in the context of bacterial dissemination also relies on factors supporting envelope biogenesis. Finally, the dissemination process requires the adaptation of the pathogen to various cellular compartments through transcriptional and post-transcriptional mechanisms.

  2. Molecular events basic to cellular radiation response. Progress report

    International Nuclear Information System (INIS)

    Kolodny, G.M.

    1974-01-01

    Work during the past year has been focused on three areas related to the cellular effects of radiation. Radiation effects on RNA and the regulation of gene expression and amino acid-nucleic acid interactions were studied. Studies on the radiation response of RNA in growing and confluent cells were continued. We have derived radiation survival curves and demonstrated repair of potentially lethal damage in 3T3 cells. Studies of giant cell formation and turnover of ribosomal RNA in irradiated cells has demonstrated differences in growing and confluent cells. We have sought evidence consistent with our hypothesis for regulation of eukaryotic gene expression with segments of RNA reutilized to prime new RNA synthesis. Data derived from the turnover of ribosomal RNA and the methylation pattern of ribosomal RNA during turnover are consistent with the possibility that a segment of 18s ribosomal RNA is being conserved during new RNA synthesis. We were unable to show reutilization of the 5' trinucleotide of 18s and 28s ribosomal RNA but did find a ribonuclease resistant oligonucleotide in 18s RNA which appeared to be reutilized. In studies of amino acid nucleic-acid interactions using nuclear magnetic resonance spectroscopy we have been able to successfully synthesize an amidate and begin an examination of the intramolecular interactions. We have also studied intermolecular interactions betweentryptophan and nucleoside monophosphates and found upfield shifts which provide evidence for preferential stacking of the 6-membered ring of tryptophan with adenine and evidence for specific geometry of interactions of tryptophan with cytosine. (U.S.)

  3. Molecular and Cellular mechanisms of Shigella flexneri dissemination

    Directory of Open Access Journals (Sweden)

    Herve eAgaisse

    2016-03-01

    Full Text Available The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery in humans. The disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. Here, we review the mechanisms supporting S. flexneri dissemination. The dissemination process primarily relies on actin assembly at the bacterial pole, which propels the pathogen throughout the cytosol of primary infected cells. Polar actin assembly is supported by polar expression of the bacterial autotransporter family member IcsA, which recruits the N-WASP/ARP2/3 actin assembly machinery. As motile bacteria encounter cell-cell contacts, they form plasma membrane protrusions that project into adjacent cells. In addition to the ARP2/3-dependent actin assembly machinery, protrusion formation relies on formins and myosins. The resolution of protrusions into vacuoles occurs through the collapse of the protrusion neck, leading to the formation of an intermediate membrane-bound compartment termed vacuole-like protrusions (VLPs. VLP formation requires tyrosine kinase and phosphoinositide signaling in protrusions, which relies on the integrity of the bacterial type 3 secretion system (T3SS. The T3SS is also required for escaping double membrane vacuoles through the activity of the T3SS translocases IpaB and IpaC, and the effector proteins VirA and IcsB. Numerous factors supporting envelope biogenesis contribute to IcsA exposure and maintenance at the bacterial pole, including LPS synthesis, membrane proteases, and periplasmic chaperones. Although less characterized, the assembly and function of the T3SS in the context of bacterial dissemination also relies on factors supporting envelope biogenesis. Finally, the dissemination process requires the adaptation of the pathogen to various cellular compartments through transcriptional and post

  4. Echinococcus-Host Interactions at Cellular and Molecular Levels.

    Science.gov (United States)

    Brehm, K; Koziol, U

    2017-01-01

    The potentially lethal zoonotic diseases alveolar and cystic echinococcosis are caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively. In both cases, metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular host-parasite interactions that regulate nutrient uptake by the parasite as well as metacestode persistence and development. Using in vitro cultivation systems for parasite larvae, and informed by recently released, comprehensive genome and transcriptome data for both parasites, these molecular host-parasite interactions have been subject to significant research during recent years. In this review, we discuss progress in this field, with emphasis on parasite development and proliferation. We review host-parasite interaction mechanisms that occur early during an infection, when the invading oncosphere stage undergoes a metamorphosis towards the metacestode, and outline the decisive role of parasite stem cells during this process. We also discuss special features of metacestode morphology, and how this parasite stage takes up nutrients from the host, utilizing newly evolved or expanded gene families. We comprehensively review mechanisms of host-parasite cross-communication via evolutionarily conserved signalling systems and how the parasite signalling systems might be exploited for the development of novel chemotherapeutics. Finally, we point to an urgent need for the development of functional genomic techniques in this parasite, which will be imperative for hypothesis-driven analyses into Echinococcus stem cell biology, developmental mechanisms and immunomodulatory activities, which are all highly relevant for the development of anti-infective measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible.

    Science.gov (United States)

    Scafidi, Joseph; Ritter, Jonathan; Talbot, Brooke M; Edwards, Jorge; Chew, Li-Jin; Gallo, Vittorio

    2018-04-15

    Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention. Mice at different postnatal ages received short courses of molecularly targeted drugs in regimens analagous to clinical treatment. Analysis of rapidly developing brain structures important for sensorimotor and cognitive function showed that, while adult administration was without effect, earlier neonatal administration of targeted therapies attenuated white matter oligodendroglia and hippocampal neuronal development more profoundly than later administration, leading to long-lasting behavioral deficits. This functional impairment was reversed by rehabilitation with physical and cognitive enrichment. Our findings demonstrate age-dependent, reversible effects of these drugs on brain development, which are important considerations as treatment options expand for pediatric cancers. Significance: Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment. Cancer Res; 78(8); 2081-95. ©2018 AACR . ©2018 American Association for Cancer Research.

  6. The roles of cellular and molecular components of a hematoma at early stage of bone healing.

    Science.gov (United States)

    Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay

    2018-04-01

    Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Cellular and molecular pathology of HTS: basis for treatment.

    Science.gov (United States)

    Armour, Alexis; Scott, Paul G; Tredget, Edward E

    2007-01-01

    Hypertrophic scar and keloids are fibroproliferative disorders of the skin which occur often unpredictably, following trauma and inflammation that compromise cosmesis and function and commonly recur following surgical attempts for improvement. Despite decades of research in these fibrotic conditions, current non-surgical methods of treatment are slow, inconvenient and often only partially effective. Fibroblasts from these conditions are activated to produce extracellular matrix proteins such as collagen I and III, proteoglycans such as versican and biglycan and growth factors, including transforming growth factor-beta and insulin like growth factor I. However, more consistently these cells produce less remodeling enzymes including collagenase and other matrix metalloproteinases, as well as the small proteoglycan decorin which is important for normal collagen fibrillogenesis. Recently, the systemic response to injury appears to influence the local healing process whereby increases in Th2 and possibly Th3 cytokines such as IL-2, IL-4 and IL-10 and TGF-beta are present in the circulating lymphocytes in these fibrotic conditions. Finally, unique bone marrow derived cells including mesenchymal and endothelial stem cells as well as fibrocytes appear to traffic into healing wounds and influence the healing tissue. On this background, clinicians are faced with patients who require treatment and the pathophysiologic basis as currently understood is reviewed for a number of emerging modalities.

  8. Testosterone deficiency syndrome: cellular and molecular mechanism of action.

    Science.gov (United States)

    Carruthers, Malcolm

    2013-02-01

    There is virtually no correlation between what are generally accepted to be the symptoms of deficient androgen in men and levels of androgens as measured in the laboratory. Now that androgen deficiency is being shown to play a part in conditions as diverse as metabolic syndrome, diabetes, and coronary heart disease, a hypothesis is needed to explain this apparent discrepancy between measured androgen levels and our understanding of the symptoms of androgen deficiency. When the possible mechanisms for androgen actions are considered, one explanation emerges that androgen may act much like insulin in persons with type 2 diabetes mellitus: the degree of androgen resistance may be variable depending on the organs or systems considered. Therefore, the symptoms can result from altered or damaged synthesis of androgen synthesis or regulation, elevated androgen binding, a reduction in tissue response, or decreased as a result of polymorphism and aging. Genomic transcription and translation may also be affected. As with diabetes, in adult male androgen deficiency, it is suggested that the definition of androgen deficiency should be based on individual physiology, with the requirements of the individual at a particular stage of life setting the baseline against which any deficiency of androgens or androgen metabolites, either absolute or relative, is determined. This approach will affect the terminology, etiology, diagnosis, and treatment of androgen deficiency.

  9. Cellular and molecular aspects of quinoa leaf senescence.

    Science.gov (United States)

    López-Fernández, María Paula; Burrieza, Hernán Pablo; Rizzo, Axel Joel; Martínez-Tosar, Leandro Julián; Maldonado, Sara

    2015-09-01

    During leaf senescence, degradation of chloroplasts precede to changes in nuclei and other cytoplasmic organelles, RuBisCO stability is progressively lost, grana lose their structure, plastidial DNA becomes distorted and degraded, the number of plastoglobuli increases and abundant senescence-associated vesicles containing electronically dense particles emerge from chloroplasts pouring their content into the central vacuole. This study examines quinoa leaf tissues during development and senescence using a range of well-established markers of programmed cell death (PCD), including: morphological changes in nuclei and chloroplasts, degradation of RuBisCO, changes in chlorophyll content, DNA degradation, variations in ploidy levels, and changes in nuclease profiles. TUNEL reaction and DNA electrophoresis demonstrated that DNA fragmentation in nuclei occurs at early senescence, which correlates with induction of specific nucleases. During senescence, metabolic activity is high and nuclei endoreduplicate, peaking at 4C. At this time, TEM images showed some healthy nuclei with condensed chromatin and nucleoli. We have found that DNA fragmentation, induction of senescence-associated nucleases and endoreduplication take place during leaf senescence. This provides a starting point for further research aiming to identify key genes involved in the senescence of quinoa leaves. Published by Elsevier Ireland Ltd.

  10. The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant talpid2

    Science.gov (United States)

    talpid2 is an avian autosomal recessive mutant with a myriad of congenital malformations, including polydactyly and facial clefting. Although phenotypically similar to talpid3, talpid2 has a distinct facial phenotype and an unknown cellular, molecular and genetic basis. We set out to determine the e...

  11. Coordinating Center: Molecular and Cellular Findings of Screen-Detected Lesions | Division of Cancer Prevention

    Science.gov (United States)

    The Molecular and Cellular Characterization of Screen‐Detected Lesions ‐ Coordinating Center and Data Management Group will provide support for the participating studies responding to RFA CA14‐10. The coordinating center supports three main domains: network coordination, statistical support and computational analysis and protocol development and database support. Support for

  12. Centre for Cellular and Molecular Biology to breed vultures for Parsis

    African Journals Online (AJOL)

    Hyderabad – Parsis worried about the growing pile of bodies in their 'Towers of Silence' can take heart. The Centre for Cellular and Molecular Biology. (CCMB) has decided to take up, on an express basis, the job of breeding vultures, which can later be transported to various parts of the country. Though the problem of ...

  13. The Need for Novel Informatics Tools for Integrating and Planning Research in Molecular and Cellular Cognition

    Science.gov (United States)

    Silva, Alcino J.; Müller, Klaus-Robert

    2015-01-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other…

  14. The induction and regulation of radiogenic transformation in vitro: Cellular and molecular mechanisms

    International Nuclear Information System (INIS)

    Borek, C.

    1987-01-01

    Rodent and human cells in culture, transformed in vitro by ionizing radiation, ultraviolet light, or chemicals into malignant cells afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions must prevail. Permissive factors include thyroid and steroid hormones, specific states of differentiation, certain stages in the cell cycle, specific genetic impairment, and inadequate antioxidants. Genetically susceptible cells require physiological states conducive to transformation. These may differ with age, tissue, and species and in part may be responsible for the observed lower sensitivity of human cells to transformation

  15. The emergence of complex behaviours in molecular magnetic materials.

    Science.gov (United States)

    Goss, Karin; Gatteschi, Dante; Bogani, Lapo

    2014-09-14

    Molecular magnetism is considered an area where magnetic phenomena that are usually difficult to demonstrate can emerge with particular clarity. Over the years, however, less understandable systems have appeared in the literature of molecular magnetic materials, in some cases showing features that hint at the spontaneous emergence of global structures out of local interactions. This ingredient is typical of a wider class of problems, called complex behaviours, where the theory of complexity is currently being developed. In this perspective we wish to focus our attention on these systems and the underlying problematic that they highlight. We particularly highlight the emergence of the signatures of complexity in several molecular magnetic systems, which may provide unexplored opportunities for physical and chemical investigations.

  16. Marine molecular biology: an emerging field of biological sciences.

    Science.gov (United States)

    Thakur, Narsinh L; Jain, Roopesh; Natalio, Filipe; Hamer, Bojan; Thakur, Archana N; Müller, Werner E G

    2008-01-01

    An appreciation of the potential applications of molecular biology is of growing importance in many areas of life sciences, including marine biology. During the past two decades, the development of sophisticated molecular technologies and instruments for biomedical research has resulted in significant advances in the biological sciences. However, the value of molecular techniques for addressing problems in marine biology has only recently begun to be cherished. It has been proven that the exploitation of molecular biological techniques will allow difficult research questions about marine organisms and ocean processes to be addressed. Marine molecular biology is a discipline, which strives to define and solve the problems regarding the sustainable exploration of marine life for human health and welfare, through the cooperation between scientists working in marine biology, molecular biology, microbiology and chemistry disciplines. Several success stories of the applications of molecular techniques in the field of marine biology are guiding further research in this area. In this review different molecular techniques are discussed, which have application in marine microbiology, marine invertebrate biology, marine ecology, marine natural products, material sciences, fisheries, conservation and bio-invasion etc. In summary, if marine biologists and molecular biologists continue to work towards strong partnership during the next decade and recognize intellectual and technological advantages and benefits of such partnership, an exciting new frontier of marine molecular biology will emerge in the future.

  17. Systematic Molecular Phenotyping: A Path Towards Precision Emergency Medicine?

    Science.gov (United States)

    Limkakeng, Alexander T.; Monte, Andrew; Kabrhel, Christopher; Puskarich, Michael; Heitsch, Laura; Tsalik, Ephraim L.; Shapiro, Nathan I.

    2016-01-01

    Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department. While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the emergency department will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end users. PMID:27288269

  18. Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine?

    Science.gov (United States)

    Limkakeng, Alexander T; Monte, Andrew A; Kabrhel, Christopher; Puskarich, Michael; Heitsch, Laura; Tsalik, Ephraim L; Shapiro, Nathan I

    2016-10-01

    Precision medicine is an emerging approach to disease treatment and prevention that considers variability in patient genes, environment, and lifestyle. However, little has been written about how such research impacts emergency care. Recent advances in analytical techniques have made it possible to characterize patients in a more comprehensive and sophisticated fashion at the molecular level, promising highly individualized diagnosis and treatment. Among these techniques are various systematic molecular phenotyping analyses (e.g., genomics, transcriptomics, proteomics, and metabolomics). Although a number of emergency physicians use such techniques in their research, widespread discussion of these approaches has been lacking in the emergency care literature and many emergency physicians may be unfamiliar with them. In this article, we briefly review the underpinnings of such studies, note how they already impact acute care, discuss areas in which they might soon be applied, and identify challenges in translation to the emergency department (ED). While such techniques hold much promise, it is unclear whether the obstacles to translating their findings to the ED will be overcome in the near future. Such obstacles include validation, cost, turnaround time, user interface, decision support, standardization, and adoption by end-users. © 2016 by the Society for Academic Emergency Medicine.

  19. Re-emergence of Chikungunya in India: Molecular studies

    Indian Academy of Sciences (India)

    Re-emergence of Chikungunya in India: Molecular studies · PowerPoint Presentation · CHIKUNGUNYA virus · Slide 4 · Slide 5 · CHIKV Genotypes · Slide 7 · In view of long absence of CHIK epidemics, it was postulated that CHIK virus has disappeared from India and South-East Asia. Serological surveys supported this view.

  20. Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.

    Science.gov (United States)

    Gao, Chao; Zhang, Long; Zhang, Ye; Wallace, Darren P; Lopez-Soler, Reynold I; Higgins, Paul J; Zhang, Wenzheng

    2017-11-01

    Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder, and/or urethra. Because of its prevalence, frequent recurrence, and rising resistance to antibiotics, UTI has become a challenge in clinical practice. Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder of the kidney and is characterized by the growth of fluid-filled cysts in both kidneys. Progressive cystic enlargement, inflammation, and interstitial fibrosis result in nephron loss with subsequent decline in kidney function. ADPKD patients frequently develop UTI; however, the cellular and molecular mechanisms responsible for the high UTI incidence in ADPKD patients remain virtually unaddressed. Emerging evidence suggests that α-intercalated cells (α-ICs) of the collecting ducts function in the innate immune defense against UTI. α-ICs inhibit bacterial growth by acidifying urine and secreting neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron. It is necessary to determine, therefore, if ADPKD patients with recurrent UTI have a reduced number and/or impaired function of α-ICs. Identification of the underlying cellular and molecular mechanisms may lead to the development of novel strategies to reduce UTI in ADPKD. Copyright © 2017 the American Physiological Society.

  1. Cellular and molecular mechanisms in malignant transformation of diploid rodent and human cells by radiation

    International Nuclear Information System (INIS)

    Borek, C.

    1985-01-01

    The development of cell culture systems has made it possible to probe into the effects of radiation at a cellular and molecular level, under defined conditions where homeostatic mechanisms do not prevail. Using in vitro systems free of host-medicated influences, one can assess qualitatively and quantitatively dose-related and time-dependent interactions of radiation with single cells and to evaluate the influences of agents that may enhance or inhibit the oncogenic potential of radiation. These systems are useful in pragmatic studies where dose response relationships and cancer risk estimates are assessed with particular focus on the low dose range of radiation where epidemiological and animal studies are limiting. The in vitro systems serve well also in mechanistic studies where cellular and molecular processes underlying transformation can be elucidated and where the role of modulating factors which determine the frequency and quality of these events can be investigated

  2. Ciona intestinalis notochord as a new model to investigate the cellular and molecular mechanisms of tubulogenesis.

    Science.gov (United States)

    Denker, Elsa; Jiang, Di

    2012-05-01

    Biological tubes are a prevalent structural design across living organisms. They provide essential functions during the development and adult life of an organism. Increasing progress has been made recently in delineating the cellular and molecular mechanisms underlying tubulogenesis. This review aims to introduce ascidian notochord morphogenesis as an interesting model system to study the cell biology of tube formation, to a wider cell and developmental biology community. We present fundamental morphological and cellular events involved in notochord morphogenesis, compare and contrast them with other more established tubulogenesis model systems, and point out some unique features, including bipolarity of the notochord cells, and using cell shape changes and cell rearrangement to connect lumens. We highlight some initial findings in the molecular mechanisms of notochord morphogenesis. Based on these findings, we present intriguing problems and put forth hypotheses that can be addressed in future studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Molecular device computer: point of departure for large scale cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Carter, F L

    1984-01-01

    Switching is possible at the molecular size level because of the conformational changes that occur. Three of the most promising switching mechanisms include electron tunnelling in short periodic arrays, soliton switching and soliton valving. Assuming a 3-d architecture and molecular dimensions, memory and switching elements with densities of 10/sup 15/ to 10 /sup 18/ elements per cc are possible. The active elements are connected together conceptionally with molecular wires like polysulfur nitride (sn)/sub x/ and polyacetylene (ch)/sub x/. Simple cellular automata involving soliton propagation in conjugated systems would include soliton valves and cyclic configurations of valves. In the latter, soliton propagation becomes isomorphous with group operations giving rise to possible non-binary finite-state machines. The development of a molecular electron device (MED) synthetic capability in combination with the above devices would suggest that large 3-d arrays of parallel processors will be possible with automata, biological, and crystallographic implications. 41 references.

  4. Advanced in study of cellular and molecular mechanisms of radiation effects on central nervous system

    International Nuclear Information System (INIS)

    Zhang Wei; Tu Yu; Wang Lili

    2008-01-01

    Along with radiation treatment extensively applied, radiation injury also is valued gradually. The effect of radiation to the cellular and molecular of central nervous system (CNS) is a complicated and moderately advanced process and the mechanism is remains incompletely clear yet. Inquiring into the possible mechanism of the CNS including the injury and the restoration of neuron, neuroglia cells, endotheliocyte cell and blood-brain barrier and the molecular level of change induced by radiation, so as to provide beneficial thought for preventing and curing radiation injury clinically. Some neuroprotective strategies are also addressed in the review. (authors)

  5. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  6. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  7. Effects of type I collagen coating on titanium osseointegration: histomorphometric, cellular and molecular analyses

    International Nuclear Information System (INIS)

    Sverzut, Alexander Tadeu; Crippa, Grasiele Edilaine; Tambasco de Oliveira, Paulo; Beloti, Marcio Mateus; Rosa, Adalberto Luiz; Morra, Marco

    2012-01-01

    The investigation of titanium (Ti) surface modifications aiming to increase implant osseointegration is one of the most active research areas in dental implantology. This study was carried out to evaluate the benefits of coating Ti with type I collagen on the osseointegration of dental implants. Acid etched Ti implants (AETi), either untreated or coated with type I collagen (ColTi), were placed in dog mandibles for three and eight weeks for histomorphometric, cellular and molecular evaluations of bone tissue response. While the histological aspects were essentially the same with both implants being surrounded by lamellar bone trabeculae, histomorphometric analysis showed more abundant bone formation in ColTi, mainly at three weeks. Cellular evaluation showed that cells harvested from bone fragments in close contact with ColTi display lower proliferative capacity and higher alkaline phosphatase activity, phenotypic features associated with more differentiated osteoblasts. Confirming these findings, molecular analyses showed that ColTi implants up-regulates the expression of a panel of genes well known as osteoblast markers. Our results present a set of evidences that coating AETi with collagen fastens the osseointegration by stimulating bone formation at the cellular and molecular levels, making this combination of morphological and biochemical modification a promising approach to treat Ti surfaces. (paper)

  8. Cellular and Axonal Diversity in Molecular Layer Heterotopia of the Rat Cerebellar Vermis

    Directory of Open Access Journals (Sweden)

    Sarah E. Van Dine

    2013-01-01

    Full Text Available Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.

  9. Base Station Ordering for Emergency Call Localization in Ultra-dense Cellular Networks

    KAUST Repository

    Elsawy, Hesham

    2017-10-04

    This paper proposes the base station ordering localization technique (BoLT) for emergency call localization in cellular networks. Exploiting the foreseen ultra-densification of the next-generation (5G and beyond) cellular networks, we utilize higher-order Voronoi tessellations to provide ubiquitous localization services that are in compliance to the public safety standards in cellular networks. The proposed localization algorithm runs at the base stations (BSs) and requires minimal operation from agents (i.e., mobile users). Particularly, BoLT requires each agent to feedback a neighbor cell list (NCL) that contains the order of neighboring BSs based on the received signal power in the pilots sent from these BSs. Moreover, this paper utilizes stochastic geometry to develop a tractable mathematical model to assess the performance of BoLT in a general network setting. The goal of this paper is to answer the following two fundamental questions: i) how many BSs should be ordered and reported by the agent to achieve a desirable localization accuracy? and ii) what is the localization error probability given that the pilot signals are subject to shadowing? Assuming that the BSs are deployed according to a Poisson point process (PPP), we answer these two questions via characterizing the tradeoff between the area of location region (ALR) and the localization error probability in terms of the number of BSs ordered by the agent. The results show that reporting the order of six neighboring BSs is sufficient to localize the agent within 10% of the cell area. Increasing the number of reported BSs to ten confines the location region to 1% of the cell area. This would translate to the range of a few meters to decimeters in the foreseen ultra-dense 5G networks.

  10. Base Station Ordering for Emergency Call Localization in Ultra-dense Cellular Networks

    KAUST Repository

    Elsawy, Hesham; Dai, Wenhan; Alouini, Mohamed-Slim; Win, Moe Z.

    2017-01-01

    This paper proposes the base station ordering localization technique (BoLT) for emergency call localization in cellular networks. Exploiting the foreseen ultra-densification of the next-generation (5G and beyond) cellular networks, we utilize higher-order Voronoi tessellations to provide ubiquitous localization services that are in compliance to the public safety standards in cellular networks. The proposed localization algorithm runs at the base stations (BSs) and requires minimal operation from agents (i.e., mobile users). Particularly, BoLT requires each agent to feedback a neighbor cell list (NCL) that contains the order of neighboring BSs based on the received signal power in the pilots sent from these BSs. Moreover, this paper utilizes stochastic geometry to develop a tractable mathematical model to assess the performance of BoLT in a general network setting. The goal of this paper is to answer the following two fundamental questions: i) how many BSs should be ordered and reported by the agent to achieve a desirable localization accuracy? and ii) what is the localization error probability given that the pilot signals are subject to shadowing? Assuming that the BSs are deployed according to a Poisson point process (PPP), we answer these two questions via characterizing the tradeoff between the area of location region (ALR) and the localization error probability in terms of the number of BSs ordered by the agent. The results show that reporting the order of six neighboring BSs is sufficient to localize the agent within 10% of the cell area. Increasing the number of reported BSs to ten confines the location region to 1% of the cell area. This would translate to the range of a few meters to decimeters in the foreseen ultra-dense 5G networks.

  11. Fast Deploy Radiation Monitoring Array Emergency Solution Based on GPS and Cellular Network

    International Nuclear Information System (INIS)

    Vax, E.; Broide, A.; Manor, A.; Marcus, E.; Seif, R.; Nir, J.; Kadmon, Y.; Sattinger, D.; Levinson, S.; Tal, N.

    2004-01-01

    Radiation monitoring of a possible contaminating source is highly important for safety and risk analysis. Since the monitoring must cover the whole contaminated area, the standard solution is to scatter an array of numerous fixed detectors in advance. The Fast Deploy Radiation Monitoring Array (FDRMA) is a solution that does not require coverage of the entire area. The FDRMA is a compact, world wide applicative, seamless and novel solution, designed for emergency cases. The system consists of GPS and IP cellular network, which make it mobile and therefore suitable for global use. The most significant advantage of the FDRMA system is minimizing the exposure time of the monitoring teams, while maintaining flexibility of the deployment area, as opposed to the Vehicle Monitoring System (VMS) [1] or the standard solution mentioned above. A detailed description of the proposed FDRMA system and its comparison to a fixed detectors' array is presented in this work

  12. Characterizing emergent properties of immunological systems with multi-cellular rule-based computational modeling.

    Science.gov (United States)

    Chavali, Arvind K; Gianchandani, Erwin P; Tung, Kenneth S; Lawrence, Michael B; Peirce, Shayn M; Papin, Jason A

    2008-12-01

    The immune system is comprised of numerous components that interact with one another to give rise to phenotypic behaviors that are sometimes unexpected. Agent-based modeling (ABM) and cellular automata (CA) belong to a class of discrete mathematical approaches in which autonomous entities detect local information and act over time according to logical rules. The power of this approach lies in the emergence of behavior that arises from interactions between agents, which would otherwise be impossible to know a priori. Recent work exploring the immune system with ABM and CA has revealed novel insights into immunological processes. Here, we summarize these applications to immunology and, particularly, how ABM can help formulate hypotheses that might drive further experimental investigations of disease mechanisms.

  13. THE MOLECULAR EVOLUTION OF THE MOST DANGEROUS EMERGING VIRUS INFECTIONS

    Directory of Open Access Journals (Sweden)

    Popov NN

    2016-03-01

    Full Text Available In this paper we reviewed what is known about the emerging viruses, the hosts that they originate in, and the molecular events that drive their emergence. When a pathogen crosses over from animals to humans, or an existing human disease suddenly increases in incidence, the infectious disease is said to be ‘emerging’. Most of the emerging pathogens originate from nonhuman animal species which has been termed natural reservoirs. The number of emerging infectious diseases has increased over the last few decades, driven by both anthropogenic and environmental factors such as population growth, urbanization, global travel and trade, intensification of livestock production. Now it has been believed that the emergence process may include four steps. On the first step the exposure of the humans to a novel virus occures. On the second step the subset of the viruses overcome the cross-species barrier. Host shifts have resulted in multiple human pandemics, such as HIV from chimps the H1N1, ‘‘spanish flu’’ from birds, SARS-CoV and virus Ebola from bats. Then some viruses enables to transmit from one human to another. And on the last step the viruses that are sufficiently transmissible between humans cause outbreaks and become endemic in human populations without the requirement of a natural reservoir. This review aims to discuss the molecular mechanisms that govern virus cross-species transmission and following stage, using the emergence of HIV, SARS-CoV, virus Ebola and influenza virus A as the models.Populations of many viruses harbour abundant genetic variability due to a combination of high mutation, recombination or reassortation rates and large population sizes. Mutations and recombinations has been associated with the increases in virulence, the evasion of host immunity and the evolution of resistance to antivirals. Genetic alterations in one species may results in the acquisition of variations that allow them to overcome cross species

  14. Molecular and cellular mechanisms of the age-dependency of opioid analgesia and tolerance

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2012-05-01

    Full Text Available Abstract The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling (RGS proteins change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.

  15. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    Science.gov (United States)

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

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. PMID:25999313

  16. Cellular and molecular screening of connective tissue dysplasia in adolescent athletes (pilot study

    Directory of Open Access Journals (Sweden)

    M. V. Dvornichenko

    2017-01-01

    Full Text Available The purpose of the study is to evaluate the cellular and molecular parameters of bone remodeling in the blood as potential markers of undifferentiated forms of connective tissue dysplasiaMaterials and methods. The structural and functional status of cellular elements of in vitro culturing of mononuclear leukocytes of peripheral blood in adolescent athletes connected with phenotypic manifestations of undifferentiated connective tissue dysplasia (UCTD were investigated. 25 pupils of sport schools from 10–14 years old (main disciplines: figure skating, gymnastics, athletics were examined with the help of express analysis. The average age of the examined adolescents was (12,0 ± 1,7 years. Clinical examination of adolescents allowed ranking the UCTD signs on a scale of 4–11,5 points.Results. A comparison of questionnaire survey results and an evaluation of bone remodeling distant markers allowed the revelation of 2 groups in the distribution of adolescent athletes: those with minimal signs of UCTD (scores lesser than 7 points – 10 pupils, and those with expressed UCTD phenotype (scores are equal or more than 7 points –15 pupils. Significant statistical decrease in the content of collagen type I degradation products (CrossLaps (by 80% and ionized calcium (by 5% has been determined in the peripheral blood of adolescent athletes with expressed UCTD phenotype. In conditions of short-term 72-h cultivation of mononuclear leukocytes in the presence of a 3D matrix imitating the properties of the mineral substance of the regenerating bone tissue, morphofunctional features of cellular reaction in adolescent athletes with clinical manifestations of UCTD, as well the heterogeneity of the cell population associated with the appearance of cells with an osteoblast-like phenotype in the blood have been revealed. The results of investigation propose the use of distant cellular and molecular parameters of bone remodeling to screen the mechanisms and dynamics

  17. Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

    Science.gov (United States)

    Ivey, Jill W; Latouche, Eduardo L; Richards, Megan L; Lesser, Glenn J; Debinski, Waldemar; Davalos, Rafael V; Verbridge, Scott S

    2017-07-25

    Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Cellular and molecular immune responses of the sea bass (Dicentrarchus labrax) experimentally infected with betanodavirus

    DEFF Research Database (Denmark)

    Scapigliati, G.; Buonocore, F.; Randelli, E.

    2010-01-01

    and acquired responses: type I IFN, Mx, IL-1, Cox-2; IL-10, TGF-β, TCRβ, CD4, CD8α, IgM, by using a quantitative PCR array system developed for sea bass. The obtained results showed a detectable increase of T cells and B cells in PBL during betanodavirus infection. Furthermore, leucocytes obtained from blood...... was also observed, while the other tested genes did not show any significant variations with respect to mock-treated fish. Overall, our work represents a first comprehensive analysis of cellular and molecular immune parameters in a fish species exposed to a pathogenic virus....

  19. The Cellular and Molecular Mechanisms of Immuno-suppression by Human Type 1 Regulatory T cells

    Directory of Open Access Journals (Sweden)

    Silvia eGregori

    2012-02-01

    Full Text Available The immuno-regulatory mechanisms of IL-10-producing type 1 regulatory T (Tr1 cells have been widely studied over the years. However, several recent discoveries have shed new light on the cellular and molecular mechanisms that human Tr1 cells use to control immune responses and induce tolerance. In this review we outline the well-known and newly discovered regulatory properties of human Tr1 cells and provide an in-depth comparison of the known suppressor mechanisms of Tr1 cells with FOXP3+ Treg. We also highlight the role that Tr1 cells play in promoting and maintaining tolerance in autoimmunity, allergy, and transplantation.

  20. A metric for characterizing the bistability of molecular quantum-dot cellular automata

    International Nuclear Information System (INIS)

    Lu Yuhui; Lent, Craig S

    2008-01-01

    Much of molecular electronics involves trying to use molecules as (a) wires, (b) diodes or (c) field-effect transistors. In each case the criterion for determining good performance is well known: for wires it is conductance, for diodes it is conductance asymmetry, while for transistors it is high transconductance. Candidate molecules can be screened in terms of these criteria by calculating molecular conductivity in forward and reverse directions, and in the presence of a gating field. Hence so much theoretical work has focused on understanding molecular conductance. In contrast a molecule used as a quantum-dot cellular automata (QCA) cell conducts no current at all. The keys to QCA functionality are (a) charge localization, (b) bistable charge switching within the cell and (c) electric field coupling between one molecular cell and its neighbor. The combination of these effects can be examined using the cell-cell response function which relates the polarization of one cell to the induced polarization of a neighboring cell. The response function can be obtained by calculating the molecular electronic structure with ab initio quantum chemistry techniques. We present an analysis of molecular QCA performance that can be applied to any candidate molecule. From the full quantum chemistry, all-electron ab initio calculations we extract parameters for a reduced-state model which reproduces the cell-cell response function very well. Techniques from electron transfer theory are used to derive analytical models of the response function and can be employed on molecules too large for full ab initio treatment. A metric is derived which characterizes molecular QCA performance the way transconductance characterizes transistor performance. This metric can be assessed from absorption measurements of the electron transfer band or quantum chemistry calculations of appropriate sophistication

  1. Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

    Science.gov (United States)

    Hyldahl, Robert D; Hubal, Monica J

    2014-02-01

    The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

  2. Cellular Automata Modelling of Photo-Induced Oxidation Processes in Molecularly Doped Polymers

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    David M. Goldie

    2016-11-01

    Full Text Available The possibility of employing cellular automata (CA to model photo-induced oxidation processes in molecularly doped polymers is explored. It is demonstrated that the oxidation dynamics generated using CA models exhibit stretched-exponential behavior. This dynamical characteristic is in general agreement with an alternative analysis conducted using standard rate equations provided the molecular doping levels are sufficiently low to prohibit the presence of safe-sites which are impenetrable to dissolved oxygen. The CA models therefore offer the advantage of exploring the effect of dopant agglomeration which is difficult to assess from standard rate equation solutions. The influence of UV-induced bleaching or darkening upon the resulting oxidation dynamics may also be easily incorporated into the CA models and these optical effects are investigated for various photo-oxidation product scenarios. Output from the CA models is evaluated for experimental photo-oxidation data obtained from a series of hydrazone-doped polymers.

  3. Molecular and cellular mechanisms of tight junction dysfunction in the irritable bowel syndrome.

    Science.gov (United States)

    Cheng, Peng; Yao, Jianning; Wang, Chunfeng; Zhang, Lianfeng; Kong, Wuming

    2015-09-01

    The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, are complex and have not been fully elucidated. The present study aimed to investigate the molecular and cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues of IBS and non‑IBS patients were examined to observe cellular changes by cell chemical tracer electron microscopy and transmission electron microscopy, and intestinal claudin‑1 protein was detected by immunohistochemistry, western blot analysis and fluorescence quantitative polymerase chain reaction. Compared with the control group, TJ broadening and the tracer extravasation phenomenon were observed in the diarrhea‑predominant IBS group, and a greater number of neuroendocrine cells and mast cells filled with high‑density particles in the endocrine package pulp as well as a certain extent of vacuolization were present. The expression of claudin‑1 in diarrhea‑predominant IBS patients was decreased, while it was increased in constipation‑predominant IBS patients. In conclusion, the results of the present study indicated that changes in cellular structure and claudin‑1 levels were associated with Tjs in IBS.

  4. The Role of Mechanical Force in Molecular and Cellular during Orthodontic Tooth Movement

    Directory of Open Access Journals (Sweden)

    Ida Bagus Narmada

    2012-10-01

    Full Text Available Application of mechanical force on abnormally positioned tooth, cause changes in tooth location and transmitted to the bone ia the periodontal ligament (PDL produce orthodontic tooth movement. This force application is further way that remodeling in the area occurs. In order to develop biological strategies for enhancing this movement of teeth in bone, the underlying mechanisms of bone resorption and apposition should be understood in detail. Analysis of gingival crevicular fluid (GCF may be a good means of examining the on going molecular and cellular process associated with gingival and bone turnover during orthodontic tooth movement. If it could be possible to biologically monitor and predict the outcome of orthodontic force, then the appliance management could be based on dividual tissue response and the effectiveness of the treatment could be improved and understanding their biology is critical to finding ways to modify bone biology to move teeth faster. The present article reviewed a short introduction to some mayors advanced mechanical force in molecular and cellular biology during orthodontic tooth movement.DOI: 10.14693/jdi.v15i3.30

  5. CURRENT APPROACHES TO THE LABORATORY DIAGNOSIS OF RHEUMATIC DISEASES: ROLE OF MOLECULAR AND CELLULAR BIOMARKERS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2016-01-01

    Full Text Available Laboratory medicine in the early 21st century has achieved advances due to the development and prompt practical introduction of innovative molecular cell technologies, which have assisted in increasing the diagnostic sensitivity and specificity of laboratory tests and in substantially expanding the spectrum of study biomarkers in rheumatology. High-technology automated analytical systems using both classical uniplex methods for immunochemical analysis (indirect immunofluorescence test, enzyme immunoassay, immunoblotting, immunodot assay, immunonephelometry, chemiluminescence immunoassay, and radioimmunoassay and multiplex diagnostic platforms based on DNA, RNA, protein and cellular microchips, polymerase chain reaction, flow cytometry, and mass spectrometry have been used in the past decade to determine biomarkers of rheumatic diseases (RD in blood, synovial fluid, urine, biopsy specimens of the synovial membrane, kidney, and other affected tissues.Present-day generation of molecular and cellular biomarkers (autoantibodies, acute-phase inflammatory proteins, cytokines, chemokines, vascular endothelial activation markers, immunoglobulins, complement components, lymphocyte subpopulations, osseous and cartilaginous tissue metabolic products, intracellular signaling molecules, proteases, and genetic, epigenetic, and transcriptomic markers is an important tool for prevention, early diagnosis, assessment of disease activity, progression rate, clinical laboratory subtypes of RD, prediction of the efficiency of therapy and the risk of adverse events during treatment. Deciphering of the key pathogenetic mechanisms of RD could identify the molecular and cellular biomarkers that might be used as therapeutic targets. Biologicals (monoclonal antibodies and hybrid protein molecules that selectively inhibit proinflammatory cytokines and membrane molecules mediating the pathological activation of immunocompetent cells are successfully used to treat RD today

  6. Clinical Findings Documenting Cellular and Molecular Abnormalities of Glia in Depressive Disorders

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    Boldizsár Czéh

    2018-02-01

    Full Text Available Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the “gliocentric theory”, glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data. Postmortem studies demonstrate glial cell loss while the in vivo imaging data reveal disturbed glial functioning and altered white matter microstructure. Molecular studies report on altered gene expression of glial specific genes. In sum, the clinical findings provide ample evidences on glial pathology and demonstrate that all major glial cell types are affected. However, we still lack convincing theories explaining how the glial abnormalities develop and how exactly contribute to the emotional and cognitive disturbances. Abnormal astrocytic functioning may lead to disturbed metabolism affecting ion homeostasis and glutamate clearance, which in turn, affect synaptic communication. Abnormal oligodendrocyte functioning may disrupt the connectivity of neuronal networks, while microglial activation indicates neuroinflammatory processes. These cellular changes may relate to each other or they may indicate different endophenotypes. A theory has been put forward that the stress-induced inflammation—mediated by microglial activation—triggers a cascade of events leading to damaged astrocytes and oligodendroglia and consequently to their dysfunctions. The clinical data support the “gliocentric” theory, but future research should clarify whether these glial changes are truly the cause or simply the consequences of this devastating disorder.

  7. Emergent 1d Ising Behavior in AN Elementary Cellular Automaton Model

    Science.gov (United States)

    Kassebaum, Paul G.; Iannacchione, Germano S.

    The fundamental nature of an evolving one-dimensional (1D) Ising model is investigated with an elementary cellular automaton (CA) simulation. The emergent CA simulation employs an ensemble of cells in one spatial dimension, each cell capable of two microstates interacting with simple nearest-neighbor rules and incorporating an external field. The behavior of the CA model provides insight into the dynamics of coupled two-state systems not expressible by exact analytical solutions. For instance, state progression graphs show the causal dynamics of a system through time in relation to the system's entropy. Unique graphical analysis techniques are introduced through difference patterns, diffusion patterns, and state progression graphs of the 1D ensemble visualizing the evolution. All analyses are consistent with the known behavior of the 1D Ising system. The CA simulation and new pattern recognition techniques are scalable (in both dimension, complexity, and size) and have many potential applications such as complex design of materials, control of agent systems, and evolutionary mechanism design.

  8. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

    Science.gov (United States)

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

    2013-04-01

    Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator

  9. Molecular mechanisms of peripheral nerve regeneration: Emerging roles of microRNAs

    Directory of Open Access Journals (Sweden)

    Di eWu

    2013-04-01

    Full Text Available microRNAs are small non-coding RNAs that suppress gene expression through target mRNA degradation or translation repression. Recent studies suggest that miRNA plays an important role in multiple physiological and pathological processes in the nervous system. In this review article, we described what is currently known about the mechanisms in peripheral nerve regeneration on the cellular and molecular levels. Recently, changes in microRNA expression profiles have been detected in different injury models, and emerging evidence strongly indicates that these changes promote neurons to survive and shift their physiology from maintaining a structure and supporting synaptic transmission toward a regenerative phenotype. We reviewed the putative mechanisms involved in miRNA mediated post-transcriptional regulation and pointed out several areas where future research is necessary to advance our understanding of how targeting miRNA machinery can be used as a therapeutic approach for treating nerve injuries.

  10. Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

    Science.gov (United States)

    Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

    2013-10-01

    Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Molecular modeling of the conformational dynamics of the cellular prion protein

    Science.gov (United States)

    Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

    2014-03-01

    Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

  12. Molecular basis of cellular localization of poly C binding protein 1 in neuronal cells

    International Nuclear Information System (INIS)

    Berry, Andrea M.; Flock, Kelly E.; Loh, Horace H.; Ko, Jane L.

    2006-01-01

    Poly C binding protein 1 (PCBP) is involved in the transcriptional regulation of neuronal mu-opioid receptor gene. In this study, we examined the molecular basis of PCBP cellular/nuclear localization in neuronal cells using EGFP fusion protein. PCBP, containing three KH domains and a variable domain, distributed in cytoplasm and nucleus with a preferential nuclear expression. Domain-deletional analyses suggested the requirement of variable and KH3 domains for strong PCBP nuclear expression. Within the nucleus, a low nucleolar PCBP expression was observed, and PCBP variable domain contributed to this restricted nucleolar expression. Furthermore, the punctate nuclear pattern of PCBP was correlated to its single-stranded (ss) DNA binding ability, with both requiring cooperativity of at least three sequential domains. Collectively, certain PCBP domains thus govern its nuclear distribution and transcriptional regulatory activity in the nucleus of neurons, whereas the low nucleolar expression implicates the disengagement of PCBP in the ribosomal RNA synthesis

  13. Stochastic narrow escape in molecular and cellular biology analysis and applications

    CERN Document Server

    Holcman, David

    2015-01-01

    This book covers recent developments in the non-standard asymptotics of the mathematical narrow escape problem in stochastic theory, as well as applications of the narrow escape problem in cell biology. The first part of the book concentrates on mathematical methods, including advanced asymptotic methods in partial equations, and is aimed primarily at applied mathematicians and theoretical physicists who are interested in biological applications. The second part of the book is intended for computational biologists, theoretical chemists, biochemists, biophysicists, and physiologists. It includes a summary of output formulas from the mathematical portion of the book and concentrates on their applications in modeling specific problems in theoretical molecular and cellular biology. Critical biological processes, such as synaptic plasticity and transmission, activation of genes by transcription factors, or double-strained DNA break repair, are controlled by diffusion in structures that have both large and small sp...

  14. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

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    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  15. Cellular and molecular basis of RV hypertrophy in congenital heart disease.

    Science.gov (United States)

    Iacobazzi, D; Suleiman, M-S; Ghorbel, M; George, S J; Caputo, M; Tulloh, R M

    2016-01-01

    RV hypertrophy (RVH) is one of the triggers of RV failure in congenital heart disease (CHD). Therefore, improving our understanding of the cellular and molecular basis of this pathology will help in developing strategic therapeutic interventions to enhance patient benefit in the future. This review describes the potential mechanisms that underlie the transition from RVH to RV failure. In particular, it addresses structural and functional remodelling that encompass contractile dysfunction, metabolic changes, shifts in gene expression and extracellular matrix remodelling. Both ischaemic stress and reactive oxygen species production are implicated in triggering these changes and will be discussed. Finally, RV remodelling in response to various CHDs as well as the potential role of biomarkers will be addressed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Proteomic characterization of cellular and molecular processes that enable the Nanoarchaeum equitans--Ignicoccus hospitalis relationship.

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    Richard J Giannone

    Full Text Available Nanoarchaeum equitans, the only cultured representative of the Nanoarchaeota, is dependent on direct physical contact with its host, the hyperthermophile Ignicoccus hospitalis. The molecular mechanisms that enable this relationship are unknown. Using whole-cell proteomics, differences in the relative abundance of >75% of predicted protein-coding genes from both Archaea were measured to identify the specific response of I. hospitalis to the presence of N. equitans on its surface. A purified N. equitans sample was also analyzed for evidence of interspecies protein transfer. The depth of cellular proteome coverage achieved here is amongst the highest reported for any organism. Based on changes in the proteome under the specific conditions of this study, I. hospitalis reacts to N. equitans by curtailing genetic information processing (replication, transcription in lieu of intensifying its energetic, protein processing and cellular membrane functions. We found no evidence of significant Ignicoccus biosynthetic enzymes being transported to N. equitans. These results suggest that, under laboratory conditions, N. equitans diverts some of its host's metabolism and cell cycle control to compensate for its own metabolic shortcomings, thus appearing to be entirely dependent on small, transferable metabolites and energetic precursors from I. hospitalis.

  17. Cellular and molecular investigations of the adhesion and mechanics of Listeria monocytogenes

    Science.gov (United States)

    Eskhan, Asma Omar

    Atomic force microscopy has been used to quantify the adherence and mechanical properties of an array of L. monocytogenes strains and their surface biopolymers. First, eight L. monocytogenes strains that represented the two major lineages of the species were compared for their adherence and mechanics at cellular and molecular levels. Our results indicated that strains of lineage' II were characterized by higher adhesion and Young's moduli, longer and more rigid surface biopolymers and lower specific and nonspecific forces when compared to lineage' I strains. Additionally, adherence and mechanical properties of eight L. monocytogenes epidemic and environmental strains were probed. Our results pointed to that environmental and epidemic strains representative of a given lineage were similar in their adherence and mechanical properties when investigated at a cellular level. However, when the molecular properties of the strains were considered, epidemic strains were characterized by higher specific and nonspecific forces, shorter, denser and more flexible biopolymers compared to environmental strains. Second, the role of environmental pH conditions of growth on the adhesion and mechanics of a pathogenic L. monocytogenes EGDe was investigated. Our results pointed to a transition in the adhesion energies for cells cultured at pH 7. In addition, when the types of molecular forces that govern the adhesion were quantified using Poisson statistical approach and using a new proposed method, specific hydrogen-bond energies dominated the bacterial adhesion process. Such a finding is instrumental to researchers designing methods to control bacterial adhesion. Similarly, bacterial cells underwent a transition in their mechanical properties. We have shown that cells cultured at pH 7 were the most rigid compared to those cultured in lower or higher pH conditions of growth. Due to transitions observed in adherence and mechanics when cells were cultured at pH 7, we hypothesized that

  18. Design of a fault-tolerant reversible control unit in molecular quantum-dot cellular automata

    Science.gov (United States)

    Bahadori, Golnaz; Houshmand, Monireh; Zomorodi-Moghadam, Mariam

    Quantum-dot cellular automata (QCA) is a promising emerging nanotechnology that has been attracting considerable attention due to its small feature size, ultra-low power consuming, and high clock frequency. Therefore, there have been many efforts to design computational units based on this technology. Despite these advantages of the QCA-based nanotechnologies, their implementation is susceptible to a high error rate. On the other hand, using the reversible computing leads to zero bit erasures and no energy dissipation. As the reversible computation does not lose information, the fault detection happens with a high probability. In this paper, first we propose a fault-tolerant control unit using reversible gates which improves on the previous design. The proposed design is then synthesized to the QCA technology and is simulated by the QCADesigner tool. Evaluation results indicate the performance of the proposed approach.

  19. Molecular basis of pathogenesis of emerging viruses infecting aquatic animals

    Directory of Open Access Journals (Sweden)

    Lang Gui

    2018-01-01

    Full Text Available Aquatic vertebrates are very abundant in the world, and they are of tremendous importance in providing global food security and nutrition. However, emergent and resurgent viruses, such as ranavirus (e.g., Rana grylio virus, RGV and Andriasd avidianus ranavirus, ADRV, herpesvirus (e.g., Carassius carassius herpesvirus, CaHV, reovirus (e.g., grass carp reovirus 109, GCRV-109, Scophthal musmaximus reovirus, SMReV and Micropterus salmoides reovirus, MsReV, and rhabdovirus (e.g., Siniper cachuatsi rhabdovirus, SCRV and Scophthal musmaximus rhabdovirus, SMRV can cause severe diseases in aquaculture animals and wild lower vertebrates, such as frogs, giant salamanders, fish, and so on. Here, we will briefly describe the symptoms produced by the aforementioned viruses and the molecular basis of the virus–host interactions. This manuscript aims to provide an overview of viral diseases in lower vertebrates with an emphasis on visible symptomatic manifestations and pathogenesis.

  20. Cellular and Molecular Mechanisms in Perioperative Hepatic Protection: A Review of Current Interventions

    Directory of Open Access Journals (Sweden)

    Zahra Talebi

    2017-05-01

    Full Text Available Liver is one of the most important organs needing great concern during the perioperative period. There are a number of different mechanisms that interact with liver cells and might affect their integrity and cell live. Though these mechanisms are not all the same, there is a great common point: all affect the metabolic pathways of the liver. Ischemia, anesthetic drug effects and other perioperative insults may affect the liver. Disturbance in an organ’s blood flow is an inherent part of diverse surgical procedures, which leads to lack of oxygen and nutrient supply. These ischemic periods can be particularly long in case of liver surgeries, such as resection of large hepatic tumors, management of hepatic trauma and liver transplant. Once the blood flow and oxygen supply are restored, the interruption of blood flow affects the oxygen dependent cells in liver, which require mitochondrial oxidative phosphorylation for their metabolism. Molecular mechanisms such as Redox status, ionic interchange disturbances as well as different mediators and cells like KC, SEC, dendritic cells, leukocytes, and lymphocytes, are involved in the process ultimately leading to cell death by apoptosis and necrosis. This review provides an overview on the cellular and molecular mechanisms involved in liver injuries, categorizing these mechanisms in 3 different classes: preoperative mechanisms, intraoperative mechanisms and postoperative mechanisms. Each of them are discussed in a different part of the manuscript

  1. [Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

    Science.gov (United States)

    Bazyan, A S

    2016-01-01

    The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

  2. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  3. Cellular and molecular responses of E. fetida coelomocytes exposed to TiO{sub 2} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bigorgne, Emilie, E-mail: emilie.bigorgne@univ-lorraine.fr; Foucaud, Laurent [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Caillet, Celine [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Giamberini, Laure; Nahmani, Johanne [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Thomas, Fabien [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Rodius, Francois [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France)

    2012-07-15

    An in vitro approach using coelomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO{sub 2} nanoparticles. Coelomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO{sub 2} nanoparticles (1-25 {mu}g/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO{sub 2} nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 {mu}g/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO{sub 2} in our experimental conditions. This in vitro approach showed that TiO{sub 2} nanoparticles were taken up by coelomocytes and they could modify the molecular response of immune and detoxification system.

  4. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  5. Investigation of cellular and molecular responses to pulsed focused ultrasound in a mouse model.

    Directory of Open Access Journals (Sweden)

    Scott R Burks

    Full Text Available Continuous focused ultrasound (cFUS has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation. pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules. We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α and cell adhesion molecules (e.g., ICAM-1 and VCAM-1 on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology.

  6. Cellular and molecular repair of X-ray-induced damage: dependence on oxygen tension and nutritional status

    International Nuclear Information System (INIS)

    Spiro, I.J.; Kennedy, K.A.; Stickler, R.; Ling, C.C.

    1985-01-01

    Cellular and molecular repair was studied at 23 0 C using split-dose recovery and alkaline elution techniques, respectively, as a function of cellular oxygen and nutrient conditions. Hypoxic cells in full medium showed a partial reduction in the level of sublethal damage (SLD) repair relative to aerated cells; the respective repair kinetics were similar with a common repair half-time of 30 min. Similarly, hypoxic cells showed a slight reduction in strand break rejoining capacity compared to aerated cells. Under nutrient deprivation, anoxic cells displayed no SLD repair or strand break repair, while aerated cells exhibited the same level of SLD and strand break repair as for well-fed cells. In addition, nutrient deprived cells at low O 2 levels displayed normal SLD and strand break repair capability. These results indicate that both nutrient and O 2 deprivation are necessary for complete inhibition of cellular and molecular repair, and low levels of O 2 can effectively reverse this inhibition

  7. Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular and cellular mechanisms.

    Directory of Open Access Journals (Sweden)

    Kelly L Robertson

    Full Text Available Observations of enhanced growth of melanized fungi under low-dose ionizing radiation in the laboratory and in the damaged Chernobyl nuclear reactor suggest they have adapted the ability to survive or even benefit from exposure to ionizing radiation. However, the cellular and molecular mechanism of fungal responses to such radiation remains poorly understood. Using the black yeast Wangiella dermatitidis as a model, we confirmed that ionizing radiation enhanced cell growth by increasing cell division and cell size. Using RNA-seq technology, we compared the transcriptomic profiles of the wild type and the melanin-deficient wdpks1 mutant under irradiation and non-irradiation conditions. It was found that more than 3000 genes were differentially expressed when these two strains were constantly exposed to a low dose of ionizing radiation and that half were regulated at least two fold in either direction. Functional analysis indicated that many genes for amino acid and carbohydrate metabolism and cell cycle progression were down-regulated and that a number of antioxidant genes and genes affecting membrane fluidity were up-regulated in both irradiated strains. However, the expression of ribosomal biogenesis genes was significantly up-regulated in the irradiated wild-type strain but not in the irradiated wdpks1 mutant, implying that melanin might help to contribute radiation energy for protein translation. Furthermore, we demonstrated that long-term exposure to low doses of radiation significantly increased survivability of both the wild-type and the wdpks1 mutant, which was correlated with reduced levels of reactive oxygen species (ROS, increased production of carotenoid and induced expression of genes encoding translesion DNA synthesis. Our results represent the first functional genomic study of how melanized fungal cells respond to low dose ionizing radiation and provide clues for the identification of biological processes, molecular pathways and

  8. Cellular and molecular changes associated with somatic embryogenesis induction in Agave tequilana.

    Science.gov (United States)

    Portillo, L; Olmedilla, A; Santacruz-Ruvalcaba, F

    2012-10-01

    In spite of the importance of somatic embryogenesis for basic research in plant embryology as well as for crop improvement and plant propagation, it is still unclear which mechanisms and cell signals are involved in acquiring embryogenic competence by a somatic cell. The aim of this work was to study cellular and molecular changes involved in the induction stage in calli of Agave tequilana Weber cultivar azul in order to gain more information on the initial stages of somatic embryogenesis in this species. Cytochemical and immunocytochemical techniques were used to identify differences between embryogenic and non-embryogenic cells from several genotypes. Presence of granular structures was detected after somatic embryogenesis induction in embryogenic cells; composition of these structures as well as changes in protein and polysaccharide distribution was studied using Coomassie brilliant blue and Periodic Acid-Schiff stains. Distribution of arabinogalactan proteins (AGPs) and pectins was investigated in embryogenic and non-embryogenic cells by immunolabelling using anti-AGP monoclonal antibodies (JIM4, JIM8 and JIM13) as well as an anti-methyl-esterified pectin-antibody (JIM7), in order to evaluate major modifications in cell wall composition in the initial stages of somatic embryogenesis. Our observations pointed out that induction of somatic embryogenesis produced accumulation of proteins and polysaccharides in embryogenic cells. Presence of JIM8, JIM13 and JIM7 epitopes were detected exclusively in embryogenic cells, which supports the idea that specific changes in cell wall are involved in the acquisition of embryogenic competence of A. tequilana.

  9. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  10. Prolactin and teleost ionocytes: new insights into cellular and molecular targets of prolactin in vertebrate epithelia

    Science.gov (United States)

    Breves, Jason P.; McCormick, Stephen D.; Karlstrom, Rolf O.

    2014-01-01

    The peptide hormone prolactin is a functionally versatile hormone produced by the vertebrate pituitary. Comparative studies over the last six decades have revealed that a conserved function for prolactin across vertebrates is the regulation of ion and water transport in a variety of tissues including those responsible for whole-organism ion homeostasis. In teleost fishes, prolactin was identified as the “freshwater-adapting hormone”, promoting ion-conserving and water-secreting processes by acting on the gill, kidney, gut and urinary bladder. In mammals, prolactin is known to regulate renal, intestinal, mammary and amniotic epithelia, with dysfunction linked to hypogonadism, infertility, and metabolic disorders. Until recently, our understanding of the cellular mechanisms of prolactin action in fishes has been hampered by a paucity of molecular tools to define and study ionocytes, specialized cells that control active ion transport across branchial and epidermal epithelia. Here we review work in teleost models indicating that prolactin regulates ion balance through action on ion transporters, tight-junction proteins, and water channels in ionocytes, and discuss recent advances in our understanding of ionocyte function in the genetically and embryonically accessible zebrafish (Danio rerio). Given the high degree of evolutionary conservation in endocrine and osmoregulatory systems, these studies in teleost models are contributing novel mechanistic insight into how prolactin participates in the development, function, and dysfunction of osmoregulatory systems across the vertebrate lineage.

  11. Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality

    Directory of Open Access Journals (Sweden)

    M.A. Al-Griw

    2016-09-01

    Full Text Available Exposures to a wide variety of environmental substances are negatively associated with many biological cell systems both in humans and rodents. Trichloroethane (TCE, a ubiquitous environmental toxicant, is used in large quantities as a dissolvent, metal degreaser, chemical intermediate, and component of consumer products. This increases the likelihood of human exposure to these compounds through dermal, inhalation and oral routes. The present in vivo study was aimed to investigate the possible cellular and molecular etiology of liver abnormality induced by early exposure to TCE using a murine model. The results showed a significant increase in liver weight. Histopathological examination revealed a TCE-induced hepatotoxicity which appeared as heavily congested central vein and blood sinusoids as well as leukocytic infiltration. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates hepatocellular apoptosis was evident in the treated mice compared to control. TCE was also found to induce oxidative stress as indicated by an increase in the levels of lipid peroxidation, an oxidative stress marker. There was also a significant decrease in the DNA content of the hepatocytes of the treated groups compared to control. Agarose gel electrophoresis also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation in the liver cells, indicating oxidative stress as the cause of DNA damage. These results suggest the need for a complete risk assessment of any new chemical prior to its arrival into the consumer market.

  12. Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors

    Directory of Open Access Journals (Sweden)

    Laura Barberi

    2015-08-01

    Full Text Available The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers, alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors.

  13. Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

    Directory of Open Access Journals (Sweden)

    Vivian Capilla-Gonzalez

    2011-06-01

    Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

  14. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    International Nuclear Information System (INIS)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees

  15. Cellular and molecular events leading to the development of skin cancer

    International Nuclear Information System (INIS)

    Melnikova, Vladislava O.; Ananthaswamy, Honnavara N.

    2005-01-01

    The transition from a normal cell to a neoplastic cell is a complex process and involves both genetic and epigenetic changes. The process of carcinogenesis begins when the DNA is damaged, which then leads to a cascade of events leading to the development of a tumor. Ultraviolet (UV) radiation causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. Upon DNA damage, the p53 tumor suppressor protein undergoes phosphorylation and translocation to the nucleus and aids in DNA repair or causes apoptosis. Excessive UV exposure overwhelms DNA repair mechanisms leading to induction of p53 mutations and loss of Fas-FasL interaction. Keratinocytes carrying p53 mutations acquire a growth advantage by virtue of their increased resistance to apoptosis. Thus, resistance to cell death is a key event in photocarcinogenesis and conversely, elimination of cells containing excessive UV-induced DNA damage is a key step in protecting against skin cancer development. Apoptosis-resistant keratinocytes undergo clonal expansion that eventually leads to formation of actinic keratoses and squamous cell carcinomas. In this article, we will review some of the cellular and molecular mechanisms involved in initiation and progression of UV-induced skin cancer

  16. Cellular and molecular events leading to the development of skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Melnikova, Vladislava O. [Department of Immunology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Unit 902, Houston, TX 77030 (United States); Ananthaswamy, Honnavara N. [Department of Immunology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Unit 902, Houston, TX 77030 (United States)]. E-mail: hanantha@mdanderson.org

    2005-04-01

    The transition from a normal cell to a neoplastic cell is a complex process and involves both genetic and epigenetic changes. The process of carcinogenesis begins when the DNA is damaged, which then leads to a cascade of events leading to the development of a tumor. Ultraviolet (UV) radiation causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. Upon DNA damage, the p53 tumor suppressor protein undergoes phosphorylation and translocation to the nucleus and aids in DNA repair or causes apoptosis. Excessive UV exposure overwhelms DNA repair mechanisms leading to induction of p53 mutations and loss of Fas-FasL interaction. Keratinocytes carrying p53 mutations acquire a growth advantage by virtue of their increased resistance to apoptosis. Thus, resistance to cell death is a key event in photocarcinogenesis and conversely, elimination of cells containing excessive UV-induced DNA damage is a key step in protecting against skin cancer development. Apoptosis-resistant keratinocytes undergo clonal expansion that eventually leads to formation of actinic keratoses and squamous cell carcinomas. In this article, we will review some of the cellular and molecular mechanisms involved in initiation and progression of UV-induced skin cancer.

  17. The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting

    Directory of Open Access Journals (Sweden)

    Ryuta Koyama

    2018-05-01

    Full Text Available The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber sprouting could lead to an understanding of central nervous system (CNS network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber sprouting by discussing mainly in vitro studies.

  18. Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis

    Science.gov (United States)

    Ruano, Juan; Suárez-Fariñas, Mayte; Shemer, Avner; Oliva, Margeaux

    2016-01-01

    Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFα/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. PMID:26849645

  19. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Directory of Open Access Journals (Sweden)

    Prarthana V Rewatkar

    Full Text Available Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  20. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Science.gov (United States)

    Rewatkar, Prarthana V; Parekh, Harendra S; Parat, Marie-Odile

    2016-01-01

    Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i) expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii) dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  1. Dose estimate of exposure to radioisotopes in molecular and cellular biology

    International Nuclear Information System (INIS)

    Onado, C.; Faretta, M.; Ubezio, P.

    1999-01-01

    A method for prospectively evaluating the annual equivalent doses and effective dose to biomedical researchers working with unsealed radioisotopes, and their classification, is presented here. Simplified formulae relate occupational data to a reasonable overestimate of the annual effective dose, and the equivalent doses to the hands and to the skin. The procedure, up to the classification of personnel and laboratories, can be made fully automatic, using a common spreadsheet on a personal computer. The method is based on occupational data, accounting for the amounts of each radioisotope used by a researcher, the time of exposure and the overall amounts employed in the laboratories where experiments are performed. The former data serve to forecast a contribution to the dose arising from a researcher's own work, the latter to a forecast of an 'environmental' contribution deriving simply from the presence in a laboratory where other people are working with radioisotopes. The estimates of the doses due to one's own radioisotope handling and to 'environment' were corrected for accidental exposure, considered as a linear function of the manipulated activity or of the time spent in the laboratories respectively, and summed up to give the effective dose. The effective dose associated with some common experiments in molecular and cellular biology is pre-evaluated by this method. (author)

  2. The cellular and molecular bases of leptin and ghrelin resistance in obesity.

    Science.gov (United States)

    Cui, Huxing; López, Miguel; Rahmouni, Kamal

    2017-06-01

    Obesity, a major risk factor for the development of diabetes mellitus, cardiovascular diseases and certain types of cancer, arises from a chronic positive energy balance that is often due to unlimited access to food and an increasingly sedentary lifestyle on the background of a genetic and epigenetic vulnerability. Our understanding of the humoral and neuronal systems that mediate the control of energy homeostasis has improved dramatically in the past few decades. However, our ability to develop effective strategies to slow the current epidemic of obesity has been hampered, largely owing to the limited knowledge of the mechanisms underlying resistance to the action of metabolic hormones such as leptin and ghrelin. The development of resistance to leptin and ghrelin, hormones that are crucial for the neuroendocrine control of energy homeostasis, is a hallmark of obesity. Intensive research over the past several years has yielded tremendous progress in our understanding of the cellular pathways that disrupt the action of leptin and ghrelin. In this Review, we discuss the molecular mechanisms underpinning resistance to leptin and ghrelin and how they can be exploited as targets for pharmacological management of obesity.

  3. Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach.

    Science.gov (United States)

    Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

    2018-01-01

    In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident. Under this endogenous network hypothesis, we established a core working network of hepatocellular carcinoma (HCC) according to the hypothesis and quantified the working network by a nonlinear dynamical system. We showed that the two stable states of the working network reproduce the main known features of normal liver and HCC at both the modular and molecular levels. Using endogenous network hypothesis and validated working network, we explored genetic mutation pattern in cancer and potential strategies to cure or relieve HCC from a totally new perspective. Patterns of genetic mutations have been traditionally analyzed by posteriori statistical association approaches in light of traditional cancer mutation theory. One may wonder the possibility of a priori determination of any mutation regularity. Here, we found that based on the endogenous network theory the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. Normal hepatocyte and cancerous hepatocyte stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable

  4. The Emergence of Multi-Cellular Robot Organisms through On-line On-board Evolution

    NARCIS (Netherlands)

    Weel, B.P.M.; Haasdijk, E.W.; Eiben, A.E.

    2012-01-01

    We investigate whether a swarm of robots can evolve controllers that cause aggregation into 'multi-cellular' robot organisms without a specific reward to do so. To this end, we create a world where aggregated robots receive more energy than individual ones and enable robots to evolve their

  5. Marine molecular biology: An emerging field of biological sciences

    Digital Repository Service at National Institute of Oceanography (India)

    Thakur, N.L.; Jain, R.; Natalio, F.; Hamer, B.; Thakur, A.N.; Muller, W.E.G.

    An appreciation of the potential applications of molecular biology is of growing importance in many areas of life sciences, including marine biology. During the past two decades, the development of sophisticated molecular technologies...

  6. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

    International Nuclear Information System (INIS)

    Esfandyari-Manesh, Mehdi; Darvishi, Behrad; Ishkuh, Fatemeh Azizi; Shahmoradi, Elnaz; Mohammadi, Ali; Javanbakht, Mehran; Dinarvand, Rassoul; Atyabi, Fatemeh

    2016-01-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC_5_0) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

  7. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Esfandyari-Manesh, Mehdi [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Darvishi, Behrad [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ishkuh, Fatemeh Azizi [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shahmoradi, Elnaz [Department of Chemical Engineering, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Mohammadi, Ali [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Javanbakht, Mehran [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-05-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC{sub 50}) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

  8. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

    Science.gov (United States)

    Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

    2015-01-01

    The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives. Copyright © 2015. Published by Elsevier España, S.L.U.

  9. Molecular and Cellular Effects Induced in Mytilus galloprovincialis Treated with Oxytetracycline at Different Temperatures.

    Directory of Open Access Journals (Sweden)

    Mohamed Banni

    Full Text Available The present study evaluated the interactive effects of temperature (16°C and 24°C and a 4-day treatment with the antibiotic oxytetracycline (OTC at 1 and 100 μg/L on cellular and molecular parameters in the mussel Mytilus galloprovincialis. Lysosomal membrane stability (LMS, a sensitive biomarker of impaired health status in this organism, was assessed in the digestive glands. In addition, oxidative stress markers and the expression of mRNAs encoding proteins involved in antioxidant defense (catalase (cat and glutathione-S-transferase (gst and the heat shock response (hsp90, hsp70, and hsp27 were evaluated in the gills, the target tissue of soluble chemicals. Finally, cAMP levels, which represent an important cell signaling pathway related to oxidative stress and the response to temperature challenges, were also determined in the gills. Exposure to heat stress as well as to OTC rendered a decrease in LMS and an increase in malonedialdehyde accumulation (MDA. CAT activity was not significantly modified, whereas GST activity decreased at 24°C. Cat and gst expression levels were reduced in animals kept at 24°C compared to 16°C in the presence or absence of OTC. At 16°C, treatment with OTC caused a significant increase in cat and gst transcript levels. Hsp27 mRNA was significantly up-regulated at all conditions compared to controls at 16°C. cAMP levels were increased at 24°C independent of the presence of OTC. PCA analysis showed that 37.21% and 25.89% of the total variance was explained by temperature and OTC treatment, respectively. Interestingly, a clear interaction was observed in animals exposed to both stressors increasing LMS and MDA accumulation and reducing hsp27 gene expression regulation. These interactions may suggest a risk for the organisms due to temperature increases in contaminated seawaters.

  10. Dietary administration of scallion extract effectively inhibits colorectal tumor growth: cellular and molecular mechanisms in mice.

    Directory of Open Access Journals (Sweden)

    Palanisamy Arulselvan

    Full Text Available Colorectal cancer is a common malignancy and a leading cause of cancer death worldwide. Diet is known to play an important role in the etiology of colon cancer and dietary chemoprevention is receiving increasing attention for prevention and/or alternative treatment of colon cancers. Allium fistulosum L., commonly known as scallion, is popularly used as a spice or vegetable worldwide, and as a traditional medicine in Asian cultures for treating a variety of diseases. In this study we evaluated the possible beneficial effects of dietary scallion on chemoprevention of colon cancer using a mouse model of colon carcinoma (CT-26 cells subcutaneously inoculated into BALB/c mice. Tumor lysates were subjected to western blotting for analysis of key inflammatory markers, ELISA for analysis of cytokines, and immunohistochemistry for analysis of inflammatory markers. Metabolite profiles of scallion extracts were analyzed by LC-MS/MS. Scallion extracts, particularly hot-water extract, orally fed to mice at 50 mg (dry weight/kg body weight resulted in significant suppression of tumor growth and enhanced the survival rate of test mice. At the molecular level, scallion extracts inhibited the key inflammatory markers COX-2 and iNOS, and suppressed the expression of various cellular markers known to be involved in tumor apoptosis (apoptosis index, proliferation (cyclin D1 and c-Myc, angiogenesis (VEGF and HIF-1α, and tumor invasion (MMP-9 and ICAM-1 when compared with vehicle control-treated mice. Our findings may warrant further investigation of the use of common scallion as a chemopreventive dietary agent to lower the risk of colon cancer.

  11. Molecular and cellular mechanisms of hexavalent chromium-induced lung cancer: an updated perspective.

    Science.gov (United States)

    Urbano, A M; Ferreira, L M R; Alpoim, M C

    2012-03-01

    For over a century, chromium (Cr) has found widespread industrial and commercial use, namely as a pigment, in the production of stainless steel and in chrome plating. The adverse health effects to the skin and respiratory tract of prolonged exposure to Cr have been known or suspected for a long time, but it was much more recently that the toxicity of this element was unequivocally attributed to its hexavalent state. Based on the combined results of extensive epidemiological studies, animal carcinogenicity studies and several types of other relevant data, authoritative regulatory agencies have found sufficient evidence to classify hexavalent chromium [Cr(VI)] compounds as encountered in the chromate production, chromate pigment production and chromium plating industries as carcinogenic to humans. Crucial for the development of novel strategies to prevent, detect and/or treat Cr(VI)-induced cancers is a detailed knowledge of the molecular and cellular mechanisms underlying these pathologies. Unfortunately, in spite of a considerable research effort, crucial facets of these mechanisms remain essentially unknown. This review is intended to provide a concise, integrated and critical perspective of the current state of knowledge concerning multiple aspects of Cr(VI) carcinogenesis. It will present recent theories of Cr(VI)-induced carcinogenesis and will include aspects not traditionally covered in other reviews, such as the possible involvement of the energy metabolism in this process. A brief discussion on the models that have been used in the studies of Cr(VI)-induced carcinogenicity will also be included, due to the impact of this parameter on the relevance of the results obtained.

  12. Molecular and Cellular Effects Induced in Mytilus galloprovincialis Treated with Oxytetracycline at Different Temperatures

    Science.gov (United States)

    Banni, Mohamed; Sforzini, Susanna; Franzellitti, Silvia; Oliveri, Caterina; Viarengo, Aldo; Fabbri, Elena

    2015-01-01

    The present study evaluatedthe interactive effects of temperature (16°C and 24°C) and a 4-day treatment with the antibiotic oxytetracycline (OTC) at 1 and 100μg/L on cellular and molecular parameters in the mussel Mytilus galloprovincialis. Lysosomal membrane stability (LMS), a sensitive biomarker of impaired health status in this organism, was assessed in the digestive glands. In addition, oxidative stress markers and the expression of mRNAs encoding proteins involved in antioxidant defense (catalase (cat) and glutathione-S-transferase (gst)) and the heat shock response (hsp90, hsp70, and hsp27) were evaluated in the gills, the target tissue of soluble chemicals. Finally, cAMP levels, which represent an important cell signaling pathway related to oxidative stress and the response to temperature challenges, were also determined in the gills. Exposure to heat stress as well as to OTC rendered a decrease in LMS and an increase in malonedialdehyde accumulation (MDA). CAT activity was not significantly modified, whereas GST activity decreased at 24°C. Cat and gst expression levels were reduced in animals kept at 24°C compared to 16°C in the presence or absence of OTC. At 16°C, treatment with OTC caused a significant increase in cat and gst transcript levels. Hsp27 mRNA was significantly up-regulated at all conditions compared to controls at 16°C. cAMP levels were increased at 24°C independent of the presence of OTC. PCA analysis showed that 37.21% and 25.89% of the total variance was explained by temperature and OTC treatment, respectively. Interestingly, a clear interaction was observed in animals exposed to both stressors increasing LMS and MDA accumulation and reducing hsp27 gene expression regulation. These interactions may suggest a risk for the organisms due to temperature increases in contaminated seawaters. PMID:26067465

  13. Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

    Directory of Open Access Journals (Sweden)

    Pamela P. Lee

    2017-06-01

    Full Text Available The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV, hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs. Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique

  14. Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Sara Anjomani Virmouni

    Full Text Available Friedreich ataxia (FRDA is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats, YG8R (90 and 190 GAA repeats and YG22R (190 GAA repeats.We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R.Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.

  15. Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment.

    Science.gov (United States)

    Alboni, S; van Dijk, R M; Poggini, S; Milior, G; Perrotta, M; Drenth, T; Brunello, N; Wolfer, D P; Limatola, C; Amrein, I; Cirulli, F; Maggi, L; Branchi, I

    2017-04-01

    Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis. To test such hypothesis, we exposed C57BL/6 mice to chronic stress in order to induce a depression-like phenotype and, subsequently, to fluoxetine treatment (21 days), while being exposed to either an enriched or a stressful condition. We measured the most commonly investigated molecular, cellular and behavioral endophenotypes of depression and SSRI outcome, including depression-like behavior, neurogenesis, brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis activity and long-term potentiation. Results showed that, in line with our hypothesis, the endophenotypes investigated were affected by the treatment according to the quality of the living environment. In particular, mice treated with fluoxetine in an enriched condition overall improved their depression-like phenotype compared with controls, whereas those treated in a stressful condition showed a distinct worsening. Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

  16. The miracle of Lidocaine: Second Look with Cellular and Molecular Perspectives

    Directory of Open Access Journals (Sweden)

    Mahnoosh Foroughi

    2018-01-01

    maintenance. Balancing the homeostasis, correction of acid base irregularity, pain management, bleedingcontrol and reduction of blood loss during surgery are part of the main skills of anesthesiologists. Today attention to cellular and molecular aspects of mentioned items are the more interesting topics. Consideration of molecular basis of these items are the main aim of the Journal of Cellular and Molecular Anesthesia.

  17. CPTAC Collaborates with Molecular & Cellular Proteomics to Address Reproducibility in Targeted Assay Development | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The journal Molecular & Cellular Proteomics (MCP), in collaboration with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins (Mol Cell Proteomics 2017; PMID: 28183812).  NCI’s participation is part of NIH’s overall effort to address the r

  18. Barriers to Real-Time Medical Direction via Cellular Communication for Prehospital Emergency Care Providers in Gujarat, India.

    Science.gov (United States)

    Lindquist, Benjamin; Strehlow, Matthew C; Rao, G V Ramana; Newberry, Jennifer A

    2016-07-08

    Many low- and middle-income countries depend on emergency medical technicians (EMTs), nurses, midwives, and layperson community health workers with limited training to provide a majority of emergency medical, trauma, and obstetric care in the prehospital setting. To improve timely patient care and expand provider scope of practice, nations leverage cellular phones and call centers for real-time online medical direction. However, there exist several barriers to adequate communication that impact the provision of emergency care. We sought to identify obstacles in the cellular communication process among GVK Emergency Management and Research Institute (GVK EMRI) EMTs in Gujarat, India. A convenience sample of practicing EMTs in Gujarat, India were surveyed regarding the barriers to call initiation and completion. 108 EMTs completed the survey. Overall, ninety-seven (89.8%) EMTs responded that the most common reason they did not initiate a call with the call center physician was insufficient time. Forty-six (42%) EMTs reported that they were unable to call the physician one or more times during a typical workweek (approximately 5-6 twelve-hour shifts/week) due to their hands being occupied performing direct patient care. Fifty-eight (54%) EMTs reported that they were unable to reach the call center physician, despite attempts, at least once a week. This study identified multiple barriers to communication, including insufficient time to call for advice and inability to reach call center physicians. Identification of simple interventions and best practices may improve communication and ensure timely and appropriate prehospital care.

  19. Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment.

    Science.gov (United States)

    Rangel-Castilla, Leonardo; Russin, Jonathan J; Martinez-Del-Campo, Eduardo; Soriano-Baron, Hector; Spetzler, Robert F; Nakaji, Peter

    2014-09-01

    Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

  20. Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C

    Directory of Open Access Journals (Sweden)

    Roy Siddhartha

    2008-11-01

    Full Text Available Abstract Background Cigarette smoke-induced cellular and molecular mechanisms of lung injury are not clear. Cigarette smoke is a complex mixture containing long-lived radicals, including p-benzosemiquinone that causes oxidative damage. Earlier we had reported that oxidative protein damage is an initial event in smoke-induced lung injury. Considering that p-benzosemiquinone may be a causative factor of lung injury, we have isolated p-benzosemiquinone and compared its pathophysiological effects with cigarette smoke. Since vitamin C is a strong antioxidant, we have also determined the modulatory effect of vitamin C for preventing the pathophysiological events. Methods Vitamin C-restricted guinea pigs were exposed to cigarette smoke (5 cigarettes/day; 2 puffs/cigarette for 21 days with and without supplementation of 15 mg vitamin C/guinea pig/day. Oxidative damage, apoptosis and lung injury were assessed in vitro, ex vivo in A549 cells as well as in vivo in guinea pigs. Inflammation was measured by neutrophilia in BALF. p-Benzosemiquinone was isolated from freshly prepared aqueous extract of cigarette smoke and characterized by various physico-chemical methods, including mass, NMR and ESR spectroscopy. p-Benzosemiquinone-induced lung damage was examined by intratracheal instillation in guinea pigs. Lung damage was measured by increased air spaces, as evidenced by histology and morphometric analysis. Oxidative protein damage, MMPs, VEGF and VEGFR2 were measured by western blot analysis, and formation of Michael adducts using MALDI-TOF-MS. Apoptosis was evidenced by TUNEL assay, activation of caspase 3, degradation of PARP and increased Bax/Bcl-2 ratio using immunoblot analysis and confocal microscopy. Results Exposure of guinea pigs to cigarette smoke resulted in progressive protein damage, inflammation, apoptosis and lung injury up to 21 days of the experimental period. Administration of 15 mg of vitamin C/guinea pig/day prevented all these

  1. Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

    Full Text Available BACKGROUND: Familial dysautonomia (FD is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion:MU (exon 20 skipping ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation. CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better

  2. The emerging molecular biology toolbox for the study of long noncoding RNA biology.

    Science.gov (United States)

    Fok, Ezio T; Scholefield, Janine; Fanucchi, Stephanie; Mhlanga, Musa M

    2017-10-01

    Long noncoding RNAs (lncRNAs) have been implicated in many biological processes. However, due to the unique nature of lncRNAs and the consequential difficulties associated with their characterization, there is a growing disparity between the rate at which lncRNAs are being discovered and the assignment of biological function to these transcripts. Here we present a molecular biology toolbox equipped to help dissect aspects of lncRNA biology and reveal functionality. We outline an approach that begins with a broad survey of genome-wide, high-throughput datasets to identify potential lncRNA candidates and then narrow the focus on specific methods that are well suited to interrogate the transcripts of interest more closely. This involves the use of imaging-based strategies to validate these candidates and observe the behaviors of these transcripts at single molecule resolution in individual cells. We also describe the use of gene editing tools and interactome capture techniques to interrogate functionality and infer mechanism, respectively. With the emergence of lncRNAs as important molecules in healthy and diseased cellular function, it remains crucial to deepen our understanding of their biology.

  3. Emergence of Distinct Spatial Patterns in Cellular Automata with Inertia: A Phase Transition-Like Behavior

    Directory of Open Access Journals (Sweden)

    Klaus Kramer

    2017-03-01

    Full Text Available We propose a Cellular Automata (CA model in which three ubiquitous and relevant processes in nature are present, namely, spatial competition, distinction between dynamically stronger and weaker agents and the existence of an inner resistance to changes in the actual state S n (=−1,0,+1 of each CA lattice cell n (which we call inertia. Considering ensembles of initial lattices, we study the average properties of the CA final stationary configuration structures resulting from the system time evolution. Assuming the inertia a (proper control parameter, we identify qualitative changes in the CA spatial patterns resembling usual phase transitions. Interestingly, some of the observed features may be associated with continuous transitions (critical phenomena. However, certain quantities seem to present jumps, typical of discontinuous transitions. We argue that these apparent contradictory findings can be attributed to the inertia parameter’s discrete character. Along the work, we also briefly discuss a few potential applications for the present CA formulation.

  4. Modelling molecular mechanisms: a framework of scientific reasoning to construct molecular-level explanations for cellular behaviour

    NARCIS (Netherlands)

    van Mil, M.H.W.; Boerwinkel, D.J.; Waarlo, A.J.

    2013-01-01

    Although molecular-level details are part of the upper-secondary biology curriculum in most countries, many studies report that students fail to connect molecular knowledge to phenomena at the level of cells, organs and organisms. Recent studies suggest that students lack a framework to reason about

  5. Modelling Molecular Mechanisms: A Framework of Scientific Reasoning to Construct Molecular-Level Explanations for Cellular Behaviour

    Science.gov (United States)

    van Mil, Marc H. W.; Boerwinkel, Dirk Jan; Waarlo, Arend Jan

    2013-01-01

    Although molecular-level details are part of the upper-secondary biology curriculum in most countries, many studies report that students fail to connect molecular knowledge to phenomena at the level of cells, organs and organisms. Recent studies suggest that students lack a framework to reason about complex systems to make this connection. In this…

  6. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    Science.gov (United States)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

  7. The emerging role of cloud computing in molecular modelling.

    Science.gov (United States)

    Ebejer, Jean-Paul; Fulle, Simone; Morris, Garrett M; Finn, Paul W

    2013-07-01

    There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. A comparative analysis of electronic and molecular quantum dot cellular automata

    International Nuclear Information System (INIS)

    Umamahesvari, H.; Ajitha, D.

    2015-01-01

    This paper presents a comparative analysis of electronic quantum-dot cellular automata (EQCA) and Magnetic quantum dot Cellular Automata (MQCA). QCA is a computing paradigm that encodes and processes information by the position of individual electrons. To enhance the high dense and ultra-low power devices, various researches have been actively carried out to find an alternative way to continue and follow Moore’s law, so called “beyond CMOS technology”. There have been several proposals for physically implementing QCA, EQCA and MQCA are the two important QCAs reported so far. This paper provides a comparative study on these two QCAs

  9. ART culture conditions change the probability of mouse embryo gestation through defined cellular and molecular responses.

    Science.gov (United States)

    Schwarzer, Caroline; Esteves, Telma Cristina; Araúzo-Bravo, Marcos J; Le Gac, Séverine; Nordhoff, Verena; Schlatt, Stefan; Boiani, Michele

    2012-09-01

    Do different human ART culture protocols prepare embryos differently for post-implantation development? The type of ART culture protocol results in distinct cellular and molecular phenotypes in vitro at the blastocyst stage as well as subsequently during in vivo development. It has been reported that ART culture medium affects human development as measured by gestation rates and birthweights. However, due to individual variation across ART patients, it is not possible as yet to pinpoint a cause-effect relationship between choice of culture medium and developmental outcome. In a prospective study, 13 human ART culture protocols were compared two at a time against in vivo and in vitro controls. Superovulated mouse oocytes were fertilized in vivo using outbred and inbred mating schemes. Zygotes were cultured in medium or in the oviduct and scored for developmental parameters 96 h later. Blastocysts were either analyzed or transferred into fosters to measure implantation rates and fetal development. In total, 5735 fertilized mouse oocytes, 1732 blastocysts, 605 fetuses and 178 newborns were examined during the course of the study (December 2010-December 2011). Mice of the B6C3F1, C57Bl/6 and CD1 strains were used as oocyte donors, sperm donors and recipients for embryo transfer, respectively. In vivo fertilized B6C3F1 oocytes were allowed to cleave in 13 human ART culture protocols compared with mouse oviduct and optimized mouse medium (KSOM(aa)). Cell lineage composition of resultant blastocysts was analyzed by immunostaining and confocal microscopy (trophectoderm, Cdx2; primitive ectoderm, Nanog; primitive endoderm, Sox17), global gene expression by microarray analysis, and rates of development to midgestation and to term. Mouse zygotes show profound variation in blastocyst (49.9-91.9%) and fetal (15.7-62.0%) development rates across the 13 ART culture protocols tested (R(2)= 0.337). Two opposite protocols, human tubal fluid/multiblast (high fetal rate) and ISM1/ISM2

  10. Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell

    Science.gov (United States)

    Sotiropoulou, Georgia; Pampalakis, Georgios; Lianidou, Evi; Mourelatos, Zissimos

    2009-01-01

    Transformation of normal cells into malignant tumors requires the acquisition of six hallmark traits, e.g., self-sufficiency in growth signals, insensitivity to antigrowth signals and self-renewal, evasion of apoptosis, limitless replication potential, angiogenesis, invasion, and metastasis, which are common to all cancers (Hanahan and Weinberg 2000). These new cellular traits evolve from defects in major regulatory microcircuits that are fundamental for normal homeostasis. The discovery of microRNAs (miRNAs) as a new class of small non-protein-coding RNAs that control gene expression post-transcriptionally by binding to various mRNA targets suggests that these tiny RNA molecules likely act as molecular switches in the extensive regulatory web that involves thousands of transcripts. Most importantly, accumulating evidence suggests that numerous microRNAs are aberrantly expressed in human cancers. In this review, we discuss the emergent roles of microRNAs as switches that function to turn on/off known cellular microcircuits. We outline recent compelling evidence that deregulated microRNA-mediated control of cellular microcircuits cooperates with other well-established regulatory mechanisms to confer the hallmark traits of the cancer cell. Furthermore, these exciting insights into aberrant microRNA control in cancer-associated circuits may be exploited for cancer therapies that will target deregulated miRNA switches. PMID:19561119

  11. RNAi: An emerging field of molecular research | Kabir | African ...

    African Journals Online (AJOL)

    RNA interference (RNAi) is a specific technique using only a few double stranded RNA (dsRNA) molecules to stop the expression which has made it one of the important areas in molecular biology. By introducing a gene into the host genome which is highly homologous to an endogenous gene, the RNA silencing is ...

  12. Selected materials of the international workshop on radiation risk and its origin at molecular and cellular level

    International Nuclear Information System (INIS)

    Pinak, Miroslav

    2003-11-01

    The workshop ''International Workshop on Radiation Risk and its Origin at Molecular and Cellular Level'' was held at The Tokai Research Establishment, Japan Atomic Energy Research Institute, on the 6th and 7th of February 2003. The Laboratory of Radiation Risk Analysis of JAERI organized it. This international workshop attracted scientists from several different scientific areas, including radiation physics, radiation biology, molecular biology, crystallography of biomolecules, modeling and bio-informatics. Several foreign and domestic keynote speakers addresses the very fundamental areas of radiation risk and tried to establish a link between the fundamental studies at the molecular and cellular level and radiation damages at the organism. The symposium consisted of 13 oral lectures, 10 poster presentations and panel discussion. The 108 participants attended the workshop. This publication comprises of proceedings of oral and poster presentations where available. For the rest of contributions the abstracts or/and selections of presentation materials are shown instead. The 5 papers are indexed individually. (J.P.N.)

  13. Functional Proteomics Defines the Molecular Switch Underlying FGF Receptor Trafficking and Cellular Outputs

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B

    2013-01-01

    The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation...

  14. Mechanisms and Regulation of Intestinal Absorption of Water-soluble Vitamins: Cellular and Molecular Aspects

    DEFF Research Database (Denmark)

    Nexø, Ebba; Said, Hamid M

    2012-01-01

    The water-soluble vitamins represent a group of structurally and functionally unrelated compounds that share the common feature of being essential for normal cellular functions, growth, and development. With the exception of some endogenous production of niacin, human cells cannot synthesize...

  15. Just Working with the Cellular Machine: A High School Game for Teaching Molecular Biology

    Science.gov (United States)

    Cardoso, Fernanda Serpa; Dumpel, Renata; Gomes da Silva, Luisa B.; Rodrigues, Carlos R.; Santos, Dilvani O.; Cabral, Lucio Mendes; Castro, Helena C.

    2008-01-01

    Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several…

  16. Characterization of the emergent properties of a synthetic quasi-cellular system

    Directory of Open Access Journals (Sweden)

    Lazzerini-Ospri Lorenzo

    2012-03-01

    Full Text Available Abstract Background The process of solutes entrapment during liposomes formation is interesting for the investigation of the relationship between the formation of compartments and the distribution of molecules inside them; a relevant issue in the studies of the origin of life. Theoretically, when no interactions are supposed among the chemical species to be entrapped, the entrapment is described by a standard Poisson process. But very recent experimental findings show that, for small liposomes (100 nm diameter, the distribution of entrapped molecules is best described by a power-law function. This is of a great importance, as the two random processes give rise to two completely different scenarios. Here we present an in silico stochastic simulation of the encapsulation of a cell-free molecular translation system (the PURE system, obtained following two different entrapment models: a pure Poisson process, and a power-law. The protein synthesis inside the liposomes has been studied in both cases, with the aim to highlight experimental observables that could be measured to assess which model gives a better representation of the real process. Results Firstly, a minimal model for in vitro protein synthesis, based on the PURE system molecular composition, has been formalized. Then, we have designed a reliable experimental simulation where stochastic factors affect the reaction course inside the compartment. To this end, 24 solutes, which represent the PURE system components, have been stochastically distributed among vesicles by following either a Poisson or a power-law distribution. The course of the protein synthesis within each vesicle has been consequently calculated, as a function of vesicle size. Our study can predict translation yield in a population of small liposomes down to the attoliter (10-18 L range. Our results show that the efficiency of protein synthesis peaks at approximately 3·10-16 L (840 nm diam. with a Poisson distribution of

  17. Molecular Mechanistic Reasoning: Toward Bridging the Gap between the Molecular and Cellular Levels in Life Science Education

    Science.gov (United States)

    van Mil, Marc H. W.; Postma, Paulien A.; Boerwinkel, Dirk Jan; Klaassen, Kees; Waarlo, Arend Jan

    2016-01-01

    Although learning about DNA, RNA, and proteins is part of the upper secondary biology curriculum in most countries, many studies report that students fail to connect molecular knowledge to phenomena at the higher level of cells, organs, and organisms. As a result, many students use memorization and rote learning as a coping strategy when presented…

  18. Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi's anemia

    International Nuclear Information System (INIS)

    Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F.

    1997-01-01

    Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to γ-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

  19. Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi`s anemia

    Energy Technology Data Exchange (ETDEWEB)

    Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F. [Institut Curie-Recherche, UMR 218, CNRS, 75 - Paris (France)

    1997-03-01

    Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to {gamma}-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

  20. Organizing the Cellular and Molecular Heterogeneity in High-Grade Serous Ovarian Cancer by Mass Cytometry

    Science.gov (United States)

    2013-10-01

    Acknowledgements The authors wish to thank Drs Scott Tanner, Olga Ornatsky, Dmitry Bandura , Mitch Winnik and Mark Nitz for their critical reading of this...Quality assurance for polychromatic flow cytometry using a suite of calibration beads. Nat Protoc 2012, 7:2067-2079. 23. Baranov VI, Quinn Z, Bandura ... Bandura DR, Tanner SD, Dick J: Multiple cellular antigen detection by ICP-MS. J Immunol Methods 2006, 308:68-76. 25. Ornatsky OI, Kinach R, Bandura DR

  1. Organizing the Cellular and Molecular Heterogeneity in High Grade Serous Ovarian Cancer by Mass Cytometry

    Science.gov (United States)

    2015-10-01

    about more informed changes to treatment modalities. To accomplish this vision with HG-SOC, we are using a single cell technology , mass cytometry... extracted from the composite MST. Clusters are represented as bubbles, the size of which corresponds to the number of cells in the cluster. The level of...Fantl WJ, Nolan GP. Transient partial permeabilization with saponin enables cellular barcoding prior to surface marker staining. Cytometry A. 2014 Dec;85

  2. Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration.

    Science.gov (United States)

    Kohler, Julia; Popov, Cvetan; Klotz, Barbara; Alberton, Paolo; Prall, Wolf Christian; Haasters, Florian; Müller-Deubert, Sigrid; Ebert, Regina; Klein-Hitpass, Ludger; Jakob, Franz; Schieker, Matthias; Docheva, Denitsa

    2013-12-01

    Although the link between altered stem cell properties and tissue aging has been recognized, the molecular and cellular processes of tendon aging have not been elucidated. As tendons contain stem/progenitor cells (TSPC), we investigated whether the molecular and cellular attributes of TSPC alter during tendon aging and degeneration. Comparing TSPC derived from young/healthy (Y-TSPC) and aged/degenerated human Achilles tendon biopsies (A-TSPC), we observed that A-TSPC exhibit a profound self-renewal and clonogenic deficits, while their multipotency was still retained. Senescence analysis showed a premature entry into senescence of the A-TSPC, a finding accompanied by an upregulation of p16(INK4A). To identify age-related molecular factors, we performed microarray and gene ontology analyses. These analyses revealed an intriguing transcriptomal shift in A-TSPC, where the most differentially expressed probesets encode for genes regulating cell adhesion, migration, and actin cytoskeleton. Time-lapse analysis showed that A-TSPC exhibit decelerated motion and delayed wound closure concomitant to a higher actin stress fiber content and a slower turnover of actin filaments. Lastly, based on the expression analyses of microarray candidates, we suggest that dysregulated cell-matrix interactions and the ROCK kinase pathway might be key players in TSPC aging. Taken together, we propose that during tendon aging and degeneration, the TSPC pool is becoming exhausted in terms of size and functional fitness. Thus, our study provides the first fundamental basis for further exploration into the molecular mechanisms behind tendon aging and degeneration as well as for the selection of novel tendon-specific therapeutical targets. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Molecular detection of Capillaria philippinensis: An emerging zoonosis in Egypt.

    Science.gov (United States)

    El-Dib, Nadia A; El-Badry, Ayman A; Ta-Tang, Thuy-Huong; Rubio, Jose M

    2015-07-01

    Human infection with Capillaria philippinensis is accidental; however, it may end fatally if not diagnosed and treated in the proper time. The first case was detected in the Philippines in 1963, but later reported in other countries around the world, including Egypt. In this report, molecular diagnosis using a specific nested PCR for detection of C. philippinensis in faeces is described based on the amplification of small ribosomal subunit. The test showed sensitivity and specificity, as it detected all the positive cases and gave no cross-reaction with human DNA and DNA of other tested parasites. This method can be very useful not only for improvement of diagnosis, but also to understand the different environmental routes of transmission by detection of C. philippinensis DNA-stages in the possible fish intermediate hosts and reservoir animal host, helping to improve strategies for surveillance and prevention of human disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

    Science.gov (United States)

    Kubben, Nard; Misteli, Tom

    2017-10-01

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

  5. MicroRNAs - A New Generation Molecular Targets for Treating Cellular Diseases

    OpenAIRE

    Paulmurugan, Ramasamy

    2013-01-01

    MicroRNAs (miRNAs) are a unique class of non-coding, small RNAs, similar to mRNAs, transcribed by cells, but for entirely different reasons. While mRNAs are transcribed to code for proteins, miRNAs are produced to regulate the production of proteins from mRNAs. miRNAs are central components that tightly and temporally regulating gene expression in cells. Dysregulation of miRNAs expressions in cellular pathogenesis, including cancer, has been reported, and it clearly supports the importance of...

  6. Cellular and exosome mediated molecular defense mechanism in bovine granulosa cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed Saeed-Zidane

    Full Text Available Various environmental insults including diseases, heat and oxidative stress could lead to abnormal growth, functions and apoptosis in granulosa cells during ovarian follicle growth and oocyte maturation. Despite the fact that cells exposed to oxidative stress are responding transcriptionally, the potential release of transcripts associated with oxidative stress response into extracellular space through exosomes is not yet determined. Therefore, here we aimed to investigate the effect of oxidative stress in bovine granulosa cells in vitro on the cellular and exosome mediated defense mechanisms. Bovine granulosa cells were aspirated from ovarian follicles and cultured in DMEM/F-12 Ham culture medium supplemented with 10% exosome-depleted fetal bovine serum. In the first experiment sub-confluent cells were treated with 5 μM H2O2 for 40 min to induce oxidative stress. Thereafter, cells were subjected to ROS and mitochondrial staining, cell proliferation and cell cycle assays. Furthermore, gene and protein expression analysis were performed in H2O2-challenged versus control group 24 hr post-treatment using qRT-PCR and immune blotting or immunocytochemistry assay, respectively. Moreover, exosomes were isolated from spent media using ultracentrifugation procedure, and subsequently used for RNA isolation and qRT-PCR. In the second experiment, exosomes released by granulosa cells under oxidative stress (StressExo or those released by granulosa cells without oxidative stress (NormalExo were co-incubated with bovine granulosa cells in vitro to proof the potential horizontal transfer of defense molecules from exosomes to granulosa cells and investigate any phenotype changes. Exposure of bovine granulosa cells to H2O2 induced the accumulation of ROS, reduced mitochondrial activity, increased expression of Nrf2 and its downstream antioxidant genes (both mRNA and protein, altered the cell cycle transitions and induced cellular apoptosis. Granulosa cells

  7. Molecular mechanisms underlying the emergence of bacterial pathogens: an ecological perspective.

    Science.gov (United States)

    Bartoli, Claudia; Roux, Fabrice; Lamichhane, Jay Ram

    2016-02-01

    The rapid emergence of new bacterial diseases negatively affects both human health and agricultural productivity. Although the molecular mechanisms underlying these disease emergences are shared between human- and plant-pathogenic bacteria, not much effort has been made to date to understand disease emergences caused by plant-pathogenic bacteria. In particular, there is a paucity of information in the literature on the role of environmental habitats in which plant-pathogenic bacteria evolve and on the stress factors to which these microbes are unceasingly exposed. In this microreview, we focus on three molecular mechanisms underlying pathogenicity in bacteria, namely mutations, genomic rearrangements and the acquisition of new DNA sequences through horizontal gene transfer (HGT). We briefly discuss the role of these mechanisms in bacterial disease emergence and elucidate how the environment can influence the occurrence and regulation of these molecular mechanisms by directly impacting disease emergence. The understanding of such molecular evolutionary mechanisms and their environmental drivers will represent an important step towards predicting bacterial disease emergence and developing sustainable management strategies for crops. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  8. Molecular targets of omega 3 and conjugated linoleic fatty acids – micromanaging cellular response

    Directory of Open Access Journals (Sweden)

    Francesco eVisioli

    2012-02-01

    Full Text Available Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and CLA, as paradigmatic molecules that can be explored both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids.

  9. Differential Cellular and Molecular Effects of Butyrate and Trichostatin A on Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Kasturi Ranganna

    2012-09-01

    Full Text Available The histone deacetylase (HDAC inhibitors, butyrate and trichostatin A (TSA, are epigenetic histone modifiers and proliferation inhibitors by downregulating cyclin D1, a positive cell cycle regulator, and upregulating p21Cip1 and INK family of proteins, negative cell cycle regulators. Our recent study indicated cyclin D1 upregulation in vascular smooth muscle cells (VSMC that are proliferation-arrested by butyrate. Here we investigate whether cyclin D1 upregulation is a unique response of VSMC to butyrate or a general response to HDAC inhibitors (HDACi by evaluating the effects of butyrate and TSA on VSMC. While butyrate and TSA inhibit VSMC proliferation via cytostatic and cytotoxic effects, respectively, they downregulate cdk4, cdk6, and cdk2, and upregulate cyclin D3, p21Cip1 and p15INK4B, and cause similar effects on key histone H3 posttranslational modifications. Conversely, cyclin D1 is upregulated by butyrate and inhibited by TSA. Assessment of glycogen synthase 3-dependent phosphorylation, subcellular localization and transcription of cyclin D1 indicates that differential effects of butyrate and TSA on cyclin D1 levels are linked to disparity in cyclin D1 gene expression. Disparity in butyrate- and TSA-induced cyclin D1 may influence transcriptional regulation of genes that are associated with changes in cellular morphology/cellular effects that these HDACi confer on VSMC, as a transcriptional modulator.

  10. Differential Modulation of Cellular Bioenergetics by Poly(L-lysine)s of Different Molecular Weights

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Wu, Lin-Ping; Parhamifar, Ladan

    2015-01-01

    Poly(L-lysine)s (PLLs), and related derivatives, have received considerable attention as nonviral vectors. High molecular weight PLLs (H-PLLs) are superior transfectants compared with low Mw PLLs (L-PLLs), but suggested to be more cytotoxic. Through a pan-integrated metabolomic approach using Sea...

  11. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

  12. Molecular events basic to cellular radiation response. Progress report, July 1, 1976--September 30, 1977

    International Nuclear Information System (INIS)

    Kolodny, G.M.

    1977-01-01

    Progress is reported on studies of the effects of x irradiation at the cellular level that lead ultimately to either malignant transformation or cell death. Experimental results consistent with the primer hypothesis for the regulation of gene expression in eukaryotes are reported. It was found that oligonucleotides can be inserted en bloc into newly synthesized RNA. Studies on amino acid-nucleic acid interactions were continued by successfully synthesizing an amidate and beginning NMR studies on the interactions between its nucleic acid and amino acid moieties. In studies on radiation induced giant cells in 3T3 cells growing in culture, it was demonstrated that conditions which potentiate potential lethal damage repair and those which prevent radiation induced giant cell formation exist. In an examination of the in vitro effects of vasopressin, no direct effect was found of vasopressin on radiation sensitivity and significant effects of radiation on lysosomal enzyme activity in cultured cells were found

  13. Molecular events basic to cellular radiation response. Progress report, July 1, 1976--September 30, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Kolodny, G.M.

    1977-01-01

    Progress is reported on studies of the effects of x irradiation at the cellular level that lead ultimately to either malignant transformation or cell death. Experimental results consistent with the primer hypothesis for the regulation of gene expression in eukaryotes are reported. It was found that oligonucleotides can be inserted en bloc into newly synthesized RNA. Studies on amino acid-nucleic acid interactions were continued by successfully synthesizing an amidate and beginning NMR studies on the interactions between its nucleic acid and amino acid moieties. In studies on radiation induced giant cells in 3T3 cells growing in culture, it was demonstrated that conditions which potentiate potential lethal damage repair and those which prevent radiation induced giant cell formation exist. In an examination of the in vitro effects of vasopressin, no direct effect was found of vasopressin on radiation sensitivity and significant effects of radiation on lysosomal enzyme activity in cultured cells were found.

  14. Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

    Science.gov (United States)

    Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

    2013-04-01

    There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Insights into the HyPer biosensor as molecular tool for monitoring cellular antioxidant capacity.

    Science.gov (United States)

    Hernández, Helen; Parra, Alejandra; Tobar, Nicolas; Molina, Jessica; Kallens, Violeta; Hidalgo, Miltha; Varela, Diego; Martínez, Jorge; Porras, Omar

    2018-06-01

    Aerobic metabolism brings inexorably the production of reactive oxygen species (ROS), which are counterbalanced by intrinsic antioxidant defenses avoiding deleterious intracellular effects. Redox balance is the resultant of metabolic functioning under environmental inputs (i.e. diet, pollution) and the activity of intrinsic antioxidant machinery. Monitoring of intracellular hydrogen peroxide has been successfully achieved by redox biosensor advent; however, to track the intrinsic disulfide bond reduction capacity represents a fundamental piece to understand better how redox homeostasis is maintained in living cells. In the present work, we compared the informative value of steady-state measurements and the kinetics of HyPer, a H 2 O 2 -sensitive fluorescent biosensor, targeted at the cytosol, mitochondrion and endoplasmic reticulum. From this set of data, biosensor signal recovery from an oxidized state raised as a suitable parameter to discriminate reducing capacity of a close environment. Biosensor recovery was pH-independent, condition demonstrated by experiments on pH-clamped cells, and sensitive to pharmacological perturbations of enzymatic disulfide reduction. Also, ten human cell lines were characterized according their H 2 O 2 -pulse responses, including their capacity to reduce disulfide bonds evaluated in terms of their migratory capacity. Finally, cellular migration experiments were conducted to study whether migratory efficiency was associated with the disulfide reduction activity. The migration efficiency of each cell type correlates with the rate of signal recovery measured from the oxidized biosensor. In addition, HyPer-expressing cells treated with N-acetyl-cysteine had accelerated recovery rates and major migratory capacities, both reversible effects upon treatment removal. Our data demonstrate that the HyPer signal recovery offers a novel methodological tool to track the cellular impact of redox active biomolecules. Copyright © 2018 The Authors

  16. Insights into the HyPer biosensor as molecular tool for monitoring cellular antioxidant capacity

    Directory of Open Access Journals (Sweden)

    Helen Hernández

    2018-06-01

    Full Text Available Aerobic metabolism brings inexorably the production of reactive oxygen species (ROS, which are counterbalanced by intrinsic antioxidant defenses avoiding deleterious intracellular effects. Redox balance is the resultant of metabolic functioning under environmental inputs (i.e. diet, pollution and the activity of intrinsic antioxidant machinery. Monitoring of intracellular hydrogen peroxide has been successfully achieved by redox biosensor advent; however, to track the intrinsic disulfide bond reduction capacity represents a fundamental piece to understand better how redox homeostasis is maintained in living cells.In the present work, we compared the informative value of steady-state measurements and the kinetics of HyPer, a H2O2-sensitive fluorescent biosensor, targeted at the cytosol, mitochondrion and endoplasmic reticulum. From this set of data, biosensor signal recovery from an oxidized state raised as a suitable parameter to discriminate reducing capacity of a close environment. Biosensor recovery was pH-independent, condition demonstrated by experiments on pH-clamped cells, and sensitive to pharmacological perturbations of enzymatic disulfide reduction. Also, ten human cell lines were characterized according their H2O2-pulse responses, including their capacity to reduce disulfide bonds evaluated in terms of their migratory capacity.Finally, cellular migration experiments were conducted to study whether migratory efficiency was associated with the disulfide reduction activity. The migration efficiency of each cell type correlates with the rate of signal recovery measured from the oxidized biosensor. In addition, HyPer-expressing cells treated with N-acetyl-cysteine had accelerated recovery rates and major migratory capacities, both reversible effects upon treatment removal. Our data demonstrate that the HyPer signal recovery offers a novel methodological tool to track the cellular impact of redox active biomolecules. Keywords: Antioxidant

  17. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    Energy Technology Data Exchange (ETDEWEB)

    Edelbrock, Michael A., E-mail: Edelbrock@findlay.edu [The University of Findlay, 1000 North Main Street, Findlay, OH 45840 (United States); Kaliyaperumal, Saravanan, E-mail: Saravanan.Kaliyaperumal@hms.harvard.edu [Division of Comparative Medicine and Pathology, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772 (United States); Williams, Kandace J., E-mail: Kandace.williams@utoledo.edu [University of Toledo College of Medicine and Life Sciences, Department of Biochemistry and Cancer Biology, 3000 Transverse Dr., Toledo, OH 43614 (United States)

    2013-03-15

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O{sup 6}meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6.

  18. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    International Nuclear Information System (INIS)

    Edelbrock, Michael A.; Kaliyaperumal, Saravanan; Williams, Kandace J.

    2013-01-01

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O 6 meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6

  19. Molecular and Cellular Organization of Taste Neurons in Adult Drosophila Pharynx

    OpenAIRE

    Yu-Chieh David Chen; Anupama Dahanukar

    2017-01-01

    Summary: The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The ...

  20. A Protoplast Transient Expression System to Enable Molecular, Cellular, and Functional Studies in Phalaenopsis orchids

    Directory of Open Access Journals (Sweden)

    Hsiang-Yin Lin

    2018-06-01

    Full Text Available The enigmatic nature of the specialized developmental programs of orchids has fascinated plant biologists for centuries. The recent releases of orchid genomes indicate that orchids possess new gene families and family expansions and contractions to regulate a diverse suite of developmental processes. However, the extremely long orchid life cycle and lack of molecular toolkit have hampered the advancement of orchid biology research. To overcome the technical difficulties and establish a platform for rapid gene regulation studies, in this study, we developed an efficient protoplast isolation and transient expression system for Phalaenopsis aphrodite. This protocol was successfully applied to protein subcellular localization and protein–protein interaction studies. Moreover, it was confirmed to be useful in delineating the PaE2F/PaDP-dependent cell cycle pathway and studying auxin response. In summary, the established orchid protoplast transient expression system provides a means to functionally characterize orchid genes at the molecular level allowing assessment of transcriptome responses to transgene expression and widening the scope of molecular studies in orchids.

  1. Molecular and Cellular Organization of Taste Neurons in Adult Drosophila Pharynx

    Directory of Open Access Journals (Sweden)

    Yu-Chieh David Chen

    2017-12-01

    Full Text Available Summary: The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons. We validate the mapping results by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons. Our results provide roadmaps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors. : Chen and Dahanukar carry out a large-scale, systematic analysis to understand the molecular organization of pharyngeal taste neurons. Taking advantage of the molecular genetic toolkit that arises from this map, they use genetic dissection strategies to probe the functional roles of selected pharyngeal neurons in food choice. Keywords: Drosophila, taste, pharynx, chemosensory receptors, gustatory receptors, ionotropic receptors, feeding

  2. A Phylogenomic Census of Molecular Functions Identifies Modern Thermophilic Archaea as the Most Ancient Form of Cellular Life

    Directory of Open Access Journals (Sweden)

    Arshan Nasir

    2014-01-01

    Full Text Available The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

  3. A phylogenomic census of molecular functions identifies modern thermophilic archaea as the most ancient form of cellular life.

    Science.gov (United States)

    Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

    2014-01-01

    The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO) definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

  4. Semiconductor quantum dots as fluorescent probes for in vitro and in vivo bio-molecular and cellular imaging

    Directory of Open Access Journals (Sweden)

    Sarwat B. Rizvi

    2010-08-01

    Full Text Available Over the years, biological imaging has seen many advances, allowing scientists to unfold many of the mysteries surrounding biological processes. The ideal imaging resolution would be in nanometres, as most biological processes occur at this scale. Nanotechnology has made this possible with functionalised nanoparticles that can bind to specific targets and trace processes at the cellular and molecular level. Quantum dots (QDs or semiconductor nanocrystals are luminescent particles that have the potential to be the next generation fluorophores. This paper is an overview of the basics of QDs and their role as fluorescent probes for various biological imaging applications. Their potential clinical applications and the limitations that need to be overcome have also been discussed.

  5. Effect of Heat Stress on Reproduction in Dairy Cows: Insights into the Cellular and Molecular Responses of the Oocyte.

    Science.gov (United States)

    Roth, Zvi

    2017-02-08

    Among the components of the female reproductive tract, the ovarian pool of follicles and their enclosed oocytes are highly sensitive to hyperthermia. Heat-induced alterations in small antral follicles can be expressed later as compromised maturation and developmental capacity of the ovulating oocyte. This review summarizes the most up-to-date information on the effects of heat stress on the oocyte with an emphasis on unclear points and open questions, some of which might involve new research directions, for instance, whether preantral follicles are heat resistant. The review focuses on the follicle-enclosed oocytes, provides new insights into the cellular and molecular responses of the oocyte to elevated temperature, points out the role of the follicle microenvironment, and discusses some mechanisms that might underlie oocyte impairment. Mechanisms include nuclear and cytoplasmic maturation, mitochondrial function, apoptotic pathways, and oxidative stress. Understanding the mechanism by which heat stress compromises fertility might enable development of new strategies to mitigate its effects.

  6. Cellular and Molecular Mechanisms of the Production of Free Radicals during Exercise and Their Function on Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    2017-06-01

    Full Text Available Physical activity is an integral part of human life. Among significant biological changes during physical activity are increase of metabolism and production of free radicals. Free radical can be defined as molecule or molecular fragments containing unpaired electron in the outer orbital, which react with nearby molecules to obtain stability. These highly reactive molecules have various deleterious effects, such as reduced force generation and increased muscle atrophy. There is evidence that ROS produced during exercise has positive adaptation effects. ROS production leads to increased expression of the anti-oxidants. These molecules, by neutralizing free radicals, neutralize the negative effects of ROS. In addition, exercise-induced ROS leads to the expression of PGC-1α  protein, having a significant impact on various aspects of cell metabolism, mitochondrial biogenesis and cellular respiration as well as metabolism of fat and glucose. This paper provides an overview of the evidence to date on the effects of ROS on exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects,  role of antioxidants, and ROS-dependent adaptations of muscle cells in response to physical exercise

  7. Induction of cellular and molecular immunomodulatory pathways by vitamin A and Flavonoids

    Science.gov (United States)

    Patel, Sapna; Vajdy, Michael

    2016-01-01

    Introduction A detailed study of reports on the immunomodulatory properties of vitamin A and select flavonoids may pave the way for using these natural compounds or compounds with similar structures in novel drug and vaccine designs against infectious and autoimmune diseases and cancers. Areas Covered Intracellular transduction pathways, cellular differentiation and functional immunomodulatory responses have been reviewed. The reported studies encompass in vitro, in vivo preclinical and clinical studies that address the role of Vitamin A and select flavonoids in induction of innate and adaptive B and T cell responses, including TH1, TH2 and Treg. Expert Opinion While the immunomodulatory role of vitamin A, and related compounds, is well-established in many preclinical studies, its role in humans has begun to gain wider acceptance. In contrast, the role of flavonoids is mostly controversial in clinical trials, due to the diversity of the various classes of these compounds, and possibly due to the purity and the selected doses of the compounds. However, current preclinical and clinical studies warrant further detailed studies of these promising immuno-modulatory compounds. PMID:26185959

  8. Development of in vitro models for cellular and molecular studies in toxicology and chemoprevention

    Energy Technology Data Exchange (ETDEWEB)

    Mace, K.; Offord, E.A.; Harris, C.C.; Pfeifer, A.M.A. [Nestle Research Center, Lausanne (Switzerland)

    1998-12-31

    Many natural dietary phytochemicals found compounds found in fruits, vegetables, spices and tea have been shown in recent years to be protective against cancer in various animal models. In the light of the potential impact of these compounds on human health it is important to elucidate the mechanisms involved. We therefore developed and characterized relevant in vitro models using immortalized human epithelial cell lines derived from target tissues in carcinogenesis, such as lung, liver and colon. Assays were established, allowing the evaluation of the cytotoxic and genotoxic effects of various procarcinogens, including nitrosamines, mycotoxins and heterocyclic amines on these metabolically-competent human epithelial cell lines. These cellular models appeared to be a useful tool to study the capacity of certain food components to block the initiation stage of carcinogenesis. The ability of carnosol and carnosic acid from rosemary as well as the synthetic dithiolethione, oltipraz, to block the formation of DNA adducts, and their effects on the expression of phase I and phase II enzymes was investigated. We have observed that both rosemary extracts and oltiprax inhibited benzo(a)pyrene- or aflatoxin B{sub 1}-induced DNA adduct formation by strongly inhibiting CYP{sub 450} activities and inducing the expression of glutathione S-transferase. These results in human cell models give some insight into the different mechanisms involved in the chemopreventive action of both natural and synthetic compounds in relation to phase I and phase II enzymes. (orig.)

  9. Understanding the genetic and molecular pathogenesis of Friedreich’s ataxia through animal and cellular models

    Science.gov (United States)

    Martelli, Alain; Napierala, Marek; Puccio, Hélène

    2012-01-01

    In 1996, a link was identified between Friedreich’s ataxia (FRDA), the most common inherited ataxia in men, and alterations in the gene encoding frataxin (FXN). Initial studies revealed that the disease is caused by a unique, most frequently biallelic, expansion of the GAA sequence in intron 1 of FXN. Since the identification of this link, there has been tremendous progress in understanding frataxin function and the mechanism of FRDA pathology, as well as in developing diagnostics and therapeutic approaches for the disease. These advances were the subject of the 4th International Friedreich’s Ataxia Conference held on 5th–7th May in the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. More than 200 scientists gathered from all over the world to present the results of research spanning all areas of investigation into FRDA (including clinical aspects, FRDA pathogenesis, genetics and epigenetics of the disease, development of new models of FRDA, and drug discovery). This review provides an update on the understanding of frataxin function, developments of animal and cellular models of the disease, and recent advances in trying to uncover potential molecules for therapy. PMID:22382366

  10. Impact of photocatalysis on fungal cells: depiction of cellular and molecular effects on Saccharomyces cerevisiae.

    Science.gov (United States)

    Thabet, Sana; Simonet, France; Lemaire, Marc; Guillard, Chantal; Cotton, Pascale

    2014-12-01

    We have investigated the antimicrobial effects of photocatalysis on the yeast model Saccharomyces cerevisiae. To accurately study the antimicrobial mechanisms of the photocatalytic process, we focused our investigations on two questions: the entry of the nanoparticles in treated cells and the fate of the intracellular environment. Transmission electronic microscopy did not reveal any entry of nanoparticles within the cells, even for long exposure times, despite degradation of the cell wall space and deconstruction of cellular compartments. In contrast to proteins located at the periphery of the cells, intracellular proteins did not disappear uniformly. Disappearance or persistence of proteins from the pool of oxidized intracellular isoforms was not correlated to their functions. Altogether, our data suggested that photocatalysis induces the establishment of an intracellular oxidative environment. This hypothesis was sustained by the detection of an increased level of superoxide ions (O2°(-)) in treated cells and by greater cell cultivability for cells expressing oxidant stress response genes during photocatalytic exposure. The increase in intracellular ROS, which was not connected to the entry of nanoparticles within the cells or to a direct contact with the plasma membrane, could be the result of an imbalance in redox status amplified by chain reactions. Moreover, we expanded our study to other yeast and filamentous fungi and pointed out that, in contrast to the laboratory model S. cerevisiae, some environmental strains are very resistant to photocatalysis. This could be related to the cell wall composition and structure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. Focused Metabolite Profiling for Dissecting Cellular and Molecular Processes of Living Organisms in Space Environments

    Science.gov (United States)

    2008-01-01

    Regulatory control in biological systems is exerted at all levels within the central dogma of biology. Metabolites are the end products of all cellular regulatory processes and reflect the ultimate outcome of potential changes suggested by genomics and proteomics caused by an environmental stimulus or genetic modification. Following on the heels of genomics, transcriptomics, and proteomics, metabolomics has become an inevitable part of complete-system biology because none of the lower "-omics" alone provide direct information about how changes in mRNA or protein are coupled to changes in biological function. The challenges are much greater than those encountered in genomics because of the greater number of metabolites and the greater diversity of their chemical structures and properties. To meet these challenges, much developmental work is needed, including (1) methodologies for unbiased extraction of metabolites and subsequent quantification, (2) algorithms for systematic identification of metabolites, (3) expertise and competency in handling a large amount of information (data set), and (4) integration of metabolomics with other "omics" and data mining (implication of the information). This article reviews the project accomplishments.

  12. Cellular and molecular studies on ataxia-telangiectasia lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Fiorilli, M.; Crescenzi, M.; Carbonari, M.; Russo, G.; Businco, L.; Aiuti, F.

    1985-01-01

    We have examined several AT-related lesions in lymphoblastoid cell lines (LCLs) derived from AT patients. Diminished sensitivity to gamma-irradiation was found in six of seven AT-LCLs. A seventh line, from a patient with apparently normal T-cell immunity, responded normally following radiation. Constitutive proteins from exponentially growing AT-LCLs were assessed by SDS-PAGE analysis and did not differ significantly from normals. IgM synthesis was also normal except for one AT-LCL that contained native IgM molecules of different sizes, corresponding to the presence of pentamers and oligomers. Analysis under reducing conditions showed normal-sized secretory mu-chains. Finally, we examined mRNAs corresponding to two oncogenes, c-myc and c-myb, in AT and normal LCLs and found marked overproduction of c-myc in one AT-LCL (i.e., ATL6). The latter findings suggest that AT cells might be prone to aberrantly express cellular oncogenes as a result of chromosomal instability and consequent transposition of oncogenes

  13. Spatiotemporal control over molecular delivery and cellular encapsulation from electropolymerized micro- and nanopatterned surfaces.

    Science.gov (United States)

    Stern, Eric; Jay, Steven M; Demento, Stacey L; Murelli, Ryan P; Reed, Mark A; Malinski, Tadeusz; Spiegel, David A; Mooney, David J; Fahmy, Tarek M

    2009-07-13

    Bioactive, patterned micro- and nanoscale surfaces that can be spatially engineered for three-dimensional ligand presentation and sustained release of signaling molecules represent a critical advance for the development of next-generation diagnostic and therapeutic devices. Lithography is ideally suited to patterning such surfaces due to its precise, easily scalable, high-throughput nature; however, to date polymers patterned by these techniques have not demonstrated the capacity for sustained release of bioactive agents. We demonstrate here a class of lithographically-defined, electropolymerized polymers with monodisperse micro- and nanopatterned features capable of sustained release of bioactive drugs and proteins. We show that precise control can be achieved over the loading capacity and release rates of encapsulated agents and illustrate this aspect using a fabricated surface releasing a model antigen (ovalbumin) and a cytokine (interleukin-2) for induction of a specific immune response. We further demonstrate the ability of this technique to enable three-dimensional control over cellular encapsulation. The efficacy of the described approach is buttressed by its simplicity, versatility, and reproducibility, rendering it ideally suited for biomaterials engineering.

  14. Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Claus-Christian Glüer

    2010-12-01

    Full Text Available Superparamagnetic iron-oxide particles (SPIO are used in different ways as contrast agents for magnetic resonance imaging (MRI: Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite, different coatings (none, dextran, carboxydextran, polystyrene and different hydrodynamic diameters (20–850 nm for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC, which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe3O4 particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.

  15. Cellular Molecular Changes in Nerium oleander (L.) Cell Culture Under Gamma Radiation Stress

    International Nuclear Information System (INIS)

    Salama, I.M.; Abd EL-Megid, M.H.M.

    2017-01-01

    This study was done to analyze the relationship between the various effects of five different doses of gamma ray treatments (control, 0, 100, 200, 300 and 400 rad) on cell suspension culture of Nerium oleander belonging to the family Apocynaceae, Plant samples were collected from Egyptian flora. The five treatments of the plants were characterized by analyzing variability in frozen biomass cell suspension culture of N. oleander through SDS PAGE and peroxidase is ozymes. The electrophorogram showed a total of 36 bands of proteins with molecular weight ranging from 10 to 225 KDa. The protein diversity analysis was done based on the presence or the absence of bands trhus interpreting their relevance. The his togram analysis clearly showed a high degree of diversity a long these five treatments of the plant. The results of electrophoretic patterns of peroxidase is ozymes that was extracted from frozen biomass cell suspension cultures after receiving the different gamma doses revealed remarkable molecular changes in all treatments. These changes in peroxidase isozymes and protein bands indicate the effect of the different irradiation treatments on the gene expiration

  16. The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health

    Directory of Open Access Journals (Sweden)

    Henrieta Škovierová

    2016-10-01

    Full Text Available Homocysteine (Hcy is a sulfur-containing non-proteinogenic amino acid derived in methionine metabolism. The increased level of Hcy in plasma, hyperhomocysteinemia, is considered to be an independent risk factor for cardio and cerebrovascular diseases. However, it is still not clear if Hcy is a marker or a causative agent of diseases. More and more research data suggest that Hcy is an important indicator for overall health status. This review represents the current understanding of molecular mechanism of Hcy metabolism and its link to hyperhomocysteinemia-related pathologies in humans. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated protein, nucleic acid and carbohydrate oxidation and lipoperoxidation, products known to be involved in cytotoxicity. Additionally, we examine the role of Hcy in thiolation of proteins, which results in their molecular and functional modifications. We also highlight the relationship between the imbalance in Hcy metabolism and pathogenesis of diseases, such as cardiovascular diseases, neurological and psychiatric disorders, chronic kidney disease, bone tissue damages, gastrointestinal disorders, cancer, and congenital defects.

  17. Tensions and opportunities in convergence: Shifting concepts of disease in emerging molecular medicine.

    NARCIS (Netherlands)

    Boenink, Marianne

    2009-01-01

    The convergence of biomedical sciences with nanotechnology as well as ICT has created a new wave of biomedical technologies, resulting in visions of a ‘molecular medicine’. Since novel technologies tend to shift concepts of disease and health, this paper investigates how the emerging field of

  18. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment

    Science.gov (United States)

    Singhal, Gaurav; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

    2014-01-01

    Recent studies on environmental enrichment (EE) have shown cytokines, cellular immune components [e.g., T lymphocytes, natural killer (NK) cells], and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise (PE), a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including interleukin (IL)-6 secretion from muscle fibers, reduced expression of Toll-like receptors on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia, and upregulation of mitogen-activated protein kinase phosphatase-1 in central nervous system. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and tumor necrosis factor-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning, and EE has paved a way toward formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immunomodulatory role of PE has been evaluated extensively, more research

  19. Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor.

    Science.gov (United States)

    Hanas, Jay S; Bruce Briggs, G; Lerner, Megan R; Lightfoot, Stan A; Larabee, Jason L; Karsies, Todd J; Epstein, Robert B; Hanas, Rushie J; Brackett, Daniel J; Hocker, James R

    2010-05-01

    Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m(3), for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the alpha-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500-1000 mg/m(3)) than at low vapor phase exposure (250 mg/m(3)) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

  20. Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

    Science.gov (United States)

    Gould, Thomas J.; Leach, Prescott T.

    2013-01-01

    Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: 1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, 2) how nicotine usurps the cellular mechanisms of synaptic plasticity, 3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal

  1. Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal Cells

    DEFF Research Database (Denmark)

    Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad

    2016-01-01

    and osteoblast differentiation genes which included several homeobox genes: TBX15, HOXA2 and HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic differentiation. Our studies demonstrate the existence of molecular......Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions, including differentiation into skeletal cells (progenitor function), hematopoiesis support, and immune regulation (nonprogenitor function). We have previously demonstrated the presence of morphological and functional...... and functional heterogeneity in cultured hBMSC. ALP can be employed to identify osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures...

  2. Molecular and cellular organization of taste neurons in adult Drosophila pharynx

    Science.gov (United States)

    Chen, Yu-Chieh (David); Dahanukar, Anupama

    2017-01-01

    SUMMARY The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons. We validate the mapping results by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons. Our results provide road maps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors. PMID:29212040

  3. The protons of space and brain tumors: II. Cellular and molecular considerations

    International Nuclear Information System (INIS)

    Nagle, W.A.; Moss, A.J. Jr.; Dalrymple, G.V.; Cox, A.B.; Wigle, J.F.; Mitchell, J.C.

    1989-01-01

    An increased incidence of highly malignant gliomas, termed glioblastoma multiforme has been observed in Rhesus monkeys irradiated with 55 MeV protons, and in humans treated with therapeutic irradiation to the head. The results suggest a radiation etiology for these tumors. In this paper, we review briefly some characteristics of glioma tumors, and summarize the genetic changes associated with malignant gliomas in experimental animals and in humans. The genetic abnormalities include cytogenetic alterations, and changes in the structure and expression of specific oncogenes. We discuss the potential for these genetic changes to contribute to several putative mechanism leading to aberrant growth stimulation and, ultimately, to tumorigenesis. In addition, we review briefly some recent data concerning the molecular nature of radiation-induced somatic cell mutation and oncogene activation, and discuss the significance of these results for the radiation etiology of malignant gliomas. Finally, some implications of these results are discussed in relation to human radiation exposure in space

  4. Cellular and molecular cues of glucose sensing in the rat olfactory bulb

    Directory of Open Access Journals (Sweden)

    Dolly eAl Koborssy

    2014-10-01

    Full Text Available In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems specifically dedicated to glucose sensing are found in areas involved in energy regulation and feeding behavior. Olfaction is a major sensory modality regulating food consumption. Nutritional status in turn modulates olfactory detection. Recently it has been proposed that some olfactory bulb (OB neurons respond to glucose similarly to hypothalamic neurons. However, the precise molecular cues governing glucose sensing in the OB are largely unknown. To decrypt these molecular mechanisms, we first used immunostaining to demonstrate a strong expression of two neuronal markers of glucose-sensitivity, insulin-dependent glucose transporter type 4 (GLUT4, and sodium glucose co-transporter type 1 (SGLT1 in specific OB layers. We showed that expression and mapping of GLUT4 but not SGLT1 were feeding state-dependent. In order to investigate the impact of metabolic status on the delivery of blood-borne glucose to the OB, we measured extracellular fluid glucose concentration using glucose biosensors simultaneously in the OB and cortex of anesthetized rats. We showed that glucose concentration in the OB is higher than in the cortex, that metabolic steady-state glucose concentration is independent of feeding state in the two brain areas, and that acute changes in glycemic conditions affect bulbar glucose concentration alone. These data provide new evidence of a direct relationship between the OB and peripheral metabolism, and emphasize the importance of glucose for the OB network, providing strong arguments toward establishing the OB as a glucose-sensing organ.

  5. Cellular and molecular responses of E. fetida cœlomocytes exposed to TiO2 nanoparticles

    Science.gov (United States)

    Bigorgne, Emilie; Foucaud, Laurent; Caillet, Céline; Giambérini, Laure; Nahmani, Johanne; Thomas, Fabien; Rodius, François

    2012-07-01

    An in vitro approach using cœlomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO2 nanoparticles. Cœlomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO2 nanoparticles (1-25 μg/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO2 nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 μg/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO2 in our experimental conditions. This in vitro approach showed that TiO2 nanoparticles were taken up by cœlomocytes and they could modify the molecular response of immune and detoxification system.

  6. Synthesis of a Neutral Mixed-Valence Diferrocenyl Carborane for Molecular Quantum-Dot Cellular Automata Applications.

    Science.gov (United States)

    Christie, John A; Forrest, Ryan P; Corcelli, Steven A; Wasio, Natalie A; Quardokus, Rebecca C; Brown, Ryan; Kandel, S Alex; Lu, Yuhui; Lent, Craig S; Henderson, Kenneth W

    2015-12-14

    The preparation of 7-Fc(+) -8-Fc-7,8-nido-[C2 B9 H10 ](-) (Fc(+) FcC2 B9 (-) ) demonstrates the successful incorporation of a carborane cage as an internal counteranion bridging between ferrocene and ferrocenium units. This neutral mixed-valence Fe(II) /Fe(III) complex overcomes the proximal electronic bias imposed by external counterions, a practical limitation in the use of molecular switches. A combination of UV/Vis-NIR spectroscopic and TD-DFT computational studies indicate that electron transfer within Fc(+) FcC2 B9 (-) is achieved through a bridge-mediated mechanism. This electronic framework therefore provides the possibility of an all-neutral null state, a key requirement for the implementation of quantum-dot cellular automata (QCA) molecular computing. The adhesion, ordering, and characterization of Fc(+) FcC2 B9 (-) on Au(111) has been observed by scanning tunneling microscopy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Molecular, cellular and physiological evidences for the anorexigenic actions of nesfatin-1 in goldfish.

    Directory of Open Access Journals (Sweden)

    Ronald Gonzalez

    2010-12-01

    Full Text Available Nesfatin-1 is a recently discovered anorexigen encoded in the precursor peptide, nucleobindin-2 (NUCB2 in mammals. To date, nesfatin-1 has not been described in any non-mammalian species, although some information is available in the sequenced genomes of several species. Our objective was to characterize nesfatin-1 in fish.In the present study, we employed molecular, immunohistochemical, and physiological studies to characterize the structure, distribution, and appetite regulatory effects of nesfatin-1 in a non-mammalian vertebrate. A very high conservation in NUCB2 sequences, especially in the nesfatin-1 region was found in lower vertebrates. Abundant expression of NUCB2 mRNA was detected in several tissues including the brain and liver of goldfish. Nesfatin-1-like immunoreactive cells are present in the feeding regulatory nucleus of the hypothalamus and in the gastrointestinal tract of goldfish. Approximately 6-fold increase in NUCB2 mRNA levels was found in the liver after 7-day food-deprivation, and a similar increase was also found after short-term fasting. This points toward a possible liver specific role for NUCB2 in the control of metabolism during food-deprivation. Meanwhile, ∼2-fold increase at 1 and 3 h post-feeding and an ∼3-fold reduction after a 7-day food-deprivation was observed in NUCB2 mRNA in the goldfish hypothalamus. In vivo, a single intraperitoneal injection of the full-length native (goldfish; gf nesfatin-1 at a dose of 50 ng/g body weight induced a 23% reduction of food intake one hour post-injection in goldfish. Furthermore, intracerebroventricular injection of gfnesfatin-1 at a dose of 5 ng/g body weight resulted in ∼50% reduction in food intake.Our results provide molecular, anatomical and functional evidences to support potential anorectic and metabolic roles for endogenous nesfatin-1 in goldfish. Collectively, we provide novel information on NUCB2 in non-mammals and an anorexigenic role for nesfatin-1 in

  8. Molecular events basic to cellular radiation response. Progress report, October 1, 1978-September 30, 1979

    International Nuclear Information System (INIS)

    Kolodny, G.M.

    1980-01-01

    Research during the past year has been directed at induction of specific protein synthesis in differentiated mammalian cells. The Primer Hypothesis for the regulation of eukaryotic gene expression suggests that RNA transcription is primed by small molecular weight RNA. It predicts that albumin mRNA transcription in a 3T3 fibroblast, which ordinarily does not produce albumin, can be initiated by RNA primer present in liver cells. In experiments this past year, mouse fibroblasts were incubated with mouse liver RNA. These cells did indeed produce albumin which was detected by counterimmunoelectrophoresis. Confluent 3T3 cell cultures were incubated with mouse liver RNA and polylysine in serum free media. Counterimmunoelectrophoresis (CIEP) of the dialyzed and lyophilized media against mouse albumin antisera gave a single precipitin line indicating albumin snthesis by the fibroblasts. The synthesis of this protein immunologicaly similar to albumin required new albumin mRNA transcription since it was not synthesized in the presence of actinomycin, could be found in media which had been incubated with RNA significantly smaller in size than albumin mRNA, and was synthesized in the absence of added poly A containing RNA. These results represent the first reported demonstration that RNA can be taken up from the media by cells in culture, and can induce in those cells the production of a differentiated cell product not ordinarily synthesized by those cells, i.e, a change in the normal transcription pattern in those cells

  9. Studies on cellular distribution of elements in human hepatocellular carcinoma samples by molecular activation analysis

    International Nuclear Information System (INIS)

    Deng Guilong; Chen Chunying; Zhang Peiqun; Zhao Jiujiang; Chai Zhifang

    2005-01-01

    The distribution patterns of 17 elements in the subcellular fractions of nuclei, mitochondria, lysosome, microsome and cytosol of human hepatocellular carcinoma (HCC) and normal liver samples were investigated by using molecular activation analysis (MAA) and differential centrifugation. Their significant difference was checked by the Studient's t-test. These elements exhibit inhomogeneous distributions in each subcellular fraction. Some elements have no significant difference between hepatocellular carcinoma and normal liver samples. However, the concentrations of Br, Ca, Cd and Cs are significantly higher in each component of hepatocarcinoma than in normal liver. The content of Fe in microsome of HCC is significantly lower, almost half of normal liver samples, but higher in other subcellular fractions than in those of normal tissues. The rare earth elements of La and Ce have the patterns similar to Fe. The concentrations of Sb and Zn in nuclei of HCC are obviously lower (P<0.05, P<0.05). The contents of K and Na are higher in cytosol of HCC (P<0.05). The distributions of Ba and Rb show no significant difference between two groups. The relationships of Fe, Cd and K with HCC were also discussed. The levels of some elements in subcellular fractions of tumor were quite different from those of normal liver, which suggested that trace elements might play important roles in the occurrence and development of hepatocellular carcinoma. (authors)

  10. Exploration of the speleotherapeutic potential through the cellular and molecular biology techniques

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-02-01

    Full Text Available Objective: Exploring the speleotherapy effects on morphology and physiology of dermal and pulmonary fibroblast obtained from Wistar rats tissue in normal conditions and after induction of experimental “astma” awareness with ovalbumin. Materials and methods: Before initiation of dermal and pulmonary fibroblast cultures, 60 of Wistar rats 75-100 g were divided into two groups: control and sensitized with ovalalbumin. 10 animals of each group were sent to Cacica and Dej salt mines and maintained in a speleotherapy regime. Another 10 animals in each group were monitored separately in INRMFB Biobase . Dermal and pulmonary fibroblast cultures were initiated by enzymatic techniques from appropriate tissue taken of each group Wistar rats. Morphological monitoring was done by phase contast microscopy; biochemical and molecular changes of cultures obtained from animals treated speleothropic compared to control, was experimental establised by electrophoresis and Western Blotting techniques.Results: Experimental data revealed the expression of several proteins after the speleotherapeutic treatment. These data were analysed compared with control, using a specific software.Conclusions: Speleotherapeutic treatment of Wistar rats caused significant differences in morphology and protein expression of dermal and pulmonary fibroblatst grown in the laboratory. These differences support the protective effects of speleotherapy compared with data obtained from animals untreated and sensitized with ovalbumin, having induced experimental asthma status.

  11. Radio-adaptation: cellular and molecular features of a response to low levels of ionizing radiation

    International Nuclear Information System (INIS)

    Rigaud, O.

    1998-01-01

    It is well established that sublethal doses of DNA damaging agents induce protective mechanisms against a subsequent high dose treatment ; for instance, the phenomenon of radio-adaptation in the case of ionizing radiations. Since the early observation described in 1984, numerous studies have confirmed the radio-adaptive response in terms of reduction of chromosomal breaks for varied biological models in vitro and in vivo. Evidence for an adaptive response against the induction of gene mutations and the lethal effect is clearly demonstrated. This paper reviews the experimental results describing various aspects of these adaptive responses expressed on these different biological end-points. The molecular mechanism underlying radio-adaptation still remains nuclear. The development of this phenomenon requires de novo synthesis of transcripts and proteins during the time interval between the two doses. Some data are consistent with the hypotheses that these gene products would be involved in the activation of DNA repair pathways and antioxidant systems. However, a major question still remains unanswered; indeed, it is not clear whether or not the radio-adaptation could affect the estimation of cancer risk related with low level exposure to ionizing radiation, a major concern in radioprotection. Until such data are available, it is yet unwise to evoke the beneficial effects of radio-adaptation. (authors)

  12. Studies on cellular distribution of elements in human hepatocellular carcinoma samples by molecular activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Guilong, Deng [Chinese Academy of Sciences, Beijing (China). Inst. of High Energy Physics, Key Laboratory of Nuclear Analytical Techniques; Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang Univ., Hangzhou (China); Chunying, Chen; Peiqun, Zhang; Jiujiang, Zhao; Zhifang, Chai [Chinese Academy of Sciences, Beijing (China). Inst. of High Energy Physics, Key Laboratory of Nuclear Analytical Techniques; Yingbin, Liu; Jianwei, Wang; Bin, Xu; Shuyou, Peng [Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang Univ., Hangzhou (China)

    2005-07-15

    The distribution patterns of 17 elements in the subcellular fractions of nuclei, mitochondria, lysosome, microsome and cytosol of human hepatocellular carcinoma (HCC) and normal liver samples were investigated by using molecular activation analysis (MAA) and differential centrifugation. Their significant difference was checked by the Studient's t-test. These elements exhibit inhomogeneous distributions in each subcellular fraction. Some elements have no significant difference between hepatocellular carcinoma and normal liver samples. However, the concentrations of Br, Ca, Cd and Cs are significantly higher in each component of hepatocarcinoma than in normal liver. The content of Fe in microsome of HCC is significantly lower, almost half of normal liver samples, but higher in other subcellular fractions than in those of normal tissues. The rare earth elements of La and Ce have the patterns similar to Fe. The concentrations of Sb and Zn in nuclei of HCC are obviously lower (P<0.05, P<0.05). The contents of K and Na are higher in cytosol of HCC (P<0.05). The distributions of Ba and Rb show no significant difference between two groups. The relationships of Fe, Cd and K with HCC were also discussed. The levels of some elements in subcellular fractions of tumor were quite different from those of normal liver, which suggested that trace elements might play important roles in the occurrence and development of hepatocellular carcinoma. (authors)

  13. Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.

    Directory of Open Access Journals (Sweden)

    Aize Pellon

    Full Text Available The filamentous fungus Lomentospora (Scedosporium prolificans is an emerging opportunistic pathogen associated with fatal infections in patients with disturbed immune function. Unfortunately, conventional therapies are hardly of any use against this fungus due to its intrinsic resistance. Therefore, we performed an integrated study of the L. prolificans responses to the first option to treat these mycoses, namely voriconazole, with the aim of unveiling mechanisms involved in the resistance to this compound. To do that, we used a wide range of techniques, including fluorescence and electron microscopy to study morphological alterations, ion chromatography to measure changes in cell-wall carbohydrate composition, and proteomics-based techniques to identify the proteins differentially expressed under the presence of the drug. Significantly, we showed drastic changes occurring in cell shape after voriconazole exposure, L. prolificans hyphae being shorter and wider than under control conditions. Interestingly, we proved that the architecture and carbohydrate composition of the cell wall had been modified in the presence of the drug. Specifically, L. prolificans constructed a more complex organelle with a higher presence of glucans and mannans. In addition to this, we identified several differentially expressed proteins, including Srp1 and heat shock protein 70 (Hsp70, as the most overexpressed under voriconazole-induced stress conditions. The mechanisms described in this study, which may be directly related to L. prolificans antifungal resistance or tolerance, could be used as targets to improve existing therapies or to develop new ones in order to successfully eliminate these mycoses.

  14. Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.

    Science.gov (United States)

    Pellon, Aize; Ramirez-Garcia, Andoni; Buldain, Idoia; Antoran, Aitziber; Rementeria, Aitor; Hernando, Fernando L

    2017-01-01

    The filamentous fungus Lomentospora (Scedosporium) prolificans is an emerging opportunistic pathogen associated with fatal infections in patients with disturbed immune function. Unfortunately, conventional therapies are hardly of any use against this fungus due to its intrinsic resistance. Therefore, we performed an integrated study of the L. prolificans responses to the first option to treat these mycoses, namely voriconazole, with the aim of unveiling mechanisms involved in the resistance to this compound. To do that, we used a wide range of techniques, including fluorescence and electron microscopy to study morphological alterations, ion chromatography to measure changes in cell-wall carbohydrate composition, and proteomics-based techniques to identify the proteins differentially expressed under the presence of the drug. Significantly, we showed drastic changes occurring in cell shape after voriconazole exposure, L. prolificans hyphae being shorter and wider than under control conditions. Interestingly, we proved that the architecture and carbohydrate composition of the cell wall had been modified in the presence of the drug. Specifically, L. prolificans constructed a more complex organelle with a higher presence of glucans and mannans. In addition to this, we identified several differentially expressed proteins, including Srp1 and heat shock protein 70 (Hsp70), as the most overexpressed under voriconazole-induced stress conditions. The mechanisms described in this study, which may be directly related to L. prolificans antifungal resistance or tolerance, could be used as targets to improve existing therapies or to develop new ones in order to successfully eliminate these mycoses.

  15. Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

    Science.gov (United States)

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N'tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

  16. Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

    Directory of Open Access Journals (Sweden)

    Vincent Muczynski

    Full Text Available Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro.Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro.We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

  17. HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

    Science.gov (United States)

    Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

    2003-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

  18. Emerging technologies in point-of-care molecular diagnostics for resource-limited settings.

    Science.gov (United States)

    Peeling, Rosanna W; McNerney, Ruth

    2014-06-01

    Emerging molecular technologies to diagnose infectious diseases at the point at which care is delivered have the potential to save many lives in developing countries where access to laboratories is poor. Molecular tests are needed to improve the specificity of syndromic management, monitor progress towards disease elimination and screen for asymptomatic infections with the goal of interrupting disease transmission and preventing long-term sequelae. In simplifying laboratory-based molecular assays for use at point-of-care, there are inevitable compromises between cost, ease of use and test performance. Despite significant technological advances, many challenges remain for the development of molecular diagnostics for resource-limited settings. There needs to be more advocacy for these technologies to be applied to infectious diseases, increased efforts to lower the barriers to market entry through streamlined and harmonized regulatory approaches, faster policy development for adoption of new technologies and novel financing mechanisms to enable countries to scale up implementation.

  19. Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

    Science.gov (United States)

    Bhargava, Rohit; Madabhushi, Anant

    2016-07-11

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

  20. Molecular profile and cellular characterization of human bone marrow mesenchymal stem cells: donor influence on chondrogenesis.

    Science.gov (United States)

    Cicione, Claudia; Díaz-Prado, Silvia; Muiños-López, Emma; Hermida-Gómez, Tamara; Blanco, Francisco J

    2010-01-01

    The use of autologous or allogenic stem cells has recently been suggested as an alternative therapeutic approach for treatment of cartilage defects. Bone marrow mesenchymal stem cells (BM-MSCs) are well-characterized multipotent cells that can differentiate into different cell types. Understanding the potential of these cells and the molecular mechanisms underlying their differentiation should lead to innovative protocols for clinical applications. The aim of this study was to evaluate the usefulness of surface antigen selection of BM-MSCs and to understand the mechanisms underlying their differentiation. MSCs were isolated from BM stroma and expanded. CD105+ subpopulation was isolated using a magnetic separator. We compared culture-expanded selected cells with non-selected cells. We analyzed the phenotypic profiles, the expression of the stem cell marker genes Nanog, Oct3/4, and Sox2 and the multi-lineage differentiation potential (adipogenic, osteogenic, and chondrogenic). The multi-lineage differentiation was confirmed using histochemistry, immunohistochemistry and/or real-time polymerase chain reaction (qPCR) techniques. The selected and non-selected cells displayed similar phenotypes and multi-lineage differentiation potentials. Analyzing each cell source individually, we could divide the six donors into two groups: one with a high percentage of CD29 (β1-integrin) expression (HL); one with a low percentage of CD29 (LL). These two groups had different chondrogenic capacities and different expression levels of the stem cell marker genes. This study showed that phenotypic profiles of donors were related to the chondrogenic potential of human BM-MSCs. The chondrogenic potential of donors was related to CD29 expression levels. The high expression of CD29 antigen seemed necessary for chondrogenic differentiation. Further investigation into the mechanisms responsible for these differences in BM-MSCs chondrogenesis is therefore warranted. Understanding the mechanisms

  1. Molecular and cellular mechanisms of vitamin D3 protection in experimental prednisolone-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    I.O. Shymanskyi

    2017-08-01

    Full Text Available Background. Osteoporosis is the most common side effect of glucocorticoid (GC therapy. Vitamin D is known to play a crucial role in bone remodeling, but the precise molecular mechanisms of its action on GC-induced impairments of cytokine systems, in particular RANK (receptor activator of nuclear factor kappa-B/RANKL (RANK ligand/OPG (osteoprotegerin, are still controversial. Thus, the purpose of the study was to evaluate GC-induced changes in the RANK/RANKL/OPG system and osteocalcin synthesis in rat bone depending on vitamin D bioavailability and vitamin D receptor (VDR expression. Materials and methods. Female Wistar rats received prednisolone (5 mg/kg b.w. with or without 100 IU of vitamin D3 (for 30 days. The levels of VDR, osteocalcin, RANK, RANKL and OPG in bone tissue were determined by western blotting. Blood serum 25OHD was assayed by enzyme-linked immunosorbent assay. The levels of Ca2+, Pi, activity of alkaline phosphatase (AP and its bone isoenzyme were determined using spectrophotometry. Results. Prednisolone significantly lowered 25OHD content in the blood serum and VDR level in bone tissue that has been accompanied by an elevation of the AP bone isoenzyme activity in the blood serum, hypocalcemia and hypophosphatemia. A significant decrease in the expression of osteocalcin, a well-known marker of bone formation, was also observed. GC-induced disturbances in vitamin D status led to a reduction of the RANK and OPG level, while RANKL level was unaffected. Vitamin D3 administration restored 25OHD and VDR levels that resulted in amelioration of GC-induced changes in bone tissue and normalization of mineral metabolism through elevation of RANK, OPG and osteocalcin levels. Conclusions. Prednisolone-induced imbalance in the RANK/RANKL/OPG and osteocalcin systems is related to the reduction of vitamin D bioavailability and impairments in VDR signaling. Thus, normalization of vitamin D bioavailability might be perspective in reducing the

  2. Two key temporally distinguishable molecular and cellular components of white adipose tissue browning during cold acclimation.

    Science.gov (United States)

    Jankovic, Aleksandra; Golic, Igor; Markelic, Milica; Stancic, Ana; Otasevic, Vesna; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato

    2015-08-01

    White to brown adipose tissue conversion and thermogenesis can be ignited by different conditions or agents and its sustainability over the long term is still unclear. Browning of rat retroperitoneal white adipose tissue (rpWAT) during cold acclimation involves two temporally apparent components: (1) a predominant non-selective browning of most adipocytes and an initial sharp but transient induction of uncoupling protein 1, peroxisome proliferator-activated receptor (PPAR) coactivator-1α, PPARγ and PPARα expression, and (2) the subsistence of relatively few thermogenically competent adipocytes after 45 days of cold acclimation. The different behaviours of two rpWAT beige/brown adipocyte subsets control temporal aspects of the browning process, and thus regulation of both components may influence body weight and the potential successfulness of anti-obesity therapies. Conversion of white into brown adipose tissue may have important implications in obesity resistance and treatment. Several browning agents or conditions ignite thermogenesis in white adipose tissue (WAT). To reveal the capacity of WAT to function in a brownish/burning mode over the long term, we investigated the progression of the rat retroperitoneal WAT (rpWAT) browning during 45 days of cold acclimation. During the early stages of cold acclimation, the majority of rpWAT adipocytes underwent multilocularization and thermogenic-profile induction, as demonstrated by the presence of a multitude of uncoupling protein 1 (UCP1)-immunopositive paucilocular adipocytes containing peroxisome proliferator-activated receptor (PPAR) coactivator-1α (PGC-1α) and PR domain-containing 16 (PRDM16) in their nuclei. After 45 days, all adipocytes remained PRDM16 immunopositive, but only a few multilocular adipocytes rich in mitochondria remained UCP1/PGC-1α immunopositive. Molecular evidence showed that thermogenic recruitment of rpWAT occurred following cold exposure, but returned to starting levels after cold

  3. Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis

    Directory of Open Access Journals (Sweden)

    Bombardini Tonino

    2005-09-01

    Full Text Available Abstract In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax, to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart

  4. Behavioral, cellular and molecular maladaptations covary with exposure to pyridostigmine bromide in a rat model of gulf war illness pain.

    Science.gov (United States)

    Cooper, B Y; Flunker, L D; Johnson, R D; Nutter, T J

    2018-08-01

    Many veterans of Operation Desert Storm (ODS) struggle with the chronic pain of Gulf War Illness (GWI). Exposure to insecticides and pyridostigmine bromide (PB) have been implicated in the etiology of this multisymptom disease. We examined the influence of 3 (DEET (N,N-diethyl-meta-toluamide), permethrin, chlorpyrifos) or 4 GW agents (DEET, permethrin, chlorpyrifos, pyridostigmine bromide (PB)) on the post-exposure ambulatory and resting behaviors of rats. In three independent studies, rats that were exposed to all 4 agents consistently developed both immediate and delayed ambulatory deficits that persisted at least 16 weeks after exposures had ceased. Rats exposed to a 3 agent protocol (PB excluded) did not develop any ambulatory deficits. Cellular and molecular studies on nociceptors harvested from 16WP (weeks post-exposure) rats indicated that vascular nociceptor Na v 1.9 mediated currents were chronically potentiated following the 4 agent protocol but not following the 3 agent protocol. Muscarinic linkages to muscle nociceptor TRPA1 were also potentiated in the 4 agent but not the 3 agent, PB excluded, protocol. Although K v 7 activity changes diverged from the behavioral data, a K v 7 opener, retigabine, transiently reversed ambulation deficits. We concluded that PB played a critical role in the development of pain-like signs in a GWI rat model and that shifts in Na v 1.9 and TRPA1 activity were critical to the expression of these pain behaviors. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Cellular and molecular research to reduce uncertainties in estimates of health effects from low-level radiation

    Energy Technology Data Exchange (ETDEWEB)

    Elkind, M.M.; Bedford, J.; Benjamin, S.A.; Waldren, C.A. (Colorado State Univ., Fort Collins, CO (USA)); Gotchy, R.L. (Science Applications International Corp., McLean, VA (USA))

    1990-10-01

    A study was undertaken by five radiation scientists to examine the feasibility of reducing the uncertainties in the estimation of risk due to protracted low doses of ionizing radiation. In addressing the question of feasibility, a review was made by the study group: of the cellular, molecular, and mammalian radiation data that are available; of the way in which altered oncogene properties could be involved in the loss of growth control that culminates in tumorigenesis; and of the progress that had been made in the genetic characterizations of several human and animal neoplasms. On the basis of this analysis, the study group concluded that, at the present time, it is feasible to mount a program of radiation research directed at the mechanism(s) of radiation-induced cancer with special reference to risk of neoplasia due to protracted, low doses of sparsely ionizing radiation. To implement a program of research, a review was made of the methods, techniques, and instruments that would be needed. This review was followed by a survey of the laboratories and institutions where scientific personnel and facilities are known to be available. A research agenda of the principal and broad objectives of the program is also discussed. 489 refs., 21 figs., 14 tabs.

  6. Cellular and molecular research to reduce uncertainties in estimates of health effects from low-level radiation

    International Nuclear Information System (INIS)

    Elkind, M.M.; Bedford, J.; Benjamin, S.A.; Waldren, C.A.; Gotchy, R.L.

    1990-10-01

    A study was undertaken by five radiation scientists to examine the feasibility of reducing the uncertainties in the estimation of risk due to protracted low doses of ionizing radiation. In addressing the question of feasibility, a review was made by the study group: of the cellular, molecular, and mammalian radiation data that are available; of the way in which altered oncogene properties could be involved in the loss of growth control that culminates in tumorigenesis; and of the progress that had been made in the genetic characterizations of several human and animal neoplasms. On the basis of this analysis, the study group concluded that, at the present time, it is feasible to mount a program of radiation research directed at the mechanism(s) of radiation-induced cancer with special reference to risk of neoplasia due to protracted, low doses of sparsely ionizing radiation. To implement a program of research, a review was made of the methods, techniques, and instruments that would be needed. This review was followed by a survey of the laboratories and institutions where scientific personnel and facilities are known to be available. A research agenda of the principal and broad objectives of the program is also discussed. 489 refs., 21 figs., 14 tabs

  7. Cellular and Molecular Mechanisms of Anterior Chamber-Associated Immune Deviation (ACAID: What We Have Learned from Knockout Mice

    Directory of Open Access Journals (Sweden)

    Julie Vendomèle

    2017-11-01

    Full Text Available Anterior chamber-associated immune deviation (ACAID is a well-known phenomenon that can occur after an antigen is introduced without any danger signal into the anterior chamber of a murine eye. It is reported to lead to an antigen-specific immune deviation throughout the body. Despite the relatively little evidence of this phenomenon in humans, it has been suggested as a potential prophylactic strategy in allograft rejections and in several autoimmune diseases. Cellular and molecular mechanisms of ACAID have been explored in different murine models mainly as proofs of concept, first by direct analyses of immune components in normal immunocompetent settings and by cell transfer experiments. Later, use of knockout (KO mice has helped considerably to decipher ACAID mechanisms. However, several factors raise questions about the reliability and validity of studies using KO murine models. This mini-review summarizes results obtained with KO mice and discusses their advantages, their potential weaknesses, and their potential methods for further progress.

  8. Cellular and Molecular Mechanisms in Vascular Smooth Muscle Cells by which Total Saponin Extracted from Tribulus Terrestris Protects Against Artherosclerosis

    Directory of Open Access Journals (Sweden)

    Mengquan Li

    2013-11-01

    Full Text Available Background/Aims: Total saponin extracted from Tribulus terrestris (TSETT has been reported to protect against atherosclerosis. We here investigate the cellular and molecular mechanisms of TSETT underlying protection against atherosclerosis. Methods: Cell proliferation was measured with Methyl thiazolyl tetrazolium (MTT; Intracellular H2O2 was measured with DCFH-DA, a fluorescent dye; Intracellular free Ca2+ was measured with a confocal laser scanning microscopy; Genes expression was measured with gene array and real-time quantitative polymerase chain reaction (RT-PCR; Phosphorylation of extracellular signal-regulated kinase 1/2 (phospho-ERK1/2 was measured with cell-based enzyme-linked immunosorbent assay (ELISA and western blotting. Results: TSETT significantly suppressed the increase in cells proliferation induced by angiotensin II, significantly suppressed the increase in the intracellular production of H2O2 induced by angiotensin II, significantly inhibited the increase in intracellular free Ca2+ induced by H2O2, significantly inhibited the increase in phospho-ERK1/2 induced by angiotensin II; significantly inhibited the increase in mRNA expression of c-fos, c-jun and pkc-α induced by angiotensin II. Conclusion: These findings provide a new insight into the antiatherosclerotic properties of TSETT and provide a pharmacological basis for the clinical application of TSETT in anti-atherosclerosis.

  9. Cellular and molecular mechanisms in vascular smooth muscle cells by which total saponin extracted from Tribulus terrestris protects against artherosclerosis.

    Science.gov (United States)

    Li, Mengquan; Guan, Yue; Liu, Jiaqi; Zhai, Fengguo; Zhang, Xiuping; Guan, Lixin

    2013-01-01

    Total saponin extracted from Tribulus terrestris (TSETT) has been reported to protect against atherosclerosis. We here investigate the cellular and molecular mechanisms of TSETT underlying protection against atherosclerosis. Cell proliferation was measured with Methyl thiazolyl tetrazolium (MTT); Intracellular H2O2 was measured with DCFH-DA, a fluorescent dye; Intracellular free Ca(2+) was measured with a confocal laser scanning microscopy; Genes expression was measured with gene array and real-time quantitative polymerase chain reaction (RT-PCR); Phosphorylation of extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) was measured with cell-based enzyme-linked immunosorbent assay (ELISA) and western blotting. TSETT significantly suppressed the increase in cells proliferation induced by angiotensin II, significantly suppressed the increase in the intracellular production of H2O2 induced by angiotensin II, significantly inhibited the increase in intracellular free Ca(2+) induced by H2O2, significantly inhibited the increase in phospho-ERK1/2 induced by angiotensin II; significantly inhibited the increase in mRNA expression of c-fos, c-jun and pkc-α induced by angiotensin II. These findings provide a new insight into the antiatherosclerotic properties of TSETT and provide a pharmacological basis for the clinical application of TSETT in anti-atherosclerosis. © 2013 S. Karger AG, Basel.

  10. Biomarkers and Molecular Analysis to Improve Bloodstream Infection Diagnostics in an Emergency Care Unit

    Science.gov (United States)

    Loonen, Anne J. M.; de Jager, Cornelis P. C.; Tosserams, Janna; Kusters, Ron; Hilbink, Mirrian; Wever, Peter C.; van den Brule, Adriaan J. C.

    2014-01-01

    Molecular pathogen detection from blood is still expensive and the exact clinical value remains to be determined. The use of biomarkers may assist in preselecting patients for immediate molecular testing besides blood culture. In this study, 140 patients with ≥ 2 SIRS criteria and clinical signs of infection presenting at the emergency department of our hospital were included. C-reactive protein (CRP), neutrophil-lymphocyte count ratio (NLCR), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels were determined. One ml EDTA blood was obtained and selective pathogen DNA isolation was performed with MolYsis (Molzym). DNA samples were analysed for the presence of pathogens, using both the MagicPlex Sepsis Test (Seegene) and SepsiTest (Molzym), and results were compared to blood cultures. Fifteen patients had to be excluded from the study, leaving 125 patients for further analysis. Of the 125 patient samples analysed, 27 presented with positive blood cultures of which 7 were considered to be contaminants. suPAR, PCT, and NLCR values were significantly higher in patients with positive blood cultures compared to patients without (p molecular assays perform poorly when one ml whole blood is used from emergency care unit patients. NLCR is a cheap, fast, easy to determine, and rapidly available biomarker, and therefore seems most promising in differentiating BSI from non-BSI patients for subsequent pathogen identification using molecular diagnostics. PMID:24475269

  11. Emergency surgery due to complications during molecular targeted therapy in advanced gastrointestinal stromal tumors (GIST)

    International Nuclear Information System (INIS)

    Rutkowski, P.; Nowecki, Z. I.; Dziewirski, W.; Ruka, W.; Siedlecki, J. A.; Grzesiakowska, U.

    2010-01-01

    Aim. The aim of the study was to assess the frequency and results of disease/treatment-related emergency operations during molecular targeted therapy of advanced gastrointestinal stromal tumors (GISTs). Methods. We analyzed emergency operations in patients with metastatic/inoperable GISTs treated with 1 st -line imatinib - IM (group I: 232 patients; median follow-up time 31 months) and 2 nd -line sunitinib - SU (group II: 43 patients; median follow-up 13 months; 35 patients in trial A6181036) enrolled into the Polish Clinical GIST Registry. Results. In group I 3 patients (1.3%) underwent emergency surgery due to disease/treatment related complications: one due to bleeding from a ruptured liver tumor (1 month after IM onset) and two due to bowel perforation on the tumor with subsequent intraperitoneal abscess (both 2 months after IM onset). IM was restarted 5-8 days after surgery and no complications in wound healing were observed. In group II 4 patients (9.5%) underwent emergency operations due to disease/treatment related complications: three due to bowel perforations on the tumor (2 days, 20 days and 10 months after SU onset; 1 subsequent death) and one due to intraperitoneal bleeding from ruptured, necrotic tumor (3.5 months after SU start). SU was restarted 12-18 days after surgery and no complications in wound healing were observed. Conclusions. Emergency operations associated with disease or therapy during imatinib treatment of advanced GISTs are rare. The frequency of emergency operations during sunitinib therapy is considered to be higher than during first line therapy with imatinib which may be associated with more advanced and more resistant disease or to the direct mechanism of sunitinib action, i.e. combining cytotoxic and antiangiogenic activity and thus leading to dramatic tumor response. Molecular targeted therapy in GISTs should always be conducted in cooperation with an experienced surgeon. (authors)

  12. The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization.

    Science.gov (United States)

    Checa, Sara; Rausch, Manuel K; Petersen, Ansgar; Kuhl, Ellen; Duda, Georg N

    2015-01-01

    Physical cues play a fundamental role in a wide range of biological processes, such as embryogenesis, wound healing, tumour invasion and connective tissue morphogenesis. Although it is well known that during these processes, cells continuously interact with the local extracellular matrix (ECM) through cell traction forces, the role of these mechanical interactions on large scale cellular and matrix organization remains largely unknown. In this study, we use a simple theoretical model to investigate cellular and matrix organization as a result of mechanical feedback signals between cells and the surrounding ECM. The model includes bi-directional coupling through cellular traction forces to deform the ECM and through matrix deformation to trigger cellular migration. In addition, we incorporate the mechanical contribution of matrix fibres and their reorganization by the cells. We show that a group of contractile cells will self-polarize at a large scale, even in homogeneous environments. In addition, our simulations mimic the experimentally observed alignment of cells in the direction of maximum stiffness and the building up of tension as a consequence of cell and fibre reorganization. Moreover, we demonstrate that cellular organization is tightly linked to the mechanical feedback loop between cells and matrix. Cells with a preference for stiff environments have a tendency to form chains, while cells with a tendency for soft environments tend to form clusters. The model presented here illustrates the potential of simple physical cues and their impact on cellular self-organization. It can be used in applications where cell-matrix interactions play a key role, such as in the design of tissue engineering scaffolds and to gain a basic understanding of pattern formation in organogenesis or tissue regeneration.

  13. Cellular and molecular properties of 90Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro

    International Nuclear Information System (INIS)

    Saki, M.; Toulany, M.; Rodemann, H.P.; Sihver, W.; Zenker, M.; Heldt, J.M.; Mosch, B.; Pietzsch, H.J.; Steinbach, J.; Baumann, M.

    2012-01-01

    Purpose: Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A''-DTPA) and radiolabeling with 90 Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI). Methods: The following cell lines were used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO), and human skin fibroblast HSF7. Binding affinity and kinetics, specificity, retention, and the combination of 90 Y-cetuximab with EBI were evaluated. Results: Control cetuximab and CHX-A''-DTPA-cetuximab blocked the proliferation activity of UT5 cells. In combination with EBI, CHX-A''-DTPA-cetuximab increased the radiosensitivity of UT5 to a similar degree as control cetuximab did. In contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was affected by either of the antibodies. Binding [ 90 Y]Y-CHX-A''-DTPA-cetuximab ( 90 Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum binding at 24 h. Retention of 90 Y-cetuximab was similar in both HNSCC cell lines; 24 h after treatment, approximately 90% of bound activity remained in the cell layer. Competition assays, using cell membranes in the absence of an internalized fraction of cetuximab, showed that the cetuximab affinity is not lost as a result of conjugation with CHX-A''-DTPA. Cetuximab and CHX-A''-DTPA-cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by cetuximab were not affected by DTPA conjugation. 90 Y-cetuximab in combination with EBI resulted in a pronounced inhibition of colony formation of HNSCC cells. Conclusions: Conjugation of CHX-A''-DTPA to cetuximab

  14. S1P-induced airway smooth muscle hyperresponsiveness and lung inflammation in vivo: molecular and cellular mechanisms.

    Science.gov (United States)

    Roviezzo, F; Sorrentino, R; Bertolino, A; De Gruttola, L; Terlizzi, M; Pinto, A; Napolitano, M; Castello, G; D'Agostino, B; Ianaro, A; Sorrentino, R; Cirino, G

    2015-04-01

    Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. BALB/c, mast cell-deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2 , IgE, IL-4 and IL-13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell-deficient Kit (W) (-sh/) (W) (-sh) mice injected with S1P did not display airway smooth muscle hyper-reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti-CD23 antibody B3B4, which blocks IgE production, inhibited both S1P-induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper-reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD4+ T-cells harvested from S1P-treated mice presented all the features elicited by S1P in the lung. S1P triggers a cascade of events that sequentially involves T-cells, IgE and mast cells reproducing several asthma-like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently-used drugs as well as in the development of new therapeutic approaches for asthma-like diseases. © 2014 The British Pharmacological Society.

  15. Sudden venting test of an emergency bearing for the magnet bearing type compound molecular pump

    International Nuclear Information System (INIS)

    Hiroki, Seiji; Abe, Tetsuya; Murakami, Yoshio; Okamoto, Masatomo; Iguchi, Masashi; Nakamura, Jyunichi; Nakazeki, Tsugito.

    1995-01-01

    The vacuum evacuation system for nuclear fusion reactors bears the role of exhausting hydrogen isotopes in large quantity together with helium continuously for long hours, and as the high vacuum pumps for this purpose, the mechanical pumps which can do continuous evacuation and decrease the quantity of staying radioactive tritium, such as turbo molecular pumps and compound molecular pumps, are promising. Because of the compatibility with tritium, oil lubrication is not desirable, accordingly, the pumps with ceramic rotating vanes and magnetic bearings are demanded. As a part of the development of a magnetic bearing type mechanical pump which can be used for nuclear fusion reactors, the compound molecular pump, in which emergency bearings were incorporated, was made for trial, and the test of sudden air intrusion was carried out, as the results, various knowledges were obtained. The constitution of the testing setup, and the test results are reported. When air was injected at the pressure rise of 3.3x10 4 Pa/s from exhaust port side, after about 2.5 s, the maximum lift of 4.2x10 3 N arose. When air was injected at the pressure rise of 2.7x10 5 Pa/s from the suction part side, after about 0.4s, the maximum lift of 6.9x10 3 N arose. In the air injection alternately from the suction port and exhaust port sides, the emergency bearings functioned normally in 10 times of the test. (K.I.)

  16. Programación fetal de la hipertensión arterial del adulto: mecanismos celulares y moleculares Fetal programming of adult arterial hypertension: cellular and molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Robinson Ramírez

    2013-02-01

    present additional evidence to support the association between low birth weight with the increased prevalence of arterial hypertension in adulthood. We review endothelial function, oxidative stress, insulin resistance and mitochondrial function, as possible cellular and molecular mechanisms.

  17. Complex formation and vectorization of a phosphorothioate oligonucleotide with an amphipathic leucine- and lysine-rich peptide: study at molecular and cellular levels.

    Science.gov (United States)

    Boukhalfa-Heniche, Fatima-Zohra; Hernández, Belén; Gaillard, Stéphane; Coïc, Yves-Marie; Huynh-Dinh, Tam; Lecouvey, Marc; Seksek, Olivier; Ghomi, Mahmoud

    2004-04-15

    Optical spectroscopic techniques such as CD, Raman scattering, and fluorescence imaging allowed us to analyze the complex formation and vectorization of a single-stranded 20-mer phosphorothioate oligodeoxynucleotide with a 15-mer amphipathic peptide at molecular and cellular levels. Different solvent mixtures (methanol and water) and molecular ratios of peptide/oligodeoxynucleotide complexes were tested in order to overcome the problems related to solubility. Optimal conditions for both spectroscopic and cellular experiments were obtained with the molecular ratio peptide/oligodeoxynucleotide equal to 21:4, corresponding to a 7:5 ratio for their respective +/- charge ratio. At the molecular level, CD and Raman spectra were consistent with a alpha-helix conformation of the peptide in water or in a methanol-water mixture. The presence of methanol increased considerably the solubility of the peptide without altering its alpha-helix conformation, as evidenced by CD and Raman spectroscopies. UV absorption melting profile of the oligodeoxynucleotide gave rise to a flat melting profile, corresponding to its random structure in solution. Raman spectra of oligodeoxynucleotide/peptide complexes could only be studied in methanol/water mixture solutions. Drastic changes observed in Raman spectra have undoubtedly shown: (a) the perturbation occurred in the peptide secondary structure, and (b) possible interaction between the lysine residues of the peptide and the oligodeoxynucleotide. At the cellular level, the complex was prepared in a mixture of 10% methanol and 90% cell medium. Cellular uptake in optimal conditions for the oligodeoxynucleotide delivery with low cytotoxicity was controlled by fluorescence imaging allowing to specifically locate the compacted oligonucleotide labeled with fluorescein at its 5'-terminus with the peptide into human glioma cells after 1 h of incubation at 37 degrees C. Copyright 2004 Wiley Periodicals, Inc.

  18. Identification of human genes involved in cellular responses to ionizing radiation: molecular and cellular studies of gene encoding the p68 helicase in mammalian cells

    International Nuclear Information System (INIS)

    Menaa, F.

    2003-12-01

    Cells submitted to genotoxic factors -like IR- activate several and important mechanisms such as repair, cell cycle arrest or 'apoptosis' to maintain genetic integrity. So, the damaged cells will induce many and different genes. The human transcriptome analysis by 'SSH' method in a human breast carcinoma cell line MCF7 γ-irradiated versus not irradiated, allowed to identify about one hundred genes. Among of these genes, we have focused our study on a radio-induced gene encoding the p68 helicase. In the conditions of irradiation used, our results show that the kinetic and the regulation of this gene expression differs between the nature of radiations used. Indeed, in γ-irradiated mammalian cells, ATM, a protein kinase activated by DSB and IR, is required to induce quickly P68 gene via the important transcription factor p53 stabilized by IR. In the case of UVC-irradiated cells, the P68 gene induction is late and the intracellular signalling pathway that lead to this induction is independent from the p53 protein. Finally, we show that the p68 protein under-expression is responsible for an increased radiosensitivity of MCF7 cells. Consequently, we can postulate that the p68 protein is involved in cellular responses to radiations to reduce the increased radiosensitivity of cells exposed to γ-rays. (author)

  19. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    Directory of Open Access Journals (Sweden)

    Baldi Alfonso

    2010-07-01

    Full Text Available Abstract Background The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. Methods A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. Results We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. Conclusions We conclude, on the basis of the definition of

  20. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    Energy Technology Data Exchange (ETDEWEB)

    Aulino, Paola [Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy and Interuniversity Institute of Myology (Italy); Faiola, Fabio [DVM Veterinarian chief, Health Status and Animal Welfare, Sapienza University of Rome, Via Scarpa 16, 00161 Rome (Italy); Adamo, Sergio; Coletti, Dario; Berardi, Emanuele; Cardillo, Veronica M; Rizzuto, Emanuele; Perniconi, Barbara; Ramina, Carla; Padula, Fabrizio [Department of Histology and Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy and Interuniversity Institute of Myology (Italy); Spugnini, Enrico P [SAFU Department, Regina Elena Cancer Institute, Via delle Messi d' Oro 156, 00158 Rome (Italy); Baldi, Alfonso [Department Biochemistry, Section of Pathology, Second University of Naples, Via L. Armanni 5, 80138 Naples (Italy)

    2010-07-08

    The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a

  1. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    International Nuclear Information System (INIS)

    Aulino, Paola; Faiola, Fabio; Adamo, Sergio; Coletti, Dario; Berardi, Emanuele; Cardillo, Veronica M; Rizzuto, Emanuele; Perniconi, Barbara; Ramina, Carla; Padula, Fabrizio; Spugnini, Enrico P; Baldi, Alfonso

    2010-01-01

    The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents

  2. A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression

    Directory of Open Access Journals (Sweden)

    María de la Luz García-Hernández

    2017-05-01

    Full Text Available ObjectiveMultiple solid cancers contain tertiary lymphoid organs (TLO. However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function.MethodsWe used multicolor immunofluorescence to stain prostate tissues, collected at different stages of cancer progression (prostatic intraepithelial neoplasia, intermediate and advanced cancer or from patients with evanescent prostate carcinoma. Tissues were stained with antibodies specific for pro-inflammatory molecules (cyclooxygenase 2, CXCL10, IL17, tumor-infiltrating immune cells (mature DC-LAMP+ dendritic cells, CD3+ T cells, CD3+Foxp3+ regulatory T cells (Treg, T bet+ Th1 cells, granzyme B+ cytotoxic cells, and stromal cell populations (lymphatic vessels, tumor neovessels, high endothelial venules (HEV, stromal cells, which promote prostate tumor growth or are critical components of tumor-associated TLO.ResultsGenerally, inflammatory cells are located at the margins of tumors. Unexpectedly, we found TLO within prostate tumors from patients at different stages of cancer and in unique samples from patients with spontaneous cancer remission. In evanescent prostate carcinomas, accumulation of Treg was compromised, while Tbet+ T cells and CD8 T cells were abundant in tumor-associated TLO. In addition, we found a global decrease in tumor neovascularization and the coverage by cells positive for cyclooxygenase 2 (COX2. Finally, consistent with tumor regression, prostate stem cell antigen was

  3. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

    Science.gov (United States)

    Wu, Hua-Hsi; Lin, Wen-chang; Tsai, Kuo-Wang

    2014-01-23

    Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

  4. The Emerging Role of Skeletal Muscle Metabolism as a Biological Target and Cellular Regulator of Cancer-Induced Muscle Wasting

    Science.gov (United States)

    Carson, James A.; Hardee, Justin P.; VanderVeen, Brandon N.

    2015-01-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle’s metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function regulation, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

  5. Differential proteome and cellular adhesion analyses of the probiotic bacterium Lactobacillus acidophilus NCFM grown on raffinose - an emerging prebiotic

    DEFF Research Database (Denmark)

    Celebioglu, Hasan Ufuk; Hansen, Morten Ejby; Majumder, Avishek

    2016-01-01

    Whole cell and surface proteomes were analyzed together with adhesive properties of the probiotic bacterium Lactobacillus acidophilus NCFM (NCFM) grown on the emerging prebiotic raffinose, exemplifying a synbiotic. Adhesion of NCFM to mucin and intestinal HT-29 cells increased three-fold after...

  6. Pre-analytical and post-analytical evaluation in the era of molecular diagnosis of sexually transmitted diseases: cellularity control and internal control

    Directory of Open Access Journals (Sweden)

    Loria Bianchi

    2014-06-01

    Full Text Available Background. Increase of molecular tests performed on DNA extracted from various biological materials should not be carried out without an adequate standardization of the pre-analytical and post-analytical phase. Materials and Methods. Aim of this study was to evaluate the role of internal control (IC to standardize pre-analytical phase and the role of cellularity control (CC in the suitability evaluation of biological matrices, and their influence on false negative results. 120 cervical swabs (CS were pre-treated and extracted following 3 different protocols. Extraction performance was evaluated by amplification of: IC, added in each mix extraction; human gene HPRT1 (CC with RT-PCR to quantify sample cellularity; L1 region of HPV with SPF10 primers. 135 urine, 135 urethral swabs, 553 CS and 332 ThinPrep swabs (TP were tested for C. trachomatis (CT and U. parvum (UP with RT-PCR and for HPV by endpoint-PCR. Samples were also tested for cellularity. Results. Extraction protocol with highest average cellularity (Ac/sample showed lowest number of samples with inhibitors; highest HPV positivity was achieved by protocol with greatest Ac/PCR. CS and TP under 300.000 cells/sample showed a significant decrease of UP (P<0.01 and HPV (P<0.005 positivity. Female urine under 40.000 cells/mL were inadequate to detect UP (P<0.05. Conclusions. Our data show that IC and CC allow optimization of pre-analytical phase, with an increase of analytical quality. Cellularity/sample allows better sample adequacy evaluation, crucial to avoid false negative results, while cellularity/PCR allows better optimization of PCR amplification. Further data are required to define the optimal cut-off for result normalization.

  7. The AMPK enzyme-complex: From the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders

    NARCIS (Netherlands)

    Antonioli, Luca; Colucci, Rocchina; Pellegrini, Carolina; Giustarini, Giulio; Sacco, Deborah; Tirotta, Erika; Caputi, Valentina; Marsilio, Ilaria; Giron, Maria Cecilia; Németh, Zoltán H; Blandizzi, Corrado; Fornai, Matteo

    2016-01-01

    Introduction: Adenosine monophosphate-activated protein kinase (AMPK), known as an enzymatic complex that regulates the energetic metabolism, is emerging as a pivotal enzyme and enzymatic pathway involved in the regulation of immune homeostatic networks. It is also involved in the molecular

  8. Delineation and interpretation of gene networks towards their effect in cellular physiology- a reverse engineering approach for the identification of critical molecular players, through the use of ontologies.

    Science.gov (United States)

    Moutselos, K; Maglogiannis, I; Chatziioannou, A

    2010-01-01

    Exploiting ontologies, provides clues regarding the involvement of certain molecular processes in the cellular phenotypic manifestation. However, identifying individual molecular actors (genes, proteins, etc.) for targeted biological validation in a generic, prioritized, fashion, based in objective measures of their effects in the cellular physiology, remains a challenge. In this work, a new meta-analysis algorithm is proposed for the holistic interpretation of the information captured in -omic experiments, that is showcased in a transcriptomic, dynamic, DNA microarray dataset, which examines the effect of mastic oil treatment in Lewis lung carcinoma cells. Through the use of the Gene Ontology this algorithm relates genes to specific cellular pathways and vice versa in order to further reverse engineer the critical role of specific genes, starting from the results of various statistical enrichment analyses. The algorithm is able to discriminate candidate hub-genes, implying critical biochemical cross-talk. Moreover, performance measures of the algorithm are derived, when evaluated with respect to the differential expression gene list of the dataset.

  9. Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China.

    Science.gov (United States)

    Du, Yingying; Chen, Mingyue; Yang, Jiayun; Jia, Yane; Han, Shufang; Holmes, Edward C; Cui, Jie

    2017-06-15

    H5N6 avian influenza virus (AIV) has posed a potential threat to public health since its emergence in China in 2013. To understand the evolution and emergence of H5N6 AIV in the avian population, we performed molecular surveillance of live poultry markets (LPMs) in Wugang Prefecture, Hunan Province, in central China, during 2014 and 2015. Wugang Prefecture is located on the Eastern Asian-Australian migratory bird flyway, and a human death due to an H5N6 virus was reported in the prefecture on 21 November 2016. In total, we sampled and sequenced the complete genomes of 175 H5N6 AIVs. Notably, our analysis revealed that H5N6 AIVs contain at least six genotypes arising from segment reassortment, including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2 and a novel NP gene that has its origins with H7N3 viruses. In addition, phylogenetic analysis revealed that genetically similar H5N6 AIVs tend to cluster according to their geographic regions of origin. These results help to reveal the evolutionary behavior of influenza viruses prior to their emergence in humans. IMPORTANCE The newly emerged H5N6 influenza A virus has caused more than 10 human deaths in China since 2013. In November 2016, a human death due to an H5N6 virus, in Wugang Prefecture, Hunan Province, was confirmed by the WHO. To better understand the evolution and emergence of H5N6 viruses, we surveyed live poultry markets (LPMs) in Wugang Prefecture before the reported human death, with a focus on revealing the diversity and genomic origins of H5N6 in birds during 2014 and 2015. In general, H5N6 viruses in this region were most closely related to H5N1 clade 2.3.4.4, with the exception of one virus with an HA gene derived from clade 2.3.2 such that it represents a novel reassortant. Clearly, the ongoing surveillance of LPMs is central to monitoring the emergence of pathogenic influenza viruses. Copyright © 2017 American Society for Microbiology.

  10. Identification of multidrug resistance protein 1 (MRP1/ABCC1) as a molecular gate for cellular export of cobalamin

    DEFF Research Database (Denmark)

    Beedholm-Ebsen, Rasmus; van de Wetering, Koen; Hardlei, Tore

    2010-01-01

    transporters by cellular gene silencing showed a role in cellular Cbl efflux of the ATP-binding cassette (ABC)-drug transporter, ABCC1, alias multidrug resistance protein 1 (MRP1), which is present in the basolateral membrane of intestinal epithelium and in other cells. The ability of MRP1 to mediate ATP...... and kidney. In contrast, Cbl accumulates in the terminal part of the intestine of these mice, suggesting a functional malabsorption because of a lower epithelial basolateral Cbl efflux. The identification of this Cbl export mechanism now allows the delineation of a coherent pathway for Cbl trafficking from...

  11. Exploring emergent properties in cellular homeostasis using OnGuard to model K+ and other ion transport in guard cells.

    Science.gov (United States)

    Blatt, Michael R; Wang, Yizhou; Leonhardt, Nathalie; Hills, Adrian

    2014-05-15

    It is widely recognized that the nature and characteristics of transport across eukaryotic membranes are so complex as to defy intuitive understanding. In these circumstances, quantitative mathematical modeling is an essential tool, both to integrate detailed knowledge of individual transporters and to extract the properties emergent from their interactions. As the first, fully integrated and quantitative modeling environment for the study of ion transport dynamics in a plant cell, OnGuard offers a unique tool for exploring homeostatic properties emerging from the interactions of ion transport, both at the plasma membrane and tonoplast in the guard cell. OnGuard has already yielded detail sufficient to guide phenotypic and mutational studies, and it represents a key step toward 'reverse engineering' of stomatal guard cell physiology, based on rational design and testing in simulation, to improve water use efficiency and carbon assimilation. Its construction from the HoTSig libraries enables translation of the software to other cell types, including growing root hairs and pollen. The problems inherent to transport are nonetheless challenging, and are compounded for those unfamiliar with conceptual 'mindset' of the modeler. Here we set out guidelines for the use of OnGuard and outline a standardized approach that will enable users to advance quickly to its application both in the classroom and laboratory. We also highlight the uncanny and emergent property of OnGuard models to reproduce the 'communication' evident between the plasma membrane and tonoplast of the guard cell. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

  12. Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

    Science.gov (United States)

    Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

    2001-01-01

    Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

  13. Rapid and Accurate Molecular Identification of the Emerging Multidrug-Resistant Pathogen Candida auris.

    Science.gov (United States)

    Kordalewska, Milena; Zhao, Yanan; Lockhart, Shawn R; Chowdhary, Anuradha; Berrio, Indira; Perlin, David S

    2017-08-01

    Candida auris is an emerging multidrug-resistant fungal pathogen causing nosocomial and invasive infections associated with high mortality. C. auris is commonly misidentified as several different yeast species by commercially available phenotypic identification platforms. Thus, there is an urgent need for a reliable diagnostic method. In this paper, we present fast, robust, easy-to-perform and interpret PCR and real-time PCR assays to identify C. auris and related species: Candida duobushaemulonii , Candida haemulonii , and Candida lusitaniae Targeting rDNA region nucleotide sequences, primers specific for C. auris only or C. auris and related species were designed. A panel of 140 clinical fungal isolates was used in both PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The identification results from the assays were 100% concordant with DNA sequencing results. These molecular assays overcome the deficiencies of existing phenotypic tests to identify C. auris and related species. Copyright © 2017 Kordalewska et al.

  14. The molecular biology of nairoviruses, an emerging group of tick-borne arboviruses.

    Science.gov (United States)

    Lasecka, Lidia; Baron, Michael D

    2014-06-01

    The nairoviruses are a rapidly emerging group of tick-borne bunyaviruses that includes pathogens of humans (Crimean-Congo hemorrhagic fever virus [CCHFV]) and livestock (Nairobi sheep disease virus [NSDV], also known as Ganjam virus), as well as a large number of viruses for which the normal vertebrate host has not been established. Studies on this group of viruses have been fairly limited, not least because CCHFV is a BSL4 human pathogen, restricting the number of labs able to study the live virus, while NSDV, although highly pathogenic in naive animals, is not seen as a threat in developed countries, making it a low priority. Nevertheless, recent years have seen significant progress in our understanding of the biology of these viruses, particularly that of CCHFV, and this article seeks to draw together our existing knowledge to generate an overall picture of their molecular biology, underlining areas of particular ignorance for future studies.

  15. Molecular surveillance of traditional and emerging pathogens associated with canine infectious respiratory disease.

    Science.gov (United States)

    Decaro, Nicola; Mari, Viviana; Larocca, Vittorio; Losurdo, Michele; Lanave, Gianvito; Lucente, Maria Stella; Corrente, Marialaura; Catella, Cristiana; Bo, Stefano; Elia, Gabriella; Torre, Giorgio; Grandolfo, Erika; Martella, Vito; Buonavoglia, Canio

    2016-08-30

    A molecular survey for traditional and emerging pathogens associated with canine infectious respiratory disease (CIRD) was conducted in Italy between 2011 and 2013 on a total of 138 dogs, including 78 early acute clinically ill CIRD animals, 22 non-clinical but exposed to clinically ill CIRD dogs and 38 CIRD convalescent dogs. The results showed that canine parainfluenza virus (CPIV) was the most commonly detected CIRD pathogen, followed by canine respiratory coronavirus (CRCoV), Bordetella bronchiseptica, Mycoplasma cynos, Mycoplasma canis and canine pneumovirus (CnPnV). Some classical CIRD agents, such as canine adenoviruses, canine distemper virus and canid herpesvirus 1, were not detected at all, as were not other emerging respiratory viruses (canine influenza virus, canine hepacivirus) and bacteria (Streptococcus equi subsp. zooepidemicus). Most severe forms of respiratory disease were observed in the presence of CPIV, CRCoV and M. cynos alone or in combination with other pathogens, whereas single CnPnV or M. canis infections were detected in dogs with no or very mild respiratory signs. Interestingly, only the association of M. cynos (alone or in combination with either CRCoV or M. canis) with severe clinical forms was statistically significant. The study, while confirming CPIV as the main responsible for CIRD occurrence, highlights the increasing role of recently discovered viruses, such as CRCoV and CnPnV, for which effective vaccines are not available in the market. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Molecular Electrical Doping of Organic Semiconductors: Fundamental Mechanisms and Emerging Dopant Design Rules.

    Science.gov (United States)

    Salzmann, Ingo; Heimel, Georg; Oehzelt, Martin; Winkler, Stefanie; Koch, Norbert

    2016-03-15

    Today's information society depends on our ability to controllably dope inorganic semiconductors, such as silicon, thereby tuning their electrical properties to application-specific demands. For optoelectronic devices, organic semiconductors, that is, conjugated polymers and molecules, have emerged as superior alternative owing to the ease of tuning their optical gap through chemical variability and their potential for low-cost, large-area processing on flexible substrates. There, the potential of molecular electrical doping for improving the performance of, for example, organic light-emitting devices or organic solar cells has only recently been established. The doping efficiency, however, remains conspicuously low, highlighting the fact that the underlying mechanisms of molecular doping in organic semiconductors are only little understood compared with their inorganic counterparts. Here, we review the broad range of phenomena observed upon molecularly doping organic semiconductors and identify two distinctly different scenarios: the pairwise formation of both organic semiconductor and dopant ions on one hand and the emergence of ground state charge transfer complexes between organic semiconductor and dopant through supramolecular hybridization of their respective frontier molecular orbitals on the other hand. Evidence for the occurrence of these two scenarios is subsequently discussed on the basis of the characteristic and strikingly different signatures of the individual species involved in the respective doping processes in a variety of spectroscopic techniques. The critical importance of a statistical view of doping, rather than a bimolecular picture, is then highlighted by employing numerical simulations, which reveal one of the main differences between inorganic and organic semiconductors to be their respective density of electronic states and the doping induced changes thereof. Engineering the density of states of doped organic semiconductors, the Fermi

  17. Ultrastructure and molecular phylogeny of Calkinsia aureus: cellular identity of a novel clade of deep-sea euglenozoans with epibiotic bacteria

    Directory of Open Access Journals (Sweden)

    Leander Brian S

    2009-01-01

    Full Text Available Abstract Background The Euglenozoa is a large group of eukaryotic flagellates with diverse modes of nutrition. The group consists of three main subclades – euglenids, kinetoplastids and diplonemids – that have been confirmed with both molecular phylogenetic analyses and a combination of shared ultrastructural characteristics. Several poorly understood lineages of putative euglenozoans live in anoxic environments, such as Calkinsia aureus, and have yet to be characterized at the molecular and ultrastructural levels. Improved understanding of these lineages is expected to shed considerable light onto the ultrastructure of prokaryote-eukaryote symbioses and the associated cellular innovations found within the Euglenozoa and beyond. Results We collected Calkinsia aureus from core samples taken from the low-oxygen seafloor of the Santa Barbara Basin (580 – 592 m depth, California. These biflagellates were distinctively orange in color and covered with a dense array of elongated epibiotic bacteria. Serial TEM sections through individually prepared cells demonstrated that C. aureus shares derived ultrastructural features with other members of the Euglenozoa (e.g. the same paraxonemal rods, microtubular root system and extrusomes. However, C. aureus also possessed several novel ultrastructural systems, such as modified mitochondria (i.e. hydrogenosome-like, an "extrusomal pocket", a highly organized extracellular matrix beneath epibiotic bacteria and a complex flagellar transition zone. Molecular phylogenies inferred from SSU rDNA sequences demonstrated that C. aureus grouped strongly within the Euglenozoa and with several environmental sequences taken from low-oxygen sediments in various locations around the world. Conclusion Calkinsia aureus possesses all of the synapomorphies for the Euglenozoa, but lacks traits that are specific to any of the three previously recognized euglenozoan subgroups. Molecular phylogenetic analyses of C. aureus

  18. Cellular and molecular responses of zebrafish to legacy and emerging pollutants: the specific cases of PAHs and metal oxide nanoparticles

    OpenAIRE

    Vicario Parés, Unai

    2016-01-01

    270 p. Diferentes tipos de xenobióticos, incluyendo compuestos orgánicos y metales, soncontinuamente vertidos al medio acuático como resultado de un sinfín deactividades de origen antropogénico. Las concentraciones de algunos de estoscontaminantes están reguladas (contaminantes prioritarios), mientras que tan solorecientemente han empezado a ser consideradas otras sustancias (contaminantesemergentes), a pesar de no tratarse necesariamente de compuestos nuevos. Latoxicidad de estos compuest...

  19. Simulating the behavior of patients who leave a public hospital emergency department without being seen by a physician: a cellular automaton and agent-based framework

    Directory of Open Access Journals (Sweden)

    Milad Yousefi

    2018-01-01

    Full Text Available The objective of this study was to develop an agent based modeling (ABM framework to simulate the behavior of patients who leave a public hospital emergency department (ED without being seen (LWBS. In doing so, the study complements computer modeling and cellular automata (CA techniques to simulate the behavior of patients in an ED. After verifying and validating the model by comparing it with data from a real case study, the significance of four preventive policies including increasing number of triage nurses, fast-track treatment, increasing the waiting room capacity and reducing treatment time were investigated by utilizing ordinary least squares regression. After applying the preventing policies in ED, an average of 42.14% reduction in the number of patients who leave without being seen and 6.05% reduction in the average length of stay (LOS of patients was reported. This study is the first to apply CA in an ED simulation. Comparing the average LOS before and after applying CA with actual times from emergency department information system showed an 11% improvement. The simulation results indicated that the most effective approach to reduce the rate of LWBS is applying fast-track treatment. The ABM approach represents a flexible tool that can be constructed to reflect any given environment. It is also a support system for decision-makers to assess the relative impact of control strategies.

  20. Simulating the behavior of patients who leave a public hospital emergency department without being seen by a physician: a cellular automaton and agent-based framework.

    Science.gov (United States)

    Yousefi, Milad; Yousefi, Moslem; Fogliatto, F S; Ferreira, R P M; Kim, J H

    2018-01-11

    The objective of this study was to develop an agent based modeling (ABM) framework to simulate the behavior of patients who leave a public hospital emergency department (ED) without being seen (LWBS). In doing so, the study complements computer modeling and cellular automata (CA) techniques to simulate the behavior of patients in an ED. After verifying and validating the model by comparing it with data from a real case study, the significance of four preventive policies including increasing number of triage nurses, fast-track treatment, increasing the waiting room capacity and reducing treatment time were investigated by utilizing ordinary least squares regression. After applying the preventing policies in ED, an average of 42.14% reduction in the number of patients who leave without being seen and 6.05% reduction in the average length of stay (LOS) of patients was reported. This study is the first to apply CA in an ED simulation. Comparing the average LOS before and after applying CA with actual times from emergency department information system showed an 11% improvement. The simulation results indicated that the most effective approach to reduce the rate of LWBS is applying fast-track treatment. The ABM approach represents a flexible tool that can be constructed to reflect any given environment. It is also a support system for decision-makers to assess the relative impact of control strategies.

  1. Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch

    Directory of Open Access Journals (Sweden)

    David Ross

    2017-08-01

    Full Text Available NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction. Other documented roles of NQO1 include its ability to function as a component of the plasma membrane redox system generating antioxidant forms of ubiquinone and vitamin E and at high levels, as a direct superoxide reductase. Emerging roles of NQO1 include its function as an efficient intracellular generator of NAD+ for enzymes including PARP and sirtuins which has gained particular attention with respect to metabolic syndrome. NQO1 interacts with a growing list of proteins, including intrinsically disordered proteins, protecting them from 20S proteasomal degradation. The interactions of NQO1 also extend to mRNA. Recent identification of NQO1 as a mRNA binding protein have been investigated in more detail using SERPIN1A1 (which encodes the serine protease inhibitor α-1-antitrypsin as a target mRNA and indicate a role of NQO1 in control of translation of α-1-antitrypsin, an important modulator of COPD and obesity related metabolic syndrome. NQO1 undergoes structural changes and alterations in its ability to bind other proteins as a result of the cellular reduced/oxidized pyridine nucleotide ratio. This suggests NQO1 may act as a cellular redox switch potentially altering its interactions with other proteins and mRNA as a result of the prevailing redox environment.

  2. A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level.

    Science.gov (United States)

    Lowery, Colin A; Matamouros, Susana; Niessen, Sherry; Zhu, Jie; Scolnick, Jonathan; Lively, Jenny M; Cravatt, Benjamin F; Miller, Samuel I; Kaufmann, Gunnar F; Janda, Kim D

    2013-07-25

    Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity.

    Science.gov (United States)

    Shen, Duanwen; Bai, Mingfeng; Tang, Rui; Xu, Baogang; Ju, Xiaoming; Pestell, Richard G; Achilefu, Samuel

    2013-01-01

    Using a newly developed near-infrared (NIR) dye that fluoresces at two different wavelengths (dichromic fluorescence, DCF), we discovered a new fluorescent substrate for Akt, also known as protein kinase B, and a method to quantitatively report this enzyme's activity in real time. Upon insulin activation of cellular Akt, the enzyme multi-phosphorylated a single serine residue of a diserine DCF substrate in a time-dependent manner, culminating in monophospho- to triphospho-serine products. The NIR DCF probe was highly selective for the Akt1 isoform, which was demonstrated using Akt1 knockout cells derived from MMTV-ErbB2 transgenic mice. The DCF mechanism provides unparalleled potential to assess the stimulation, sustainability, and reversibility of Akt activation longitudinally. Importantly, NIR fluorescence provides a pathway to translate findings from cells to living organisms, a condition that could eventually facilitate the use of these probes in humans.

  4. Emerging treatments in lung cancer – targeting the RLIP76 molecular transporter

    Directory of Open Access Journals (Sweden)

    Goldfinger LE

    2013-11-01

    Full Text Available Lawrence E Goldfinger,1,2 Seunghyung Lee1 1Department of Anatomy and Cell Biology, The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA; 2Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA Abstract: Multidrug resistance in lung cancer cells is a significant obstacle in the treatment of lung cancer. Resistance to chemotherapeutic agents is often the result of efflux of the drugs from cancer cells, mediated by adenosine triphosphate (ATP-dependent drug transport across the plasma membrane. Thus, identifying molecular targets in the cancer cell transport machinery could be a key factor in successful combinatorial therapy, along with chemotherapeutic drugs. The transport protein Ral-interacting protein of 76 kDa (RLIP76, also known as Ral-binding protein 1 (RalBP1, is a highly promising target for lung cancer treatment. RLIP76 is an ATP-dependent non-ATP-binding cassette (ABC transporter, responsible for the major transport function in many cells, including many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolites and environmental toxins. RLIP76 is expressed in most human tissues, and is overexpressed in non-small-cell lung cancer cell lines and in many tumor types. The blockade of RLIP76 by various approaches has been shown to increase the sensitivity to radiation and chemotherapeutic drugs, and leads to apoptosis in cells. In xenograft tumor models in mice, RLIP76 blockade or depletion results in complete and sustained regression across many cancer cell types, including lung cancer cells. In addition to its transport function, RLIP76 has many other cellular and physiological functions based on its domain structure, which includes a unique Ral-binding domain and a Rho GTPase activating protein (RhoGAP-catalytic domain as well as docking sites for multiple signaling proteins. As a Ral effector, RhoGAP, and adapter protein, RLIP76

  5. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    Directory of Open Access Journals (Sweden)

    Lioshina L. G.

    2009-02-01

    Full Text Available The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with Azospirillum

  6. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    OpenAIRE

    Lioshina L. G.

    2009-01-01

    The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with...

  7. Metal Dependence of Signal Transmission through MolecularQuantum-Dot Cellular Automata (QCA: A Theoretical Studyon Fe, Ru, and Os Mixed-Valence Complexes

    Directory of Open Access Journals (Sweden)

    Ken Tokunaga

    2010-08-01

    Full Text Available Dynamic behavior of signal transmission through metal complexes [L5M-BL-ML5]5+ (M=Fe, Ru, Os, BL=pyrazine (py, 4,4’-bipyridine (bpy, L=NH3, which are simplified models of the molecular quantum-dot cellular automata (molecular QCA, is discussed from the viewpoint of one-electron theory, density functional theory. It is found that for py complexes, the signal transmission time (tst is Fe(0.6 fs < Os(0.7 fs < Ru(1.1 fs and the signal amplitude (A is Fe(0.05 e < Os(0.06 e < Ru(0.10 e. For bpy complexes, tst and A are Fe(1.4 fs < Os(1.7 fs < Ru(2.5 fs and Os(0.11 e < Ru(0.12 e molecular orbitals.

  8. Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia.

    Science.gov (United States)

    Alikhani, Mehdi; Mirzaei, Mehdi; Sabbaghian, Marjan; Parsamatin, Pouria; Karamzadeh, Razieh; Adib, Samane; Sodeifi, Niloofar; Gilani, Mohammad Ali Sadighi; Zabet-Moghaddam, Masoud; Parker, Lindsay; Wu, Yunqi; Gupta, Vivek; Haynes, Paul A; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2017-06-06

    Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction. The obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue, and to a lesser extent in maturation arrest samples. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated

  9. Assessment of beta-emitter radionuclides in biological samples using liquid scintillation counting. Application to the study of internal doses in molecular and cellular biology techniques

    International Nuclear Information System (INIS)

    Sierra, I.; Delgado, A.; Navarro, T.; Macias, M. T.

    2007-01-01

    The radioisotopic techniques used in Molecular and Cellular Biology involve external and internal irradiation risk. It is necessary to control the possible internal contamination associated to the development of these techniques. The internal contamination risk can be due to physical and chemical properties of the labelled compounds, aerosols generated during the performance technique. The aim of this work was to estimate the possible intake of specific beta emitters during the technique development and to propose the required criterions to perform Individual Monitoring. The most representative radioisotopic techniques were selected attending their potential risk of internal contamination. Techniques were analysed applying IAEA methodology according to the used activity in each technique. It was necessary to identify the worker groups that would require individual monitoring on the base of their specific risk. Different measurement procedures were applied to study the possible intake in group risk and more than 160 persons were measured by in vitro bioassay. (Author) 96 refs

  10. An in vitro strategy to evaluate the phototoxicity of solar UV at the molecular and cellular level: application to photoprotection assessment.

    Science.gov (United States)

    Marrot, L; Belaidi, J P; Chaubo, C; Meunier, J R; Perez, P; Agapakis-Causse, C

    1998-09-01

    Skin cancers are among the most common human cancers and have an increasing incidence. The ultraviolet radiation components of sunlight play a major role in skin tumor induction and development. Cellular DNA has been identified as a target for most of the biological effects of UV, and the induction of photodamage is considered as the initiating step of photocarcinogenesis. Thus, effective photoprotection of DNA against harmful overex-posure to solar UV is a critical issue. The efficiency of a sunscreen is usually tested with respect to its ability to prevent skin erythema, but conceivably, more data are required at the molecular and cellular level in order to ascertain protection against photocarcinogenic risk. In the present study, we define a strategy based on the use of various in vitro models and solar-simulated light to evaluate photodamage and photoprotection: -Supercoiled circular plasmid DNA for detection of structural alterations. -The yeast Saccharomyces cerevisiae to evaluate cytotoxicity and genotoxicity. -The single-cell gel electrophoresis or comet assay to determine DNA damage and DNA repair in human keratinocytes. -p53 expression as a hallmark for genotoxic stress. -Induction of pigmentation in human melanocytes. In conditions where light source, spectrum and control of radiation delivery were precisely defined, we have demonstrated that the wide spectrum UVA sunscreen Mexoryl SX protects from the cytotoxicity and genotoxicity of solar UV.

  11. Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer

    International Nuclear Information System (INIS)

    Ding, Lina; Zhao, Yang; Warren, Christopher L; Sullivan, Ruth; Eliceiri, Kevin W; Shull, James D

    2013-01-01

    We are using ACI and BN rats, which differ markedly in their susceptibility to 17β-estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell proliferation and epithelial density were evaluated by quantitative immunohistochemistry. Apoptosis was evaluated by quantitative western blotting and flow cytometry. Mammary gland differentiation was examined by immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and quantitative western blotting assays. Extracellular matrix (ECM) associated collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation (SHG) microscopy. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the ECM. Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in

  12. Viral-Cellular DNA Junctions as Molecular Markers for Assessing Intra-Tumor Heterogeneity in Cervical Cancer and for the Detection of Circulating Tumor DNA

    Directory of Open Access Journals (Sweden)

    Katrin Carow

    2017-09-01

    Full Text Available The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients. For intra-tumor heterogeneity analyses tumors of 8 patients with up to 5 integration sites per tumor were included. Tumor islands were micro-dissected from cryosections of several tissue blocks representing different regions of the tumor. Each micro-dissected tumor area served as template for a single junction-specific PCR. For the detection of circulating tumor-DNA (ctDNA junction-specific PCR-assays were applied to sera of 21 patients. Samples were collected preoperatively and during the course of disease. In 7 of 8 tumors the integration site(s were shown to be homogenously distributed throughout different tumor regions. Only one tumor displayed intra-tumor heterogeneity. In 5 of 21 analyzed preoperative serum samples we specifically detected junction fragments. Junction-based detection of ctDNA was significantly associated with reduced recurrence-free survival. Our study provides evidence that HPV-DNA integration is as an early step in cervical carcinogenesis. Clonality with respect to HPV integration opens new perspectives for the application of viral-cellular junction sites as molecular biomarkers in a clinical setting such as disease monitoring.

  13. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  14. Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study

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    Saber Imani

    2015-08-01

    Full Text Available Sulfur mustard (SM, bis- (2-chloroethyl sulphide is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD and compared with mustard lung.

  15. RISC in PD: The Impact of MicroRNAs in Parkinson’s Disease Cellular and Molecular Pathogenesis

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    Sabrina Mahalia Heman-Ackah

    2013-11-01

    Full Text Available Parkinson’s disease (PD is a debilitating neurodegenerative disease characterized primarily by the selective death of dopaminergic (DA neurons in the substantia nigra pars compacta of the midbrain. Although several genetic forms of PD have been identified, the precise molecular mechanisms underlying DA neuron loss in PD remain elusive. In recent years, microRNAs (miRNAs have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes. Although their role in PD pathogenesis is still a very active area of investigation, several seminal studies have contributed significantly to our understanding of the roles these small non-coding RNAs play in the disease process. Among these are studies which have demonstrated specific miRNAs that target and down-regulate the expression of PD-related genes as well as those demonstrating a reciprocal relationship in which PD-related genes act to regulate miRNA processing machinery. Concurrently, a wealth of knowledge has become available regarding the molecular mechanisms that unify the underlying etiology of genetic and sporadic PD pathogenesis, including dysregulated protein quality control by the ubiquitin-proteasome system and autophagy pathway, activation of programmed cell death, mitochondrial damage and aberrant DA neurodevelopment and maintenance. Following a discussion of the interactions between PD-related genes and miRNAs, this review highlights those studies which have elucidated the roles of these pathways in PD pathogenesis. We highlight the potential of miRNAs to serve a critical regulatory role in the implicated disease pathways, given their capacity to modulate the expression of entire families of related genes. Although few studies have directly linked miRNA regulation of these pathways to PD, a strong foundation for investigation has been laid and this area holds promise to reveal novel therapeutic targets for PD.

  16. Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

    Directory of Open Access Journals (Sweden)

    Valérie Rodrigues

    2018-01-01

    Full Text Available The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86 and by measuring the production of nitric oxide (NO and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein. We also characterized an intriguing ubiquitination complex that could be involved in

  17. Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

    Science.gov (United States)

    Rodrigues, Valérie; Fernandez, Bernard; Vercoutere, Arthur; Chamayou, Léo; Andersen, Alexandre; Vigy, Oana; Demettre, Edith; Seveno, Martial; Aprelon, Rosalie; Giraud-Girard, Ken; Stachurski, Frédéric; Loire, Etienne; Vachiéry, Nathalie; Holzmuller, Philippe

    2018-01-01

    The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein). We also characterized an intriguing ubiquitination complex that could be involved in saliva

  18. Molecular dynamics studies of simple membrane-water interfaces: Structure and functions in the beginnings of cellular life

    Science.gov (United States)

    Pohorille, Andrew; Wilson, Michael A.

    1995-01-01

    Molecular dynamics computer simulations of the structure and functions of a simple membrane are performed in order to examine whether membranes provide an environment capable of promoting protobiological evolution. Our model membrane is composed of glycerol 1-monooleate. It is found that the bilayer surface fluctuates in time and space, occasionally creating thinning defects in the membrane. These defects are essential for passive transport of simple ions across membranes because they reduce the Born barrier to this process by approximately 40%. Negative ions are transferred across the bilayer more readily than positive ions due to favorable interactions with the electric field at the membrane-water interface. Passive transport of neutral molecules is, in general, more complex than predicted by the solubility-diffusion model. In particular, molecules which exhibit sufficient hydrophilicity and lipophilicity concentrate near membrane surfaces and experience 'interfacial resistance' to transport. The membrane-water interface forms an environment suitable for heterogeneous catalysis. Several possible mechanisms leading to an increase of reaction rates at the interface are discussed. We conclude that vesicles have many properties that make them very good candidates for earliest protocells. Some potentially fruitful directions of experimental and theoretical research on this subject are proposed.

  19. Host and Non-Host roots in rice: cellular and molecular approaches reveal differential responses to arbuscular mycorrhizal fungi.

    Directory of Open Access Journals (Sweden)

    Valentina eFiorilli

    2015-08-01

    Full Text Available Oryza sativa, a model plant for Arbuscular Mycorrhizal (AM symbiosis, has both host and non-host roots. Large lateral (LLR and fine lateral (FLR roots display opposite responses: LLR support AM colonization, but FLR do not. Our research aimed to study the molecular, morphological and physiological aspects related to the non-host behavior of FLR. RNA-seq analysis revealed that LLR and FLR displayed divergent expression profiles, including changes in many metabolic pathways. Compared with LLR, FLR showed down-regulation of genes instrumental for AM establishment and gibberellin signaling, and a higher expression of nutrient transporters. Consistent with the transcriptomic data, FLR had higher phosphorus content. Light and electron microscopy demonstrated that, surprisingly, in the Selenio cultivar, FLR have a two-layered cortex, which is theoretically compatible with AM colonization. According to RNA-seq, a gibberellin inhibitor treatment increased anticlinal divisions leading to a higher number of cortex cells in FLR.We propose that some of the differentially regulated genes that lead to the anatomical and physiological properties of the two root types also function as genetic factors regulating fungal colonization. The rice root apparatus offers a unique tool to study AM symbiosis, allowing direct comparisons of host and non-host roots in the same individual plant.

  20. 2013 Russell Ross memorial lecture in vascular biology: cellular and molecular mechanisms of diabetes mellitus-accelerated atherosclerosis.

    Science.gov (United States)

    Bornfeldt, Karin E

    2014-04-01

    Adults with diabetes mellitus are much more likely to have cardiovascular disease than those without diabetes mellitus. Genetically engineered mouse models have started to provide important insight into the mechanisms whereby diabetes mellitus promotes atherosclerosis. Such models have demonstrated that diabetes mellitus promotes formation of atherosclerotic lesions, progression of lesions into advanced hemorrhaged lesions, and that it prevents lesion regression. The proatherosclerotic effects of diabetes mellitus are driven in part by the altered function of myeloid cells. The protein S100A9 and the receptor for advanced glycation end-products are important modulators of the effect of diabetes mellitus on myelopoiesis, which might promote monocyte accumulation in lesions. Furthermore, myeloid cell expression of the enzyme acyl-CoA synthetase 1 (ACSL1), which converts long-chain fatty acids into their acyl-CoA derivatives, has emerged as causal to diabetes mellitus-induced lesion initiation. The protective effects of myeloid ACSL1-deficiency in diabetic mice, but not in nondiabetic mice, indicate that myeloid cells are activated by diabetes mellitus through mechanisms that play minor roles in the absence of diabetes mellitus. The roles of reactive oxygen species and insulin resistance in diabetes mellitus-accelerated atherosclerosis are also discussed, primarily in relation to endothelial cells. Translational studies addressing whether the mechanisms identified in mouse models are equally important in humans with diabetes mellitus will be paramount.

  1. Biological chemistry as a foundation of DNA genealogy: the emergence of "molecular history".

    Science.gov (United States)

    Klyosov, A A

    2011-05-01

    This paper presents the basis of DNA genealogy, a new field of science, which is currently emerging as an unusual blend of biochemistry, history, linguistics, and chemical kinetics. The methodology of the new approach is comprised of chemical (biological) kinetics applied to a pattern of mutations in non-recombinant fragments of DNA (Y chromosome and mtDNA, the latter not being considered in this overview). The goal of the analysis is to translate DNA mutation patterns into time spans to the most recent common ancestors of a given population or tribe and to the dating of ancient migration routes. To illustrate this approach, time spans to the common ancestors are calculated for ethnic Russians, that is Eastern Slavs (R1a1 tribe), Western Slavs (I1 and I2 tribes), and Northern (or Uralic) Slavs (N1c tribe), which were found to live around 4600 years before present (R1a1), 3650 ybp (I1), 3000 and 10,500 ybp (I2, two principal DNA lineages), and 3525 ybp (N1c) (confidence intervals are given in the main text). The data were compared with the respective dates for the nearest common ancestor of the R1a1 "Indo-European" population in India, who lived 4050 years before present, whose descendants represent the majority of the upper castes in India today (up to 72%). Furthermore, it was found that the haplotypes of ethnic Russians of the R1a1 haplogroup (up to 62% of the population in the Russian Federation) and those of the R1a1 Indians (more than 100 million today) are practically identical to each other, up to 67-marker haplotypes. This essentially solves a 200-year-old mystery of who were the Aryans who arrived in India around 3500 years before the present. Haplotypes and time spans to the ancient common ancestors were also compared for the ethnic Russians of haplogroups I1 and I2, on one hand, and the respective I1 and I2 populations in Eastern and Western Europe and Scandinavia, on the other. It is suggested that the approach described in this overview lays the

  2. Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro.

    Science.gov (United States)

    Gyenge, Emina Besic; Hiestand, Seraina; Graefe, Susanna; Walt, Heinrich; Maake, Caroline

    2011-06-01

    Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction. Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling. Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Factor VII deficiency: Unveiling the cellular and molecular mechanisms underlying three model alterations of the enzyme catalytic domain.

    Science.gov (United States)

    Chollet, Maria Eugenia; Andersen, Elisabeth; Skarpen, Ellen; Myklebust, Christiane F; Koehler, Christian; Morth, Jens Preben; Chuansumrit, Ampaiwan; Pinotti, Mirko; Bernardi, Francesco; Thiede, Bernd; Sandset, Per Morten; Skretting, Grethe

    2018-03-01

    Activated factor (F) VII is a vitamin K-dependent glycoprotein that initiates blood coagulation upon interaction with tissue factor. FVII deficiency is the most common of the rare congenital bleeding disorders. While the mutational pattern has been extensively characterized, the pathogenic molecular mechanisms of mutations, particularly at the intracellular level, have been poorly defined. Here, we aimed at elucidating the mechanisms underlying altered FVII biosynthesis in the presence of three mutation types in the catalytic domain: a missense change, a microdeletion and a frameshift/elongation, associated with severe or moderate to severe phenotypes. Using CHO-K1 cells transiently transfected with expression vectors containing the wild-type FVII cDNA (FVIIwt) or harboring the p.I289del, p.G420V or p.A354V-p.P464Hfs mutations, we found that the secretion of the FVII mutants was severely decreased compared to FVIIwt. The synthesis rate of the mutants was slower than the FVIIwt and delayed, and no degradation of the FVII mutants by proteasomes, lysosomes or cysteine proteases was observed. Confocal immunofluorescence microscopy studies showed that FVII variants were localized into the endoplasmic reticulum (ER) but were not detectable within the Golgi apparatus. These findings suggested that a common pathogenic mechanism, possibly a defective folding of the mutant proteins, was triggered by the FVII mutations. The misfolded state led to impaired trafficking of these proteins causing ER retention, which would explain the low to very low FVII plasma levels observed in patients carrying these mutations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Molecular and cellular characterization of a Salmonella enterica serovar Paratyphi a outbreak strain and the human immune response to infection.

    Science.gov (United States)

    Gal-Mor, Ohad; Suez, Jotham; Elhadad, Dana; Porwollik, Steffen; Leshem, Eyal; Valinsky, Lea; McClelland, Michael; Schwartz, Eliezer; Rahav, Galia

    2012-02-01

    Enteric fever is an invasive life-threatening systemic disease caused by the Salmonella enterica human-adapted serovars Typhi and Paratyphi. Increasing incidence of infections with Salmonella enterica serovar Paratyphi A and the spreading of its antibiotic-resistant derivates pose a significant health concern in some areas of the world. Herein, we describe a molecular and phenotypic characterization of an S. Paratyphi A strain accounted for a recent paratyphoid outbreak in Nepal that affected at least 37 travelers. Pulsed-field gel electrophoresis analysis of the outbreak isolates revealed one genetic clone (pulsotype), confirming a single infecting source. Genetic profiling of the outbreak strain demonstrated the contribution of specific bacteriophages as a prime source of genetic diversity among clinical isolates of S. Paratyphi A. Phenotypic characterization in comparison with the S. Paratyphi A ATCC 9150 reference sequenced strain showed differences in flagellar morphology and increased abilities of the outbreak strain with respect to its motility, invasion into nonphagocytic cells, intracellular multiplication, survival within macrophages, and higher induction of interleukin-8 (IL-8) secreted by host cells. Collectively, these differences suggest an enhanced virulence potential of this strain and demonstrate an interesting phenotypic variation among S. Paratyphi A isolates. In vivo profiling of 16 inflammatory cytokines in patients infected with the outbreak strain revealed a common profile of a remarkable gamma interferon (IFN-γ) induction together with elevated concentrations of tumor necrosis factor alpha (TNF-α), IL-6, IL-8, IL-10, and IL-15, but not IL-12, which was previously demonstrated as elevated in nontyphoidal Salmonella infections. This apparent profile implies a distinct immune response to paratyphoid infections.

  5. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  6. Cellular decomposition in vikalloys

    International Nuclear Information System (INIS)

    Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

    1981-01-01

    Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

  7. Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

    Science.gov (United States)

    Angelovski, Goran; Gottschalk, Sven; Milošević, Milena; Engelmann, Jörn; Hagberg, Gisela E; Kadjane, Pascal; Andjus, Pavle; Logothetis, Nikos K

    2014-05-21

    Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.

  8. Molecular, Cellular and Pharmaceutical Aspects of Biomaterials in Dentistry and Oral and Maxillofacial Surgery. An Internationalization of Higher Education and Research Perspective.

    Science.gov (United States)

    Wisniewska, Lidia M; Dohan Ehrenfest, David M; Galindo-Moreno, Pablo; Segovia, Jesus D; Inchingolo, Francesco; Wang, Hom-Lay; Fernandes-Cruz, Manuel

    2017-01-01

    In dentistry and oral and maxillofacial surgery, the development of implantable biomaterials and the understanding of their molecular, cellular and pharmaceutical aspects are currently major fields of research and education, with a considerable impact on the daily clinical practice and the evolution of therapeutic strategies. In the era of globalized economy of knowledge and science, this scientific domain needs the development of global cooperation and a paradigm evolution in the organizational culture of the dental sciences and related dental industry. Despite political pressure and theoretical efforts, the internationalization of higher education and research today in dentistry and biomaterials remains in general quite superficial and mostly dependent on the efforts of a few leaders of internationalization working through their personal networks, as it was assessed through the FAST scores (Fast Assessment Screening Test) calculated in various dental schools and groups worldwide through the ISAIAS program (Intercultural Sensitivity Academic Index &Advanced Standards). Cooperation in a multipolar multicultural community requires the development of strong intercultural competences, and this process remains limited in most institutions. These limits of international scientific cooperation can be observed through different markers, particularly the difficult and limited production of ISO standards (International Organization for Standardization) and the relatively low SCIENTI scores (Scientific Cooperation Internationalization Effort &Network Test &Index) of the specialized dental literature, particularly in comparison to the most significant medical literature. However, as an analytical tool to assess the scientific international cooperation effort between fields and periods, the SCIENTI screening system also highlighted a significant increase of the internationalization effort in the last years in the best dental biomaterials publications. Finally, an

  9. Mixed-valence molecular four-dot unit for quantum cellular automata: Vibronic self-trapping and cell-cell response.

    Science.gov (United States)

    Tsukerblat, Boris; Palii, Andrew; Clemente-Juan, Juan Modesto; Coronado, Eugenio

    2015-10-07

    Our interest in this article is prompted by the vibronic problem of charge polarized states in the four-dot molecular quantum cellular automata (mQCA), a paradigm for nanoelectronics, in which binary information is encoded in charge configuration of the mQCA cell. Here, we report the evaluation of the electronic levels and adiabatic potentials of mixed-valence (MV) tetra-ruthenium (2Ru(ii) + 2Ru(iii)) derivatives (assembled as two coupled Creutz-Taube complexes) for which molecular implementations of quantum cellular automata (QCA) was proposed. The cell based on this molecule includes two holes shared among four spinless sites and correspondingly we employ the model which takes into account the two relevant electron transfer processes (through the side and through the diagonal of the square) as well as the difference in Coulomb energies for different instant positions of localization of the hole pair. The combined Jahn-Teller (JT) and pseudo JT vibronic coupling is treated within the conventional Piepho-Krauzs-Schatz model adapted to a bi-electronic MV species with the square-planar topology. The adiabatic potentials are evaluated for the low lying Coulomb levels in which the antipodal sites are occupied, the case just actual for utilization in mQCA. The conditions for the vibronic self-trapping in spin-singlet and spin-triplet states are revealed in terms of the two actual transfer pathways parameters and the strength of the vibronic coupling. Spin related effects in degrees of the localization which are found for spin-singlet and spin-triplet states are discussed. The polarization of the cell is evaluated and we demonstrate how the partial delocalization caused by the joint action of the vibronic coupling and electron transfer processes influences polarization of a four-dot cell. The results obtained within the adiabatic approach are compared with those based on the numerical solution of the dynamic vibronic problem. Finally, the Coulomb interaction between

  10. Molecular profiling--a tool for addressing emerging gaps in the comparative risk assessment of GMOs.

    Science.gov (United States)

    Heinemann, Jack A; Kurenbach, Brigitta; Quist, David

    2011-10-01

    Assessing the risks of genetically modified organisms (GMOs) is required by both international agreement and domestic legislation. Many view the use of the "omics" tools for profiling classes of molecules as useful in risk assessment, but no consensus has formed on the need or value of these techniques for assessing the risks of all GMOs. In this and many other cases, experts support case-by-case use of molecular profiling techniques for risk assessment. We review the latest research on the applicability and usefulness of molecular profiling techniques for GMO risk assessment. As more and more kinds of GMOs and traits are developed, broader use of molecular profiling in a risk assessment may be required to supplement the comparative approach to risk assessment. The literature-based discussions on the use of profiling appear to have settled on two findings: 1. profiling techniques are reliable and relevant, at least no less so than other techniques used in risk assessment; and 2. although not required routinely, regulators should be aware of when they are needed. The dismissal of routine molecular profiling may be confusing to regulators who then lack guidance on when molecular profiling might be worthwhile. Molecular profiling is an important way to increase confidence in risk assessments if the profiles are properly designed to address relevant risks and are applied at the correct stage of the assessment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA Mode of Action within the Neurodegenerative Pathway: Facts and Controversy

    Directory of Open Access Journals (Sweden)

    Nicolas Delcourt

    2017-12-01

    Full Text Available The implication of the cyanotoxin β-N-methylamino-l-alanine (BMAA in long-lasting neurodegenerative disorders is still a matter of controversy. It has been alleged that chronic ingestion of BMAA through the food chain could be a causative agent of amyotrophic lateral sclerosis (ALS and several related pathologies including Parkinson syndrome. Both in vitro and in vivo studies of the BMAA mode of action have focused on different molecular targets, demonstrating its toxicity to neuronal cells, especially motoneurons, and linking it to human neurodegenerative diseases. Historically, the hypothesis of BMAA-induced excitotoxicity following the stimulation of glutamate receptors has been established. However, in this paradigm, most studies have shown acute, rather than chronic effects of BMAA. More recently, the interaction of this toxin with neuromelanin, a pigment present in the nervous system, has opened a new research perspective. The issues raised by this toxin are related to its kinetics of action, and its possible incorporation into cellular proteins. It appears that BMAA neurotoxic activity involves different targets through several mechanisms known to favour the development of neurodegenerative processes.

  12. Cellular and molecular insight into the inhibition of primary root growth of Arabidopsis induced by peptaibols, a class of linear peptide antibiotics mainly produced by Trichoderma spp.

    Science.gov (United States)

    Shi, Wei-Ling; Chen, Xiu-Lan; Wang, Li-Xia; Gong, Zhi-Ting; Li, Shuyu; Li, Chun-Long; Xie, Bin-Bin; Zhang, Wei; Shi, Mei; Li, Chuanyou; Zhang, Yu-Zhong; Song, Xiao-Yan

    2016-04-01

    Trichoderma spp. are well known biocontrol agents that produce a variety of antibiotics. Peptaibols are a class of linear peptide antibiotics mainly produced by Trichoderma Alamethicin, the most studied peptaibol, is reported as toxic to plants at certain concentrations, while the mechanisms involved are unclear. We illustrated the toxic mechanisms of peptaibols by studying the growth-inhibitory effect of Trichokonin VI (TK VI), a peptaibol from Trichoderma longibrachiatum SMF2, on Arabidopsis primary roots. TK VI inhibited root growth by suppressing cell division and cell elongation, and disrupting root stem cell niche maintenance. TK VI increased auxin content and disrupted auxin response gradients in root tips. Further, we screened the Arabidopsis TK VI-resistant mutant tkr1. tkr1 harbors a point mutation in GORK, which encodes gated outwardly rectifying K(+)channel proteins. This mutation alleviated TK VI-induced suppression of K(+)efflux in roots, thereby stabilizing the auxin gradient. The tkr1 mutant also resisted the phytotoxicity of alamethicin. Our results indicate that GORK channels play a key role in peptaibol-plant interaction and that there is an inter-relationship between GORK channels and maintenance of auxin homeostasis. The cellular and molecular insight into the peptaibol-induced inhibition of plant root growth advances our understanding of Trichoderma-plant interactions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  13. Cellular dosimetry

    International Nuclear Information System (INIS)

    Humm, J.L.; Chin, L.M.

    1989-01-01

    Radiation dose is a useful predictive parameter for describing radiation toxicity in conventional radiotherapy. Traditionally, in vitro radiation biology dose-effect relations are expressed in the form of cell survival curves, a semilog plot of cell survival versus dose. However, the characteristic linear or linear quadratic survival curve shape, for high- and low-LET radiations respectively, is only strictly valid when the radiation dose is uniform across the entire target population. With an external beam of 60 Co gamma rays or x-rays, a uniform field may be readily achievable. When radionuclides are incorporated into a cell milieu, several new problems emerge which can result in a departure from uniformity in energy deposition throughout a cell population. This nonuniformity can have very important consequences for the shape of the survival curve. Cases in which perturbations of source uniformity may arise include: 1. Elemental sources may equilibrate in the cell medium with partition coefficients between the extracellular, cytosol, and nuclear compartments. The effect of preferential cell internalization or binding to cell membrane of some radionuclides can increase or decrease the slope of the survival curve. 2. Radionuclides bound to antibodies, hormones, metabolite precursors, etc., may result in a source localization pattern characteristic of the carrier agent, i.e., the sources may bind to cell surface receptors or antigens, be internalized, bind to secreted antigen concentrated around a fraction of the cell population, or become directly incorporated into the cell DNA. We propose to relate the distribution of energy deposition in cell nuclei to biological correlates of cellular inactivation. The probability of each cell's survival is weighted by its individual radiation burden, and the summation of these probabilities for the cell population can be used to predict the number or fraction of cell survivors

  14. The emerging molecular biology toolbox for the study of long noncoding RNA biology

    CSIR Research Space (South Africa)

    Fok, Ezio T

    2017-10-01

    Full Text Available cellular function, it remains crucial to deepen our understanding of their biology. First draft submitted: 4 May 2017; Accepted for publication: 4 July 2017; Published online: 6 September 2017 Keywords: CRISPR/Cas9 • epigenetic regulation • functional... efficient in the nucleus and preferably effective at the site of transcription. The use of targeted nucleases such as CRISPR/Cas9 for such purposes is possible, however, their application has to be carefully considered. Mutations to the sequence are usually...

  15. The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders.

    Science.gov (United States)

    Antonioli, Luca; Colucci, Rocchina; Pellegrini, Carolina; Giustarini, Giulio; Sacco, Deborah; Tirotta, Erika; Caputi, Valentina; Marsilio, Ilaria; Giron, Maria Cecilia; Németh, Zoltán H; Blandizzi, Corrado; Fornai, Matteo

    2016-01-01

    Adenosine monophosphate-activated protein kinase (AMPK), known as an enzymatic complex that regulates the energetic metabolism, is emerging as a pivotal enzyme and enzymatic pathway involved in the regulation of immune homeostatic networks. It is also involved in the molecular mechanisms underlying the pathophysiology of chronic inflammatory diseases. AMPK is expressed in several immune cell types including macrophages, lymphocytes, neutrophils and dendritic cells, and governs a broad array of cell functions, which include cytokine production, chemotaxis, cytotoxicity, apoptosis and proliferation. Based on its wide variety of immunoregulatory actions, the AMPK system has been targeted to reveal its impact on the course of immune-related diseases, such as atherosclerosis, psoriasis, joint inflammation and inflammatory bowel diseases. The identification of AMPK subunits responsible for specific anti-inflammatory actions and the understanding of the underlying molecular mechanisms will promote the generation of novel AMPK activators, endowed with improved pharmacodynamic and pharmacokinetic profiles. These new tools will aid us to utilize AMPK pathway activation in the management of acute and chronic inflammatory diseases, while minimizing potential adverse reactions related to the effects of AMPK on metabolic energy.

  16. Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features.

    Science.gov (United States)

    Teymouri, Manouchehr; Pirro, Matteo; Johnston, Thomas P; Sahebkar, Amirhosein

    2017-05-06

    Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively studied for its effects on human papilloma virus (HPV) infection as well as primary and malignant squamous cervical cancers. HPV infections, especially those related to HPV 16 and 18 types, have been established as the leading cause of cervical cancer; however, there are also additional contributory factors involved in the etiopathogenesis of cervical cancers. Curcumin has emerged as having promising chemopreventive and anticancer effects against both HPV-related and nonrelated cervical cancers. In this review, we first discuss the biological relevance of curcumin and both its pharmacological effects and pharmaceutical considerations from a chemical point of view. Next, the signaling pathways that are modulated by curcumin and are relevant to the elimination of HPV infection and treatment of cervical cancer are discussed. We also present counter arguments regarding the effects of curcumin on signaling pathways and molecular markers dysregulated by benzo(a)pyrene (Bap), a carcinogen found in pathological cervical lesions of women who smoke frequently, and estradiol, as two important risk factors involved in persistent HPV-infection and cervical cancer. Finally, various strategies to enhance the pharmacological activity and pharmacokinetic characteristics of curcumin are discussed with examples of studies in experimental models of cervical cancer. © 2016 BioFactors, 43(3):331-346, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  17. Cellular gravity

    NARCIS (Netherlands)

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  18. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    DEFF Research Database (Denmark)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H

    2016-01-01

    with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration...

  19. Cellular and molecular biology group

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Model DNA polymers have been employed to measure physico-chemical effects of X-irradiation and the influence of known base sequences on the transcription by RNA polymerases. These experiments allow quantitative estimates of the fidelity of transcription in the presence of physical and chemical agents. Cells in culture provide the basic system for studying radiation effects on DNA synthesis, organization of DNA in the nucleus, effects of pollutants on genetic information transfer and gene expression, nucleic acid structure, proliferation capacity, histone phosphorylation, and chromatin structure and function. Mathematical models of the immune response have been formulated, and the biochemical properties of the cell surface have been characterized. The use of flow systems to provide rapid karyotype analysis has been established for relatively simple karyotypes, and a series of cell-cycle-dependent, temperature-sensitive mutant mammalian cell lines have been derived and appear useful for cycle progression and mutagenesis studies

  20. The re-emergence of tuberculosis: what have we learnt from molecular epidemiology?

    NARCIS (Netherlands)

    Borgdorff, M.W.; Soolingen, D. van

    2013-01-01

    Tuberculosis (TB) has re-emerged over the past two decades: in industrialized countries in association with immigration, and in Africa owing to the human immunodeficiency virus epidemic. Drug-resistant TB is a major threat worldwide. The variable and uncertain impact of TB control necessitates not

  1. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY THE EMERGING PATHOGEN HEPATITIS E IN WATER SAMPLES

    Science.gov (United States)

    Hepatitis E virus (HEV) is an emerging pathogen that causes significant illness in the developing world. Like the hepatitis A virus, it is transmitted via the fecal-oral route and can cause short-term, acute hepatitis. In addition, hepatitis E has been found to cause a signific...

  2. Molecular and immunological tools for the evaluation of the cellular immune response in the neotropical monkey Saimiri sciureus, a non-human primate model for malaria research.

    Science.gov (United States)

    Riccio, Evelyn K P; Pratt-Riccio, Lilian R; Bianco-Júnior, Cesare; Sanchez, Violette; Totino, Paulo R R; Carvalho, Leonardo J M; Daniel-Ribeiro, Cláudio Tadeu

    2015-04-18

    The neotropical, non-human primates (NHP) of the genus Saimiri and Aotus are recommended by the World Health Organization as experimental models for the study of human malaria because these animals can be infected with the same Plasmodium that cause malaria in humans. However, one limitation is the lack of immunological tools to assess the immune response in these models. The present study focuses on the development and comparative use of molecular and immunological methods to evaluate the cellular immune response in Saimiri sciureus. Blood samples were obtained from nineteen uninfected Saimiri. Peripheral blood mononuclear cells (PBMC) from these animals and splenocytes from one splenectomized animal were cultured for 6, 12, 18, 24, 48, 72 and 96 hrs in the presence of phorbol-12-myristate-13-acetate and ionomycin. The cytokine levels in the supernatant were detected using human and NHP cytometric bead array Th1/Th2 cytokine kits, the Bio-Plex Pro Human Cytokine Th1/Th2 Assay, enzyme-linked immunosorbent assay, enzyme-linked immunospot assays and intracellular cytokine secretion assays. Cytokine gene expression was examined through TaqMan® Gene Expression Real-Time PCR using predesigned human gene-specific primers and probes or primers and probes designed based on published S. sciureus cytokine sequences. The use of five assays based on monoclonal antibodies specific for human cytokines facilitated the detection of IL-2, IL-4 and/or IFN-γ. TaqMan array plates facilitated the detection of 12 of the 28 cytokines assayed. However, only seven cytokines (IL-1A, IL-2, IL-10, IL-12B, IL-17, IFN-β, and TNF) presented relative expression levels of at least 70% of the gene expression observed in human PBMC. The use of primers and probes specific for S. sciureus cytokines facilitated the detection of transcripts that showed relative expression below the threshold of 70%. The most efficient evaluation of cytokine gene expression, in PBMC and splenocytes, was observed

  3. Cellular and molecular properties of {sup 90}Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Saki, M.; Toulany, M.; Rodemann, H.P. [Tuebingen Univ. (Germany). Div. of Radiobiology and Molecular Environmental Research; Sihver, W.; Zenker, M.; Heldt, J.M.; Mosch, B.; Pietzsch, H.J.; Steinbach, J. [Helmholtz-Zentrum Dresden-Rossendorf (HZDR) e.V., Dresden (Germany). Inst. of Radiopharmacy; Baumann, M. [Technische Univ. Dresden (Germany). Dept. of Radiation Oncology

    2012-09-15

    Purpose: Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A''-DTPA) and radiolabeling with {sup 90}Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI). Methods: The following cell lines were used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO), and human skin fibroblast HSF7. Binding affinity and kinetics, specificity, retention, and the combination of {sup 90}Y-cetuximab with EBI were evaluated. Results: Control cetuximab and CHX-A''-DTPA-cetuximab blocked the proliferation activity of UT5 cells. In combination with EBI, CHX-A''-DTPA-cetuximab increased the radiosensitivity of UT5 to a similar degree as control cetuximab did. In contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was affected by either of the antibodies. Binding [{sup 90}Y]Y-CHX-A''-DTPA-cetuximab ({sup 90}Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum binding at 24 h. Retention of {sup 90}Y-cetuximab was similar in both HNSCC cell lines; 24 h after treatment, approximately 90% of bound activity remained in the cell layer. Competition assays, using cell membranes in the absence of an internalized fraction of cetuximab, showed that the cetuximab affinity is not lost as a result of conjugation with CHX-A''-DTPA. Cetuximab and CHX-A''-DTPA-cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by cetuximab were not affected by DTPA conjugation. {sup 90}Y-cetuximab in combination with EBI resulted in a pronounced inhibition of

  4. Task Group 7B: Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture and Chance in the Maintenance of Human Healthspan

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Arya, Suresh; Grant, Christine; Miller, Linda; Ono, Santa Jeremy; Patil, Chris; Shay, Jerry; Topol, Eric; Torry, Michael; Weier, Heinz-Ulrich G.; Tse, Iris; Lin, Su-Ju; Miller, Richard

    2007-11-14

    The degree to which an individual organism maintains healthspan and lifespan is a function of complex interactions between genetic inheritance ('nature'), environment, including cultural inheritance (nurture) and stochastic events ('luck' or 'chance'). This task group will focus upon the role of chance because it is so poorly understood and because it appears to be of major importance in the determination of individual variations in healthspan and lifespan within species. The major factor determining variations in healthspan and lifespan between species is genetic inheritance. Broader aspects of cellular and molecular mechanisms of biological aging will also be considered, given their importance for understanding the cellular and molecular basis of successful aging. The task force will consider the cellular and molecular basis for nature, nurture and chance in healthspan and life span determination. On the basis of comparisons between identical and non-identical twins, geneticists have estimated that genes control no more than about a quarter of the inter-individual differences in lifespan (Herskind 1996). Twin studies of very old individuals, however, show substantially greater genetic contributions to Healthspan (McClearn 2004; Reed 2003). The environment clearly plays an important role in the length and the quality of life. Tobacco smoke, for example has the potential to impact upon multiple body systems in ways that appear to accelerate the rates at which those systems age (Bernhard 2007). To document the role of chance events on aging, one must rigorously control both the genetic composition of an organism and its environment. This has been done to a remarkable degree in a species of nematodes, Caenorhabditis elegans (Vanfleteren 1998). The results confirm hundreds of previous studies with a wide range of species, especially those with inbred rodents housed under apparently identical but less well controlled environments. One

  5. Is central dogma a global property of cellular information flow?

    Science.gov (United States)

    Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

    2012-01-01

    The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

  6. Is central dogma a global property of cellular information flow?

    Directory of Open Access Journals (Sweden)

    Vincent ePiras

    2012-11-01

    Full Text Available The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcript to protein show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

  7. Piezo proteins: regulators of mechanosensation and other cellular processes.

    Science.gov (United States)

    Bagriantsev, Sviatoslav N; Gracheva, Elena O; Gallagher, Patrick G

    2014-11-14

    Piezo proteins have recently been identified as ion channels mediating mechanosensory transduction in mammalian cells. Characterization of these channels has yielded important insights into mechanisms of somatosensation, as well as other mechano-associated biologic processes such as sensing of shear stress, particularly in the vasculature, and regulation of urine flow and bladder distention. Other roles for Piezo proteins have emerged, some unexpected, including participation in cellular development, volume regulation, cellular migration, proliferation, and elongation. Mutations in human Piezo proteins have been associated with a variety of disorders including hereditary xerocytosis and several syndromes with muscular contracture as a prominent feature. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Recombinase polymerase amplification: Emergence as a critical molecular technology for rapid, low-resource diagnostics.

    Science.gov (United States)

    James, Ameh; Macdonald, Joanne

    2015-01-01

    Isothermal molecular diagnostics are bridging the technology gap between traditional diagnostics and polymerase chain reaction-based methods. These new techniques enable timely and accurate testing, especially in settings where there is a lack of infrastructure to support polymerase chain reaction facilities. Despite this, there is a significant lack of uptake of these technologies in developing countries where they are highly needed. Among these novel isothermal technologies, recombinase polymerase amplification (RPA) holds particular potential for use in developing countries. This rapid nucleic acid amplification approach is fast, highly sensitive and specific, and amenable to countries with a high burden of infectious diseases. Implementation of RPA technology in developing countries is critically required to assess limitations and potentials of the diagnosis of infectious disease, and may help identify impediments that prevent adoption of new molecular technologies in low resource- and low skill settings. This review focuses on approaching diagnosis of infectious disease with RPA.

  9. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus

    OpenAIRE

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A.; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G.

    2013-01-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ?10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular e...

  10. Autosomal Dominant STAT3 Deficiency and Hyper-IgE Syndrome Molecular, Cellular, and Clinical Features From a French National Survey

    Science.gov (United States)

    Chandesris, Marie-Olivia; Melki, Isabelle; Natividad, Angels; Puel, Anne; Fieschi, Claire; Yun, Ling; Thumerelle, Caroline; Oksenhendler, Eric; Boutboul, David; Thomas, Caroline; Hoarau, Cyrille; Lebranchu, Yvon; Stephan, Jean-Louis; Cazorla, Celine; Aladjidi, Nathalie; Micheau, Marguerite; Tron, Fran[cedil]cois; Baruchel, Andre; Barlogis, Vincent; Palenzuela, Gilles; Mathey, Catherine; Dominique, Stephane; Body, Gerard; Munzer, Martine; Fouyssac, Fanny; Jaussaud, Rolland; Bader-Meunier, Brigitte; Mahlaoui, Nizar; Blanche, Stephane; Debre, Marianne; Le Bourgeois, Muriel; Gandemer, Virginie; Lambert, Nathalie; Grandin, Virginie; Ndaga, Stephanie; Jacques, Corinne; Harre, Chantal; Forveille, Monique; Alyanakian, Marie-Alexandra; Durandy, Anne; Bodemer, Christine; Suarez, Felipe; Hermine, Olivier; Lortholary, Olivier; Casanova, Jean-Laurent; Fischer, Alain; Picard, Capucine

    2013-01-01

    Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic

  11. Emerging connections between RNA and autophagy

    DEFF Research Database (Denmark)

    Frankel, Lisa B; Lubas, Michal; Lund, Anders H

    2017-01-01

    in yeast, plants and animals, reviewing the molecular mechanisms and biological importance in normal physiology, stress and disease. In addition, we explore emerging evidence of core autophagy regulation mediated by RNA-binding proteins and noncoding RNAs, and point to gaps in our current knowledge......Macroautophagy/autophagy is a key catabolic process, essential for maintaining cellular homeostasis and survival through the removal and recycling of unwanted cellular material. Emerging evidence has revealed intricate connections between the RNA and autophagy research fields. While a majority...... of the connection between RNA and autophagy. Finally, we discuss the pathological implications of RNA-protein aggregation, primarily in the context of neurodegenerative disease....

  12. Membrane Lipid Oscillation: An Emerging System of Molecular Dynamics in the Plant Membrane.

    Science.gov (United States)

    Nakamura, Yuki

    2018-03-01

    Biological rhythm represents a major biological process of living organisms. However, rhythmic oscillation of membrane lipid content is poorly described in plants. The development of lipidomic technology has led to the illustration of precise molecular profiles of membrane lipids under various growth conditions. Compared with conventional lipid signaling, which produces unpredictable lipid changes in response to ever-changing environmental conditions, lipid oscillation generates a fairly predictable lipid profile, adding a new layer of biological function to the membrane system and possible cross-talk with the other chronobiological processes. This mini review covers recent studies elucidating membrane lipid oscillation in plants.

  13. Population dynamics and rates of molecular evolution of a recently emerged paramyxovirus, avian metapneumovirus subtype C.

    Science.gov (United States)

    Padhi, Abinash; Poss, Mary

    2009-02-01

    We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 x 10(-3) to 7 x 10(-3) substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes examined show a concordant demographic pattern which is characterized by a rapid increase in population size followed by stable population grown until the present.

  14. Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases

    Directory of Open Access Journals (Sweden)

    Kinji Ohno

    2012-01-01

    Full Text Available Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson's disease and three models of Alzheimer's disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson's disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.

  15. Emerging Intestinal Microsporidia Infection in HIV(+/AIDS Patients in Iran: Microscopic and Molecular Detection.

    Directory of Open Access Journals (Sweden)

    Hamed Mirjalali

    2014-06-01

    Full Text Available Species of Microsporidia have been known as opportunistic obligate intracellular parasites particularly in immunocompromised patients. Enterocytozoon bieneusi is one of most prevalent intestinal microsporida parasites in HIV(+/AIDS patients. In this study, intestinal microsporidia infection was determined in HIV(+/AIDS patients using microscopic and molecular methods.Stool samples were collected from HIV(+/AIDS patients during 12 months. All of the stool specimens washed with PBS (pH: 7.5. Slim slides were prepared from each sample and were examined using light microscope with 1000X magnification. DNA extraction carried out in microscopic positive samples. DNA amplification and genus/species identification also performed by Nested-PCR and sequencing techniques.From 81 stool samples, 25 were infected with microsporidia species and E. bieneusi were identified in all of positive samples. No Encephalitozoon spp. was identified in 81 collected samples using specific primers.E. bieneusi is the most prevalent intestinal microsporidia in immunocompromised patients of Iran. On the other hand, Nested-PCR using specific primers for ssu rRNA gene is an appropriate molecular method for identification of E. bieneusi.

  16. Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases

    Science.gov (United States)

    Ohno, Kinji; Ito, Mikako; Ichihara, Masatoshi; Ito, Masafumi

    2012-01-01

    Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson's disease and three models of Alzheimer's disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson's disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease. PMID:22720117

  17. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

    Science.gov (United States)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

    2016-02-25

    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. A molecular arms race between host innate antiviral response and emerging human coronaviruses.

    Science.gov (United States)

    Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

    2016-02-01

    Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

  19. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters

    Science.gov (United States)

    Gahete, Manuel D.; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D.; Castaño, Justo P.; Marazuela, Mónica

    2015-01-01

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value. PMID:26124083

  20. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G

    2013-03-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ~10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular epidemiology of SFTSV before and after its identification is limited. To address this we undertake phylogenetic, evolutionary and structural analyses of all available SFTSV genetic sequences, including a new SFTSV complete genome isolated from a patient from Henan in 2011. Our discovery of a mosaic L segment sequence, which is descended from two major circulating lineages of SFTSV in China, represents the first evidence that homologous recombination plays a role in SFTSV evolution. Selection analyses indicate that negative selection is predominant in SFTSV genes, yet differences in selective forces among genes are consistent between Phlebovirus species. Further analysis reveals structural conservation between SFTSV and Rift Valley fever virus in the residues of their nucleocapsids that are responsible for oligomerisation and RNA-binding, suggesting the viruses share similar modes of higher-order assembly. We reconstruct the epidemic history of SFTSV using molecular clock and coalescent-based methods, revealing that the extant SFTSV lineages originated 50-150 years ago, and that the viral population experienced a recent growth phase that concurs with and extends the earliest serological reports of SFTSV infection. Taken together, our combined structural and phylogenetic analyses shed light into the evolutionary behaviour of SFTSV in the context of other, better-known, pathogenic Phleboviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. The electronic conductance of polypyrrole (PPy molecular wires and emergence of Fano resonance phenomena

    Directory of Open Access Journals (Sweden)

    M Mardaani

    2012-06-01

    Full Text Available In this paper, we studied the electronic conductance of a polypyrrole polymer, which is embedded between two semi-infinite simple chains by using Green’s function technique in tight-binding approach. We first reduced the center polymer to a one dimensional chain with renormalized onsite and hopping energies by renormalization method. Then, we calculated the system conductivity as a function of incoming electron energy, polymer length and contact hopping terms. The results showed that by increasing polymer length and decreasing contact hopping energies, the conductance decreases in the gap regions. This means that for larger gaps, the electron tunneling happens with more difficulty. Moreover, at the resonance area, due to the existence of nitrogen atom in the polymer cyclic structure, the Fano resonance will emerge. Furthermore, the polymer can behave like a metallic chain by variation of the value of nitrogen on-site term.

  2. Molecular confocal laser endomicroscopy

    DEFF Research Database (Denmark)

    Karstensen, John Gásdal; Klausen, Pia Helene; Saftoiu, Adrian

    2014-01-01

    While flexible endoscopy is essential for macroscopic evaluation, confocal laser endomicroscopy (CLE) has recently emerged as an endoscopic method enabling visualization at a cellular level. Two systems are currently available, one based on miniprobes that can be inserted via a conventional...... during on-going endoscopy), a novel world of molecular evaluation opens up. The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas, subsequently resulting in immediate individualization of treatment regimens, but also for improving...

  3. Brilliant molecular nanocrystals emerging from sol-gel thin films: towards a new generation of fluorescent biochips

    International Nuclear Information System (INIS)

    Dubuisson, E; Monnier, V; Sanz-Menez, N; Ibanez, A; Boury, B; Usson, Y; Pansu, R B

    2009-01-01

    To develop highly sensitive biosensors, we made directly available to biological aqueous solutions organic nanocrystals previously grown in the pores of sol-gel films. Through the controlled dissolution of the sol-gel surface, we obtained emerging nanocrystals that remained strongly anchored to the sol-gel coating for good mechanical stability of the final sensing device. We demonstrated that in the presence of a solution of DNA functionalized with a molecular probe, the nanocrystal fluorescence is strongly quenched by Foerster resonance energy transfer thus opening the way towards very sensitive fluorescent biosensors through biomolecules grafted onto fluorescent nanocrystals. Finally, this controlled dissolution, involving weak concentrated NaOH solution, is a generic process that can be used for the thinning of any kind of sol-gel layer.

  4. Mixed-Valence Molecular Unit for Quantum Cellular Automata: Beyond the Born-Oppenheimer Paradigm through the Symmetry-Assisted Vibronic Approach.

    Science.gov (United States)

    Clemente-Juan, Juan Modesto; Palii, Andrew; Coronado, Eugenio; Tsukerblat, Boris

    2016-08-09

    In this article, we focus on the electron-vibrational problem of the tetrameric mixed-valence (MV) complexes proposed for implementation as four-dot molecular quantum cellular automata (mQCA).1 Although the adiabatic approximation explored in ref 2 is an appropriate tool for the qualitative analysis of the basic characteristics of mQCA, like vibronic trapping of the electrons encoding binary information and cell-cell response, it loses its accuracy providing moderate vibronic coupling and fails in the description of the discrete pattern of the vibronic levels. Therefore, a precise solution of the quantum-mechanical vibronic problem is of primary importance for the evaluation of the shapes of the electron transfer optical absorption bands and quantitative analysis of the main parameters of tetrameric quantum cells. Here, we go beyond the Born-Oppenheimer paradigm and present a solution of the quantum-mechanical pseudo Jahn-Teller (JT) vibronic problem in bielectronic MV species (exemplified by the tetra-ruthenium complexes) based on the recently developed symmetry-assisted approach.3,4 The mathematical approach to the vibronic eigenproblem takes into consideration the point symmetry basis, and therefore, the total matrix of the JT Hamiltonian is blocked to the maximum extent. The submatrices correspond to the irreducible representations (irreps) of the point group. With this tool, we also extend the theory of the mQCA cell beyond the limit of prevailing Coulomb repulsion in the electronic pair (adopted in ref 2), and therefore, the general pseudo-JT problems for spin-singlet ((1)B1g, 2(1)A1g, (1)B2g, (1)Eu) ⊗ (b1g + eu) and spin-triplet states ((3)A2g, (3)B1g, 2(3)Eu) ⊗ (b1g + eu) in a square-planar bielectronic system are solved. The obtained symmetry-adapted electron-vibrational functions are employed for the calculation of the profiles (shape functions) of the charge transfer absorption bands in the tetrameric MV complexes and for the discussion of the

  5. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    International Nuclear Information System (INIS)

    Damodaran, T.V.; Attia, M.K.; Abou-Donia, M.B.

    2011-01-01

    Organophosphorus-ester induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral, distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken that results in mild ataxia in 7–14 days and severe paralysis as the disease progresses with a single dose. White leghorn layer hens were treated with DFP (1.7 mg/kg, sc) after prophylactic treatment with atropine (1 mg/kg, sc) in normal saline and eserine (1 mg/kg, sc) in dimethyl sulfoxide. Control groups were treated with vehicle propylene glycol (0.1 ml/kg, sc), atropine in normal saline and eserine in dimethyl sulfoxide. The hens were euthanized at different time points such as 1, 2, 5, 10 and 20 days, and the tissues from cerebrum, midbrain, cerebellum, brainstem and spinal cord were quickly dissected and frozen for mRNA (northern) studies. Northern blots were probed with BCL2, GADD45, beta actin, and 28S RNA to investigate their expression pattern. Another set of hens was treated for a series of time points and perfused with phosphate buffered saline and fixative for histological studies. Various staining protocols such as Hematoxylin and Eosin (H and E); Sevier-Munger; Cresyl echt Violet for Nissl substance; and Gallocynin stain for Nissl granules were used to assess various patterns of cell death and degenerative changes. Complex cell death mechanisms may be involved in the neuronal and axonal degeneration. These data indicate altered and differential mRNA expressions of BCL2 (anti apoptotic gene) and GADD45 (DNA damage inducible gene) in various tissues. Increased cell death and other degenerative changes noted in the susceptible regions (spinal cord and cerebellum) than the resistant region (cerebrum), may indicate complex molecular pathways via altered BCL2 and GADD45 gene expression, causing the homeostatic imbalance between cell survival and cell death mechanisms. Semi quantitative

  6. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    Science.gov (United States)

    Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

    2010-01-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

  7. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    International Nuclear Information System (INIS)

    Monette, Michelle Y.; Yada, Takashi; Matey, Victoria; McCormick, Stephen D.

    2010-01-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 μg l -1 Al), acid and low Al (LAl: pH 5.4, 11 μg l -1 Al), acid and moderate Al (MAl: pH 5.3, 42 μg l -1 Al), and acid and high Al (HAl: pH 5.4, 56 μg l -1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na + /K + -ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl - channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose

  8. Molecular evolution of Zika virus during its emergence in the 20(th century.

    Directory of Open Access Journals (Sweden)

    Oumar Faye

    Full Text Available Zika virus (ZIKV is a mosquito-borne flavivirus first isolated in Uganda in 1947. Although entomological and virologic surveillance have reported ZIKV enzootic activity in diverse countries of Africa and Asia, few human cases were reported until 2007, when a Zika fever epidemic took place in Micronesia. In the context of West Africa, the WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever at Institut Pasteur of Dakar (http://www.pasteur.fr/recherche/banques/CRORA/ reports the periodic circulation of ZIKV since 1968. Despite several reports on ZIKV, the genetic relationships among viral strains from West Africa remain poorly understood. To evaluate the viral spread and its molecular epidemiology, we investigated 37 ZIKV isolates collected from 1968 to 2002 in six localities in Senegal and Côte d'Ivoire. In addition, we included strains from six other countries. Our results suggested that these two countries in West Africa experienced at least two independent introductions of ZIKV during the 20(th century, and that apparently these viral lineages were not restricted by mosquito vector species. Moreover, we present evidence that ZIKV has possibly undergone recombination in nature and that a loss of the N154 glycosylation site in the envelope protein was a possible adaptive response to the Aedes dalzieli vector.

  9. Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

    Directory of Open Access Journals (Sweden)

    Iosif A. Mendichovszky

    2016-11-01

    Full Text Available Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT or magnetic resonance imaging (MRI. A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL or metastases (e.g., bronchial, renal. Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma. Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism.

  10. Molecular switches at the synapse emerge from receptor and kinase traffic.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Changes in the synaptic connection strengths between neurons are believed to play a role in memory formation. An important mechanism for changing synaptic strength is through movement of neurotransmitter receptors and regulatory proteins to and from the synapse. Several activity-triggered biochemical events control these movements. Here we use computer models to explore how these putative memory-related changes can be stabilised long after the initial trigger, and beyond the lifetime of synaptic molecules. We base our models on published biochemical data and experiments on the activity-dependent movement of a glutamate receptor, AMPAR, and a calcium-dependent kinase, CaMKII. We find that both of these molecules participate in distinct bistable switches. These simulated switches are effective for long periods despite molecular turnover and biochemical fluctuations arising from the small numbers of molecules in the synapse. The AMPAR switch arises from a novel self-recruitment process where the presence of sufficient receptors biases the receptor movement cycle to insert still more receptors into the synapse. The CaMKII switch arises from autophosphorylation of the kinase. The switches may function in a tightly coupled manner, or relatively independently. The latter case leads to multiple stable states of the synapse. We propose that similar self-recruitment cycles may be important for maintaining levels of many molecules that undergo regulated movement, and that these may lead to combinatorial possible stable states of systems like the synapse.

  11. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  12. Emerging trends in molecular interactions between plants and the broad host range fungal pathogens Botrytis cinerea and Sclerotinia sclerotiorum

    Directory of Open Access Journals (Sweden)

    Malick eMbengue

    2016-03-01

    Full Text Available Fungal plant pathogens are major threats to food security worldwide. Sclerotinia sclerotiorum and Botrytis cinerea are closely related Ascomycete plant pathogens causing mold diseases on hundreds of plant species. There is no genetic source of complete plant resistance to these broad host range pathogens known to date. Instead, natural plant populations show a continuum of resistance levels controlled by multiple genes, a phenotype designated as quantitative disease resistance. Little is known about the molecular mechanisms controlling the interaction between plants and S. sclerotiorum and B. cinerea but significant advances were made on this topic in the last years. This minireview highlights a selection of nine themes that emerged in recent research reports on the molecular bases of plant-S. sclerotiorum and plant-B. cinerea interactions. On the fungal side, this includes progress on understanding the role of oxalic acid, on the study of fungal small secreted proteins. Next, we discuss the exchanges of small RNA between organisms and the control of cell death in plant and fungi during pathogenic interactions. Finally on the plant side, we highlight defense priming by mechanical signals, the characterization of plant Receptor-like proteins and the hormone abscisic acid in the response to B. cinerea and S. sclerotiorum , the role of plant general transcription machinery and plant small bioactive peptides. These represent nine trends we selected as remarkable in our understanding of fungal molecules causing disease and plant mechanisms associated with disease resistance to two devastating broad host range fungi.

  13. Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life

    Science.gov (United States)

    Dhar, Nisha; Weinberg, Marc S.; Michod, Richard E.; Durand, Pierre M.

    2017-09-01

    In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3' end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life.

  14. Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life

    Science.gov (United States)

    Weinberg, Marc S.; Michod, Richard E.

    2017-01-01

    In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3′ end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life. PMID:28989747

  15. Non-Coding RNAs in Saliva: Emerging Biomarkers for Molecular Diagnostics

    Directory of Open Access Journals (Sweden)

    Blanca Majem

    2015-04-01

    Full Text Available Saliva is a complex body fluid that comprises secretions from the major and minor salivary glands, which are extensively supplied by blood. Therefore, molecules such as proteins, DNA, RNA, etc., present in plasma could be also present in saliva. Many studies have reported that saliva body fluid can be useful for discriminating several oral diseases, but also systemic diseases including cancer. Most of these studies revealed messenger RNA (mRNA and proteomic biomarker signatures rather than specific non-coding RNA (ncRNA profiles. NcRNAs are emerging as new regulators of diverse biological functions, playing an important role in oncogenesis and tumor progression. Indeed, the small size of these molecules makes them very stable in different body fluids and not as susceptible as mRNAs to degradation by ribonucleases (RNases. Therefore, the development of a non-invasive salivary test, based on ncRNAs profiles, could have a significant applicability to clinical practice, not only by reducing the cost of the health system, but also by benefitting the patient. Here, we summarize the current status and clinical implications of the ncRNAs present in human saliva as a source of biological information.

  16. Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

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    Ari Ercole

    2017-08-01

    Full Text Available Traumatic brain injury (TBI is understood as an interplay between the initial injury, subsequent secondary injuries, and a complex host response all of which are highly heterogeneous. An understanding of the underlying biology suggests a number of windows where mechanistically inspired interventions could be targeted. Unfortunately, biologically plausible therapies have to-date failed to translate into clinical practice. While a number of stereotypical pathways are now understood to be involved, current clinical characterization is too crude for it to be possible to characterize the biological phenotype in a truly mechanistically meaningful way. In this review, we examine current and emerging technologies for fuller biochemical characterization by the simultaneous measurement of multiple, diverse biomarkers. We describe how clinically available techniques such as cerebral microdialysis can be leveraged to give mechanistic insights into TBI pathobiology and how multiplex proteomic and metabolomic techniques can give a more complete description of the underlying biology. We also describe spatially resolved label-free multiplex techniques capable of probing structural differences in chemical signatures. Finally, we touch on the bioinformatics challenges that result from the acquisition of such large amounts of chemical data in the search for a more mechanistically complete description of the TBI phenotype.

  17. Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

    Directory of Open Access Journals (Sweden)

    Chang Hsiu-Li

    2006-02-01

    Full Text Available Abstract Background Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. Methods Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs. Results Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the

  18. Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

    Science.gov (United States)

    Tahara, Hideaki; Sato, Marimo; Thurin, Magdalena; Wang, Ena; Butterfield, Lisa H; Disis, Mary L; Fox, Bernard A; Lee, Peter P; Khleif, Samir N; Wigginton, Jon M; Ambs, Stefan; Akutsu, Yasunori; Chaussabel, Damien; Doki, Yuichiro; Eremin, Oleg; Fridman, Wolf Hervé; Hirohashi, Yoshihiko; Imai, Kohzoh; Jacobson, James; Jinushi, Masahisa; Kanamoto, Akira; Kashani-Sabet, Mohammed; Kato, Kazunori; Kawakami, Yutaka; Kirkwood, John M; Kleen, Thomas O; Lehmann, Paul V; Liotta, Lance; Lotze, Michael T; Maio, Michele; Malyguine, Anatoli; Masucci, Giuseppe; Matsubara, Hisahiro; Mayrand-Chung, Shawmarie; Nakamura, Kiminori; Nishikawa, Hiroyoshi; Palucka, A Karolina; Petricoin, Emanuel F; Pos, Zoltan; Ribas, Antoni; Rivoltini, Licia; Sato, Noriyuki; Shiku, Hiroshi; Slingluff, Craig L; Streicher, Howard; Stroncek, David F; Takeuchi, Hiroya; Toyota, Minoru; Wada, Hisashi; Wu, Xifeng; Wulfkuhle, Julia; Yaguchi, Tomonori; Zeskind, Benjamin; Zhao, Yingdong; Zocca, Mai-Britt; Marincola, Francesco M

    2009-01-01

    might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions. PMID:19534815

  19. Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

    Directory of Open Access Journals (Sweden)

    Rivoltini Licia

    2009-06-01

    were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.

  20. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  1. The interaction between radiation and complexes of cis-Pt(II) and Rh(II): studies at the molecular and cellular level

    International Nuclear Information System (INIS)

    Chibber, R.

    1985-01-01

    As a first step in gaining an understanding of the relative cellular effects of the transition metal/nitroimidazole complexes the authors have examined the effect of radiation given to cells in the presence of metal complexes not containing a nitroimidazole ligand. The compounds used in the cellular work are a series of Rh(II) carboxylates, cisplatin and JM8 (CBDCA, cis-diammine-1, 1-cyclobutane dicarboxylate platinum (II)). In radiation chemical experiments, Rh(II) acetate and cisplatin were chosen to represent model systems. Results from these radiation chemical and cellular experiments then allow interpretation of the changes in biological response caused by these agents, which are discussed in terms of the mechanism(s) thought to be operative in radiosensitization. (author)

  2. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  3. New molecular probes of vascular inflammation

    International Nuclear Information System (INIS)

    Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (Department of Nuclear Medicine, University Hospital Münster, Münster, and DFG CRC 656 Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" >VRACHIMIS, Alexis; HONOLD, Lisa; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >FAUST, Andreas; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >HERMANN, Sven; SCHÄFERS, Michael

    2016-01-01

    New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential.

  4. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    Energy Technology Data Exchange (ETDEWEB)

    Monette, Michelle Y., E-mail: michelle.monette@yale.edu [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States); Yada, Takashi [Freshwater Fisheries Research Department, National Research Institute of Fisheries Science, Nikko (Japan); Matey, Victoria [Department of Biology, San Diego State University, San Diego, CA 92182 (United States); McCormick, Stephen D. [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States)

    2010-08-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 {mu}g l{sup -1} Al), acid and low Al (LAl: pH 5.4, 11 {mu}g l{sup -1} Al), acid and moderate Al (MAl: pH 5.3, 42 {mu}g l{sup -1} Al), and acid and high Al (HAl: pH 5.4, 56 {mu}g l{sup -1} Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na{sup +}/K{sup +}-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl{sup -} channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time

  5. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    KAUST Repository

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  6. Non-hemagglutinating flaviviruses: molecular mechanisms for the emergence of new strains via adaptation to European ticks.

    Directory of Open Access Journals (Sweden)

    Maxim A Khasnatinov

    2009-10-01

    Full Text Available Tick-borne encephalitis virus (TBEV causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards

  7. General perspectives for molecular nuclear imaging

    International Nuclear Information System (INIS)

    Chung, June Key

    2004-01-01

    Molecular imaging provides a visualization of normal as well as abnormal cellular processes at a molecular or genetic level rather than at an anatomical level. Conventional medical imaging methods utilize the imaging signals produced by nonspecific physico-chemical interaction. However, molecular imaging methods utilize the imaging signals derived from specific cellular or molecular events. Because molecular and genetic changes precede anatomical change in the course of disease development, molecular imaging can detect early events in disease progression. In the near future, through molecular imaging we can understand basic mechanisms of disease, and diagnose earlier and, subsequently, treat earlier intractable disease such as cancer, neuro-degenerative diseases, and immunologic disorders. In beginning period, nuclear medicine started as a molecular imaging, and has had a leading role in the field of molecular imaging. But recently molecular imaging has been rapidly developed. Besides nuclear imaging, molecular imaging methods such as optical imaging, magnetic resonance imaging are emerging. Each imaging modalities have their advantages and weaknesses. The opportunities from molecular imaging look bright. We should try nuclear medicine continues to have a leading role in molecular imaging

  8. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  9. A molecular clock dates the common ancestor of European-type porcine reproductive and respiratory syndrome virus at more than 10 years before the emergence of disease

    DEFF Research Database (Denmark)

    Forsberg, Roald; Oleksiewicz, Martin B.; Krabbe Petersen, Anne Mette

    2001-01-01

    an accurate molecular clock for the European PRRSV ORF 3 gene, place the root in the genealogy, estimate the rate of nucleotide substitution, and date the most recent common viral ancestor of the data set to 1979; more than 10 years before the onset of the European epidemic. Based on these findings, we...... conclude that PRRSV virus most likely entered the pig population some time before the epidemic emergence of the virus, and hence, that emergence of European-type PRRSV is not the result of a recent species transmission event. Together, our results show that ORF3 sequencing is a valuable epidemiologic tool...... for examining the emergence and spread of PRRSV in Europe. As such, the panel of well-characterized and highly divergent ORF3 sequences described in this study provides a reference point for future molecular epidemiologic studies....

  10. On the holistic approach in cellular and cancer biology: nonlinearity, complexity, and quasi-determinism of the dynamic cellular network.

    Science.gov (United States)

    Waliszewski, P; Molski, M; Konarski, J

    1998-06-01

    A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self

  11. Cellularized Cellular Solids via Freeze-Casting.

    Science.gov (United States)

    Christoph, Sarah; Kwiatoszynski, Julien; Coradin, Thibaud; Fernandes, Francisco M

    2016-02-01

    The elaboration of metabolically active cell-containing materials is a decisive step toward the successful application of cell based technologies. The present work unveils a new process allowing to simultaneously encapsulate living cells and shaping cell-containing materials into solid-state macroporous foams with precisely controlled morphology. Our strategy is based on freeze casting, an ice templating materials processing technique that has recently emerged for the structuration of colloids into macroporous materials. Our results indicate that it is possible to combine the precise structuration of the materials with cellular metabolic activity for the model organism Saccharomyces cerevisiae. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Molecular epidemiology of HIV-1 among the HIV infected people of Manipur, Northeastern India: Emergence of unique recombinant forms.

    Science.gov (United States)

    Sharma, Adhikarimayum Lakhikumar; Singh, Thiyam Ramsing; Devi, Khuraijam Ranjana; Singh, Lisam Shanjukumar

    2017-06-01

    According to the Joint National Programme on HIV/AIDS (UNAIDS), the northeastern region of India has the highest HIV prevalence in the country. This study was conducted to determine the current HIV-1 molecular epidemiology of Manipur, a state in northeast India. Blood samples from HIV-1 seropositive subjects were collected between June 2011 and February 2014. The partial regions of HIV-1 genes; pol and tat-vpu-env were independently amplified, sequenced, analyzed, and genotyped. Based on all sequences generated from 110 samples using pol and/or tat-vpu-env gene, the overall HIV-1 genotypes distribution of Manipur was as follows: 65.45% (72/110) subtype C, 32.73% (36/110) unique recombinant forms (URFs), and 1.82% (2/110) subtype B. The distribution of HIV-1 genotypes among the risk groups was: heterosexual: 58.33% (35/60) subtype C, 38.33% (23/60) URFs, and 3.34% (2/60) subtype B; intravenous drug users (IDUs): 85.36% (35/41) subtype C, 9.76% (4/41) URFs, and 4.88% (2/41) subtype B; mother to child (MTC): 50% (3/6) URFs and 50% (3/6) subtype C and blood transfusion: 100% (3/3) subtype C. The findings for the first time revealed the emergence of URFs of HIV-1 in Manipur which is predominant among the sexual and MTC risk groups as compared to IDUs. Taking together, this study illustrated that Manipur is the "recombinant hotspot of HIV" of India. The results will provide the clinical importance for continuous monitoring of HIV-infections in order to design appropriate prevention measures to limit the spread of new HIV infections. © 2016 Wiley Periodicals, Inc.

  13. Emergence of dengue virus 4 genotype II in Guangzhou, China, 2010: Survey and molecular epidemiology of one community outbreak

    Directory of Open Access Journals (Sweden)

    Jing Qin-Long

    2012-04-01

    Full Text Available Abstract Background The re-emergence of dengue virus 4 (DENV-4 has become a public health concern in South America, Southeast Asia and South Asia. However, it has not been known to have caused a local outbreak in China for the past 20 years. The purpose of this study was to elucidate the epidemiology of one local community outbreak caused by DENV-4 in Guangzhou city, China, in 2010; and to determine the molecular characteristics of the genotype II virus involved. Case presentations During September and October of 2010, one imported case, a Guangzhou resident who travelled back from Thailand, resulted in 18 secondary autochthonous cases in Guangzhou City, with an incidence rate of 5.53 per 10,000 residents. In indigenous cases, 14 serum samples tested positive for IgM against DENV and 7 for IgG from a total of 15 submitted serum samples, accompanied by 5 DENV-4 isolates. With identical envelope gene nucleotide sequences, the two isolates (D10168-GZ from the imported index case and Guangzhou 10660 from the first isolate in the autochthonous cases were grouped into DENV-4 genotype II after comparison to 32 previous DENV-4 isolates from GenBank that originated from different areas. Conclusions Based on epidemiological and phylogenetic analyses, the outbreak, which was absent for 20 years after the DENV-4 genotype I outbreak in 1990, was confirmed as DENV-4 genotype II and initially traced to the imported index case, a Guangzhou resident who travelled back from Thailand.

  14. Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

    Directory of Open Access Journals (Sweden)

    Ding X

    2012-02-01

    Full Text Available Wei Fan1,2,*, Xin Wu1,*, Baoyue Ding3,*, Jing Gao4, Zhen Cai1, Wei Zhang1, Dongfeng Yin1, Xiang Wang1, Quangang Zhu1, Jiyong Liu1, Xueying Ding4, Shen Gao1 1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, The 425th Hospital of PLA, Sanya, 3Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, 4Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workBackground: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.Methods: This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.Results: Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to

  15. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Giovanni Dalmasso

    Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

  16. Cellular senescence and organismal aging.

    Science.gov (United States)

    Jeyapalan, Jessie C; Sedivy, John M

    2008-01-01

    Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

  17. Quantum Biology at the Cellular Level - elements of the research program

    OpenAIRE

    Bordonaro, Michael; Ogryzko, Vasily

    2013-01-01

    Quantum Biology is emerging as a new field at the intersection between fundamental physics and biology, promising novel insights into the nature and origin of biological order. We discuss several elements of QBCL (Quantum Biology at Cellular Level), a research program designed to extend the reach of quantum concepts to higher than molecular levels of biological organization. Key words. decoherence, macroscopic superpositions, basis-dependence, formal superposition, non-classical correlations,...

  18. Cellular strategies to cope with protein aggregation

    NARCIS (Netherlands)

    Scior, Annika; Juenemann, Katrin; Kirstein, Janine

    2016-01-01

    Nature has evolved several mechanisms to detoxify intracellular protein aggregates that arise upon proteotoxic challenges. These include the controlled deposition of misfolded proteins at distinct cellular sites, the protein disaggregation and refolding by molecular chaperones and/or degradation of

  19. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sakane, K.K. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Monteiro, C.J.; Silva, W.; Silva, A.R. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Santos, P.M. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Lima, K.F. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Moraes, K.C.M. [Instituto de Biociências, Departamento de Biologia, Universidade Estadual Paulista ‘‘Júlio de Mesquita Filho’’, Rio Claro, SP (Brazil)

    2013-11-29

    Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

  20. Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions

    Directory of Open Access Journals (Sweden)

    Z.K. Tuong

    2018-06-01

    Full Text Available Currently available vaccines prevent HPV infection and development of HPV-associated malignancies, but do not cure existing HPV infections and dysplastic lesions. Persistence of infection(s in immunocompetent patients may reflect induction of local immunosuppressive mechanisms by HPV, providing a target for therapeutic intervention. We have proposed that a mouse, expressing HPV16 E7 oncoprotein under a Keratin 14 promoter (K14E7 mice, and which develops epithelial hyperplasia, may assist with understanding local immune suppression mechanisms that support persistence of HPV oncogene-induced epithelial hyperplasia. K14E7 skin grafts recruit immune cells from immunocompetent hosts, but consistently fail to be rejected. Here, we review the literature on HPV-associated local immunoregulation, and compare the findings with published observations on the K14E7 transgenic murine model, including comparison of the transcriptome of human HPV-infected pre-malignancies with that of murine K14E7 transgenic skin. We argue from the similarity of i the literature findings and ii the transcriptome profiles that murine K14E7 transgenic skin recapitulates the cellular and secreted protein profiles of high-grade HPV-associated lesions in human subjects. We propose that the K14E7 mouse may be an appropriate model to further study the immunoregulatory effects of HPV E7 expression, and can facilitate development and testing of therapeutic vaccines.

  1. The Emerging Role of Complement Lectin Pathway in Trypanosomatids: Molecular Bases in Activation, Genetic Deficiencies, Susceptibility to Infection, and Complement System-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Ingrid Evans-Osses

    2013-01-01

    Full Text Available The innate immune system is evolutionary and ancient and is the pivotal line of the host defense system to protect against invading pathogens and abnormal self-derived components. Cellular and molecular components are involved in recognition and effector mechanisms for a successful innate immune response. The complement lectin pathway (CLP was discovered in 1990. These new components at the complement world are very efficient. Mannan-binding lectin (MBL and ficolin not only recognize many molecular patterns of pathogens rapidly to activate complement but also display several strategies to evade innate immunity. Many studies have shown a relation between the deficit of complement factors and susceptibility to infection. The recently discovered CLP was shown to be important in host defense against protozoan microbes. Although the recognition of pathogen-associated molecular patterns by MBL and Ficolins reveal efficient complement activations, an increase in deficiency of complement factors and diversity of parasite strategies of immune evasion demonstrate the unsuccessful effort to control the infection. In the present paper, we will discuss basic aspects of complement activation, the structure of the lectin pathway components, genetic deficiency of complement factors, and new therapeutic opportunities to target the complement system to control infection.

  2. On Elementary and Algebraic Cellular Automata

    Science.gov (United States)

    Gulak, Yuriy

    In this paper we study elementary cellular automata from an algebraic viewpoint. The goal is to relate the emergent complex behavior observed in such systems with the properties of corresponding algebraic structures. We introduce algebraic cellular automata as a natural generalization of elementary ones and discuss their applications as generic models of complex systems.

  3. Information theory based approaches to cellular signaling.

    Science.gov (United States)

    Waltermann, Christian; Klipp, Edda

    2011-10-01

    Cells interact with their environment and they have to react adequately to internal and external changes such changes in nutrient composition, physical properties like temperature or osmolarity and other stresses. More specifically, they must be able to evaluate whether the external change is significant or just in the range of noise. Based on multiple external parameters they have to compute an optimal response. Cellular signaling pathways are considered as the major means of information perception and transmission in cells. Here, we review different attempts to quantify information processing on the level of individual cells. We refer to Shannon entropy, mutual information, and informal measures of signaling pathway cross-talk and specificity. Information theory in systems biology has been successfully applied to identification of optimal pathway structures, mutual information and entropy as system response in sensitivity analysis, and quantification of input and output information. While the study of information transmission within the framework of information theory in technical systems is an advanced field with high impact in engineering and telecommunication, its application to biological objects and processes is still restricted to specific fields such as neuroscience, structural and molecular biology. However, in systems biology dealing with a holistic understanding of biochemical systems and cellular signaling only recently a number of examples for the application of information theory have emerged. This article is part of a Special Issue entitled Systems Biology of Microorganisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Study of the impact of radionuclides discharges from nuclear industry in the northern Cotentin area on the oyster Crassostrea gigas: expression of cellular stress molecular markers

    International Nuclear Information System (INIS)

    Farcy, E.

    2006-11-01

    This thesis explores the potential radiological impact of radionuclide discharges from the nuclear industry on the Pacific oyster, Crassostrea gigas. One of the major goals of this research was to identify markers that could be used to monitor the effects of low-level chronic irradiation. We decided to focalize on the expression of stress-induced genes involved in the regulation of cellular stress, focusing on transcription. First, homology cloning was used to identify four new cDNAs encoding stress markers. Then data collected at various sites enabled to evidence that mRNA levels for each of the genes of interest naturally vary to a significant degree, based on individual differences and seasonal factors. Comparing oysters from exposed sites with those from a reference site located on the Atlantic coast did not suggest any relationship between mRNA levels changes and the oysters exposure to liquid radioactive waste from the A.R.E.V.A. reprocessing plant. In the environment, we found that those radionuclide releases resulted in a very small increase in radioactivity in oysters, especially compared with their natural radioactivity. In the laboratory, by exposing the oysters to higher radionuclide concentrations than those found in the environment, we were able to identify two genes as potential candidates for studying the effects of chronic exposure to low doses of ionizing radiations in the oyster: genes encoding MT and MXR. We confirmed that transcriptional induction of these two genes occurs in response to high doses of acute irradiation. Finally, the comparison between environmental results and the laboratory results underlined the complementarity of these two approaches. In particular, it revealed that seasonal variations in mRNA levels probably have a significant effect on the stress response. (author)

  5. New Markov-Shannon Entropy models to assess connectivity quality in complex networks: from molecular to cellular pathway, Parasite-Host, Neural, Industry, and Legal-Social networks.

    Science.gov (United States)

    Riera-Fernández, Pablo; Munteanu, Cristian R; Escobar, Manuel; Prado-Prado, Francisco; Martín-Romalde, Raquel; Pereira, David; Villalba, Karen; Duardo-Sánchez, Aliuska; González-Díaz, Humberto

    2012-01-21

    Graph and Complex Network theory is expanding its application to different levels of matter organization such as molecular, biological, technological, and social networks. A network is a set of items, usually called nodes, with connections between them, which are called links or edges. There are many different experimental and/or theoretical methods to assign node-node links depending on the type of network we want to construct. Unfortunately, the use of a method for experimental reevaluation of the entire network is very expensive in terms of time and resources; thus the development of cheaper theoretical methods is of major importance. In addition, different methods to link nodes in the same type of network are not totally accurate in such a way that they do not always coincide. In this sense, the development of computational methods useful to evaluate connectivity quality in complex networks (a posteriori of network assemble) is a goal of major interest. In this work, we report for the first time a new method to calculate numerical quality scores S(L(ij)) for network links L(ij) (connectivity) based on the Markov-Shannon Entropy indices of order k-th (θ(k)) for network nodes. The algorithm may be summarized as follows: (i) first, the θ(k)(j) values are calculated for all j-th nodes in a complex network already constructed; (ii) A Linear Discriminant Analysis (LDA) is used to seek a linear equation that discriminates connected or linked (L(ij)=1) pairs of nodes experimentally confirmed from non-linked ones (L(ij)=0); (iii) the new model is validated with external series of pairs of nodes; (iv) the equation obtained is used to re-evaluate the connectivity quality of the network, connecting/disconnecting nodes based on the quality scores calculated with the new connectivity function. This method was used to study different types of large networks. The linear models obtained produced the following results in terms of overall accuracy for network reconstruction

  6. GENESIS: a hybrid-parallel and multi-scale molecular dynamics simulator with enhanced sampling algorithms for biomolecular and cellular simulations.

    Science.gov (United States)

    Jung, Jaewoon; Mori, Takaharu; Kobayashi, Chigusa; Matsunaga, Yasuhiro; Yoda, Takao; Feig, Michael; Sugita, Yuji

    2015-07-01

    GENESIS (Generalized-Ensemble Simulation System) is a new software package for molecular dynamics (MD) simulations of macromolecules. It has two MD simulators, called ATDYN and SPDYN. ATDYN is parallelized based on an atomic decomposition algorithm for the simulations of all-atom force-field models as well as coarse-grained Go-like models. SPDYN is highly parallelized based on a domain decomposition scheme, allowing large-scale MD simulations on supercomputers. Hybrid schemes combining OpenMP and MPI are used in both simulators to target modern multicore computer architectures. Key advantages of GENESIS are (1) the highly parallel performance of SPDYN for very large biological systems consisting of more than one million atoms and (2) the availability of various REMD algorithms (T-REMD, REUS, multi-dimensional REMD for both all-atom and Go-like models under the NVT, NPT, NPAT, and NPγT ensembles). The former is achieved by a combination of the midpoint cell method and the efficient three-dimensional Fast Fourier Transform algorithm, where the domain decomposition space is shared in real-space and reciprocal-space calculations. Other features in SPDYN, such as avoiding concurrent memory access, reducing communication times, and usage of parallel input/output files, also contribute to the performance. We show the REMD simulation results of a mixed (POPC/DMPC) lipid bilayer as a real application using GENESIS. GENESIS is released as free software under the GPLv2 licence and can be easily modified for the development of new algorithms and molecular models. WIREs Comput Mol Sci 2015, 5:310-323. doi: 10.1002/wcms.1220.

  7. Cardiovascular Molecular Imaging

    International Nuclear Information System (INIS)

    Lee, Kyung Han

    2009-01-01

    Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis. Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field

  8. Gene expression reaction norms unravel the molecular and cellular processes underpinning the plastic phenotypes of Alternanthera philoxeroides in contrasting hydrological conditions

    Directory of Open Access Journals (Sweden)

    Lexuan eGao

    2015-11-01

    Full Text Available Alternanthera philoxeroides is an amphibious invasive weed that can colonize both aquatic and terrestrial habitats. Individuals growing in different habitats exhibit extensive phenotypic variation but little genetic differentiation. Little is known about the molecular basis underlying environment-induced phenotypic changes. Variation in transcript abundance in A. philoxeroides was characterized throughout the time-courses of pond and upland treatments using RNA-Sequencing. 7,805 genes demonstrated variable expression in response to different treatments,forming 11 transcriptionally coordinated gene groups. Functional enrichment analysis of plastically expressed genes revealed pathway changes in hormone-mediated signaling, osmotic adjustment, cell wall remodeling and programmed cell death, providing a mechanistic understanding of the biological processes underlying the phenotypic changes in A. philoxeroides. Both transcriptional modulation of environmentally sensitive loci and environmentally dependent control of regulatory loci influenced the plastic responses to the environment. Phenotypic responses and gene expression patterns to contrasting hydrological conditions were compared between A. philoxeroides and its alien congener A. pungens. The terricolous A. pungens displayed limited phenotypic plasticity to different treatments. It was postulated based on gene expression comparison that the interspecific variation in plasticity between A. philoxeroides and A. pungens was not due to environmentally-mediated changes in hormone levels but to variations in the type and relative abundance of different signal transducers and receptors expressed in the target tissue.

  9. Molecular and Cellular Dynamics in the Skin, the Lymph Nodes, and the Blood of the Immune Response to Intradermal Injection of Modified Vaccinia Ankara Vaccine

    Directory of Open Access Journals (Sweden)

    Pierre Rosenbaum

    2018-04-01

    Full Text Available New vaccine design approaches would be greatly facilitated by a better understanding of the early systemic changes, and those that occur at the site of injection, responsible for the installation of a durable and oriented protective response. We performed a detailed characterization of very early infection and host response events following the intradermal administration of the modified vaccinia virus Ankara as a live attenuated vaccine model in non-human primates. Integrated analysis of the data obtained from in vivo imaging, histology, flow cytometry, multiplex cytokine, and transcriptomic analysis using tools derived from systems biology, such as co-expression networks, showed a strong early local and systemic inflammatory response that peaked at 24 h, which was then progressively replaced by an adaptive response during the installation of the host response to the vaccine. Granulocytes, macrophages, and monocytoid cells were massively recruited during the local innate response in association with local productions of GM-CSF, IL-1β, MIP1α, MIP1β, and TNFα. We also observed a rapid and transient granulocyte recruitment and the release of IL-6 and IL-1RA, followed by a persistent phase involving inflammatory monocytes. This systemic inflammation was confirmed by molecular signatures, such as upregulations of IL-6 and TNF pathways and acute phase response signaling. Such comprehensive approaches improve our understanding of the spatiotemporal orchestration of vaccine-elicited immune response, in a live-attenuated vaccine model, and thus contribute to rational vaccine development.

  10. Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.

    2009-11-01

    We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

  11. Molecular Diagnostics Update for the Emerging (If Not Already Widespread) Sexually Transmitted Infection Agent Mycoplasma genitalium: Just About Ready for Prime Time.

    Science.gov (United States)

    Munson, Erik

    2017-10-01

    Mycoplasma genitalium is an important and emerging agent of sexually transmitted infection in females and males, carrying the potential for postinfection genital tract sequelae. Past efforts to identify this organism on a routine basis, which were problematic due to the fastidious nature of the bacterium and its antigenic intricacies, have recently become supplemented by molecular diagnostics. A number of these assays are available commercially. This minireview describes the format and performance indices of a number of M. genitalium DNA- and RNA-based amplification assays; many of these assays have contributed to an improved clinical and epidemiologic understanding of this organism. Copyright © 2017 American Society for Microbiology.

  12. Profiling and functional data on the developing olfactory/GnRH system reveal cellular and molecular pathways essential for this process and potentially relevant for the Kallmann syndrome

    Directory of Open Access Journals (Sweden)

    Giulia eGaraffo

    2013-12-01

    Full Text Available During embryonic development, immature neurons in the olfactory epithelium (OE extend axons through the nasal mesenchyme, to contact projection neurons in the olfactory bulb. Axon navigation is accompanied by migration of the GnRH+ neurons, which enter the anterior forebrain and home in the septo-hypothalamic area. This process can be interrupted at various points and lead to the onset of the Kallmann syndrome (KS, a disorder characterized by anosmia and central hypogonadotropic hypogonadism. Several genes has been identified in human and mice that cause KS or a KS-like phenotype. In mice a set of transcription factors appears to be required for olfactory connectivity and GnRH neuron migration; thus we explored the transcriptional network underlying this developmental process by profiling the OE and the adjacent mesenchyme at three embryonic ages. We also profiled the OE from embryos null for Dlx5, a homeogene that causes a KS-like phenotype when deleted. We identified 20 interesting genes belonging to the following categories: 1 transmembrane adhesion/receptor, 2 axon-glia interaction, 3 scaffold/adapter for signalling, 4 synaptic proteins. We tested some of them in zebrafish embryos: the depletion of five (of six Dlx5 targets affected axonal extension and targeting, while three (of three affected GnRH neuron position and neurite organization. Thus, we confirmed the importance of cell-cell and cell-matrix interactions and identified new molecules needed for olfactory connection and GnRH neuron migration. Using available and newly generated data, we predicted/prioritized putative KS-disease genes, by building conserved co-expression networks with all known disease genes in human and mouse. The results show the overall validity of approaches based on high-throughput data and predictive bioinformatics to identify genes potentially relevant for the molecular pathogenesis of KS. A number of candidate will be discussed, that should be tested in

  13. Probing Cellular Dynamics with Mesoscopic Simulations

    DEFF Research Database (Denmark)

    Shillcock, Julian C.

    2010-01-01

    Cellular processes span a huge range of length and time scales from the molecular to the near-macroscopic. Understanding how effects on one scale influence, and are themselves influenced by, those on lower and higher scales is a critical issue for the construction of models in Systems Biology....... Advances in computing hardware and software now allow explicit simulation of some aspects of cellular dynamics close to the molecular scale. Vesicle fusion is one example of such a process. Experiments, however, typically probe cellular behavior from the molecular scale up to microns. Standard particle...... soon be coupled to Mass Action models allowing the parameters in such models to be continuously tuned according to the finer resolution simulation. This will help realize the goal of a computational cellular simulation that is able to capture the dynamics of membrane-associated processes...

  14. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    cross-linked or branched networks. It is a highly dynamical system in which filaments are able to elongate or slide one on the other with the contribution of very active cellular proteins like molecular motors. The versatile properties of this cytoskeleton ensure the diversity of mechanical behaviors to explain cell rigidity as well as cell motility.

  15. Laboratory testing in the emergency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC and Academy of Emergency Medicine and Care (AcEMC consensus report

    Directory of Open Access Journals (Sweden)

    Giuseppe Lippi

    2017-04-01

    Full Text Available The mainstay of patient-oriented laboratory testing in emergency settings entails selecting number and type of tests according to valid criteria of appropriateness. Since the pattern of urgent tests requesting is variable across different institutions, we designed a joined survey between the Academy of Emergency Medicine and Care (AcEMC and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC for reaching tentative consensus about the most informative diagnostic tests in emergency settings. A survey, containing the most commonly performed urgent laboratory tests and the relative clinical indications, was disseminated to eight relevant members of AcEMC and eight relevant members of SIBioC. All contributors were asked to provide numerical scores for the different laboratory parameters, where 1 indicated strongly recommended, 2 recommended in specific circumstances, and 3 strongly discouraged. The mean results of the survey were presented as the mean of responders’ values, and the parameters were finally classified as strongly recommended (mean value, 1.0-1.5, somehow recommended (mean value, 1.5-2.0, discouraged (mean value, 2.0-2.5 and strongly discouraged (mean value, 2.5-3.0. The results of the survey allowed defining a hierarchy of priority, wherein 24 tests were strongly recommended. The use of 5 common tests was instead strongly discouraged. For 16 additional parameters in the list, the consensus ranged between somehow recommended and discouraged. We hope that results presented in this joint AcEMC-SIBioC consensus document may help harmonizing panel of tests and requesting patters in emergency setting, at least at a national level.

  16. Progress on molecular imaging

    International Nuclear Information System (INIS)

    Chen Quan; Zhang Yongxue

    2011-01-01

    Molecular imaging is a new era of medical imaging,which can non-invasively monitor biological processes at the cellular and molecular level in vivo, including molecular imaging of nuclear medicine, magnetic resonance molecular imaging, ultrasound molecular imaging,optical molecular imaging and molecular imaging with X-ray. Recently, with the development of multi-subjects amalgamation, multimodal molecular imaging technology has been applied in clinical imaging, such as PET-CT and PET-MRI. We believe that with development of molecular probe and multi-modal imaging, more and more molecular imaging techniques will be applied in clinical diagnosis and treatment. (authors)

  17. Participation in a Year-Long CURE Embedded into Major Core Genetics and Cellular and Molecular Biology Laboratory Courses Results in Gains in Foundational Biological Concepts and Experimental Design Skills by Novice Undergraduate Researchers†

    Science.gov (United States)

    Peteroy-Kelly, Marcy A.; Marcello, Matthew R.; Crispo, Erika; Buraei, Zafir; Strahs, Daniel; Isaacson, Marisa; Jaworski, Leslie; Lopatto, David; Zuzga, David

    2017-01-01

    This two-year study describes the assessment of student learning gains arising from participation in a year-long curriculum consisting of a classroom undergraduate research experience (CURE) embedded into second-year, major core Genetics and Cellular and Molecular Biology (CMB) laboratory courses. For the first course in our CURE, students used micro-array or RNAseq analyses to identify genes important for environmental stress responses by Saccharomyces cerevisiae. The students were tasked with creating overexpressing mutants of their genes and designing their own original experiments to investigate the functions of those genes using the overexpression and null mutants in the second CURE course. In order to evaluate student learning gains, we employed three validated concept inventories in a pretest/posttest format and compared gains on the posttest versus the pretest with student laboratory final grades. Our results demonstrated that there was a significant correlation between students earning lower grades in the Genetics laboratory for both years of this study and gains on the Genetics Concept Assessment (GCA). We also demonstrated a correlation between students earning lower grades in the Genetics laboratory and gains on the Introductory Molecular and Cell Biology Assessment (IMCA) for year 1 of the study. Students furthermore demonstrated significant gains in identifying the variable properties of experimental subjects when assessed using the Rubric for Experimental (RED) design tool. Results from the administration of the CURE survey support these findings. Our results suggest that a year-long CURE enables lower performing students to experience greater gains in their foundational skills for success in the STEM disciplines. PMID:28904646

  18. Population Dynamics and Rates of Molecular Evolution of a Recently Emerged Paramyxovirus, Avian Metapneumovirus Subtype C▿ †

    OpenAIRE

    Padhi, Abinash; Poss, Mary

    2008-01-01

    We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 × 10−3 to 7 × 10−3 substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes exam...

  19. Population Dynamics and Rates of Molecular Evolution of a Recently Emerged Paramyxovirus, Avian Metapneumovirus Subtype C▿ †

    Science.gov (United States)

    Padhi, Abinash; Poss, Mary

    2009-01-01

    We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 × 10−3 to 7 × 10−3 substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes examined show a concordant demographic pattern which is characterized by a rapid increase in population size followed by stable population grown until the present. PMID:19052092

  20. New palladium(II) and platinum(II) 5,5-diethylbarbiturate complexes with 2-phenylpyridine, 2,2'-bipyridine and 2,2'-dipyridylamine: synthesis, structures, DNA binding, molecular docking, cellular uptake, antioxidant activity and cytotoxicity.

    Science.gov (United States)

    Icsel, Ceyda; Yilmaz, Veysel T; Kaya, Yunus; Samli, Hale; Harrison, William T A; Buyukgungor, Orhan

    2015-04-21

    Novel palladium(ii) and platinum(ii) complexes of 5,5-diethylbarbiturate (barb) with 2-phenylpyridine (Hppy), 2,2'-bipyridine (bpy) and 2,2'-dipyridylamine (dpya) have been prepared and characterized by elemental analysis, IR, UV-Vis, NMR and ESI-MS. Single-crystal diffraction measurements show that complex consists of binuclear [Pd2(μ-barb-κN,O)2(ppy-κN,C)2] moieties, while complexes are mononuclear, [M(barb-κN)2(L-κN,N')] (L = bpy or dpya). has a composition of [Pt(dpya-κN,N')2][Ag(barb-κN)2]2·4H2O and was assumed to have a structure of [Pt(barb-κN)(Hppy-κN)(ppy-κN,C)]·3H2O. The complexes were found to exhibit significant DNA binding affinity by a non-covalent binding mode, in accordance with molecular docking studies. In addition, complexes and displayed strong binding with supercoiled pUC19 plasmid DNA. Cellular uptake studies were performed to assess the subcellular localization of the selected complexes. A moderate radical scavenging activity of and was confirmed by DPPH and ABTS tests. Complexes , , and showed selectivity against HT-29 (colon) cell line.

  1. Simulations of living cell origins using a cellular automata model.

    Science.gov (United States)

    Ishida, Takeshi

    2014-04-01

    Understanding the generalized mechanisms of cell self-assembly is fundamental for applications in various fields, such as mass producing molecular machines in nanotechnology. Thus, the details of real cellular reaction networks and the necessary conditions for self-organized cells must be elucidated. We constructed a 2-dimensional cellular automata model to investigate the emergence of biological cell formation, which incorporated a looped membrane and a membrane-bound information system (akin to a genetic code and gene expression system). In particular, with an artificial reaction system coupled with a thermal system, the simultaneous formation of a looped membrane and an inner reaction process resulted in a more stable structure. These double structures inspired the primitive biological cell formation process from chemical evolution stage. With a model to simulate cellular self-organization in a 2-dimensional cellular automata model, 3 phenomena could be realized: (1) an inner reaction system developed as an information carrier precursor (akin to DNA); (2) a cell border emerged (akin to a cell membrane); and (3) these cell structures could divide into 2. This double-structured cell was considered to be a primary biological cell. The outer loop evolved toward a lipid bilayer membrane, and inner polymeric particles evolved toward precursor information carriers (evolved toward DNA). This model did not completely clarify all the necessary and sufficient conditions for biological cell self-organization. Further, our virtual cells remained unstable and fragile. However, the "garbage bag model" of Dyson proposed that the first living cells were deficient; thus, it would be reasonable that the earliest cells were more unstable and fragile than the simplest current unicellular organisms.

  2. The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research.

    Science.gov (United States)

    Iyegbe, Conrad; Campbell, Desmond; Butler, Amy; Ajnakina, Olesya; Sham, Pak

    2014-02-01

    Schizophrenia is a devastating mental disorder. The level of risk in the general population is sustained by the persistence of social, environmental and biological factors, as well as their interactions. Socio-environmental risk factors for schizophrenia are well established and robust. The same can belatedly be said of genetic risk factors for the disorder. Recent progress in schizophrenia genetics is primarily fuelled by genome-wide association, which is able to leverage substantial proportions of additional explained variance previously classified as 'missing'. Here, we provide an outline of the emerging genetic landscape of schizophrenia and demonstrate how this knowledge can be turned into a simple empirical measure of genetic risk, known as a polygenic risk score. We highlight the statistical framework used to assess the clinical potential of the new score and finally, draw relevance to and discuss the clinical implications for the study of gene-environment interaction.

  3. Molecular and cellular mechanisms of pulmonary fibrosis

    Science.gov (United States)

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  4. Cellular and molecular biology of filamentous fungi

    National Research Council Canada - National Science Library

    Borkovich, Katherine A; Ebbole, Daniel J

    2010-01-01

    ... AND EXPRESSION OF THE GENETIC CODE / 61 6 Mitotic Cell Cycle Control / 63 COLIN P. C. DE SOUZA AND STEPHEN A. OSMANI 7 Meiosis / 81 CLAIRE BURNS, PATRICIA J. PUKKILA, AND MIRIAM E. ZOLAN 8 DNA Repa...

  5. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2013-01-01

    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  6. Molecular and Cellular Basis of Aging

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2016-01-01

    KEY FACTS • Signs of biological aging appear progressively and exponentially during the period of survival beyond the ELS of a species. • There are no gerontogenes evolved with a specific function of causing aging and eventual death. • The role of genes in aging and longevity is mainly at the level...... of longevity-assurance in evolutionary terms. • The phenotype of aging is highly differential and heterogeneous at all levels of biological organization. • Aging is characterized by a stochastic occurrence, accumulation, and heterogeneity of damage in macromolecules. • Mild stress-induced activation of defense...

  7. Testes, embryology of: Cellular molecular changes

    DEFF Research Database (Denmark)

    Svingen, Terje; Pelliniemi, L. J.

    2015-01-01

    Testis is the male gonad containing two functional parts: the seminiferous tubules for the production and transport of male germ cells (spermatogenesis) and the interstitial compartment containing Leydig cells that produce androgens. It develops from an undifferentiated precursor structure (the g...

  8. Cellular and molecular basis of tooth eruption

    Science.gov (United States)

    Wise, GE

    2009-01-01

    Objectives Tooth eruption requires the presence of a dental follicle (DF), alveolar bone resorption for an eruption pathway, and alveolar bone formation at the base of the bony crypt. The objectives of our investigations have been to determine how the DF regulates both the osteoclastogenesis and osteogenesis needed for eruption. Material & Methods Multiple experimental methods have been employed. Results The DF regulates osteoclastogenesis and osteogenesis by regulating the expression of critical genes in both a chronological and spatial fashion. In the rat 1st mandibular molar there is a major burst of osteoclastogenesis at day 3 postnatally and a minor burst at day 10. At day 3, the DF maximally expresses colony-stimulating factor-1 (CSF-1) to down-regulate the expression of osteoprotegerin such that osteoclastogenesis can occur. At day 10, the minor burst of osteoclastogenesis is promoted by upregulation of VEGF and RANKL in the DF. Spatially, the bone resorption is in the coronal portion of the bony crypt and genes such as RANKL are expressed more in the coronal region of the DF than in its basal one-half. For osteogenesis, bone formation begins at day 3 at the base of the bony crypt and maximal growth is at days 9–14. Osteo-inductive genes such as BMP-2 appear to promote this and are expressed more in the basal half of the DF than in the coronal. Conclusion The osteoclastogenesis and osteogenesis needed for eruption are regulated by differential gene expression in the DF both chronologically and spatially. PMID:19419449

  9. Magnetic effects in cellular and molecular systems

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    Brief discussions are presented of six aspects of the phenomenon. Individual topics discussed include: (1) mechanisms of magnetic field interactions with retinal rods; (2) orientation of biological membranes and cells in magnetic fields; (3) enzyme-substrate reactions in high magnetic fields; (4) effects on cell function resulting from exposure to strong magnetic fields at 4 0 K; (5) effects of a transverse magnetic field on the dose distribution of high energy electrons and in the responses of mammalian cells in vitro to x rays; and (6) effect of magnetic fields on the drug-induced contractility of the ciliate Spirostomum

  10. Molecular and Cellular Mechanisms of Septic Shock

    Science.gov (United States)

    1988-03-01

    due to gastric dilation - volvulus (6Y). The LAL-chromogenic procedure iýs sensitive and reliable for detecting plasma LPS. LPS has a short initial T 1/2...portal injections of endotoxin. and intestinal ischemia. Endotoxin (LPS) was quantitated in canine plasma using the Limulus amebocyte lysate (LAL...CV=1O), and stability of diluted, heat-treated, frozen samples (at least 8 wk). Analysis of canine plasma samples following sublethal IV (jugular or

  11. Molecular and cellular effects of radiations

    International Nuclear Information System (INIS)

    Peak, M.J.; Peak, J.G.; Ito, A.; Roth, R.M.

    1985-01-01

    This program is concerned with the basic nature of the biological effects of mutagenic and carcinogenic environmental radiations, including those solar ultraviolet and visible radiations responsible for the most common form of human cancer: cancer of the skin. Concentrating on the damages to DNA caused by these radiations, the program attempts to delineate the basic mechanisms whereby such damage may occur. 14 refs

  12. The cellular and molecular biology of medulloblastoma

    NARCIS (Netherlands)

    Peringa, A; Fung, KM; Muragaki, Y; Trojanowski, JQ

    1995-01-01

    Medulloblastomas are prototypical of primitive neuroectodermal tumors which are some of the most frequent malignant brain tumors of childhood. The cell biology of medulloblastomas is still poorly understood, but recent studies of the expression of trophic factors and their receptors in

  13. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

    NARCIS (Netherlands)

    Mulder, Willem J. M.; Strijkers, Gustav J.; van Tilborg, Geralda A. F.; Griffioen, Arjan W.; Nicolay, Klaas

    2006-01-01

    In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the

  14. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  15. Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

    Science.gov (United States)

    Crist, Colin

    2017-01-01

    Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Assessment of beta-emitter radionuclides in biological samples using liquid scintillation counting. Application to the study of internal doses in molecular and cellular biology techniques; Evaluacion en muestras biologicas de radionucleidos emisores beta mediante espectrometria de centelleo en fase liquida. Aplicaciones al estudio de dosis internas en tecnicas de investigacion de biologia molecular y celular

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, I.; Delgado, A.; Navarro, T.; Macias, M. T.

    2007-07-01

    The radioisotopic techniques used in Molecular and Cellular Biology involve external and internal irradiation risk. It is necessary to control the possible internal contamination associated to the development of these techniques. The internal contamination risk can be due to physical and chemical properties of the labelled compounds, aerosols generated during the performance technique. The aim of this work was to estimate the possible intake of specific beta emitters during the technique development and to propose the required criterions to perform Individual Monitoring. The most representative radioisotopic techniques were selected attending their potential risk of internal contamination. Techniques were analysed applying IAEA methodology according to the used activity in each technique. It was necessary to identify the worker groups that would require individual monitoring on the base of their specific risk. Different measurement procedures were applied to study the possible intake in group risk and more than 160 persons were measured by in vitro bioassay. (Author) 96 refs.

  17. A single midcycle dose of levonorgestrel similar to emergency contraceptive does not alter the expression of the L-selectin ligand or molecular markers of endometrial receptivity.

    Science.gov (United States)

    Palomino, Wilder Alberto; Kohen, Paulina; Devoto, Luigi

    2010-10-01

    To examine the effects of a single-dose of 1.5 mg of levonorgestrel (commonly used as emergency contraceptive) on endometrial receptivity biomarkers through the oral or vaginal route. Prospective randomized single-blinded trial. Affiliated Hospital and University Research Center. Fertile normal women previously sterilized by tubal ligation. Levonorgestrel (1.5 mg) was administered on the day of LH surge either orally (n = 14) or vaginally (n = 13). Molecular assessment of endometrial progesterone receptors, L-selectin ligand, glicodelin-A and αvβ3 integrin by Immunohistochemistry and reverse transcriptase-polymerase chain reaction. Plasma progesterone concentration and endometrial dating were not different. The pattern of progesterone receptors and glycodelin-A expression was not affected during the early and midsecretory phase. Some endometrial biopsies from the group in which levonorgetrel was orally administered showed areas of glandular atrophy and stromal decidualization. However, the expression of the progesterone receptor, L-selectin ligand, αvβ3 integrin, and glycodelin-A were not different between the groups. Levonorgestrel, given as emergency contraceptive on the day of LH surge, does not disrupt either ovulation or progesterone production by the corpus luteum. The contraceptive mechanism of levonorgestrel at the time of LH surge does not include changes in the progesterone receptors or the endometrial receptivity biomarkers. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Application of molecularly imprinted and non-imprinted polymers for removal of emerging contaminants in water and wastewater treatment: a review.

    Science.gov (United States)

    Murray, Audrey; Ormeci, Banu

    2012-11-01

    Over the past decade, several studies have reported trace levels of endocrine disrupting compounds, pharmaceuticals, and personal care products in surface waters, drinking water, and wastewater effluents. There has also been an increased concern about the ecological and human health impact of these contaminants, and their removal from water and wastewater has become a priority. Traditional treatment processes are limited in their ability to remove emerging contaminants from water, and there is a need for new technologies that are effective and feasible. This paper presents a review on recent research results on molecularly imprinted (MIP) and non-imprinted (NIP) polymers and evaluates their potential as a treatment method for the removal of emerging contaminants from water and wastewater. It also discusses the relative benefits and limitations of using MIP or NIP for water and wastewater treatment. MIP, and in particular NIP, offer promising applications for wastewater treatment, but their toxicity and possible health effects should be carefully studied before they are considered for drinking water treatment. More research is also required to determine how best to incorporate MIP and NIP in treatment plants.

  19. The emergence of sarcomeric, graded-polarity and spindle-like patterns in bundles of short cytoskeletal polymers and two opposite molecular motors

    International Nuclear Information System (INIS)

    Craig, E M; Dey, S; Mogilner, A

    2011-01-01

    We use linear stability analysis and numerical solutions of partial differential equations to investigate pattern formation in the one-dimensional system of short dynamic polymers and one (plus-end directed) or two (one is plus-end, another minus-end directed) molecular motors. If polymer sliding and motor gliding rates are slow and/or the polymer turnover rate is fast, then the polymer-motor bundle has mixed polarity and homogeneous motor distribution. However, if motor gliding is fast, a sarcomeric pattern with periodic bands of alternating polymer polarity separated by motor aggregates evolves. On the other hand, if polymer sliding is fast, a graded-polarity bundle with motors at the center emerges. In the presence of the second, minus-end directed motor, the sarcomeric pattern is more ubiquitous, while the graded-polarity pattern is destabilized. However, if the minus-end motor is weaker than the plus-end directed one, and/or polymer nucleation is autocatalytic, and/or long polymers are present in the bundle, then a spindle-like architecture with a sorted-out polarity emerges with the plus-end motors at the center and minus-end motors at the edges. We discuss modeling implications for actin-myosin fibers and in vitro and meiotic spindles.

  20. Cellular Mechanosensing: Getting to the nucleus of it all

    Science.gov (United States)

    Fedorchak, Gregory R.; Kaminski, Ashley; Lammerding, Jan

    2014-01-01

    Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins. PMID:25008017

  1. Cellular consequences of sleep deprivation in the brain.

    Science.gov (United States)

    Cirelli, Chiara

    2006-10-01

    Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

  2. Molecular Diagnostics

    OpenAIRE

    Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  3. Estimating cellular network performance during hurricanes

    International Nuclear Information System (INIS)

    Booker, Graham; Torres, Jacob; Guikema, Seth; Sprintson, Alex; Brumbelow, Kelly

    2010-01-01

    Cellular networks serve a critical role during and immediately after a hurricane, allowing citizens to contact emergency services when land-line communication is lost and serving as a backup communication channel for emergency responders. However, due to their ubiquitous deployment and limited design for extreme loading events, basic network elements, such as cellular towers and antennas are prone to failures during adverse weather conditions such as hurricanes. Accordingly, a systematic and computationally feasible approach is required for assessing and improving the reliability of cellular networks during hurricanes. In this paper we develop a new multi-disciplinary approach to efficiently and accurately assess cellular network reliability during hurricanes. We show how the performance of a cellular network during and immediately after future hurricanes can be estimated based on a combination of hurricane wind field models, structural reliability analysis, Monte Carlo simulation, and cellular network models and simulation tools. We then demonstrate the use of this approach for assessing the improvement in system reliability that can be achieved with discrete topological changes in the system. Our results suggest that adding redundancy, particularly through a mesh topology or through the addition of an optical fiber ring around the perimeter of the system can be an effective way to significantly increase the reliability of some cellular systems during hurricanes.

  4. Molecular epidemiology of the emerging zoonosis agent Anaplasma phagocytophilum (Foggie, 1949) in dogs and ixodid ticks in Brazil.

    Science.gov (United States)

    Santos, Huarrisson A; Thomé, Sandra M G; Baldani, Cristiane D; Silva, Claudia B; Peixoto, Maristela P; Pires, Marcus S; Vitari, Gabriela L V; Costa, Renata L; Santos, Tiago M; Angelo, Isabele C; Santos, Leandro A; Faccini, João L H; Massard, Carlos L

    2013-12-11

    Anaplasma phagocytophilum is an emerging pathogen of humans, dogs and other animals, and it is transmitted by ixodid ticks. The objective of the current study was a) detect A. phagocytophilum in dogs and ixodid ticks using real-time Polymerase Chain Reaction (qPCR); and b) Determine important variables associated to host, environment and potential tick vectors that are related to the presence of A. phagocytophilum in dogs domiciled in Rio de Janeiro, Brazil. We tested blood samples from 398 dogs and samples from 235 ticks, including 194 Rhipicephalus sanguineus sensu lato, 15 Amblyomma cajennense, 8 Amblyomma ovale and 18 pools of Amblyomma sp. nymphs. A semi-structured questionnaire was applied by interviewing each dog owner. Deoxyribonucleic acid obtained from ticks and dog buffy coat samples were amplified by qPCR (msp2 gene). The sequencing of 16S rRNA and groESL heat shock operon genes and a phylogenetic analysis was performed. The multiple logistic regression model was created as a function of testing positive dogs for A. phagocytophilum. Among the 398 blood samples from dogs, 6.03% were positive for A. phagocytophilum. Anaplasma phagocytophilum was detected in one A. cajennense female tick and in five R. sanguineus sensu lato ticks (four males and one female). The partial sequences of the 16S rRNA, and groESL genes obtained were highly similar to strains of A. phagocytophilum isolated from wild birds from Brazil and human pathogenic strains. The tick species collected in positive dogs were R. sanguineus sensu lato and A. cajennense, with A.cajennense being predominant. Tick infestation history (OR = 2.86, CI = 1.98-14.87), dog size (OR = 2.41, IC: 1.51-12.67), the access to forest areas (OR = 3:51, CI: 1.52-16.32), hygiene conditions of the environment in which the dogs lived (OR = 4.35, CI: 1.86-18.63) and Amblyomma sp. infestation (OR = 6.12; CI: 2.11-28.15) were associated with A. phagocytophilum infection in dogs. This is the

  5. Wireless Cellular Mobile Communications

    OpenAIRE

    Zalud, V.

    2002-01-01

    In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

  6. Biomechanics of cellular solids.

    Science.gov (United States)

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  7. Prevalence and molecular epidemiology of Canine parvovirus 2 in diarrheic dogs in Colombia, South America: A possible new CPV-2a is emerging?

    Science.gov (United States)

    Duque-García, Yeison; Echeverri-Zuluaga, Manuela; Trejos-Suarez, Juanita; Ruiz-Saenz, Julian

    2017-03-01

    Since its identification in 1978, Canine parvovirus type 2 (CPV-2) has been considered a pathogen of great importance in the canine population because it causes severe enteritis with high mortality rates in pups. CPV-2 is a virus belonging to the family Parvoviridae. Currently, there are three described antigenic variants (CPV-2a, CPV-2b, and CPV-2c). CPV-2c is an emerging virus that is seen as a global health hazard. The objective of this work was to confirm the presence of CPV-2 in dogs with acute gastroenteritis compatible with parvovirus and to molecularly characterize the antigenic variants circulating in two regions of Colombia. An analytical cross-sectional study was conducted with fecal samples collected from 71 dogs showing signs of acute diarrhea. The samples were processed and polymerase chain reaction (PCR), restriction fragment length polymorphism analysis (RFLP), sequencing and phylogenetic analysis was performed to detect and characterize CPV. A total of 70.42% of the individuals were confirmed positive for CPV-2. Statistically differences were found in the presentation of CPV-2 between the evaluated regions. Phylogenetic analyses confirmed the presence of the antigenic variants CPV-2a/2b. Moreover, we found the presence of two conserved substitutions Asn428Asp and Ala514Ser in the VP2 protein suggesting the presence of a possible new CPV-2a variant circulating in Colombia. This study demonstrates the importance of the CPV 2a/2b in the region and highlights the importance of performing molecular studies for the early detection of new antigenic variants of CPV-2. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Molecular characterization of resistance to Rifampicin in an emerging hospital-associated Methicillin-resistant Staphylococcus aureus clone ST228, Spain

    Directory of Open Access Journals (Sweden)

    Liñares Josefina

    2010-03-01

    Full Text Available Abstract Background Methicillin-resistant S. aureus (MRSA has been endemic in Hospital Universitari de Bellvitge, Barcelona, since 1990. During the 1990-95 period the Iberian clone (ST-247; SCCmec-I was dominant. Isolates of clonal complex 5 (ST-125; SCCmec-IV gradually replaced the Iberian clone from 1996 to 2003. A new multiresistant MRSA phenotype showing rifampicin resistance emerged in 2004 and rapidly increased from 25% in 2004 to 45% in 2006. The aims of this study were i the molecular characterisation of rifampicin resistant MRSA isolates, ii the study of the rifampicin resistance expression by disk diffusion, microdilution and E-test, and iii the analysis of the rpoB gene mutations involved in rifampicin resistance. Results A sample of representative 108 rifampicin-resistant MRSA isolates belonged to a single PFGE genotype, ST-228, SCCmec type I and spa type t041. Of 108 isolates, 104 (96% had a low-level rifampicin resistance (MICs, 2 to 4 mg/L and 4 a high-level rifampicin resistance (MICs, 128 - ≥ 256 mg/L. Disk diffusion and E-test methods failed to identify a low-level rifampicin resistance in 20 and 12 isolates, respectively. A low-level rifampicin resistance was associated with amino acid substitution 481His/Asn in the beta-subunit of RNA polymerase. Isolates with a high-level rifampicin resistance carried additional mutations in the rpoB gene. Conclusions The emergence of MRSA clone ST228-SCCmecI, related to the Southern Germany clone, involved a therapeutical challenge for treating serious MRSA infections. Decreased susceptibility to rifampicin in MRSA strains of ST228-SCCmecI was associated with one or two specific mutations in the rpoB gene. One fifth of isolates with low-level rifampicin-resistance were missed by the diffusion methods.

  9. Molecular Characterization of Methicillin Resistant Staphylococcus aureus Strains Isolated from Intensive Care Units in Iran: ST22-SCCmec IV/t790 Emerges as the Major Clone.

    Science.gov (United States)

    Goudarzi, Mehdi; Goudarzi, Hossein; Sá Figueiredo, Agnes Marie; Udo, Edet E; Fazeli, Maryam; Asadzadeh, Mohammad; Seyedjavadi, Sima Sadat

    2016-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran. A total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing. The MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 μg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%). The circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.

  10. Domain 4 (D4 of Perfringolysin O to Visualize Cholesterol in Cellular Membranes—The Update

    Directory of Open Access Journals (Sweden)

    Masashi Maekawa

    2017-03-01

    Full Text Available The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine. Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4 of Perfringolysin O (PFO, theta toxin, a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes.

  11. Domain 4 (D4) of Perfringolysin O to Visualize Cholesterol in Cellular Membranes-The Update.

    Science.gov (United States)

    Maekawa, Masashi

    2017-03-03

    The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking) in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine). Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4) of Perfringolysin O (PFO, theta toxin), a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes.

  12. Partial differential equations for self-organization in cellular and developmental biology

    International Nuclear Information System (INIS)

    Baker, R E; Gaffney, E A; Maini, P K

    2008-01-01

    Understanding the mechanisms governing and regulating the emergence of structure and heterogeneity within cellular systems, such as the developing embryo, represents a multiscale challenge typifying current integrative biology research, namely, explaining the macroscale behaviour of a system from microscale dynamics. This review will focus upon modelling how cell-based dynamics orchestrate the emergence of higher level structure. After surveying representative biological examples and the models used to describe them, we will assess how developments at the scale of molecular biology have impacted on current theoretical frameworks, and the new modelling opportunities that are emerging as a result. We shall restrict our survey of mathematical approaches to partial differential equations and the tools required for their analysis. We will discuss the gap between the modelling abstraction and biological reality, the challenges this presents and highlight some open problems in the field. (invited article)

  13. Cellular Signaling in Health and Disease

    CERN Document Server

    Beckerman, Martin

    2009-01-01

    In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular sign...

  14. Linearizable cellular automata

    International Nuclear Information System (INIS)

    Nobe, Atsushi; Yura, Fumitaka

    2007-01-01

    The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

  15. The Correlation Between Candida Colonization of Distinct Body Sites and Invasive Candidiasis in Emergency Intensive Care Units: Statistical and Molecular Biological Analysis.

    Science.gov (United States)

    Li, Zhen; Jiang, Cen; Dong, Danfeng; Zhang, Lihua; Tian, Yuan; Ni, Qi; Mao, Enqiang; Peng, Yibing

    2016-08-01

    Both statistical and molecular biological methods were used to evaluate the association between Candida colonization of different body sites and invasive candidiasis (IC) and analyse the potential infection sources of IC. Candida surveillance cultures from the urine, sputum, rectum and skin were performed on patients admitted to an emergency intensive care units (EICU) of a tertiary care hospital in Shanghai, China, from February 2014 to January 2015. Specimens were collected once a week at admission and thereafter. The patients' clinical data were collected, and Candida isolates were genotyped using polymorphic microsatellite markers. A total of 111 patients were enrolled. Patients with positive urine (23.3 vs. 2.5 %, p = 0.001) and rectal swab (13.6 vs. 0 %, p = 0.010) cultures were more likely to develop IC. However, the risk for IC was not significantly different among patients with and without respiratory (10.0 vs. 5.8 %, p = 0.503) and skin (33.3 vs. 6.5 %, p = 0.056) colonization. Gene microevolution frequently occurred at rectal swab and urine sites, and IC with possible source of infection was caused by rectal isolates (2/7), urine isolates (4/7) and sputum isolate (1/7).The colonization of gut and urinary tract maybe more relevant indicators of IC, which should be taken into consideration when selecting practical body sites for Candida surveillance cultures.

  16. Emergency procedures

    International Nuclear Information System (INIS)

    Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail

    2004-01-01

    The following subjects are discussed - Emergency Procedures: emergency equipment, emergency procedures; emergency procedure involving X-Ray equipment; emergency procedure involving radioactive sources

  17. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  18. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  19. Optimized Energy Procurement for Cellular Networks with Uncertain Renewable Energy Generation

    KAUST Repository

    Rached, Nadhir B.; Ghazzai, Hakim; Kadri, Abdullah; Alouini, Mohamed-Slim

    2017-01-01

    Renewable energy (RE) is an emerging solution for reducing carbon dioxide (CO2) emissions from cellular networks. One of the challenges of using RE sources is to handle its inherent uncertainty. In this paper, a RE powered cellular network

  20. Combination of multilocus sequence typing and pulsed-field gel electrophoresis reveals an association of molecular clonality with the emergence of extensive-drug resistance (XDR) in Salmonella.

    Science.gov (United States)

    Cao, Yongzhong; Shen, Yongxiu; Cheng, Lingling; Zhang, Xiaorong; Wang, Chao; Wang, Yan; Zhou, Xiaohui; Chao, Guoxiang; Wu, Yantao

    2018-03-01

    Salmonellae is one of the most important foodborne pathogens and becomes resistant to multiple antibiotics, which represents a significant challenge to food industry and public health. However, a molecular signature that can be used to distinguish antimicrobial resistance profile, particularly multi-drug resistance or extensive-drug resistance (XDR). In the current study, 168 isolates from the chicken and pork production chains and ill chickens were characterized by serotyping, antimicrobial susceptibility test, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The results showed that these isolates belonged to 13 serotypes, 14 multilocus sequence types (STs), 94 PFGE genotypes, and 70 antimicrobial resistant profiles. S. Enteritidis, S. Indiana, and S. Derby were the predominant serotypes, corresponding to the ST11, ST17, and ST40 clones, respectively and the PFGE Cluster A, Cluster E, and Cluster D, respectively. Among the ST11-S. Enteritidis (Cluster A) and the ST40-S. Derby (Cluster D) clones, the majority of isolates were resistant to 4-8 antimicrobial agents, whereas in the ST17S. Indiana (Cluster E) clone, isolates showed extensive-drug resistance (XDR) to 9-16 antimicrobial agents. The bla TEM-1-like gene was prevalent in the ST11 and ST17 clones corresponding to high ampicillin resistance. The bla TEM-1-like , bla CTX-M , bla OXA-1-like , sul1, aaC4, aac(6')-1b, dfrA17, and floR gene complex was highly prevalent among isolates of ST17, corresponding to an XDR phenotype. These results demonstrated the association of the resistant phenotypes and genotypes with ST clone and PFGE cluster. Our results also indicated that the newly identified gene complex comprising bla TEM-1-like , bla CTX-M , bla OXA-1-like , sul1, aaC4, aac(6')-1b, dfrA17, and floR, was responsible for the emergence of the ST17S. Indiana XDR clone. ST17 could be potentially used as a molecular signature to distinguish S. Indiana XDR clone. Copyright © 2017

  1. Cellular metabolism regulates contact sites between vacuoles and mitochondria

    NARCIS (Netherlands)

    Hönscher, Carina; Mari, Muriel; Auffarth, Kathrin; Bohnert, Maria; Griffith, Janice; Geerts, Willie; van der Laan, Martin; Cabrera, Margarita; Reggiori, Fulvio; Ungermann, Christian

    2014-01-01

    Emerging evidence suggests that contact sites between different organelles form central hubs in the coordination of cellular physiology. Although recent work has emphasized the crucial role of the endoplasmic reticulum in interorganellar crosstalk, the cooperative behavior of other organelles is

  2. Magnetohydrodynamics cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu.

    1990-02-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  3. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  4. Magnetohydrodynamic cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

    1990-03-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

  5. Magnetohydrodynamic cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu

    1990-01-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  6. Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

    Science.gov (United States)

    Swart, A. Leoni; Harrison, Christopher F.; Eichinger, Ludwig; Steinert, Michael; Hilbi, Hubert

    2018-01-01

    Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors. PMID:29552544

  7. Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

    Directory of Open Access Journals (Sweden)

    A. Leoni Swart

    2018-03-01

    Full Text Available Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV. LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors.

  8. Antioxidant responses and cellular adjustments to oxidative stress.

    Science.gov (United States)

    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-12-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. Copyright © 2015. Published by Elsevier B.V.

  9. Cellular MR Imaging

    Directory of Open Access Journals (Sweden)

    Michel Modo

    2005-07-01

    Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

  10. Involvement of Sib Proteins in the Regulation of Cellular Adhesion in Dictyostelium discoideum▿ †

    OpenAIRE

    Cornillon, Sophie; Froquet, Romain; Cosson, Pierre

    2008-01-01

    Molecular mechanisms ensuring cellular adhesion have been studied in detail in Dictyostelium amoebae, but little is known about the regulation of cellular adhesion in these cells. Here, we show that cellular adhesion is regulated in Dictyostelium, notably by the concentration of a cellular secreted factor accumulating in the medium. This constitutes a quorum-sensing mechanism allowing coordinated regulation of cellular adhesion in a Dictyostelium population. In order to understand the mechani...

  11. Algorithmic crystal chemistry: A cellular automata approach

    International Nuclear Information System (INIS)

    Krivovichev, S. V.

    2012-01-01

    Atomic-molecular mechanisms of crystal growth can be modeled based on crystallochemical information using cellular automata (a particular case of finite deterministic automata). In particular, the formation of heteropolyhedral layered complexes in uranyl selenates can be modeled applying a one-dimensional three-colored cellular automaton. The use of the theory of calculations (in particular, the theory of automata) in crystallography allows one to interpret crystal growth as a computational process (the realization of an algorithm or program with a finite number of steps).

  12. Emerging Targets in Photopharmacology

    NARCIS (Netherlands)

    Lerch, Michael M.; Hansen, Mickel J.; van Dam, Gooitzen M.; Szymanski, Wiktor; Feringa, Ben L.

    2016-01-01

    The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology

  13. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  14. Molecular farming

    NARCIS (Netherlands)

    Merck, K.B.; Vereijken, J.M.

    2006-01-01

    Molecular Farming is a new and emerging technology that promises relatively cheap and flexible production of large quantities of pharmaceuticals in genetically modified plants. Many stakeholders are involved in the production of pharmaceuticals in plants, which complicates the discussion on the

  15. Translational Cellular Research on the International Space Station

    Science.gov (United States)

    Love, John; Cooley, Vic

    2016-01-01

    The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a

  16. Passive Noise Filtering by Cellular Compartmentalization.

    Science.gov (United States)

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Molecular epidemiology of extended-spectrum β-lactamase-producing Escherichia coli in the community and hospital in Korea: emergence of ST131 producing CTX-M-15

    Directory of Open Access Journals (Sweden)

    Park Sun

    2012-06-01

    Full Text Available Abstract Background The prevalence of extended-spectrum β-lactamase (ESBL-producing Escherichia coli has been increased not only in the hospital but also in the community worldwide. This study was aimed to characterize ESBL- producing E. coli isolates and to investigate the molecular epidemiology of community isolates in comparison with hospital isolates at a single center in Korea. Methods A total of 142 ESBL-producing E. coli isolates were collected at Daejeon St Mary’s Hospital in Korea from January 2008 to September 2009. The ESBLs were characterized by PCR sequencing using specific primers. The genetic relatedness was determined by pulsed field gel electrophoresis (PFGE and multilocus sequence typing (MLST. Results Of 142 isolates, 139 were positive for CTX-M type ESBLs; CTX-M-14 (n = 69, 49.6 %, CTX-M-15 (n = 53, 38.1 % and both CTX-M-14 and -15 (n = 17, 12.2 %. CTX-M-14 and CTX-M-15 were detected in both community and hospital isolates whereas isolates producing both CTX-M14 and-15 were mainly identified in the hospital. CTX-M producing E. coli isolates were genetically heterogeneous, revealing 75 distinct PFGE types. By MLST, 21 distinctive STs including 5 major STs (ST131, ST405, ST38, ST10, and ST648 were identified. Major STs were distributed in both community and hospital isolates, and ST131 was the predominant clone regardless of the locations of acquisition. No specific major STs were confined to a single type of ESBLs. However, ST131 clones were significantly associated with CTX-M-15 and the majority of them were multidrug-resistant. Distinctively, we identified a hospital epidemic caused by the dissemination of an epidemic strain, ST131-PFGE type 10, characterized by multidrug resistance and co-producing both CTX-Ms with OXA-1 or TEM-1b. Conclusions The epidemiology of ESBL-producing E. coli is a complex and evolving phenomenon attributed to the horizontal transfer of genetic elements and clonal spread of

  18. Wireless Cellular Mobile Communications

    Directory of Open Access Journals (Sweden)

    V. Zalud

    2002-12-01

    Full Text Available In this article is briefly reviewed the history of wireless cellularmobile communications, examined the progress in current secondgeneration (2G cellular standards and discussed their migration to thethird generation (3G. The European 2G cellular standard GSM and itsevolution phases GPRS and EDGE are described somewhat in detail. Thethird generation standard UMTS taking up on GSM/GPRS core network andequipped with a new advanced access network on the basis of codedivision multiple access (CDMA is investigated too. A sketch of theperspective of mobile communication beyond 3G concludes this article.

  19. Terminal addition in a cellular world.

    Science.gov (United States)

    Torday, J S; Miller, William B

    2018-07-01

    Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

  20. Radiolabelled cellular blood elements

    International Nuclear Information System (INIS)

    Sinzinger, H.

    1990-01-01

    This book reports on radiolabelled cellular blood elements, covering new advances made during the past several years, in particular the use of Tc-99 as a tracer for blood elements. Coverage extends to several radiolabelled monoclonal antibodies that are specific for blood components and may label blood elements in vivo

  1. Building synthetic cellular organization

    OpenAIRE

    Polka, Jessica K.; Silver, Pamela A.

    2013-01-01

    The elaborate spatial organization of cells enhances, restricts, and regulates protein–protein interactions. However, the biological significance of this organization has been difficult to study without ways of directly perturbing it. We highlight synthetic biology tools for engineering novel cellular organization, describing how they have been, and can be, used to advance cell biology.

  2. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  3. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  5. Cellular and Chemical Neuroscience of Mammalian Sleep

    OpenAIRE

    Datta, Subimal

    2010-01-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

  6. Diabetic Emergencies

    Science.gov (United States)

    ... Campaigns Share this! EmergencyCareForYou » Emergency 101 » Diabetic Emergencies Diabetic Emergencies It is estimated that more than 20 ... they have it. The best way to prevent diabetic emergencies is to effectively manage the disease through ...

  7. Towards Massive Machine Type Cellular Communications

    OpenAIRE

    Dawy, Zaher; Saad, Walid; Ghosh, Arunabha; Andrews, Jeffrey G.; Yaacoub, Elias

    2015-01-01

    Cellular networks have been engineered and optimized to carrying ever-increasing amounts of mobile data, but over the last few years, a new class of applications based on machine-centric communications has begun to emerge. Automated devices such as sensors, tracking devices, and meters - often referred to as machine-to-machine (M2M) or machine-type communications (MTC) - introduce an attractive revenue stream for mobile network operators, if a massive number of them can be efficiently support...

  8. EMERGING APPLICATIONS OF NANOMEDICINE FOR THERAPY AND DIAGNOSIS OF CARDIOVASCULAR DISEASES

    Science.gov (United States)

    Godin, Biana; Sakamoto, Jason H.; Serda, Rita E.; Grattoni, Alessandro; Bouamrani, Ali; Ferrari, Mauro

    2010-01-01

    Nanomedicine is an emerging field of medicine which utilizes nanotechnology concepts for advanced therapy and diagnostics. This convergent discipline, which merges research areas such as chemistry, biology, physics, mathematics and engineering thus bridging the gap between molecular and cellular interactions, has a potential to revolutionize current medical practice. This review presents recent developments in nanomedicine research, which are poised to have an important impact on cardiovascular disease and treatment by improving therapy and diagnosis of such cardiovascular disorders as atherosclerosis, restenosis and myocardial infarction. Specifically, we discuss the use of nanoparticles for molecular imaging and advanced therapeutics, specially designed drug eluting stents and in vivo/ex vivo early detection techniques. PMID:20172613

  9. Nested cellular automata

    International Nuclear Information System (INIS)

    Quasthoff, U.

    1985-07-01

    Cellular automata by definition consist of a finite or infinite number of cells, say of unit length, with each cell having the same transition function. These cells are usually considered as the smallest elements and so the space filled with these cells becomes discrete. Nevertheless, large pictures created by such cellular automata look very fractal. So we try to replace each cell by a couple of smaller cells, which have the same transition functions as the large ones. There are automata where this replacement does not destroy the macroscopic structure. In these cases this nesting process can be iterated. The paper contains large classes of automata with the above properties. In the case of one dimensional automata with two states and next neighbour interaction and a nesting function of the same type a complete classification is given. (author)

  10. Predictability in cellular automata.

    Science.gov (United States)

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

  11. Probabilistic cellular automata.

    Science.gov (United States)

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

  12. Wavefront cellular learning automata.

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure f